rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q 1 SIG_CHEMOTAXIS Genes related to chemotaxis ACTR2, ACTR3, AKT1, AKT2, AKT3, ANGPTL2, ARHGAP1, ARHGAP4, ARHGEF11, BTK, CDC42, CFL1, CFL2, GDI1, GDI2, INPPL1, ITPR1, ITPR2, ITPR3, LIMK1, MYLK, MYLK2, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDK1, PIK3CA, PIK3CD, PIK3CG, PIK3R1, PITX2, PPP1R13B, PTEN, RACGAP1, RHO, ROCK1, ROCK2, RPS4X, SAG, WASF1, WASL 44 ACTR2(7), ACTR3(3), AKT1(8), AKT2(4), AKT3(8), ANGPTL2(9), ARHGAP1(2), ARHGAP4(15), ARHGEF11(22), BTK(11), CDC42(5), CFL1(1), CFL2(8), GDI1(4), GDI2(3), INPPL1(23), ITPR1(31), ITPR2(38), ITPR3(23), LIMK1(7), MYLK(17), MYLK2(7), PAK1(3), PAK2(6), PAK3(14), PAK4(2), PAK6(3), PAK7(12), PDK1(7), PIK3CA(138), PIK3CD(10), PIK3CG(25), PIK3R1(67), PITX2(10), PPP1R13B(7), PTEN(198), RACGAP1(8), RHO(8), ROCK1(27), ROCK2(15), RPS4X(4), SAG(5), WASF1(3), WASL(8) 24593100 836 210 656 135 193 221 160 34 189 39 <1.00e-15 <2.46e-14 2 EIF4PATHWAY The eIF-4F complex recognizes 5' mRNA caps, recruits RNA helicases, and maintains mRNA-ribosome bridging. AKT1, EIF4A1, EIF4A2, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FRAP1, GHR, IRS1, MAPK1, MAPK14, MAPK3, MKNK1, PABPC1, PDK2, PDPK1, PIK3CA, PIK3R1, PRKCA, PRKCB1, PTEN, RPS6KB1 22 AKT1(8), EIF4A1(4), EIF4A2(6), EIF4E(4), EIF4G1(15), EIF4G2(8), EIF4G3(26), GHR(10), IRS1(17), MAPK1(2), MAPK14(6), MAPK3(4), MKNK1(6), PABPC1(11), PDK2(5), PDPK1(3), PIK3CA(138), PIK3R1(67), PRKCA(10), PTEN(198), RPS6KB1(3) 9912525 551 208 382 44 101 111 133 26 149 31 <1.00e-15 <2.46e-14 3 IGF1MTORPATHWAY Growth factor IGF-1 activates AKT, Gsk3-beta, and mTOR to promote muscle hypertrophy. AKT1, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF4E, EIF4EBP1, FRAP1, GSK3B, IGF1, IGF1R, INPPL1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1 19 AKT1(8), EIF2B5(6), EIF2S1(1), EIF2S2(5), EIF2S3(6), EIF4E(4), GSK3B(11), IGF1(3), IGF1R(13), INPPL1(23), PDK2(5), PDPK1(3), PIK3CA(138), PIK3R1(67), PPP2CA(6), PTEN(198), RPS6(6), RPS6KB1(3) 6967089 506 208 333 43 91 92 121 20 149 33 <1.00e-15 <2.46e-14 4 MTORPATHWAY Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation. AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2 21 AKT1(8), EIF4A1(4), EIF4A2(6), EIF4B(6), EIF4E(4), EIF4G1(15), EIF4G2(8), EIF4G3(26), MKNK1(6), PDK2(5), PDPK1(3), PIK3CA(138), PIK3R1(67), PPP2CA(6), PTEN(198), RPS6(6), RPS6KB1(3), TSC1(13), TSC2(14) 9012929 536 208 366 42 96 113 124 25 147 31 <1.00e-15 <2.46e-14 5 SIG_INSULIN_RECEPTOR_PATHWAY_IN_CARDIAC_MYOCYTES Genes related to the insulin receptor pathway AKT1, AKT2, AKT3, BRD4, CAP1, CBL, CDC42, CDKN2A, F2RL2, FLOT1, FLOT2, FOXO1A, GRB2, GSK3A, GSK3B, IGFBP1, INPPL1, IRS1, IRS2, IRS4, LNPEP, MAPK1, MAPK3, PARD3, PARD6A, PDK1, PIK3CA, PIK3CD, PIK3R1, PPYR1, PSCD3, PTEN, PTPN1, RAF1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SERPINB6, SFN, SHC1, SLC2A4, SORBS1, SOS1, SOS2, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 48 AKT1(8), AKT2(4), AKT3(8), BRD4(9), CAP1(7), CBL(10), CDC42(5), CDKN2A(1), F2RL2(3), FLOT1(1), FLOT2(3), GRB2(3), GSK3A(9), GSK3B(11), IGFBP1(5), INPPL1(23), IRS1(17), IRS4(20), LNPEP(9), MAPK1(2), MAPK3(4), PARD3(27), PARD6A(1), PDK1(7), PIK3CA(138), PIK3CD(10), PIK3R1(67), PPYR1(7), PTEN(198), PTPN1(4), RAF1(7), RPS6KA1(5), RPS6KA2(16), RPS6KA3(17), RPS6KB1(3), SERPINB6(4), SHC1(11), SLC2A4(4), SORBS1(22), SOS1(21), SOS2(22), YWHAB(1), YWHAE(1), YWHAG(3), YWHAH(4), YWHAQ(3), YWHAZ(1) 20132165 766 208 583 117 159 183 167 32 188 37 <1.00e-15 <2.46e-14 6 METPATHWAY The hepatocyte growth factor receptor c-Met stimulates proliferation and alters cell motility and adhesion on binding the ligand HGF. ACTA1, CRK, CRKL, DOCK1, ELK1, FOS, GAB1, GRB2, GRF2, HGF, HRAS, ITGA1, ITGB1, JUN, MAP2K1, MAP2K2, MAP4K1, MAPK1, MAPK3, MAPK8, MET, PAK1, PIK3CA, PIK3R1, PTEN, PTK2, PTK2B, PTPN11, PXN, RAF1, RAP1A, RAP1B, RASA1, SOS1, SRC, STAT3 34 ACTA1(4), CRK(1), CRKL(5), DOCK1(32), ELK1(2), FOS(6), GAB1(10), GRB2(3), HGF(15), ITGA1(20), ITGB1(12), JUN(1), MAP2K1(2), MAP4K1(13), MAPK1(2), MAPK3(4), MAPK8(7), MET(10), PAK1(3), PIK3CA(138), PIK3R1(67), PTEN(198), PTK2(11), PTK2B(16), PTPN11(8), PXN(6), RAF1(7), RAP1A(3), RAP1B(2), RASA1(29), SOS1(21), SRC(2), STAT3(12) 15458520 672 205 498 85 136 158 146 27 170 35 <1.00e-15 <2.46e-14 7 PTENPATHWAY PTEN suppresses AKT-induced cell proliferation and antagonizes the action of PI3K. AKT1, BCAR1, CDKN1B, FOXO3A, GRB2, ILK, ITGB1, MAPK1, MAPK3, PDK2, PDPK1, PIK3CA, PIK3R1, PTEN, PTK2, SHC1, SOS1, TNFSF6 15 AKT1(8), CDKN1B(5), GRB2(3), ILK(8), ITGB1(12), MAPK1(2), MAPK3(4), PDK2(5), PDPK1(3), PIK3CA(138), PIK3R1(67), PTEN(198), PTK2(11), SHC1(11), SOS1(21) 6356683 496 203 321 30 86 92 124 20 141 33 <1.00e-15 <2.46e-14 8 ST_PHOSPHOINOSITIDE_3_KINASE_PATHWAY The phosphoinositide-3 kinase pathway produces the lipid second messenger PIP3 and regulates cell growth, survival, and movement. A1BG, AKT1, AKT2, AKT3, BAD, BTK, CDKN2A, CSL4, DAF, DAPP1, FOXO1A, GRB2, GSK3A, GSK3B, IARS, IGFBP1, INPP5D, P14, PDK1, PIK3CA, PPP1R13B, PSCD3, PTEN, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SOS1, SOS2, TEC, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 33 A1BG(3), AKT1(8), AKT2(4), AKT3(8), BAD(2), BTK(11), CDKN2A(1), DAPP1(7), GRB2(3), GSK3A(9), GSK3B(11), IARS(13), IGFBP1(5), INPP5D(14), PDK1(7), PIK3CA(138), PPP1R13B(7), PTEN(198), RPS6KA1(5), RPS6KA2(16), RPS6KA3(17), RPS6KB1(3), SHC1(11), SOS1(21), SOS2(22), TEC(5), YWHAB(1), YWHAE(1), YWHAG(3), YWHAH(4), YWHAQ(3), YWHAZ(1) 12586696 562 201 396 60 115 137 132 22 132 24 <1.00e-15 <2.46e-14 9 SA_PTEN_PATHWAY PTEN is a tumor suppressor that dephosphorylates the lipid messenger phosphatidylinositol triphosphate. AKT1, AKT2, AKT3, BPNT1, GRB2, ILK, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIP3-E, PTEN, PTK2B, RBL2, SHC1, SOS1 16 AKT1(8), AKT2(4), AKT3(8), BPNT1(1), GRB2(3), ILK(8), MAPK1(2), MAPK3(4), PDK1(7), PIK3CA(138), PIK3CD(10), PTEN(198), PTK2B(16), RBL2(21), SHC1(11), SOS1(21) 6977366 460 198 293 36 98 93 112 20 112 25 <1.00e-15 <2.46e-14 10 HSA04210_APOPTOSIS Genes involved in apoptosis AIFM1, AKT1, AKT2, AKT3, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CAPN1, CAPN2, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHP, CHUK, CSF2RB, CYCS, DFFA, DFFB, ENDOG, FADD, FAS, FASLG, IKBKB, IKBKG, IL1A, IL1B, IL1R1, IL1RAP, IL3, IL3RA, IRAK1, IRAK2, IRAK3, IRAK4, MAP3K14, MYD88, NFKB1, NFKB2, NFKBIA, NGFB, NTRK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RELA, RIPK1, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF1A, TNFSF10, TP53, TRADD, TRAF2 79 AIFM1(12), AKT1(8), AKT2(4), AKT3(8), APAF1(19), ATM(54), BAD(2), BAX(4), BCL2L1(3), BID(3), BIRC2(13), BIRC3(3), CAPN1(4), CAPN2(6), CASP10(10), CASP3(4), CASP6(4), CASP7(4), CASP8(21), CASP9(3), CFLAR(7), CHUK(11), CSF2RB(11), CYCS(3), DFFA(1), DFFB(3), FADD(1), FAS(7), FASLG(6), IKBKB(15), IL1A(1), IL1B(2), IL1R1(5), IL1RAP(2), IL3RA(11), IRAK1(5), IRAK2(7), IRAK3(13), IRAK4(6), MAP3K14(12), MYD88(1), NFKB1(12), NFKB2(10), NFKBIA(3), NTRK1(11), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PPP3CA(4), PPP3CB(7), PPP3CC(6), PPP3R1(2), PPP3R2(1), PRKACA(4), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), RELA(6), RIPK1(8), TNF(1), TNFRSF10A(3), TNFRSF10B(5), TNFRSF10C(3), TNFRSF10D(10), TNFRSF1A(6), TNFSF10(1), TP53(40), TRAF2(5) 28018448 775 186 659 164 177 260 136 44 141 17 <1.00e-15 <2.46e-14 11 GSK3PATHWAY Bacterial lipopolysaccharide activates AKT to promote the survival and activation of macrophages and inhibits Gsk3-beta to promote beta-catenin accumulation in the nucleus. AKT1, APC, AXIN1, CCND1, CD14, CTNNB1, DVL1, FZD1, GJA1, GNAI1, GSK3B, IRAK1, LBP, LEF1, LY96, MYD88, NFKB1, PDPK1, PIK3CA, PIK3R1, PPP2CA, PRKR, RELA, TIRAP, TLR4, TOLLIP, WNT1 24 AKT1(8), APC(53), AXIN1(8), CCND1(10), CD14(2), CTNNB1(66), FZD1(2), GJA1(6), GNAI1(4), GSK3B(11), IRAK1(5), LBP(4), LEF1(9), LY96(4), MYD88(1), NFKB1(12), PDPK1(3), PIK3CA(138), PIK3R1(67), PPP2CA(6), RELA(6), TIRAP(3), TLR4(14), WNT1(1) 9896751 443 180 302 51 100 134 89 35 68 17 <1.00e-15 <2.46e-14 12 HSA04650_NATURAL_KILLER_CELL_MEDIATED_CYTOTOXICITY Genes involved in natural killer cell mediated cytotoxicity ARAF, BID, BRAF, CASP3, CD244, CD247, CD48, CHP, CSF2, FAS, FASLG, FCER1G, FCGR3A, FCGR3B, FYN, GRB2, GZMB, HCST, HLA-A, HLA-B, HLA-C, HLA-E, HLA-G, HRAS, ICAM1, ICAM2, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNG, IFNGR1, IFNGR2, ITGAL, ITGB2, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DS1, KIR2DS2, KIR3DL1, KIR3DL2, KLRC1, KLRC2, KLRC3, KLRD1, KLRK1, KRAS, LAT, LCK, LCP2, LOC652578, MAP2K1, MAP2K2, MAPK1, MAPK3, MICA, MICB, NCR1, NCR2, NCR3, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NRAS, PAK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRF1, PRKCA, PRKCB1, PRKCG, PTK2B, PTPN11, PTPN6, RAC1, RAC2, RAC3, RAF1, SH2D1A, SH2D1B, SH3BP2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SYK, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFSF10, TYROBP, ULBP1, ULBP2, ULBP3, VAV1, VAV2, VAV3, ZAP70 122 ARAF(8), BID(3), BRAF(12), CASP3(4), CD244(4), CD247(5), CD48(4), FAS(7), FASLG(6), FCER1G(1), FCGR3A(2), FCGR3B(5), FYN(7), GRB2(3), GZMB(2), HCST(2), HLA-A(5), HLA-B(3), HLA-E(2), HLA-G(3), ICAM1(3), ICAM2(5), IFNA10(2), IFNA13(3), IFNA14(3), IFNA16(2), IFNA17(2), IFNA2(1), IFNA21(2), IFNA4(3), IFNA5(2), IFNA6(6), IFNA7(2), IFNA8(2), IFNAR1(9), IFNAR2(8), IFNB1(4), IFNG(5), IFNGR1(6), IFNGR2(4), ITGAL(13), ITGB2(14), KIR2DL1(6), KIR2DL3(2), KIR2DL4(3), KIR3DL1(7), KIR3DL2(7), KLRC1(2), KLRC2(3), KLRC3(1), KLRD1(2), KLRK1(1), KRAS(29), LCK(5), LCP2(7), MAP2K1(2), MAPK1(2), MAPK3(4), MICB(3), NCR1(5), NCR2(5), NFAT5(13), NFATC2(15), NFATC3(12), NFATC4(8), NRAS(10), PAK1(3), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PLCG1(12), PLCG2(27), PPP3CA(4), PPP3CB(7), PPP3CC(6), PPP3R1(2), PPP3R2(1), PRF1(8), PRKCA(10), PRKCG(10), PTK2B(16), PTPN11(8), RAC2(2), RAF1(7), SH2D1A(3), SH2D1B(2), SH3BP2(10), SHC1(11), SHC3(9), SHC4(7), SOS1(21), SOS2(22), SYK(6), TNF(1), TNFRSF10A(3), TNFRSF10B(5), TNFRSF10C(3), TNFRSF10D(10), TNFSF10(1), TYROBP(1), ULBP1(2), ULBP2(5), ULBP3(1), VAV1(16), VAV2(5), VAV3(13), ZAP70(10) 37982119 912 179 781 215 262 304 162 48 117 19 <1.00e-15 <2.46e-14 13 ST_ADRENERGIC Adrenergic receptors respond to epinephrine and norepinephrine signaling. AKT1, APC, AR, ASAH1, BF, BRAF, CAMP, CCL13, CCL15, CCL16, DAG1, EGFR, GAS, GNA11, GNA15, GNAI1, GNAQ, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, MAPK10, MAPK14, PHKA2, PIK3CA, PIK3CD, PIK3R1, PITX2, PTX1, PTX3, RAF1, SRC 33 AKT1(8), APC(53), AR(5), ASAH1(9), BRAF(12), CAMP(1), CCL13(2), CCL15(2), CCL16(1), DAG1(7), EGFR(20), GNA11(3), GNA15(1), GNAI1(4), ITPKB(6), ITPR1(31), ITPR2(38), ITPR3(23), KCNJ3(15), KCNJ5(6), KCNJ9(4), MAPK1(2), MAPK10(9), MAPK14(6), PHKA2(15), PIK3CA(138), PIK3CD(10), PIK3R1(67), PITX2(10), PTX3(2), RAF1(7), SRC(2) 18416145 519 173 422 102 133 166 101 23 75 21 <1.00e-15 <2.46e-14 14 PPARAPATHWAY Peroxisome proliferators regulate gene expression via PPAR/RXR heterodimers which bind to peroxisome-proliferator response elements (PPREs). ACOX1, APOA1, APOA2, CD36, CITED2, CPT1B, CREBBP, DUSP1, DUT, EHHADH, EP300, FABP1, FAT, FRA8B, HSD17B4, HSPA1A, HSPCA, INS, JUN, LPL, MAPK1, MAPK3, ME1, MRPL11, MYC, NCOA1, NCOR1, NCOR2, NFKBIA, NOS2A, NR0B2, NR1H3, NR2F1, NRIP1, PDGFA, PIK3CA, PIK3R1, PPARA, PPARBP, PPARGC1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PTGS2, RB1, RELA, RXRA, SP1, SRA1, STAT5A, STAT5B, TNF 46 ACOX1(4), APOA2(2), CD36(7), CITED2(1), CREBBP(37), DUSP1(2), DUT(1), EHHADH(9), EP300(29), FABP1(5), HSD17B4(10), JUN(1), LPL(11), MAPK1(2), MAPK3(4), ME1(10), MRPL11(1), MYC(7), NCOA1(17), NCOR1(24), NCOR2(24), NFKBIA(3), NR0B2(2), NR1H3(5), NR2F1(5), NRIP1(18), PIK3CA(138), PIK3R1(67), PPARA(2), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PRKCA(10), PTGS2(7), RB1(31), RELA(6), RXRA(1), SP1(6), SRA1(3), STAT5A(5), STAT5B(5), TNF(1) 20595586 552 170 455 104 132 172 107 31 91 19 <1.00e-15 <2.46e-14 15 RACCYCDPATHWAY Ras, Rac, and Rho coordinate to induce cyclin D1 expression and activate cdk2 to promote the G1/S transition. AKT1, ARHA, CCND1, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, E2F1, HRAS, MAPK1, MAPK3, NFKB1, NFKBIA, PAK1, PIK3CA, PIK3R1, RAC1, RAF1, RB1, RELA, TFDP1 22 AKT1(8), CCND1(10), CDK2(5), CDK4(4), CDK6(3), CDKN1A(1), CDKN1B(5), E2F1(12), MAPK1(2), MAPK3(4), NFKB1(12), NFKBIA(3), PAK1(3), PIK3CA(138), PIK3R1(67), RAF1(7), RB1(31), RELA(6) 7013216 321 168 225 30 69 81 79 20 57 15 <1.00e-15 <2.46e-14 16 PAR1PATHWAY Activated extracellular thrombin cleaves and activates the G-protein coupled receptors PAR1 and PAR4, which activate platelets. ADCY1, ARHA, ARHGEF1, F2, F2R, F2RL3, GNA12, GNA13, GNAI1, GNAQ, GNB1, GNGT1, MAP3K7, PIK3CA, PIK3R1, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2B, ROCK1 18 ADCY1(17), ARHGEF1(11), F2(9), F2R(8), GNA12(10), GNA13(9), GNAI1(4), GNB1(3), MAP3K7(8), PIK3CA(138), PIK3R1(67), PLCB1(6), PPP1R12B(18), PRKCA(10), PTK2B(16), ROCK1(27) 8804043 361 167 269 44 100 94 77 21 52 17 <1.00e-15 <2.46e-14 17 HCMVPATHWAY Cytomegalovirus activates MAP kinase pathways in the host cell, inducing transcription of viral genes. AKT1, CREB1, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NFKB1, PIK3CA, PIK3R1, RB1, RELA, SP1 15 AKT1(8), CREB1(5), MAP2K1(2), MAP2K3(8), MAP2K6(9), MAP3K1(31), MAPK1(2), MAPK14(6), MAPK3(4), NFKB1(12), PIK3CA(138), PIK3R1(67), RB1(31), RELA(6), SP1(6) 6777084 335 166 240 27 74 85 80 23 56 17 <1.00e-15 <2.46e-14 18 INSULINPATHWAY Insulin regulates glucose levels via Ras-mediated transcriptional activation. CSNK2A1, ELK1, FOS, GRB2, HRAS, INS, INSR, IRS1, JUN, MAP2K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PTPN11, RAF1, RASA1, SHC1, SLC2A4, SOS1, SRF 20 CSNK2A1(9), ELK1(2), FOS(6), GRB2(3), INSR(18), IRS1(17), JUN(1), MAP2K1(2), MAPK3(4), MAPK8(7), PIK3CA(138), PIK3R1(67), PTPN11(8), RAF1(7), RASA1(29), SHC1(11), SLC2A4(4), SOS1(21), SRF(3) 8735450 357 164 263 40 94 97 74 18 59 15 <1.00e-15 <2.46e-14 19 IGF1PATHWAY Growth factor IGF-1 stimulates growth and inhibits apoptosis by activating the MAP kinase pathway in a variety of cell types. CSNK2A1, ELK1, FOS, GRB2, HRAS, IGF1, IGF1R, IRS1, JUN, MAP2K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PTPN11, RAF1, RASA1, SHC1, SOS1, SRF 20 CSNK2A1(9), ELK1(2), FOS(6), GRB2(3), IGF1(3), IGF1R(13), IRS1(17), JUN(1), MAP2K1(2), MAPK3(4), MAPK8(7), PIK3CA(138), PIK3R1(67), PTPN11(8), RAF1(7), RASA1(29), SHC1(11), SOS1(21), SRF(3) 8569106 351 162 257 35 91 91 75 20 59 15 <1.00e-15 <2.46e-14 20 PLCPATHWAY Phospholipase C hydrolyzes the membrane lipid PIP2 to DAG, which activates protein kinase C, and IP3, which causes calcium influx. AKT1, PIK3CA, PIK3R1, PLCB1, PLCG1, PRKCA, PRKCB1, VAV1 7 AKT1(8), PIK3CA(138), PIK3R1(67), PLCB1(6), PLCG1(12), PRKCA(10), VAV1(16) 4554623 257 159 161 29 64 57 64 15 44 13 <1.00e-15 <2.46e-14 21 NKCELLSPATHWAY Natural killer (NK) lymphocytes are inhibited by MHC and activated by surface glycoproteins on tumor or virus-infected cells, which undergo perforin-mediated lysis. B2M, HLA-A, IL18, ITGB1, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LAT, MAP2K1, MAPK3, PAK1, PIK3CA, PIK3R1, PTK2B, PTPN6, RAC1, SYK, VAV1 20 B2M(2), HLA-A(5), IL18(1), ITGB1(12), KLRC1(2), KLRC2(3), KLRC3(1), KLRC4(3), KLRD1(2), MAP2K1(2), MAPK3(4), PAK1(3), PIK3CA(138), PIK3R1(67), PTK2B(16), SYK(6), VAV1(16) 6553380 283 155 191 28 72 66 67 16 49 13 <1.00e-15 <2.46e-14 22 HSA04110_CELL_CYCLE Genes involved in cell cycle ABL1, ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, ATM, ATR, BUB1, BUB1B, BUB3, CCNA1, CCNA2, CCNB1, CCNB2, CCNB3, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNH, CDC14A, CDC14B, CDC16, CDC2, CDC20, CDC23, CDC25A, CDC25B, CDC25C, CDC26, CDC27, CDC45L, CDC6, CDC7, CDK2, CDK4, CDK6, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CHEK1, CHEK2, CREBBP, CUL1, DBF4, E2F1, E2F2, E2F3, EP300, ESPL1, FZR1, GADD45A, GADD45B, GADD45G, GSK3B, hCG_1982709, HDAC1, HDAC2, LOC440917, LOC728919, MAD1L1, MAD2L1, MAD2L2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, PKMYT1, PLK1, PRKDC, PTTG1, PTTG2, RB1, RBL1, RBL2, RBX1, SFN, SKP1, SKP2, SMAD2, SMAD3, SMAD4, SMC1A, SMC1B, TFDP1, TGFB1, TGFB2, TGFB3, TP53, WEE1, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 104 ABL1(9), ANAPC1(30), ANAPC10(2), ANAPC2(6), ANAPC4(5), ANAPC5(12), ANAPC7(3), ATM(54), ATR(38), BUB1(9), BUB1B(6), BUB3(5), CCNA1(4), CCNA2(3), CCNB1(8), CCNB2(4), CCNB3(20), CCND1(10), CCND2(7), CCND3(5), CCNE2(6), CCNH(3), CDC14A(8), CDC14B(6), CDC16(1), CDC20(5), CDC23(4), CDC25A(9), CDC25B(3), CDC25C(8), CDC27(22), CDC6(3), CDC7(13), CDK2(5), CDK4(4), CDK6(3), CDK7(6), CDKN1A(1), CDKN1B(5), CDKN2A(1), CDKN2C(3), CDKN2D(3), CHEK1(4), CHEK2(14), CREBBP(37), CUL1(12), DBF4(11), E2F1(12), E2F2(1), E2F3(5), EP300(29), ESPL1(10), GSK3B(11), HDAC1(4), HDAC2(5), MAD1L1(15), MAD2L1(5), MAD2L2(3), MCM2(10), MCM3(9), MCM4(9), MCM5(12), MCM6(9), MCM7(5), MDM2(6), PCNA(3), PLK1(6), PRKDC(70), PTTG1(5), PTTG2(1), RB1(31), RBL1(17), RBL2(21), RBX1(1), SKP1(2), SKP2(6), SMAD2(12), SMAD3(4), SMAD4(5), SMC1A(19), SMC1B(22), TGFB1(4), TGFB2(6), TGFB3(9), TP53(40), WEE1(1), YWHAB(1), YWHAE(1), YWHAG(3), YWHAH(4), YWHAQ(3), YWHAZ(1) 47280892 898 134 856 189 208 354 120 52 140 24 <1.00e-15 <2.46e-14 23 PITX2PATHWAY The bicoid-related transcription factor Pitx2 is activated by Wnt binding to the Frizzled receptor and induces tissue-specific cell proliferation. APC, AXIN1, CREBBP, CTNNB1, DVL1, EP300, FZD1, GSK3B, HDAC1, HTATIP, LDB1, LEF1, PITX2, PPARBP, TRRAP, WNT1 13 APC(53), AXIN1(8), CREBBP(37), CTNNB1(66), EP300(29), FZD1(2), GSK3B(11), HDAC1(4), LDB1(3), LEF1(9), PITX2(10), TRRAP(72), WNT1(1) 10889796 305 121 252 50 75 121 40 24 37 8 <1.00e-15 <2.46e-14 24 WNTPATHWAY The Wnt glycoprotein binds to membrane-bound receptors such as Frizzled to activate a number of signaling pathways, including that of beta-catenin. APC, AXIN1, BTRC, CCND1, CREBBP, CSNK1A1, CSNK1D, CSNK2A1, CTBP1, CTNNB1, DVL1, FRAT1, FZD1, GSK3B, HDAC1, MADH4, MAP3K7, MAP3K7IP1, MYC, NLK, PPARD, PPP2CA, TCF1, TLE1, WIF1, WNT1 20 APC(53), AXIN1(8), BTRC(13), CCND1(10), CREBBP(37), CSNK1A1(5), CSNK2A1(9), CTNNB1(66), FZD1(2), GSK3B(11), HDAC1(4), MAP3K7(8), MYC(7), NLK(5), PPARD(6), PPP2CA(6), TLE1(12), WIF1(5), WNT1(1) 9313591 268 118 218 45 70 107 33 21 29 8 <1.00e-15 <2.46e-14 25 RNAPATHWAY dsRNA-activated protein kinase phosphorylates elF2a, which generally inhibits translation, and activates NF-kB to provoke inflammation. CHUK, DNAJC3, EIF2S1, EIF2S2, MAP3K14, NFKB1, NFKBIA, PRKR, RELA, TP53 9 CHUK(11), DNAJC3(8), EIF2S1(1), EIF2S2(5), MAP3K14(12), NFKB1(12), NFKBIA(3), RELA(6), TP53(40) 3408618 98 57 87 11 21 31 18 7 21 0 <1.00e-15 <2.46e-14 26 CXCR4PATHWAY CXCR4 is a G-protein coupled receptor that responds to the ligand SDF-1 by activating Ras and PI3 kinase to promote lymphocyte chemotaxis. BCAR1, CRK, CXCL12, CXCR4, GNAI1, GNAQ, GNB1, GNGT1, HRAS, MAP2K1, MAPK1, MAPK3, NFKB1, PIK3C2G, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTK2, PTK2B, PXN, RAF1, RELA 22 CRK(1), CXCL12(3), CXCR4(1), GNAI1(4), GNB1(3), MAP2K1(2), MAPK1(2), MAPK3(4), NFKB1(12), PIK3C2G(22), PIK3CA(138), PIK3R1(67), PLCG1(12), PRKCA(10), PTK2(11), PTK2B(16), PXN(6), RAF1(7), RELA(6) 9319566 327 157 236 53 83 78 78 21 54 13 1.11e-15 2.53e-14 27 CTLA4PATHWAY T cell activation requires interaction with an antigen-MHC-I complex on an antigen-presenting cell (APC), as well as CD28 interaction with the APC's CD80 or 86. CD28, CD3D, CD3E, CD3G, CD3Z, CD80, CD86, CTLA4, GRB2, HLA-DRA, HLA-DRB1, ICOS, ICOSL, IL2, ITK, LCK, PIK3CA, PIK3R1, PTPN11, TRA@, TRB@ 17 CD28(6), CD3D(3), CD3E(2), CD3G(2), CD80(7), CD86(6), CTLA4(2), GRB2(3), HLA-DRB1(1), ICOS(2), IL2(4), ITK(10), LCK(5), PIK3CA(138), PIK3R1(67), PTPN11(8) 4556296 266 152 177 17 64 68 66 13 44 11 1.11e-15 2.53e-14 28 ST_B_CELL_ANTIGEN_RECEPTOR B cell receptors bind antigens and promote B cell activation. AKT1, AKT2, AKT3, BAD, BCR, BLNK, BTK, CD19, CSK, DAG1, EPHB2, GRB2, ITPKA, ITPKB, LYN, MAP2K1, MAP2K2, MAPK1, NFAT5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PAG, PI3, PIK3CA, PIK3CD, PIK3R1, PLCG2, PPP1R13B, RAF1, SERPINA4, SHC1, SOS1, SOS2, SYK, VAV1 37 AKT1(8), AKT2(4), AKT3(8), BAD(2), BCR(6), BLNK(4), BTK(11), CD19(7), CSK(1), DAG1(7), EPHB2(10), GRB2(3), ITPKB(6), LYN(7), MAP2K1(2), MAPK1(2), NFAT5(13), NFKB1(12), NFKB2(10), NFKBIA(3), NFKBIB(3), NFKBIE(6), NFKBIL1(2), PI3(3), PIK3CA(138), PIK3CD(10), PIK3R1(67), PLCG2(27), PPP1R13B(7), RAF1(7), SERPINA4(8), SHC1(11), SOS1(21), SOS2(22), SYK(6), VAV1(16) 17391791 480 172 379 102 121 156 97 24 65 17 1.33e-15 2.93e-14 29 TRKAPATHWAY Nerve growth factor (NGF) promotes neuronal survival and proliferation by binding its receptor TrkA, which activates PI3K/AKT, Ras, and the MAP kinase pathway. AKT1, DPM2, GRB2, HRAS, KLK2, NGFB, NTRK1, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, SHC1, SOS1 12 AKT1(8), DPM2(4), GRB2(3), KLK2(2), NTRK1(11), PIK3CA(138), PIK3R1(67), PLCG1(12), PRKCA(10), SHC1(11), SOS1(21) 5473339 287 161 191 29 74 74 65 16 45 13 1.67e-15 3.54e-14 30 HSA05130_PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EHEC Genes involved in pathogenic Escherichia coli infection - EHEC ABL1, ACTB, ACTG1, ARHGEF2, ARPC5, ARPC5L, CD14, CDC42, CDH1, CLDN1, CTNNB1, CTTN, EZR, FYN, HCLS1, ITGB1, KRT18, LOC643224, LOC654264, LY96, NCK1, NCK2, NCL, OCLN, PRKCA, RHOA, ROCK1, ROCK2, TLR4, TLR5, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8, WAS, WASL, YWHAQ, YWHAZ 51 ABL1(9), ACTB(5), ARHGEF2(10), ARPC5(1), CD14(2), CDC42(5), CDH1(15), CLDN1(2), CTNNB1(66), CTTN(8), EZR(6), FYN(7), HCLS1(8), ITGB1(12), LY96(4), NCK1(4), NCK2(8), NCL(2), OCLN(5), PRKCA(10), RHOA(4), ROCK1(27), ROCK2(15), TLR4(14), TLR5(8), TUBA1A(5), TUBA1B(4), TUBA1C(9), TUBA3C(7), TUBA3D(5), TUBA3E(15), TUBA4A(7), TUBA8(11), TUBAL3(5), TUBB1(8), TUBB2A(4), TUBB2B(2), TUBB2C(1), TUBB4(9), TUBB4Q(4), TUBB6(4), TUBB8(3), WAS(14), WASL(8), YWHAQ(3), YWHAZ(1) 18644629 386 114 336 97 91 175 37 24 57 2 1.78e-15 3.65e-14 31 HSA04370_VEGF_SIGNALING_PATHWAY Genes involved in VEGF signaling pathway AKT1, AKT2, AKT3, BAD, CASP9, CDC42, CHP, HRAS, KDR, KRAS, MAP2K1, MAP2K2, MAPK1, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPKAPK2, MAPKAPK3, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NOS3, NRAS, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCG1, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCA, PRKCB1, PRKCG, PTGS2, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, SH2D2A, SHC2, SPHK1, SPHK2, SRC, VEGFA 64 AKT1(8), AKT2(4), AKT3(8), BAD(2), CASP9(3), CDC42(5), KDR(23), KRAS(29), MAP2K1(2), MAPK1(2), MAPK13(2), MAPK14(6), MAPK3(4), MAPKAPK2(6), MAPKAPK3(4), NFAT5(13), NFATC2(15), NFATC3(12), NFATC4(8), NOS3(11), NRAS(10), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PLA2G10(1), PLA2G12A(1), PLA2G12B(3), PLA2G1B(1), PLA2G2D(2), PLA2G2E(3), PLA2G2F(3), PLA2G3(5), PLA2G4A(11), PLA2G5(2), PLA2G6(6), PLCG1(12), PLCG2(27), PPP3CA(4), PPP3CB(7), PPP3CC(6), PPP3R1(2), PPP3R2(1), PRKCA(10), PRKCG(10), PTGS2(7), PTK2(11), PXN(6), RAC2(2), RAF1(7), SPHK1(2), SPHK2(1), SRC(2), VEGFA(1) 22792474 612 172 489 131 178 183 119 35 86 11 2.00e-15 3.97e-14 32 HSA04150_MTOR_SIGNALING_PATHWAY Genes involved in mTOR signaling pathway AKT1, AKT2, AKT3, BRAF, CAB39, DDIT4, EIF4B, EIF4EBP1, FIGF, FRAP1, GBL, HIF1A, IGF1, INS, KIAA1303, LYK5, MAPK1, MAPK3, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PRKAA1, PRKAA2, RHEB, RICTOR, RPS6, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6, RPS6KB1, RPS6KB2, STK11, TSC1, TSC2, ULK1, ULK2, ULK3, VEGFA, VEGFB, VEGFC 41 AKT1(8), AKT2(4), AKT3(8), BRAF(12), CAB39(6), DDIT4(3), EIF4B(6), FIGF(5), HIF1A(17), IGF1(3), MAPK1(2), MAPK3(4), PDPK1(3), PGF(2), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PRKAA1(6), PRKAA2(9), RHEB(2), RICTOR(25), RPS6(6), RPS6KA1(5), RPS6KA2(16), RPS6KA3(17), RPS6KA6(15), RPS6KB1(3), RPS6KB2(6), TSC1(13), TSC2(14), ULK2(10), ULK3(5), VEGFA(1), VEGFB(2), VEGFC(7) 16389186 524 171 421 91 134 160 97 33 89 11 2.55e-15 4.56e-14 33 PMLPATHWAY Ring-shaped PML nuclear bodies regulate transcription and are required co-activators in p53- and DAXX-mediated apoptosis. CREBBP, DAXX, HRAS, PAX3, PML, PRAM-1, RARA, RB1, SIRT1, SP100, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TP53, UBL1 13 CREBBP(37), DAXX(11), PAX3(4), PML(10), RARA(3), RB1(31), SIRT1(8), SP100(15), TNF(1), TNFRSF1A(6), TNFRSF1B(3), TP53(40) 6433641 169 67 156 33 46 60 21 7 31 4 2.55e-15 4.56e-14 34 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 7 ATM(54), ATR(38), CDC25C(8), CHEK1(4), CHEK2(14), TP53(40), YWHAH(4) 5751057 162 75 146 19 31 45 26 10 44 6 2.66e-15 4.56e-14 35 ST_DIFFERENTIATION_PATHWAY_IN_PC12_CELLS Rat-derived PC12 cells respond to nerve growth factor (NGF) and PACAP to differentiate into neuronal cells. AKT1, ASAH1, ATF1, BRAF, CAMP, CREB1, CREB3, CREB5, CREBBP, CRKL, DAG1, EGR1, EGR2, EGR3, EGR4, ELK1, FRS2, GAS, GNAQ, GRF2, JUN, MAP1B, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, NTRK1, OPN1LW, PACAP, PIK3C2G, PIK3CA, PIK3CD, PIK3R1, PTPN11, RPS6KA3, SH2B, SHC1, SRC, TERF2IP, TH, TUBA3 37 AKT1(8), ASAH1(9), ATF1(6), BRAF(12), CAMP(1), CREB1(5), CREB3(2), CREB5(6), CREBBP(37), CRKL(5), DAG1(7), EGR1(8), EGR2(8), EGR3(9), ELK1(2), FRS2(7), JUN(1), MAP1B(42), MAP2K4(6), MAPK1(2), MAPK10(9), MAPK3(4), MAPK8(7), MAPK8IP1(5), MAPK9(7), NTRK1(11), OPN1LW(4), PIK3C2G(22), PIK3CA(138), PIK3CD(10), PIK3R1(67), PTPN11(8), RPS6KA3(17), SHC1(11), SRC(2), TERF2IP(4) 16072989 509 169 412 99 136 160 92 25 78 18 2.78e-15 4.56e-14 36 ERK5PATHWAY Signaling between a tissue and its innervating axon stimulates retrograde transport via Trk receptors, which activate Erk5, which induces transcription of anti-apoptotic factors. AKT1, CREB1, GRB2, HRAS, MAPK1, MAPK3, MAPK7, MEF2A, MEF2B, MEF2C, MEF2D, NTRK1, PIK3CA, PIK3R1, PLCG1, RPS6KA1, SHC1 17 AKT1(8), CREB1(5), GRB2(3), MAPK1(2), MAPK3(4), MAPK7(17), MEF2A(5), MEF2B(3), MEF2C(11), MEF2D(7), NTRK1(11), PIK3CA(138), PIK3R1(67), PLCG1(12), RPS6KA1(5), SHC1(11) 6538323 309 166 212 34 75 88 66 16 53 11 2.78e-15 4.56e-14 37 HSA04916_MELANOGENESIS Genes involved in melanogenesis ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ASIP, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CREB1, CREB3, CREB3L1, CREB3L2, CREB3L3, CREB3L4, CREBBP, CTNNB1, DCT, DVL1, DVL2, DVL3, EDN1, EDNRB, EP300, FZD1, FZD10, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, GNAI1, GNAI2, GNAI3, GNAO1, GNAQ, GNAS, GSK3B, HRAS, KIT, KITLG, KRAS, LEF1, LOC652788, MAP2K1, MAP2K2, MAPK1, MAPK3, MC1R, MITF, NRAS, PLCB1, PLCB2, PLCB3, PLCB4, POMC, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, RAF1, TCF7, TCF7L1, TCF7L2, TYR, TYRP1, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B 95 ADCY1(17), ADCY2(17), ADCY3(8), ADCY4(8), ADCY5(11), ADCY6(16), ADCY7(6), ADCY8(16), ADCY9(25), CALM2(3), CALM3(1), CALML6(4), CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), CREB1(5), CREB3(2), CREB3L1(6), CREB3L2(8), CREB3L3(9), CREB3L4(8), CREBBP(37), CTNNB1(66), DCT(15), DVL2(12), DVL3(7), EDN1(2), EDNRB(2), EP300(29), FZD1(2), FZD10(7), FZD2(6), FZD3(7), FZD4(4), FZD6(15), FZD7(5), FZD9(7), GNAI1(4), GNAI2(7), GNAI3(3), GNAO1(5), GNAS(25), GSK3B(11), KIT(28), KITLG(2), KRAS(29), LEF1(9), MAP2K1(2), MAPK1(2), MAPK3(4), MITF(3), NRAS(10), PLCB1(6), PLCB2(9), PLCB3(9), PLCB4(20), POMC(2), PRKACA(4), PRKACB(2), PRKACG(6), PRKCA(10), PRKCG(10), PRKX(4), RAF1(7), TCF7(4), TCF7L1(5), TCF7L2(18), TYR(10), TYRP1(6), WNT1(1), WNT10A(4), WNT10B(1), WNT11(4), WNT16(6), WNT2(4), WNT2B(9), WNT3(5), WNT4(4), WNT5A(9), WNT5B(4), WNT7A(2), WNT7B(1), WNT8A(1), WNT8B(4), WNT9A(1), WNT9B(1) 34969763 755 152 664 244 205 298 111 52 87 2 2.78e-15 4.56e-14 38 HSA04910_INSULIN_SIGNALING_PATHWAY Genes involved in insulin signaling pathway ACACA, ACACB, AKT1, AKT2, AKT3, ARAF, BAD, BRAF, CALM1, CALM2, CALM3, CALML3, CALML6, CBL, CBLB, CBLC, CRK, CRKL, EIF4EBP1, ELK1, EXOC7, FASN, FBP1, FBP2, FLOT1, FLOT2, FOXO1, FRAP1, G6PC, G6PC2, GCK, GRB2, GSK3B, GYS1, GYS2, HRAS, IKBKB, INPP5D, INS, INSR, IRS1, IRS2, IRS4, KIAA1303, KRAS, LIPE, MAP2K1, MAP2K2, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MKNK1, MKNK2, NRAS, PCK1, PCK2, PDE3A, PDE3B, PDPK1, PFKL, PFKM, PFKP, PHKA1, PHKA2, PHKB, PHKG1, PHKG2, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PKLR, PKM2, PPARGC1A, PPP1CA, PPP1CB, PPP1CC, PPP1R3A, PPP1R3B, PPP1R3C, PPP1R3D, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKACA, PRKACB, PRKACG, PRKAG1, PRKAG2, PRKAG3, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCI, PRKCZ, PRKX, PRKY, PTPN1, PTPRF, PYGB, PYGL, PYGM, RAF1, RAPGEF1, RHEB, RHOQ, RPS6, RPS6KB1, RPS6KB2, SH2B2, SHC1, SHC2, SHC3, SHC4, SKIP, SLC2A4, SOCS1, SOCS2, SOCS3, SOCS4, SORBS1, SOS1, SOS2, SREBF1, TRIP10, TSC1, TSC2 123 ACACA(27), ACACB(31), AKT1(8), AKT2(4), AKT3(8), ARAF(8), BAD(2), BRAF(12), CALM2(3), CALM3(1), CALML6(4), CBL(10), CBLB(15), CBLC(5), CRK(1), CRKL(5), ELK1(2), EXOC7(8), FBP1(4), FLOT1(1), FLOT2(3), FOXO1(11), G6PC(6), G6PC2(9), GCK(5), GRB2(3), GSK3B(11), GYS1(12), GYS2(19), IKBKB(15), INPP5D(14), INSR(18), IRS1(17), IRS4(20), KRAS(29), LIPE(7), MAP2K1(2), MAPK1(2), MAPK10(9), MAPK3(4), MAPK8(7), MAPK9(7), MKNK1(6), MKNK2(4), NRAS(10), PCK1(15), PCK2(7), PDE3A(17), PDE3B(15), PDPK1(3), PFKM(7), PFKP(11), PHKA1(17), PHKA2(15), PHKB(14), PHKG1(6), PHKG2(3), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PKLR(10), PKM2(5), PPARGC1A(13), PPP1CA(6), PPP1CB(7), PPP1CC(2), PPP1R3A(23), PPP1R3B(3), PPP1R3C(3), PRKAA1(6), PRKAA2(9), PRKAB1(7), PRKAB2(2), PRKACA(4), PRKACB(2), PRKACG(6), PRKAG1(2), PRKAG2(4), PRKAG3(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PRKCI(8), PRKCZ(4), PRKX(4), PTPN1(4), PTPRF(34), PYGB(10), PYGL(9), PYGM(10), RAF1(7), RAPGEF1(18), RHEB(2), RHOQ(1), RPS6(6), RPS6KB1(3), RPS6KB2(6), SH2B2(2), SHC1(11), SHC3(9), SHC4(7), SLC2A4(4), SOCS2(7), SOCS4(4), SORBS1(22), SOS1(21), SOS2(22), SREBF1(6), TRIP10(6), TSC1(13), TSC2(14) 50888597 1233 195 1088 286 324 456 197 55 176 25 2.89e-15 4.56e-14 39 G1PATHWAY CDK4/6-cyclin D and CDK2-cyclin E phosphorylate Rb, which allows the transcription of genes needed for the G1/S cell cycle transition. ABL1, ATM, ATR, CCNA1, CCND1, CCNE1, CDC2, CDC25A, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, DHFR, E2F1, GSK3B, HDAC1, MADH3, MADH4, RB1, SKP2, TFDP1, TGFB1, TGFB2, TGFB3, TP53 24 ABL1(9), ATM(54), ATR(38), CCNA1(4), CCND1(10), CDC25A(9), CDK2(5), CDK4(4), CDK6(3), CDKN1A(1), CDKN1B(5), CDKN2A(1), DHFR(3), E2F1(12), GSK3B(11), HDAC1(4), RB1(31), SKP2(6), TGFB1(4), TGFB2(6), TGFB3(9), TP53(40) 10496163 269 92 251 55 53 95 40 12 57 12 2.89e-15 4.56e-14 40 TIDPATHWAY On ligand binding, interferon gamma receptors stimulate JAK2 kinase to phosphorylate STAT transcription factors, which promote expression of interferon responsive genes. DNAJA3, HSPA1A, IFNG, IFNGR1, IFNGR2, IKBKB, JAK2, LIN7A, NFKB1, NFKBIA, RB1, RELA, TIP-1, TNF, TNFRSF1A, TNFRSF1B, TP53, USH1C, WT1 17 DNAJA3(7), IFNG(5), IFNGR1(6), IFNGR2(4), IKBKB(15), JAK2(21), LIN7A(8), NFKB1(12), NFKBIA(3), RB1(31), RELA(6), TNF(1), TNFRSF1A(6), TNFRSF1B(3), TP53(40), USH1C(10), WT1(3) 6203006 181 72 168 44 37 56 34 10 34 10 3.11e-15 4.66e-14 41 TERTPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. HDAC1, MAX, MYC, SP1, SP3, TP53, WT1, ZNF42 7 HDAC1(4), MAX(8), MYC(7), SP1(6), SP3(12), TP53(40), WT1(3) 2433020 80 53 68 12 19 29 11 4 15 2 3.11e-15 4.66e-14 42 APOPTOSIS_GENMAPP APAF1, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, FADD, FAS, FASLG, GZMB, IKBKG, JUN, MAP2K4, MAP3K1, MAP3K14, MAPK10, MCL1, MDM2, MYC, NFKB1, NFKBIA, PARP1, PRF1, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TNFSF10, TP53, TRADD, TRAF1, TRAF2 40 APAF1(19), BAK1(4), BAX(4), BCL2L1(3), BID(3), BIRC2(13), BIRC3(3), CASP2(9), CASP3(4), CASP6(4), CASP7(4), CASP8(21), CASP9(3), CYCS(3), FADD(1), FAS(7), FASLG(6), GZMB(2), JUN(1), MAP2K4(6), MAP3K1(31), MAP3K14(12), MAPK10(9), MCL1(1), MDM2(6), MYC(7), NFKB1(12), NFKBIA(3), PARP1(11), PRF1(8), RELA(6), RIPK1(8), TNF(1), TNFRSF1A(6), TNFRSF1B(3), TNFSF10(1), TP53(40), TRAF1(5), TRAF2(5) 12750650 295 91 278 69 70 100 46 23 52 4 3.22e-15 4.66e-14 43 FCER1PATHWAY In mast cells, Fc epsilon receptor 1 activates BTK, PKC, and the MAP kinase pathway to promote degranulation and arachnidonic acid release. BTK, CALM1, CALM2, CALM3, ELK1, FCER1A, FCER1G, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP2K4, MAP2K7, MAP3K1, MAPK1, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, PAK2, PIK3CA, PIK3R1, PLA2G4A, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCB1, RAF1, SHC1, SOS1, SYK, SYT1, VAV1 36 BTK(11), CALM2(3), CALM3(1), ELK1(2), FCER1A(6), FCER1G(1), FOS(6), GRB2(3), JUN(1), LYN(7), MAP2K1(2), MAP2K4(6), MAP3K1(31), MAPK1(2), MAPK3(4), MAPK8(7), NFATC2(15), NFATC3(12), NFATC4(8), PAK2(6), PIK3CA(138), PIK3R1(67), PLA2G4A(11), PLCG1(12), PPP3CA(4), PPP3CB(7), PPP3CC(6), RAF1(7), SHC1(11), SOS1(21), SYK(6), SYT1(4), VAV1(16) 14521640 444 166 347 68 127 116 87 25 72 17 3.33e-15 4.66e-14 44 BADPATHWAY When phosphorylated, BAD is inhibited by sequestration; when non-phosphorylated, it promotes apoptosis by inactivating pro-survival BCL-XL and BCL-2. ADCY1, AKT1, BAD, BAX, BCL2, BCL2L1, CSF2RB, IGF1, IGF1R, IL3, IL3RA, KIT, KITLG, PIK3CA, PIK3R1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, YWHAH 22 ADCY1(17), AKT1(8), BAD(2), BAX(4), BCL2L1(3), CSF2RB(11), IGF1(3), IGF1R(13), IL3RA(11), KIT(28), KITLG(2), PIK3CA(138), PIK3R1(67), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), YWHAH(4) 7329891 340 165 245 47 86 97 70 21 53 13 3.33e-15 4.66e-14 45 ARFPATHWAY Cyclin-dependent kinase inhibitor 2A is a tumor suppressor that induces G1 arrest and can activate the p53 pathway, leading to G2/M arrest. ABL1, CDKN2A, E2F1, MDM2, MYC, PIK3CA, PIK3R1, POLR1A, POLR1B, POLR1C, POLR1D, RAC1, RB1, TBX2, TP53, TWIST1 15 ABL1(9), CDKN2A(1), E2F1(12), MDM2(6), MYC(7), PIK3CA(138), PIK3R1(67), POLR1A(15), POLR1B(16), POLR1C(4), POLR1D(2), RB1(31), TBX2(4), TP53(40) 7008436 352 168 249 48 91 84 72 24 66 15 4.00e-15 5.24e-14 46 HSA04010_MAPK_SIGNALING_PATHWAY Genes involved in MAPK signaling pathway ACVR1B, ACVR1C, AKT1, AKT2, AKT3, ARRB1, ARRB2, ATF2, ATF4, BDNF, BRAF, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, CACNA1I, CACNA1S, CACNA2D1, CACNA2D2, CACNA2D3, CACNA2D4, CACNB1, CACNB2, CACNB3, CACNB4, CACNG1, CACNG2, CACNG3, CACNG4, CACNG5, CACNG6, CACNG7, CACNG8, CASP3, CD14, CDC25B, CDC42, CHP, CHUK, CRK, CRKL, DAXX, DDIT3, DUSP1, DUSP10, DUSP14, DUSP16, DUSP2, DUSP3, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8, DUSP9, ECSIT, EGF, EGFR, ELK1, ELK4, EVI1, FAS, FASLG, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14, FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FLNA, FLNB, FLNC, FOS, GADD45A, GADD45B, GADD45G, GNA12, GNG12, GRB2, HRAS, IKBKB, IKBKG, IL1A, IL1B, IL1R1, IL1R2, JUN, JUND, KRAS, LOC653852, MAP2K1, MAP2K1IP1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K10, MAP3K12, MAP3K13, MAP3K14, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K8, MAP4K1, MAP4K2, MAP4K3, MAP4K4, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK7, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MAPKAPK2, MAPKAPK3, MAPKAPK5, MAPT, MAX, MEF2C, MKNK1, MKNK2, MOS, MRAS, MYC, NF1, NFATC2, NFATC4, NFKB1, NFKB2, NGFB, NLK, NR4A1, NRAS, NTF3, NTF5, NTRK1, NTRK2, PAK1, PAK2, PDGFA, PDGFB, PDGFRA, PDGFRB, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PPM1A, PPM1B, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PPP5C, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PTPN5, PTPN7, PTPRR, RAC1, RAC2, RAC3, RAF1, RAP1A, RAP1B, RAPGEF2, RASA1, RASA2, RASGRF1, RASGRF2, RASGRP1, RASGRP2, RASGRP3, RASGRP4, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KA5, RPS6KA6, RRAS, RRAS2, SOS1, SOS2, SRF, STK3, STK4, STMN1, TAOK1, TAOK2, TAOK3, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TNF, TNFRSF1A, TP53, TRAF2, TRAF6, ZAK 231 ACVR1B(6), ACVR1C(7), AKT1(8), AKT2(4), AKT3(8), ARRB1(7), ARRB2(3), ATF2(6), ATF4(4), BDNF(8), BRAF(12), CACNA1A(19), CACNA1B(1), CACNA1C(30), CACNA1D(34), CACNA1E(47), CACNA1F(36), CACNA1G(20), CACNA1I(13), CACNA1S(33), CACNA2D1(14), CACNA2D2(9), CACNA2D3(20), CACNA2D4(18), CACNB1(9), CACNB2(11), CACNB3(6), CACNB4(14), CACNG2(3), CACNG3(9), CACNG4(6), CACNG5(4), CACNG6(6), CACNG7(10), CASP3(4), CD14(2), CDC25B(3), CDC42(5), CHUK(11), CRK(1), CRKL(5), DAXX(11), DDIT3(1), DUSP1(2), DUSP10(7), DUSP14(3), DUSP16(13), DUSP2(4), DUSP3(2), DUSP4(1), DUSP5(5), DUSP6(1), DUSP7(4), DUSP9(8), ECSIT(5), EGF(24), EGFR(20), ELK1(2), ELK4(3), FAS(7), FASLG(6), FGF1(1), FGF10(1), FGF11(2), FGF12(4), FGF13(6), FGF14(3), FGF16(1), FGF17(1), FGF18(2), FGF21(3), FGF23(6), FGF5(8), FGF6(2), FGF7(6), FGF8(2), FGF9(2), FGFR1(10), FGFR2(27), FGFR4(11), FLNA(31), FLNB(38), FLNC(34), FOS(6), GNA12(10), GNG12(2), GRB2(3), IKBKB(15), IL1A(1), IL1B(2), IL1R1(5), IL1R2(7), JUN(1), KRAS(29), MAP2K1(2), MAP2K3(8), MAP2K4(6), MAP2K5(2), MAP2K6(9), MAP3K1(31), MAP3K10(7), MAP3K12(8), MAP3K13(13), MAP3K14(12), MAP3K2(8), MAP3K3(9), MAP3K4(23), MAP3K5(21), MAP3K6(7), MAP3K7(8), MAP3K8(12), MAP4K1(13), MAP4K2(6), MAP4K3(21), MAP4K4(14), MAPK1(2), MAPK10(9), MAPK13(2), MAPK14(6), MAPK3(4), MAPK7(17), MAPK8(7), MAPK8IP1(5), MAPK9(7), MAPKAPK2(6), MAPKAPK3(4), MAPKAPK5(6), MAPT(11), MAX(8), MEF2C(11), MKNK1(6), MKNK2(4), MOS(8), MRAS(3), MYC(7), NF1(40), NFATC2(15), NFATC4(8), NFKB1(12), NFKB2(10), NLK(5), NR4A1(4), NRAS(10), NTF3(6), NTRK1(11), NTRK2(15), PAK1(3), PAK2(6), PDGFB(4), PDGFRA(29), PDGFRB(12), PLA2G10(1), PLA2G12A(1), PLA2G12B(3), PLA2G1B(1), PLA2G2D(2), PLA2G2E(3), PLA2G2F(3), PLA2G3(5), PLA2G4A(11), PLA2G5(2), PLA2G6(6), PPM1A(7), PPM1B(6), PPP3CA(4), PPP3CB(7), PPP3CC(6), PPP3R1(2), PPP3R2(1), PPP5C(7), PRKACA(4), PRKACB(2), PRKACG(6), PRKCA(10), PRKCG(10), PRKX(4), PTPN5(5), PTPN7(5), PTPRR(18), RAC2(2), RAF1(7), RAP1A(3), RAP1B(2), RAPGEF2(38), RASA1(29), RASA2(8), RASGRF1(13), RASGRF2(17), RASGRP1(8), RASGRP2(5), RASGRP3(8), RASGRP4(7), RPS6KA1(5), RPS6KA2(16), RPS6KA3(17), RPS6KA4(5), RPS6KA5(7), RPS6KA6(15), RRAS(1), RRAS2(5), SOS1(21), SOS2(22), SRF(3), STK3(9), STK4(6), STMN1(6), TAOK1(10), TAOK2(10), TAOK3(4), TGFB1(4), TGFB2(6), TGFB3(9), TGFBR1(8), TGFBR2(6), TNF(1), TNFRSF1A(6), TP53(40), TRAF2(5), TRAF6(4), ZAK(12) 95420750 2002 170 1898 575 552 765 258 131 270 26 4.11e-15 5.24e-14 47 IL7PATHWAY IL-7 is required for B and T cell development and proliferation and may contribute to activation of VDJ recombination. BCL2, CREBBP, EP300, FYN, IL2RG, IL7, IL7R, JAK1, JAK3, LCK, NMI, PIK3CA, PIK3R1, PTK2B, STAT5A, STAT5B 16 CREBBP(37), EP300(29), FYN(7), IL2RG(11), IL7(2), IL7R(9), JAK1(31), JAK3(9), LCK(5), NMI(1), PIK3CA(138), PIK3R1(67), PTK2B(16), STAT5A(5), STAT5B(5) 9637675 372 163 274 55 96 96 75 20 68 17 4.22e-15 5.24e-14 48 HSA04670_LEUKOCYTE_TRANSENDOTHELIAL_MIGRATION Genes involved in Leukocyte transendothelial migration ACTN1, ACTN2, ACTN3, ACTN4, ARHGAP5, BCAR1, CD99, CDC42, CDH5, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTNND1, CXCL12, CXCR4, CYBA, CYBB, ESAM, EZR, F11R, GNAI1, GNAI2, GNAI3, GRLF1, ICAM1, ITGA4, ITGAL, ITGAM, ITGB1, ITGB2, ITK, JAM2, JAM3, MAPK11, MAPK12, MAPK13, MAPK14, MLLT4, MMP2, MMP9, MRCL3, MRLC2, MSN, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLPF, NCF1, NCF2, NCF4, NOX1, NOX3, OCLN, PECAM1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCG, PTK2, PTK2B, PTPN11, PXN, RAC1, RAC2, RAP1A, RAP1B, RAPGEF3, RAPGEF4, RASSF5, RHOA, RHOH, ROCK1, ROCK2, SIPA1, THY1, TXK, VASP, VAV1, VAV2, VAV3, VCAM1, VCL 103 ACTN1(13), ACTN2(9), ACTN3(10), ACTN4(11), ARHGAP5(24), CD99(2), CDC42(5), CDH5(9), CLDN1(2), CLDN10(9), CLDN11(1), CLDN15(4), CLDN16(6), CLDN17(2), CLDN18(4), CLDN19(2), CLDN2(4), CLDN20(4), CLDN22(3), CLDN6(1), CLDN7(1), CLDN8(5), CLDN9(2), CTNNA1(18), CTNNA2(13), CTNNA3(13), CTNNB1(66), CTNND1(22), CXCL12(3), CXCR4(1), CYBB(12), ESAM(1), EZR(6), F11R(2), GNAI1(4), GNAI2(7), GNAI3(3), ICAM1(3), ITGA4(12), ITGAL(13), ITGAM(24), ITGB1(12), ITGB2(14), ITK(10), JAM2(9), JAM3(3), MAPK13(2), MAPK14(6), MLLT4(32), MMP2(11), MMP9(14), MSN(15), MYL2(1), MYL5(3), MYL7(4), MYL9(3), MYLPF(2), NCF1(5), NCF2(6), NCF4(8), NOX1(11), NOX3(5), OCLN(5), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PLCG1(12), PLCG2(27), PRKCA(10), PRKCG(10), PTK2(11), PTK2B(16), PTPN11(8), PXN(6), RAC2(2), RAP1A(3), RAP1B(2), RAPGEF3(11), RAPGEF4(10), RASSF5(3), RHOA(4), RHOH(2), ROCK1(27), ROCK2(15), SIPA1(3), THY1(1), TXK(6), VASP(2), VAV1(16), VAV2(5), VAV3(13), VCAM1(9), VCL(14) 41763816 1064 194 910 272 284 385 161 61 152 21 4.44e-15 5.24e-14 49 IL2RBPATHWAY The beta subunit of the IL-2 receptor is required for IL-2 and IL-15 signal recognition and activates JAK kinase on ligand binding. AKT1, BAD, BCL2, BCL2L1, CBL, CFLAR, CRKL, E2F1, FOS, GRB2, HRAS, IL2RA, IL2RB, IL2RG, IRS1, JAK1, JAK3, MAPK1, MAPK3, MYC, NMI, PIK3CA, PIK3R1, PPIA, PTPN6, RAF1, RPS6KB1, SHC1, SOCS1, SOCS3, SOS1, STAT5A, STAT5B, SYK, TNFRSF6, TNFSF6, ZNFN1A3 33 AKT1(8), BAD(2), BCL2L1(3), CBL(10), CFLAR(7), CRKL(5), E2F1(12), FOS(6), GRB2(3), IL2RA(3), IL2RB(6), IL2RG(11), IRS1(17), JAK1(31), JAK3(9), MAPK1(2), MAPK3(4), MYC(7), NMI(1), PIK3CA(138), PIK3R1(67), PPIA(2), RAF1(7), RPS6KB1(3), SHC1(11), SOS1(21), STAT5A(5), STAT5B(5), SYK(6) 12455485 412 169 309 48 102 127 76 22 66 19 4.55e-15 5.24e-14 50 WNT_SIGNALING Wnt signaling genes APC, ARHA, AXIN1, C2orf31, CCND1, CCND2, CCND3, CSNK1E, CSNK1E, LOC400927, CTNNB1, DIPA, DVL1, DVL2, DVL3, FBXW2, FOSL1, FRAT1, FZD1, FZD10, FZD2, FZD3, FZD5, FZD6, FZD7, FZD8, FZD9, GSK3B, JUN, LDLR, MAPK10, MAPK9, MYC, PAFAH1B1, PLAU, PPP2R5C, PPP2R5E, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCM, PRKCQ, PRKCZ, PRKD1, RAC1, RHOA, SFRP4, TCF7, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B 55 APC(53), AXIN1(8), CCND1(10), CCND2(7), CCND3(5), CSNK1E(10), CTNNB1(66), DVL2(12), DVL3(7), FBXW2(3), FOSL1(4), FZD1(2), FZD10(7), FZD2(6), FZD3(7), FZD6(15), FZD7(5), FZD9(7), GSK3B(11), JUN(1), LDLR(12), MAPK10(9), MAPK9(7), MYC(7), PAFAH1B1(1), PLAU(5), PPP2R5C(6), PPP2R5E(7), PRKCA(10), PRKCD(7), PRKCE(11), PRKCG(10), PRKCH(9), PRKCI(8), PRKCQ(13), PRKCZ(4), PRKD1(8), RHOA(4), SFRP4(10), TCF7(4), WNT1(1), WNT10A(4), WNT10B(1), WNT11(4), WNT16(6), WNT2(4), WNT2B(9), WNT3(5), WNT4(4), WNT5A(9), WNT5B(4), WNT7A(2), WNT7B(1) 18913504 452 127 394 137 130 171 60 36 45 10 4.55e-15 5.24e-14 51 CREBPATHWAY CREB is a transcription factor that binds to cAMP-responsive elements (CREs) to activate transcription in response to extracellular signaling. ADCY1, AKT1, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CREB1, GNAS, GRB2, HRAS, MAPK1, MAPK14, MAPK3, PIK3CA, PIK3R1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, RAC1, RPS6KA1, RPS6KA5, SOS1 26 ADCY1(17), AKT1(8), CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), CREB1(5), GNAS(25), GRB2(3), MAPK1(2), MAPK14(6), MAPK3(4), PIK3CA(138), PIK3R1(67), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PRKCA(10), RPS6KA1(5), RPS6KA5(7), SOS1(21) 9587963 372 166 273 45 87 111 74 23 62 15 4.77e-15 5.24e-14 52 HSA04012_ERBB_SIGNALING_PATHWAY Genes involved in ErbB signaling pathway ABL1, ABL2, AKT1, AKT2, AKT3, ARAF, AREG, BAD, BRAF, BTC, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CBL, CBLB, CBLC, CDKN1A, CDKN1B, CRK, CRKL, EGF, EGFR, EIF4EBP1, ELK1, ERBB2, ERBB3, ERBB4, EREG, FRAP1, GAB1, GRB2, GSK3B, HBEGF, HRAS, JUN, KRAS, MAP2K1, MAP2K2, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MYC, NCK1, NCK2, NRAS, NRG1, NRG2, NRG3, NRG4, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCG, PTK2, RAF1, RPS6KB1, RPS6KB2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SRC, STAT5A, STAT5B, TGFA 82 ABL1(9), ABL2(19), AKT1(8), AKT2(4), AKT3(8), ARAF(8), BAD(2), BRAF(12), BTC(5), CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), CBL(10), CBLB(15), CBLC(5), CDKN1A(1), CDKN1B(5), CRK(1), CRKL(5), EGF(24), EGFR(20), ELK1(2), ERBB2(6), ERBB3(16), ERBB4(29), EREG(4), GAB1(10), GRB2(3), GSK3B(11), HBEGF(3), JUN(1), KRAS(29), MAP2K1(2), MAP2K4(6), MAPK1(2), MAPK10(9), MAPK3(4), MAPK8(7), MAPK9(7), MYC(7), NCK1(4), NCK2(8), NRAS(10), NRG1(25), NRG2(6), NRG3(15), PAK1(3), PAK2(6), PAK3(14), PAK4(2), PAK6(3), PAK7(12), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PLCG1(12), PLCG2(27), PRKCA(10), PRKCG(10), PTK2(11), RAF1(7), RPS6KB1(3), RPS6KB2(6), SHC1(11), SHC3(9), SHC4(7), SOS1(21), SOS2(22), SRC(2), STAT5A(5), STAT5B(5), TGFA(3) 34252763 902 182 771 169 241 306 163 50 123 19 5.11e-15 5.24e-14 53 HSA04020_CALCIUM_SIGNALING_PATHWAY Genes involved in calcium signaling pathway ADCY1, ADCY2, ADCY3, ADCY4, ADCY7, ADCY8, ADCY9, ADORA2A, ADORA2B, ADRA1A, ADRA1B, ADRA1D, ADRB1, ADRB2, ADRB3, AGTR1, ATP2A1, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, ATP2B4, AVPR1A, AVPR1B, BDKRB1, BDKRB2, BST1, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, CACNA1I, CACNA1S, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CCKAR, CCKBR, CD38, CHP, CHRM1, CHRM2, CHRM3, CHRM5, CHRNA7, CYSLTR1, CYSLTR2, DRD1, EDNRA, EDNRB, EGFR, ERBB2, ERBB3, ERBB4, F2R, GNA11, GNA14, GNA15, GNAL, GNAQ, GNAS, GRIN1, GRIN2A, GRIN2C, GRIN2D, GRM1, GRM5, GRPR, HRH1, HRH2, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, LHCGR, LTB4R2, MLCK, MYLK, MYLK2, NOS1, NOS2A, NOS3, NTSR1, OXTR, P2RX1, P2RX2, P2RX3, P2RX4, P2RX5, P2RX7, P2RXL1, PDE1A, PDE1B, PDE1C, PDGFRA, PDGFRB, PHKA1, PHKA2, PHKB, PHKG1, PHKG2, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCZ1, PLN, PPID, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PTAFR, PTGER1, PTGER3, PTGFR, PTK2B, RYR1, RYR2, RYR3, SLC25A4, SLC25A5, SLC25A6, SLC8A1, SLC8A2, SLC8A3, SPHK1, SPHK2, TACR1, TACR2, TACR3, TBXA2R, TNNC1, TNNC2, TRHR, TRPC1, VDAC1, VDAC2, VDAC3 163 ADCY1(17), ADCY2(17), ADCY3(8), ADCY4(8), ADCY7(6), ADCY8(16), ADCY9(25), ADORA2A(5), ADORA2B(2), ADRA1A(11), ADRA1B(7), ADRB1(2), ADRB2(8), ATP2A1(16), ATP2A2(9), ATP2A3(12), ATP2B1(17), ATP2B2(12), ATP2B3(21), ATP2B4(18), AVPR1A(8), AVPR1B(3), BDKRB1(5), BDKRB2(9), BST1(5), CACNA1A(19), CACNA1B(1), CACNA1C(30), CACNA1D(34), CACNA1E(47), CACNA1F(36), CACNA1G(20), CACNA1I(13), CACNA1S(33), CALM2(3), CALM3(1), CALML6(4), CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), CAMK4(5), CCKAR(12), CCKBR(7), CD38(7), CHRM1(6), CHRM2(9), CHRM3(9), CHRM5(13), CHRNA7(6), CYSLTR1(5), CYSLTR2(6), DRD1(6), EDNRA(6), EDNRB(2), EGFR(20), ERBB2(6), ERBB3(16), ERBB4(29), F2R(8), GNA11(3), GNA14(5), GNA15(1), GNAL(6), GNAS(25), GRIN1(5), GRIN2A(25), GRIN2C(6), GRIN2D(8), GRM1(22), GRM5(22), GRPR(4), HRH1(9), HRH2(3), HTR2A(15), HTR2B(2), HTR2C(18), HTR4(7), HTR5A(9), HTR6(4), HTR7(4), ITPKB(6), ITPR1(31), ITPR2(38), ITPR3(23), LHCGR(16), LTB4R2(3), MYLK(17), MYLK2(7), NOS1(21), NOS3(11), NTSR1(4), OXTR(4), P2RX1(9), P2RX3(9), P2RX4(2), P2RX5(8), P2RX7(3), PDE1A(12), PDE1B(9), PDE1C(14), PDGFRA(29), PDGFRB(12), PHKA1(17), PHKA2(15), PHKB(14), PHKG1(6), PHKG2(3), PLCB1(6), PLCB2(9), PLCB3(9), PLCB4(20), PLCD1(5), PLCD3(7), PLCD4(13), PLCE1(36), PLCG1(12), PLCG2(27), PLCZ1(16), PLN(1), PPID(6), PPP3CA(4), PPP3CB(7), PPP3CC(6), PPP3R1(2), PPP3R2(1), PRKACA(4), PRKACB(2), PRKACG(6), PRKCA(10), PRKCG(10), PRKX(4), PTAFR(6), PTGER3(9), PTGFR(10), PTK2B(16), RYR1(80), RYR2(111), RYR3(87), SLC25A4(3), SLC25A5(4), SLC25A6(6), SLC8A1(20), SLC8A2(6), SLC8A3(14), SPHK1(2), SPHK2(1), TACR1(6), TACR2(4), TACR3(9), TNNC1(2), TNNC2(4), TRHR(5), TRPC1(15), VDAC1(2), VDAC3(4) 91936847 1906 151 1852 660 552 781 263 95 192 23 5.11e-15 5.24e-14 54 HSA05131_PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EPEC Genes involved in pathogenic Escherichia coli infection - EPEC ABL1, ACTB, ACTG1, ARHGEF2, ARPC5, ARPC5L, CD14, CDC42, CDH1, CLDN1, CTNNB1, CTTN, EZR, FYN, HCLS1, ITGB1, KRT18, LOC643224, LOC654264, LY96, NCK1, NCK2, NCL, OCLN, PRKCA, RHOA, ROCK1, ROCK2, TLR4, TLR5, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8, WAS, WASL, YWHAQ, YWHAZ 51 ABL1(9), ACTB(5), ARHGEF2(10), ARPC5(1), CD14(2), CDC42(5), CDH1(15), CLDN1(2), CTNNB1(66), CTTN(8), EZR(6), FYN(7), HCLS1(8), ITGB1(12), LY96(4), NCK1(4), NCK2(8), NCL(2), OCLN(5), PRKCA(10), RHOA(4), ROCK1(27), ROCK2(15), TLR4(14), TLR5(8), TUBA1A(5), TUBA1B(4), TUBA1C(9), TUBA3C(7), TUBA3D(5), TUBA3E(15), TUBA4A(7), TUBA8(11), TUBAL3(5), TUBB1(8), TUBB2A(4), TUBB2B(2), TUBB2C(1), TUBB4(9), TUBB4Q(4), TUBB6(4), TUBB8(3), WAS(14), WASL(8), YWHAQ(3), YWHAZ(1) 18644629 386 114 336 97 91 175 37 24 57 2 5.11e-15 5.24e-14 55 ATMPATHWAY The tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair. ABL1, ATM, BRCA1, CDKN1A, CHEK1, CHEK2, GADD45A, JUN, MAPK8, MDM2, MRE11A, NBS1, NFKB1, NFKBIA, RAD50, RAD51, RBBP8, RELA, TP53, TP73 18 ABL1(9), ATM(54), BRCA1(19), CDKN1A(1), CHEK1(4), CHEK2(14), JUN(1), MAPK8(7), MDM2(6), MRE11A(12), NFKB1(12), NFKBIA(3), RAD50(19), RAD51(4), RBBP8(10), RELA(6), TP53(40) 10230395 221 81 204 42 37 76 38 13 51 6 5.11e-15 5.24e-14 56 HSA04662_B_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in B cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, BLNK, BTK, CARD11, CD19, CD22, CD72, CD79A, CD79B, CD81, CHP, CHUK, CR2, FCGR2B, FOS, GSK3B, HRAS, IFITM1, IKBKB, IKBKG, INPP5D, JUN, KRAS, LILRB3, LYN, MALT1, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCB1, PTPN6, RAC1, RAC2, RAC3, RASGRP3, SYK, VAV1, VAV2, VAV3 60 AKT1(8), AKT2(4), AKT3(8), BCL10(2), BLNK(4), BTK(11), CARD11(16), CD19(7), CD22(13), CD72(3), CD79A(1), CD79B(2), CHUK(11), CR2(28), FCGR2B(4), FOS(6), GSK3B(11), IKBKB(15), INPP5D(14), JUN(1), KRAS(29), LILRB3(2), LYN(7), MALT1(4), NFAT5(13), NFATC2(15), NFATC3(12), NFATC4(8), NFKB1(12), NFKB2(10), NFKBIA(3), NFKBIB(3), NFKBIE(6), NRAS(10), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PLCG2(27), PPP3CA(4), PPP3CB(7), PPP3CC(6), PPP3R1(2), PPP3R2(1), RAC2(2), RASGRP3(8), SYK(6), VAV1(16), VAV2(5), VAV3(13) 24626799 679 177 554 151 194 216 128 32 96 13 5.22e-15 5.24e-14 57 SA_G1_AND_S_PHASES Cdk2, 4, and 6 bind cyclin D in G1, while cdk2/cyclin E promotes the G1/S transition. ARF1, ARF3, CCND1, CDK2, CDK4, CDKN1A, CDKN1B, CDKN2A, CFL1, E2F1, E2F2, MDM2, NXT1, PRB1, TP53 15 ARF1(4), ARF3(2), CCND1(10), CDK2(5), CDK4(4), CDKN1A(1), CDKN1B(5), CDKN2A(1), CFL1(1), E2F1(12), E2F2(1), MDM2(6), PRB1(4), TP53(40) 2760211 96 61 83 20 23 30 14 9 20 0 5.33e-15 5.24e-14 58 PDGFPATHWAY Platelet-derived growth factor (PDGF) receptor is phosphorylated on ligand binding and promotes cell proliferation. CSNK2A1, ELK1, FOS, GRB2, HRAS, JAK1, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, PDGFA, PDGFRA, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, SRF, STAT1, STAT3, STAT5A 25 CSNK2A1(9), ELK1(2), FOS(6), GRB2(3), JAK1(31), JUN(1), MAP2K1(2), MAP2K4(6), MAP3K1(31), MAPK3(4), MAPK8(7), PDGFRA(29), PIK3CA(138), PIK3R1(67), PLCG1(12), PRKCA(10), RAF1(7), RASA1(29), SHC1(11), SOS1(21), SRF(3), STAT1(14), STAT3(12), STAT5A(5) 12097702 460 169 352 49 117 114 89 30 85 25 5.55e-15 5.24e-14 59 TPOPATHWAY Thrombopoietin binds to its receptor and activates cell growth through the Erk and JNK MAP kinase pathways, protein kinase C, and JAK/STAT activation. CSNK2A1, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAPK3, MPL, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, STAT1, STAT3, STAT5A, STAT5B, THPO 22 CSNK2A1(9), FOS(6), GRB2(3), JAK2(21), JUN(1), MAP2K1(2), MAPK3(4), MPL(5), PIK3CA(138), PIK3R1(67), PLCG1(12), PRKCA(10), RAF1(7), RASA1(29), SHC1(11), SOS1(21), STAT1(14), STAT3(12), STAT5A(5), STAT5B(5), THPO(11) 10505484 393 161 295 44 99 103 84 22 64 21 5.55e-15 5.24e-14 60 P53PATHWAY p53 induces cell cycle arrest or apoptosis under conditions of DNA damage. APAF1, ATM, BAX, BCL2, CCND1, CCNE1, CDK2, CDK4, CDKN1A, E2F1, GADD45A, MDM2, PCNA, RB1, TIMP3, TP53 16 APAF1(19), ATM(54), BAX(4), CCND1(10), CDK2(5), CDK4(4), CDKN1A(1), E2F1(12), MDM2(6), PCNA(3), RB1(31), TIMP3(8), TP53(40) 6289285 197 84 179 34 46 58 31 10 44 8 5.55e-15 5.24e-14 61 TELPATHWAY Telomerase is a ribonucleotide protein that adds telomeric repeats to the 3' ends of chromosomes. AKT1, BCL2, EGFR, G22P1, HSPCA, IGF1R, KRAS2, MYC, POLR2A, PPP2CA, PRKCA, RB1, TEP1, TERF1, TERT, TNKS, TP53, XRCC5 15 AKT1(8), EGFR(20), IGF1R(13), MYC(7), POLR2A(25), PPP2CA(6), PRKCA(10), RB1(31), TEP1(19), TERF1(2), TERT(6), TNKS(20), TP53(40), XRCC5(7) 9669940 214 77 196 62 53 83 27 11 36 4 5.55e-15 5.24e-14 62 EGFPATHWAY The epidermal growth factor (EGF) peptide stimulates the EGF receptor to promote cell proliferation via the MAP kinase and Ras pathways. CSNK2A1, EGF, EGFR, ELK1, FOS, GRB2, HRAS, JAK1, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, SRF, STAT1, STAT3, STAT5A 26 CSNK2A1(9), EGF(24), EGFR(20), ELK1(2), FOS(6), GRB2(3), JAK1(31), JUN(1), MAP2K1(2), MAP2K4(6), MAP3K1(31), MAPK3(4), MAPK8(7), PIK3CA(138), PIK3R1(67), PLCG1(12), PRKCA(10), RAF1(7), RASA1(29), SHC1(11), SOS1(21), SRF(3), STAT1(14), STAT3(12), STAT5A(5) 13116798 475 169 368 59 123 120 91 30 88 23 5.66e-15 5.24e-14 63 ST_INTERLEUKIN_4_PATHWAY Like IL-13, IL-4 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor. AKT1, AKT2, AKT3, CISH, GRB2, IARS, IL13RA1, IL2RG, IL4, IL4R, INPP5D, JAK1, JAK2, JAK3, NR0B2, PI3, PIK3CA, PPP1R13B, RPS6KB1, SERPINA4, SHC1, SOS1, SOS2, SRC, STAT6, TYK2 26 AKT1(8), AKT2(4), AKT3(8), GRB2(3), IARS(13), IL13RA1(14), IL2RG(11), IL4R(6), INPP5D(14), JAK1(31), JAK2(21), JAK3(9), NR0B2(2), PI3(3), PIK3CA(138), PPP1R13B(7), RPS6KB1(3), SERPINA4(8), SHC1(11), SOS1(21), SOS2(22), SRC(2), STAT6(10), TYK2(7) 12832627 376 137 283 60 94 125 78 21 42 16 5.66e-15 5.24e-14 64 PS1PATHWAY Presenilin is required for gamma-secretase activity to activate Notch signaling; presenilin also inhibits beta-catenin in the Wnt/Frizzled pathway. ADAM17, APC, AXIN1, BTRC, CTNNB1, DLL1, DVL1, FZD1, GSK3B, NOTCH1, PSEN1, RBPSUH, TCF1, WNT1 10 ADAM17(11), APC(53), AXIN1(8), BTRC(13), CTNNB1(66), DLL1(8), FZD1(2), GSK3B(11), PSEN1(4), WNT1(1) 5451112 177 98 130 41 37 78 21 20 15 6 5.66e-15 5.24e-14 65 HSA04115_P53_SIGNALING_PATHWAY Genes involved in p53 signaling pathway APAF1, ATM, ATR, BAI1, BAX, BBC3, BID, CASP3, CASP8, CASP9, CCNB1, CCNB2, CCNB3, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNG1, CCNG2, CD82, CDC2, CDK2, CDK4, CDK6, CDKN1A, CDKN2A, CHEK1, CHEK2, CYCS, DDB2, EI24, FAS, GADD45A, GADD45B, GADD45G, GTSE1, IGF1, IGFBP3, LRDD, MDM2, MDM4, P53AIP1, PERP, PMAIP1, PPM1D, PTEN, RCHY1, RFWD2, RPRM, RRM2, RRM2B, SCOTIN, SERPINB5, SERPINE1, SESN1, SESN2, SESN3, SFN, SIAH1, STEAP3, THBS1, TNFRSF10B, TP53, TP53I3, TP73, TSC2, ZMAT3 60 APAF1(19), ATM(54), ATR(38), BAI1(8), BAX(4), BID(3), CASP3(4), CASP8(21), CASP9(3), CCNB1(8), CCNB2(4), CCNB3(20), CCND1(10), CCND2(7), CCND3(5), CCNE2(6), CCNG1(6), CCNG2(4), CD82(2), CDK2(5), CDK4(4), CDK6(3), CDKN1A(1), CDKN2A(1), CHEK1(4), CHEK2(14), CYCS(3), DDB2(5), EI24(7), FAS(7), GTSE1(2), IGF1(3), IGFBP3(7), MDM2(6), MDM4(1), PERP(3), PMAIP1(1), PPM1D(14), PTEN(198), RCHY1(5), RFWD2(6), RRM2(5), RRM2B(5), SERPINB5(1), SERPINE1(5), SESN1(7), SESN2(3), SESN3(14), SIAH1(3), STEAP3(5), THBS1(12), TNFRSF10B(5), TP53(40), TP53I3(5), TSC2(14), ZMAT3(10) 20733728 660 189 560 119 106 184 124 35 181 30 5.77e-15 5.24e-14 66 GLEEVECPATHWAY The drug Gleevec specifically targets the abnormal bcr-abl protein, an apoptosis inhibitor present in chronic myeloid leukemia. AKT1, BCL2, BCR, CRKL, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, MYC, PIK3CA, PIK3R1, RAF1, SOS1, STAT1, STAT5A, STAT5B 22 AKT1(8), BCR(6), CRKL(5), FOS(6), GRB2(3), JAK2(21), JUN(1), MAP2K1(2), MAP2K4(6), MAP3K1(31), MAPK3(4), MAPK8(7), MYC(7), PIK3CA(138), PIK3R1(67), RAF1(7), SOS1(21), STAT1(14), STAT5A(5), STAT5B(5) 9536817 364 167 266 36 94 92 80 23 54 21 5.77e-15 5.24e-14 67 HSA04630_JAK_STAT_SIGNALING_PATHWAY Genes involved in Jak-STAT signaling pathway AKT1, AKT2, AKT3, BCL2L1, CBL, CBLB, CBLC, CCND1, CCND2, CCND3, CISH, CLCF1, CNTF, CNTFR, CREBBP, CRLF2, CSF2, CSF2RA, CSF2RB, CSF3, CSF3R, CTF1, EP300, EPO, EPOR, GH1, GH2, GHR, GRB2, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNE1, IFNG, IFNGR1, IFNGR2, IFNK, IFNW1, IL10, IL10RA, IL10RB, IL11, IL11RA, IL12A, IL12B, IL12RB1, IL12RB2, IL13, IL13RA1, IL13RA2, IL15, IL15RA, IL19, IL2, IL20, IL20RA, IL21, IL21R, IL22, IL22RA1, IL22RA2, IL23A, IL23R, IL24, IL26, IL28A, IL28B, IL28RA, IL29, IL2RA, IL2RB, IL2RG, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL6ST, IL7, IL7R, IL9, IL9R, IRF9, JAK1, JAK2, JAK3, LEP, LEPR, LIF, LIFR, MPL, MYC, OSM, OSMR, PIAS1, PIAS2, PIAS3, PIAS4, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIM1, PRL, PRLR, PTPN11, PTPN6, SOCS1, SOCS2, SOCS3, SOCS4, SOCS5, SOCS7, SOS1, SOS2, SPRED1, SPRED2, SPRY1, SPRY2, SPRY3, SPRY4, STAM, STAM2, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, TPO, TSLP, TYK2 148 AKT1(8), AKT2(4), AKT3(8), BCL2L1(3), CBL(10), CBLB(15), CBLC(5), CCND1(10), CCND2(7), CCND3(5), CLCF1(2), CNTF(3), CNTFR(2), CREBBP(37), CSF2RA(9), CSF2RB(11), CSF3(1), CSF3R(11), EP300(29), EPO(2), EPOR(4), GH1(6), GH2(5), GHR(10), GRB2(3), IFNA10(2), IFNA13(3), IFNA14(3), IFNA16(2), IFNA17(2), IFNA2(1), IFNA21(2), IFNA4(3), IFNA5(2), IFNA6(6), IFNA7(2), IFNA8(2), IFNAR1(9), IFNAR2(8), IFNB1(4), IFNG(5), IFNGR1(6), IFNGR2(4), IFNK(2), IFNW1(2), IL10(4), IL10RA(7), IL10RB(9), IL11RA(7), IL12A(7), IL12B(3), IL12RB1(16), IL12RB2(11), IL13RA1(14), IL13RA2(3), IL15(1), IL15RA(3), IL19(1), IL2(4), IL20(6), IL20RA(3), IL21(2), IL21R(6), IL22RA1(2), IL22RA2(1), IL23A(4), IL23R(8), IL24(7), IL26(7), IL28A(2), IL28B(4), IL28RA(8), IL29(2), IL2RA(3), IL2RB(6), IL2RG(11), IL3RA(11), IL4R(6), IL5(2), IL5RA(9), IL6(2), IL6R(12), IL6ST(10), IL7(2), IL7R(9), IRF9(6), JAK1(31), JAK2(21), JAK3(9), LEP(2), LEPR(15), LIF(3), LIFR(22), MPL(5), MYC(7), OSM(3), OSMR(12), PIAS1(5), PIAS2(12), PIAS3(9), PIAS4(4), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PIM1(4), PRL(6), PRLR(6), PTPN11(8), SOCS2(7), SOCS4(4), SOCS5(12), SOCS7(4), SOS1(21), SOS2(22), SPRED1(8), SPRED2(7), SPRY1(4), SPRY2(6), SPRY4(2), STAM(7), STAM2(7), STAT1(14), STAT2(12), STAT3(12), STAT4(9), STAT5A(5), STAT5B(5), STAT6(10), TPO(18), TSLP(2), TYK2(7) 49995454 1189 191 1069 271 316 413 191 68 170 31 5.88e-15 5.24e-14 68 P53HYPOXIAPATHWAY Hypoxia induces p53 accumulation and consequent apoptosis with p53-mediated cell cycle arrest, which is present under conditions of DNA damage. ABCB1, AKT1, ATM, BAX, CDKN1A, CPB2, CSNK1A1, CSNK1D, FHL2, GADD45A, HIC1, HIF1A, HSPA1A, HSPCA, IGFBP3, MAPK8, MDM2, NFKBIB, NQO1, TP53 17 ABCB1(28), AKT1(8), ATM(54), BAX(4), CDKN1A(1), CPB2(7), CSNK1A1(5), FHL2(1), HIF1A(17), IGFBP3(7), MAPK8(7), MDM2(6), NFKBIB(3), NQO1(3), TP53(40) 7045959 191 86 172 42 50 57 29 9 40 6 5.88e-15 5.24e-14 69 HSA04620_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY Genes involved in Toll-like receptor signaling pathway AKT1, AKT2, AKT3, CASP8, CCL3, CCL4, CCL5, CD14, CD40, CD80, CD86, CHUK, CXCL10, CXCL11, CXCL9, FADD, FOS, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IKBKB, IKBKE, IKBKG, IL12A, IL12B, IL1B, IL6, IL8, IRAK1, IRAK4, IRF3, IRF5, IRF7, JUN, LBP, LY96, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K8, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK9, MYD88, NFKB1, NFKB2, NFKBIA, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, RAC1, RELA, RIPK1, SPP1, STAT1, TBK1, TICAM1, TICAM2, TIRAP, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TNF, TOLLIP, TRAF3, TRAF6 93 AKT1(8), AKT2(4), AKT3(8), CASP8(21), CCL3(1), CCL4(1), CCL5(4), CD14(2), CD40(4), CD80(7), CD86(6), CHUK(11), CXCL10(2), CXCL11(1), CXCL9(2), FADD(1), FOS(6), IFNA10(2), IFNA13(3), IFNA14(3), IFNA16(2), IFNA17(2), IFNA2(1), IFNA21(2), IFNA4(3), IFNA5(2), IFNA6(6), IFNA7(2), IFNA8(2), IFNAR1(9), IFNAR2(8), IFNB1(4), IKBKB(15), IKBKE(3), IL12A(7), IL12B(3), IL1B(2), IL6(2), IL8(3), IRAK1(5), IRAK4(6), IRF3(6), IRF5(3), JUN(1), LBP(4), LY96(4), MAP2K1(2), MAP2K3(8), MAP2K4(6), MAP2K6(9), MAP3K7(8), MAP3K8(12), MAPK1(2), MAPK10(9), MAPK13(2), MAPK14(6), MAPK3(4), MAPK8(7), MAPK9(7), MYD88(1), NFKB1(12), NFKB2(10), NFKBIA(3), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), RELA(6), RIPK1(8), SPP1(3), STAT1(14), TBK1(6), TICAM1(8), TICAM2(5), TIRAP(3), TLR1(12), TLR2(12), TLR3(6), TLR4(14), TLR5(8), TLR6(10), TLR7(15), TLR8(18), TLR9(7), TNF(1), TRAF3(6), TRAF6(4) 30048514 757 177 655 156 186 258 141 42 117 13 6.00e-15 5.24e-14 70 CELL2CELLPATHWAY Epithelial cell adhesion proteins such as cadherins transduce signals into the cell via catenins, which alter cell shape and motility. ACTN1, ACTN2, ACTN3, BCAR1, CSK, CTNNA1, CTNNA2, CTNNB1, PECAM1, PTK2, PXN, SRC, VCL 12 ACTN1(13), ACTN2(9), ACTN3(10), CSK(1), CTNNA1(18), CTNNA2(13), CTNNB1(66), PTK2(11), PXN(6), SRC(2), VCL(14) 6633684 163 89 113 48 43 71 17 14 18 0 6.00e-15 5.24e-14 71 GHPATHWAY Growth hormone receptors dimerize on ligand binding and activate the JAK2 protein kinase. GH1, GHR, GRB2, HRAS, INS, INSR, IRS1, JAK2, MAP2K1, MAPK1, MAPK3, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTPN6, RAF1, RPS6KA1, SHC1, SLC2A4, SOCS1, SOS1, SRF, STAT5A, STAT5B, TCF1 23 GH1(6), GHR(10), GRB2(3), INSR(18), IRS1(17), JAK2(21), MAP2K1(2), MAPK1(2), MAPK3(4), PIK3CA(138), PIK3R1(67), PLCG1(12), PRKCA(10), RAF1(7), RPS6KA1(5), SHC1(11), SLC2A4(4), SOS1(21), SRF(3), STAT5A(5), STAT5B(5) 11375683 371 163 276 55 93 101 82 21 55 19 6.11e-15 5.24e-14 72 TCRPATHWAY T cell receptors bind to foreign peptides presented by MHC molecules and induce T cell activation. CALM1, CALM2, CALM3, CD3D, CD3E, CD3G, CD3Z, ELK1, FOS, FYN, GRB2, HRAS, JUN, LAT, LCK, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKBIA, PIK3CA, PIK3R1, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, PTPN7, RAC1, RAF1, RASA1, RELA, SHC1, SOS1, SYT1, TRA@, TRB@, VAV1, ZAP70 42 CALM2(3), CALM3(1), CD3D(3), CD3E(2), CD3G(2), ELK1(2), FOS(6), FYN(7), GRB2(3), JUN(1), LCK(5), MAP2K1(2), MAP2K4(6), MAP3K1(31), MAPK3(4), MAPK8(7), NFATC2(15), NFATC3(12), NFATC4(8), NFKB1(12), NFKBIA(3), PIK3CA(138), PIK3R1(67), PLCG1(12), PPP3CA(4), PPP3CB(7), PPP3CC(6), PRKCA(10), PTPN7(5), RAF1(7), RASA1(29), RELA(6), SHC1(11), SOS1(21), SYT1(4), VAV1(16), ZAP70(10) 16411891 488 169 389 74 130 133 92 28 86 19 6.22e-15 5.24e-14 73 IGF1RPATHWAY Insulin-like growth factor receptor IGF-1R promotes cell growth and inhibits apoptosis on binding of ligands IGF-1 and 2 via Ras activation and the AKT pathway. AKT1, BAD, GRB2, HRAS, IGF1R, IRS1, MAP2K1, MAPK1, MAPK3, PIK3CA, PIK3R1, RAF1, SHC1, SOS1, YWHAH 15 AKT1(8), BAD(2), GRB2(3), IGF1R(13), IRS1(17), MAP2K1(2), MAPK1(2), MAPK3(4), PIK3CA(138), PIK3R1(67), RAF1(7), SHC1(11), SOS1(21), YWHAH(4) 6614803 299 163 205 29 72 80 70 17 47 13 6.22e-15 5.24e-14 74 EDG1PATHWAY The lipid S1P is an EDG1 ligand promoting chemotaxis via Rac1 and cell survival and proliferation via ERK activation. ADCY1, AKT1, ARHA, ASAH1, EDG1, GNAI1, GNB1, GNGT1, ITGAV, ITGB3, MAPK1, MAPK3, PDGFA, PDGFRA, PIK3CA, PIK3R1, PLCB1, PRKCA, PRKCB1, PTK2, RAC1, SKIP, SMPD1, SMPD2, SPHK1, SRC 21 ADCY1(17), AKT1(8), ASAH1(9), GNAI1(4), GNB1(3), ITGAV(10), ITGB3(16), MAPK1(2), MAPK3(4), PDGFRA(29), PIK3CA(138), PIK3R1(67), PLCB1(6), PRKCA(10), PTK2(11), SMPD1(12), SMPD2(5), SPHK1(2), SRC(2) 9367366 355 166 260 48 84 102 77 22 57 13 6.33e-15 5.24e-14 75 ST_WNT_BETA_CATENIN_PATHWAY Beta-catenin is degraded in the absence of Wnt signaling; when extracellular Wnt binds Frizzled receptors, beta-catenin accumulates in the nucleus and may promote cell survival. AKT1, AKT2, AKT3, ANKRD6, APC, AXIN1, AXIN2, C22orf2, CER1, CSNK1A1, CTNNB1, DACT1, DKK1, DKK2, DKK3, DKK4, DVL1, FRAT1, FSTL1, GSK3A, GSK3B, IDAX, LAMR1, LRP1, MVP, NKD1, NKD2, PIN1, PSEN1, PTPRA, SENP2, SFRP1, TSHB, WIF1 28 AKT1(8), AKT2(4), AKT3(8), ANKRD6(14), APC(53), AXIN1(8), AXIN2(1), CER1(2), CSNK1A1(5), CTNNB1(66), DACT1(14), DKK1(4), DKK2(4), DKK3(3), DKK4(3), FSTL1(3), GSK3A(9), GSK3B(11), LRP1(53), MVP(12), NKD1(4), PIN1(1), PSEN1(4), PTPRA(11), SENP2(11), SFRP1(5), TSHB(3), WIF1(5) 13346716 329 115 274 78 92 133 39 26 33 6 6.44e-15 5.24e-14 76 HSA04530_TIGHT_JUNCTION Genes involved in tight junction ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, AMOTL1, ASH1L, CASK, CDC42, CDK4, CGN, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CRB3, CSDA, CSNK2A1, CSNK2A2, CSNK2B, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTTN, EPB41, EPB41L1, EPB41L2, EPB41L3, EXOC3, EXOC4, F11R, GNAI1, GNAI2, GNAI3, HCLS1, HRAS, IGSF5, INADL, JAM2, JAM3, KRAS, LLGL1, LLGL2, MAGI1, MAGI2, MAGI3, MLLT4, MPDZ, MPP5, MRAS, MRCL3, MRLC2, MYH1, MYH10, MYH11, MYH13, MYH14, MYH15, MYH2, MYH3, MYH4, MYH6, MYH7, MYH7B, MYH8, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLPF, NRAS, OCLN, PARD3, PARD6A, PARD6B, PARD6G, PPM1J, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PPP2R3A, PPP2R3B, PPP2R4, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCQ, PRKCZ, PTEN, RAB13, RAB3B, RHOA, RRAS, RRAS2, SPTAN1, SRC, SYMPK, TJAP1, TJP1, TJP2, TJP3, VAPA, YES1, ZAK 126 ACTB(5), ACTN1(13), ACTN2(9), ACTN3(10), ACTN4(11), AKT1(8), AKT2(4), AKT3(8), AMOTL1(14), ASH1L(40), CASK(20), CDC42(5), CDK4(4), CGN(15), CLDN1(2), CLDN10(9), CLDN11(1), CLDN15(4), CLDN16(6), CLDN17(2), CLDN18(4), CLDN19(2), CLDN2(4), CLDN20(4), CLDN22(3), CLDN6(1), CLDN7(1), CLDN8(5), CLDN9(2), CRB3(1), CSDA(6), CSNK2A1(9), CSNK2A2(5), CTNNA1(18), CTNNA2(13), CTNNA3(13), CTNNB1(66), CTTN(8), EPB41(11), EPB41L1(11), EPB41L2(13), EPB41L3(18), EXOC3(12), EXOC4(4), F11R(2), GNAI1(4), GNAI2(7), GNAI3(3), HCLS1(8), IGSF5(9), INADL(17), JAM2(9), JAM3(3), KRAS(29), LLGL1(14), LLGL2(5), MAGI1(32), MAGI2(26), MAGI3(17), MLLT4(32), MPDZ(22), MPP5(5), MRAS(3), MYH1(44), MYH10(29), MYH11(39), MYH13(27), MYH14(22), MYH15(22), MYH2(37), MYH3(30), MYH4(36), MYH6(23), MYH7(28), MYH7B(15), MYH8(35), MYH9(26), MYL2(1), MYL5(3), MYL7(4), MYL9(3), MYLPF(2), NRAS(10), OCLN(5), PARD3(27), PARD6A(1), PARD6B(3), PPM1J(3), PPP2CA(6), PPP2CB(2), PPP2R1A(27), PPP2R1B(9), PPP2R2A(15), PPP2R2B(12), PPP2R2C(3), PPP2R3A(13), PPP2R4(7), PRKCA(10), PRKCD(7), PRKCE(11), PRKCG(10), PRKCH(9), PRKCI(8), PRKCQ(13), PRKCZ(4), PTEN(198), RAB13(3), RAB3B(1), RHOA(4), RRAS(1), RRAS2(5), SPTAN1(29), SRC(2), SYMPK(20), TJAP1(8), TJP1(33), TJP2(16), TJP3(6), VAPA(5), YES1(5), ZAK(12) 66353331 1660 209 1466 422 421 596 271 82 253 37 6.55e-15 5.24e-14 77 PHOSPHATIDYLINOSITOL_SIGNALING_SYSTEM ACVR1, ACVR1B, ACVRL1, AKT1, AURKB, BMPR1A, BMPR2, BUB1, CDC2L5, CDIPT, CDKL1, CDKL2, CDS1, CDS2, CLK1, CLK2, CLK4, COL4A3BP, CSNK2A1, CSNK2A1, CSNK2A1P, CSNK2A2, CSNK2B, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKQ, DGKZ, IMPA1, INPP1, INPP4A, INPP4B, INPP5A, INPPL1, ITPKA, ITPKB, MAP3K10, MOS, NEK1, NEK3, OCRL, PAK4, PCTK1, PCTK2, PIK3C2A, PIK3C2B, PIK3C2G, PIK3CA, PIK3CB, PIK3CG, PIK4CA, PIK4CA, LOC220686, PIM2, PIP5K2B, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCG1, PLCG2, PLK3, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCQ, PRKCZ, PRKD1, PRKG1, RAF1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KB1, STK11, TGFBR1, VRK1 79 ACVR1(9), ACVR1B(6), ACVRL1(3), AKT1(8), AURKB(5), BMPR1A(8), BMPR2(14), BUB1(9), CDIPT(1), CDKL1(7), CDKL2(6), CDS1(3), CDS2(2), CLK1(9), CLK2(10), CLK4(6), COL4A3BP(3), CSNK2A1(9), CSNK2A2(5), DGKA(15), DGKB(17), DGKD(21), DGKE(4), DGKG(13), DGKH(11), DGKZ(9), IMPA1(4), INPP1(2), INPP4A(23), INPP4B(17), INPP5A(6), INPPL1(23), ITPKB(6), MAP3K10(7), MOS(8), NEK1(20), NEK3(12), OCRL(20), PAK4(2), PIK3C2A(20), PIK3C2B(15), PIK3C2G(22), PIK3CA(138), PIK3CB(19), PIK3CG(25), PIM2(3), PLCB1(6), PLCB2(9), PLCB3(9), PLCB4(20), PLCD1(5), PLCG1(12), PLCG2(27), PLK3(12), PRKACA(4), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PRKCA(10), PRKCD(7), PRKCE(11), PRKCG(10), PRKCH(9), PRKCQ(13), PRKCZ(4), PRKD1(8), PRKG1(9), RAF1(7), RPS6KA1(5), RPS6KA2(16), RPS6KA3(17), RPS6KA4(5), RPS6KB1(3), TGFBR1(8), VRK1(12) 38669961 892 169 789 239 250 310 154 50 116 12 6.55e-15 5.24e-14 78 CDC42RACPATHWAY PI3 kinase stimulates cell migration by activating cdc42, which activates ARP2/3, which in turn promotes formation of new actin fibers. ACTR2, ACTR3, ARHA, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, PAK1, PDGFRA, PIK3CA, PIK3R1, RAC1, WASL 14 ACTR2(7), ACTR3(3), ARPC1A(7), ARPC1B(3), ARPC2(2), ARPC3(2), CDC42(5), PAK1(3), PDGFRA(29), PIK3CA(138), PIK3R1(67), WASL(8) 4771157 274 155 183 14 72 64 65 13 47 13 6.99e-15 5.52e-14 79 CHEMICALPATHWAY DNA damage promotes Bid cleavage, which stimulates mitochondrial cytochrome c release and consequent caspase activation, resulting in apoptosis. ADPRT, AKT1, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, CASP3, CASP6, CASP7, CASP9, CYCS, EIF2S1, PRKCA, PRKCB1, PTK2, PXN, STAT1, TLN1, TP53 20 AKT1(8), APAF1(19), ATM(54), BAD(2), BAX(4), BCL2L1(3), BID(3), CASP3(4), CASP6(4), CASP7(4), CASP9(3), CYCS(3), EIF2S1(1), PRKCA(10), PTK2(11), PXN(6), STAT1(14), TLN1(28), TP53(40) 9696230 221 85 203 49 57 73 37 10 40 4 7.33e-15 5.52e-14 80 HSA04810_REGULATION_OF_ACTIN_CYTOSKELETON Genes involved in regulation of actin cytoskeleton ABI2, ACTN1, ACTN2, ACTN3, ACTN4, APC, APC2, ARAF, ARHGEF1, ARHGEF12, ARHGEF4, ARHGEF6, ARHGEF7, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, ARPC5, ARPC5L, BAIAP2, BCAR1, BDKRB1, BDKRB2, BRAF, C3orf10, CD14, CDC42, CFL1, CFL2, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CRK, CRKL, CSK, CYFIP1, CYFIP2, DIAPH1, DIAPH2, DIAPH3, DOCK1, EGF, EGFR, EZR, F2, F2R, FGD1, FGD3, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14, FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FN1, GIT1, GNA12, GNA13, GNG12, GRLF1, GSN, HRAS, INS, IQGAP1, IQGAP2, IQGAP3, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, KRAS, LIMK1, LIMK2, LOC200025, LOC645126, LOC653888, MAP2K1, MAP2K2, MAPK1, MAPK3, MLCK, MOS, MRAS, MRCL3, MRLC2, MSN, MYH10, MYH14, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, NCKAP1, NCKAP1L, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDGFA, PDGFB, PDGFRA, PDGFRB, PFN1, PFN2, PFN3, PFN4, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R12B, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RDX, RHOA, ROCK1, ROCK2, RRAS, RRAS2, SCIN, SLC9A1, SOS1, SOS2, SSH1, SSH2, SSH3, TIAM1, TIAM2, TMSB4X, TMSB4Y, TMSL3, VAV1, VAV2, VAV3, VCL, WAS, WASF1, WASF2, WASL 193 ABI2(4), ACTN1(13), ACTN2(9), ACTN3(10), ACTN4(11), APC(53), ARAF(8), ARHGEF1(11), ARHGEF12(25), ARHGEF4(5), ARHGEF6(19), ARHGEF7(13), ARPC1A(7), ARPC1B(3), ARPC2(2), ARPC3(2), ARPC5(1), BAIAP2(1), BDKRB1(5), BDKRB2(9), BRAF(12), CD14(2), CDC42(5), CFL1(1), CFL2(8), CHRM1(6), CHRM2(9), CHRM3(9), CHRM4(9), CHRM5(13), CRK(1), CRKL(5), CSK(1), CYFIP1(13), CYFIP2(20), DIAPH1(11), DIAPH2(22), DIAPH3(26), DOCK1(32), EGF(24), EGFR(20), EZR(6), F2(9), F2R(8), FGD1(12), FGD3(12), FGF1(1), FGF10(1), FGF11(2), FGF12(4), FGF13(6), FGF14(3), FGF16(1), FGF17(1), FGF18(2), FGF21(3), FGF23(6), FGF5(8), FGF6(2), FGF7(6), FGF8(2), FGF9(2), FGFR1(10), FGFR2(27), FGFR4(11), FN1(39), GIT1(9), GNA12(10), GNA13(9), GNG12(2), GSN(5), IQGAP1(12), IQGAP2(26), IQGAP3(18), ITGA1(20), ITGA10(11), ITGA11(12), ITGA2(21), ITGA2B(11), ITGA3(6), ITGA4(12), ITGA5(12), ITGA6(12), ITGA7(10), ITGA8(16), ITGA9(15), ITGAD(11), ITGAE(14), ITGAL(13), ITGAM(24), ITGAV(10), ITGAX(9), ITGB1(12), ITGB2(14), ITGB3(16), ITGB4(12), ITGB5(8), ITGB6(6), ITGB7(8), ITGB8(5), KRAS(29), LIMK1(7), LIMK2(16), MAP2K1(2), MAPK1(2), MAPK3(4), MOS(8), MRAS(3), MSN(15), MYH10(29), MYH14(22), MYH9(26), MYL2(1), MYL5(3), MYL7(4), MYL9(3), MYLK(17), MYLK2(7), MYLPF(2), NCKAP1(10), NCKAP1L(18), NRAS(10), PAK1(3), PAK2(6), PAK3(14), PAK4(2), PAK6(3), PAK7(12), PDGFB(4), PDGFRA(29), PDGFRB(12), PFN1(1), PFN2(3), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PIP4K2A(4), PIP4K2B(9), PIP4K2C(4), PIP5K1A(7), PIP5K1B(6), PIP5K1C(5), PPP1CA(6), PPP1CB(7), PPP1CC(2), PPP1R12A(12), PPP1R12B(18), PTK2(11), PXN(6), RAC2(2), RAF1(7), RDX(12), RHOA(4), ROCK1(27), ROCK2(15), RRAS(1), RRAS2(5), SCIN(3), SLC9A1(10), SOS1(21), SOS2(22), SSH1(13), SSH2(15), SSH3(3), TIAM1(26), TIAM2(21), TMSL3(1), VAV1(16), VAV2(5), VAV3(13), VCL(14), WAS(14), WASF1(3), WASF2(5), WASL(8) 93008284 2044 200 1873 577 544 770 304 108 281 37 7.44e-15 5.52e-14 81 NFATPATHWAY Cardiac hypertrophy is induced by NF-ATc4 and GATA4, which are stimulated through calcineurin activated by CaMK. ACTA1, AGT, AKT1, CALM1, CALM2, CALM3, CALR, CAMK1, CAMK1G, CAMK4, CREBBP, CSNK1A1, CTF1, DTR, EDN1, ELSPBP1, F2, FGF2, FKBP1A, GATA4, GSK3B, HAND1, HAND2, HRAS, IGF1, LIF, MAP2K1, MAPK1, MAPK14, MAPK3, MAPK8, MEF2C, MYH2, NFATC1, NFATC2, NFATC3, NFATC4, NKX2-5, NPPA, PIK3CA, PIK3R1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RAF1, RPS6KB1, SYT1 50 ACTA1(4), AGT(7), AKT1(8), CALM2(3), CALM3(1), CALR(4), CAMK1(9), CAMK1G(5), CAMK4(5), CREBBP(37), CSNK1A1(5), EDN1(2), ELSPBP1(6), F2(9), GATA4(1), GSK3B(11), HAND1(5), HAND2(2), IGF1(3), LIF(3), MAP2K1(2), MAPK1(2), MAPK14(6), MAPK3(4), MAPK8(7), MEF2C(11), MYH2(37), NFATC2(15), NFATC3(12), NFATC4(8), NPPA(1), PIK3CA(138), PIK3R1(67), PPP3CA(4), PPP3CB(7), PPP3CC(6), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), RAF1(7), RPS6KB1(3), SYT1(4) 16973302 500 173 400 97 132 152 95 25 83 13 7.44e-15 5.52e-14 82 INOSITOL_PHOSPHATE_METABOLISM IMPA1, INPP1, INPP4A, INPP4B, INPP5A, INPPL1, ITPKA, ITPKB, MIOX, OCRL, PIK3C2A, PIK3C2B, PIK3C2G, PIK3CA, PIK3CB, PIK3CG, PIK4CA, PIK4CA, LOC220686, PIP5K2B, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCG1, PLCG2 22 IMPA1(4), INPP1(2), INPP4A(23), INPP4B(17), INPP5A(6), INPPL1(23), ITPKB(6), OCRL(20), PIK3C2A(20), PIK3C2B(15), PIK3C2G(22), PIK3CA(138), PIK3CB(19), PIK3CG(25), PLCB1(6), PLCB2(9), PLCB3(9), PLCB4(20), PLCD1(5), PLCG1(12), PLCG2(27) 15636336 428 144 340 92 122 136 81 23 58 8 7.44e-15 5.52e-14 83 RBPATHWAY The ATM protein kinase recognizes DNA damage and blocks cell cycle progression by phosphorylating chk1 and p53, which normally inhibits Rb to allow G1/S transitions. ATM, CDC2, CDC25A, CDC25B, CDC25C, CDK2, CDK4, CHEK1, MYT1, RB1, TP53, WEE1, YWHAH 12 ATM(54), CDC25A(9), CDC25B(3), CDC25C(8), CDK2(5), CDK4(4), CHEK1(4), RB1(31), TP53(40), WEE1(1), YWHAH(4) 6235032 163 76 146 25 36 44 29 5 41 8 7.44e-15 5.52e-14 84 G2PATHWAY Activated Cdc2-cyclin B kinase regulates the G2/M transition; DNA damage stimulates the DNA-PK/ATM/ATR kinases, which inactivate Cdc2. ATM, ATR, BRCA1, CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CDC34, CDKN1A, CDKN2D, CHEK1, CHEK2, EP300, GADD45A, MDM2, MYT1, PLK, PRKDC, RPS6KA1, TP53, WEE1, YWHAH, YWHAQ 21 ATM(54), ATR(38), BRCA1(19), CCNB1(8), CDC25A(9), CDC25B(3), CDC25C(8), CDKN1A(1), CDKN2D(3), CHEK1(4), CHEK2(14), EP300(29), MDM2(6), PRKDC(70), RPS6KA1(5), TP53(40), WEE1(1), YWHAH(4), YWHAQ(3) 15115316 319 89 298 49 56 102 56 22 74 9 8.22e-15 6.02e-14 85 HSA04070_PHOSPHATIDYLINOSITOL_SIGNALING_SYSTEM Genes involved in phosphatidylinositol signaling system CALM1, CALM2, CALM3, CALML3, CALML6, CARKL, CDIPT, CDS1, CDS2, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKI, DGKQ, DGKZ, FN3K, IMPA1, IMPA2, INPP1, INPP4A, INPP4B, INPP5A, INPP5B, INPP5D, INPP5E, INPPL1, ITGB1BP3, ITPK1, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, OCRL, PI4KA, PI4KB, PIB5PA, PIK3C2A, PIK3C2B, PIK3C2G, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCZ1, PRKCA, PRKCB1, PRKCG, PTEN, PTPMT1, SKIP, SYNJ1, SYNJ2 70 CALM2(3), CALM3(1), CALML6(4), CDIPT(1), CDS1(3), CDS2(2), DGKA(15), DGKB(17), DGKD(21), DGKE(4), DGKG(13), DGKH(11), DGKI(21), DGKZ(9), IMPA1(4), IMPA2(6), INPP1(2), INPP4A(23), INPP4B(17), INPP5A(6), INPP5B(8), INPP5D(14), INPPL1(23), ITGB1BP3(1), ITPK1(2), ITPKB(6), ITPR1(31), ITPR2(38), ITPR3(23), OCRL(20), PI4KA(18), PI4KB(12), PIK3C2A(20), PIK3C2B(15), PIK3C2G(22), PIK3C3(11), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PIP4K2A(4), PIP4K2B(9), PIP4K2C(4), PIP5K1A(7), PIP5K1B(6), PIP5K1C(5), PLCB1(6), PLCB2(9), PLCB3(9), PLCB4(20), PLCD1(5), PLCD3(7), PLCD4(13), PLCE1(36), PLCG1(12), PLCG2(27), PLCZ1(16), PRKCA(10), PRKCG(10), PTEN(198), PTPMT1(1), SYNJ1(27), SYNJ2(13) 42203337 1180 207 994 262 281 346 227 54 229 43 8.33e-15 6.03e-14 86 HSA04310_WNT_SIGNALING_PATHWAY Genes involved in Wnt signaling pathway APC, APC2, AXIN1, AXIN2, BTRC, CACYBP, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CCND1, CCND2, CCND3, CER1, CHD8, CHP, CREBBP, CSNK1A1, CSNK1A1L, CSNK1E, CSNK2A1, CSNK2A2, CSNK2B, CTBP1, CTBP2, CTNNB1, CTNNBIP1, CUL1, CXXC4, DAAM1, DAAM2, DKK1, DKK2, DKK4, DVL1, DVL2, DVL3, EP300, FBXW11, FOSL1, FRAT1, FRAT2, FZD1, FZD10, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, GSK3B, JUN, LEF1, LOC652788, LRP5, LRP6, MAP3K7, MAPK10, MAPK8, MAPK9, MMP7, MYC, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NKD1, NKD2, NLK, PLCB1, PLCB2, PLCB3, PLCB4, PORCN, PPARD, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRICKLE1, PRICKLE2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PSEN1, RAC1, RAC2, RAC3, RBX1, RHOA, ROCK1, ROCK2, RUVBL1, SENP2, SFRP1, SFRP2, SFRP4, SFRP5, SIAH1, SKP1, SMAD2, SMAD3, SMAD4, SOX17, TBL1X, TBL1XR1, TBL1Y, TCF7, TCF7L1, TCF7L2, TP53, VANGL1, VANGL2, WIF1, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B 135 APC(53), AXIN1(8), AXIN2(1), BTRC(13), CACYBP(4), CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), CCND1(10), CCND2(7), CCND3(5), CER1(2), CHD8(39), CREBBP(37), CSNK1A1(5), CSNK1A1L(4), CSNK1E(10), CSNK2A1(9), CSNK2A2(5), CTBP2(7), CTNNB1(66), CTNNBIP1(2), CUL1(12), CXXC4(1), DAAM1(17), DAAM2(14), DKK1(4), DKK2(4), DKK4(3), DVL2(12), DVL3(7), EP300(29), FBXW11(5), FOSL1(4), FZD1(2), FZD10(7), FZD2(6), FZD3(7), FZD4(4), FZD6(15), FZD7(5), FZD9(7), GSK3B(11), JUN(1), LEF1(9), LRP5(18), LRP6(18), MAP3K7(8), MAPK10(9), MAPK8(7), MAPK9(7), MMP7(3), MYC(7), NFAT5(13), NFATC2(15), NFATC3(12), NFATC4(8), NKD1(4), NLK(5), PLCB1(6), PLCB2(9), PLCB3(9), PLCB4(20), PORCN(12), PPARD(6), PPP2CA(6), PPP2CB(2), PPP2R1A(27), PPP2R1B(9), PPP2R2A(15), PPP2R2B(12), PPP2R2C(3), PPP3CA(4), PPP3CB(7), PPP3CC(6), PPP3R1(2), PPP3R2(1), PRICKLE1(8), PRICKLE2(6), PRKACA(4), PRKACB(2), PRKACG(6), PRKCA(10), PRKCG(10), PRKX(4), PSEN1(4), RAC2(2), RBX1(1), RHOA(4), ROCK1(27), ROCK2(15), RUVBL1(2), SENP2(11), SFRP1(5), SFRP2(3), SFRP4(10), SFRP5(2), SIAH1(3), SKP1(2), SMAD2(12), SMAD3(4), SMAD4(5), TBL1X(7), TBL1XR1(15), TCF7(4), TCF7L1(5), TCF7L2(18), TP53(40), VANGL1(5), VANGL2(10), WIF1(5), WNT1(1), WNT10A(4), WNT10B(1), WNT11(4), WNT16(6), WNT2(4), WNT2B(9), WNT3(5), WNT4(4), WNT5A(9), WNT5B(4), WNT7A(2), WNT7B(1), WNT8A(1), WNT8B(4), WNT9A(1), WNT9B(1) 52544867 1120 178 1035 309 298 440 148 64 152 18 8.66e-15 6.20e-14 87 HSA04660_T_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in T cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, CARD11, CBL, CBLB, CBLC, CD247, CD28, CD3D, CD3E, CD3G, CD4, CD40LG, CD8A, CD8B, CDC42, CDK4, CHP, CHUK, CSF2, CTLA4, FOS, FYN, GRAP2, GRB2, HRAS, ICOS, IFNG, IKBKB, IKBKG, IL10, IL2, IL4, IL5, ITK, JUN, KRAS, LAT, LCK, LCP2, MALT1, MAP3K14, MAP3K8, NCK1, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDCD1, PDK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCQ, PTPN6, PTPRC, RASGRP1, RHOA, SOS1, SOS2, TEC, TNF, VAV1, VAV2, VAV3, ZAP70 91 AKT1(8), AKT2(4), AKT3(8), BCL10(2), CARD11(16), CBL(10), CBLB(15), CBLC(5), CD247(5), CD28(6), CD3D(3), CD3E(2), CD3G(2), CD4(8), CD40LG(7), CD8A(3), CD8B(1), CDC42(5), CDK4(4), CHUK(11), CTLA4(2), FOS(6), FYN(7), GRAP2(3), GRB2(3), ICOS(2), IFNG(5), IKBKB(15), IL10(4), IL2(4), IL5(2), ITK(10), JUN(1), KRAS(29), LCK(5), LCP2(7), MALT1(4), MAP3K14(12), MAP3K8(12), NCK1(4), NCK2(8), NFAT5(13), NFATC2(15), NFATC3(12), NFATC4(8), NFKB1(12), NFKB2(10), NFKBIA(3), NFKBIB(3), NFKBIE(6), NRAS(10), PAK1(3), PAK2(6), PAK3(14), PAK4(2), PAK6(3), PAK7(12), PDK1(7), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PLCG1(12), PPP3CA(4), PPP3CB(7), PPP3CC(6), PPP3R1(2), PPP3R2(1), PRKCQ(13), PTPRC(15), RASGRP1(8), RHOA(4), SOS1(21), SOS2(22), TEC(5), TNF(1), VAV1(16), VAV2(5), VAV3(13), ZAP70(10) 34057500 853 180 722 192 236 282 152 44 122 17 8.77e-15 6.21e-14 88 ST_INTEGRIN_SIGNALING_PATHWAY Integrins are transmembrane receptors that mediate cell growth, survival, and migration by binding to ligands in the extracellular matrix. ABL1, ACK1, ACTN1, ACTR2, ACTR3, AKT1, AKT2, AKT3, ANGPTL2, ARHGEF6, ARHGEF7, BCAR1, BRAF, CAV1, CDC42, CDKN2A, CRK, CSE1L, DDEF1, DOCK1, EPHB2, FYN, GRAF, GRB2, GRB7, GRF2, GRLF1, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGB3BP, MAP2K4, MAP2K7, MAP3K11, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MRAS, MYLK, MYLK2, P4HB, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PIK3CA, PIK3CB, PKLR, PLCG1, PLCG2, PTEN, PTK2, RAF1, RALA, RHO, ROCK1, ROCK2, SHC1, SOS1, SOS2, SRC, TERF2IP, TLN1, TLN2, VASP, WAS, ZYX 74 ABL1(9), ACTN1(13), ACTR2(7), ACTR3(3), AKT1(8), AKT2(4), AKT3(8), ANGPTL2(9), ARHGEF6(19), ARHGEF7(13), BRAF(12), CDC42(5), CDKN2A(1), CRK(1), CSE1L(15), DOCK1(32), EPHB2(10), FYN(7), GRB2(3), GRB7(3), ILK(8), ITGA1(20), ITGA10(11), ITGA11(12), ITGA2(21), ITGA3(6), ITGA4(12), ITGA5(12), ITGA6(12), ITGA7(10), ITGA8(16), ITGA9(15), ITGB3BP(2), MAP2K4(6), MAP3K11(5), MAPK1(2), MAPK10(9), MAPK8(7), MAPK8IP1(5), MAPK9(7), MRAS(3), MYLK(17), MYLK2(7), P4HB(1), PAK1(3), PAK2(6), PAK3(14), PAK4(2), PAK6(3), PAK7(12), PIK3CA(138), PIK3CB(19), PKLR(10), PLCG1(12), PLCG2(27), PTEN(198), PTK2(11), RAF1(7), RALA(4), RHO(8), ROCK1(27), ROCK2(15), SHC1(11), SOS1(21), SOS2(22), SRC(2), TERF2IP(4), TLN1(28), TLN2(29), VASP(2), WAS(14), ZYX(12) 41356082 1069 204 884 204 250 325 197 49 220 28 9.44e-15 6.61e-14 89 LONGEVITYPATHWAY Caloric restriction in animals often increases lifespan, which may occur via decreased IGF receptor expression and consequent expression of stress-resistance proteins. AKT1, CAT, FOXO3A, GH1, GHR, HRAS, IGF1, IGF1R, PIK3CA, PIK3R1, SHC1, SOD1, SOD2, SOD3 12 AKT1(8), CAT(5), GH1(6), GHR(10), IGF1(3), IGF1R(13), PIK3CA(138), PIK3R1(67), SHC1(11), SOD1(2), SOD2(3) 4561793 266 160 174 25 61 71 65 16 42 11 9.66e-15 6.69e-14 90 ACHPATHWAY Nicotinic acetylcholine receptors are ligand-gated ion channels that primarily mediate neuromuscular signaling and may inhibit neuronal apoptosis via the AKT pathway. AKT1, BAD, CHRNB1, CHRNG, FOXO3A, MUSK, PIK3CA, PIK3R1, PTK2, PTK2B, RAPSN, SRC, TERT, TNFSF6, YWHAH 13 AKT1(8), BAD(2), CHRNB1(3), CHRNG(9), MUSK(16), PIK3CA(138), PIK3R1(67), PTK2(11), PTK2B(16), RAPSN(4), SRC(2), TERT(6), YWHAH(4) 5431992 286 160 194 42 77 72 67 17 42 11 9.88e-15 6.76e-14 91 ECMPATHWAY Extracellular matrix induces integrin-mediated FAK phosphorylation in epithelial cells, leading to PI3 and MAP kinase activation and actin reorganization. ARHA, ARHGAP5, DIAPH1, FYN, GSN, HRAS, ITGA1, ITGB1, MAP2K1, MAPK1, MAPK3, MYL2, MYLK, PFN1, PIK3CA, PIK3R1, PTK2, PXN, RAF1, ROCK1, SHC1, SRC, TLN1 22 ARHGAP5(24), DIAPH1(11), FYN(7), GSN(5), ITGA1(20), ITGB1(12), MAP2K1(2), MAPK1(2), MAPK3(4), MYL2(1), MYLK(17), PFN1(1), PIK3CA(138), PIK3R1(67), PTK2(11), PXN(6), RAF1(7), ROCK1(27), SHC1(11), SRC(2), TLN1(28) 13320665 403 163 309 47 106 118 80 18 66 15 9.99e-15 6.76e-14 92 SIG_BCR_SIGNALING_PATHWAY Members of the BCR signaling pathway AKT1, AKT2, AKT3, BAD, BCL2, BCR, BLNK, BTK, CD19, CD22, CD81, CR2, CSK, DAG1, FLOT1, FLOT2, GRB2, GSK3A, GSK3B, INPP5D, ITPR1, ITPR2, ITPR3, LYN, MAP4K1, MAPK1, MAPK3, NFATC1, NFATC2, NR0B2, PDK1, PIK3CA, PIK3CD, PIK3R1, PLCG2, PPP1R13B, PPP3CA, PPP3CB, PPP3CC, PTPRC, RAF1, SHC1, SOS1, SOS2, SYK, VAV1 45 AKT1(8), AKT2(4), AKT3(8), BAD(2), BCR(6), BLNK(4), BTK(11), CD19(7), CD22(13), CR2(28), CSK(1), DAG1(7), FLOT1(1), FLOT2(3), GRB2(3), GSK3A(9), GSK3B(11), INPP5D(14), ITPR1(31), ITPR2(38), ITPR3(23), LYN(7), MAP4K1(13), MAPK1(2), MAPK3(4), NFATC2(15), NR0B2(2), PDK1(7), PIK3CA(138), PIK3CD(10), PIK3R1(67), PLCG2(27), PPP1R13B(7), PPP3CA(4), PPP3CB(7), PPP3CC(6), PTPRC(15), RAF1(7), SHC1(11), SOS1(21), SOS2(22), SYK(6), VAV1(16) 25226450 646 172 543 151 176 217 121 27 86 19 1.03e-14 6.84e-14 93 ALKPATHWAY Activin receptor-like kinase 3 (ALK3) is required during gestation for cardiac muscle development. ACVR1, APC, ATF2, AXIN1, BMP10, BMP2, BMP4, BMP5, BMP7, BMPR1A, BMPR2, CHRD, CTNNB1, DVL1, FZD1, GATA4, GSK3B, MADH1, MADH4, MADH5, MADH6, MAP3K7, MEF2C, MYL2, NKX2-5, NOG, NPPA, NPPB, RFC1, TCF1, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, WNT1 30 ACVR1(9), APC(53), ATF2(6), AXIN1(8), BMP10(6), BMP2(5), BMP4(7), BMP5(16), BMP7(15), BMPR1A(8), BMPR2(14), CHRD(14), CTNNB1(66), FZD1(2), GATA4(1), GSK3B(11), MAP3K7(8), MEF2C(11), MYL2(1), NOG(1), NPPA(1), NPPB(2), RFC1(15), TGFB1(4), TGFB2(6), TGFB3(9), TGFBR1(8), TGFBR2(6), TGFBR3(8), WNT1(1) 11902439 322 112 270 54 81 140 42 24 29 6 1.03e-14 6.84e-14 94 APOPTOSIS APAF1, BAD, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BCL2L11, BID, BIRC2, BIRC3, BIRC4, BIRC5, BNIP3L, CASP1, CASP10, CASP1, COPl, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CHUK, CYCS, DFFA, DFFB, FADD, FAS, FASLG, GZMB, HELLS, HRK, IKBKB, IKBKG, IRF1, IRF2, IRF3, IRF4, IRF5, IRF6, IRF7, JUN, LTA, MAP2K4, MAP3K1, MAPK10, MDM2, MYC, NFKB1, NFKBIA, NFKBIB, NFKBIE, PRF1, RELA, RIPK1, TNF, TNFRSF10B, TNFRSF1A, TNFRSF1B, TNFRSF21, TNFRSF25, TNFRSF25, PLEKHG5, TNFSF10, TP53, TP73, TRADD, TRAF1, TRAF2, TRAF3 63 APAF1(19), BAD(2), BAK1(4), BAX(4), BCL2L1(3), BCL2L11(4), BID(3), BIRC2(13), BIRC3(3), BIRC5(4), BNIP3L(2), CASP1(7), CASP10(10), CASP2(9), CASP3(4), CASP4(8), CASP6(4), CASP7(4), CASP8(21), CASP9(3), CHUK(11), CYCS(3), DFFA(1), DFFB(3), FADD(1), FAS(7), FASLG(6), GZMB(2), HELLS(14), IKBKB(15), IRF1(2), IRF2(6), IRF3(6), IRF4(6), IRF5(3), IRF6(9), JUN(1), LTA(3), MAP2K4(6), MAP3K1(31), MAPK10(9), MDM2(6), MYC(7), NFKB1(12), NFKBIA(3), NFKBIB(3), NFKBIE(6), PLEKHG5(5), PRF1(8), RELA(6), RIPK1(8), TNF(1), TNFRSF10B(5), TNFRSF1A(6), TNFRSF1B(3), TNFRSF21(3), TNFRSF25(1), TNFSF10(1), TP53(40), TRAF1(5), TRAF2(5), TRAF3(6) 19001456 416 99 396 108 100 149 56 27 80 4 1.07e-14 6.98e-14 95 HSA00562_INOSITOL_PHOSPHATE_METABOLISM Genes involved in inositol phosphate metabolism CARKL, FN3K, IMPA1, IMPA2, INPP1, INPP4A, INPP4B, INPP5A, INPP5B, INPP5E, INPPL1, IPMK, ISYNA1, ITGB1BP3, ITPK1, ITPKA, ITPKB, MINPP1, MIOX, OCRL, PI4KA, PI4KB, PIB5PA, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCZ1, PTEN, PTPMT1, SKIP, SYNJ1, SYNJ2 44 IMPA1(4), IMPA2(6), INPP1(2), INPP4A(23), INPP4B(17), INPP5A(6), INPP5B(8), INPPL1(23), IPMK(7), ITGB1BP3(1), ITPK1(2), ITPKB(6), MINPP1(5), OCRL(20), PI4KA(18), PI4KB(12), PIK3C3(11), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIP4K2A(4), PIP4K2B(9), PIP4K2C(4), PIP5K1A(7), PIP5K1B(6), PIP5K1C(5), PLCB1(6), PLCB2(9), PLCB3(9), PLCB4(20), PLCD1(5), PLCD3(7), PLCD4(13), PLCE1(36), PLCG1(12), PLCG2(27), PLCZ1(16), PTEN(198), PTPMT1(1), SYNJ1(27), SYNJ2(13) 24395208 797 198 628 151 187 214 165 38 167 26 1.09e-14 7.05e-14 96 HDACPATHWAY Myocyte enhancer factor MEF2 activates transcription of genes required for muscle cell differentiation and is inhibited by histone deacetylases. AKT1, AVP, CABIN1, CALM1, CALM2, CALM3, CAMK1, CAMK1G, HDAC5, IGF1, IGF1R, INS, INSR, MAP2K6, MAPK14, MAPK7, MEF2A, MEF2B, MEF2C, MEF2D, MYOD1, NFATC1, NFATC2, PIK3CA, PIK3R1, PPP3CA, PPP3CB, PPP3CC, SYT1, YWHAH 28 AKT1(8), CABIN1(15), CALM2(3), CALM3(1), CAMK1(9), CAMK1G(5), HDAC5(15), IGF1(3), IGF1R(13), INSR(18), MAP2K6(9), MAPK14(6), MAPK7(17), MEF2A(5), MEF2B(3), MEF2C(11), MEF2D(7), MYOD1(3), NFATC2(15), PIK3CA(138), PIK3R1(67), PPP3CA(4), PPP3CB(7), PPP3CC(6), SYT1(4), YWHAH(4) 11307568 396 171 301 70 97 125 79 22 62 11 1.21e-14 7.77e-14 97 RASPATHWAY Ras activation stimulates many signaling cascades, including PI3K/AKT activation to inhibit apoptosis. AKT1, ARHA, BAD, BCL2L1, CASP9, CDC42, CHUK, ELK1, H2AFX, HRAS, MAP2K1, MAPK3, MLLT7, NFKB1, PIK3CA, PIK3R1, RAC1, RAF1, RALA, RALBP1, RALGDS, RELA, RHOA 21 AKT1(8), BAD(2), BCL2L1(3), CASP9(3), CDC42(5), CHUK(11), ELK1(2), H2AFX(1), MAP2K1(2), MAPK3(4), NFKB1(12), PIK3CA(138), PIK3R1(67), RAF1(7), RALA(4), RALBP1(7), RALGDS(10), RELA(6), RHOA(4) 6509643 296 162 202 20 70 79 73 15 48 11 1.24e-14 7.90e-14 98 RAC1PATHWAY Rac-1 is a Rho family G protein that stimulates formation of actin-dependent structures such as filopodia and lamellopodia. ARFIP2, CDK5, CDK5R1, CFL1, CHN1, LIMK1, MAP3K1, MYL2, MYLK, NCF2, PAK1, PDGFRA, PIK3CA, PIK3R1, PLD1, PPP1R12B, RAC1, RALBP1, RPS6KB1, TRIO, VAV1, WASF1 22 ARFIP2(2), CDK5(1), CDK5R1(5), CFL1(1), CHN1(1), LIMK1(7), MAP3K1(31), MYL2(1), MYLK(17), NCF2(6), PAK1(3), PDGFRA(29), PIK3CA(138), PIK3R1(67), PLD1(16), PPP1R12B(18), RALBP1(7), RPS6KB1(3), TRIO(38), VAV1(16), WASF1(3) 12394062 410 163 311 55 108 110 75 22 76 19 1.35e-14 8.51e-14 99 SIG_PIP3_SIGNALING_IN_B_LYMPHOCYTES Genes related to PIP3 signaling in B lymphocytes AKT1, AKT2, AKT3, BCR, BTK, CD19, CDKN2A, DAPP1, FLOT1, FLOT2, FOXO3A, GAB1, ITPR1, ITPR2, ITPR3, LYN, NR0B2, P101-PI3K, PDK1, PHF11, PIK3CA, PITX2, PLCG2, PPP1R13B, PREX1, PSCD3, PTEN, PTPRC, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SAG, SYK, TEC, VAV1 33 AKT1(8), AKT2(4), AKT3(8), BCR(6), BTK(11), CD19(7), CDKN2A(1), DAPP1(7), FLOT1(1), FLOT2(3), GAB1(10), ITPR1(31), ITPR2(38), ITPR3(23), LYN(7), NR0B2(2), PDK1(7), PHF11(4), PIK3CA(138), PITX2(10), PLCG2(27), PPP1R13B(7), PREX1(25), PTEN(198), PTPRC(15), RPS6KA1(5), RPS6KA2(16), RPS6KA3(17), RPS6KB1(3), SAG(5), SYK(6), TEC(5), VAV1(16) 19405366 671 201 505 125 146 191 142 30 138 24 1.44e-14 8.89e-14 100 HSA04664_FC_EPSILON_RI_SIGNALING_PATHWAY Genes involved in Fc epsilon RI signaling pathway AKT1, AKT2, AKT3, BTK, CSF2, FCER1A, FCER1G, FYN, GAB2, GRB2, HRAS, IL13, IL3, IL4, IL5, INPP5D, KRAS, LAT, LCP2, LYN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK9, MS4A2, NRAS, PDK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCD, PRKCE, RAC1, RAC2, RAC3, RAF1, SOS1, SOS2, SYK, TNF, VAV1, VAV2, VAV3 69 AKT1(8), AKT2(4), AKT3(8), BTK(11), FCER1A(6), FCER1G(1), FYN(7), GAB2(12), GRB2(3), IL5(2), INPP5D(14), KRAS(29), LCP2(7), LYN(7), MAP2K1(2), MAP2K3(8), MAP2K4(6), MAP2K6(9), MAPK1(2), MAPK10(9), MAPK13(2), MAPK14(6), MAPK3(4), MAPK8(7), MAPK9(7), MS4A2(4), NRAS(10), PDK1(7), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PLA2G10(1), PLA2G12A(1), PLA2G12B(3), PLA2G1B(1), PLA2G2D(2), PLA2G2E(3), PLA2G2F(3), PLA2G3(5), PLA2G4A(11), PLA2G5(2), PLA2G6(6), PLCG1(12), PLCG2(27), PRKCA(10), PRKCD(7), PRKCE(11), RAC2(2), RAF1(7), SOS1(21), SOS2(22), SYK(6), TNF(1), VAV1(16), VAV2(5), VAV3(13) 23564205 679 177 549 135 185 207 131 37 100 19 1.44e-14 8.89e-14 101 NGFPATHWAY Nerve growth factor (NGF) stimulates neural survival and proliferation via the TrkA and p75 receptors, which induce DAG and IP3 production and activate Ras. CSNK2A1, DPM2, ELK1, FOS, GRB2, HRAS, JUN, KLK2, MAP2K1, MAPK3, MAPK8, NGFB, NGFR, PIK3CA, PIK3R1, PLCG1, RAF1, SHC1, SOS1 18 CSNK2A1(9), DPM2(4), ELK1(2), FOS(6), GRB2(3), JUN(1), KLK2(2), MAP2K1(2), MAPK3(4), MAPK8(7), NGFR(4), PIK3CA(138), PIK3R1(67), PLCG1(12), RAF1(7), SHC1(11), SOS1(21) 6623407 300 156 206 21 82 72 68 17 48 13 1.62e-14 9.86e-14 102 GCRPATHWAY Corticosteroids activate the glucocorticoid receptor (GR), which inhibits NF-kB and activates Annexin-1, thus inhibiting the inflammatory response. ADRB2, AKT1, ANXA1, CALM1, CALM2, CALM3, CRN, GNAS, GNB1, GNGT1, HSPCA, NFKB1, NOS3, NPPA, NR3C1, PIK3CA, PIK3R1, RELA, SYT1 17 ADRB2(8), AKT1(8), ANXA1(4), CALM2(3), CALM3(1), GNAS(25), GNB1(3), NFKB1(12), NOS3(11), NPPA(1), NR3C1(13), PIK3CA(138), PIK3R1(67), RELA(6), SYT1(4) 5881790 304 162 209 26 77 83 70 13 50 11 1.63e-14 9.86e-14 103 SIG_PIP3_SIGNALING_IN_CARDIAC_MYOCTES Genes related to PIP3 signaling in cardiac myocytes AKT1, AKT2, AKT3, BAD, BCL2L1, CDC42, CDK2, CDKN1B, CDKN2A, CREB1, CREB3, CREB5, EBP, ERBB4, F2RL2, FOXO3A, FRAP1, GAB1, GADD45A, GRB2, GSK3A, GSK3B, IFI27, IGF1, IGFBP1, INPPL1, IRS1, IRS2, IRS4, MET, MYC, NOLC1, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARD3, PARD6A, PDK1, PIK3CA, PIK3CD, PPP1R13B, PREX1, PSCD3, PTEN, PTK2, PTPN1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SLC2A4, SOS1, SOS2, TSC1, TSC2, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 62 AKT1(8), AKT2(4), AKT3(8), BAD(2), BCL2L1(3), CDC42(5), CDK2(5), CDKN1B(5), CDKN2A(1), CREB1(5), CREB3(2), CREB5(6), ERBB4(29), F2RL2(3), GAB1(10), GRB2(3), GSK3A(9), GSK3B(11), IFI27(1), IGF1(3), IGFBP1(5), INPPL1(23), IRS1(17), IRS4(20), MET(10), MYC(7), NOLC1(10), PAK1(3), PAK2(6), PAK3(14), PAK4(2), PAK6(3), PAK7(12), PARD3(27), PARD6A(1), PDK1(7), PIK3CA(138), PIK3CD(10), PPP1R13B(7), PREX1(25), PTEN(198), PTK2(11), PTPN1(4), RPS6KA1(5), RPS6KA2(16), RPS6KA3(17), RPS6KB1(3), SHC1(11), SLC2A4(4), SOS1(21), SOS2(22), TSC1(13), TSC2(14), YWHAB(1), YWHAE(1), YWHAG(3), YWHAH(4), YWHAQ(3), YWHAZ(1) 25549578 822 203 648 135 167 247 174 40 168 26 1.74e-14 1.04e-13 104 HSA04510_FOCAL_ADHESION Genes involved in focal adhesion ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, ARHGAP5, BAD, BCAR1, BCL2, BIRC2, BIRC3, BIRC4, BRAF, CAPN2, CAV1, CAV2, CAV3, CCND1, CCND2, CCND3, CDC42, CHAD, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, COMP, CRK, CRKL, CTNNB1, DIAPH1, DOCK1, EGF, EGFR, ELK1, ERBB2, FARP2, FIGF, FLNA, FLNB, FLNC, FLT1, FN1, FYN, GRB2, GRLF1, GSK3B, HGF, HRAS, IBSP, IGF1, IGF1R, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAV, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, JUN, KDR, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, LOC653852, MAP2K1, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MET, MLCK, MRCL3, MRLC2, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARVA, PARVB, PARVG, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP5K1C, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PRKCA, PRKCB1, PRKCG, PTEN, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RAP1A, RAP1B, RAPGEF1, RELN, RHOA, ROCK1, ROCK2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SPP1, SRC, THBS1, THBS2, THBS3, THBS4, TLN1, TLN2, TNC, TNN, TNR, TNXB, VASP, VAV1, VAV2, VAV3, VCL, VEGFA, VEGFB, VEGFC, VTN, VWF, ZYX 185 ACTB(5), ACTN1(13), ACTN2(9), ACTN3(10), ACTN4(11), AKT1(8), AKT2(4), AKT3(8), ARHGAP5(24), BAD(2), BIRC2(13), BIRC3(3), BRAF(12), CAPN2(6), CAV2(1), CCND1(10), CCND2(7), CCND3(5), CDC42(5), CHAD(3), COL11A1(36), COL11A2(13), COL1A1(12), COL1A2(22), COL2A1(14), COL3A1(18), COL4A1(23), COL4A2(11), COL4A4(24), COL4A6(35), COL5A1(33), COL5A2(24), COL5A3(23), COL6A3(54), COL6A6(38), COMP(7), CRK(1), CRKL(5), CTNNB1(66), DIAPH1(11), DOCK1(32), EGF(24), EGFR(20), ELK1(2), ERBB2(6), FARP2(18), FIGF(5), FLNA(31), FLNB(38), FLNC(34), FLT1(23), FN1(39), FYN(7), GRB2(3), GSK3B(11), HGF(15), IBSP(6), IGF1(3), IGF1R(13), ILK(8), ITGA1(20), ITGA10(11), ITGA11(12), ITGA2(21), ITGA2B(11), ITGA3(6), ITGA4(12), ITGA5(12), ITGA6(12), ITGA7(10), ITGA8(16), ITGA9(15), ITGAV(10), ITGB1(12), ITGB3(16), ITGB4(12), ITGB5(8), ITGB6(6), ITGB7(8), ITGB8(5), JUN(1), KDR(23), LAMA1(39), LAMA2(62), LAMA3(35), LAMA4(22), LAMB1(22), LAMB2(27), LAMB3(16), LAMB4(27), LAMC1(17), LAMC2(12), LAMC3(13), MAP2K1(2), MAPK1(2), MAPK10(9), MAPK3(4), MAPK8(7), MAPK9(7), MET(10), MYL2(1), MYL5(3), MYL7(4), MYL9(3), MYLK(17), MYLK2(7), MYLPF(2), PAK1(3), PAK2(6), PAK3(14), PAK4(2), PAK6(3), PAK7(12), PARVA(2), PARVB(2), PARVG(3), PDGFB(4), PDGFC(4), PDGFD(6), PDGFRA(29), PDGFRB(12), PDPK1(3), PGF(2), PIK3CA(138), PIK3CB(19), PIK3CD(10), PIK3CG(25), PIK3R1(67), PIK3R2(4), PIK3R3(8), PIK3R5(8), PIP5K1C(5), PPP1CA(6), PPP1CB(7), PPP1CC(2), PPP1R12A(12), PRKCA(10), PRKCG(10), PTEN(198), PTK2(11), PXN(6), RAC2(2), RAF1(7), RAP1A(3), RAP1B(2), RAPGEF1(18), RELN(48), RHOA(4), ROCK1(27), ROCK2(15), SHC1(11), SHC3(9), SHC4(7), SOS1(21), SOS2(22), SPP1(3), SRC(2), THBS1(12), THBS2(22), THBS3(6), THBS4(9), TLN1(28), TLN2(29), TNC(19), TNN(16), TNR(16), TNXB(25), VASP(2), VAV1(16), VAV2(5), VAV3(13), VCL(14), VEGFA(1), VEGFB(2), VEGFC(7), VWF(31), ZYX(12) 124168387 2735 218 2466 716 658 1022 416 134 427 78 2.24e-14 1.33e-13 105 CELL_CYCLE_KEGG ABL1, ASK, ATM, BUB1, BUB1B, BUB3, CCNA1, CCNA2, CCNB1, CCNB2, CCNB3, CCND2, CCND3, CCNE1, CCNE2, CCNH, CDAN1, CDC14A, CDC14B, CDC14B, CDC14C, CDC2, CDC20, CDC25A, CDC25B, CDC25C, CDC45L, CDC6, CDC7, CDH1, CDK2, CDK4, CDKN1A, CDKN2A, CHEK1, CHEK2, DTX4, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, EP300, ESPL1, FLJ14001, GADD45A, GSK3B, HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7A, HDAC8, MAD1L1, MAD2L1, MAD2L2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MPEG1, MPL, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, PLK1, PRKDC, PTPRA, PTTG1, PTTG2, PTTG3, RB1, RBL1, SKP2, SMAD4, SMC1L1, TBC1D8, TFDP1, TGFB1, TP53, WEE1 82 ABL1(9), ATM(54), BUB1(9), BUB1B(6), BUB3(5), CCNA1(4), CCNA2(3), CCNB1(8), CCNB2(4), CCNB3(20), CCND2(7), CCND3(5), CCNE2(6), CCNH(3), CDAN1(12), CDC14A(8), CDC14B(6), CDC20(5), CDC25A(9), CDC25B(3), CDC25C(8), CDC6(3), CDC7(13), CDH1(15), CDK2(5), CDK4(4), CDKN1A(1), CDKN2A(1), CHEK1(4), CHEK2(14), DTX4(7), E2F1(12), E2F2(1), E2F3(5), E2F4(3), E2F5(1), E2F6(3), EP300(29), ESPL1(10), GSK3B(11), HDAC1(4), HDAC2(5), HDAC3(10), HDAC4(18), HDAC5(15), HDAC6(22), HDAC8(3), MAD1L1(15), MAD2L1(5), MAD2L2(3), MCM2(10), MCM3(9), MCM4(9), MCM5(12), MCM6(9), MCM7(5), MDM2(6), MPEG1(13), MPL(5), PCNA(3), PLK1(6), PRKDC(70), PTPRA(11), PTTG1(5), PTTG2(1), RB1(31), RBL1(17), SKP2(6), SMAD4(5), TBC1D8(12), TGFB1(4), TP53(40), WEE1(1) 39010775 726 121 691 171 165 304 93 31 116 17 3.06e-14 1.80e-13 106 ST_DICTYOSTELIUM_DISCOIDEUM_CAMP_CHEMOTAXIS_PATHWAY The fungus Dictyostelium discoideum is a model system for cytoskeletal organization during chemotaxis. ACTR2, ACTR3, AKT1, ANGPTL2, BF, DAG1, DGKA, ETFA, GCA, ITGA9, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, MAP2K1, MAPK1, MAPK3, NR1I3, PAK1, PDE3A, PDE3B, PI3, PIK3C2G, PIK3CA, PIK3CD, PIK3R1, PLDN, PSME1, RIPK3, RPS4X, SGCB, VASP 31 ACTR2(7), ACTR3(3), AKT1(8), ANGPTL2(9), DAG1(7), DGKA(15), ETFA(4), GCA(3), ITGA9(15), ITPKB(6), ITPR1(31), ITPR2(38), ITPR3(23), MAP2K1(2), MAPK1(2), MAPK3(4), NR1I3(7), PAK1(3), PDE3A(17), PDE3B(15), PI3(3), PIK3C2G(22), PIK3CA(138), PIK3CD(10), PIK3R1(67), PLDN(4), PSME1(2), RIPK3(2), RPS4X(4), SGCB(4), VASP(2) 17180993 477 166 382 93 124 148 97 19 72 17 3.31e-14 1.92e-13 107 SIG_CD40PATHWAYMAP Genes related to CD40 signaling DUSP1, GORASP1, IKBKG, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MAPKAPK5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PIK3CA, PIK3CD, PIK3R1, SYT1, TNFRSF5, TRAF2, TRAF3, TRAF5, TRAF6 27 DUSP1(2), GORASP1(7), MAP2K4(6), MAPK1(2), MAPK10(9), MAPK13(2), MAPK14(6), MAPK3(4), MAPK8(7), MAPK8IP1(5), MAPK9(7), MAPKAPK5(6), NFKB1(12), NFKB2(10), NFKBIA(3), NFKBIB(3), NFKBIE(6), NFKBIL1(2), PIK3CA(138), PIK3CD(10), PIK3R1(67), SYT1(4), TRAF2(5), TRAF3(6), TRAF5(8), TRAF6(4) 9658946 341 165 251 39 86 95 73 15 59 13 3.67e-14 2.12e-13 108 SIG_IL4RECEPTOR_IN_B_LYPHOCYTES Genes related to IL4 rceptor signaling in B lymphocytes AKT1, AKT2, AKT3, BAD, BCL2, GRB2, GSK3A, GSK3B, IL4R, IRS1, IRS2, JAK1, JAK3, MAP4K1, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIK3R1, PPP1R13B, RAF1, SHC1, SOCS1, SOS1, SOS2, STAT6 25 AKT1(8), AKT2(4), AKT3(8), BAD(2), GRB2(3), GSK3A(9), GSK3B(11), IL4R(6), IRS1(17), JAK1(31), JAK3(9), MAP4K1(13), MAPK1(2), MAPK3(4), PDK1(7), PIK3CA(138), PIK3CD(10), PIK3R1(67), PPP1R13B(7), RAF1(7), SHC1(11), SOS1(21), SOS2(22), STAT6(10) 12221982 427 169 322 50 98 125 88 22 73 21 3.83e-14 2.18e-13 109 HSA04520_ADHERENS_JUNCTION Genes involved in adherens junction ACP1, ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, ACVR1B, ACVR1C, BAIAP2, CDC42, CDH1, CREBBP, CSNK2A1, CSNK2A2, CSNK2B, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTNND1, EGFR, EP300, ERBB2, FARP2, FER, FGFR1, FYN, IGF1R, INSR, IQGAP1, LEF1, LMO7, MAP3K7, MAPK1, MAPK3, MET, MLLT4, NLK, PARD3, PTPN1, PTPN6, PTPRB, PTPRF, PTPRJ, PTPRM, PVRL1, PVRL2, PVRL3, PVRL4, RAC1, RAC2, RAC3, RHOA, SMAD2, SMAD3, SMAD4, SNAI1, SNAI2, SORBS1, SRC, SSX2IP, TCF7, TCF7L1, TCF7L2, TGFBR1, TGFBR2, TJP1, VCL, WAS, WASF1, WASF2, WASF3, WASL, YES1 74 ACP1(4), ACTB(5), ACTN1(13), ACTN2(9), ACTN3(10), ACTN4(11), ACVR1B(6), ACVR1C(7), BAIAP2(1), CDC42(5), CDH1(15), CREBBP(37), CSNK2A1(9), CSNK2A2(5), CTNNA1(18), CTNNA2(13), CTNNA3(13), CTNNB1(66), CTNND1(22), EGFR(20), EP300(29), ERBB2(6), FARP2(18), FER(14), FGFR1(10), FYN(7), IGF1R(13), INSR(18), IQGAP1(12), LEF1(9), LMO7(27), MAP3K7(8), MAPK1(2), MAPK3(4), MET(10), MLLT4(32), NLK(5), PARD3(27), PTPN1(4), PTPRB(31), PTPRF(34), PTPRJ(16), PTPRM(19), PVRL1(9), PVRL2(5), PVRL3(9), PVRL4(5), RAC2(2), RHOA(4), SMAD2(12), SMAD3(4), SMAD4(5), SNAI1(2), SNAI2(8), SORBS1(22), SRC(2), SSX2IP(10), TCF7(4), TCF7L1(5), TCF7L2(18), TGFBR1(8), TGFBR2(6), TJP1(33), VCL(14), WAS(14), WASF1(3), WASF2(5), WASF3(9), WASL(8), YES1(5) 41473192 875 149 804 229 235 346 108 54 118 14 4.33e-14 2.45e-13 110 AKTPATHWAY Second messenger PIP3 promotes cell survival by activating the anti-apoptotic kinase AKT. AKT1, BAD, CASP9, CHUK, FOXO1A, FOXO3A, GH1, GHR, HSPCA, MLLT7, NFKB1, NFKBIA, PDPK1, PIK3CA, PIK3R1, PPP2CA, RELA, TNFSF6, YWHAH 14 AKT1(8), BAD(2), CASP9(3), CHUK(11), GH1(6), GHR(10), NFKB1(12), NFKBIA(3), PDPK1(3), PIK3CA(138), PIK3R1(67), PPP2CA(6), RELA(6), YWHAH(4) 5035491 279 160 187 12 64 71 72 16 45 11 5.68e-14 3.18e-13 111 VEGFPATHWAY Vascular endothelial growth factor (VEGF) is upregulated by hypoxic conditions and promotes normal blood vessel formation and angiogenesis related to tumor growth or cardiac disease. ARNT, EIF1, EIF1A, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, ELAVL1, FLT1, FLT4, HIF1A, HRAS, KDR, NOS3, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTK2, PXN, SHC1, VEGF, VHL 25 ARNT(7), EIF1(1), EIF2B1(1), EIF2B2(4), EIF2B3(8), EIF2B4(5), EIF2B5(6), EIF2S1(1), EIF2S2(5), EIF2S3(6), ELAVL1(6), FLT1(23), FLT4(10), HIF1A(17), KDR(23), NOS3(11), PIK3CA(138), PIK3R1(67), PLCG1(12), PRKCA(10), PTK2(11), PXN(6), SHC1(11), VHL(2) 11075738 391 157 299 57 101 117 77 21 64 11 5.77e-14 3.20e-13 112 SA_TRKA_RECEPTOR The TrkA receptor binds nerve growth factor to activate MAP kinase pathways and promote cell growth. AKT1, AKT2, AKT3, ARHA, CDKN1A, ELK1, GRB2, HRAS, MAP2K1, MAP2K2, NGFB, NGFR, NTRK1, PIK3CA, PIK3CD, SHC1, SOS1 14 AKT1(8), AKT2(4), AKT3(8), CDKN1A(1), ELK1(2), GRB2(3), MAP2K1(2), NGFR(4), NTRK1(11), PIK3CA(138), PIK3CD(10), SHC1(11), SOS1(21) 5241748 223 129 140 25 72 70 53 13 13 2 6.83e-14 3.76e-13 113 FBW7PATHWAY Cyclin E interacts with cell cycle checkpoint kinase cdk2 to allow transcription of genes required for S phase, including transcription of additional cyclin E. CCNE1, CDC34, CDK2, CUL1, E2F1, FBXW7, RB1, SKP1A, TFDP1 7 CDK2(5), CUL1(12), E2F1(12), FBXW7(34), RB1(31) 2851031 94 47 85 10 17 37 11 5 18 6 1.35e-13 7.38e-13 114 ATRBRCAPATHWAY BRCA1 and 2 block cell cycle progression in response to DNA damage and promote double-stranded break repair; mutations induce breast cancer susceptibility. ATM, ATR, BRCA1, BRCA2, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, HUS1, MRE11A, NBS1, RAD1, RAD17, RAD50, RAD51, RAD9A, TP53, TREX1 21 ATM(54), ATR(38), BRCA1(19), BRCA2(51), CHEK1(4), CHEK2(14), FANCC(8), FANCD2(17), FANCE(10), FANCF(4), FANCG(8), HUS1(5), MRE11A(12), RAD1(3), RAD17(9), RAD50(19), RAD51(4), RAD9A(2), TP53(40), TREX1(1) 15726439 322 90 303 45 69 111 55 16 61 10 3.50e-13 1.89e-12 115 ST_JNK_MAPK_PATHWAY JNKs are MAP kinases regulated by several levels of kinases (MAPKK, MAPKKK) and phosphorylate transcription factors and regulatory proteins. AKT1, ATF2, CDC42, DLD, DUSP10, DUSP4, DUSP8, GAB1, GADD45A, GCK, IL1R1, JUN, MAP2K4, MAP2K5, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K9, MAPK10, MAPK7, MAPK8, MAPK9, MYEF2, NFATC3, NR2C2, PAPPA, SHC1, TP53, TRAF6, ZAK 36 AKT1(8), ATF2(6), CDC42(5), DLD(7), DUSP10(7), DUSP4(1), GAB1(10), GCK(5), IL1R1(5), JUN(1), MAP2K4(6), MAP2K5(2), MAP3K1(31), MAP3K10(7), MAP3K11(5), MAP3K12(8), MAP3K13(13), MAP3K2(8), MAP3K3(9), MAP3K4(23), MAP3K5(21), MAP3K7(8), MAP3K9(6), MAPK10(9), MAPK7(17), MAPK8(7), MAPK9(7), MYEF2(6), NFATC3(12), NR2C2(8), PAPPA(32), SHC1(11), TP53(40), TRAF6(4), ZAK(12) 17052411 367 98 346 98 108 140 43 17 55 4 7.75e-13 4.15e-12 116 HSA04080_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION Genes involved in neuroactive ligand-receptor interaction ADCYAP1R1, ADORA1, ADORA2A, ADORA2B, ADORA3, ADRA1A, ADRA1B, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, ADRB3, AGTR1, AGTR2, AGTRL1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BRS3, C3AR1, C5AR1, CALCR, CALCRL, CCKAR, CCKBR, CGA, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CNR1, CNR2, CRHR1, CRHR2, CTSG, CYSLTR1, CYSLTR2, DRD1, DRD2, DRD3, DRD4, DRD5, EDG1, EDG2, EDG3, EDG4, EDG5, EDG6, EDG7, EDG8, EDNRA, EDNRB, F2, F2R, F2RL1, F2RL2, F2RL3, FPR1, FPRL1, FPRL2, FSHB, FSHR, GABBR1, GABBR2, GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GABRB1, GABRB2, GABRB3, GABRD, GABRE, GABRG1, GABRG2, GABRG3, GABRP, GABRQ, GABRR1, GABRR2, GALR1, GALR2, GALR3, GCGR, GH1, GH2, GHR, GHRHR, GHSR, GIPR, GLP1R, GLP2R, GLRA1, GLRA2, GLRA3, GLRB, GNRHR, GPR156, GPR23, GPR35, GPR50, GPR63, GPR83, GRIA1, GRIA2, GRIA3, GRIA4, GRID1, GRID2, GRIK1, GRIK2, GRIK3, GRIK4, GRIK5, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRIN3A, GRIN3B, GRM1, GRM2, GRM3, GRM4, GRM5, GRM6, GRM7, GRM8, GRPR, GZMA, HCRTR1, HCRTR2, HRH1, HRH2, HRH3, HRH4, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, KISS1R, LEP, LEPR, LHB, LHCGR, LTB4R, LTB4R2, MAS1, MC1R, MC2R, MC3R, MC4R, MC5R, MCHR1, MCHR2, MLNR, MTNR1A, MTNR1B, NMBR, NMUR1, NMUR2, NPBWR1, NPBWR2, NPFFR1, NPFFR2, NPY1R, NPY2R, NPY5R, NR3C1, NTSR1, NTSR2, OPRD1, OPRK1, OPRL1, OPRM1, OXTR, P2RX1, P2RX2, P2RX3, P2RX4, P2RX5, P2RX7, P2RXL1, P2RY1, P2RY10, P2RY11, P2RY13, P2RY14, P2RY2, P2RY4, P2RY5, P2RY6, P2RY8, PARD3, PPYR1, PRL, PRLHR, PRLR, PRSS1, PRSS2, PRSS3, PTAFR, PTGDR, PTGER1, PTGER2, PTGER3, PTGER4, PTGFR, PTGIR, PTH2R, PTHR1, RXFP1, RXFP2, SCTR, SSTR1, SSTR2, SSTR3, SSTR4, SSTR5, TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, TAAR9, TACR1, TACR2, TACR3, TBXA2R, THRA, THRB, TRHR, TRPV1, TSHB, TSHR, TSPO, UTS2R, VIPR1, VIPR2 220 ADCYAP1R1(7), ADORA1(6), ADORA2A(5), ADORA2B(2), ADORA3(5), ADRA1A(11), ADRA1B(7), ADRA2B(5), ADRB1(2), ADRB2(8), AGTR2(8), AVPR1A(8), AVPR1B(3), AVPR2(5), BDKRB1(5), BDKRB2(9), BRS3(13), C3AR1(7), C5AR1(5), CALCR(5), CALCRL(9), CCKAR(12), CCKBR(7), CGA(1), CHRM1(6), CHRM2(9), CHRM3(9), CHRM4(9), CHRM5(13), CNR1(8), CNR2(3), CRHR1(2), CRHR2(2), CTSG(3), CYSLTR1(5), CYSLTR2(6), DRD1(6), DRD2(10), DRD3(5), DRD5(11), EDNRA(6), EDNRB(2), F2(9), F2R(8), F2RL1(3), F2RL2(3), FPR1(4), FSHR(17), GABBR1(17), GABBR2(14), GABRA1(10), GABRA2(12), GABRA3(15), GABRA4(17), GABRA5(8), GABRA6(8), GABRB1(8), GABRB2(16), GABRB3(15), GABRE(7), GABRG1(8), GABRG2(19), GABRG3(14), GABRP(5), GABRQ(7), GABRR1(5), GABRR2(2), GALR1(2), GALR3(3), GH1(6), GH2(5), GHR(10), GHRHR(2), GHSR(7), GIPR(4), GLP1R(8), GLP2R(17), GLRA1(9), GLRA2(6), GLRA3(11), GLRB(8), GNRHR(4), GPR156(6), GPR50(8), GPR63(5), GPR83(5), GRIA1(12), GRIA2(25), GRIA3(26), GRIA4(23), GRID1(16), GRID2(13), GRIK1(16), GRIK2(15), GRIK3(17), GRIK4(8), GRIK5(19), GRIN1(5), GRIN2A(25), GRIN2B(23), GRIN2C(6), GRIN2D(8), GRIN3A(15), GRM1(22), GRM2(7), GRM3(20), GRM4(16), GRM5(22), GRM6(15), GRM7(15), GRM8(24), GRPR(4), GZMA(6), HCRTR1(1), HCRTR2(8), HRH1(9), HRH2(3), HRH4(4), HTR1A(13), HTR1B(6), HTR1D(6), HTR1E(6), HTR1F(15), HTR2A(15), HTR2B(2), HTR2C(18), HTR4(7), HTR5A(9), HTR6(4), HTR7(4), LEP(2), LEPR(15), LHB(3), LHCGR(16), LTB4R(3), LTB4R2(3), MAS1(2), MC2R(2), MC3R(8), MC4R(7), MC5R(12), MCHR1(7), MCHR2(1), MLNR(3), MTNR1A(6), MTNR1B(4), NMBR(4), NMUR1(8), NMUR2(7), NPBWR1(2), NPFFR1(2), NPFFR2(12), NPY1R(6), NPY2R(4), NPY5R(10), NR3C1(13), NTSR1(4), NTSR2(2), OPRD1(2), OPRK1(9), OPRM1(11), OXTR(4), P2RX1(9), P2RX3(9), P2RX4(2), P2RX5(8), P2RX7(3), P2RY1(2), P2RY10(6), P2RY11(7), P2RY13(3), P2RY14(5), P2RY2(6), P2RY4(7), P2RY6(3), PARD3(27), PPYR1(7), PRL(6), PRLHR(2), PRLR(6), PRSS1(7), PRSS3(2), PTAFR(6), PTGDR(6), PTGER2(5), PTGER3(9), PTGER4(8), PTGFR(10), PTGIR(3), PTH2R(7), RXFP1(16), RXFP2(17), SCTR(4), SSTR1(12), SSTR2(3), SSTR3(6), SSTR4(12), TAAR1(6), TAAR2(5), TAAR5(8), TAAR6(5), TAAR8(3), TAAR9(8), TACR1(6), TACR2(4), TACR3(9), THRA(5), THRB(4), TRHR(5), TRPV1(6), TSHB(3), TSHR(12), VIPR1(3) 73228883 1737 151 1671 557 504 721 265 78 167 2 2.24e-12 1.19e-11 117 CALCIUM_REGULATION_IN_CARDIAC_CELLS ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADRA1A, ADRA1B, ADRA1D, ADRB1, ADRB2, ADRB3, ANXA6, ARRB1, ARRB2, ATP1A4, ATP1B1, ATP1B2, ATP1B3, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1S, CACNB1, CACNB3, CALM1, CALM2, CALM3, CALR, CAMK1, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CASQ1, CASQ2, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, FXYD2, GJA1, GJA12, GJA4, GJA5, GJB1, GJB2, GJB3, GJB4, GJB5, GJB6, GNA11, GNAI2, GNAI3, GNAO1, GNAQ, GNAZ, GNB1, GNB2, GNB3, GNB4, GNB5, GNG12, GNG13, GNG2, GNG3, GNG4, GNG5, GNG7, GNGT1, GRK4, GRK5, GRK6, ITPR1, ITPR2, ITPR3, KCNB1, KCNJ3, KCNJ5, MGC11266, MYCBP, NME7, PEA15, PKIA, PKIB, PKIG, PLCB3, PLN, PRKACA, PRKACB, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCQ, PRKCZ, PRKD1, RGS1, RGS10, RGS11, RGS14, RGS16, RGS17, RGS18, RGS19, RGS2, RGS20, RGS3, RGS4, RGS5, RGS6, RGS7, RGS9, RYR1, RYR2, RYR3, SARA1, SFN, SLC8A1, SLC8A3, USP5, YWHAB, YWHAH, YWHAQ, YWHAQ, MIB1 135 ADCY1(17), ADCY2(17), ADCY3(8), ADCY4(8), ADCY5(11), ADCY6(16), ADCY7(6), ADCY8(16), ADCY9(25), ADRA1A(11), ADRA1B(7), ADRB1(2), ADRB2(8), ANXA6(10), ARRB1(7), ARRB2(3), ATP1A4(24), ATP1B1(3), ATP1B2(7), ATP1B3(4), ATP2A2(9), ATP2A3(12), ATP2B1(17), ATP2B2(12), ATP2B3(21), CACNA1A(19), CACNA1B(1), CACNA1C(30), CACNA1D(34), CACNA1E(47), CACNA1S(33), CACNB1(9), CACNB3(6), CALM2(3), CALM3(1), CALR(4), CAMK1(9), CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), CAMK4(5), CASQ1(7), CASQ2(8), CHRM1(6), CHRM2(9), CHRM3(9), CHRM4(9), CHRM5(13), GJA1(6), GJA4(2), GJB1(1), GJB2(3), GJB3(2), GJB4(5), GJB5(3), GJB6(4), GNA11(3), GNAI2(7), GNAI3(3), GNAO1(5), GNAZ(7), GNB1(3), GNB2(5), GNB3(4), GNB4(3), GNB5(3), GNG12(2), GNG13(2), GNG2(2), GNG3(3), GNG4(5), GRK4(14), GRK5(10), GRK6(3), ITPR1(31), ITPR2(38), ITPR3(23), KCNB1(17), KCNJ3(15), KCNJ5(6), MIB1(8), MYCBP(1), NME7(4), PEA15(2), PKIG(2), PLCB3(9), PLN(1), PRKACA(4), PRKACB(2), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PRKCA(10), PRKCD(7), PRKCE(11), PRKCG(10), PRKCH(9), PRKCQ(13), PRKCZ(4), PRKD1(8), RGS1(6), RGS10(3), RGS14(5), RGS16(3), RGS17(5), RGS18(2), RGS2(3), RGS20(5), RGS3(15), RGS4(6), RGS5(4), RGS6(7), RGS7(9), RGS9(19), RYR1(80), RYR2(111), RYR3(87), SLC8A1(20), SLC8A3(14), USP5(13), YWHAB(1), YWHAH(4), YWHAQ(3) 65714962 1359 140 1322 465 398 569 152 73 146 21 3.25e-12 1.71e-11 118 G1_TO_S_CELL_CYCLE_REACTOME ATM, CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNG2, CCNH, CDC25A, CDC45L, CDK2, CDK4, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CREB3, CREB3L1, CREB3L3, CREB3L4, CREBL1, CREBL1, TNXB, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, FLJ14001, GADD45A, GBA2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MNAT1, MYC, MYT1, NACA, NACA, FKSG17, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, POLA2, POLE, POLE2, PRIM1, PRIM2A, RB1, RBL1, RPA1, RPA2, RPA3, TFDP1, TFDP2, TP53, WEE1 63 ATM(54), CCNA1(4), CCNB1(8), CCND1(10), CCND2(7), CCND3(5), CCNE2(6), CCNG2(4), CCNH(3), CDC25A(9), CDK2(5), CDK4(4), CDK7(6), CDKN1A(1), CDKN1B(5), CDKN2A(1), CDKN2C(3), CDKN2D(3), CREB3(2), CREB3L1(6), CREB3L3(9), CREB3L4(8), E2F1(12), E2F2(1), E2F3(5), E2F4(3), E2F5(1), E2F6(3), GBA2(13), MCM2(10), MCM3(9), MCM4(9), MCM5(12), MCM6(9), MCM7(5), MDM2(6), MNAT1(2), MYC(7), NACA(20), PCNA(3), POLE(1), POLE2(4), PRIM1(2), RB1(31), RBL1(17), RPA1(6), RPA2(2), RPA3(4), TFDP2(8), TNXB(25), TP53(40), WEE1(1) 26464948 434 99 410 100 114 166 55 25 66 8 9.66e-11 5.04e-10 119 HSA04730_LONG_TERM_DEPRESSION Genes involved in long-term depression ARAF, BRAF, C7orf16, CACNA1A, CRH, CRHR1, GNA11, GNA12, GNA13, GNAI1, GNAI2, GNAI3, GNAO1, GNAQ, GNAS, GNAZ, GRIA1, GRIA2, GRIA3, GRID2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, IGF1, IGF1R, ITPR1, ITPR2, ITPR3, KRAS, LYN, MAP2K1, MAP2K2, MAPK1, MAPK3, NOS1, NOS2A, NOS3, NPR1, NPR2, NRAS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCB1, PLCB2, PLCB3, PLCB4, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, RAF1, RYR1 73 ARAF(8), BRAF(12), C7orf16(3), CACNA1A(19), CRHR1(2), GNA11(3), GNA12(10), GNA13(9), GNAI1(4), GNAI2(7), GNAI3(3), GNAO1(5), GNAS(25), GNAZ(7), GRIA1(12), GRIA2(25), GRIA3(26), GRID2(13), GRM1(22), GRM5(22), GUCY1A2(10), GUCY1A3(12), GUCY1B3(7), GUCY2C(12), GUCY2D(7), GUCY2F(25), IGF1(3), IGF1R(13), ITPR1(31), ITPR2(38), ITPR3(23), KRAS(29), LYN(7), MAP2K1(2), MAPK1(2), MAPK3(4), NOS1(21), NOS3(11), NPR1(14), NPR2(16), NRAS(10), PLA2G10(1), PLA2G12A(1), PLA2G12B(3), PLA2G1B(1), PLA2G2D(2), PLA2G2E(3), PLA2G2F(3), PLA2G3(5), PLA2G4A(11), PLA2G5(2), PLA2G6(6), PLCB1(6), PLCB2(9), PLCB3(9), PLCB4(20), PPP2CA(6), PPP2CB(2), PPP2R1A(27), PPP2R1B(9), PPP2R2A(15), PPP2R2B(12), PPP2R2C(3), PRKCA(10), PRKCG(10), PRKG1(9), PRKG2(10), RAF1(7), RYR1(80) 37961804 816 124 761 238 217 330 141 35 89 4 1.50e-08 7.77e-08 120 ST_FAS_SIGNALING_PATHWAY The Fas receptor induces apoptosis and NF-kB activation when bound to Fas ligand. ADPRT, ALG2, BAK1, BAX, BFAR, BIRC4, BTK, CAD, CASP10, CASP3, CASP8, CASP8AP2, CD7, CDK2AP1, CSNK1A1, DAXX, DEDD, DEDD2, DFFA, DIABLO, EGFR, EPHB2, FADD, FAF1, FAIM2, FREQ, HRB, HSPB1, IL1A, IL8, MAP2K4, MAP2K7, MAP3K1, MAP3K5, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MCP, MET, NFAT5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, NR0B2, PFN1, PFN2, PTPN13, RALBP1, RIPK1, ROCK1, SMPD1, TNFRSF6, TNFRSF6B, TP53, TPX2, TRAF2, TUFM, VIL2 54 ALG2(2), BAK1(4), BAX(4), BFAR(9), BTK(11), CAD(38), CASP10(10), CASP3(4), CASP8(21), CASP8AP2(18), CDK2AP1(1), CSNK1A1(5), DAXX(11), DEDD(1), DEDD2(2), DFFA(1), DIABLO(2), EGFR(20), EPHB2(10), FADD(1), FAF1(8), FAIM2(2), IL1A(1), IL8(3), MAP2K4(6), MAP3K1(31), MAP3K5(21), MAPK1(2), MAPK10(9), MAPK8(7), MAPK8IP1(5), MAPK9(7), MET(10), NFAT5(13), NFKB1(12), NFKB2(10), NFKBIA(3), NFKBIB(3), NFKBIE(6), NFKBIL1(2), NR0B2(2), PFN1(1), PFN2(3), PTPN13(27), RALBP1(7), RIPK1(8), ROCK1(27), SMPD1(12), TP53(40), TPX2(14), TRAF2(5), TUFM(13) 24163856 495 101 470 116 116 193 68 23 85 10 5.95e-08 3.06e-07 121 HSA04360_AXON_GUIDANCE Genes involved in axon guidance ABL1, ABLIM1, ABLIM2, ABLIM3, ARHGEF12, CDC42, CDK5, CFL1, CFL2, CHP, CXCL12, CXCR4, DCC, DPYSL2, DPYSL5, EFNA1, EFNA2, EFNA3, EFNA4, EFNA5, EFNB1, EFNB2, EFNB3, EPHA1, EPHA2, EPHA3, EPHA4, EPHA5, EPHA6, EPHA7, EPHA8, EPHB1, EPHB2, EPHB3, EPHB4, EPHB6, FES, FYN, GNAI1, GNAI2, GNAI3, GSK3B, HRAS, ITGB1, KRAS, L1CAM, LIMK1, LIMK2, LRRC4C, MAPK1, MAPK3, MET, NCK1, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NGEF, NRAS, NRP1, NTN1, NTN2L, NTN4, NTNG1, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PLXNA1, PLXNA2, PLXNA3, PLXNB1, PLXNB2, PLXNB3, PLXNC1, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PTK2, RAC1, RAC2, RAC3, RASA1, RGS3, RHOA, RHOD, RND1, ROBO1, ROBO2, ROBO3, ROCK1, ROCK2, SEMA3A, SEMA3B, SEMA3C, SEMA3D, SEMA3E, SEMA3F, SEMA3G, SEMA4A, SEMA4B, SEMA4C, SEMA4D, SEMA4F, SEMA4G, SEMA5A, SEMA5B, SEMA6A, SEMA6B, SEMA6C, SEMA6D, SEMA7A, SLIT1, SLIT2, SLIT3, SRGAP1, SRGAP2, SRGAP3, UNC5A, UNC5B, UNC5C, UNC5D 122 ABL1(9), ABLIM1(8), ABLIM2(5), ABLIM3(9), ARHGEF12(25), CDC42(5), CDK5(1), CFL1(1), CFL2(8), CXCL12(3), CXCR4(1), DCC(35), DPYSL2(11), DPYSL5(5), EFNA1(2), EFNA3(1), EFNA4(3), EFNA5(1), EFNB1(7), EFNB3(2), EPHA1(14), EPHA2(5), EPHA3(14), EPHA4(17), EPHA5(24), EPHA6(21), EPHA7(9), EPHA8(12), EPHB1(25), EPHB2(10), EPHB3(6), EPHB4(4), EPHB6(10), FES(16), FYN(7), GNAI1(4), GNAI2(7), GNAI3(3), GSK3B(11), ITGB1(12), KRAS(29), L1CAM(16), LIMK1(7), LIMK2(16), LRRC4C(9), MAPK1(2), MAPK3(4), MET(10), NCK1(4), NCK2(8), NFAT5(13), NFATC2(15), NFATC3(12), NFATC4(8), NGEF(13), NRAS(10), NRP1(16), NTN1(4), NTN4(5), NTNG1(11), PAK1(3), PAK2(6), PAK3(14), PAK4(2), PAK6(3), PAK7(12), PLXNA1(22), PLXNA2(29), PLXNA3(19), PLXNB1(12), PLXNC1(29), PPP3CA(4), PPP3CB(7), PPP3CC(6), PPP3R1(2), PPP3R2(1), PTK2(11), RAC2(2), RASA1(29), RGS3(15), RHOA(4), RHOD(3), RND1(7), ROBO1(25), ROBO2(27), ROBO3(16), ROCK1(27), ROCK2(15), SEMA3A(10), SEMA3B(8), SEMA3C(10), SEMA3D(9), SEMA3E(8), SEMA3F(6), SEMA3G(5), SEMA4A(7), SEMA4B(5), SEMA4C(8), SEMA4D(12), SEMA4F(15), SEMA4G(10), SEMA5A(19), SEMA5B(13), SEMA6A(13), SEMA6C(7), SEMA6D(23), SEMA7A(11), SLIT1(11), SLIT2(30), SLIT3(21), SRGAP1(21), SRGAP2(18), SRGAP3(13), UNC5A(11), UNC5B(9), UNC5C(8), UNC5D(14) 64216432 1292 134 1224 392 356 482 189 56 197 12 2.59e-07 1.32e-06 122 CARM_ERPATHWAY Methyltransferase CARM1 methylates CBP and co-activates estrogen receptors via Grip1. BRCA1, CARM1, CCND1, CREBBP, EP300, ERCC3, ESR1, GRIP1, GTF2A1, GTF2E1, GTF2F1, HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HIST2H3C, MEF2C, NCOR2, NR0B1, NRIP1, PELP1, POLR2A, PPARBP, PPARGC1, REA, SHARP, SRA1, TBP 25 BRCA1(19), CARM1(6), CCND1(10), CREBBP(37), EP300(29), ERCC3(11), ESR1(15), GRIP1(12), GTF2A1(5), GTF2E1(4), GTF2F1(6), HDAC1(4), HDAC2(5), HDAC3(10), HDAC4(18), HDAC5(15), HDAC6(22), MEF2C(11), NCOR2(24), NR0B1(8), NRIP1(18), PELP1(13), POLR2A(25), SRA1(3), TBP(5) 15123681 335 81 322 104 56 167 42 14 54 2 5.60e-07 2.83e-06 123 HIVNEFPATHWAY HIV-infected CD4 helper T cells may express Fas ligand, which binds to the Fas receptors of uninfected cells and induces apoptosis. ACTG1, ADPRT, APAF1, ARHGDIB, BAG4, BCL2, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CDC2L1, CDC2L2, CFLAR, CHUK, CRADD, CYCS, DAXX, DFFA, DFFB, FADD, GSN, LMNA, LMNB1, LMNB2, MAP2K7, MAP3K1, MAP3K14, MAP3K5, MAPK8, MDM2, NFKB1, NFKBIA, NUMA1, PAK2, PRKCD, PRKDC, PSEN1, PSEN2, PTK2, RASA1, RB1, RELA, RIPK1, SPTAN1, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TRADD, TRAF1, TRAF2 49 APAF1(19), ARHGDIB(2), BAG4(4), BID(3), BIRC2(13), BIRC3(3), CASP2(9), CASP3(4), CASP6(4), CASP7(4), CASP8(21), CASP9(3), CFLAR(7), CHUK(11), CRADD(3), CYCS(3), DAXX(11), DFFA(1), DFFB(3), FADD(1), GSN(5), LMNA(8), LMNB1(5), MAP3K1(31), MAP3K14(12), MAP3K5(21), MAPK8(7), MDM2(6), NFKB1(12), NFKBIA(3), NUMA1(28), PAK2(6), PRKCD(7), PRKDC(70), PSEN1(4), PSEN2(5), PTK2(11), RASA1(29), RB1(31), RELA(6), RIPK1(8), SPTAN1(29), TNF(1), TNFRSF1A(6), TNFRSF1B(3), TRAF1(5), TRAF2(5) 23868452 493 87 480 110 118 183 67 32 82 11 1.27e-06 6.37e-06 124 TGFBPATHWAY The TGF-beta receptor responds to ligand binding by activating the SMAD family of transcriptional regulations, commonly blocking cell growth. APC, CDH1, CREBBP, EP300, MADH2, MADH3, MADH4, MADH7, MADHIP, MAP2K1, MAP3K7, MAP3K7IP1, MAPK3, SKIL, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2 13 APC(53), CDH1(15), CREBBP(37), EP300(29), MAP2K1(2), MAP3K7(8), MAPK3(4), SKIL(13), TGFB1(4), TGFB2(6), TGFB3(9), TGFBR1(8), TGFBR2(6) 8955569 194 67 188 48 48 71 27 11 31 6 1.65e-06 8.20e-06 125 CELLCYCLEPATHWAY Cyclins interact with cyclin-dependent kinases to form active kinase complexes that regulate progression through the cell cycle. CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNH, CDC2, CDC25A, CDK2, CDK4, CDK6, CDK7, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CDKN2D, E2F1, RB1, RBL1, TFDP1 21 CCNA1(4), CCNB1(8), CCND1(10), CCND2(7), CCND3(5), CCNH(3), CDC25A(9), CDK2(5), CDK4(4), CDK6(3), CDK7(6), CDKN1A(1), CDKN1B(5), CDKN2A(1), CDKN2C(3), CDKN2D(3), E2F1(12), RB1(31), RBL1(17) 5378217 137 49 129 24 28 51 19 10 25 4 4.66e-06 0.000023 126 HSA04912_GNRH_SIGNALING_PATHWAY Genes involved in GnRH signaling pathway ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ATF4, CACNA1C, CACNA1D, CACNA1F, CACNA1S, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CDC42, CGA, EGFR, ELK1, FSHB, GNA11, GNAQ, GNAS, GNRH1, GNRH2, GNRHR, GRB2, HBEGF, HRAS, ITPR1, ITPR2, ITPR3, JUN, KRAS, LHB, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K1, MAP3K2, MAP3K3, MAP3K4, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK7, MAPK8, MAPK9, MMP14, MMP2, NRAS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCB1, PLCB2, PLCB3, PLCB4, PLD1, PLD2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCD, PRKX, PRKY, PTK2B, RAF1, SOS1, SOS2, SRC 91 ADCY1(17), ADCY2(17), ADCY3(8), ADCY4(8), ADCY5(11), ADCY6(16), ADCY7(6), ADCY8(16), ADCY9(25), ATF4(4), CACNA1C(30), CACNA1D(34), CACNA1F(36), CACNA1S(33), CALM2(3), CALM3(1), CALML6(4), CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), CDC42(5), CGA(1), EGFR(20), ELK1(2), GNA11(3), GNAS(25), GNRH1(1), GNRH2(1), GNRHR(4), GRB2(3), HBEGF(3), ITPR1(31), ITPR2(38), ITPR3(23), JUN(1), KRAS(29), LHB(3), MAP2K1(2), MAP2K3(8), MAP2K4(6), MAP2K6(9), MAP3K1(31), MAP3K2(8), MAP3K3(9), MAP3K4(23), MAPK1(2), MAPK10(9), MAPK13(2), MAPK14(6), MAPK3(4), MAPK7(17), MAPK8(7), MAPK9(7), MMP14(5), MMP2(11), NRAS(10), PLA2G10(1), PLA2G12A(1), PLA2G12B(3), PLA2G1B(1), PLA2G2D(2), PLA2G2E(3), PLA2G2F(3), PLA2G3(5), PLA2G4A(11), PLA2G5(2), PLA2G6(6), PLCB1(6), PLCB2(9), PLCB3(9), PLCB4(20), PLD1(16), PLD2(7), PRKACA(4), PRKACB(2), PRKACG(6), PRKCA(10), PRKCD(7), PRKX(4), PTK2B(16), RAF1(7), SOS1(21), SOS2(22), SRC(2) 43541259 869 120 821 256 245 355 114 45 96 14 9.54e-06 0.000047 127 IL4PATHWAY IL-4 promotes Th2 cell differentiation via a heterodimeric receptor that activates Stat6/JAK and MAP kinase pathways. AKT1, GRB2, IL2RG, IL4, IL4R, IRS1, JAK1, JAK3, RPS6KB1, SHC1, STAT6 11 AKT1(8), GRB2(3), IL2RG(11), IL4R(6), IRS1(17), JAK1(31), JAK3(9), RPS6KB1(3), SHC1(11), STAT6(10) 5226452 109 51 99 25 21 46 11 5 20 6 0.000012 0.000057 128 HSA04120_UBIQUITIN_MEDIATED_PROTEOLYSIS Genes involved in ubiquitin mediated proteolysis ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, BTRC, CDC16, CDC20, CDC23, CDC26, CDC27, CUL1, CUL2, CUL3, FBXW11, FBXW7, FZR1, ITCH, LOC728919, RBX1, SKP1, SKP2, SMURF1, SMURF2, TCEB1, TCEB2, UBA1, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2D4, UBE2E1, UBE2E2, UBE2E3, VHL, WWP1, WWP2 38 ANAPC1(30), ANAPC10(2), ANAPC2(6), ANAPC4(5), ANAPC5(12), ANAPC7(3), BTRC(13), CDC16(1), CDC20(5), CDC23(4), CDC27(22), CUL1(12), CUL2(7), CUL3(18), FBXW11(5), FBXW7(34), ITCH(8), RBX1(1), SKP1(2), SKP2(6), SMURF1(10), SMURF2(4), TCEB1(2), UBA1(20), UBE2C(1), UBE2D2(3), UBE2D3(3), UBE2D4(1), UBE2E1(3), UBE2E2(3), UBE2E3(8), VHL(2), WWP1(18), WWP2(7) 13986997 281 76 269 53 54 121 41 26 37 2 0.000017 0.000083 129 SKP2E2FPATHWAY E2F-1, a transcription factor that promotes the G1/S transition, is repressed by Rb and activated by cdk2/cyclin E. CCNA1, CCNE1, CDC34, CDK2, CUL1, E2F1, RB1, SKP1A, SKP2, TFDP1 8 CCNA1(4), CDK2(5), CUL1(12), E2F1(12), RB1(31), SKP2(6) 2920341 70 35 67 10 14 26 12 3 11 4 0.000031 0.00015 130 HSA04350_TGF_BETA_SIGNALING_PATHWAY Genes involved in TGF-beta signaling pathway ACVR1, ACVR1B, ACVR1C, ACVR2A, ACVR2B, ACVRL1, AMH, AMHR2, BMP2, BMP4, BMP5, BMP6, BMP7, BMP8A, BMP8B, BMPR1A, BMPR1B, BMPR2, CDKN2B, CHRD, COMP, CREBBP, CUL1, DCN, E2F4, E2F5, EP300, FST, GDF5, GDF6, GDF7, hCG_1982709, ID1, ID2, ID3, ID4, IFNG, INHBA, INHBB, INHBC, INHBE, LEFTY1, LEFTY2, LTBP1, MAPK1, MAPK3, MYC, NODAL, NOG, PITX2, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, RBL1, RBL2, RBX1, RHOA, ROCK1, ROCK2, RPS6KB1, RPS6KB2, SKP1, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6, SMAD7, SMAD9, SMURF1, SMURF2, SP1, TFDP1, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, THBS1, THBS2, THBS3, THBS4, TNF, ZFYVE16, ZFYVE9 84 ACVR1(9), ACVR1B(6), ACVR1C(7), ACVR2A(14), ACVR2B(8), ACVRL1(3), AMHR2(4), BMP2(5), BMP4(7), BMP5(16), BMP6(6), BMP7(15), BMP8A(3), BMP8B(1), BMPR1A(8), BMPR1B(6), BMPR2(14), CHRD(14), COMP(7), CREBBP(37), CUL1(12), DCN(11), E2F4(3), E2F5(1), EP300(29), FST(7), GDF5(8), GDF6(4), ID1(2), ID2(1), IFNG(5), INHBA(7), INHBB(3), INHBC(4), INHBE(7), LEFTY1(2), LEFTY2(3), LTBP1(19), MAPK1(2), MAPK3(4), MYC(7), NODAL(2), NOG(1), PITX2(10), PPP2CA(6), PPP2CB(2), PPP2R1A(27), PPP2R1B(9), PPP2R2A(15), PPP2R2B(12), PPP2R2C(3), RBL1(17), RBL2(21), RBX1(1), RHOA(4), ROCK1(27), ROCK2(15), RPS6KB1(3), RPS6KB2(6), SKP1(2), SMAD1(1), SMAD2(12), SMAD3(4), SMAD4(5), SMAD5(9), SMAD7(6), SMAD9(1), SMURF1(10), SMURF2(4), SP1(6), TGFB1(4), TGFB2(6), TGFB3(9), TGFBR1(8), TGFBR2(6), THBS1(12), THBS2(22), THBS3(6), THBS4(9), TNF(1), ZFYVE16(22), ZFYVE9(16) 33286008 693 107 658 176 199 255 88 32 108 11 0.000034 0.00016 131 HSA04320_DORSO_VENTRAL_AXIS_FORMATION Genes involved in dorso-ventral axis formation BRAF, CPEB1, EGFR, ERBB2, ERBB4, ETS1, ETS2, ETV6, ETV7, FMN2, GRB2, KRAS, MAP2K1, MAPK1, MAPK3, NOTCH1, NOTCH2, NOTCH3, NOTCH4, PIWIL1, PIWIL2, PIWIL3, PIWIL4, RAF1, SOS1, SOS2, SPIRE1, SPIRE2 26 BRAF(12), CPEB1(10), EGFR(20), ERBB2(6), ERBB4(29), ETS1(6), ETS2(5), ETV6(9), ETV7(4), FMN2(22), GRB2(3), KRAS(29), MAP2K1(2), MAPK1(2), MAPK3(4), NOTCH2(17), NOTCH3(31), NOTCH4(15), PIWIL1(17), PIWIL2(16), PIWIL3(7), PIWIL4(13), RAF1(7), SOS1(21), SOS2(22), SPIRE1(9) 16203483 338 88 304 55 86 136 59 18 33 6 0.000042 0.00020 132 P27PATHWAY p27 blocks the G1/S transition by inhibiting the checkpoint kinase cdk2/cyclin E and is inhibited by cdk2-mediated ubiquitination. CCNE1, CDK2, CDKN1B, CKS1B, CUL1, E2F1, NEDD8, RB1, RBX1, SKP1A, SKP2, TFDP1, UBE2M 12 CDK2(5), CDKN1B(5), CUL1(12), E2F1(12), RB1(31), RBX1(1), SKP2(6), UBE2M(1) 2997060 73 35 70 11 13 30 12 3 11 4 0.000058 0.00027 133 P38MAPKPATHWAY The Rho family GTPases activate the p38 MAPKs under environmental stress or in the presence of pro-inflammatory cytokines. ATF2, CDC42, CREB1, DAXX, DDIT3, ELK1, GRB2, HMGN1, HRAS, HSPB1, HSPB2, MAP2K4, MAP2K6, MAP3K1, MAP3K5, MAP3K7, MAP3K9, MAPK14, MAPKAPK2, MAPKAPK5, MAX, MEF2A, MEF2B, MEF2C, MEF2D, MKNK1, MYC, PDZGEF1, PLA2G4A, RAC1, RIPK1, RPS6KA5, SHC1, STAT1, TGFB1, TGFB2, TGFB3, TGFBR1, TRADD, TRAF2 37 ATF2(6), CDC42(5), CREB1(5), DAXX(11), DDIT3(1), ELK1(2), GRB2(3), HMGN1(1), HSPB2(1), MAP2K4(6), MAP2K6(9), MAP3K1(31), MAP3K5(21), MAP3K7(8), MAP3K9(6), MAPK14(6), MAPKAPK2(6), MAPKAPK5(6), MAX(8), MEF2A(5), MEF2B(3), MEF2C(11), MEF2D(7), MKNK1(6), MYC(7), PLA2G4A(11), RIPK1(8), RPS6KA5(7), SHC1(11), STAT1(14), TGFB1(4), TGFB2(6), TGFB3(9), TGFBR1(8), TRAF2(5) 12697831 264 73 257 68 68 112 30 16 36 2 0.000091 0.00042 134 SMOOTH_MUSCLE_CONTRACTION ACTA1, ACTA2, ACTC, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADM, ADMR, ARRB1, ARRB2, ATF1, ATF2, ATF3, ATF4, ATF5, ATP2A2, ATP2A3, CACNB3, CALCA, CALM1, CALM2, CALM3, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CMKOR1, CNN1, CNN2, CORIN, CREB3, CREBL1, CREBL1, TNXB, CRH, CRHR1, DGKZ, EDG2, ETS2, FOS, GABPA, GABPB2, GBA2, GJA1, GNAQ, GNB1, GNB2, GNB3, GNB4, GNB5, GNG12, GNG13, GNG2, GNG3, GNG4, GNG5, GNG7, GNGT1, GRK4, GRK5, GRK6, GSTO1, GUCA2A, GUCA2B, GUCY1A3, HEAB, IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP6, IL1B, IL6, ITPR1, ITPR2, ITPR3, JUN, LGR7, LGR8, MAFF, MGC11266, MYL2, MYL4, MYLK2, NFKB1, NOS1, NOS3, OXT, OXTR, PDE4B, PDE4D, PKIA, PKIB, PKIG, PLCB3, PLCD1, PLCG1, PLCG2, PRKACA, PRKACB, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCH, PRKCQ, PRKCZ, PRKD1, RAMP1, RAMP2, RAMP3, RCP9, RGS1, RGS10, RGS11, RGS14, RGS16, RGS17, RGS18, RGS19, RGS2, RGS20, RGS3, RGS4, RGS5, RGS6, RGS7, RGS9, RLN1, RYR1, RYR2, RYR3, SARA1, SFN, SLC8A1, SP1, USP5, YWHAB, YWHAH, YWHAQ, YWHAQ, MIB1 135 ACTA1(4), ACTA2(7), ADCY1(17), ADCY2(17), ADCY3(8), ADCY4(8), ADCY5(11), ADCY6(16), ADCY7(6), ADCY8(16), ADCY9(25), ADM(2), ARRB1(7), ARRB2(3), ATF1(6), ATF2(6), ATF3(4), ATF4(4), ATF5(9), ATP2A2(9), ATP2A3(12), CACNB3(6), CALCA(1), CALM2(3), CALM3(1), CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), CNN1(3), CORIN(11), CREB3(2), CRHR1(2), DGKZ(9), ETS2(5), FOS(6), GABPA(5), GABPB2(10), GBA2(13), GJA1(6), GNB1(3), GNB2(5), GNB3(4), GNB4(3), GNB5(3), GNG12(2), GNG13(2), GNG2(2), GNG3(3), GNG4(5), GRK4(14), GRK5(10), GRK6(3), GSTO1(3), GUCA2A(1), GUCA2B(1), GUCY1A3(12), IGFBP1(5), IGFBP2(4), IGFBP3(7), IGFBP6(2), IL1B(2), IL6(2), ITPR1(31), ITPR2(38), ITPR3(23), JUN(1), MIB1(8), MYL2(1), MYL4(1), MYLK2(7), NFKB1(12), NOS1(21), NOS3(11), OXTR(4), PDE4B(17), PDE4D(7), PKIG(2), PLCB3(9), PLCD1(5), PLCG1(12), PLCG2(27), PRKACA(4), PRKACB(2), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PRKCA(10), PRKCD(7), PRKCE(11), PRKCH(9), PRKCQ(13), PRKCZ(4), PRKD1(8), RAMP1(2), RAMP2(1), RAMP3(2), RGS1(6), RGS10(3), RGS14(5), RGS16(3), RGS17(5), RGS18(2), RGS2(3), RGS20(5), RGS3(15), RGS4(6), RGS5(4), RGS6(7), RGS7(9), RGS9(19), RLN1(3), RYR1(80), RYR2(111), RYR3(87), SLC8A1(20), SP1(6), TNXB(25), USP5(13), YWHAB(1), YWHAH(4), YWHAQ(3) 60185458 1179 120 1147 405 347 483 147 57 126 19 0.000095 0.00044 135 PELP1PATHWAY Pelp1 acts downstream of activated estrogen receptor to promote cell proliferation and is overexpressed in many breast tumors. CREBBP, EP300, ESR1, MAPK1, MAPK3, PELP1, SRC 7 CREBBP(37), EP300(29), ESR1(15), MAPK1(2), MAPK3(4), PELP1(13), SRC(2) 4923400 102 45 98 24 24 39 15 6 18 0 0.00020 0.00090 136 CDC25PATHWAY The protein phosphatase Cdc25 is phosphorylated by Chk1 and activates Cdc2 to stimulate eukaryotic cells into M phase. ATM, CDC2, CDC25A, CDC25B, CDC25C, CHEK1, MYT1, WEE1, YWHAH 8 ATM(54), CDC25A(9), CDC25B(3), CDC25C(8), CHEK1(4), WEE1(1), YWHAH(4) 4817762 83 42 77 16 16 24 16 0 23 4 0.00027 0.0012 137 IL6PATHWAY IL-6 binding to its receptor activates JAK kinases and a variety of transcription factors, with effects in neuronal differentiation, bone loss, and inflammation. CEBPB, CSNK2A1, ELK1, FOS, GRB2, HRAS, IL6, IL6R, IL6ST, JAK1, JAK2, JAK3, JUN, MAP2K1, MAPK3, PTPN11, RAF1, SHC1, SOS1, SRF, STAT3 20 CSNK2A1(9), ELK1(2), FOS(6), GRB2(3), IL6(2), IL6R(12), IL6ST(10), JAK1(31), JAK2(21), JAK3(9), JUN(1), MAP2K1(2), MAPK3(4), PTPN11(8), RAF1(7), SHC1(11), SOS1(21), SRF(3), STAT3(12) 8232833 174 57 163 33 40 58 22 14 26 14 0.00031 0.0014 138 ETSPATHWAY The Ets transcription factors are activated by Ras and promote macrophage differentiation. CSF1, CSF1R, DDX20, E2F1, E2F4, ETS1, ETS2, ETV3, FOS, HDAC2, HDAC5, HRAS, JUN, NCOR2, RBL1, RBL2, SIN3A, SIN3B 18 CSF1(5), CSF1R(7), DDX20(6), E2F1(12), E2F4(3), ETS1(6), ETS2(5), ETV3(12), FOS(6), HDAC2(5), HDAC5(15), JUN(1), NCOR2(24), RBL1(17), RBL2(21), SIN3A(28), SIN3B(15) 8035658 188 58 178 44 44 75 22 15 29 3 0.00038 0.0017 139 GPCRDB_CLASS_A_RHODOPSIN_LIKE ADORA1, ADORA2A, ADORA2B, ADORA3, ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2C, ADRB1, ADRB2, ADRB3, AGTR1, AGTR2, AGTRL1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BLR1, BRS3, C3AR1, C5R1, CCBP2, CCKAR, CCKBR, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CCRL1, CCRL2, CHML, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CMKLR1, CMKOR1, CNR1, CNR2, CX3CR1, CXCR3, CXCR4, DRD1, DRD2, DRD3, DRD4, DRD5, EDNRA, EDNRB, ELA3A, F2R, F2RL1, F2RL2, F2RL3, FPR1, FPRL1, FPRL2, FSHR, GALR1, GALR2, GALR3, GALT, GHSR, GNB2L1, GPR10, GPR147, GPR17, GPR173, GPR174, GPR23, GPR24, GPR27, GPR3, GPR30, GPR35, GPR37, GPR37L1, GPR4, GPR44, GPR50, GPR6, GPR63, GPR74, GPR77, GPR83, GPR85, GPR87, GPR92, GRPR, HCRTR1, HCRTR2, HRH1, HRH2, HRH3, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, HTR7, LOC93164, IL8RA, IL8RB, LHCGR, LTB4R, MAS1, MC1R, MC3R, MC4R, MC5R, MLNR, MTNR1A, MTNR1B, NMBR, NMUR1, NMUR2, NPY1R, NPY2R, NPY5R, NPY6R, NTSR1, NTSR2, OPN1SW, OPN3, OPRD1, OPRK1, OPRL1, OPRM1, OR10A5, OR11A1, OR12D3, OR1C1, OR1F1, OR1Q1, OR2H1, OR5V1, OR5V1, OR12D3, OR7A5, OR7C1, OR8B8, OXTR, P2RY1, P2RY10, P2RY11, P2RY12, P2RY13, P2RY14, P2RY2, P2RY5, P2RY6, PPYR1, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, Rgr, RGR, RHO, RRH, SSTR1, SSTR2, SSTR3, SSTR4, SUCNR1, TBXA2R, TRHR 148 ADORA1(6), ADORA2A(5), ADORA2B(2), ADORA3(5), ADRA1A(11), ADRA1B(7), ADRB1(2), ADRB2(8), AGTR2(8), AVPR1A(8), AVPR1B(3), AVPR2(5), BDKRB1(5), BDKRB2(9), BRS3(13), C3AR1(7), CCBP2(3), CCKAR(12), CCKBR(7), CCR1(5), CCR2(6), CCR3(5), CCR4(5), CCR6(5), CCR7(5), CCR8(6), CCR9(2), CCRL1(4), CCRL2(5), CHML(9), CHRM1(6), CHRM2(9), CHRM3(9), CHRM4(9), CHRM5(13), CMKLR1(11), CNR1(8), CNR2(3), CX3CR1(4), CXCR3(5), CXCR4(1), DRD1(6), DRD2(10), DRD3(5), DRD5(11), EDNRA(6), EDNRB(2), F2R(8), F2RL1(3), F2RL2(3), FPR1(4), FSHR(17), GALR1(2), GALR3(3), GALT(2), GHSR(7), GNB2L1(2), GPR17(4), GPR174(11), GPR3(5), GPR37(9), GPR37L1(5), GPR4(7), GPR50(8), GPR6(4), GPR63(5), GPR77(3), GPR83(5), GPR85(7), GPR87(8), GRPR(4), HCRTR1(1), HCRTR2(8), HRH1(9), HRH2(3), HTR1A(13), HTR1B(6), HTR1D(6), HTR1E(6), HTR1F(15), HTR2A(15), HTR2B(2), HTR2C(18), HTR4(7), HTR5A(9), HTR6(4), HTR7(4), LHCGR(16), LTB4R(3), MAS1(2), MC3R(8), MC4R(7), MC5R(12), MLNR(3), MTNR1A(6), MTNR1B(4), NMBR(4), NMUR1(8), NMUR2(7), NPY1R(6), NPY2R(4), NPY5R(10), NTSR1(4), NTSR2(2), OPN1SW(6), OPN3(2), OPRD1(2), OPRK1(9), OPRM1(11), OR10A5(5), OR11A1(3), OR12D3(8), OR1F1(3), OR1Q1(3), OR2H1(2), OR5V1(9), OR7A5(6), OR7C1(10), OR8B8(3), OXTR(4), P2RY1(2), P2RY10(6), P2RY11(7), P2RY12(3), P2RY13(3), P2RY14(5), P2RY2(6), P2RY6(3), PPYR1(7), PTAFR(6), PTGDR(6), PTGER2(5), PTGER4(8), PTGFR(10), PTGIR(3), RGR(6), RHO(8), RRH(3), SSTR1(12), SSTR2(3), SSTR3(6), SSTR4(12), SUCNR1(3), TRHR(5) 39016511 893 109 866 313 251 397 132 39 74 0 0.00049 0.0022 140 HSA04720_LONG_TERM_POTENTIATION Genes involved in long-term potentiation ADCY1, ADCY8, ARAF, ATF4, BRAF, CACNA1C, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CHP, CREBBP, EP300, GNAQ, GRIA1, GRIA2, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRM1, GRM5, HRAS, ITPR1, ITPR2, ITPR3, KRAS, MAP2K1, MAP2K2, MAPK1, MAPK3, NRAS, PLCB1, PLCB2, PLCB3, PLCB4, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R1A, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, RAF1, RAP1A, RAP1B, RAPGEF3, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6 66 ADCY1(17), ADCY8(16), ARAF(8), ATF4(4), BRAF(12), CACNA1C(30), CALM2(3), CALM3(1), CALML6(4), CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), CAMK4(5), CREBBP(37), EP300(29), GRIA1(12), GRIA2(25), GRIN1(5), GRIN2A(25), GRIN2B(23), GRIN2C(6), GRIN2D(8), GRM1(22), GRM5(22), ITPR1(31), ITPR2(38), ITPR3(23), KRAS(29), MAP2K1(2), MAPK1(2), MAPK3(4), NRAS(10), PLCB1(6), PLCB2(9), PLCB3(9), PLCB4(20), PPP1CA(6), PPP1CB(7), PPP1CC(2), PPP1R12A(12), PPP1R1A(4), PPP3CA(4), PPP3CB(7), PPP3CC(6), PPP3R1(2), PPP3R2(1), PRKACA(4), PRKACB(2), PRKACG(6), PRKCA(10), PRKCG(10), PRKX(4), RAF1(7), RAP1A(3), RAP1B(2), RAPGEF3(11), RPS6KA1(5), RPS6KA2(16), RPS6KA3(17), RPS6KA6(15) 34784060 685 108 641 214 177 261 129 26 90 2 0.00051 0.0022 141 MTA3PATHWAY The estrogen receptor regulates proliferation in mammary epithelia via MTA3 activation; loss of either protein is implicated in breast cancer. ALDOA, CTSD, ESR1, GAPD, GREB1, HSPB1, HSPB2, MTA1, MTA3, PDZK1, TUBA1, TUBA2, TUBA3, TUBA4, TUBA6, TUBA8 9 ALDOA(6), CTSD(5), ESR1(15), GREB1(16), HSPB2(1), MTA1(4), MTA3(5), PDZK1(4), TUBA8(11) 3412920 67 37 65 17 13 30 8 7 9 0 0.00055 0.0024 142 ST_P38_MAPK_PATHWAY p38 is a MAP kinase regulated by cytokines and cellular stress. AKT1, ATF1, CDC42, CREB1, CREB3, CREB5, DUSP1, DUSP10, EEF2K, EIF4E, ELK1, GADD45A, HSPB1, IL1R1, MAP2K3, MAP2K4, MAP2K6, MAP3K10, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAPK1, MAPK11, MAPK12, MAPK13, MAPK14, MAPKAPK2, MAPKAPK5, MKNK1, MKNK2, MYEF2, NFKB1, NR2C2, SRF, TRAF6 32 AKT1(8), ATF1(6), CDC42(5), CREB1(5), CREB3(2), CREB5(6), DUSP1(2), DUSP10(7), EEF2K(11), EIF4E(4), ELK1(2), IL1R1(5), MAP2K3(8), MAP2K4(6), MAP2K6(9), MAP3K10(7), MAP3K4(23), MAP3K5(21), MAP3K7(8), MAPK1(2), MAPK13(2), MAPK14(6), MAPKAPK2(6), MAPKAPK5(6), MKNK1(6), MKNK2(4), MYEF2(6), NFKB1(12), NR2C2(8), SRF(3), TRAF6(4) 11095097 210 64 203 61 49 100 30 9 22 0 0.00065 0.0028 143 TERCPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. NFYA, NFYB, NFYC, RB1, SP1, SP3 6 NFYA(7), NFYB(2), NFYC(1), RB1(31), SP1(6), SP3(12) 2386176 59 32 56 12 9 21 13 2 10 4 0.00066 0.0028 144 HSA04920_ADIPOCYTOKINE_SIGNALING_PATHWAY Genes involved in adipocytokine signaling pathway ACACB, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADIPOQ, ADIPOR1, ADIPOR2, AGRP, AKT1, AKT2, AKT3, CAMKK1, CAMKK2, CD36, CHUK, CPT1A, CPT1B, CPT1C, CPT2, FRAP1, G6PC, G6PC2, IKBKB, IKBKG, IRS1, IRS2, IRS4, JAK1, JAK2, JAK3, LEP, LEPR, MAPK10, MAPK8, MAPK9, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NPY, PCK1, PCK2, POMC, PPARA, PPARGC1A, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3, PRKCQ, PTPN11, RELA, RXRA, RXRB, RXRG, SLC2A1, SLC2A4, SOCS3, STAT3, STK11, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF2, TYK2 67 ACACB(31), ACSL1(13), ACSL3(10), ACSL4(24), ACSL5(18), ACSL6(13), ADIPOQ(3), ADIPOR1(2), ADIPOR2(9), AGRP(2), AKT1(8), AKT2(4), AKT3(8), CAMKK1(8), CAMKK2(6), CD36(7), CHUK(11), CPT1A(10), CPT1C(15), CPT2(7), G6PC(6), G6PC2(9), IKBKB(15), IRS1(17), IRS4(20), JAK1(31), JAK2(21), JAK3(9), LEP(2), LEPR(15), MAPK10(9), MAPK8(7), MAPK9(7), NFKB1(12), NFKB2(10), NFKBIA(3), NFKBIB(3), NFKBIE(6), NPY(2), PCK1(15), PCK2(7), POMC(2), PPARA(2), PPARGC1A(13), PRKAA1(6), PRKAA2(9), PRKAB1(7), PRKAB2(2), PRKAG1(2), PRKAG2(4), PRKAG3(6), PRKCQ(13), PTPN11(8), RELA(6), RXRA(1), RXRG(10), SLC2A1(6), SLC2A4(4), STAT3(12), TNF(1), TNFRSF1A(6), TNFRSF1B(3), TRAF2(5), TYK2(7) 28077242 570 96 548 169 126 240 83 29 76 16 0.00088 0.0038 145 STRESSPATHWAY Tumor necrosis factor receptor TNFR1 promotes apoptosis and activates the pro-inflammatory NF-kB, while TNFR2 activates stress-activated protein kinases (SAPKs). ATF1, CASP2, CHUK, CRADD, IKBKB, IKBKG, JUN, LTA, MAP2K3, MAP2K4, MAP2K6, MAP3K1, MAP3K14, MAP4K2, MAPK14, MAPK8, NFKB1, NFKBIA, RELA, RIPK1, TANK, TNF, TNFRSF1A, TRADD, TRAF2 23 ATF1(6), CASP2(9), CHUK(11), CRADD(3), IKBKB(15), JUN(1), LTA(3), MAP2K3(8), MAP2K4(6), MAP2K6(9), MAP3K1(31), MAP3K14(12), MAP4K2(6), MAPK14(6), MAPK8(7), NFKB1(12), NFKBIA(3), RELA(6), RIPK1(8), TANK(4), TNF(1), TNFRSF1A(6), TRAF2(5) 8049998 178 54 175 37 32 70 28 18 28 2 0.00092 0.0039 146 HISTONE_METHYLTRANSFERASE Genes with HMT activity AOF2, KDM6A, ASH1L, ASH2L, C17orf79, CARM1, CTCFL, DOT1L, EED, EHMT1, EHMT2, EZH1, EZH2, FBXL10, FBXL11, FBXO11, HCFC1, HSF4, JMJD1A, JMJD1B, JMJD2A, JMJD2B, JMJD2C, JMJD2D, JMJD3, JMJD4, JMJD6, MEN1, MLL, MLL2, MLL3, MLL4, MLL5, NSD1, OGT, PAXIP1, PPP1CA, PPP1CB, PPP1CC, PRDM2, PRDM6, PRDM7, PRDM9, PRMT1, PRMT5, PRMT6, PRMT7, PRMT8, RBBP5, SATB1, SETD1A, SETD1B, SETD2, SETD7, SETD8, SETDB1, SETDB2, SETMAR, SMYD3, STK38, SUV39H1, SUV39H2, SUV420H1, SUV420H2, SUZ12, WHSC1, WHSC1L1 55 ASH1L(40), ASH2L(11), C17orf79(4), CARM1(6), CTCFL(15), DOT1L(8), EED(6), EHMT2(6), EZH1(11), EZH2(14), FBXO11(8), HCFC1(27), HSF4(2), JMJD4(3), JMJD6(3), KDM6A(10), MEN1(5), MLL(38), MLL2(64), MLL3(71), MLL4(53), MLL5(22), NSD1(36), OGT(19), PAXIP1(2), PPP1CA(6), PPP1CB(7), PPP1CC(2), PRDM2(23), PRDM9(28), PRMT1(7), PRMT5(11), PRMT6(6), PRMT7(4), PRMT8(9), RBBP5(9), SATB1(14), SETD1A(12), SETD2(31), SETD7(6), SETD8(3), SETDB1(19), SETDB2(12), SETMAR(6), SMYD3(4), STK38(7), SUV39H1(10), SUV39H2(6), SUV420H1(11), SUZ12(8), WHSC1(25), WHSC1L1(24) 40754041 794 110 767 181 185 298 116 34 140 21 0.00093 0.0039 147 ST_MYOCYTE_AD_PATHWAY Cardiac myocytes have a variety of adrenergic receptors that induce subtype-specific signaling effects. ADRB1, AKT1, APC, ASAH1, BF, CAMP, CAV3, DAG1, DLG4, EPHB2, GAS, GNAI1, GNAQ, HTATIP, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, PITX2, PLB, PTX1, PTX3, RAC1, RHO, RYR1 23 ADRB1(2), AKT1(8), APC(53), ASAH1(9), CAMP(1), DAG1(7), DLG4(13), EPHB2(10), GNAI1(4), ITPR1(31), ITPR2(38), ITPR3(23), KCNJ3(15), KCNJ5(6), KCNJ9(4), MAPK1(2), PITX2(10), PTX3(2), RHO(8), RYR1(80) 16262038 326 78 310 116 95 139 41 12 31 8 0.0012 0.0052 148 SHHPATHWAY Sonic hedgehog (Shh) signaling in the developing CNS induces neuronal proliferation via interaction with the patched (Ptc-1) and smoothened receptors. DYRK1A, DYRK1B, GLI, GLI2, GLI3, GSK3B, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTCH, SHH, SMO, SUFU 14 DYRK1A(17), DYRK1B(4), GLI2(11), GLI3(21), GSK3B(11), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), SHH(7), SMO(6), SUFU(7) 5503931 113 45 110 50 32 44 6 3 24 4 0.0013 0.0052 149 ST_GA13_PATHWAY G-alpha-13 influences the actin cytoskeleton and activates protein kinase D, PI3K, and Pyk2. AKT1, AKT2, AKT3, ARHGEF11, BCL2, BF, CDC42, DLG4, GNA13, IKBKG, LPA, MAP2K4, MAP3K1, MAP3K5, MAPK8, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PDK1, PHKA2, PI3, PIK3CB, PLD1, PLD2, PLD3, PRKCM, PTK2, RDX, ROCK1, ROCK2, SERPINA4, SRF, TBXA2R 33 AKT1(8), AKT2(4), AKT3(8), ARHGEF11(22), CDC42(5), DLG4(13), GNA13(9), LPA(14), MAP2K4(6), MAP3K1(31), MAP3K5(21), MAPK8(7), NFKB1(12), NFKB2(10), NFKBIA(3), NFKBIB(3), NFKBIE(6), NFKBIL1(2), PDK1(7), PHKA2(15), PI3(3), PIK3CB(19), PLD1(16), PLD2(7), PLD3(3), PTK2(11), RDX(12), ROCK1(27), ROCK2(15), SERPINA4(8), SRF(3) 16795725 330 75 316 81 77 130 39 17 57 10 0.0013 0.0053 150 HSA04540_GAP_JUNCTION Genes involved in gap junction ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADRB1, CDC2, CSNK1D, DRD1, DRD2, EDG2, EGF, EGFR, GJA1, GJD2, GNA11, GNAI1, GNAI2, GNAI3, GNAQ, GNAS, GRB2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, HTR2A, HTR2B, HTR2C, ITPR1, ITPR2, ITPR3, KRAS, LOC643224, LOC654264, MAP2K1, MAP2K2, MAP2K5, MAP3K2, MAPK1, MAPK3, MAPK7, NPR1, NPR2, NRAS, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PLCB1, PLCB2, PLCB3, PLCB4, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, PRKX, PRKY, RAF1, SOS1, SOS2, SRC, TJP1, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8 90 ADCY1(17), ADCY2(17), ADCY3(8), ADCY4(8), ADCY5(11), ADCY6(16), ADCY7(6), ADCY8(16), ADCY9(25), ADRB1(2), DRD1(6), DRD2(10), EGF(24), EGFR(20), GJA1(6), GJD2(8), GNA11(3), GNAI1(4), GNAI2(7), GNAI3(3), GNAS(25), GRB2(3), GRM1(22), GRM5(22), GUCY1A2(10), GUCY1A3(12), GUCY1B3(7), GUCY2C(12), GUCY2D(7), GUCY2F(25), HTR2A(15), HTR2B(2), HTR2C(18), ITPR1(31), ITPR2(38), ITPR3(23), KRAS(29), MAP2K1(2), MAP2K5(2), MAP3K2(8), MAPK1(2), MAPK3(4), MAPK7(17), NPR1(14), NPR2(16), NRAS(10), PDGFB(4), PDGFC(4), PDGFD(6), PDGFRA(29), PDGFRB(12), PLCB1(6), PLCB2(9), PLCB3(9), PLCB4(20), PRKACA(4), PRKACB(2), PRKACG(6), PRKCA(10), PRKCG(10), PRKG1(9), PRKG2(10), PRKX(4), RAF1(7), SOS1(21), SOS2(22), SRC(2), TJP1(33), TUBA1A(5), TUBA1B(4), TUBA1C(9), TUBA3C(7), TUBA3D(5), TUBA3E(15), TUBA4A(7), TUBA8(11), TUBAL3(5), TUBB1(8), TUBB2A(4), TUBB2B(2), TUBB2C(1), TUBB4(9), TUBB4Q(4), TUBB6(4), TUBB8(3) 45084004 935 117 884 272 265 370 147 42 101 10 0.0014 0.0056 151 STARCH_AND_SUCROSE_METABOLISM AGL, AMY1A, AMY1B, AMY1C, AMY2A, AMY2B, AMY2B, RNPC3, ENPP1, ENPP3, G6PC, GAA, GANAB, GBA3, GBE1, GCK, GPI, GUSB, GYS1, GYS2, HK1, HK2, HK3, MGAM, PGM1, PGM3, PYGB, PYGL, PYGM, SI, UCHL1, UCHL3, UGDH, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4, UXS1 41 AGL(18), AMY2A(7), AMY2B(11), ENPP1(11), ENPP3(16), G6PC(6), GAA(5), GANAB(13), GBA3(9), GBE1(12), GCK(5), GPI(9), GUSB(5), GYS1(12), GYS2(19), HK1(13), HK2(8), HK3(12), MGAM(49), PGM1(9), PGM3(6), PYGB(10), PYGL(9), PYGM(10), RNPC3(7), SI(47), UCHL1(5), UCHL3(1), UGDH(3), UGT1A1(6), UGT1A10(8), UGT1A3(4), UGT1A4(4), UGT1A5(7), UGT1A6(5), UGT1A7(9), UGT1A8(4), UGT1A9(4), UGT2B15(9), UGT2B4(10), UXS1(5) 19445518 422 81 410 98 120 153 66 26 57 0 0.0015 0.0060 152 CERAMIDEPATHWAY Ceramide is a lipid signaling molecule that can activate proliferative or apoptotic pathways, depending on signaling context, localization, and cell type. BAD, BAX, BCL2, CASP8, CYCS, FADD, MAP2K1, MAP2K4, MAP3K1, MAPK1, MAPK3, MAPK8, NFKB1, NSMAF, PDCD8, RAF1, RELA, RIPK1, SMPD1, TNFRSF1A, TRADD, TRAF2 20 BAD(2), BAX(4), CASP8(21), CYCS(3), FADD(1), MAP2K1(2), MAP2K4(6), MAP3K1(31), MAPK1(2), MAPK3(4), MAPK8(7), NFKB1(12), NSMAF(11), RAF1(7), RELA(6), RIPK1(8), SMPD1(12), TNFRSF1A(6), TRAF2(5) 7028273 150 52 146 24 30 47 28 10 33 2 0.0016 0.0065 153 G_PROTEIN_SIGNALING ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, AKAP1, AKAP10, AKAP11, AKAP12, AKAP2, PALM2_AKAP2, AKAP3, AKAP4, AKAP5, AKAP6, AKAP7, AKAP8, AKAP9, ARHGEF1, CALM1, CALM2, CALM3, CHMP1B, GNA11, GNA12, GNA13, GNA14, GNA15, GNAI2, GNAI3, GNAL, GNAO1, GNAQ, GNAZ, GNB1, GNB2, GNB3, GNB5, GNG10, GNG10, LOC552891, GNG12, GNG13, GNG3, GNG4, GNG5, GNG7, GNGT1, GNGT2, HRAS, IL18BP, ITPR1, KCNJ3, KRAS, MGC11266, NRAS, PALM2, PALM2_AKAP2, PALM2_AKAP2, PDE1A, PDE1B, PDE1C, PDE4A, PDE4B, PDE4C, PDE4D, PDE7A, PDE7B, PDE8A, PDE8B, PLCB3, PPP3CA, PPP3CC, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCQ, PRKCZ, PRKD1, PRKD3, RHOA, RRAS, SARA1, SLC9A1, USP5 92 ADCY1(17), ADCY2(17), ADCY3(8), ADCY4(8), ADCY5(11), ADCY6(16), ADCY7(6), ADCY8(16), ADCY9(25), AKAP1(8), AKAP10(7), AKAP11(32), AKAP12(20), AKAP3(15), AKAP4(1), AKAP5(2), AKAP6(30), AKAP7(4), AKAP8(2), AKAP9(57), ARHGEF1(11), CALM2(3), CALM3(1), CHMP1B(3), GNA11(3), GNA12(10), GNA13(9), GNA14(5), GNA15(1), GNAI2(7), GNAI3(3), GNAL(6), GNAO1(5), GNAZ(7), GNB1(3), GNB2(5), GNB3(4), GNB5(3), GNG12(2), GNG13(2), GNG3(3), GNG4(5), GNGT2(1), ITPR1(31), KCNJ3(15), KRAS(29), NRAS(10), PALM2(6), PDE1A(12), PDE1B(9), PDE1C(14), PDE4A(12), PDE4B(17), PDE4C(6), PDE4D(7), PDE7A(3), PDE7B(4), PDE8A(7), PDE8B(20), PLCB3(9), PPP3CA(4), PPP3CC(6), PRKACA(4), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PRKCA(10), PRKCD(7), PRKCE(11), PRKCG(10), PRKCH(9), PRKCI(8), PRKCQ(13), PRKCZ(4), PRKD1(8), PRKD3(10), RHOA(4), RRAS(1), SLC9A1(10), USP5(13) 40211511 776 110 729 268 219 298 122 41 85 11 0.0016 0.0065 154 IFNGPATHWAY IFN gamma signaling pathway IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 6 IFNG(5), IFNGR1(6), IFNGR2(4), JAK1(31), JAK2(21), STAT1(14) 2937549 81 34 72 18 14 19 13 5 18 12 0.0016 0.0066 155 AT1RPATHWAY Binding of angiotensin II to AT1-R activates Ca2+ signaling and the JNK pathway. AGT, AGTR1, ATF2, CALM1, CALM2, CALM3, EGFR, ELK1, GNAQ, GRB2, HRAS, JUN, MAP2K1, MAP2K2, MAP2K4, MAP3K1, MAPK1, MAPK3, MAPK8, MEF2A, MEF2B, MEF2C, MEF2D, PAK1, PRKCA, PRKCB1, PTK2, PTK2B, RAC1, RAF1, SHC1, SOS1, SRC, SYT1 32 AGT(7), ATF2(6), CALM2(3), CALM3(1), EGFR(20), ELK1(2), GRB2(3), JUN(1), MAP2K1(2), MAP2K4(6), MAP3K1(31), MAPK1(2), MAPK3(4), MAPK8(7), MEF2A(5), MEF2B(3), MEF2C(11), MEF2D(7), PAK1(3), PRKCA(10), PTK2(11), PTK2B(16), RAF1(7), SHC1(11), SOS1(21), SRC(2), SYT1(4) 11558518 206 65 200 65 53 74 26 17 32 4 0.0017 0.0068 156 CARM1PATHWAY The methyltransferase CARM1 interacts with transcription factors such as CBP/p300 and methylates histones H3 and H4. CARM1, CREB1, CREBBP, EP300, NCOA3, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RARA, RXRA 13 CARM1(6), CREB1(5), CREBBP(37), EP300(29), NCOA3(8), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), RARA(3), RXRA(1) 6964699 118 52 114 39 31 43 12 6 24 2 0.0017 0.0068 157 TOLLPATHWAY Toll-like receptors are activated by bacterial lipoproteins, lipopolysaccharides, and other surface molecules, and activate pro-inflammatory factors such as NF-kB. CD14, CHUK, ELK1, FOS, IKBKB, IKBKG, IRAK1, JUN, LY96, MAP2K3, MAP2K4, MAP2K6, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAPK14, MAPK8, MYD88, NFKB1, NFKBIA, PGLYRP, PPARA, PRKR, RELA, SITPEC, TIRAP, TLR10, TLR2, TLR3, TLR4, TLR6, TLR7, TLR9, TOLLIP, TRAF6 30 CD14(2), CHUK(11), ELK1(2), FOS(6), IKBKB(15), IRAK1(5), JUN(1), LY96(4), MAP2K3(8), MAP2K4(6), MAP2K6(9), MAP3K1(31), MAP3K14(12), MAP3K7(8), MAPK14(6), MAPK8(7), MYD88(1), NFKB1(12), NFKBIA(3), PPARA(2), RELA(6), TIRAP(3), TLR10(19), TLR2(12), TLR3(6), TLR4(14), TLR6(10), TLR7(15), TLR9(7), TRAF6(4) 12515474 247 65 243 60 57 90 42 20 34 4 0.0019 0.0073 158 HSA04330_NOTCH_SIGNALING_PATHWAY Genes involved in Notch signaling pathway ADAM17, APH1A, CIR, CREBBP, CTBP1, CTBP2, DLL1, DLL3, DLL4, DTX1, DTX2, DTX3, DTX3L, DTX4, DVL1, DVL2, DVL3, EP300, GCN5L2, HDAC1, HDAC2, HES1, JAG1, JAG2, LFNG, LOC652788, MAML1, MAML2, MAML3, MFNG, NCOR2, NCSTN, NOTCH1, NOTCH2, NOTCH3, NOTCH4, NUMB, NUMBL, PCAF, PSEN1, PSEN2, PSENEN, PTCRA, RBPJ, RBPJL, RFNG, SNW1 37 ADAM17(11), APH1A(1), CREBBP(37), CTBP2(7), DLL1(8), DLL3(5), DLL4(2), DTX1(5), DTX2(4), DTX3(5), DTX3L(8), DTX4(7), DVL2(12), DVL3(7), EP300(29), HDAC1(4), HDAC2(5), HES1(1), JAG1(15), MAML1(8), MAML2(9), MAML3(16), MFNG(5), NCOR2(24), NCSTN(10), NOTCH2(17), NOTCH3(31), NOTCH4(15), NUMB(11), NUMBL(4), PSEN1(4), PSEN2(5), PTCRA(1), RBPJ(7), RBPJL(8), SNW1(5) 19803062 353 80 347 115 91 159 40 17 42 4 0.0021 0.0082 159 RELAPATHWAY Acetylated NF-kB proteins are immune to IkB regulation and promote transcription until the histone deacetylase HDAC3 deacetylates the RelA subunit of NF-kB. CHUK, CREBBP, EP300, FADD, HDAC3, IKBKB, IKBKG, NFKB1, NFKBIA, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF6 14 CHUK(11), CREBBP(37), EP300(29), FADD(1), HDAC3(10), IKBKB(15), NFKB1(12), NFKBIA(3), RELA(6), RIPK1(8), TNF(1), TNFRSF1A(6), TNFRSF1B(3), TRAF6(4) 7582992 146 51 141 43 27 59 25 7 28 0 0.0022 0.0084 160 SPRYPATHWAY Four members of the Sprouty protein family block proliferative EGF signals by binding Grb-2, preventing Ras and MAP kinase activation. CBL, EGF, EGFR, GRB2, HRAS, MAP2K1, MAPK1, MAPK3, PTPRB, RAF1, RASA1, SHC1, SOS1, SPRY1, SPRY2, SPRY3, SPRY4, SRC 18 CBL(10), EGF(24), EGFR(20), GRB2(3), MAP2K1(2), MAPK1(2), MAPK3(4), PTPRB(31), RAF1(7), RASA1(29), SHC1(11), SOS1(21), SPRY1(4), SPRY2(6), SPRY4(2), SRC(2) 8758872 178 58 173 42 45 65 29 9 26 4 0.0023 0.0088 161 ST_T_CELL_SIGNAL_TRANSDUCTION On activation of the T cell receptor, phospholipase C is activated to produce second messengers DAG and PIP3, both required for T cell activation. CBL, CD28, CD3D, CSK, CTLA4, DAG1, DTYMK, EPHB2, FBXW7, GRAP2, GRB2, ITK, ITPKA, ITPKB, LAT, LCK, LCP2, MAPK1, NCK1, NFAT5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PAG, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PLCG1, PTPRC, RAF1, RASGRP1, RASGRP2, RASGRP3, RASGRP4, SOS1, SOS2, VAV1, ZAP70 42 CBL(10), CD28(6), CD3D(3), CSK(1), CTLA4(2), DAG1(7), EPHB2(10), FBXW7(34), GRAP2(3), GRB2(3), ITK(10), ITPKB(6), LCK(5), LCP2(7), MAPK1(2), NCK1(4), NFAT5(13), NFKB1(12), NFKB2(10), NFKBIA(3), NFKBIB(3), NFKBIE(6), NFKBIL1(2), PAK1(3), PAK2(6), PAK3(14), PAK4(2), PAK6(3), PAK7(12), PLCG1(12), PTPRC(15), RAF1(7), RASGRP1(8), RASGRP2(5), RASGRP3(8), RASGRP4(7), SOS1(21), SOS2(22), VAV1(16), ZAP70(10) 18814319 333 74 316 109 88 131 38 15 53 8 0.0024 0.0093 162 PYK2PATHWAY Pyk2 and Rac1 stimulate the JNK cascade and activate MKK3, which activates p38. BCAR1, CALM1, CALM2, CALM3, CRKL, GNAQ, GRB2, HRAS, JUN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP3K1, MAPK1, MAPK14, MAPK3, MAPK8, PAK1, PLCG1, PRKCA, PRKCB1, PTK2B, RAC1, RAF1, SHC1, SOS1, SRC, SYT1 26 CALM2(3), CALM3(1), CRKL(5), GRB2(3), JUN(1), MAP2K1(2), MAP2K3(8), MAP2K4(6), MAP3K1(31), MAPK1(2), MAPK14(6), MAPK3(4), MAPK8(7), PAK1(3), PLCG1(12), PRKCA(10), PTK2B(16), RAF1(7), SHC1(11), SOS1(21), SRC(2), SYT1(4) 9197915 165 59 159 48 44 55 21 16 25 4 0.0025 0.0097 163 TNFR1PATHWAY Tumor necrosis factor alpha binds to its receptor TNFR1 and induces caspase-dependent apoptosis. ADPRT, ARHGDIB, BAG4, CASP2, CASP3, CASP8, CRADD, DFFA, DFFB, FADD, JUN, LMNA, LMNB1, LMNB2, MADD, MAP2K4, MAP3K1, MAP3K7, MAPK8, PAK1, PAK2, PRKDC, RB1, RIPK1, SPTAN1, TNF, TNFRSF1A, TRADD, TRAF2 26 ARHGDIB(2), BAG4(4), CASP2(9), CASP3(4), CASP8(21), CRADD(3), DFFA(1), DFFB(3), FADD(1), JUN(1), LMNA(8), LMNB1(5), MADD(21), MAP2K4(6), MAP3K1(31), MAP3K7(8), MAPK8(7), PAK1(3), PAK2(6), PRKDC(70), RB1(31), RIPK1(8), SPTAN1(29), TNF(1), TNFRSF1A(6), TRAF2(5) 13556797 294 64 287 60 70 100 42 21 52 9 0.0028 0.011 164 ST_STAT3_PATHWAY The transcription factor STAT3 is involved in cell growth regulation and is commonly upregulated in tumors. CISH, IL6, IL6R, JAK1, JAK2, JAK3, PIAS3, PTPRU, REG1A, SRC, STAT3 11 IL6(2), IL6R(12), JAK1(31), JAK2(21), JAK3(9), PIAS3(9), PTPRU(20), REG1A(4), SRC(2), STAT3(12) 5261824 122 44 113 28 23 41 16 6 24 12 0.0029 0.011 165 ST_G_ALPHA_I_PATHWAY Gi and Go proteins are members of the same family that transduce cellular signals through both their alpha and beta subunits. AKT1, AKT2, AKT3, ASAH1, BF, BRAF, DAG1, DRD2, EGFR, EPHB2, GRB2, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, PI3, PIK3CB, PITX2, PLCB1, PLCB2, PLCB3, PLCB4, RAF1, RAP1GA1, RGS20, SHC1, SOS1, SOS2, SRC, STAT3, TERF2IP 33 AKT1(8), AKT2(4), AKT3(8), ASAH1(9), BRAF(12), DAG1(7), DRD2(10), EGFR(20), EPHB2(10), GRB2(3), ITPKB(6), ITPR1(31), ITPR2(38), ITPR3(23), KCNJ3(15), KCNJ5(6), KCNJ9(4), MAPK1(2), PI3(3), PIK3CB(19), PITX2(10), PLCB1(6), PLCB2(9), PLCB3(9), PLCB4(20), RAF1(7), RGS20(5), SHC1(11), SOS1(21), SOS2(22), SRC(2), STAT3(12), TERF2IP(4) 20426374 376 80 361 119 93 157 56 17 47 6 0.0029 0.011 166 IL2PATHWAY IL-2 promotes proliferation via JAK and MAP kinase and has surface receptors on activated B cells, LPS-treated monocytes, and many T cells. CSNK2A1, ELK1, FOS, GRB2, HRAS, IL2, IL2RA, IL2RB, IL2RG, JAK1, JAK3, JUN, LCK, MAP2K1, MAPK3, MAPK8, RAF1, SHC1, SOS1, STAT5A, STAT5B, SYK 22 CSNK2A1(9), ELK1(2), FOS(6), GRB2(3), IL2(4), IL2RA(3), IL2RB(6), IL2RG(11), JAK1(31), JAK3(9), JUN(1), LCK(5), MAP2K1(2), MAPK3(4), MAPK8(7), RAF1(7), SHC1(11), SOS1(21), STAT5A(5), STAT5B(5), SYK(6) 8110704 158 55 148 28 44 56 15 11 24 8 0.0032 0.012 167 SA_B_CELL_RECEPTOR_COMPLEXES Antigen binding to B cell receptors activates protein tyrosine kinases, such as the Src family, which ultimate activate MAP kinases. ATF2, BCR, BLNK, ELK1, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP3K1, MAPK1, MAPK3, MAPK8IP3, PAPPA, RAC1, RPS6KA1, RPS6KA3, SHC1, SOS1, SYK, VAV1, VAV2, VAV3 23 ATF2(6), BCR(6), BLNK(4), ELK1(2), FOS(6), GRB2(3), JUN(1), LYN(7), MAP2K1(2), MAP3K1(31), MAPK1(2), MAPK3(4), PAPPA(32), RPS6KA1(5), RPS6KA3(17), SHC1(11), SOS1(21), SYK(6), VAV1(16), VAV2(5), VAV3(13) 9933557 200 61 192 55 60 66 27 12 29 6 0.0039 0.015 168 PPARGPATHWAY PPAR-gamma is a nuclear hormone receptor that is activated by fatty acids and regulates transcription through co-activations like Src-1 and Tif2. CREBBP, EP300, LPL, NCOA1, NCOA2, PPARBP, PPARG, PPARGC1, RXRA 7 CREBBP(37), EP300(29), LPL(11), NCOA1(17), NCOA2(16), PPARG(5), RXRA(1) 6354293 116 50 113 35 29 42 17 8 20 0 0.0040 0.015 169 NO1PATHWAY Shear stress in endothelial cells increases cytoplasmic calcium, which activates nitric oxide synthase III to release NO, which in turn regulates cardiac contractions. ACTA1, AKT1, BDK, BDKRB2, CALM1, CALM2, CALM3, CAV1, CHRM1, CHRNA1, FLT1, FLT4, HSPCA, KDR, NOS3, PDE2A, PDE3A, PDE3B, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKG1, PRKG2, RYR2, SLC7A1, SYT1, TNNI1, VEGF 28 ACTA1(4), AKT1(8), BDKRB2(9), CALM2(3), CALM3(1), CHRM1(6), CHRNA1(6), FLT1(23), FLT4(10), KDR(23), NOS3(11), PDE2A(14), PDE3A(17), PDE3B(15), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PRKG1(9), PRKG2(10), RYR2(111), SLC7A1(6), SYT1(4), TNNI1(1) 13391409 320 66 310 104 76 137 42 15 39 11 0.0049 0.018 170 SA_DIACYLGLYCEROL_SIGNALING DAG (diacylglycerol) signaling activity ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP 9 ESR1(15), ESR2(8), PDE1A(12), PDE1B(9), PLCB1(6), PLCB2(9), PRL(6), VIP(2) 3710236 67 38 64 22 19 26 11 4 7 0 0.0056 0.020 171 NTHIPATHWAY Hemophilus influenzae infections activate NF-kB via several pathways, inducing the inflammatory response. CHUK, CREBBP, DUSP1, EP300, IKBKB, IL1B, IL8, MADH3, MADH4, MAP2K3, MAP2K6, MAP3K14, MAP3K7, MAPK11, MAPK14, MYD88, NFKB1, NFKBIA, NR3C1, RELA, TGFBR1, TGFBR2, TLR2, TNF 21 CHUK(11), CREBBP(37), DUSP1(2), EP300(29), IKBKB(15), IL1B(2), IL8(3), MAP2K3(8), MAP2K6(9), MAP3K14(12), MAP3K7(8), MAPK14(6), MYD88(1), NFKB1(12), NFKBIA(3), NR3C1(13), RELA(6), TGFBR1(8), TGFBR2(6), TLR2(12), TNF(1) 9997609 204 57 199 58 50 77 33 12 32 0 0.0058 0.021 172 MONOAMINE_GPCRS ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2C, ADRB1, ADRB2, ADRB3, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, DRD1, DRD2, DRD3, DRD4, DRD5, HRH1, HRH2, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, HTR7, LOC93164 27 ADRA1A(11), ADRA1B(7), ADRB1(2), ADRB2(8), CHRM1(6), CHRM2(9), CHRM3(9), CHRM4(9), CHRM5(13), DRD1(6), DRD2(10), DRD3(5), DRD5(11), HRH1(9), HRH2(3), HTR1A(13), HTR1B(6), HTR1D(6), HTR1E(6), HTR1F(15), HTR2A(15), HTR2B(2), HTR2C(18), HTR4(7), HTR5A(9), HTR6(4), HTR7(4) 8011280 223 58 212 81 75 89 36 8 15 0 0.0058 0.021 173 HSA04060_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION Genes involved in cytokine-cytokine receptor interaction ACVR1, ACVR1B, ACVR2A, ACVR2B, AMH, AMHR2, BMP2, BMP7, BMPR1A, BMPR1B, BMPR2, CCL1, CCL11, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL2, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CCL3, CCL4, CCL5, CCL7, CCL8, CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CD27, CD40, CD40LG, CD70, CLCF1, CNTF, CNTFR, CRLF2, CSF1, CSF1R, CSF2, CSF2RA, CSF2RB, CSF3, CSF3R, CTF1, CX3CL1, CX3CR1, CXCL1, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL16, CXCL2, CXCL3, CXCL5, CXCL6, CXCL9, CXCR3, CXCR4, CXCR6, EDA, EDA2R, EDAR, EGF, EGFR, EPO, EPOR, FAS, FASLG, FLJ78302, FLT1, FLT3, FLT3LG, FLT4, GDF5, GH1, GH2, GHR, HGF, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNE1, IFNG, IFNGR1, IFNGR2, IFNK, IFNW1, IL10, IL10RA, IL10RB, IL11, IL11RA, IL12A, IL12B, IL12RB1, IL12RB2, IL13, IL13RA1, IL15, IL15RA, IL17A, IL17B, IL17RA, IL17RB, IL18, IL18R1, IL18RAP, IL19, IL1A, IL1B, IL1R1, IL1R2, IL1RAP, IL2, IL20, IL20RA, IL21, IL21R, IL22, IL22RA1, IL22RA2, IL23A, IL23R, IL24, IL25, IL26, IL28A, IL28B, IL28RA, IL29, IL2RA, IL2RB, IL2RG, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL6ST, IL7, IL7R, IL8, IL8RA, IL8RB, IL9, IL9R, INHBA, INHBB, INHBC, INHBE, KDR, KIT, KITLG, LEP, LEPR, LIF, LIFR, LOC728045, LTA, LTB, LTBR, MET, MPL, NGFR, OSM, OSMR, PDGFB, PDGFC, PDGFRA, PDGFRB, PF4, PF4V1, PLEKHO2, PPBP, PRL, PRLR, RELT, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF11A, TNFRSF11B, TNFRSF12A, TNFRSF13B, TNFRSF13C, TNFRSF14, TNFRSF17, TNFRSF18, TNFRSF19, TNFRSF1A, TNFRSF1B, TNFRSF21, TNFRSF25, TNFRSF4, TNFRSF6B, TNFRSF8, TNFRSF9, TNFSF10, TNFSF11, TNFSF12, TNFSF13, TNFSF13B, TNFSF14, TNFSF15, TNFSF18, TNFSF4, TNFSF8, TNFSF9, TPO, TSLP, VEGFA, VEGFB, VEGFC, XCL1, XCL2, XCR1 242 ACVR1(9), ACVR1B(6), ACVR2A(14), ACVR2B(8), AMHR2(4), BMP2(5), BMP7(15), BMPR1A(8), BMPR1B(6), BMPR2(14), CCL1(1), CCL13(2), CCL14(1), CCL15(2), CCL16(1), CCL17(1), CCL18(2), CCL23(3), CCL24(3), CCL25(1), CCL28(4), CCL3(1), CCL4(1), CCL5(4), CCL7(4), CCR1(5), CCR2(6), CCR3(5), CCR4(5), CCR6(5), CCR7(5), CCR8(6), CCR9(2), CD27(2), CD40(4), CD40LG(7), CD70(2), CLCF1(2), CNTF(3), CNTFR(2), CSF1(5), CSF1R(7), CSF2RA(9), CSF2RB(11), CSF3(1), CSF3R(11), CX3CL1(4), CX3CR1(4), CXCL1(1), CXCL10(2), CXCL11(1), CXCL12(3), CXCL13(2), CXCL14(1), CXCL16(3), CXCL2(2), CXCL3(1), CXCL5(3), CXCL6(1), CXCL9(2), CXCR3(5), CXCR4(1), CXCR6(3), EDA(7), EDA2R(9), EGF(24), EGFR(20), EPO(2), EPOR(4), FAS(7), FASLG(6), FLT1(23), FLT3(9), FLT3LG(4), FLT4(10), GDF5(8), GH1(6), GH2(5), GHR(10), HGF(15), IFNA10(2), IFNA13(3), IFNA14(3), IFNA16(2), IFNA17(2), IFNA2(1), IFNA21(2), IFNA4(3), IFNA5(2), IFNA6(6), IFNA7(2), IFNA8(2), IFNAR1(9), IFNAR2(8), IFNB1(4), IFNG(5), IFNGR1(6), IFNGR2(4), IFNK(2), IFNW1(2), IL10(4), IL10RA(7), IL10RB(9), IL11RA(7), IL12A(7), IL12B(3), IL12RB1(16), IL12RB2(11), IL13RA1(14), IL15(1), IL15RA(3), IL17RA(10), IL17RB(5), IL18(1), IL18R1(5), IL18RAP(12), IL19(1), IL1A(1), IL1B(2), IL1R1(5), IL1R2(7), IL1RAP(2), IL2(4), IL20(6), IL20RA(3), IL21(2), IL21R(6), IL22RA1(2), IL22RA2(1), IL23A(4), IL23R(8), IL24(7), IL25(2), IL26(7), IL28A(2), IL28B(4), IL28RA(8), IL29(2), IL2RA(3), IL2RB(6), IL2RG(11), IL3RA(11), IL4R(6), IL5(2), IL5RA(9), IL6(2), IL6R(12), IL6ST(10), IL7(2), IL7R(9), IL8(3), INHBA(7), INHBB(3), INHBC(4), INHBE(7), KDR(23), KIT(28), KITLG(2), LEP(2), LEPR(15), LIF(3), LIFR(22), LTA(3), LTB(1), LTBR(7), MET(10), MPL(5), NGFR(4), OSM(3), OSMR(12), PDGFB(4), PDGFC(4), PDGFRA(29), PDGFRB(12), PF4(1), PF4V1(1), PLEKHO2(3), PRL(6), PRLR(6), RELT(1), TGFB1(4), TGFB2(6), TGFB3(9), TGFBR1(8), TGFBR2(6), TNF(1), TNFRSF10A(3), TNFRSF10B(5), TNFRSF10C(3), TNFRSF10D(10), TNFRSF11A(6), TNFRSF11B(6), TNFRSF13B(4), TNFRSF14(2), TNFRSF17(2), TNFRSF19(3), TNFRSF1A(6), TNFRSF1B(3), TNFRSF21(3), TNFRSF25(1), TNFRSF8(8), TNFRSF9(3), TNFSF10(1), TNFSF11(6), TNFSF12(4), TNFSF13B(3), TNFSF14(6), TNFSF15(3), TNFSF18(3), TNFSF4(5), TNFSF8(1), TPO(18), TSLP(2), VEGFA(1), VEGFB(2), VEGFC(7), XCL1(1), XCL2(1), XCR1(7) 60159885 1191 116 1157 360 341 459 162 64 161 4 0.0069 0.024 174 SA_REG_CASCADE_OF_CYCLIN_EXPR Expression of cyclins regulates progression through the cell cycle by activating cyclin-dependent kinases. CCNA1, CCNA2, CCND1, CCNE1, CCNE2, CDK2, CDK4, CDKN1B, CDKN2A, E2F1, E2F2, E2F4, PRB1 13 CCNA1(4), CCNA2(3), CCND1(10), CCNE2(6), CDK2(5), CDK4(4), CDKN1B(5), CDKN2A(1), E2F1(12), E2F2(1), E2F4(3), PRB1(4) 2867522 58 33 54 12 10 20 12 6 10 0 0.0074 0.026 175 ST_GAQ_PATHWAY G-alpha-q activates phospholipase C, resulting in calcium influx and increasing protein kinase C activity. ADRBK1, AKT1, AKT2, AKT3, BF, DAG1, GNAQ, IKBKG, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PDK1, PHKA2, PIK3CB, PITX2, PLD1, PLD2, PLD3, VN1R1 25 ADRBK1(3), AKT1(8), AKT2(4), AKT3(8), DAG1(7), ITPKB(6), ITPR1(31), ITPR2(38), ITPR3(23), NFKB1(12), NFKB2(10), NFKBIA(3), NFKBIB(3), NFKBIE(6), NFKBIL1(2), PDK1(7), PHKA2(15), PIK3CB(19), PITX2(10), PLD1(16), PLD2(7), PLD3(3), VN1R1(5) 15193469 246 68 238 77 63 109 29 10 33 2 0.0075 0.026 176 FASPATHWAY Binding of the Fas ligand to the Fas receptor induces caspase activation and consequent apoptosis in the Fas-expressing cell. ADPRT, ARHGDIB, CASP10, CASP3, CASP6, CASP7, CASP8, CFLAR, DAXX, DFFA, DFFB, FADD, FAF1, JUN, LMNA, LMNB1, LMNB2, MAP2K4, MAP3K1, MAP3K7, MAPK8, PAK1, PAK2, PRKDC, PTPN13, RB1, RIPK2, SPTAN1, TNFRSF6, TNFSF6 26 ARHGDIB(2), CASP10(10), CASP3(4), CASP6(4), CASP7(4), CASP8(21), CFLAR(7), DAXX(11), DFFA(1), DFFB(3), FADD(1), FAF1(8), JUN(1), LMNA(8), LMNB1(5), MAP2K4(6), MAP3K1(31), MAP3K7(8), MAPK8(7), PAK1(3), PAK2(6), PRKDC(70), PTPN13(27), RB1(31), RIPK2(7), SPTAN1(29) 14667430 315 64 307 61 78 104 47 21 54 11 0.0082 0.029 177 ST_INTERFERON_GAMMA_PATHWAY The interferon gamma pathway resembles the JAK-STAT pathway and activates STAT transcription factors. CISH, IFNG, IFNGR1, JAK1, JAK2, PLA2G2A, PTPRU, REG1A, STAT1, STATIP1 9 IFNG(5), IFNGR1(6), JAK1(31), JAK2(21), PTPRU(20), REG1A(4), STAT1(14) 4004445 101 39 92 23 16 31 15 5 22 12 0.0083 0.029 178 OVARIAN_INFERTILITY_GENES ATM, BMPR1B, CCND2, CDK4, CDKN1B, CEBPB, DAZL, DMC1, EGR1, ESR2, FSHR, GJA4, INHA, LHCGR, MLH1, MSH5, NCOR1, NR5A1, NRIP1, PGR, PRLR, PTGER2, SMPD1, VDR, ZP2 23 ATM(54), BMPR1B(6), CCND2(7), CDK4(4), CDKN1B(5), DAZL(5), DMC1(8), EGR1(8), ESR2(8), FSHR(17), GJA4(2), INHA(3), LHCGR(16), MLH1(8), MSH5(15), NCOR1(24), NRIP1(18), PGR(9), PRLR(6), PTGER2(5), SMPD1(12), VDR(9), ZP2(15) 11973900 264 60 253 64 52 112 37 9 48 6 0.0095 0.033 179 HSA01430_CELL_COMMUNICATION Genes involved in cell communication ACTB, ACTG1, CHAD, COL11A1, COL11A2, COL17A1, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, COMP, DES, DSC1, DSC2, DSC3, DSG1, DSG2, DSG3, DSG4, FN1, GJA1, GJA10, GJA3, GJA4, GJA5, GJA8, GJA9, GJB1, GJB2, GJB3, GJB4, GJB5, GJB6, GJB7, GJC1, GJC2, GJC3, GJD2, GJD3, GJD4, IBSP, INA, ITGA6, ITGB4, KRT1, KRT10, KRT12, KRT13, KRT14, KRT15, KRT16, KRT17, KRT18, KRT19, KRT2, KRT20, KRT23, KRT24, KRT25, KRT27, KRT28, KRT3, KRT31, KRT32, KRT33A, KRT33B, KRT34, KRT35, KRT36, KRT37, KRT38, KRT39, KRT4, KRT40, KRT5, KRT6A, KRT6B, KRT6C, KRT7, KRT71, KRT72, KRT73, KRT74, KRT75, KRT76, KRT77, KRT78, KRT79, KRT8, KRT81, KRT82, KRT83, KRT84, KRT85, KRT86, KRT9, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, LMNA, LMNB1, LMNB2, LOC728760, NES, PRPH, RELN, SPP1, THBS1, THBS2, THBS3, THBS4, TNC, TNN, TNR, TNXB, VIM, VTN, VWF 126 ACTB(5), CHAD(3), COL11A1(36), COL11A2(13), COL17A1(24), COL1A1(12), COL1A2(22), COL2A1(14), COL3A1(18), COL4A1(23), COL4A2(11), COL4A4(24), COL4A6(35), COL5A1(33), COL5A2(24), COL5A3(23), COL6A3(54), COL6A6(38), COMP(7), DES(5), DSC2(17), DSC3(22), DSG1(18), DSG2(8), DSG4(18), FN1(39), GJA1(6), GJA10(7), GJA4(2), GJA8(6), GJA9(12), GJB1(1), GJB2(3), GJB3(2), GJB4(5), GJB5(3), GJB6(4), GJB7(8), GJC1(2), GJC3(4), GJD2(8), GJD4(3), IBSP(6), INA(2), ITGA6(12), ITGB4(12), KRT1(8), KRT10(1), KRT12(7), KRT13(9), KRT14(3), KRT15(10), KRT16(8), KRT17(4), KRT19(4), KRT2(9), KRT20(4), KRT23(9), KRT24(5), KRT25(6), KRT27(7), KRT28(5), KRT3(9), KRT31(12), KRT32(9), KRT33A(7), KRT33B(4), KRT34(9), KRT35(7), KRT36(7), KRT37(7), KRT38(9), KRT4(10), KRT5(6), KRT6A(5), KRT6B(10), KRT6C(6), KRT7(1), KRT71(5), KRT72(7), KRT73(4), KRT74(3), KRT75(7), KRT76(10), KRT77(4), KRT78(4), KRT79(5), KRT8(4), KRT81(5), KRT82(5), KRT83(3), KRT84(9), KRT85(5), KRT86(1), KRT9(13), LAMA1(39), LAMA2(62), LAMA3(35), LAMA4(22), LAMB1(22), LAMB2(27), LAMB3(16), LAMB4(27), LAMC1(17), LAMC2(12), LAMC3(13), LMNA(8), LMNB1(5), NES(31), PRPH(2), RELN(48), SPP1(3), THBS1(12), THBS2(22), THBS3(6), THBS4(9), TNC(19), TNN(16), TNR(16), TNXB(25), VIM(8), VWF(31) 78537790 1518 126 1482 477 426 632 200 71 156 33 0.011 0.037 180 TRANSLATION_FACTORS ANKHD1, ANKHD1, MASK_BP3, EEF1A2, EEF1B2, EEF1D, EEF1G, EEF2, EEF2K, EIF1AX, EIF1AY, EIF2AK1, EIF2AK2, EIF2AK3, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF3S1, EIF3S10, EIF3S2, EIF3S3, EIF3S4, EIF3S5, EIF3S6, EIF3S7, EIF3S8, EIF3S9, EIF4A1, EIF4A2, EIF4E, EIF4EBP1, EIF4EBP2, EIF4G1, EIF4G3, EIF5, EIF5A, EIF5B, ETF1, GSPT2, ITGB4BP, KIAA0664, PABPC1, PABPC3, PABPC1, LOC341315, PAIP1, PAIP1, LOC388345, SLC35A4, SUI1, WBSCR1 35 ANKHD1(3), EEF1B2(3), EEF1D(9), EEF1G(4), EEF2(8), EEF2K(11), EIF1AX(4), EIF2AK1(12), EIF2AK2(16), EIF2AK3(14), EIF2B1(1), EIF2B2(4), EIF2B3(8), EIF2B4(5), EIF2B5(6), EIF2S1(1), EIF2S2(5), EIF2S3(6), EIF4A1(4), EIF4A2(6), EIF4E(4), EIF4EBP2(1), EIF4G1(15), EIF4G3(26), EIF5(3), EIF5A(7), EIF5B(17), ETF1(5), GSPT2(14), KIAA0664(12), PABPC1(11), PABPC3(13), PAIP1(4), SLC35A4(4) 14350994 266 75 260 60 70 108 37 11 36 4 0.011 0.037 181 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 4 CDK5(1), FOSB(5), GRIA2(25), PPP1R1B(4) 1220573 35 22 32 4 4 13 6 0 12 0 0.011 0.037 182 ARENRF2PATHWAY Nrf1 and nrf2 are transcription factors that bind to antioxidant response elements (AREs), promoters of genes involved in oxidative damage control. CREB1, FOS, FXYD2, JUN, KEAP1, MAFF, MAFG, MAFK, MAPK1, MAPK14, MAPK8, NFE2L2, PRKCA, PRKCB1 9 CREB1(5), FOS(6), JUN(1), KEAP1(8), MAPK1(2), MAPK14(6), MAPK8(7), NFE2L2(13), PRKCA(10) 2895007 58 33 55 10 9 21 12 7 9 0 0.011 0.037 183 CALCINEURIN_NF_AT_SIGNALING Mouse genes associated with signal transduction through calcium, calcineurin, and NF-AT. ACTB, BAD, BCL2, CABIN1, CALM1, CALM2, CALM3, CAMK2B, CAMK4, CD3E, CD3G, CD3Z, CD69, CDKN1A, CEBPB, CNR1, CREBBP, CSF2, CSNK2A1, CSNK2B, CTLA4, EGR2, EGR3, EP300, FCER1A, FCGR3A, FKBP1B, FLJ14639, FOS, FOSL1, GAPD, GATA3, GATA4, GRLF1, GSK3A, GSK3B, HRAS, ICOS, IFNA1, IFNB1, IFNG, IL10, IL13, IL1B, IL2, IL2RA, IL3, IL4, IL6, IL8, IL8RA, ITK, JUNB, KPNA5, KPNB3, MAP2K7, MAPK14, MAPK8, MAPK9, MEF2A, MEF2B, MEF2D, MYF5, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB2, NFKBIB, NFKBIE, NPPB, NUP214, OPRD1, P2RX7, PAK1, PIN1, PPIA, PPP3CB, PPP3CC, PPP3R1, PTPRC, RELA, RPL13A, SFN, SLA, SP1, SP3, TGFB1, TNF, TNFSF5, TNFSF6, TRAF2, TRPV6, VAV1, VAV2, VAV3, VEGF, XPO5 89 ACTB(5), BAD(2), CABIN1(15), CALM2(3), CALM3(1), CAMK2B(2), CAMK4(5), CD3E(2), CD3G(2), CD69(4), CDKN1A(1), CNR1(8), CREBBP(37), CSNK2A1(9), CTLA4(2), EGR2(8), EGR3(9), EP300(29), FCER1A(6), FCGR3A(2), FKBP1B(1), FOS(6), FOSL1(4), GATA3(4), GATA4(1), GSK3A(9), GSK3B(11), ICOS(2), IFNB1(4), IFNG(5), IL10(4), IL1B(2), IL2(4), IL2RA(3), IL6(2), IL8(3), ITK(10), KPNA5(6), MAPK14(6), MAPK8(7), MAPK9(7), MEF2A(5), MEF2B(3), MEF2D(7), MYF5(4), NCK2(8), NFAT5(13), NFATC2(15), NFATC3(12), NFATC4(8), NFKB2(10), NFKBIB(3), NFKBIE(6), NPPB(2), NUP214(20), OPRD1(2), P2RX7(3), PAK1(3), PIN1(1), PPIA(2), PPP3CB(7), PPP3CC(6), PPP3R1(2), PTPRC(15), RELA(6), SLA(9), SP1(6), SP3(12), TGFB1(4), TNF(1), TRAF2(5), TRPV6(14), VAV1(16), VAV2(5), VAV3(13), XPO5(10) 30824308 511 91 497 172 141 198 65 24 81 2 0.012 0.039 184 ST_IL_13_PATHWAY Like IL-4, IL-13 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor. IL13, IL13RA1, IL13RA2, IL4R, JAK1, JAK2, TYK2 7 IL13RA1(14), IL13RA2(3), IL4R(6), JAK1(31), JAK2(21), TYK2(7) 3662914 82 34 74 19 12 20 14 7 17 12 0.012 0.041 185 ST_INTERLEUKIN_13_PATHWAY IL-13 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor. IL13, IL13RA1, IL13RA2, IL4R, JAK1, JAK2, TYK2 7 IL13RA1(14), IL13RA2(3), IL4R(6), JAK1(31), JAK2(21), TYK2(7) 3662914 82 34 74 19 12 20 14 7 17 12 0.012 0.041 186 FLUMAZENILPATHWAY Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 9 GABRA1(10), GABRA2(12), GABRA3(15), GABRA4(17), GABRA5(8), GABRA6(8), PRKCE(11), SOD1(2) 2802036 83 35 78 32 30 30 9 4 10 0 0.013 0.042 187 TCAPOPTOSISPATHWAY HIV infection upregulates Fas ligand in macrophages and CD4 in helper T cells, leading to widespread Fas-induced T cell apoptosis. CCR5, CD28, CD3D, CD3E, CD3G, CD3Z, CD4, TNFRSF6, TNFSF6, TRA@, TRB@ 5 CD28(6), CD3D(3), CD3E(2), CD3G(2), CD4(8) 907722 21 16 21 6 1 13 1 0 6 0 0.013 0.042 188 STAT3PATHWAY The STAT transcription factors are phosphorylated and activated by JAK kinases in response to cytokine signaling. FRAP1, JAK1, JAK2, JAK3, MAPK1, MAPK3, STAT3, TYK2 7 JAK1(31), JAK2(21), JAK3(9), MAPK1(2), MAPK3(4), STAT3(12), TYK2(7) 4046509 86 36 78 25 12 28 11 6 17 12 0.013 0.042 189 ALTERNATIVEPATHWAY The alternative complement pathway is an antibody-independent mechanism of immune activation that results in cell lysis via the membrane attack complex. BF, C3, C5, C6, C7, C8A, C9, DF, PFC 6 C3(24), C5(20), C6(23), C7(21), C8A(12), C9(20) 4324705 120 39 114 23 25 45 22 7 17 4 0.014 0.044 190 ST_JAK_STAT_PATHWAY The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway transduces extracellular signals to promote gene activation. CISH, JAK1, JAK2, JAK3, PIAS1, PIAS3, PTPRU, REG1A, SOAT1 9 JAK1(31), JAK2(21), JAK3(9), PIAS1(5), PIAS3(9), PTPRU(20), REG1A(4), SOAT1(10) 4821347 109 41 100 25 21 38 13 6 19 12 0.014 0.044 191 GPCRDB_CLASS_C_METABOTROPIC_GLUTAMATE_PHEROMONE CASR, GABBR1, GPCR5A, GPR51, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GRM1, GRM2, GRM3, GRM4, GRM5, GRM7, GRM8 13 CASR(21), GABBR1(17), GPRC5A(5), GPRC5B(8), GPRC5C(4), GPRC5D(4), GRM1(22), GRM2(7), GRM3(20), GRM4(16), GRM5(22), GRM7(15), GRM8(24) 7183145 185 52 179 57 63 55 32 7 26 2 0.014 0.045 192 STEMPATHWAY In the absence of infection, bone marrow stromal cells release hematopoietic cytokines; activated macrophages and Th cells induce hematopoiesis during infection. CD4, CD8A, CSF1, CSF2, CSF3, EPO, IL11, IL2, IL3, IL4, IL5, IL6, IL7, IL8, IL9 14 CD4(8), CD8A(3), CSF1(5), CSF3(1), EPO(2), IL2(4), IL5(2), IL6(2), IL7(2), IL8(3) 2125427 32 25 32 12 12 10 4 0 6 0 0.014 0.046 193 HBXPATHWAY Hbx is a hepatitis B protein that activates a number of transcription factors, possibly by inducing calcium release from the mitochondrion to the cytoplasm. CREB1, GRB2, HBXIP, HRAS, PTK2B, SHC1, SOS1, SRC 8 CREB1(5), GRB2(3), HBXIP(1), PTK2B(16), SHC1(11), SOS1(21), SRC(2) 2976267 59 33 57 15 15 28 6 4 4 2 0.015 0.046 194 IL1RPATHWAY The cytokine IL-1 stimulates its primary receptor, IL-1R1, which induces transcription of inflammation-related genes such as interferons. CHUK, IFNA1, IFNB1, IKBKB, IL1A, IL1B, IL1R1, IL1RAP, IL1RN, IL6, IRAK1, IRAK2, IRAK3, JUN, MAP2K3, MAP2K6, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MAPK14, MAPK8, MYD88, NFKB1, NFKBIA, RELA, SITPEC, TGFB1, TGFB2, TGFB3, TNF, TOLLIP, TRAF6 30 CHUK(11), IFNB1(4), IKBKB(15), IL1A(1), IL1B(2), IL1R1(5), IL1RAP(2), IL1RN(1), IL6(2), IRAK1(5), IRAK2(7), IRAK3(13), JUN(1), MAP2K3(8), MAP2K6(9), MAP3K1(31), MAP3K14(12), MAP3K7(8), MAPK14(6), MAPK8(7), MYD88(1), NFKB1(12), NFKBIA(3), RELA(6), TGFB1(4), TGFB2(6), TGFB3(9), TNF(1), TRAF6(4) 10060705 196 55 190 46 41 82 30 14 27 2 0.015 0.048 195 INFLAMPATHWAY Interleukins and TNF serve as signals to coordinate the inflammatory response, in which macrophages recruit and activate neutrophils, fibroblasts, and T cells. CD4, CSF1, CSF2, CSF3, HLA-DRA, HLA-DRB1, IFNA1, IFNB1, IFNG, IL10, IL11, IL12A, IL12B, IL13, IL15, IL1A, IL2, IL3, IL4, IL5, IL6, IL7, IL8, LTA, PDGFA, TGFB1, TGFB2, TGFB3, TNF 27 CD4(8), CSF1(5), CSF3(1), HLA-DRB1(1), IFNB1(4), IFNG(5), IL10(4), IL12A(7), IL12B(3), IL15(1), IL1A(1), IL2(4), IL5(2), IL6(2), IL7(2), IL8(3), LTA(3), TGFB1(4), TGFB2(6), TGFB3(9), TNF(1) 4610788 76 39 74 27 23 34 10 1 8 0 0.016 0.051 196 AMIPATHWAY Endogenous anti-thrombosis pathways are overwhelmed in plaque-narrowed blood vessels, resulting in potentially lethal myocardial infarction. ADCY1, CD3D, CD3E, CD3G, CD3Z, CD4, CREBBP, CSK, GNAS, GNB1, GNGT1, HLA-DRA, HLA-DRB1, LCK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTPRC, TRA@, TRB@, ZAP70 21 ADCY1(17), CD3D(3), CD3E(2), CD3G(2), CD4(8), CREBBP(37), CSK(1), GNAS(25), GNB1(3), HLA-DRB1(1), LCK(5), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PTPRC(15), ZAP70(10) 7527066 158 53 153 47 38 74 13 8 23 2 0.018 0.056 197 CSKPATHWAY Csk inhibits T-cell activation by phosphorylating Lck; Csk is regulated by cAMP-dependent kinases and is opposed by the T-cell activator CD45. ADCY1, CD3D, CD3E, CD3G, CD3Z, CD4, CREBBP, CSK, GNAS, GNB1, GNGT1, HLA-DRA, HLA-DRB1, LCK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTPRC, TRA@, TRB@, ZAP70 21 ADCY1(17), CD3D(3), CD3E(2), CD3G(2), CD4(8), CREBBP(37), CSK(1), GNAS(25), GNB1(3), HLA-DRB1(1), LCK(5), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PTPRC(15), ZAP70(10) 7527066 158 53 153 47 38 74 13 8 23 2 0.018 0.056 198 NUCLEAR_RECEPTORS ALK, AR, ESR1, ESR2, ESRRA, HNF4A, NPM1, NR0B1, NR1D2, NR1H2, NR1H3, NR1I2, NR1I3, NR2C2, NR2E1, NR2F1, NR2F2, NR2F6, NR3C1, NR4A1, NR4A2, NR5A1, NR5A2, PGR, PPARA, PPARD, PPARG, RARA, RARB, RARG, ROR1, RORA, RORC, RXRA, RXRB, RXRG, THRA, THRA, NR1D1, THRB, VDR 38 ALK(21), AR(5), ESR1(15), ESR2(8), ESRRA(2), HNF4A(15), NPM1(3), NR0B1(8), NR1D1(3), NR1D2(5), NR1H2(4), NR1H3(5), NR1I2(5), NR1I3(7), NR2C2(8), NR2E1(6), NR2F1(5), NR2F2(6), NR3C1(13), NR4A1(4), NR4A2(13), NR5A2(14), PGR(9), PPARA(2), PPARD(6), PPARG(5), RARA(3), RARB(6), RARG(6), ROR1(11), RORA(9), RORC(8), RXRA(1), RXRG(10), THRA(5), THRB(4), VDR(9) 14060609 269 66 257 77 81 114 33 17 22 2 0.018 0.057 199 MRNA_PROCESSING_REACTOME BRUNOL4, C10orf9, C20orf14, CD2BP2, CDC40, CLK2, CLK3, CLK4, COL2A1, CPSF1, CPSF2, CPSF3, CPSF4, CSTF1, CSTF2, CSTF2T, CSTF3, CUGBP1, CUGBP2, DDIT3, DDX1, DDX20, DHX15, DHX16, DHX38, DHX8, DHX9, DICER1, DNAJC8, FLJ10748, FNBP3, FUS, FUSIP1, GIPC1, HEAB, HNRPA2B1, HNRPA3, HNRPA3P1, HNRPA3, LOC387933, HNRPA3P1, HNRPA3, LOC389395, HNRPAB, HNRPC, HNRPC, HNRPCL1, LOC390615, LOC440563, HNRPD, HNRPH1, HNRPH2, HNRPL, HNRPR, HNRPU, HRMT1L2, LSM2, LSM7, METTL3, NCBP1, NCBP2, NONO, NUDT21, NXF1, PABPN1, PAPOLA, PHF5A, POLR2A, PPM1G, PRPF18, PRPF3, PRPF4, PRPF4B, PRPF8, PSKH1, PTBP1, PTBP2, RBM17, RBM5, RNGTT, RNMT, RNPC2, RNPS1, SF3A1, SF3A2, SF3A3, SF3B1, SF3B2, SF3B4, SF3B5, SF4, SFRS10, SFRS12, SFRS14, SFRS16, SFRS2, SFRS4, SFRS5, SFRS6, SFRS7, SFRS8, SFRS9, SMC1L1, SNRP70, SNRPA, SNRPA1, SNRPB, SNRPB2, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, SNRPN, SNRPN, PAR1, SNRPN, SNURF, SPOP, SRPK1, SRPK2, SRRM1, SUPT5H, TMP21, TXNL4A, U2AF1, U2AF2, WDR57, XRN2 89 CD2BP2(3), CDC40(8), CLK2(10), CLK3(5), CLK4(6), COL2A1(14), CPSF1(9), CPSF2(10), CPSF3(8), CPSF4(3), CSTF1(4), CSTF2(12), CSTF2T(8), CSTF3(12), DDIT3(1), DDX1(6), DDX20(6), DHX15(10), DHX16(16), DHX38(14), DHX8(10), DHX9(18), DICER1(39), DNAJC8(1), FUS(3), GIPC1(1), METTL3(8), NCBP1(9), NCBP2(4), NONO(15), NXF1(4), PABPN1(4), PAPOLA(10), PHF5A(1), POLR2A(25), PPM1G(7), PRPF18(4), PRPF3(11), PRPF4(6), PRPF4B(25), PRPF8(27), PSKH1(6), PTBP1(2), PTBP2(6), RBM17(9), RBM5(5), RNGTT(13), RNMT(7), RNPS1(1), SF3A1(9), SF3A3(6), SF3B1(18), SF3B2(10), SF3B4(4), SF3B5(2), SNRPA(2), SNRPB(3), SNRPB2(1), SNRPD1(1), SNRPD2(2), SNRPD3(2), SNRPE(2), SNRPG(1), SPOP(19), SRPK1(14), SRPK2(7), SRRM1(10), SUPT5H(20), U2AF1(3), U2AF2(6), XRN2(14) 36318201 602 101 583 169 178 225 83 42 70 4 0.019 0.058 200 SA_FAS_SIGNALING The TNF-type receptor Fas induces apoptosis on ligand binding. BCL2, CASP3, CASP8, CFL1, CFLAR, P11, PDE6D, TNFRSF6, TNFSF6 6 CASP3(4), CASP8(21), CFL1(1), CFLAR(7), PDE6D(1) 1303506 34 21 33 7 5 13 6 1 9 0 0.021 0.066 201 TNFR2PATHWAY Tumor necrosis factor beta, produced by activated lymphocytes, binds to its receptor TNFR2 to induce activation in immune cells and apoptosis in many other cells. CHUK, DUSP1, IKBKAP, IKBKB, IKBKG, LTA, MAP3K1, MAP3K14, NFKB1, NFKBIA, RELA, RIPK1, TANK, TNFAIP3, TNFRSF1B, TRAF1, TRAF2, TRAF3 17 CHUK(11), DUSP1(2), IKBKAP(14), IKBKB(15), LTA(3), MAP3K1(31), MAP3K14(12), NFKB1(12), NFKBIA(3), RELA(6), RIPK1(8), TANK(4), TNFAIP3(2), TNFRSF1B(3), TRAF1(5), TRAF2(5), TRAF3(6) 7832986 142 47 139 35 29 56 17 13 25 2 0.022 0.067 202 MAPKPATHWAY The mitogen-activated protein (MAP) kinase pathway is a common signaling mechanism and has four main sub-pathways: Erk, JNK/SAPK, p53, and ERK5. ARAF1, ATF2, BRAF, CEBPA, CHUK, CREB1, DAXX, ELK1, FOS, GRB2, HRAS, IKBKB, JUN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K14, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8, MAP3K9, MAP4K1, MAP4K2, MAP4K3, MAP4K4, MAP4K5, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK4, MAPK6, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, MAPKAPK5, MAX, MEF2A, MEF2B, MEF2C, MEF2D, MKNK1, MKNK2, MYC, NFKB1, NFKBIA, PAK1, PAK2, PDZGEF1, RAC1, RAF1, RELA, RIPK1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KA5, RPS6KB1, RPS6KB2, SHC1, SP1, STAT1, TGFB1, TGFB2, TGFB3, TGFBR1, TRADD, TRAF2 79 ATF2(6), BRAF(12), CHUK(11), CREB1(5), DAXX(11), ELK1(2), FOS(6), GRB2(3), IKBKB(15), JUN(1), MAP2K1(2), MAP2K3(8), MAP2K4(6), MAP2K5(2), MAP2K6(9), MAP3K1(31), MAP3K10(7), MAP3K11(5), MAP3K12(8), MAP3K13(13), MAP3K14(12), MAP3K2(8), MAP3K3(9), MAP3K4(23), MAP3K5(21), MAP3K6(7), MAP3K7(8), MAP3K8(12), MAP3K9(6), MAP4K1(13), MAP4K2(6), MAP4K3(21), MAP4K4(14), MAP4K5(7), MAPK1(2), MAPK10(9), MAPK13(2), MAPK14(6), MAPK3(4), MAPK4(6), MAPK6(11), MAPK7(17), MAPK8(7), MAPK9(7), MAPKAPK2(6), MAPKAPK3(4), MAPKAPK5(6), MAX(8), MEF2A(5), MEF2B(3), MEF2C(11), MEF2D(7), MKNK1(6), MKNK2(4), MYC(7), NFKB1(12), NFKBIA(3), PAK1(3), PAK2(6), RAF1(7), RELA(6), RIPK1(8), RPS6KA1(5), RPS6KA2(16), RPS6KA3(17), RPS6KA4(5), RPS6KA5(7), RPS6KB1(3), RPS6KB2(6), SHC1(11), SP1(6), STAT1(14), TGFB1(4), TGFB2(6), TGFB3(9), TGFBR1(8), TRAF2(5) 31929205 635 97 619 151 149 261 84 40 95 6 0.022 0.068 203 HSA04640_HEMATOPOIETIC_CELL_LINEAGE Genes involved in hematopoietic cell lineage ANPEP, CD14, CD19, CD1A, CD1B, CD1C, CD1D, CD1E, CD2, CD22, CD24, CD33, CD34, CD36, CD37, CD38, CD3D, CD3E, CD3G, CD4, CD44, CD5, CD55, CD59, CD7, CD8A, CD8B, CD9, CR1, CR2, CSF1, CSF1R, CSF2, CSF2RA, CSF3, CSF3R, DNTT, EPO, EPOR, FCER2, FCGR1A, FLT3, FLT3LG, GP1BA, GP1BB, GP5, GP9, GYPA, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, IL11, IL11RA, IL1A, IL1B, IL1R1, IL1R2, IL2RA, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL7, IL7R, IL9R, ITGA1, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGAM, ITGB3, KIT, KITLG, MME, MS4A1, TFRC, THPO, TNF, TPO 83 ANPEP(13), CD14(2), CD19(7), CD1A(5), CD1B(3), CD1C(15), CD1D(3), CD1E(6), CD2(4), CD22(13), CD33(11), CD34(4), CD36(7), CD37(1), CD38(7), CD3D(3), CD3E(2), CD3G(2), CD4(8), CD44(12), CD5(7), CD55(6), CD59(2), CD8A(3), CD8B(1), CD9(4), CR1(28), CR2(28), CSF1(5), CSF1R(7), CSF2RA(9), CSF3(1), CSF3R(11), DNTT(6), EPO(2), EPOR(4), FCER2(2), FCGR1A(7), FLT3(9), FLT3LG(4), GP1BA(11), GP5(5), GYPA(2), HLA-DRB1(1), HLA-DRB5(1), IL11RA(7), IL1A(1), IL1B(2), IL1R1(5), IL1R2(7), IL2RA(3), IL3RA(11), IL4R(6), IL5(2), IL5RA(9), IL6(2), IL6R(12), IL7(2), IL7R(9), ITGA1(20), ITGA2(21), ITGA2B(11), ITGA3(6), ITGA4(12), ITGA5(12), ITGA6(12), ITGAM(24), ITGB3(16), KIT(28), KITLG(2), MME(8), MS4A1(6), TFRC(6), THPO(11), TNF(1), TPO(18) 29103747 586 92 569 185 170 221 78 27 84 6 0.022 0.068 204 KERATINOCYTEPATHWAY Keratinocyte differentiation, which models the differentiation of epidermal cells, requires the four main MAP kinase pathways. BCL2, CEBPA, CHUK, DAXX, EGF, EGFR, ETS1, ETS2, FOS, HOXA7, HRAS, IKBKB, JUN, MAP2K1, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K1, MAP3K14, MAP3K5, MAPK1, MAPK13, MAPK14, MAPK3, MAPK8, NFKB1, NFKBIA, PPP2CA, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCQ, RAF1, RELA, RIPK1, SP1, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TRAF2 41 CHUK(11), DAXX(11), EGF(24), EGFR(20), ETS1(6), ETS2(5), FOS(6), HOXA7(8), IKBKB(15), JUN(1), MAP2K1(2), MAP2K3(8), MAP2K4(6), MAP2K6(9), MAP3K1(31), MAP3K14(12), MAP3K5(21), MAPK1(2), MAPK13(2), MAPK14(6), MAPK3(4), MAPK8(7), NFKB1(12), NFKBIA(3), PPP2CA(6), PRKCA(10), PRKCD(7), PRKCE(11), PRKCG(10), PRKCH(9), PRKCQ(13), RAF1(7), RELA(6), RIPK1(8), SP1(6), TNF(1), TNFRSF1A(6), TNFRSF1B(3), TRAF2(5) 16685307 340 69 333 95 80 136 56 22 44 2 0.023 0.069 205 STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR 10 EPX(14), GBA3(9), LPO(6), MPO(9), PRDX1(1), PRDX2(4), PRDX5(3), PRDX6(2), TPO(18), TYR(10) 3243469 76 36 75 23 27 31 10 1 7 0 0.023 0.069 206 PURINE_METABOLISM 1_Sep, ADA, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADK, ADSL, ADSS, AK1, AK2, AK5, ALLC, AMPD1, AMPD2, AMPD3, APRT, ATIC, ATP1B1, ATP5A1, ATP5B, ATP5C1, ATP5D, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP5I, ATP5J, ATP5J2, CANT1, DCK, DGUOK, ECGF1, ENPP1, ENPP3, ENTPD1, ENTPD2, FHIT, GART, GDA, GMPS, GUCY1A2, GUCY1A3, GUCY1B2, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, GUK1, HPRT1, IMPDH1, IMPDH2, ITPA, NME1, NME2, NP, NPR1, NPR2, NT5C, NT5E, NT5M, NUDT2, PAICS, PAPSS1, PAPSS2, PDE1A, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A, PDE6B, PDE6C, PDE6G, PDE7B, PDE8A, PDE9A, PFAS, PKLR, PKM2, POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT, POLS, PPAT, PRPS1, PRPS1L1, PRPS2, PRUNE, RRM1, RRM2, SAC 106 ADA(3), ADCY1(17), ADCY2(17), ADCY3(8), ADCY4(8), ADCY5(11), ADCY6(16), ADCY7(6), ADCY8(16), ADK(1), ADSL(7), ADSS(8), AK1(2), AK2(4), AK5(6), ALLC(10), AMPD1(21), AMPD2(9), AMPD3(4), ATIC(9), ATP1B1(3), ATP5A1(11), ATP5B(4), ATP5C1(1), ATP5F1(5), ATP5G1(4), ATP5G2(1), ATP5I(1), ATP5J(4), CANT1(5), DCK(4), DGUOK(3), ENPP1(11), ENPP3(16), ENTPD1(6), FHIT(2), GART(8), GDA(5), GMPS(13), GUCY1A2(10), GUCY1A3(12), GUCY1B3(7), GUCY2C(12), GUCY2D(7), GUCY2F(25), GUK1(6), HPRT1(2), IMPDH1(5), IMPDH2(10), ITPA(1), NPR1(14), NPR2(16), NT5C(1), NT5E(6), NT5M(4), NUDT2(3), PAICS(4), PAPSS1(6), PAPSS2(6), PDE1A(12), PDE4A(12), PDE4B(17), PDE4C(6), PDE4D(7), PDE5A(14), PDE6B(6), PDE6C(14), PDE7B(4), PDE8A(7), PDE9A(10), PFAS(10), PKLR(10), PKM2(5), POLB(4), POLD1(15), POLD2(6), POLE(1), POLG(7), POLL(8), POLQ(23), POLR1B(16), POLR2A(25), POLR2B(20), POLR2C(5), POLR2D(3), POLR2E(1), POLR2F(2), POLR2H(3), POLR2K(2), PPAT(10), PRPS1(3), PRPS1L1(5), PRPS2(10), PRUNE(4), RRM1(4), RRM2(5) 42966703 763 100 751 225 195 326 98 46 96 2 0.024 0.073 207 NDKDYNAMINPATHWAY Endocytotic role of NDK, Phosphins and Dynamin AMPH, AP2A1, AP2M1, BIN1, CALM1, CALM2, CALM3, DNM1, EPN1, EPS15, NME1, NME2, PICALM, PPP3CA, PPP3CB, PPP3CC, SYNJ1, SYNJ2, SYT1 19 AMPH(17), AP2A1(7), AP2M1(6), BIN1(3), CALM2(3), CALM3(1), DNM1(5), EPN1(9), EPS15(12), PICALM(13), PPP3CA(4), PPP3CB(7), PPP3CC(6), SYNJ1(27), SYNJ2(13), SYT1(4) 7528739 137 52 133 51 38 48 24 7 20 0 0.025 0.074 208 CHONDROITIN B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 7 B3GAT3(4), B4GALT7(4), HS3ST1(5), HS3ST2(4), HS3ST3A1(3), XYLT1(15), XYLT2(9) 2082646 44 27 43 16 14 19 5 1 5 0 0.025 0.075 209 HEPARAN_SULFATE_BIOSYNTHESIS B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 7 B3GAT3(4), B4GALT7(4), HS3ST1(5), HS3ST2(4), HS3ST3A1(3), XYLT1(15), XYLT2(9) 2082646 44 27 43 16 14 19 5 1 5 0 0.025 0.075 210 PEPTIDE_GPCRS AGTR1, AGTR2, ATP8A1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BLR1, BRS3, C3AR1, C5R1, CCKAR, CCKBR, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CX3CR1, CXCR3, CXCR4, CXCR6, EDNRA, EDNRB, ELA3A, FPR1, FPRL1, FPRL2, FSHR, FY, GALR1, GALR2, GALR3, GALT, GHSR, GNB2L1, GNRHR, GPR77, GRPR, IL8RA, IL8RB, LHCGR, MC1R, MC2R, MC3R, MC4R, MC5R, NMBR, NPY1R, NPY2R, NPY5R, NPY6R, NTSR1, NTSR2, OPRD1, OPRK1, OPRL1, OPRM1, OXTR, PPYR1, SSTR1, SSTR2, SSTR3, SSTR4, TAC4, TACR1, TACR2, TACR3, TRHR, TSHR 63 AGTR2(8), ATP8A1(14), AVPR1A(8), AVPR1B(3), AVPR2(5), BDKRB1(5), BDKRB2(9), BRS3(13), C3AR1(7), CCKAR(12), CCKBR(7), CCR1(5), CCR2(6), CCR3(5), CCR4(5), CCR6(5), CCR7(5), CCR8(6), CX3CR1(4), CXCR3(5), CXCR4(1), CXCR6(3), EDNRA(6), EDNRB(2), FPR1(4), FSHR(17), GALR1(2), GALR3(3), GALT(2), GHSR(7), GNB2L1(2), GNRHR(4), GPR77(3), GRPR(4), LHCGR(16), MC2R(2), MC3R(8), MC4R(7), MC5R(12), NMBR(4), NPY1R(6), NPY2R(4), NPY5R(10), NTSR1(4), NTSR2(2), OPRD1(2), OPRK1(9), OPRM1(11), OXTR(4), PPYR1(7), SSTR1(12), SSTR2(3), SSTR3(6), SSTR4(12), TAC4(1), TACR1(6), TACR2(4), TACR3(9), TRHR(5), TSHR(12) 17007718 375 72 368 138 96 174 50 15 40 0 0.026 0.076 211 HSA04610_COMPLEMENT_AND_COAGULATION_CASCADES Genes involved in complement and coagulation cascades A2M, BDKRB1, BDKRB2, C1QA, C1QB, C1QC, C1R, C1S, C2, C3, C3AR1, C4A, C4B, C4BPA, C4BPB, C5, C5AR1, C6, C7, C8A, C8B, C8G, C9, CD46, CD55, CD59, CFB, CFD, CFH, CFI, CPB2, CR1, CR2, F10, F11, F12, F13A1, F13B, F2, F2R, F3, F5, F7, F8, F9, FGA, FGB, FGG, KLKB1, KNG1, MASP1, MASP2, MBL2, PLAT, PLAU, PLAUR, PLG, PROC, PROS1, SERPINA1, SERPINA5, SERPINC1, SERPIND1, SERPINE1, SERPINF2, SERPING1, TFPI, THBD, VWF 64 A2M(21), BDKRB1(5), BDKRB2(9), C1QA(6), C1QB(3), C1QC(6), C1R(15), C1S(9), C2(6), C3(24), C3AR1(7), C4BPA(8), C4BPB(4), C5(20), C5AR1(5), C6(23), C7(21), C8A(12), C8B(4), C9(20), CD46(1), CD55(6), CD59(2), CFB(8), CFH(17), CFI(9), CPB2(7), CR1(28), CR2(28), F10(10), F11(10), F12(3), F13A1(10), F13B(13), F2(9), F2R(8), F3(6), F5(46), F7(2), F8(41), F9(11), FGA(30), FGB(6), FGG(12), KLKB1(13), KNG1(8), MASP1(14), MASP2(6), MBL2(3), PLAT(6), PLAU(5), PLAUR(5), PLG(13), PROC(7), SERPINA1(4), SERPINA5(3), SERPINC1(9), SERPIND1(6), SERPINE1(5), SERPINF2(5), SERPING1(7), TFPI(11), VWF(31) 31318799 712 92 682 185 196 299 93 35 81 8 0.029 0.085 212 HSA00232_CAFFEINE_METABOLISM Genes involved in caffeine metabolism CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH 7 CYP1A2(6), CYP2A13(7), CYP2A6(11), CYP2A7(5), NAT1(10), NAT2(3), XDH(10) 2863937 52 32 48 21 18 25 5 1 3 0 0.030 0.088 213 ST_TYPE_I_INTERFERON_PATHWAY Type I interferon is an antiviral cytokine that induces a JAK-STAT type pathway leading to ISGF3 activation and a cellular antiviral response. IFNAR1, IFNB1, ISGF3G, JAK1, PTPRU, REG1A, STAT1, STAT2, TYK2 8 IFNAR1(9), IFNB1(4), JAK1(31), PTPRU(20), REG1A(4), STAT1(14), STAT2(12), TYK2(7) 4324227 101 39 92 25 20 37 14 6 18 6 0.032 0.092 214 GPCRDB_OTHER ADORA3, ALG6, C5R1, CCKBR, CCR2, CCR3, CCR5, CELSR1, CELSR2, CELSR3, CHRM2, CHRM3, CIDEB, CXCR3, DRD4, EBI2, EDG1, EDNRA, ELA3A, EMR2, EMR3, F2R, FSHR, FY, GHRHR, GNRHR, GPR, GPR116, GPR132, GPR133, GPR135, GPR143, GPR145, GPR17, GPR18, GPR55, GPR56, GPR61, GPR73L1, GPR77, GPR84, GPR88, GRCA, GRM1, GRPR, HRH4, IL8RA, IL8RB, LGR6, LGR7, LPHN2, LPHN3, LTB4R2, MASS1, NTSR1, OR2A9P, OR2M4, OR5E1P, OR7E19P, OR7E47P, OR7E37P, OR7E18P, OR7E35P, LOC441453, OR8G1, LOC442754, OR8G2, P2RY11, P2RY13, PTGFR, RLN3R1, SMO, SSTR2, TAAR5, TSHR, VN1R1 48 ADORA3(5), ALG6(5), CCKBR(7), CCR2(6), CCR3(5), CELSR2(30), CELSR3(23), CHRM2(9), CHRM3(9), CIDEB(3), CXCR3(5), EDNRA(6), EMR2(5), EMR3(8), F2R(8), FSHR(17), GHRHR(2), GNRHR(4), GPR116(20), GPR132(8), GPR133(11), GPR143(13), GPR17(4), GPR18(2), GPR55(4), GPR56(3), GPR61(7), GPR77(3), GPR84(6), GRM1(22), GRPR(4), HRH4(4), LGR6(18), LPHN2(30), LPHN3(29), LTB4R2(3), NTSR1(4), OR8G1(1), OR8G2(6), P2RY11(7), P2RY13(3), PTGFR(10), SMO(6), SSTR2(3), TAAR5(8), TSHR(12), VN1R1(5) 20282496 413 80 408 120 119 165 59 26 42 2 0.032 0.093 215 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(11), GOT1(6), GOT2(5), TAT(9), TYR(10) 1635238 41 24 40 5 8 17 7 3 6 0 0.035 0.100 216 PHENYLALANINE_METABOLISM ABP1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, DDC, EPX, GOT1, GOT2, HPD, LPO, MAOA, MAOB, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TAT, TPO 22 ABP1(12), ALDH3A1(6), ALDH3B1(5), ALDH3B2(8), AOC2(6), AOC3(14), DDC(11), EPX(14), GOT1(6), GOT2(5), HPD(7), LPO(6), MAOA(14), MAOB(7), MPO(9), PRDX1(1), PRDX2(4), PRDX5(3), PRDX6(2), TAT(9), TPO(18) 7537821 167 50 162 51 48 66 23 8 22 0 0.036 0.10 217 HSA05050_DENTATORUBROPALLIDOLUYSIAN_ATROPHY Genes involved in dentatorubropallidoluysian atrophy (DRPLA) ATN1, BAIAP2, CASP1, CASP3, CASP7, CASP8, GAPDH, INS, INSR, ITCH, MAGI1, MAGI2, RERE, WWP1, WWP2 14 ATN1(9), BAIAP2(1), CASP1(7), CASP3(4), CASP7(4), CASP8(21), GAPDH(2), INSR(18), ITCH(8), MAGI1(32), MAGI2(26), RERE(14), WWP1(18), WWP2(7) 8025142 171 52 168 43 35 83 24 6 23 0 0.037 0.10 218 GAMMA_HEXACHLOROCYCLOHEXANE_DEGRADATION ACP1, ACP2, ACP5, ACPP, ACPT, ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, CYP19A1, CYP1A1, CYP1A2, CYP2A6, CYP2A6, CYP2A7, CYP2A7P1, CYP2A13, CYP2B6, CYP2C18, CYP2C19, CYP2C19, CYP2C9, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP3A4, CYP3A5, CYP3A7, CYP4B1, CYP4F8, CYP51A1, PON1 31 ACP1(4), ACP2(2), ACP5(4), ACPP(5), ACPT(7), ALPI(3), ALPL(3), ALPP(4), ALPPL2(5), CYP19A1(12), CYP1A1(9), CYP1A2(6), CYP2A13(7), CYP2A6(11), CYP2A7(5), CYP2B6(11), CYP2C18(5), CYP2C19(7), CYP2C8(4), CYP2C9(5), CYP2D6(2), CYP2E1(5), CYP2F1(5), CYP2J2(5), CYP3A4(14), CYP3A5(7), CYP3A7(9), CYP4B1(4), CYP4F8(9), CYP51A1(4), PON1(12) 10164909 195 55 190 60 57 74 31 11 20 2 0.039 0.11 219 ST_ERK1_ERK2_MAPK_PATHWAY The Erk1 and Erk2 MAP kinase pathways are regulated by Raf, Mos, and Tpl-2. ARAF1, ATF1, BAD, BRAF, COPEB, CREB1, CREB3, CREB5, DUSP4, DUSP6, DUSP9, EEF2K, EIF4E, GRB2, HTATIP, MAP2K1, MAP2K2, MAP3K8, MAPK1, MAPK3, MKNK1, MKNK2, MOS, NFKB1, RAP1A, RPS6KA1, RPS6KA2, RPS6KA3, SHC1, SOS1, SOS2, TRAF3 28 ATF1(6), BAD(2), BRAF(12), CREB1(5), CREB3(2), CREB5(6), DUSP4(1), DUSP6(1), DUSP9(8), EEF2K(11), EIF4E(4), GRB2(3), MAP2K1(2), MAP3K8(12), MAPK1(2), MAPK3(4), MKNK1(6), MKNK2(4), MOS(8), NFKB1(12), RAP1A(3), RPS6KA1(5), RPS6KA2(16), RPS6KA3(17), SHC1(11), SOS1(21), SOS2(22), TRAF3(6) 9970363 212 59 204 48 42 91 32 12 31 4 0.040 0.11 220 GABAPATHWAY Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter whose receptor is regulated by Plic-1, gephyrin, and GABARAP, which promote receptor clustering. DNM1, GABARAP, GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPHN, NSF, SRC, UBQLN1 12 DNM1(5), GABARAP(2), GABRA1(10), GABRA2(12), GABRA3(15), GABRA4(17), GABRA5(8), GABRA6(8), GPHN(13), NSF(3), SRC(2), UBQLN1(8) 4203532 103 40 97 33 31 41 12 6 13 0 0.041 0.12 221 THELPERPATHWAY Helper T cells coordinate the actions of B cells, macrophages, and other immune cells via surface molecules such as T cell receptor/CD3 and their characteristic marker CD4. CD2, CD28, CD3D, CD3E, CD3G, CD3Z, CD4, ICAM1, ITGAL, ITGB2, PTPRC, THY1, TRA@, TRB@ 11 CD2(4), CD28(6), CD3D(3), CD3E(2), CD3G(2), CD4(8), ICAM1(3), ITGAL(13), ITGB2(14), PTPRC(15), THY1(1) 3855787 71 36 70 29 14 38 7 2 10 0 0.042 0.12 222 NFKBPATHWAY Inactive nuclear factor kB (NF-kB) is inhibited by the IkB family in the cytoplasm; active NF-kB is localized in the nucleus and regulates transcription of a variety of genes. CHUK, FADD, IKBKB, IKBKG, IL1A, IL1R1, IRAK1, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MYD88, NFKB1, NFKBIA, RELA, RIPK1, TLR4, TNF, TNFAIP3, TNFRSF1A, TNFRSF1B, TRADD, TRAF6 20 CHUK(11), FADD(1), IKBKB(15), IL1A(1), IL1R1(5), IRAK1(5), MAP3K1(31), MAP3K14(12), MAP3K7(8), MYD88(1), NFKB1(12), NFKBIA(3), RELA(6), RIPK1(8), TLR4(14), TNF(1), TNFAIP3(2), TNFRSF1A(6), TNFRSF1B(3), TRAF6(4) 8233550 149 49 146 41 34 54 21 13 25 2 0.042 0.12 223 BCRPATHWAY B cell antigen receptors (BCRs) activate tyrosine kinases and transiently increase tyrosine phosphorylation on binding to antigen. BLNK, BTK, CALM1, CALM2, CALM3, CD79A, CD79B, ELK1, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP3K1, MAPK14, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, RAC1, RAF1, SHC1, SOS1, SYK, SYT1, VAV1 34 BLNK(4), BTK(11), CALM2(3), CALM3(1), CD79A(1), CD79B(2), ELK1(2), FOS(6), GRB2(3), JUN(1), LYN(7), MAP2K1(2), MAP3K1(31), MAPK14(6), MAPK3(4), MAPK8(7), NFATC2(15), NFATC3(12), NFATC4(8), PLCG1(12), PPP3CA(4), PPP3CB(7), PPP3CC(6), PRKCA(10), RAF1(7), SHC1(11), SOS1(21), SYK(6), SYT1(4), VAV1(16) 13078319 230 64 222 66 72 74 31 16 31 6 0.042 0.12 224 IL18PATHWAY Pro-inflammatory IL-18 is activated in macrophages by caspase-1 cleavage and, in conjunction with IL-12, stimulates Th1 cell differentiation. CASP1, IFNG, IL12A, IL12B, IL18, IL2 6 CASP1(7), IFNG(5), IL12A(7), IL12B(3), IL18(1), IL2(4) 1094142 27 20 26 7 9 8 5 2 3 0 0.043 0.12 225 VIPPATHWAY Apoptosis of activated T cells is inhibited by vasoactive intestinal peptide (VIP) and its relative PACAP. CALM1, CALM2, CALM3, CHUK, EGR2, EGR3, GNAQ, MAP3K1, MYC, NFATC1, NFATC2, NFKB1, NFKBIA, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RELA, SYT1, VIP, VIPR2 27 CALM2(3), CALM3(1), CHUK(11), EGR2(8), EGR3(9), MAP3K1(31), MYC(7), NFATC2(15), NFKB1(12), NFKBIA(3), PLCG1(12), PPP3CA(4), PPP3CB(7), PPP3CC(6), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), RELA(6), SYT1(4), VIP(2) 9279653 170 52 164 51 39 62 22 14 29 4 0.044 0.12 226 HSA00940_PHENYLPROPANOID_BIOSYNTHESIS Genes involved in phenylpropanoid biosynthesis EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO 7 EPX(14), GBA(4), GBA3(9), LPO(6), MPO(9), PRDX6(2), TPO(18) 2853182 62 34 61 20 25 21 7 2 7 0 0.045 0.12 227 HSA01032_GLYCAN_STRUCTURES_DEGRADATION Genes involved in degradation of glycan structures AGA, ARSB, FLJ21865, FUCA1, FUCA2, GALNS, GBA, GLB1, GNS, GUSB, HEXA, HEXB, HGSNAT, HPSE, HPSE2, HYAL1, HYAL2, IDS, IDUA, LCT, MAN2B1, MAN2B2, MAN2C1, MANBA, NAGLU, NEU1, NEU2, NEU3, NEU4, SPAM1 27 AGA(4), ARSB(6), FUCA1(3), FUCA2(3), GBA(4), GLB1(9), GNS(2), GUSB(5), HEXA(3), HEXB(4), HGSNAT(9), HPSE(4), HPSE2(5), HYAL1(4), HYAL2(1), IDS(6), LCT(30), MAN2B1(20), MAN2B2(9), MAN2C1(8), MANBA(14), NAGLU(3), NEU2(5), NEU3(3), SPAM1(12) 11375922 176 58 171 72 49 79 21 11 16 0 0.045 0.12 228 LAIRPATHWAY The local acute inflammatory response is mediated by activated macrophages and mast cells or by complement activation. BDK, C3, C5, C6, C7, ICAM1, IL1A, IL6, IL8, ITGA4, ITGAL, ITGB1, ITGB2, SELP, SELPLG, TNF, VCAM1 16 C3(24), C5(20), C6(23), C7(21), ICAM1(3), IL1A(1), IL6(2), IL8(3), ITGA4(12), ITGAL(13), ITGB1(12), ITGB2(14), SELP(15), SELPLG(11), TNF(1), VCAM1(9) 8463946 184 52 176 47 44 82 19 9 26 4 0.046 0.12 229 ALANINE_AND_ASPARTATE_METABOLISM AARS, ABAT, ADSL, ADSS, AGXT, AGXT2, ASL, ASNS, ASPA, ASS, CAD, CRAT, DARS, DDO, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, PC 20 AARS(10), ABAT(9), ADSL(7), ADSS(8), AGXT(5), AGXT2(9), ASL(4), ASNS(9), ASPA(5), CAD(38), CRAT(3), DARS(4), DDO(9), GAD1(8), GAD2(12), GOT1(6), GOT2(5), GPT2(7), NARS(7), PC(8) 8647259 173 56 171 51 40 77 26 5 25 0 0.047 0.13 230 BLYMPHOCYTEPATHWAY B cells express the major histocompatibility complex (class II MHC), immunoglobulins, adhesion proteins, and other factors on their cell surface. CD80, CR1, CR2, FCGR2B, HLA-DRA, HLA-DRB1, ICAM1, ITGAL, ITGB2, PTPRC, TNFRSF5 10 CD80(7), CR1(28), CR2(28), FCGR2B(4), HLA-DRB1(1), ICAM1(3), ITGAL(13), ITGB2(14), PTPRC(15) 5313926 113 43 110 35 34 47 14 4 12 2 0.051 0.14 231 ERKPATHWAY Cell growth is promoted by Ras activation of the anti-apoptotic p44/42 MAP kinase pathway. DPM2, EGFR, ELK1, GNAS, GNB1, GNGT1, GRB2, HRAS, IGF1R, ITGB1, KLK2, MAP2K1, MAP2K2, MAPK1, MAPK3, MKNK1, MKNK2, MYC, NGFB, NGFR, PDGFRA, PPP2CA, PTPRR, RAF1, RPS6KA1, RPS6KA5, SHC1, SOS1, SRC, STAT3 28 DPM2(4), EGFR(20), ELK1(2), GNAS(25), GNB1(3), GRB2(3), IGF1R(13), ITGB1(12), KLK2(2), MAP2K1(2), MAPK1(2), MAPK3(4), MKNK1(6), MKNK2(4), MYC(7), NGFR(4), PDGFRA(29), PPP2CA(6), PTPRR(18), RAF1(7), RPS6KA1(5), RPS6KA5(7), SHC1(11), SOS1(21), SRC(2), STAT3(12) 10992088 231 61 223 50 56 98 32 12 29 4 0.051 0.14 232 GSPATHWAY Activated G-protein coupled receptors stimulate cAMP production and thus activate protein kinase A, involved in a number of signal transduction pathways. ADCY1, GNAS, GNB1, GNGT1, PRKACA, PRKAR1A 6 ADCY1(17), GNAS(25), GNB1(3), PRKACA(4), PRKAR1A(4) 2068545 53 29 51 10 14 27 3 4 5 0 0.053 0.14 233 ST_TUMOR_NECROSIS_FACTOR_PATHWAY Tumor necrosis factor is a pro-inflammatory cytokine that activates NF-kB and c-Jun. BAG4, BIRC2, BIRC3, CASP3, CASP8, CFLAR, FADD, HRB, IKBKG, JUN, MAP2K4, MAP3K3, MAP3K7, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, NR2C2, RALBP1, RIPK1, TNF, TNFAIP3, TNFRSF1A, TNFRSF1B, TRADD, TRAF2 26 BAG4(4), BIRC2(13), BIRC3(3), CASP3(4), CASP8(21), CFLAR(7), FADD(1), JUN(1), MAP2K4(6), MAP3K3(9), MAP3K7(8), NFKB1(12), NFKB2(10), NFKBIA(3), NFKBIB(3), NFKBIE(6), NFKBIL1(2), NR2C2(8), RALBP1(7), RIPK1(8), TNF(1), TNFAIP3(2), TNFRSF1A(6), TNFRSF1B(3), TRAF2(5) 8982098 153 53 149 36 32 64 25 6 26 0 0.054 0.14 234 PTDINSPATHWAY Phosphoinositide 3 kinase (PI3K) phosphorylate inositol rings of phosphoinositide lipids, influencing vesicle trafficking, cell proliferation, and migration. AKT1, AP2A1, AP2M1, ARF1, BAD, BTK, EEA1, GRASP, GSK3A, GSK3B, LYN, PDPK1, PFKL, PFKM, PFKP, PFKX, PLCG1, PRKCE, PRKCZ, RAB5A, RAC1, RPS6KB1, VAV2 21 AKT1(8), AP2A1(7), AP2M1(6), ARF1(4), BAD(2), BTK(11), EEA1(20), GRASP(3), GSK3A(9), GSK3B(11), LYN(7), PDPK1(3), PFKM(7), PFKP(11), PLCG1(12), PRKCE(11), PRKCZ(4), RAB5A(2), RPS6KB1(3), VAV2(5) 8006261 146 52 138 54 43 60 19 7 17 0 0.055 0.14 235 HSA00680_METHANE_METABOLISM Genes involved in methane metabolism ADH5, CAT, EPX, LPO, MPO, MTHFR, PRDX6, SHMT1, SHMT2, TPO 10 ADH5(3), CAT(5), EPX(14), LPO(6), MPO(9), MTHFR(7), PRDX6(2), SHMT1(6), SHMT2(8), TPO(18) 3889486 78 37 77 19 26 30 7 2 11 2 0.056 0.15 236 PROSTAGLANDIN_SYNTHESIS_REGULATION ANXA1, ANXA2, ANXA3, ANXA4, ANXA5, ANXA6, ANXA8, CYP11A1, EDN1, EDNRA, EDNRB, HPGD, HSD11B1, HSD11B2, PLA2G4A, PRL, PTGDR, PTGDS, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, PTGIS, PTGS1, PTGS2, S100A6, SCGB1A1, TBXAS1 27 ANXA1(4), ANXA2(1), ANXA3(8), ANXA4(8), ANXA5(3), ANXA6(10), CYP11A1(10), EDN1(2), EDNRA(6), EDNRB(2), HPGD(2), HSD11B1(4), PLA2G4A(11), PRL(6), PTGDR(6), PTGDS(6), PTGER2(5), PTGER4(8), PTGFR(10), PTGIR(3), PTGIS(8), PTGS1(8), PTGS2(7), SCGB1A1(1), TBXAS1(6) 7229033 145 48 144 43 45 54 19 7 20 0 0.056 0.15 237 IL5PATHWAY Pro-inflammatory IL-5 is secretes by activated T cells, eosinophils, and mast cells, and stimulates the proliferation and activation of eosinophils in bone marrow. CCL11, CCR3, CD4, HLA-DRA, HLA-DRB1, IL1B, IL4, IL5, IL5RA, IL6 10 CCR3(5), CD4(8), HLA-DRB1(1), IL1B(2), IL5(2), IL5RA(9), IL6(2) 1925145 29 21 27 11 3 15 1 0 10 0 0.058 0.15 238 HSA04340_HEDGEHOG_SIGNALING_PATHWAY Genes involved in Hedgehog signaling pathway BMP2, BMP4, BMP5, BMP6, BMP7, BMP8A, BMP8B, BTRC, CSNK1A1, CSNK1A1L, CSNK1D, CSNK1E, CSNK1G1, CSNK1G2, CSNK1G3, DHH, FBXW11, GAS1, GLI1, GLI2, GLI3, GSK3B, HHIP, IHH, LRP2, PRKACA, PRKACB, PRKACG, PRKX, PRKY, PTCH1, PTCH2, RAB23, SHH, SMO, STK36, SUFU, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B, ZIC2 54 BMP2(5), BMP4(7), BMP5(16), BMP6(6), BMP7(15), BMP8A(3), BMP8B(1), BTRC(13), CSNK1A1(5), CSNK1A1L(4), CSNK1E(10), CSNK1G1(8), CSNK1G3(11), DHH(2), FBXW11(5), GLI1(12), GLI2(11), GLI3(21), GSK3B(11), HHIP(12), IHH(3), LRP2(72), PRKACA(4), PRKACB(2), PRKACG(6), PRKX(4), PTCH1(23), PTCH2(21), RAB23(4), SHH(7), SMO(6), STK36(11), SUFU(7), WNT1(1), WNT10A(4), WNT10B(1), WNT11(4), WNT16(6), WNT2(4), WNT2B(9), WNT3(5), WNT4(4), WNT5A(9), WNT5B(4), WNT7A(2), WNT7B(1), WNT8A(1), WNT8B(4), WNT9A(1), WNT9B(1), ZIC2(1) 19982790 410 78 395 130 131 163 46 14 54 2 0.059 0.15 239 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 CMBL(4) 181162 4 4 4 1 2 1 0 0 1 0 0.060 0.15 240 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 7 CARS(10), CTH(5), GOT1(6), GOT2(5), LDHA(6), LDHB(2), LDHC(3) 2295356 37 28 36 17 8 14 3 4 8 0 0.060 0.15 241 HSA00471_D_GLUTAMINE_AND_D_GLUTAMATE_METABOLISM Genes involved in D-glutamine and D-glutamate metabolism GLS, GLS2, GLUD1, GLUD2 4 GLS(10), GLS2(9), GLUD1(4), GLUD2(9) 1451447 32 21 31 11 8 12 5 1 6 0 0.061 0.16 242 METHANE_METABOLISM ADH5, ATP6V0C, SHMT1, CAT, EPX, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, SHMT1, SHMT2, TPO 13 ADH5(3), ATP6V0C(2), CAT(5), EPX(14), LPO(6), MPO(9), PRDX1(1), PRDX2(4), PRDX5(3), PRDX6(2), SHMT1(6), SHMT2(8), TPO(18) 3906933 81 38 80 23 28 34 7 2 8 2 0.063 0.16 243 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 2 FAH(7), GSTZ1(4) 463421 11 10 11 1 0 6 1 2 2 0 0.064 0.16 244 IFNAPATHWAY Interferon alpha, active in the immune response, binds to the IFN receptor and activates Jak1 and Tyk2, which phosphorylate Stat1 and Stat2. IFNA1, IFNAR1, IFNAR2, IFNB1, ISGF3G, JAK1, STAT1, STAT2, TYK2 8 IFNAR1(9), IFNAR2(8), IFNB1(4), JAK1(31), STAT1(14), STAT2(12), TYK2(7) 3819937 85 33 75 21 17 25 14 7 16 6 0.065 0.16 245 EGFR_SMRTEPATHWAY EGF receptor activation inhibits SMRT, a transcriptional co-repressor that interacts with transcription factor complexes and gene silencers. EGF, EGFR, MAP2K1, MAP3K1, MAPK14, NCOR2, RARA, RXRA, THRA, THRB, ZNF145 10 EGF(24), EGFR(20), MAP2K1(2), MAP3K1(31), MAPK14(6), NCOR2(24), RARA(3), RXRA(1), THRA(5), THRB(4) 5296718 120 42 116 36 33 41 16 11 17 2 0.068 0.17 246 HSA00590_ARACHIDONIC_ACID_METABOLISM Genes involved in arachidonic acid metabolism AKR1C3, ALOX12, ALOX12B, ALOX15, ALOX15B, ALOX5, CBR1, CBR3, CYP2B6, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2E1, CYP2J2, CYP2U1, CYP4A11, CYP4A22, CYP4F2, CYP4F3, DHRS4, EPHX2, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, LTA4H, LTC4S, PGDS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PTGDS, PTGES, PTGES2, PTGIS, PTGS1, PTGS2, TBXAS1 49 AKR1C3(3), ALOX12(6), ALOX12B(10), ALOX15(12), ALOX15B(12), ALOX5(7), CBR1(2), CBR3(2), CYP2B6(11), CYP2C18(5), CYP2C19(7), CYP2C8(4), CYP2C9(5), CYP2E1(5), CYP2J2(5), CYP2U1(2), CYP4A11(5), CYP4A22(8), CYP4F2(11), CYP4F3(8), EPHX2(7), GGT1(10), GPX3(4), GPX5(7), GPX6(6), GPX7(1), LTA4H(6), PLA2G10(1), PLA2G12A(1), PLA2G12B(3), PLA2G1B(1), PLA2G2D(2), PLA2G2E(3), PLA2G2F(3), PLA2G3(5), PLA2G4A(11), PLA2G5(2), PLA2G6(6), PTGDS(6), PTGES(2), PTGES2(2), PTGIS(8), PTGS1(8), PTGS2(7), TBXAS1(6) 12931334 248 63 242 75 67 103 34 13 29 2 0.070 0.17 247 CHOLESTEROL_BIOSYNTHESIS C10orf110, CYP51A1, DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, HMGCS1, IDI1, LSS, MVD, MVK, NSDHL, PMVK, SC4MOL, SC5DL, SQLE 15 CYP51A1(4), DHCR7(4), FDFT1(3), FDPS(7), HMGCR(15), HMGCS1(4), IDI1(4), MVD(3), MVK(7), NSDHL(9), PMVK(2), SC4MOL(3), SC5DL(3), SQLE(6) 4147606 74 36 73 29 19 22 12 7 14 0 0.070 0.17 248 DREAMPATHWAY The transcription factor DREAM blocks expression of the prodynorphin gene, which encodes the ligand of an opioid receptor that blocks pain signaling. CREB1, CREM, CSEN, FOS, JUN, MAPK3, OPRK1, POLR2A, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 13 CREB1(5), CREM(5), FOS(6), JUN(1), MAPK3(4), OPRK1(9), POLR2A(25), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5) 4326378 84 38 82 22 17 42 7 5 11 2 0.071 0.18 249 IL10PATHWAY The cytokine IL-10 inhibits the inflammatory response by macrophages via activation of heme oxygenase 1. BLVRA, BLVRB, HMOX1, IL10, IL10RA, IL10RB, IL1A, IL6, JAK1, STAT1, STAT3, STAT5A, TNF 13 BLVRA(2), BLVRB(1), HMOX1(3), IL10(4), IL10RA(7), IL10RB(9), IL1A(1), IL6(2), JAK1(31), STAT1(14), STAT3(12), STAT5A(5), TNF(1) 4269018 92 35 84 26 20 34 9 3 20 6 0.071 0.18 250 PROSTAGLANDIN_AND_LEUKOTRIENE_METABOLISM AKR1C3, ALOX12, ALOX15, ALOX5, CBR1, CBR3, CYP4F2, CYP4F3, CYP4F3, CYP4F2, EPX, GGT1, LPO, LTA4H, MPO, PGDS, PLA2G1B, PLA2G2A, PLA2G2E, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PRDX1, PRDX2, PRDX5, PRDX6, PTGDS, PTGES2, PTGIS, PTGS1, PTGS2, TBXAS1, TPO 31 AKR1C3(3), ALOX12(6), ALOX15(12), ALOX5(7), CBR1(2), CBR3(2), CYP4F2(11), CYP4F3(8), EPX(14), GGT1(10), LPO(6), LTA4H(6), MPO(9), PLA2G1B(1), PLA2G2E(3), PLA2G3(5), PLA2G4A(11), PLA2G5(2), PLA2G6(6), PRDX1(1), PRDX2(4), PRDX5(3), PRDX6(2), PTGDS(6), PTGES2(2), PTGIS(8), PTGS1(8), PTGS2(7), TBXAS1(6), TPO(18) 9229941 189 55 185 61 55 83 26 7 18 0 0.073 0.18 251 AGPCRPATHWAY G-protein coupled receptors (GPCRs) transduce extracellular signals across the plasma membrane; attenuation occurs by signal molecule degradation or receptor-mediated endocytosis. ARRB1, GNAS, GNB1, GNGT1, GPRK2L, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1 11 ARRB1(7), GNAS(25), GNB1(3), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PRKCA(10) 3037929 74 34 70 21 18 35 5 4 10 2 0.077 0.19 252 TALL1PATHWAY APRIL and BAFF bind to BCMA and TACI receptors on B cell surfaces, promoting immunoglobulin production and cell proliferation. CHUK, MAP3K14, MAPK14, MAPK8, NFKB1, RELA, TNFRSF13B, TNFRSF13C, TNFRSF17, TNFSF13, TNFSF13B, TRAF2, TRAF3, TRAF5, TRAF6 14 CHUK(11), MAP3K14(12), MAPK14(6), MAPK8(7), NFKB1(12), RELA(6), TNFRSF13B(4), TNFRSF17(2), TNFSF13B(3), TRAF2(5), TRAF3(6), TRAF5(8), TRAF6(4) 4964508 86 39 85 19 18 33 14 4 17 0 0.079 0.19 253 HSA00591_LINOLEIC_ACID_METABOLISM Genes involved in linoleic acid metabolism AKR1B10, ALOX15, ALOX5, CYP1A2, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2E1, CYP2J2, CYP3A4, CYP3A43, CYP3A5, CYP3A7, HSD3B7, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, RDH11, RDH12, RDH13, RDH14 31 AKR1B10(4), ALOX15(12), ALOX5(7), CYP1A2(6), CYP2C18(5), CYP2C19(7), CYP2C8(4), CYP2C9(5), CYP2E1(5), CYP2J2(5), CYP3A4(14), CYP3A43(5), CYP3A5(7), CYP3A7(9), HSD3B7(3), PLA2G10(1), PLA2G12A(1), PLA2G12B(3), PLA2G1B(1), PLA2G2D(2), PLA2G2E(3), PLA2G2F(3), PLA2G3(5), PLA2G4A(11), PLA2G5(2), PLA2G6(6), RDH11(3), RDH12(6), RDH13(5), RDH14(3) 8182643 153 51 150 44 37 60 25 8 23 0 0.079 0.19 254 D4GDIPATHWAY D4-GDI inhibits the pro-apoptotic Rho GTPases and is cleaved by caspase-3. ADPRT, APAF1, ARHGAP5, ARHGDIB, CASP1, CASP10, CASP3, CASP8, CASP9, CYCS, GZMB, JUN, PRF1 12 APAF1(19), ARHGAP5(24), ARHGDIB(2), CASP1(7), CASP10(10), CASP3(4), CASP8(21), CASP9(3), CYCS(3), GZMB(2), JUN(1), PRF1(8) 4567768 104 37 100 21 25 33 16 4 24 2 0.080 0.19 255 HSA00430_TAURINE_AND_HYPOTAURINE_METABOLISM Genes involved in taurine and hypotaurine metabolism BAAT, CDO1, CSAD, GAD1, GAD2, GGT1, GGTL3, GGTL4 6 BAAT(7), CDO1(4), CSAD(10), GAD1(8), GAD2(12), GGT1(10) 2029827 51 28 50 9 15 13 16 1 6 0 0.080 0.19 256 CLASSICPATHWAY The classic complement pathway is initiated by antibodies and promotes phagocytosis and lysis of foreign cells as well as activating the inflammatory response. C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C9 11 C1QA(6), C1QB(3), C1R(15), C1S(9), C2(6), C3(24), C5(20), C6(23), C7(21), C8A(12), C9(20) 6178389 159 43 152 39 31 66 26 9 23 4 0.082 0.20 257 IL17PATHWAY Activated T cells secrete IL-17, which stimulates fibroblasts and other cells to secrete inflammatory and hematopoietic cytokines. CD2, CD34, CD3D, CD3E, CD3G, CD3Z, CD4, CD58, CD8A, CSF3, IL17, IL3, IL6, IL8, KITLG, TRA@, TRB@ 13 CD2(4), CD34(4), CD3D(3), CD3E(2), CD3G(2), CD4(8), CD58(1), CD8A(3), CSF3(1), IL6(2), IL8(3), KITLG(2) 2198083 35 23 35 8 6 18 3 0 8 0 0.084 0.20 258 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 5 DBH(12), GAD1(8), HDC(10), PNMT(3), TPH1(14) 1856313 47 27 46 7 12 18 9 1 5 2 0.089 0.21 259 UBIQUINONE_BIOSYNTHESIS NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 12 NDUFA1(1), NDUFA10(8), NDUFA4(2), NDUFA5(7), NDUFA8(6), NDUFB5(2), NDUFB6(1), NDUFS1(13), NDUFS2(5), NDUFV1(4), NDUFV2(3) 2258789 52 27 51 15 14 25 4 3 6 0 0.090 0.21 260 ANDROGEN_AND_ESTROGEN_METABOLISM AKR1C4, AKR1D1, ARSB, ARSD, ARSE, CYP11B1, CYP11B2, HSD11B1, HSD11B2, HSD17B2, HSD17B3, HSD17B8, HSD3B1, HSD3B2, SRD5A1, SRD5A2, STS, SULT1E1, SULT2A1, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4 30 AKR1C4(5), AKR1D1(8), ARSB(6), ARSD(9), ARSE(7), CYP11B1(6), CYP11B2(7), HSD11B1(4), HSD17B2(3), HSD17B3(6), HSD17B8(2), HSD3B1(1), HSD3B2(5), SRD5A1(4), SRD5A2(4), STS(9), SULT1E1(13), SULT2A1(7), UGT1A1(6), UGT1A10(8), UGT1A3(4), UGT1A4(4), UGT1A5(7), UGT1A6(5), UGT1A7(9), UGT1A8(4), UGT1A9(4), UGT2B15(9), UGT2B4(10) 9296383 176 53 167 51 50 70 22 14 20 0 0.091 0.21 261 HSA00625_TETRACHLOROETHENE_DEGRADATION Genes involved in tetrachloroethene degradation AKR1B10, EPHX2, HSD3B7, RDH11, RDH12, RDH13, RDH14 7 AKR1B10(4), EPHX2(7), HSD3B7(3), RDH11(3), RDH12(6), RDH13(5), RDH14(3) 1650056 31 23 31 8 10 15 3 1 2 0 0.092 0.22 262 HSA00252_ALANINE_AND_ASPARTATE_METABOLISM Genes involved in alanine and aspartate metabolism AARS, AARS2, ABAT, ACY3, ADSL, ADSS, ADSSL1, AGXT, AGXT2, ASL, ASNS, ASPA, ASRGL1, ASS1, CAD, CRAT, DARS, DARS2, DDO, DLAT, DLD, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, NARS2, PC, PDHA1, PDHA2, PDHB 32 AARS(10), AARS2(13), ABAT(9), ACY3(4), ADSL(7), ADSS(8), ADSSL1(6), AGXT(5), AGXT2(9), ASL(4), ASNS(9), ASPA(5), ASRGL1(2), ASS1(3), CAD(38), CRAT(3), DARS(4), DARS2(7), DDO(9), DLAT(2), DLD(7), GAD1(8), GAD2(12), GOT1(6), GOT2(5), GPT2(7), NARS(7), NARS2(7), PC(8), PDHA1(4), PDHA2(10), PDHB(7) 12629716 245 64 241 82 60 102 37 10 36 0 0.092 0.22 263 HSA00512_O_GLYCAN_BIOSYNTHESIS Genes involved in O-glycan biosynthesis B3GNT6, B4GALT5, C1GALT1, C1GALT1C1, GALNT1, GALNT10, GALNT11, GALNT12, GALNT13, GALNT14, GALNT17, GALNT2, GALNT3, GALNT4, GALNT5, GALNT6, GALNT7, GALNT8, GALNT9, GALNTL1, GALNTL2, GALNTL4, GALNTL5, GCNT1, GCNT3, GCNT4, OGT, ST3GAL1, ST3GAL2, ST6GALNAC1, WBSCR17 29 B4GALT5(2), C1GALT1(4), C1GALT1C1(5), GALNT1(8), GALNT10(5), GALNT11(14), GALNT12(2), GALNT13(19), GALNT14(11), GALNT2(8), GALNT3(10), GALNT4(8), GALNT5(7), GALNT6(2), GALNT7(11), GALNT8(13), GALNTL1(12), GALNTL2(13), GALNTL4(6), GALNTL5(10), GCNT1(8), GCNT3(7), GCNT4(1), OGT(19), ST3GAL1(2), ST3GAL2(4), ST6GALNAC1(4), WBSCR17(14) 11174445 229 61 220 71 57 88 38 14 32 0 0.096 0.23 264 HSA00260_GLYCINE_SERINE_AND_THREONINE_METABOLISM Genes involved in glycine, serine and threonine metabolism ABP1, AGXT, AGXT2, AKR1B10, ALAS1, ALAS2, AMT, AOC2, AOC3, BHMT, CBS, CHDH, CHKA, CHKB, CTH, DAO, DLD, DMGDH, GAMT, GARS, GATM, GCAT, GLDC, GNMT, HSD3B7, MAOA, MAOB, PEMT, PHGDH, PIPOX, PISD, PSAT1, PSPH, RDH11, RDH12, RDH13, RDH14, SARDH, SARS, SARS2, SDS, SHMT1, SHMT2, TARS, TARS2 44 ABP1(12), AGXT(5), AGXT2(9), AKR1B10(4), ALAS1(12), ALAS2(11), AMT(5), AOC2(6), AOC3(14), BHMT(2), CBS(13), CHDH(5), CHKA(8), CTH(5), DAO(5), DLD(7), DMGDH(6), GARS(8), GATM(8), GLDC(20), GNMT(3), HSD3B7(3), MAOA(14), MAOB(7), PEMT(2), PHGDH(7), PIPOX(6), PISD(5), PSAT1(5), PSPH(1), RDH11(3), RDH12(6), RDH13(5), RDH14(3), SARDH(9), SARS(4), SARS2(7), SDS(3), SHMT1(6), SHMT2(8), TARS(10), TARS2(10) 14500847 292 61 284 87 80 123 40 12 35 2 0.097 0.23 265 NKTPATHWAY T cell differentiation into Th1 and Th2 cells occurs by differential chemokine receptor expression, which mediates tissue localization and immune response. CCL3, CCL4, CCR1, CCR2, CCR3, CCR4, CCR5, CCR7, CD28, CD4, CSF2, CXCR3, CXCR4, IFNG, IFNGR1, IFNGR2, IL12A, IL12B, IL12RB1, IL12RB2, IL18R1, IL2, IL4, IL4R, IL5, TGFB1, TGFB2, TGFB3, TNFSF5 27 CCL3(1), CCL4(1), CCR1(5), CCR2(6), CCR3(5), CCR4(5), CCR7(5), CD28(6), CD4(8), CXCR3(5), CXCR4(1), IFNG(5), IFNGR1(6), IFNGR2(4), IL12A(7), IL12B(3), IL12RB1(16), IL12RB2(11), IL18R1(5), IL2(4), IL4R(6), IL5(2), TGFB1(4), TGFB2(6), TGFB3(9) 6817236 136 47 134 45 27 63 15 8 23 0 0.098 0.23 266 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 BGN(4), DCN(11), FMOD(5), KERA(8), LUM(12) 1308286 40 21 37 12 12 14 3 2 9 0 0.10 0.23 267 HSA00532_CHONDROITIN_SULFATE_BIOSYNTHESIS Genes involved in chondroitin sulfate biosynthesis B3GALT6, B3GAT1, B3GAT2, B3GAT3, B4GALT7, ChGn, CHPF, CHST11, CHST12, CHST13, CHST14, CHST3, CHST7, CHSY-2, CHSY1, CSGlcA-T, DSE, GALNAC4S-6ST, GALNACT-2, UST, XYLT1, XYLT2 15 B3GAT1(4), B3GAT2(1), B3GAT3(4), B4GALT7(4), CHPF(5), CHST11(9), CHST12(5), CHST14(2), CHST3(4), CHST7(4), CHSY1(1), DSE(17), UST(4), XYLT1(15), XYLT2(9) 4638512 88 36 86 40 24 39 15 2 8 0 0.10 0.23 268 41BBPATHWAY TNF-type receptor 4-1BB is bound by TRAF1 to activate the MAP kinase pathway in activated T cells. ATF2, CHUK, IFNG, IKBKB, IL2, IL4, JUN, MAP3K1, MAP3K5, MAP4K5, MAPK14, MAPK8, NFKB1, NFKBIA, RELA, TNFRSF9, TNFSF9, TRAF2 17 ATF2(6), CHUK(11), IFNG(5), IKBKB(15), IL2(4), JUN(1), MAP3K1(31), MAP3K5(21), MAP4K5(7), MAPK14(6), MAPK8(7), NFKB1(12), NFKBIA(3), RELA(6), TNFRSF9(3), TRAF2(5) 6841853 143 41 137 37 33 55 18 11 24 2 0.10 0.23 269 CD40PATHWAY The CD40 receptor is a TNF-type receptor that regulates immunoglobulin expression in B cells and moderates T cell activation via T-cell expression of its ligand. CHUK, DUSP1, IKBKAP, IKBKB, IKBKG, MAP3K1, MAP3K14, NFKB1, NFKBIA, RELA, TNFAIP3, TNFRSF5, TNFSF5, TRAF3, TRAF6 12 CHUK(11), DUSP1(2), IKBKAP(14), IKBKB(15), MAP3K1(31), MAP3K14(12), NFKB1(12), NFKBIA(3), RELA(6), TNFAIP3(2), TRAF3(6), TRAF6(4) 6332305 118 41 115 27 24 44 16 11 21 2 0.10 0.24 270 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP1(4), ACP2(2), ACP5(4), ACPP(5), ACPT(7), ENPP1(11), ENPP3(16), FLAD1(8), RFK(2), TYR(10) 3401209 69 32 69 20 17 26 15 6 5 0 0.10 0.24 271 RNA_POLYMERASE POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT 13 POLR1B(16), POLR2A(25), POLR2B(20), POLR2C(5), POLR2D(3), POLR2E(1), POLR2F(2), POLR2H(3), POLR2K(2) 3981262 77 35 76 25 19 31 7 6 14 0 0.11 0.24 272 STRIATED_MUSCLE_CONTRACTION ACTA1, ACTA2, ACTC, ACTN2, ACTN3, ACTN4, C9orf97, DES, DES, FAM48A, DMD, MYBPC1, MYBPC2, MYBPC3, MYH3, MYH6, MYH6, MYH7, MYH8, MYL1, MYL2, MYL3, MYL4, MYL9, MYOM1, NEB, TCAP, TMOD1, TNNC2, TNNI1, TNNI2, TNNI3, TNNT1, TNNT2, TNNT3, TPM1, TPM2, TPM3, TPM4, TPM4, TTN, VIM 35 ACTA1(4), ACTA2(7), ACTN2(9), ACTN3(10), ACTN4(11), DES(5), DMD(83), FAM48A(7), MYBPC1(20), MYBPC2(9), MYBPC3(14), MYH3(30), MYH6(23), MYH7(28), MYH8(35), MYL1(7), MYL2(1), MYL4(1), MYL9(3), MYOM1(34), NEB(127), TMOD1(2), TNNC2(4), TNNI1(1), TNNI3(5), TNNT1(5), TNNT2(8), TPM1(2), TPM2(1), TPM3(6), TPM4(6), TTN(652), VIM(8) 49100638 1168 105 1133 243 337 414 192 62 64 99 0.11 0.25 273 SIG_REGULATION_OF_THE_ACTIN_CYTOSKELETON_BY_RHO_GTPASES Genes related to regulation of the actin cytoskeleton ACTG1, ACTG2, ACTR2, ACTR3, AKT1, ANGPTL2, CDC42, CFL1, CFL2, FLNA, FLNC, FSCN1, FSCN2, FSCN3, GDI1, GDI2, LIMK1, MYH2, MYLK, MYLK2, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PFN1, PFN2, RHO, ROCK1, ROCK2, RPS4X, VASP, WASF1, WASL 34 ACTG2(1), ACTR2(7), ACTR3(3), AKT1(8), ANGPTL2(9), CDC42(5), CFL1(1), CFL2(8), FLNA(31), FLNC(34), FSCN1(2), FSCN3(5), GDI1(4), GDI2(3), LIMK1(7), MYH2(37), MYLK(17), MYLK2(7), PAK1(3), PAK2(6), PAK3(14), PAK4(2), PAK6(3), PAK7(12), PFN1(1), PFN2(3), RHO(8), ROCK1(27), ROCK2(15), RPS4X(4), VASP(2), WASF1(3), WASL(8) 16003679 300 66 292 84 89 121 33 10 45 2 0.12 0.26 274 HSA00272_CYSTEINE_METABOLISM Genes involved in cysteine metabolism CARS, CARS2, CDO1, CTH, GOT1, GOT2, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, MPST, SDS, SULT1B1, SULT1C2, SULT1C4, SULT4A1 16 CARS(10), CARS2(1), CDO1(4), CTH(5), GOT1(6), GOT2(5), LDHA(6), LDHAL6A(8), LDHAL6B(2), LDHB(2), LDHC(3), SDS(3), SULT1B1(4), SULT1C2(7), SULT1C4(4), SULT4A1(3) 4208312 73 37 68 35 20 23 10 6 14 0 0.12 0.27 275 BIOSYNTHESIS_OF_STEROIDS DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, IDI1, LSS, MVD, MVK, NQO1, NQO2, PMVK, SC5DL, SQLE, VKORC1 14 DHCR7(4), FDFT1(3), FDPS(7), HMGCR(15), IDI1(4), MVD(3), MVK(7), NQO1(3), NQO2(4), PMVK(2), SC5DL(3), SQLE(6), VKORC1(3) 3405750 64 32 62 27 13 24 9 7 11 0 0.12 0.27 276 VOBESITYPATHWAY The adipose tissue of obese individuals overexpresses a key glucocorticoid-metabolizing enzyme, activating inactive circulating corticosteroids and inducing insulin resistance. APM1, HSD11B1, LPL, NR3C1, PPARG, RETN, RXRA, TNF 7 HSD11B1(4), LPL(11), NR3C1(13), PPARG(5), RETN(2), RXRA(1), TNF(1) 1975096 37 23 35 10 13 12 2 2 8 0 0.12 0.27 277 CHREBPPATHWAY Carbohydrate responsive element binding protein (chREBP) is a transcription factor inhibited by cAMP and activated by high carbohydrate levels. ADCY1, BG1, BUCS1, GNAS, GNB1, GNGT1, PPP2CA, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKACB, PRKACG, PRKAG1, PRKAG2, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, WBSCR14 17 ADCY1(17), GNAS(25), GNB1(3), PPP2CA(6), PRKAA1(6), PRKAA2(9), PRKAB1(7), PRKAB2(2), PRKACB(2), PRKACG(6), PRKAG1(2), PRKAG2(4), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5) 4941803 110 40 105 28 22 57 8 6 15 2 0.12 0.27 278 HSA01030_GLYCAN_STRUCTURES_BIOSYNTHESIS_1 Genes involved in glycan structures - biosynthesis 1 A4GNT, ALG1, ALG10, ALG10B, ALG11, ALG12, ALG13, ALG14, ALG2, ALG3, ALG6, ALG8, ALG9, B3GALT6, B3GNT1, B3GNT2, B3GNT6, B3GNT7, B4GALT1, B4GALT2, B4GALT3, B4GALT4, B4GALT5, B4GALT7, C1GALT1, C1GALT1C1, ChGn, CHPF, CHST1, CHST11, CHST12, CHST13, CHST14, CHST2, CHST3, CHST4, CHST6, CHST7, CHSY-2, CHSY1, CSGlcA-T, DAD1, DDOST, DPAGT1, EXT1, EXT2, EXTL1, EXTL2, EXTL3, FUT11, FUT8, GALNAC4S-6ST, GALNACT-2, GALNT1, GALNT10, GALNT11, GALNT12, GALNT13, GALNT14, GALNT17, GALNT2, GALNT3, GALNT4, GALNT5, GALNT6, GALNT7, GALNT8, GALNT9, GALNTL1, GALNTL2, GALNTL4, GALNTL5, GANAB, GCNT1, GCNT3, GCNT4, GCS1, HS2ST1, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, HS3ST5, HS6ST1, HS6ST2, HS6ST3, LOC728969, MAN1A1, MAN1A2, MAN1B1, MAN1C1, MAN2A1, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT5, MGAT5B, NDST1, NDST2, NDST3, NDST4, OGT, RPN1, RPN2, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST6GAL1, ST6GALNAC1, STT3B, UST, WBSCR17, XYLT1, XYLT2 103 A4GNT(6), ALG1(2), ALG10(9), ALG10B(8), ALG11(6), ALG12(1), ALG13(17), ALG14(2), ALG2(2), ALG3(5), ALG6(5), ALG8(8), ALG9(6), B3GNT1(7), B3GNT2(4), B3GNT7(3), B4GALT1(2), B4GALT2(5), B4GALT3(8), B4GALT4(3), B4GALT5(2), B4GALT7(4), C1GALT1(4), C1GALT1C1(5), CHPF(5), CHST1(10), CHST11(9), CHST12(5), CHST14(2), CHST2(5), CHST3(4), CHST4(6), CHST7(4), CHSY1(1), DAD1(1), DDOST(3), DPAGT1(4), EXT1(12), EXT2(8), EXTL1(13), EXTL2(10), EXTL3(10), FUT11(2), FUT8(13), GALNT1(8), GALNT10(5), GALNT11(14), GALNT12(2), GALNT13(19), GALNT14(11), GALNT2(8), GALNT3(10), GALNT4(8), GALNT5(7), GALNT6(2), GALNT7(11), GALNT8(13), GALNTL1(12), GALNTL2(13), GALNTL4(6), GALNTL5(10), GANAB(13), GCNT1(8), GCNT3(7), GCNT4(1), HS2ST1(5), HS3ST1(5), HS3ST2(4), HS3ST3A1(3), HS3ST5(10), HS6ST2(11), HS6ST3(2), MAN1A1(11), MAN1A2(9), MAN1B1(4), MAN1C1(7), MAN2A1(23), MGAT1(3), MGAT2(2), MGAT3(4), MGAT4A(4), MGAT4B(7), MGAT5(9), MGAT5B(7), NDST1(13), NDST2(7), NDST3(17), NDST4(11), OGT(19), RPN1(6), RPN2(9), ST3GAL1(2), ST3GAL2(4), ST3GAL3(6), ST3GAL4(4), ST6GAL1(10), ST6GALNAC1(4), STT3B(6), UST(4), WBSCR17(14), XYLT1(15), XYLT2(9) 37057667 729 96 698 227 186 299 114 33 91 6 0.12 0.28 279 SODDPATHWAY Some members of the tumor necrosis factor receptor family have cytoplasmic death domains that promote apoptosis when active and are repressed by silencers called SODDs. BAG4, BIRC3, CASP8, FADD, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF2 9 BAG4(4), BIRC3(3), CASP8(21), FADD(1), RIPK1(8), TNF(1), TNFRSF1A(6), TNFRSF1B(3), TRAF2(5) 2728663 52 27 51 12 9 17 9 3 14 0 0.13 0.28 280 MRPPATHWAY Cancer cells resistant to numerous drugs are called multidrug-resistant (MDR) and express ATP-binding cassette transporter proteins that pump the drugs out of cells. ABCB1, ABCB11, ABCB4, ABCC1, ABCC3, GSTP1 6 ABCB1(28), ABCB11(18), ABCB4(29), ABCC1(23), ABCC3(14), GSTP1(2) 5203986 114 39 110 39 39 34 12 7 20 2 0.13 0.28 281 BIOPEPTIDESPATHWAY Extracellular signaling peptides exert biological effects via G-protein coupled receptors (GPCRs), which activate intracellular GTPases. AGT, AGTR2, BDK, CALM1, CALM2, CALM3, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CDK5, F2, FYN, GNA11, GNAI1, GNB1, GNGT1, GRB2, HRAS, JAK2, MAP2K1, MAP2K2, MAPK1, MAPK14, MAPK3, MAPK8, MAPT, MYLK, PLCG1, PRKCA, PRKCB1, PTK2B, RAF1, SHC1, SOS1, STAT1, STAT3, STAT5A, SYT1 36 AGT(7), AGTR2(8), CALM2(3), CALM3(1), CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), CDK5(1), F2(9), FYN(7), GNA11(3), GNAI1(4), GNB1(3), GRB2(3), JAK2(21), MAP2K1(2), MAPK1(2), MAPK14(6), MAPK3(4), MAPK8(7), MAPT(11), MYLK(17), PLCG1(12), PRKCA(10), PTK2B(16), RAF1(7), SHC1(11), SOS1(21), STAT1(14), STAT3(12), STAT5A(5), SYT1(4) 14175090 256 65 248 73 66 103 35 13 31 8 0.13 0.28 282 SA_CASPASE_CASCADE Apoptosis is mediated by caspases, cysteine proteases arranged in a proteolytic cascade. ADPRT, APAF1, BIRC2, BIRC3, BIRC4, CASP10, CASP3, CASP7, CASP8, CASP9, DFFA, DFFB, GZMB, PRF1, SCAP, SREBF1, SREBF2, TNFRSF6, TNFSF6 15 APAF1(19), BIRC2(13), BIRC3(3), CASP10(10), CASP3(4), CASP7(4), CASP8(21), CASP9(3), DFFA(1), DFFB(3), GZMB(2), PRF1(8), SCAP(16), SREBF1(6), SREBF2(10) 5852632 123 43 118 33 34 42 16 7 24 0 0.13 0.28 283 GLYCOLYSISPATHWAY Glycolysis is an evolutionarily conserved pathway by which one glucose molecule is converted to two pyruvate molecules for a gain of 2 ATP. ALDOB, ENO1, GAPD, GPI, HK1, PFKL, PGAM1, PGK1, PKLR, TPI1 8 ALDOB(9), ENO1(5), GPI(9), HK1(13), PGAM1(2), PGK1(6), PKLR(10), TPI1(1) 2575703 55 27 53 14 16 22 4 3 8 2 0.13 0.28 284 SMALL_LIGAND_GPCRS C9orf47, CNR1, CNR2, DNMT1, EDG1, EDG2, EDG5, EDG6, MTNR1A, MTNR1B, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, TBXA2R 11 CNR1(8), CNR2(3), DNMT1(15), MTNR1A(6), MTNR1B(4), PTAFR(6), PTGDR(6), PTGER2(5), PTGER4(8), PTGFR(10), PTGIR(3) 3471953 74 36 70 28 18 36 12 4 4 0 0.13 0.28 285 PGC1APATHWAY PCG-1a is expressed in skeletal muscle, heart muscle, and brown fat, and is a coactivator for receptors such as glucocorticoid receptor and thyroid hormone receptor. CALM1, CALM2, CALM3, CAMK1, CAMK1G, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, ESRRA, HDAC5, MEF2A, MEF2B, MEF2C, MEF2D, PPARA, PPARGC1, PPP3CA, PPP3CB, PPP3CC, SLC2A4, SYT1, YWHAH 23 CALM2(3), CALM3(1), CAMK1(9), CAMK1G(5), CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), CAMK4(5), ESRRA(2), HDAC5(15), MEF2A(5), MEF2B(3), MEF2C(11), MEF2D(7), PPARA(2), PPP3CA(4), PPP3CB(7), PPP3CC(6), SLC2A4(4), SYT1(4), YWHAH(4) 6774216 122 42 120 37 28 52 16 4 22 0 0.13 0.28 286 RIBOSOMAL_PROTEINS ANK2, APG10L, RPS23, B3GALT4, CDR1, DGKI, FAU, IL6ST, KIAA1394, LOC133957, MRPL19, NET_5, PIGK, RPL10, RPL11, RPL12, RPL13, RPL13, LOC388344, RPL13A, RPL13A, LOC283340, LOC387930, RPL14, RPL14, RPL14L, RPL15, RPL15, LOC136321, LOC402694, RPL17, RPL17, dJ612B15.1, RPL18, RPL18A, LOC285053, LOC347544, LOC390354, RPL18A, LOC390354, RPL19, RPL21, RPL21, LOC387753, LOC388143, LOC388532, LOC388621, LOC389156, LOC390488, LOC402336, LOC440487, LOC440575, RPL21, LOC387753, LOC388143, LOC388532, LOC388621, LOC389156, LOC390488, LOC440487, LOC440575, RPL22, RPL23, RPL24, RPL24, SLC36A2, RPL26, LOC391126, LOC392501, LOC400055, LOC441073, LOC441533, RPL27, RPL27A, RPL27A, LOC389435, RPL28, RPL29, RPL29, LOC283412, LOC284064, LOC389655, LOC391738, LOC401911, RPL3, RPL30, RPL31, RPL32, RPL34, LOC342994, RPL35, RPL35A, RPL36, RPL37, RPL38, RPL39, RPL3L, RPL4, RPL41, RPL5, RPL5, LOC388907, RPL5, RNU66, LOC388907, RPL6, RPL7, RPL7, LOC389305, RPL7, LOC90193, LOC388401, LOC389305, LOC392550, LOC439954, RPL7A, RPL7A, LOC133748, LOC388474, RPL7A, RNU36B, LOC133748, LOC388474, RPL8, RPL9, RPLP0, RPLP0, RPLP0_like, RPLP1, RPLP2, RPS10, RPS10, LOC158104, LOC388885, LOC389127, LOC390842, LOC401817, RPS10, LOC388885, RPS11, RPS12, RPS13, RPS14, RPS15, RPS16, RPS16, LOC441876, RPS17, RPS17, LOC402057, RPS18, RPS19, RPS2, RPS2, LOC91561, LOC148430, LOC286444, LOC400963, LOC440589, RPS20, RPS21, RPS23, RPS24, RPS25, RPS26, RPS26L, LOC440440, RPS27, RPS27A, RPS27A, LOC388720, LOC389425, RPS28, RPS29, RPS3, RPS3A, RPS3A, LOC146053, LOC400652, LOC401016, LOC439992, RPS4X, RPS4Y1, RPS5, RPS6, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6, RPS6KB1, RPS6KB2, RPS7, RPS8, RPS9, RPSA, LOC388524, LOC388654, SCDR10, TBC1D10C, TSPAN9, UBA52, UBB, UBC 90 ANK2(42), B3GALT4(6), CDR1(2), DGKI(21), FAU(1), IL6ST(10), MRPL19(6), PIGK(6), RPL10(5), RPL11(4), RPL12(1), RPL14(2), RPL15(1), RPL17(5), RPL18(4), RPL18A(4), RPL19(4), RPL21(2), RPL22(15), RPL23(1), RPL24(3), RPL27(1), RPL27A(1), RPL28(2), RPL29(3), RPL3(5), RPL30(2), RPL31(1), RPL35(1), RPL35A(2), RPL37(3), RPL38(1), RPL39(5), RPL3L(3), RPL4(4), RPL5(6), RPL6(2), RPL7(2), RPL8(1), RPL9(1), RPLP0(6), RPS10(2), RPS12(3), RPS13(1), RPS14(1), RPS18(4), RPS20(3), RPS21(2), RPS24(4), RPS25(1), RPS27(2), RPS27A(3), RPS29(2), RPS3(2), RPS3A(2), RPS4X(4), RPS5(1), RPS6(6), RPS6KA1(5), RPS6KA2(16), RPS6KA3(17), RPS6KA6(15), RPS6KB1(3), RPS6KB2(6), RPS7(3), RPS8(5), RPS9(1), RPSA(1), SLC36A2(5), TBC1D10C(2), TSPAN9(4), UBB(3), UBC(5) 17897515 331 69 311 106 89 119 45 16 60 2 0.13 0.28 287 HSA00511_N_GLYCAN_DEGRADATION Genes involved in N-glycan degradation AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2B1, MAN2B2, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 14 AGA(4), FUCA1(3), FUCA2(3), GLB1(9), HEXA(3), HEXB(4), LCT(30), MAN2B1(20), MAN2B2(9), MAN2C1(8), MANBA(14), NEU2(5), NEU3(3) 6820343 115 47 112 33 32 51 15 6 11 0 0.13 0.29 288 HSA04512_ECM_RECEPTOR_INTERACTION Genes involved in ECM-receptor interaction AGRN, CD36, CD44, CD47, CHAD, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, DAG1, FN1, FNDC1, FNDC3A, FNDC4, FNDC5, GP1BA, GP1BB, GP5, GP6, GP9, HMMR, HSPG2, IBSP, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAV, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, RELN, SDC1, SDC2, SDC3, SDC4, SPP1, SV2A, SV2B, SV2C, THBS1, THBS2, THBS3, THBS4, TNC, TNN, TNR, TNXB, VTN, VWF 82 CD36(7), CD44(12), CD47(8), CHAD(3), COL11A1(36), COL11A2(13), COL1A1(12), COL1A2(22), COL2A1(14), COL3A1(18), COL4A1(23), COL4A2(11), COL4A4(24), COL4A6(35), COL5A1(33), COL5A2(24), COL5A3(23), COL6A3(54), COL6A6(38), DAG1(7), FN1(39), FNDC1(37), FNDC3A(9), FNDC4(4), FNDC5(1), GP1BA(11), GP5(5), GP6(3), HMMR(12), HSPG2(37), IBSP(6), ITGA1(20), ITGA10(11), ITGA11(12), ITGA2(21), ITGA2B(11), ITGA3(6), ITGA4(12), ITGA5(12), ITGA6(12), ITGA7(10), ITGA8(16), ITGA9(15), ITGAV(10), ITGB1(12), ITGB3(16), ITGB4(12), ITGB5(8), ITGB6(6), ITGB7(8), ITGB8(5), LAMA1(39), LAMA2(62), LAMA3(35), LAMA4(22), LAMB1(22), LAMB2(27), LAMB3(16), LAMB4(27), LAMC1(17), LAMC2(12), LAMC3(13), RELN(48), SDC1(1), SDC2(2), SDC3(2), SDC4(8), SPP1(3), SV2A(17), SV2B(15), SV2C(16), THBS1(12), THBS2(22), THBS3(6), THBS4(9), TNC(19), TNN(16), TNR(16), TNXB(25), VWF(31) 74339038 1376 122 1347 404 357 568 178 69 171 33 0.13 0.29 289 ST_GRANULE_CELL_SURVIVAL_PATHWAY The survival and differentiation of granule cells in the brain is controlled by pro-growth PACAP and pro-apoptotic ceramides. ADPRT, APC, ASAH1, CAMP, CASP3, CERK, CREB1, CREB3, CREB5, CXCL2, DAG1, EPHB2, FOS, GNAQ, IL8RB, ITPKA, ITPKB, JUN, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, PACAP 21 APC(53), ASAH1(9), CAMP(1), CASP3(4), CERK(8), CREB1(5), CREB3(2), CREB5(6), CXCL2(2), DAG1(7), EPHB2(10), FOS(6), ITPKB(6), JUN(1), MAP2K4(6), MAPK1(2), MAPK10(9), MAPK8(7), MAPK8IP1(5), MAPK9(7) 8413278 156 46 153 49 42 55 15 8 28 8 0.14 0.29 290 AKAP13PATHWAY A-kinase anchor protein 13 (AKAP13) localizes protein kinase A holoenzyme and is a nucleotide exchange factor for Rho/Rac. AKAP13, ARHA, EDG2, EDG4, EDG7, GNA12, PRKACB, PRKACG, PRKAG1, PRKAR2A, PRKAR2B 7 AKAP13(32), GNA12(10), PRKACB(2), PRKACG(6), PRKAG1(2), PRKAR2A(4), PRKAR2B(5) 3482708 61 34 58 17 12 29 5 4 11 0 0.14 0.29 291 COMPPATHWAY Both the classic and alternative immune complement pathways promote inflammation, foreign cell lysis, and phagocytosis. BF, C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C9, DF, MASP1, MASP2, MBL2 14 C1QA(6), C1QB(3), C1R(15), C1S(9), C2(6), C3(24), C5(20), C6(23), C7(21), C8A(12), C9(20), MASP1(14), MASP2(6), MBL2(3) 7443416 182 46 174 50 39 80 27 9 23 4 0.14 0.29 292 DEATHPATHWAY Death receptors such as Fas and DR3, 4, and 5 transduce pro-apoptotic signaling by oligomerizing to activate the caspase cascade. APAF1, BCL2, BID, BIRC2, BIRC3, BIRC4, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHUK, CYCS, DFFA, DFFB, FADD, GAS2, LMNA, MAP3K14, NFKB1, NFKBIA, RELA, RIPK1, SPTAN1, TNFRSF10A, TNFRSF10B, TNFRSF25, TNFSF10, TNFSF12, TRADD, TRAF2 31 APAF1(19), BID(3), BIRC2(13), BIRC3(3), CASP10(10), CASP3(4), CASP6(4), CASP7(4), CASP8(21), CASP9(3), CFLAR(7), CHUK(11), CYCS(3), DFFA(1), DFFB(3), FADD(1), GAS2(7), LMNA(8), MAP3K14(12), NFKB1(12), NFKBIA(3), RELA(6), RIPK1(8), SPTAN1(29), TNFRSF10A(3), TNFRSF10B(5), TNFRSF25(1), TNFSF10(1), TNFSF12(4), TRAF2(5) 11288209 214 57 210 55 53 82 28 10 41 0 0.14 0.30 293 PLCEPATHWAY Gs-coupled receptors activate adenylyl cyclase, which activates Epac1, leading to the stimulation of PLC and subsequent DAG and IP3 production. ADCY1, ADRB2, GNAS, PLCE1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTGER1, RAP2B 11 ADCY1(17), ADRB2(8), GNAS(25), PLCE1(36), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5) 4771874 115 41 110 29 25 51 17 6 14 2 0.14 0.30 294 GLYCINE_SERINE_AND_THREONINE_METABOLISM ABP1, AGXT, AGXT2, ALAS1, ALAS2, AMT, AOC2, AOC3, ATP6V0C, SHMT1, BHMT, CBS, CHDH, CHKA, CHKB, CHKB, CPT1B, CTH, DAO, DLD, DMGDH, GAMT, GARS, GATM, GCAT, GLDC, MAOA, MAOB, PEMT, PISD, PLCB2, PLCG1, PLCG2, PSPH, SARDH, SARS, SHMT1, SHMT2, TARS 36 ABP1(12), AGXT(5), AGXT2(9), ALAS1(12), ALAS2(11), AMT(5), AOC2(6), AOC3(14), ATP6V0C(2), BHMT(2), CBS(13), CHDH(5), CHKA(8), CTH(5), DAO(5), DLD(7), DMGDH(6), GARS(8), GATM(8), GLDC(20), MAOA(14), MAOB(7), PEMT(2), PISD(5), PLCB2(9), PLCG1(12), PLCG2(27), PSPH(1), SARDH(9), SARS(4), SHMT1(6), SHMT2(8), TARS(10) 14110560 277 61 268 77 75 111 37 15 37 2 0.14 0.30 295 HSA00521_STREPTOMYCIN_BIOSYNTHESIS Genes involved in streptomycin biosynthesis GCK, HK1, HK2, HK3, IMPA1, IMPA2, ISYNA1, PGM1, PGM3, TGDS 9 GCK(5), HK1(13), HK2(8), HK3(12), IMPA1(4), IMPA2(6), PGM1(9), PGM3(6), TGDS(3) 3699003 66 32 64 25 20 24 9 5 8 0 0.15 0.31 296 EPOPATHWAY Erythropoietin, which activates the MAPK pathway, stimulates erythrocyte production and is an effective treatment for anemia. CSNK2A1, ELK1, EPO, EPOR, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAPK3, MAPK8, PLCG1, PTPN6, RAF1, SHC1, SOS1, STAT5A, STAT5B 19 CSNK2A1(9), ELK1(2), EPO(2), EPOR(4), FOS(6), GRB2(3), JAK2(21), JUN(1), MAP2K1(2), MAPK3(4), MAPK8(7), PLCG1(12), RAF1(7), SHC1(11), SOS1(21), STAT5A(5), STAT5B(5) 7451064 122 44 116 24 34 42 15 9 14 8 0.15 0.31 297 P35ALZHEIMERSPATHWAY p35, a neuron-specific activator of cyclin-dependent kinase 5, is cleaved to p25 in Alzheimer's disease and promotoes hyperphosphorylated tau formation and apoptosis. APP, CAPN1, CAPNS1, CAPNS2, CDK5, CDK5R1, CSNK1A1, CSNK1D, GSK3B, MAPT, PPP2CA 11 APP(22), CAPN1(4), CAPNS1(3), CAPNS2(6), CDK5(1), CDK5R1(5), CSNK1A1(5), GSK3B(11), MAPT(11), PPP2CA(6) 3096006 74 31 72 18 14 34 8 3 15 0 0.15 0.31 298 SETPATHWAY Cytotoxic T cells release perforin, which to allow entry into target cells of granzyme B, which activates caspases, and granzyme A, which induces caspase-independent apoptosis. ANP32A, APEX1, CREBBP, DFFA, DFFB, GZMA, GZMB, HMGB2, NME1, PRF1, SET 11 ANP32A(5), APEX1(3), CREBBP(37), DFFA(1), DFFB(3), GZMA(6), GZMB(2), HMGB2(3), PRF1(8), SET(6) 3605076 74 33 72 23 18 29 7 5 15 0 0.15 0.31 299 HSA04514_CELL_ADHESION_MOLECULES Genes involved in cell adhesion molecules (CAMs) ALCAM, CADM1, CADM3, CD2, CD22, CD226, CD274, CD276, CD28, CD34, CD4, CD40, CD40LG, CD58, CD6, CD80, CD86, CD8A, CD8B, CD99, CDH1, CDH15, CDH2, CDH3, CDH4, CDH5, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CNTN1, CNTN2, CNTNAP1, CNTNAP2, CTLA4, ESAM, F11R, GLG1, HLA-A, HLA-A29.1, HLA-B, HLA-C, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-E, HLA-F, HLA-G, ICAM1, ICAM2, ICAM3, ICOS, ICOSLG, ITGA4, ITGA6, ITGA8, ITGA9, ITGAL, ITGAM, ITGAV, ITGB1, ITGB2, ITGB7, ITGB8, JAM2, JAM3, L1CAM, MADCAM1, MAG, MPZ, MPZL1, NCAM1, NCAM2, NEGR1, NEO1, NFASC, NLGN1, NLGN2, NLGN3, NRCAM, NRXN1, NRXN2, NRXN3, OCLN, PDCD1, PDCD1LG2, PECAM1, PTPRC, PTPRF, PTPRM, PVR, PVRL1, PVRL2, PVRL3, SDC1, SDC2, SDC3, SDC4, SELE, SELL, SELP, SELPLG, SIGLEC1, SPN, VCAM1, VCAN 124 ALCAM(13), CADM1(5), CADM3(6), CD2(4), CD22(13), CD226(5), CD274(3), CD276(2), CD28(6), CD34(4), CD4(8), CD40(4), CD40LG(7), CD58(1), CD6(8), CD80(7), CD86(6), CD8A(3), CD8B(1), CD99(2), CDH1(15), CDH2(14), CDH3(8), CDH4(19), CDH5(9), CLDN1(2), CLDN10(9), CLDN11(1), CLDN15(4), CLDN16(6), CLDN17(2), CLDN18(4), CLDN19(2), CLDN2(4), CLDN20(4), CLDN22(3), CLDN6(1), CLDN7(1), CLDN8(5), CLDN9(2), CNTN1(17), CNTN2(7), CNTNAP1(13), CNTNAP2(33), CTLA4(2), ESAM(1), F11R(2), GLG1(4), HLA-A(5), HLA-B(3), HLA-DMA(4), HLA-DMB(2), HLA-DOA(3), HLA-DOB(4), HLA-DPA1(1), HLA-DPB1(2), HLA-DQA1(2), HLA-DQA2(1), HLA-DQB1(1), HLA-DRB1(1), HLA-DRB5(1), HLA-E(2), HLA-F(3), HLA-G(3), ICAM1(3), ICAM2(5), ICAM3(5), ICOS(2), ICOSLG(2), ITGA4(12), ITGA6(12), ITGA8(16), ITGA9(15), ITGAL(13), ITGAM(24), ITGAV(10), ITGB1(12), ITGB2(14), ITGB7(8), ITGB8(5), JAM2(9), JAM3(3), L1CAM(16), MAG(10), MPZ(3), MPZL1(2), NCAM1(13), NCAM2(35), NEGR1(3), NEO1(16), NFASC(33), NLGN1(12), NLGN2(3), NLGN3(21), NRCAM(14), NRXN1(39), NRXN2(22), NRXN3(24), OCLN(5), PTPRC(15), PTPRF(34), PTPRM(19), PVR(2), PVRL1(9), PVRL2(5), PVRL3(9), SDC1(1), SDC2(2), SDC3(2), SDC4(8), SELE(10), SELL(4), SELP(15), SELPLG(11), SIGLEC1(10), SPN(4), VCAM1(9), VCAN(59) 50075041 1009 113 979 310 283 413 135 48 113 17 0.15 0.31 300 HSA00770_PANTOTHENATE_AND_COA_BIOSYNTHESIS Genes involved in pantothenate and CoA biosynthesis BCAT1, BCAT2, COASY, DPYD, DPYS, ENPP1, ENPP3, ILVBL, PANK1, PANK2, PANK3, PANK4, PPCDC, PPCS, UPB1, VNN1 16 BCAT1(9), BCAT2(6), COASY(11), DPYD(16), DPYS(3), ENPP1(11), ENPP3(16), ILVBL(7), PANK1(3), PANK2(8), PANK3(7), PANK4(8), PPCDC(1), PPCS(4), UPB1(9), VNN1(7) 5766114 126 42 124 32 32 48 20 6 20 0 0.16 0.32 301 C21_STEROID_HORMONE_METABOLISM AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 AKR1C4(5), AKR1D1(8), CYP11A1(10), CYP11B1(6), CYP11B2(7), CYP17A1(3), CYP21A2(7), HSD11B1(4), HSD3B1(1), HSD3B2(5) 3168901 56 29 55 21 8 30 7 3 8 0 0.16 0.32 302 HSA00140_C21_STEROID_HORMONE_METABOLISM Genes involved in C21-steroid hormone metabolism AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 AKR1C4(5), AKR1D1(8), CYP11A1(10), CYP11B1(6), CYP11B2(7), CYP17A1(3), CYP21A2(7), HSD11B1(4), HSD3B1(1), HSD3B2(5) 3168901 56 29 55 21 8 30 7 3 8 0 0.16 0.32 303 BBCELLPATHWAY Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 4 CD28(6), CD4(8), HLA-DRB1(1) 866136 15 11 15 5 2 9 0 0 4 0 0.16 0.32 304 COMPLEMENT_ACTIVATION_CLASSICAL C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C9, DAF, MASP1 13 C1QA(6), C1QB(3), C1R(15), C1S(9), C2(6), C3(24), C5(20), C6(23), C7(21), C8A(12), C8B(4), C9(20), MASP1(14) 7357376 177 45 168 46 36 78 27 9 23 4 0.16 0.32 305 ERBB3PATHWAY Neuregulins bind to the receptor tyrosine kinases ErbB3 and ErbB4, surface-localized receptors whose overexpression induces tumor formation. EGF, EGFR, ERBB3, NRG1, UBE2D1 5 EGF(24), EGFR(20), ERBB3(16), NRG1(25) 3597189 85 35 82 17 23 36 13 6 7 0 0.16 0.32 306 TOB1PATHWAY TGF-beta signaling activates SMADs, which interact with intracellular Tob to maintain unstimulated T cells by repressing IL-2 expression. CD28, CD3D, CD3E, CD3G, CD3Z, IFNG, IL2, IL2RA, IL4, MADH3, MADH4, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, TOB1, TOB2, TRA@, TRB@ 16 CD28(6), CD3D(3), CD3E(2), CD3G(2), IFNG(5), IL2(4), IL2RA(3), TGFB1(4), TGFB2(6), TGFB3(9), TGFBR1(8), TGFBR2(6), TGFBR3(8), TOB1(2), TOB2(6) 3716928 74 33 74 25 16 33 11 6 8 0 0.16 0.32 307 MPRPATHWAY Progesterone binding to its intracellular receptor activates the MAPK pathway and induces oocyte maturation; binding to membrane receptor inhibits adenylyl cyclase. ACTA1, ADCY1, CAP1, CCNB1, CDC2, CDC25C, GNAI1, GNAS, GNB1, GNGT1, HRAS, MAPK1, MAPK3, MYT1, PIN1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RPS6KA1, SRC 22 ACTA1(4), ADCY1(17), CAP1(7), CCNB1(8), CDC25C(8), GNAI1(4), GNAS(25), GNB1(3), MAPK1(2), MAPK3(4), PIN1(1), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), RPS6KA1(5), SRC(2) 6510121 119 45 113 28 24 54 13 5 21 2 0.16 0.32 308 STATIN_PATHWAY_PHARMGKB ABCA1, APOA1, APOA1, LOC440837, APOA4, APOC1, APOC2, APOC3, APOC3, LOC440838, APOE, CETP, CYP7A1, DGAT1, HMGCR, LCAT, LDLR, LIPC, LPL, LRP1, SCARB1, SOAT1 14 ABCA1(30), APOC1(1), APOE(1), CETP(6), CYP7A1(12), HMGCR(15), LCAT(2), LDLR(12), LIPC(8), LPL(11), LRP1(53), SCARB1(8), SOAT1(10) 8783728 169 54 166 43 53 67 26 8 15 0 0.16 0.33 309 HSA00592_ALPHA_LINOLENIC_ACID_METABOLISM Genes involved in alpha-Linolenic acid metabolism ACOX1, ACOX3, FADS2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6 15 ACOX1(4), ACOX3(8), FADS2(2), PLA2G10(1), PLA2G12A(1), PLA2G12B(3), PLA2G1B(1), PLA2G2D(2), PLA2G2E(3), PLA2G2F(3), PLA2G3(5), PLA2G4A(11), PLA2G5(2), PLA2G6(6) 3392127 52 31 52 22 10 23 7 3 9 0 0.16 0.33 310 OXIDATIVE_PHOSPHORYLATION ATP12A, ATP4B, ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ATP7A, ATP7B, COX10, COX4I1, COX5A, COX5B, COX6A1, COX6A2, COX6B1, COX6C, COX7A1, COX7A2, COX7B, COX7C, COX8A, NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2, PP, PPA2, SDHA, SDHA, SDHAL2, SDHB, UQCRB, UQCRC1, UQCRFS1, UQCRH 55 ATP12A(17), ATP4B(2), ATP5E(1), ATP5O(1), ATP6AP1(7), ATP6V0A1(5), ATP6V0A4(14), ATP6V0B(2), ATP6V0C(2), ATP6V0D1(3), ATP6V1A(7), ATP6V1B1(15), ATP6V1B2(7), ATP6V1C1(3), ATP6V1C2(9), ATP6V1D(4), ATP6V1E1(3), ATP6V1F(2), ATP6V1G1(1), ATP6V1G2(4), ATP6V1G3(2), ATP6V1H(5), ATP7B(13), COX10(5), COX4I1(2), COX5A(1), COX5B(1), COX6A1(2), COX6B1(4), COX6C(2), COX7A1(4), COX7A2(2), COX7B(2), COX7C(2), COX8A(1), NDUFA1(1), NDUFA10(8), NDUFA4(2), NDUFA5(7), NDUFA8(6), NDUFB5(2), NDUFB6(1), NDUFS1(13), NDUFS2(5), NDUFV1(4), NDUFV2(3), PPA2(5), SDHA(12), SDHB(1), SHMT1(6), UQCRB(3), UQCRC1(6), UQCRH(1) 12060418 243 63 239 69 70 101 28 9 35 0 0.16 0.33 311 TYROSINE_METABOLISM ABP1, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, AOX1, COMT, DBH, DCT, DDC, FAH, GOT1, GOT2, GSTZ1, HGD, HPD, MAOA, MAOB, PNMT, TAT, TH, TPO, TYR 29 ABP1(12), ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH6(9), ADH7(6), ADHFE1(7), ALDH3A1(6), ALDH3B1(5), ALDH3B2(8), AOC2(6), AOC3(14), AOX1(19), DBH(12), DCT(15), DDC(11), FAH(7), GOT1(6), GOT2(5), GSTZ1(4), HPD(7), MAOA(14), MAOB(7), PNMT(3), TAT(9), TPO(18), TYR(10) 10362323 240 53 232 56 63 96 38 13 30 0 0.17 0.33 312 HIFPATHWAY Under normal conditions, hypoxia inducible factor HIF-1 is degraded; under hypoxic conditions, it activates transcription of genes controlled by hpoxic response elements (HREs). ARNT, ASPH, COPS5, CREB1, EDN1, EP300, EPO, HIF1A, HSPCA, JUN, LDHA, NOS3, P4HB, VEGF, VHL 13 ARNT(7), ASPH(14), COPS5(6), CREB1(5), EDN1(2), EP300(29), EPO(2), HIF1A(17), JUN(1), LDHA(6), NOS3(11), P4HB(1), VHL(2) 5601682 103 37 102 17 27 33 20 4 19 0 0.17 0.33 313 HSA00230_PURINE_METABOLISM Genes involved in purine metabolism ADA, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADK, ADSL, ADSS, ADSSL1, AK1, AK2, AK3L1, AK5, AK7, ALLC, AMPD1, AMPD2, AMPD3, APRT, ATIC, CANT1, DCK, DGUOK, ECGF1, ENPP1, ENPP3, ENTPD1, ENTPD2, ENTPD3, ENTPD4, ENTPD5, ENTPD6, ENTPD8, FHIT, GART, GDA, GMPR, GMPR2, GMPS, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, GUK1, HPRT1, IMPDH1, IMPDH2, ITPA, NME1, NME2, NME4, NME6, NME7, NP, NPR1, NPR2, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT2, NUDT5, NUDT9, PAICS, PAPSS1, PAPSS2, PDE10A, PDE11A, PDE1A, PDE1C, PDE2A, PDE3B, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A, PDE6D, PDE6G, PDE6H, PDE7A, PDE7B, PDE8A, PDE8B, PDE9A, PFAS, PKLR, PKM2, PNPT1, POLA1, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, PPAT, PRIM1, PRIM2, PRPS1, PRPS1L1, PRPS2, PRUNE, RFC5, RRM1, RRM2, RRM2B, SAC, XDH, ZNRD1 138 ADA(3), ADCY1(17), ADCY2(17), ADCY3(8), ADCY4(8), ADCY5(11), ADCY6(16), ADCY7(6), ADCY8(16), ADCY9(25), ADK(1), ADSL(7), ADSS(8), ADSSL1(6), AK1(2), AK2(4), AK5(6), AK7(15), ALLC(10), AMPD1(21), AMPD2(9), AMPD3(4), ATIC(9), CANT1(5), DCK(4), DGUOK(3), ENPP1(11), ENPP3(16), ENTPD1(6), ENTPD3(8), ENTPD4(4), ENTPD5(2), ENTPD6(15), FHIT(2), GART(8), GDA(5), GMPR(7), GMPR2(4), GMPS(13), GUCY1A2(10), GUCY1A3(12), GUCY1B3(7), GUCY2C(12), GUCY2D(7), GUCY2F(25), GUK1(6), HPRT1(2), IMPDH1(5), IMPDH2(10), ITPA(1), NME6(2), NME7(4), NPR1(14), NPR2(16), NT5C(1), NT5C1A(2), NT5C1B(10), NT5C2(7), NT5C3(8), NT5E(6), NT5M(4), NUDT2(3), NUDT5(1), NUDT9(1), PAICS(4), PAPSS1(6), PAPSS2(6), PDE10A(14), PDE11A(12), PDE1A(12), PDE1C(14), PDE2A(14), PDE3B(15), PDE4A(12), PDE4B(17), PDE4C(6), PDE4D(7), PDE5A(14), PDE6D(1), PDE7A(3), PDE7B(4), PDE8A(7), PDE8B(20), PDE9A(10), PFAS(10), PKLR(10), PKM2(5), PNPT1(9), POLA1(26), POLD1(15), POLD2(6), POLD3(6), POLD4(1), POLE(1), POLE2(4), POLE3(2), POLR1A(15), POLR1B(16), POLR1C(4), POLR1D(2), POLR2A(25), POLR2B(20), POLR2C(5), POLR2D(3), POLR2E(1), POLR2F(2), POLR2H(3), POLR2K(2), POLR3A(9), POLR3B(7), POLR3G(2), POLR3GL(2), POLR3H(3), PPAT(10), PRIM1(2), PRIM2(7), PRPS1(3), PRPS1L1(5), PRPS2(10), PRUNE(4), RFC5(7), RRM1(4), RRM2(5), RRM2B(5), XDH(10), ZNRD1(1) 55894213 1005 106 983 294 269 415 137 59 121 4 0.17 0.33 314 HSA03030_DNA_POLYMERASE Genes involved in DNA polymerase POLA1, POLA2, POLB, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLG, POLG2, POLH, POLI, POLK, POLL, POLM, POLQ, POLS, PRIM1, PRIM2, REV1, REV3L, RFC5 24 POLA1(26), POLB(4), POLD1(15), POLD2(6), POLD3(6), POLD4(1), POLE(1), POLE2(4), POLE3(2), POLG(7), POLG2(8), POLH(13), POLI(13), POLK(12), POLL(8), POLM(12), POLQ(23), PRIM1(2), PRIM2(7), REV1(13), REV3L(40), RFC5(7) 14673883 230 65 220 55 61 84 35 11 37 2 0.18 0.35 315 O_GLYCAN_BIOSYNTHESIS GALNT1, GALNT10, GALNT2, GALNT3, GALNT4, GALNT6, GALNT7, GALNT8, GALNT9, GCNT1, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, WBSCR17 14 GALNT1(8), GALNT10(5), GALNT2(8), GALNT3(10), GALNT4(8), GALNT6(2), GALNT7(11), GALNT8(13), GCNT1(8), ST3GAL1(2), ST3GAL2(4), ST3GAL4(4), WBSCR17(14) 4989603 97 40 95 30 24 38 20 7 8 0 0.18 0.36 316 PHOTOSYNTHESIS ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, FDXR 22 ATP5E(1), ATP5O(1), ATP6AP1(7), ATP6V0A1(5), ATP6V0A4(14), ATP6V0B(2), ATP6V0C(2), ATP6V0D1(3), ATP6V1A(7), ATP6V1B1(15), ATP6V1B2(7), ATP6V1C1(3), ATP6V1C2(9), ATP6V1D(4), ATP6V1E1(3), ATP6V1F(2), ATP6V1G1(1), ATP6V1G2(4), ATP6V1G3(2), ATP6V1H(5), FDXR(6), SHMT1(6) 5607418 109 41 108 33 24 51 12 4 18 0 0.19 0.36 317 HSA00534_HEPARAN_SULFATE_BIOSYNTHESIS Genes involved in heparan sulfate biosynthesis EXT1, EXT2, EXTL1, EXTL2, EXTL3, GLCE, HS2ST1, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, HS3ST5, HS6ST1, HS6ST2, HS6ST3, LOC728969, NDST1, NDST2, NDST3, NDST4 17 EXT1(12), EXT2(8), EXTL1(13), EXTL2(10), EXTL3(10), GLCE(5), HS2ST1(5), HS3ST1(5), HS3ST2(4), HS3ST3A1(3), HS3ST5(10), HS6ST2(11), HS6ST3(2), NDST1(13), NDST2(7), NDST3(17), NDST4(11) 6906144 146 47 143 48 36 60 21 8 19 2 0.19 0.36 318 CTLPATHWAY Cytotoxic T lymphocytes induce apoptosis in infected cells presenting antigen-MHC-I complexes via the perforin and Fas/Fas ligand pathways. B2M, CD3D, CD3E, CD3G, CD3Z, GZMB, HLA-A, ICAM1, ITGAL, ITGB2, PRF1, TNFRSF6, TNFSF6, TRA@, TRB@ 10 B2M(2), CD3D(3), CD3E(2), CD3G(2), GZMB(2), HLA-A(5), ICAM1(3), ITGAL(13), ITGB2(14), PRF1(8) 2865849 54 30 52 22 13 30 6 0 5 0 0.19 0.36 319 GLUTAMATE_METABOLISM ABAT, ALDH4A1, ALDH5A1, CAD, CPS1, EPRS, GAD1, GAD2, GCLC, GCLM, GFPT1, GLS, GLS2, GLUD1, GLUL, GMPS, GOT1, GOT2, GPT, GPT2, GSS, NADSYN1, PPAT, QARS 23 ABAT(9), ALDH4A1(2), ALDH5A1(9), CAD(38), CPS1(24), EPRS(11), GAD1(8), GAD2(12), GCLC(8), GCLM(3), GFPT1(11), GLS(10), GLS2(9), GLUD1(4), GLUL(6), GMPS(13), GOT1(6), GOT2(5), GPT2(7), GSS(5), NADSYN1(12), PPAT(10), QARS(6) 11208144 228 58 221 60 48 99 36 10 31 4 0.19 0.36 320 MITRPATHWAY The MyoD/MEF2 transcription factors induce muscle cell differentiation and are repressed by the transcriptional repressor MITR. CAMK1, CAMK1G, HDAC9, MEF2A, MEF2B, MEF2C, MEF2D, MYOD1, YWHAH 9 CAMK1(9), CAMK1G(5), HDAC9(19), MEF2A(5), MEF2B(3), MEF2C(11), MEF2D(7), MYOD1(3), YWHAH(4) 2814942 66 28 62 15 15 27 7 3 14 0 0.19 0.37 321 ATP_SYNTHESIS ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP5E(1), ATP5O(1), ATP6AP1(7), ATP6V0A1(5), ATP6V0A4(14), ATP6V0B(2), ATP6V0C(2), ATP6V0D1(3), ATP6V1A(7), ATP6V1B1(15), ATP6V1B2(7), ATP6V1C1(3), ATP6V1C2(9), ATP6V1D(4), ATP6V1E1(3), ATP6V1F(2), ATP6V1G1(1), ATP6V1G2(4), ATP6V1G3(2), ATP6V1H(5), SHMT1(6) 5321096 103 40 102 33 24 48 10 4 17 0 0.19 0.37 322 FLAGELLAR_ASSEMBLY ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP5E(1), ATP5O(1), ATP6AP1(7), ATP6V0A1(5), ATP6V0A4(14), ATP6V0B(2), ATP6V0C(2), ATP6V0D1(3), ATP6V1A(7), ATP6V1B1(15), ATP6V1B2(7), ATP6V1C1(3), ATP6V1C2(9), ATP6V1D(4), ATP6V1E1(3), ATP6V1F(2), ATP6V1G1(1), ATP6V1G2(4), ATP6V1G3(2), ATP6V1H(5), SHMT1(6) 5321096 103 40 102 33 24 48 10 4 17 0 0.19 0.37 323 TYPE_III_SECRETION_SYSTEM ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP5E(1), ATP5O(1), ATP6AP1(7), ATP6V0A1(5), ATP6V0A4(14), ATP6V0B(2), ATP6V0C(2), ATP6V0D1(3), ATP6V1A(7), ATP6V1B1(15), ATP6V1B2(7), ATP6V1C1(3), ATP6V1C2(9), ATP6V1D(4), ATP6V1E1(3), ATP6V1F(2), ATP6V1G1(1), ATP6V1G2(4), ATP6V1G3(2), ATP6V1H(5), SHMT1(6) 5321096 103 40 102 33 24 48 10 4 17 0 0.19 0.37 324 STREPTOMYCIN_BIOSYNTHESIS GCK, HK1, HK2, HK3, IMPA1, PGM1, PGM3, TGDS 8 GCK(5), HK1(13), HK2(8), HK3(12), IMPA1(4), PGM1(9), PGM3(6), TGDS(3) 3521187 60 30 58 25 20 19 9 5 7 0 0.20 0.37 325 IL3PATHWAY IL-3 promotes proliferation and differentiation of hematopoietic cells via a heterodimeric receptor that activates the Stat5 and MAP kinase pathways. CSF2RB, FOS, GRB2, HRAS, IL3, IL3RA, JAK2, MAP2K1, MAPK3, PTPN6, RAF1, SHC1, SOS1, STAT5A, STAT5B 15 CSF2RB(11), FOS(6), GRB2(3), IL3RA(11), JAK2(21), MAP2K1(2), MAPK3(4), RAF1(7), SHC1(11), SOS1(21), STAT5A(5), STAT5B(5) 5983843 107 39 104 24 28 45 13 8 5 8 0.20 0.38 326 HSA01031_GLYCAN_STRUCTURES_BIOSYNTHESIS_2 Genes involved in glycan structures - biosynthesis 2 A4GALT, ABO, B3GALNT1, B3GALT1, B3GALT2, B3GALT4, B3GALT5, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT4, B4GALT6, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GBGT1, GCNT2, PIGA, PIGB, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGU, PIGV, PIGX, PIGZ, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST3GAL5, ST3GAL6, ST6GALNAC3, ST6GALNAC4, ST6GALNAC5, ST6GALNAC6, ST8SIA1, ST8SIA5, UGCG, UGCGL1, UGCGL2 56 B3GALNT1(5), B3GALT1(10), B3GALT2(8), B3GALT4(6), B3GALT5(6), B3GNT1(7), B3GNT2(4), B3GNT3(2), B3GNT4(5), B3GNT5(6), B4GALNT1(5), B4GALT1(2), B4GALT2(5), B4GALT3(8), B4GALT4(3), B4GALT6(5), FUT1(5), FUT2(3), FUT3(9), FUT6(13), FUT9(12), GBGT1(6), GCNT2(17), PIGA(8), PIGB(10), PIGC(4), PIGF(4), PIGG(12), PIGH(3), PIGK(6), PIGL(1), PIGN(9), PIGO(15), PIGP(2), PIGS(3), PIGT(10), PIGU(3), PIGV(6), PIGX(2), PIGZ(6), ST3GAL1(2), ST3GAL2(4), ST3GAL3(6), ST3GAL4(4), ST3GAL5(2), ST3GAL6(8), ST6GALNAC3(10), ST6GALNAC4(5), ST6GALNAC5(5), ST6GALNAC6(8), ST8SIA1(4), ST8SIA5(8), UGCG(5) 15546233 327 66 316 73 89 147 37 19 35 0 0.20 0.38 327 HSA00740_RIBOFLAVIN_METABOLISM Genes involved in riboflavin metabolism ACP1, ACP2, ACP5, ACP6, ACPP, ACPT, ENPP1, ENPP3, FLAD1, LHPP, MTMR1, MTMR2, MTMR6, PHPT1, RFK, TYR 16 ACP1(4), ACP2(2), ACP5(4), ACP6(3), ACPP(5), ACPT(7), ENPP1(11), ENPP3(16), FLAD1(8), LHPP(2), MTMR1(16), MTMR2(4), MTMR6(8), PHPT1(2), RFK(2), TYR(10) 5220238 104 38 102 34 23 38 22 7 14 0 0.20 0.38 328 ASBCELLPATHWAY B cells require interaction with helper T cells to produce antigen-specific immunoglobulins as a key element of the human immune response. CD28, CD4, CD80, HLA-DRA, HLA-DRB1, IL10, IL2, IL4, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 8 CD28(6), CD4(8), CD80(7), HLA-DRB1(1), IL10(4), IL2(4) 1439736 30 17 30 11 5 15 5 0 5 0 0.20 0.38 329 AHSPPATHWAY Alpha-hemoglobin stabilizing protein (AHSP) prevents precitipation of hemoglobin alpha-subunits. ALAD, ALAS1, ALAS2, CPO, ERAF, FECH, GATA1, HBA1, HBA2, HBB, HMBS, UROD, UROS 10 ALAD(3), ALAS1(12), ALAS2(11), CPO(4), FECH(5), GATA1(9), HBB(3), HMBS(7), UROD(2), UROS(3) 2819483 59 27 57 12 10 29 6 3 11 0 0.20 0.38 330 HSA02010_ABC_TRANSPORTERS_GENERAL Genes involved in ABC transporters - general ABCA1, ABCA10, ABCA12, ABCA13, ABCA2, ABCA3, ABCA4, ABCA5, ABCA6, ABCA7, ABCA8, ABCA9, ABCB1, ABCB10, ABCB11, ABCB4, ABCB5, ABCB6, ABCB7, ABCB8, ABCB9, ABCC1, ABCC10, ABCC11, ABCC12, ABCC2, ABCC3, ABCC4, ABCC5, ABCC6, ABCC8, ABCC9, ABCD1, ABCD2, ABCD3, ABCD4, ABCG1, ABCG2, ABCG4, ABCG5, ABCG8, CFTR, TAP1, TAP2 42 ABCA1(30), ABCA10(27), ABCA12(50), ABCA13(82), ABCA3(19), ABCA4(26), ABCA5(27), ABCA6(24), ABCA8(29), ABCA9(29), ABCB1(28), ABCB10(12), ABCB11(18), ABCB4(29), ABCB5(26), ABCB6(13), ABCB7(16), ABCB8(6), ABCB9(11), ABCC1(23), ABCC10(14), ABCC11(23), ABCC12(24), ABCC2(30), ABCC3(14), ABCC4(12), ABCC5(20), ABCC6(16), ABCC8(19), ABCC9(34), ABCD1(14), ABCD2(8), ABCD3(9), ABCD4(3), ABCG1(9), ABCG2(8), ABCG4(10), ABCG5(3), ABCG8(9), CFTR(13), TAP1(7), TAP2(2) 39201258 826 101 796 202 216 325 105 49 111 20 0.21 0.38 331 GATA3PATHWAY GATA-3 is a transcription factor that promotes differentiation of helper T cells into Th2 cells, which secrete cytokines IL4, IL5, and IL13. GATA3, IL13, IL4, IL5, JUNB, MAF, MAP2K3, MAPK14, NFATC1, NFATC2, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 15 GATA3(4), IL5(2), MAF(2), MAP2K3(8), MAPK14(6), NFATC2(15), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5) 3513778 66 32 64 23 11 32 4 6 11 2 0.21 0.38 332 CFTRPATHWAY The cAMP-regulated chloride channel CFTR (deficient in cystic fibrosis) is regulated by the surface-localized beta-adrenergic receptor. ADCY1, ADRB2, CFTR, GNAS, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, SLC9A3R1, VIL2 11 ADCY1(17), ADRB2(8), CFTR(13), GNAS(25), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), SLC9A3R1(3) 4170072 95 36 90 23 21 44 9 5 14 2 0.21 0.39 333 SA_BONE_MORPHOGENETIC Bone morphogenetic protein binds to its receptor to induce ectopic bone formation and promote development of the viscera. BMP1, BMPR1A, BMPR1B, BMPR2, MADH1, MADH4, MADH6 4 BMP1(20), BMPR1A(8), BMPR1B(6), BMPR2(14) 2144786 48 26 47 8 14 18 9 2 5 0 0.21 0.39 334 TCYTOTOXICPATHWAY Cytotoxic T cells release perforin and granzyme to lyse foreign cell targets and express Fas ligand to promote Fas-induced apoptosis. CD2, CD28, CD3D, CD3E, CD3G, CD3Z, CD8A, ICAM1, ITGAL, ITGB2, PTPRC, THY1, TRA@, TRB@ 11 CD2(4), CD28(6), CD3D(3), CD3E(2), CD3G(2), CD8A(3), ICAM1(3), ITGAL(13), ITGB2(14), PTPRC(15), THY1(1) 3648096 66 32 65 27 16 33 7 2 8 0 0.21 0.39 335 HSA00251_GLUTAMATE_METABOLISM Genes involved in glutamate metabolism ABAT, ADC, ALDH4A1, ALDH5A1, CAD, CPS1, EARS2, EPRS, GAD1, GAD2, GCLC, GCLM, GFPT1, GFPT2, GLS, GLS2, GLUD1, GLUD2, GLUL, GMPS, GNPNAT1, GOT1, GOT2, GPT, GPT2, GSR, GSS, NADSYN1, NAGK, PPAT, QARS 30 ABAT(9), ADC(8), ALDH4A1(2), ALDH5A1(9), CAD(38), CPS1(24), EARS2(4), EPRS(11), GAD1(8), GAD2(12), GCLC(8), GCLM(3), GFPT1(11), GFPT2(12), GLS(10), GLS2(9), GLUD1(4), GLUD2(9), GLUL(6), GMPS(13), GNPNAT1(2), GOT1(6), GOT2(5), GPT2(7), GSR(5), GSS(5), NADSYN1(12), NAGK(3), PPAT(10), QARS(6) 13372528 271 62 264 78 60 122 39 10 36 4 0.22 0.40 336 EPHA4PATHWAY Eph Kinases and ephrins support platelet aggregation ACTA1, EPHA4, EPHB1, FYN, ITGA1, ITGB1, L1CAM, LYN, RAP1B, SELP 10 ACTA1(4), EPHA4(17), EPHB1(25), FYN(7), ITGA1(20), ITGB1(12), L1CAM(16), LYN(7), RAP1B(2), SELP(15) 5669558 125 41 120 38 33 58 12 4 18 0 0.22 0.40 337 TUBBYPATHWAY Tubby is activated by phospholipase C activity and hydrolysis of PIP2, after which it enters the nucleus and regulates transcription. CHRM1, GNAQ, GNB1, GNGT1, HTR2C, PLCB1, TUB 7 CHRM1(6), GNB1(3), HTR2C(18), PLCB1(6), TUB(12) 2477713 45 27 43 11 15 15 8 3 4 0 0.22 0.41 338 PANTOTHENATE_AND_COA_BIOSYNTHESIS BCAT1, COASY, DPYD, DPYS, ENPP1, ENPP3, PANK1, PANK2, PANK3, PANK4, PPCS, UPB1 12 BCAT1(9), COASY(11), DPYD(16), DPYS(3), ENPP1(11), ENPP3(16), PANK1(3), PANK2(8), PANK3(7), PANK4(8), PPCS(4), UPB1(9) 4559642 105 36 104 23 27 36 17 5 20 0 0.22 0.41 339 PYRIMIDINE_METABOLISM AK3, AK3L1, AK3L1, AK3L2, CAD, CANT1, CDA, CMPK, CTPS, CTPS2, DCK, DCTD, DHODH, DPYD, DPYS, DTYMK, DUT, ECGF1, ENTPD1, ITPA, NME1, NME2, NP, NT5C, NT5E, NT5M, NUDT2, POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT, POLS, RRM1, RRM2, TK1, TK2, TXNRD1, TYMS, UCK1, UCK2, UMPS, UNG, UPB1, UPP1 53 CAD(38), CANT1(5), CDA(1), CTPS(10), CTPS2(10), DCK(4), DCTD(5), DHODH(3), DPYD(16), DPYS(3), DUT(1), ENTPD1(6), ITPA(1), NT5C(1), NT5E(6), NT5M(4), NUDT2(3), POLB(4), POLD1(15), POLD2(6), POLE(1), POLG(7), POLL(8), POLQ(23), POLR1B(16), POLR2A(25), POLR2B(20), POLR2C(5), POLR2D(3), POLR2E(1), POLR2F(2), POLR2H(3), POLR2K(2), RRM1(4), RRM2(5), TK1(2), TK2(7), TXNRD1(10), TYMS(1), UCK1(5), UCK2(6), UMPS(7), UNG(1), UPB1(9), UPP1(4) 19174731 319 71 312 92 64 138 43 23 51 0 0.22 0.41 340 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT1(6), GOT2(5), TAT(9) 900313 20 14 19 3 5 7 3 3 2 0 0.23 0.41 341 HSA00565_ETHER_LIPID_METABOLISM Genes involved in ether lipid metabolism AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, AGPS, CHPT1, ENPP2, ENPP6, LYCAT, PAFAH1B1, PAFAH1B2, PAFAH1B3, PAFAH2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLD1, PLD2, PPAP2A, PPAP2B, PPAP2C 29 AGPAT1(2), AGPAT2(1), AGPAT3(6), AGPAT4(4), AGPAT6(8), AGPS(10), ENPP2(20), ENPP6(9), PAFAH1B1(1), PAFAH1B2(3), PAFAH2(6), PLA2G10(1), PLA2G12A(1), PLA2G12B(3), PLA2G1B(1), PLA2G2D(2), PLA2G2E(3), PLA2G2F(3), PLA2G3(5), PLA2G4A(11), PLA2G5(2), PLA2G6(6), PLD1(16), PLD2(7), PPAP2A(4), PPAP2B(3) 7669749 138 46 135 42 33 56 17 7 23 2 0.23 0.41 342 LDLPATHWAY Low density lipoproteins (LDL) are present in blood plasma, contain cholesterol and triglycerides, and contribute to atherogenic plaque formation. ACAT1, CCL2, CSF1, IL6, LDLR, LPL 6 ACAT1(6), CSF1(5), IL6(2), LDLR(12), LPL(11) 1875911 36 22 35 9 13 14 3 1 5 0 0.23 0.41 343 MITOCHONDRIAL_FATTY_ACID_BETAOXIDATION ACADL, ACADM, ACADS, ACADVL, ACSL1, ACSL3, ACSL4, CPT1A, CPT2, DCI, EHHADH, HADHA, HADHSC, MGC5139, PECR, SCP2, SLC25A20 15 ACADL(7), ACADM(6), ACADS(5), ACADVL(6), ACSL1(13), ACSL3(10), ACSL4(24), CPT1A(10), CPT2(7), EHHADH(9), HADHA(7), PECR(5), SCP2(13), SLC25A20(5) 5836619 127 39 122 33 33 49 24 8 13 0 0.23 0.42 344 HSA00360_PHENYLALANINE_METABOLISM Genes involved in phenylalanine metabolism ABP1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, ARD1A, DDC, EPX, ESCO1, ESCO2, GOT1, GOT2, HPD, LPO, LYCAT, MAOA, MAOB, MIF, MPO, MYST3, MYST4, NAT5, NAT6, PNPLA3, PRDX6, SH3GLB1, TAT, TPO 26 ABP1(12), ALDH3A1(6), ALDH3B1(5), ALDH3B2(8), AOC2(6), AOC3(14), DDC(11), EPX(14), ESCO1(11), ESCO2(6), GOT1(6), GOT2(5), HPD(7), LPO(6), MAOA(14), MAOB(7), MPO(9), NAT6(2), PNPLA3(6), PRDX6(2), SH3GLB1(8), TAT(9), TPO(18) 11884275 192 55 187 61 56 73 28 8 27 0 0.24 0.43 345 AMINOACYL_TRNA_BIOSYNTHESIS AARS, CARS, DARS, EPRS, FARS2, FARSLB, GARS, HARS, HARSL, IARS, KARS, LARS, LARS2, MARS, MARS2, NARS, QARS, RARS, SARS, TARS, WARS, WARS2, YARS 21 AARS(10), CARS(10), DARS(4), EPRS(11), FARS2(2), GARS(8), HARS(4), IARS(13), KARS(7), LARS(23), LARS2(9), MARS(12), MARS2(7), NARS(7), QARS(6), RARS(11), SARS(4), TARS(10), WARS(6), WARS2(5), YARS(8) 11301115 177 52 176 68 39 80 32 7 19 0 0.24 0.43 346 CITRATE_CYCLE_TCA_CYCLE ACO1, ACO2, CS, DLD, DLST, DLSTP, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, MDH1, MDH2, PC, PCK1, SDHA, SDHA, SDHAL2, SDHB, SUCLA2, SUCLG1, SUCLG2 20 ACO1(13), ACO2(8), CS(5), DLD(7), DLST(10), FH(11), IDH1(4), IDH2(7), IDH3A(5), IDH3B(5), IDH3G(9), MDH1(2), MDH2(5), PC(8), PCK1(15), SDHA(12), SDHB(1), SUCLA2(5), SUCLG1(1), SUCLG2(14) 7193183 147 46 143 56 44 62 20 9 12 0 0.24 0.43 347 HSA00533_KERATAN_SULFATE_BIOSYNTHESIS Genes involved in keratan sulfate biosynthesis B3GNT1, B3GNT2, B3GNT7, B4GALT1, B4GALT2, B4GALT3, B4GALT4, CHST1, CHST2, CHST4, CHST6, FUT8, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 15 B3GNT1(7), B3GNT2(4), B3GNT7(3), B4GALT1(2), B4GALT2(5), B4GALT3(8), B4GALT4(3), CHST1(10), CHST2(5), CHST4(6), FUT8(13), ST3GAL1(2), ST3GAL2(4), ST3GAL3(6), ST3GAL4(4) 3844793 82 35 76 32 20 38 11 3 10 0 0.25 0.45 348 CASPASEPATHWAY Caspases are cysteine proteases active in apoptosis; caspase-8 and 9 cleave and activate other caspases, while 3, 6, and 7 cleave cellular targets. ADPRT, APAF1, ARHGDIB, BIRC2, BIRC3, BIRC4, CASP1, CASP10, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CYCS, DFFA, DFFB, GZMB, LMNA, LMNB1, LMNB2, PRF1 20 APAF1(19), ARHGDIB(2), BIRC2(13), BIRC3(3), CASP1(7), CASP10(10), CASP2(9), CASP3(4), CASP4(8), CASP6(4), CASP7(4), CASP8(21), CASP9(3), CYCS(3), DFFA(1), DFFB(3), GZMB(2), LMNA(8), LMNB1(5), PRF1(8) 6439855 137 41 131 37 38 48 20 4 27 0 0.26 0.45 349 HSA00361_GAMMA_HEXACHLOROCYCLOHEXANE_DEGRADATION Genes involved in gamma-hexachlorocyclohexane degradation ACP1, ACP2, ACP5, ACP6, ACPP, ACPT, ALPI, ALPL, ALPP, ALPPL2, CMBL, CYP3A4, CYP3A43, CYP3A5, CYP3A7, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, PON1, PON2, PON3 23 ACP1(4), ACP2(2), ACP5(4), ACP6(3), ACPP(5), ACPT(7), ALPI(3), ALPL(3), ALPP(4), ALPPL2(5), CMBL(4), CYP3A4(14), CYP3A43(5), CYP3A5(7), CYP3A7(9), DHRS1(4), DHRS2(3), DHRS3(2), DHRS7(9), DHRSX(4), PON1(12), PON2(8), PON3(1) 6073229 122 41 119 36 33 42 25 8 14 0 0.26 0.46 350 HSA00061_FATTY_ACID_BIOSYNTHESIS Genes involved in fatty acid biosynthesis ACACA, ACACB, FASN, MCAT, OLAH, OXSM 5 ACACA(27), ACACB(31), MCAT(3), OLAH(7), OXSM(6) 4227432 74 35 71 25 20 27 11 2 10 4 0.26 0.46 351 MYOSINPATHWAY Myosin light chain kinase phosphorylates myosin and promotes muscle contraction and platelet formation; myosin phosphatase antagonizes these processes. ARHGAP5, ARHGEF1, GNA12, GNA13, GNAQ, GNB1, GNGT1, MYL2, MYLK, PLCB1, PPP1R12B, PRKCA, PRKCB1, PRKCL1, ROCK1 13 ARHGAP5(24), ARHGEF1(11), GNA12(10), GNA13(9), GNB1(3), MYL2(1), MYLK(17), PLCB1(6), PPP1R12B(18), PRKCA(10), ROCK1(27) 7293563 136 43 132 32 39 46 17 7 19 8 0.27 0.47 352 INTEGRIN_MEDIATED_CELL_ADHESION_KEGG AKT1, AKT3, BCAR1, CAPN1, CAPN10, CAPN11, CAPN2, CAPN3, CAPN5, CAPN6, CAPN7, CAPN9, CAPNS1, CAV1, CAV2, CAV3, CDC42, CRK, CSK, DKFZp434E1119, DOCK1, FLJ14825, FLJ40125, FYN, GIT2, GRB2, ILK, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, LOC283874, PDPK1, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAPK10, MAPK12, MAPK4, MAPK6, MAPK7, MGC17301, MYLK2, PAK1, PAK2, PAK3, PAK4, PAK6, PDPK1, PIK3R2, PTK2, PXN, RAC1, RAC2, RAC3, RAP1B, RAPGEF1, RHO, ROCK1, ROCK2, SDCCAG8, SEPP1, SHC1, SHC3, SORBS1, SOS1, SRC, TLN1, TNS, TNS1, VASP, VAV2, VAV3, VCL, ZYX 86 AKT1(8), AKT3(8), CAPN1(4), CAPN10(8), CAPN11(8), CAPN2(6), CAPN3(13), CAPN5(6), CAPN6(6), CAPN7(8), CAPN9(12), CAPNS1(3), CAV2(1), CDC42(5), CRK(1), CSK(1), DOCK1(32), FYN(7), GIT2(9), GRB2(3), ILK(8), ITGA10(11), ITGA11(12), ITGA2(21), ITGA2B(11), ITGA3(6), ITGA4(12), ITGA5(12), ITGA6(12), ITGA7(10), ITGA8(16), ITGA9(15), ITGAD(11), ITGAE(14), ITGAL(13), ITGAM(24), ITGAV(10), ITGAX(9), ITGB1(12), ITGB2(14), ITGB3(16), ITGB4(12), ITGB5(8), ITGB6(6), ITGB7(8), ITGB8(5), MAP2K1(2), MAP2K3(8), MAP2K6(9), MAPK10(9), MAPK4(6), MAPK6(11), MAPK7(17), MYLK2(7), PAK1(3), PAK2(6), PAK3(14), PAK4(2), PAK6(3), PDPK1(3), PIK3R2(4), PTK2(11), PXN(6), RAC2(2), RAP1B(2), RAPGEF1(18), RHO(8), ROCK1(27), ROCK2(15), SDCCAG8(14), SEPP1(4), SHC1(11), SHC3(9), SORBS1(22), SOS1(21), SRC(2), TLN1(28), TNS1(20), VASP(2), VAV2(5), VAV3(13), VCL(14), ZYX(12) 45473574 827 99 800 281 225 335 101 37 117 12 0.27 0.47 353 PEPIPATHWAY Proepithelin (PEPI) induces epithelial cells to secrete IL-8, which promotes elastase secretion by neutrophils. ELA1, ELA2, ELA2A, ELA2B, ELA3B, GRN, IL8, SLPI 3 GRN(4), IL8(3), SLPI(3) 610167 10 10 9 1 3 3 2 0 2 0 0.27 0.47 354 HSA00280_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION Genes involved in valine, leucine and isoleucine degradation ABAT, ACAA1, ACAA2, ACADM, ACADS, ACAT1, ACAT2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH7A1, ALDH9A1, AOX1, AUH, BCAT1, BCAT2, BCKDHA, BCKDHB, DBT, DLD, ECHS1, EHHADH, HADH, HADHA, HADHB, HIBADH, HIBCH, HMGCL, HMGCS1, HMGCS2, HSD17B10, HSD17B4, IVD, MCCC1, MCCC2, MCEE, MUT, OXCT1, OXCT2, PCCA, PCCB 44 ABAT(9), ACAA1(5), ACAA2(2), ACADM(6), ACADS(5), ACAT1(6), ACAT2(5), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH6A1(5), ALDH7A1(2), ALDH9A1(4), AOX1(19), AUH(4), BCAT1(9), BCAT2(6), BCKDHA(7), BCKDHB(3), DBT(3), DLD(7), ECHS1(3), EHHADH(9), HADH(1), HADHA(7), HADHB(5), HIBADH(4), HIBCH(7), HMGCL(3), HMGCS1(4), HMGCS2(8), HSD17B10(4), HSD17B4(10), IVD(4), MCCC1(11), MCCC2(7), MUT(7), OXCT1(10), OXCT2(2), PCCA(10), PCCB(8) 14626083 248 59 245 60 61 108 42 15 20 2 0.27 0.47 355 SRCRPTPPATHWAY Activation of Src by Protein-tyrosine phosphatase alpha CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CSK, GRB2, PRKCA, PRKCB1, PTPRA, SRC 9 CCNB1(8), CDC25A(9), CDC25B(3), CDC25C(8), CSK(1), GRB2(3), PRKCA(10), PTPRA(11), SRC(2) 3211443 55 30 52 23 12 18 11 4 10 0 0.27 0.47 356 HSA00970_AMINOACYL_TRNA_BIOSYNTHESIS Genes involved in aminoacyl-tRNA biosynthesis AARS, AARS2, CARS, CARS2, DARS, DARS2, EARS2, EPRS, FARS2, FARSA, FARSB, GARS, HARS, HARS2, IARS, IARS2, KARS, LARS, LARS2, MARS, MARS2, MTFMT, NARS, NARS2, PARS2, QARS, RARS, RARS2, SARS, SARS2, TARS, TARS2, VARS, VARS2, WARS, WARS2, YARS, YARS2 38 AARS(10), AARS2(13), CARS(10), CARS2(1), DARS(4), DARS2(7), EARS2(4), EPRS(11), FARS2(2), FARSA(6), FARSB(7), GARS(8), HARS(4), HARS2(8), IARS(13), IARS2(21), KARS(7), LARS(23), LARS2(9), MARS(12), MARS2(7), MTFMT(1), NARS(7), NARS2(7), PARS2(4), QARS(6), RARS(11), RARS2(7), SARS(4), SARS2(7), TARS(10), TARS2(10), VARS(8), VARS2(5), WARS(6), WARS2(5), YARS(8), YARS2(3) 19103987 296 71 293 99 82 120 50 12 32 0 0.28 0.48 357 FIBRINOLYSISPATHWAY Thrombin cleavage of fibrinogen results in rapid formation of fibrin threads that form a mesh to capture platelets and other blood cells into a clot. CPB2, F13A1, F2, F2R, FGA, FGB, FGG, PLAT, PLAU, PLG, SERPINB2, SERPINE1 12 CPB2(7), F13A1(10), F2(9), F2R(8), FGA(30), FGB(6), FGG(12), PLAT(6), PLAU(5), PLG(13), SERPINB2(9), SERPINE1(5) 4749169 120 40 115 23 42 42 21 7 8 0 0.28 0.48 358 HSA00052_GALACTOSE_METABOLISM Genes involved in galactose metabolism AKR1B1, AKR1B10, B4GALT1, B4GALT2, G6PC, G6PC2, GAA, GALE, GALK1, GALK2, GALT, GANC, GCK, GLA, GLB1, HK1, HK2, HK3, HSD3B7, LALBA, LCT, MGAM, PFKL, PFKM, PFKP, PGM1, PGM3, RDH11, RDH12, RDH13, RDH14, UGP2 31 AKR1B1(2), AKR1B10(4), B4GALT1(2), B4GALT2(5), G6PC(6), G6PC2(9), GAA(5), GALE(2), GALK1(3), GALK2(3), GALT(2), GANC(17), GCK(5), GLA(3), GLB1(9), HK1(13), HK2(8), HK3(12), HSD3B7(3), LALBA(1), LCT(30), MGAM(49), PFKM(7), PFKP(11), PGM1(9), PGM3(6), RDH11(3), RDH12(6), RDH13(5), RDH14(3), UGP2(8) 12427761 251 61 244 77 75 110 28 17 21 0 0.28 0.48 359 HSA00500_STARCH_AND_SUCROSE_METABOLISM Genes involved in starch and sucrose metabolism AGL, AMY1A, AMY1B, AMY1C, AMY2A, AMY2B, ASCC3, ASCC3L1, ATP13A2, DDX18, DDX19A, DDX23, DDX4, DDX41, DDX47, DDX50, DDX51, DDX52, DDX54, DDX55, DDX56, DHX58, ENPP1, ENPP3, ENTPD7, EP400, ERCC2, ERCC3, G6PC, G6PC2, GAA, GANC, GBA, GBA3, GBE1, GCK, GPI, GUSB, GYS1, GYS2, HK1, HK2, HK3, IFIH1, LYZL1, MGAM, MOV10L1, NUDT5, NUDT8, PGM1, PGM3, PYGB, PYGL, PYGM, RAD54B, RAD54L, RUVBL2, SETX, SI, SKIV2L2, SMARCA2, SMARCA5, TREH, UGDH, UGP2, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, UXS1 79 AGL(18), AMY2A(7), AMY2B(11), ASCC3(25), ATP13A2(6), DDX18(14), DDX19A(1), DDX23(12), DDX4(18), DDX41(2), DDX47(8), DDX50(11), DDX52(7), DDX54(8), DDX55(5), DDX56(6), DHX58(5), ENPP1(11), ENPP3(16), ENTPD7(7), ERCC2(4), ERCC3(11), G6PC(6), G6PC2(9), GAA(5), GANC(17), GBA(4), GBA3(9), GBE1(12), GCK(5), GPI(9), GUSB(5), GYS1(12), GYS2(19), HK1(13), HK2(8), HK3(12), IFIH1(5), LYZL1(2), MGAM(49), NUDT5(1), NUDT8(1), PGM1(9), PGM3(6), PYGB(10), PYGL(9), PYGM(10), RAD54B(14), RAD54L(5), RUVBL2(6), SETX(41), SI(47), SKIV2L2(20), SMARCA2(24), SMARCA5(19), TREH(4), UGDH(3), UGP2(8), UGT1A1(6), UGT1A10(8), UGT1A3(4), UGT1A4(4), UGT1A5(7), UGT1A6(5), UGT1A7(9), UGT1A8(4), UGT1A9(4), UGT2A1(9), UGT2A3(5), UGT2B10(14), UGT2B11(22), UGT2B15(9), UGT2B17(4), UGT2B28(14), UGT2B4(10), UGT2B7(10), UXS1(5) 42214570 804 91 776 203 212 294 139 48 104 7 0.28 0.49 360 VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION ACAA1, ACAA2, ACADL, ACADM, ACADS, ACADSB, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH9A1, AOX1, BCAT1, BCKDHA, BCKDHB, ECHS1, EHHADH, HADHA, HADHB, HIBADH, HMGCL, IVD, MCCC1, MCCC2, MCEE, MUT, OXCT1, PCCA, PCCB, SDS 36 ACAA1(5), ACAA2(2), ACADL(7), ACADM(6), ACADS(5), ACADSB(4), ACAT1(6), ACAT2(5), ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH6A1(5), ALDH9A1(4), AOX1(19), BCAT1(9), BCKDHA(7), BCKDHB(3), ECHS1(3), EHHADH(9), HADHA(7), HADHB(5), HIBADH(4), HMGCL(3), IVD(4), MCCC1(11), MCCC2(7), MUT(7), OXCT1(10), PCCA(10), PCCB(8), SDS(3) 12155301 210 55 208 61 52 88 33 16 19 2 0.29 0.49 361 N_GLYCAN_DEGRADATION AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 12 AGA(4), FUCA1(3), FUCA2(3), GLB1(9), HEXA(3), HEXB(4), LCT(30), MAN2C1(8), MANBA(14), NEU2(5), NEU3(3) 5536196 86 39 85 28 27 30 14 5 10 0 0.29 0.49 362 RECKPATHWAY RECK is a membrane-anchored inhibitor of matrix metalloproteinases, which are expressed by tumor cells and promote metastasis. HRAS, MMP14, MMP2, MMP9, RECK, TIMP1, TIMP2, TIMP3, TIMP4 9 MMP14(5), MMP2(11), MMP9(14), RECK(16), TIMP1(5), TIMP2(3), TIMP3(8), TIMP4(1) 2612748 63 28 61 22 21 27 8 1 6 0 0.29 0.50 363 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 GLUL(6), PGLYRP2(8) 652231 14 12 13 7 5 5 1 0 3 0 0.29 0.50 364 UBIQUITIN_MEDIATED_PROTEOLYSIS CDC34, HIP2, NRF1, UBE1, UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2E1, UBE2E3, UBE2G1, UBE2G2, UBE2G2, TAX1BP3, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2L3, UBE2L6, UBE2M, UBE2N, UBE2S, UBE3A 22 NRF1(6), TAX1BP3(1), UBE2A(4), UBE2B(3), UBE2C(1), UBE2D2(3), UBE2D3(3), UBE2E1(3), UBE2E3(8), UBE2G1(2), UBE2H(3), UBE2J1(5), UBE2L3(4), UBE2L6(1), UBE2M(1), UBE2N(4), UBE3A(13) 3369183 65 31 65 23 12 26 14 1 12 0 0.29 0.50 365 IL22BPPATHWAY IL-22 is produced by T cells and induces the acute phase inflammatory response in hepatocytes. IL10RA, IL22, IL22RA1, IL22RA2, JAK1, JAK2, JAK3, SOCS3, STAT1, STAT3, STAT5A, STAT5B, TYK2 13 IL10RA(7), IL22RA1(2), IL22RA2(1), JAK1(31), JAK2(21), JAK3(9), STAT1(14), STAT3(12), STAT5A(5), STAT5B(5), TYK2(7) 6305298 114 39 105 39 19 46 13 7 17 12 0.30 0.50 366 CYANOAMINO_ACID_METABOLISM ATP6V0C, SHMT1, GBA3, GGT1, SHMT1, SHMT2 5 ATP6V0C(2), GBA3(9), GGT1(10), SHMT1(6), SHMT2(8) 1487297 35 20 32 7 12 11 4 0 6 2 0.30 0.50 367 RANKLPATHWAY RANK is a TNF-type receptor that promotes osteoclast differentiation and consequent bone resorbtion on binding RANK ligand produced by osteoblasts. FOS, FOSL1, FOSL2, IFNAR1, IFNAR2, IFNB1, ISGF3G, MAPK8, NFKB1, PRKR, RELA, TNFRSF11A, TNFSF11, TRAF6 12 FOS(6), FOSL1(4), FOSL2(7), IFNAR1(9), IFNAR2(8), IFNB1(4), MAPK8(7), NFKB1(12), RELA(6), TNFRSF11A(6), TNFSF11(6), TRAF6(4) 3892354 79 33 75 16 20 28 18 4 9 0 0.31 0.52 368 HEME_BIOSYNTHESIS ALAD, ALAS1, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, UROS 9 ALAD(3), ALAS1(12), ALAS2(11), CPOX(8), FECH(5), HMBS(7), UROD(2), UROS(3) 2723883 51 24 49 9 9 25 6 3 8 0 0.31 0.52 369 IRINOTECAN_PATHWAY_PHARMGKB ABCC1, ABCC2, ABCG2, BCHE, CES1, CES2, CES4, CYP3A4, CYP3A5, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6 17 ABCC1(23), ABCC2(30), ABCG2(8), BCHE(18), CES1(12), CES2(3), CYP3A4(14), CYP3A5(7), UGT1A1(6), UGT1A10(8), UGT1A3(4), UGT1A4(4), UGT1A5(7), UGT1A6(5), UGT1A7(9), UGT1A8(4), UGT1A9(4) 8174517 166 45 160 44 37 71 25 13 18 2 0.31 0.52 370 HSA00150_ANDROGEN_AND_ESTROGEN_METABOLISM Genes involved in androgen and estrogen metabolism AKR1C4, AKR1D1, ARSD, ARSE, CARM1, CYP11B1, CYP11B2, CYP19A1, HEMK1, HSD11B1, HSD11B2, HSD17B1, HSD17B12, HSD17B2, HSD17B3, HSD17B7, HSD17B8, HSD3B1, HSD3B2, LCMT1, LCMT2, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, SRD5A1, SRD5A2, STS, SULT1E1, SULT2A1, SULT2B1, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, WBSCR22 54 AKR1C4(5), AKR1D1(8), ARSD(9), ARSE(7), CARM1(6), CYP11B1(6), CYP11B2(7), CYP19A1(12), HEMK1(2), HSD11B1(4), HSD17B1(3), HSD17B12(4), HSD17B2(3), HSD17B3(6), HSD17B7(4), HSD17B8(2), HSD3B1(1), HSD3B2(5), LCMT1(4), LCMT2(13), METTL2B(3), METTL6(2), PRMT3(10), PRMT5(11), PRMT6(6), PRMT7(4), PRMT8(9), SRD5A1(4), SRD5A2(4), STS(9), SULT1E1(13), SULT2A1(7), SULT2B1(4), UGT1A1(6), UGT1A10(8), UGT1A3(4), UGT1A4(4), UGT1A5(7), UGT1A6(5), UGT1A7(9), UGT1A8(4), UGT1A9(4), UGT2A1(9), UGT2A3(5), UGT2B10(14), UGT2B11(22), UGT2B15(9), UGT2B17(4), UGT2B28(14), UGT2B4(10), UGT2B7(10), WBSCR22(9) 16832770 354 61 340 92 96 136 50 23 43 6 0.31 0.52 371 EXTRINSICPATHWAY The extrinsic prothrombin activation pathway requires the release of thromboplastin from damaged tissues to activate the blood clotting cascade. F10, F2, F2R, F3, F5, F7, FGA, FGB, FGG, PROC, PROS1, SERPINC1, TFPI 13 F10(10), F2(9), F2R(8), F3(6), F5(46), F7(2), FGA(30), FGB(6), FGG(12), PROC(7), SERPINC1(9), TFPI(11) 5539542 156 41 150 31 53 59 22 10 12 0 0.32 0.52 372 GLUCOCORTICOID_MINERALOCORTICOID_METABOLISM CPN2, CYP11A1, CYP11B2, CYP17A1, HSD11B1, HSD11B2, HSD3B1, HSD3B2 8 CPN2(5), CYP11A1(10), CYP11B2(7), CYP17A1(3), HSD11B1(4), HSD3B1(1), HSD3B2(5) 2460027 35 24 34 16 7 16 5 1 6 0 0.32 0.52 373 VITCBPATHWAY Vitamin C (ascorbic acid), in addition to its role in collagen modification, serves as an antioxidant and is imported into cells by Svct2 in the brain and Svct1 in intestinal epithelium. COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6, P4HB, SLC23A1, SLC23A2, SLC2A1, SLC2A3 11 COL4A1(23), COL4A2(11), COL4A3(24), COL4A4(24), COL4A5(27), COL4A6(35), P4HB(1), SLC23A1(11), SLC23A2(5), SLC2A1(6), SLC2A3(14) 8897731 181 50 173 55 49 73 17 10 24 8 0.32 0.53 374 HSA00630_GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM Genes involved in glyoxylate and dicarboxylate metabolism ACO1, ACO2, AFMID, CS, GRHPR, HAO1, HAO2, HYI, LOC441996, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 13 ACO1(13), ACO2(8), AFMID(6), CS(5), GRHPR(4), HAO1(2), HAO2(7), HYI(2), MDH1(2), MDH2(5), MTHFD1(6), MTHFD1L(12), MTHFD2(3) 4704715 75 36 73 29 27 27 9 5 7 0 0.32 0.53 375 ERBB4PATHWAY ErbB4 (aka HER4) is a receptor tyrosine kinase that binds neuregulins as well as members of the EGF family, which also target EGF receptors. ADAM17, ERBB4, NRG2, NRG3, PRKCA, PRKCB1, PSEN1 6 ADAM17(11), ERBB4(29), NRG2(6), NRG3(15), PRKCA(10), PSEN1(4) 3085490 75 28 74 22 15 28 14 9 9 0 0.32 0.53 376 HSA00190_OXIDATIVE_PHOSPHORYLATION Genes involved in oxidative phosphorylation ATP12A, ATP4A, ATP4B, ATP5A1, ATP5B, ATP5C1, ATP5D, ATP5E, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP5I, ATP5J, ATP5J2, ATP5L, ATP5O, ATP6, ATP6AP1, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E1, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ATP8, COX1, COX10, COX15, COX17, COX2, COX3, COX4I1, COX4I2, COX5A, COX5B, COX6A1, COX6A2, COX6B1, COX6B2, COX6C, COX7A1, COX7A2, COX7B, COX7B2, COX7C, COX8A, COX8C, CYC1, CYTB, LHPP, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA1, NDUFA10, NDUFA11, NDUFA12, NDUFA13, NDUFA2, NDUFA3, NDUFA4, NDUFA4L2, NDUFA5, NDUFA6, NDUFA7, NDUFA8, NDUFA9, NDUFAB1, NDUFB1, NDUFB10, NDUFB11, NDUFB2, NDUFB3, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFB8, NDUFB9, NDUFC1, NDUFC2, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS5, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NDUFV3, PPA1, PPA2, SDHA, SDHB, SDHC, SDHD, TCIRG1, UCRC, UQCR, UQCRB, UQCRC1, UQCRC2, UQCRFS1, UQCRH, UQCRQ 107 ATP12A(17), ATP4A(13), ATP4B(2), ATP5A1(11), ATP5B(4), ATP5C1(1), ATP5E(1), ATP5F1(5), ATP5G1(4), ATP5G2(1), ATP5I(1), ATP5J(4), ATP5L(1), ATP5O(1), ATP6AP1(7), ATP6V0A1(5), ATP6V0A2(11), ATP6V0A4(14), ATP6V0B(2), ATP6V0C(2), ATP6V0D1(3), ATP6V0D2(10), ATP6V1A(7), ATP6V1B1(15), ATP6V1B2(7), ATP6V1C1(3), ATP6V1C2(9), ATP6V1D(4), ATP6V1E1(3), ATP6V1E2(4), ATP6V1F(2), ATP6V1G1(1), ATP6V1G2(4), ATP6V1G3(2), ATP6V1H(5), COX10(5), COX15(4), COX4I1(2), COX4I2(2), COX5A(1), COX5B(1), COX6A1(2), COX6B1(4), COX6C(2), COX7A1(4), COX7A2(2), COX7B(2), COX7B2(2), COX7C(2), COX8A(1), COX8C(2), CYC1(2), LHPP(2), NDUFA1(1), NDUFA10(8), NDUFA13(1), NDUFA2(3), NDUFA3(4), NDUFA4(2), NDUFA4L2(1), NDUFA5(7), NDUFA6(3), NDUFA8(6), NDUFA9(4), NDUFAB1(2), NDUFB1(1), NDUFB5(2), NDUFB6(1), NDUFB8(1), NDUFC1(1), NDUFC2(2), NDUFS1(13), NDUFS2(5), NDUFS4(2), NDUFS5(1), NDUFS8(3), NDUFV1(4), NDUFV2(3), NDUFV3(2), PPA1(5), PPA2(5), SDHA(12), SDHB(1), SDHC(6), SDHD(1), TCIRG1(8), UQCRB(3), UQCRC1(6), UQCRC2(4), UQCRH(1), UQCRQ(2) 18836546 365 72 361 98 99 156 39 19 52 0 0.32 0.53 377 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 ALDH1A1(6), ALDH1A2(9), BCMO1(4), RDH5(6) 1363973 25 18 25 16 8 9 1 1 6 0 0.33 0.53 378 AMINOSUGARS_METABOLISM CMAS, CYB5R3, GCK, GFPT1, GNE, GNPDA1, GNPDA2, HEXA, HEXB, HK1, HK2, HK3, PGM3, RENBP, UAP1 15 CMAS(6), CYB5R3(5), GCK(5), GFPT1(11), GNE(8), GNPDA1(3), GNPDA2(5), HEXA(3), HEXB(4), HK1(13), HK2(8), HK3(12), PGM3(6), RENBP(6), UAP1(8) 5825386 103 40 100 37 25 40 17 10 11 0 0.33 0.53 379 HSA00072_SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES Genes involved in synthesis and degradation of ketone bodies ACAT1, ACAT2, BDH1, BDH2, HMGCL, HMGCS1, HMGCS2, OXCT1, OXCT2 9 ACAT1(6), ACAT2(5), BDH1(6), BDH2(6), HMGCL(3), HMGCS1(4), HMGCS2(8), OXCT1(10), OXCT2(2) 2438278 50 28 49 7 17 22 3 2 4 2 0.33 0.54 380 GANGLIOSIDE_BIOSYNTHESIS B3GALT4, GALGT, SIAT4A, SIAT4B, SIAT7B, SIAT7D, SIAT9, ST3GAL1, ST3GAL2, ST3GAL4, ST3GAL5, ST6GALNAC2, ST6GALNAC4, ST8SIA1 8 B3GALT4(6), ST3GAL1(2), ST3GAL2(4), ST3GAL4(4), ST3GAL5(2), ST6GALNAC2(3), ST6GALNAC4(5), ST8SIA1(4) 1830979 30 21 30 11 13 10 5 0 2 0 0.33 0.54 381 MITOCHONDRIAPATHWAY Pro-apoptotic signaling induces mitochondria to release cytochrome c, which stimulates Apaf-1 to activate caspase 9. APAF1, BAK1, BAX, BCL2, BCL2L1, BID, BIK, BIRC2, BIRC3, BIRC4, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, DFFA, DFFB, DIABLO, ENDOG, PDCD8 18 APAF1(19), BAK1(4), BAX(4), BCL2L1(3), BID(3), BIK(1), BIRC2(13), BIRC3(3), CASP3(4), CASP6(4), CASP7(4), CASP8(21), CASP9(3), CYCS(3), DFFA(1), DFFB(3), DIABLO(2) 4604335 95 33 92 26 20 31 18 4 22 0 0.33 0.54 382 EPONFKBPATHWAY The cytokine erythropoietin (Epo) prevents stress-induced neuronal apoptosis by stimulating anti-apoptotic pathways through JAK2 kinase and NF-kB. ARNT, CDKN1A, EPO, EPOR, GRIN1, HIF1A, JAK2, NFKB1, NFKBIA, RELA, SOD2 11 ARNT(7), CDKN1A(1), EPO(2), EPOR(4), GRIN1(5), HIF1A(17), JAK2(21), NFKB1(12), NFKBIA(3), RELA(6), SOD2(3) 4247030 81 30 80 20 15 27 17 5 11 6 0.34 0.54 383 PTC1PATHWAY The binding of extracellular signaling protein Sonic hedgehog to the Patched receptor (Ptc1) allows progression through G1 and may inhibit the G2/M transition. CCNB1, CCNH, CDC2, CDC25A, CDC25B, CDC25C, CDK7, MNAT1, PTCH, SHH, XPO1 9 CCNB1(8), CCNH(3), CDC25A(9), CDC25B(3), CDC25C(8), CDK7(6), MNAT1(2), SHH(7), XPO1(15) 3028608 61 28 58 13 16 22 11 3 9 0 0.34 0.55 384 APOPTOSIS_KEGG APAF1, BAD, BAX, BCL2, BCL2A1, BCL2L1, BCL2L2, BOK, CASP1, CASP1, COPl, CASP10, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CD40, CD40LG, CRADD, CYCS, DAXX, DFFA, DFFB, FADD, FAS, FASLG, HRK, IKBKE, LTA, MCL1, NFKB1, NFKBIA, NGFB, NGFR, NR3C1, NTRK1, PTPN13, RIPK1, SFRS2IP, TFG, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF1, TRAF2, TRAF3, TRAF6 45 APAF1(19), BAD(2), BAX(4), BCL2A1(2), BCL2L1(3), BCL2L2(2), CASP1(7), CASP10(10), CASP2(9), CASP3(4), CASP4(8), CASP6(4), CASP7(4), CASP8(21), CASP9(3), CD40(4), CD40LG(7), CRADD(3), CYCS(3), DAXX(11), DFFA(1), DFFB(3), FADD(1), FAS(7), FASLG(6), IKBKE(3), LTA(3), MCL1(1), NFKB1(12), NFKBIA(3), NGFR(4), NR3C1(13), NTRK1(11), PTPN13(27), RIPK1(8), TFG(5), TNF(1), TNFRSF1A(6), TNFRSF1B(3), TRAF1(5), TRAF2(5), TRAF3(6), TRAF6(4) 15088548 268 60 263 73 70 99 42 13 42 2 0.34 0.55 385 SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES ACAT1, ACAT2, BDH, HMGCL, OXCT1 4 ACAT1(6), ACAT2(5), HMGCL(3), OXCT1(10) 1166798 24 18 24 1 6 12 2 0 2 2 0.35 0.55 386 HSA00071_FATTY_ACID_METABOLISM Genes involved in fatty acid metabolism ACAA1, ACAA2, ACADL, ACADM, ACADS, ACADSB, ACADVL, ACAT1, ACAT2, ACOX1, ACOX3, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, CPT1A, CPT1B, CPT1C, CPT2, CYP4A11, CYP4A22, DCI, ECHS1, EHHADH, GCDH, HADH, HADHA, HADHB, HSD17B10, HSD17B4, PECI 47 ACAA1(5), ACAA2(2), ACADL(7), ACADM(6), ACADS(5), ACADSB(4), ACADVL(6), ACAT1(6), ACAT2(5), ACOX1(4), ACOX3(8), ACSL1(13), ACSL3(10), ACSL4(24), ACSL5(18), ACSL6(13), ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH5(3), ADH6(9), ADH7(6), ADHFE1(7), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH7A1(2), ALDH9A1(4), CPT1A(10), CPT1C(15), CPT2(7), CYP4A11(5), CYP4A22(8), ECHS1(3), EHHADH(9), GCDH(5), HADH(1), HADHA(7), HADHB(5), HSD17B10(4), HSD17B4(10) 16802656 293 57 286 73 74 127 44 15 31 2 0.35 0.56 387 NO2IL12PATHWAY Macrophages activate NK cells by releasing IL-12, which induces NK cytotoxic activity in coordination with NO produced by inducible nitric oxide synthase II. CCR5, CD2, CD3D, CD3E, CD3G, CD3Z, CD4, CXCR3, IFNG, IL12A, IL12B, IL12RB1, IL12RB2, JAK2, NOS2A, STAT4, TYK2 14 CD2(4), CD3D(3), CD3E(2), CD3G(2), CD4(8), CXCR3(5), IFNG(5), IL12A(7), IL12B(3), IL12RB1(16), IL12RB2(11), JAK2(21), STAT4(9), TYK2(7) 4986735 103 36 100 26 19 44 12 8 14 6 0.36 0.57 388 INTRINSICPATHWAY The intrinsic prothrombin activation pathway is activated by traumatized blood vessels and induces clot formation. COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6, F10, F11, F12, F2, F2R, F5, F8, F9, FGA, FGB, FGG, KLKB1, KNG, PROC, PROS1, SERPINC1, SERPING1 22 COL4A1(23), COL4A2(11), COL4A3(24), COL4A4(24), COL4A5(27), COL4A6(35), F10(10), F11(10), F12(3), F2(9), F2R(8), F5(46), F8(41), F9(11), FGA(30), FGB(6), FGG(12), KLKB1(13), PROC(7), SERPINC1(9), SERPING1(7) 15568221 366 64 351 82 105 142 48 23 40 8 0.36 0.57 389 NEUTROPHILPATHWAY Neutrophils are phagocytotic leukocytes that destroy foreign cells with reactive oxygen species or enzymatic digestion and express CD11 and CD18. CD44, ICAM1, ITGAL, ITGAM, ITGB2, PECAM1, SELE, SELL 8 CD44(12), ICAM1(3), ITGAL(13), ITGAM(24), ITGB2(14), SELE(10), SELL(4) 4144977 80 34 78 24 19 33 12 4 10 2 0.36 0.58 390 SA_G2_AND_M_PHASES Cdc25 activates the cdc2/cyclin B complex to induce the G2/M transition. CDC2, CDC25A, CDC25B, CDK7, CDKN1A, CHEK1, NEK1, WEE1 7 CDC25A(9), CDC25B(3), CDK7(6), CDKN1A(1), CHEK1(4), NEK1(20), WEE1(1) 2580483 44 26 41 12 13 15 5 3 8 0 0.37 0.58 391 HSA00350_TYROSINE_METABOLISM Genes involved in tyrosine metabolism ABP1, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, AOX1, ARD1A, CARM1, COMT, DBH, DCT, DDC, ECH1, ESCO1, ESCO2, FAH, GOT1, GOT2, GSTZ1, HEMK1, HGD, HPD, LCMT1, LCMT2, LYCAT, MAOA, MAOB, METTL2B, METTL6, MIF, MYST3, MYST4, NAT5, NAT6, PNMT, PNPLA3, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, SH3GLB1, TAT, TH, TPO, TYR, TYRP1, WBSCR22 52 ABP1(12), ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH5(3), ADH6(9), ADH7(6), ADHFE1(7), ALDH3A1(6), ALDH3B1(5), ALDH3B2(8), AOC2(6), AOC3(14), AOX1(19), CARM1(6), DBH(12), DCT(15), DDC(11), ECH1(6), ESCO1(11), ESCO2(6), FAH(7), GOT1(6), GOT2(5), GSTZ1(4), HEMK1(2), HPD(7), LCMT1(4), LCMT2(13), MAOA(14), MAOB(7), METTL2B(3), METTL6(2), NAT6(2), PNMT(3), PNPLA3(6), PRMT3(10), PRMT5(11), PRMT6(6), PRMT7(4), PRMT8(9), SH3GLB1(8), TAT(9), TPO(18), TYR(10), TYRP1(6), WBSCR22(9) 19924235 367 64 357 92 94 149 55 19 46 4 0.37 0.58 392 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(13), ACO2(8), FH(11), IDH1(4), IDH2(7), MDH1(2), MDH2(5), SDHB(1), SUCLA2(5) 3132573 56 30 55 30 18 24 4 5 5 0 0.37 0.58 393 HSA00640_PROPANOATE_METABOLISM Genes involved in propanoate metabolism ABAT, ACACA, ACACB, ACADM, ACAT1, ACAT2, ACSS1, ACSS2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH7A1, ALDH9A1, ECHS1, EHHADH, HADHA, HIBCH, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, LOC283398, MCEE, MLYCD, MUT, PCCA, PCCB, SUCLA2, SUCLG1, SUCLG2 33 ABAT(9), ACACA(27), ACACB(31), ACADM(6), ACAT1(6), ACAT2(5), ACSS1(4), ACSS2(11), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH6A1(5), ALDH7A1(2), ALDH9A1(4), ECHS1(3), EHHADH(9), HADHA(7), HIBCH(7), LDHA(6), LDHAL6A(8), LDHAL6B(2), LDHB(2), LDHC(3), MLYCD(5), MUT(7), PCCA(10), PCCB(8), SUCLA2(5), SUCLG1(1), SUCLG2(14) 13781457 224 55 218 53 62 86 34 15 23 4 0.37 0.58 394 GALACTOSE_METABOLISM AKR1B1, B4GALT1, B4GALT2, FBP2, G6PC, GAA, GALE, GALK1, GALK2, GALT, GANAB, GCK, GLA, GLB1, HK1, HK2, HK3, LALBA, LCT, MGAM, PFKM, PFKP, PGM1, PGM3 24 AKR1B1(2), B4GALT1(2), B4GALT2(5), G6PC(6), GAA(5), GALE(2), GALK1(3), GALK2(3), GALT(2), GANAB(13), GCK(5), GLA(3), GLB1(9), HK1(13), HK2(8), HK3(12), LALBA(1), LCT(30), MGAM(49), PFKM(7), PFKP(11), PGM1(9), PGM3(6) 10815706 206 55 200 71 62 91 23 12 18 0 0.37 0.58 395 BUTANOATE_METABOLISM AACS, ABAT, ACADS, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH5A1, ALDH9A1, BDH, BUCS1, ECHS1, EHHADH, GAD1, GAD2, HADHA, HMGCL, L2HGDH, OXCT1, PDHA1, PDHA2, PDHB, SDHB, SDS 27 AACS(9), ABAT(9), ACADS(5), ACAT1(6), ACAT2(5), ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH5A1(9), ALDH9A1(4), ECHS1(3), EHHADH(9), GAD1(8), GAD2(12), HADHA(7), HMGCL(3), L2HGDH(3), OXCT1(10), PDHA1(4), PDHA2(10), PDHB(7), SDHB(1), SDS(3) 8755048 159 47 154 44 39 68 22 11 17 2 0.38 0.59 396 IONPATHWAY Activated phospholipase C hydrolyzes the lipid PIP3 into second messengers DAG, which activates protein kinase C, and IP3, which induces calcium influx into the cytoplasm. P2RY2, PLCG1, PRKCA, PRKCB1, PTK2B 4 P2RY2(6), PLCG1(12), PRKCA(10), PTK2B(16) 2362515 44 25 42 24 12 17 6 5 4 0 0.38 0.59 397 FREEPATHWAY Neutrophils release superoxide to induce lysis in invading bacteria; in neighboring endothelial cells, superoxide dismutase scavenges radicals but produces pro-apoptotic peroxides. GPX1, GSR, GSS, IL8, NFKB1, NOX1, RELA, SOD1, TNF, XDH 10 GSR(5), GSS(5), IL8(3), NFKB1(12), NOX1(11), RELA(6), SOD1(2), TNF(1), XDH(10) 3572811 55 28 54 18 16 17 10 3 9 0 0.38 0.59 398 INTEGRINPATHWAY Integrins are cell surface receptors commonly present at focal adhensions that interact with the extracellular matrix and transduce extracellular signaling. ACTA1, ACTN1, ACTN2, ACTN3, ARHA, BCAR1, BCR, CAPN1, CAPNS1, CAPNS2, CAV1, CRKL, CSK, FYN, GRB2, GRF2, HRAS, ITGA1, ITGB1, JUN, MAP2K1, MAP2K2, MAPK1, MAPK3, MAPK8, PPP1R12B, PTK2, PXN, RAF1, RAP1A, ROCK1, SHC1, SOS1, SRC, TLN1, TNS, VCL, ZYX 33 ACTA1(4), ACTN1(13), ACTN2(9), ACTN3(10), BCR(6), CAPN1(4), CAPNS1(3), CAPNS2(6), CRKL(5), CSK(1), FYN(7), GRB2(3), ITGA1(20), ITGB1(12), JUN(1), MAP2K1(2), MAPK1(2), MAPK3(4), MAPK8(7), PPP1R12B(18), PTK2(11), PXN(6), RAF1(7), RAP1A(3), ROCK1(27), SHC1(11), SOS1(21), SRC(2), TLN1(28), VCL(14), ZYX(12) 15465451 279 64 270 75 85 111 28 9 40 6 0.39 0.60 399 HSA00020_CITRATE_CYCLE Genes involved in citrate cycle (TCA cycle) ACLY, ACO1, ACO2, CLYBL, CS, DLD, DLST, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, LOC283398, LOC441996, MDH1, MDH2, OGDH, OGDHL, PC, PCK1, PCK2, SDHA, SDHB, SDHC, SDHD, SUCLA2, SUCLG1, SUCLG2 27 ACLY(9), ACO1(13), ACO2(8), CLYBL(10), CS(5), DLD(7), DLST(10), FH(11), IDH1(4), IDH2(7), IDH3A(5), IDH3B(5), IDH3G(9), MDH1(2), MDH2(5), OGDH(11), OGDHL(18), PC(8), PCK1(15), PCK2(7), SDHA(12), SDHB(1), SDHC(6), SDHD(1), SUCLA2(5), SUCLG1(1), SUCLG2(14) 10465332 209 55 202 76 53 95 29 13 19 0 0.39 0.60 400 HSA03020_RNA_POLYMERASE Genes involved in RNA polymerase POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, ZNRD1 23 POLR1A(15), POLR1B(16), POLR1C(4), POLR1D(2), POLR2A(25), POLR2B(20), POLR2C(5), POLR2D(3), POLR2E(1), POLR2F(2), POLR2H(3), POLR2K(2), POLR3A(9), POLR3B(7), POLR3G(2), POLR3GL(2), POLR3H(3), ZNRD1(1) 8165674 122 43 120 42 34 47 10 11 20 0 0.39 0.61 401 HSA00604_GLYCOSPHINGOLIPID_BIOSYNTHESIS_GANGLIOSERIES Genes involved in glycosphingolipid biosynthesis - ganglioseries B3GALT4, B4GALNT1, GLB1, HEXA, HEXB, LCT, SLC33A1, ST3GAL1, ST3GAL2, ST3GAL5, ST6GALNAC3, ST6GALNAC4, ST6GALNAC5, ST6GALNAC6, ST8SIA1, ST8SIA5 16 B3GALT4(6), B4GALNT1(5), GLB1(9), HEXA(3), HEXB(4), LCT(30), SLC33A1(8), ST3GAL1(2), ST3GAL2(4), ST3GAL5(2), ST6GALNAC3(10), ST6GALNAC4(5), ST6GALNAC5(5), ST6GALNAC6(8), ST8SIA1(4), ST8SIA5(8) 5684376 113 39 110 36 35 44 12 8 14 0 0.39 0.61 402 MSPPATHWAY Macrophage stimulating protein is synthesized as pro-MSP by the liver and, on proteolysis, binds to monocyte receptor kinase RON to induce macrophage development. CCL2, CSF1, IL1B, MST1, MST1R, TNF 6 CSF1(5), IL1B(2), MST1(6), MST1R(17), TNF(1) 2108219 31 19 30 13 12 10 1 1 7 0 0.40 0.61 403 HSA00530_AMINOSUGARS_METABOLISM Genes involved in aminosugars metabolism AMDHD2, CHIA, CHIT1, CMAS, CTBS, CYB5R1, CYB5R3, GFPT1, GFPT2, GNE, GNPDA1, GNPDA2, GNPNAT1, HEXA, HEXB, HK1, HK2, HK3, LHPP, MTMR1, MTMR2, MTMR6, NAGK, NANS, NPL, PGM3, PHPT1, RENBP, UAP1 29 AMDHD2(7), CHIA(8), CHIT1(5), CMAS(6), CTBS(4), CYB5R1(5), CYB5R3(5), GFPT1(11), GFPT2(12), GNE(8), GNPDA1(3), GNPDA2(5), GNPNAT1(2), HEXA(3), HEXB(4), HK1(13), HK2(8), HK3(12), LHPP(2), MTMR1(16), MTMR2(4), MTMR6(8), NAGK(3), NANS(6), NPL(6), PGM3(6), PHPT1(2), RENBP(6), UAP1(8) 9847039 188 50 183 64 45 77 28 13 25 0 0.40 0.61 404 LYMPHOCYTEPATHWAY B and T cell lymphocytes interact with other cells via transmembrane adhesion proteins such as CD44, which interacts with endothelial cells. CD44, ICAM1, ITGA4, ITGAL, ITGB1, ITGB2, PECAM1, SELE, SELL 9 CD44(12), ICAM1(3), ITGA4(12), ITGAL(13), ITGB1(12), ITGB2(14), SELE(10), SELL(4) 4673645 80 34 78 26 21 32 11 6 10 0 0.41 0.62 405 CARDIACEGFPATHWAY Cardiac hypertrophy, a response to high blood pressure, is stimulated by GPCR ligands such as angiotensin II that activate the EGF pathway. ADAM12, AGT, AGTR2, ARHA, EDN1, EDNRA, EDNRB, EGF, EGFR, FOS, HRAS, JUN, MYC, NFKB1, PLCG1, PRKCA, PRKCB1, RELA 16 ADAM12(12), AGT(7), AGTR2(8), EDN1(2), EDNRA(6), EDNRB(2), EGF(24), EGFR(20), FOS(6), JUN(1), MYC(7), NFKB1(12), PLCG1(12), PRKCA(10), RELA(6) 7244568 135 43 130 49 33 55 23 8 16 0 0.41 0.62 406 HSA00602_GLYCOSPHINGOLIPID_BIOSYNTHESIS_NEO_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - neo-lactoseries ABO, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALT1, B4GALT2, B4GALT3, B4GALT4, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GCNT2, ST3GAL6, ST8SIA1 18 B3GNT1(7), B3GNT2(4), B3GNT3(2), B3GNT4(5), B3GNT5(6), B4GALT1(2), B4GALT2(5), B4GALT3(8), B4GALT4(3), FUT1(5), FUT2(3), FUT3(9), FUT6(13), FUT9(12), GCNT2(17), ST3GAL6(8), ST8SIA1(4) 4921727 113 35 107 25 27 59 9 6 12 0 0.42 0.63 407 DNA_REPLICATION_REACTOME ASK, CDC45L, CDC6, CDC7, CDK2, CDT1, DIAPH2, GMNN, MCM10, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, NACA, NACA, FKSG17, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, POLA, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, PRIM1, PRIM2A, RFC1, RFC2, RFC3, RFC4, RFC5, RPA1, RPA2, RPA3, RPA4, RPS27A, RPS27A, LOC388720, LOC389425, UBA52, UBB, UBC 41 CDC6(3), CDC7(13), CDK2(5), DIAPH2(22), GMNN(3), MCM10(8), MCM2(10), MCM3(9), MCM4(9), MCM5(12), MCM6(9), MCM7(5), NACA(20), PCNA(3), POLD1(15), POLD2(6), POLD3(6), POLD4(1), POLE(1), POLE2(4), PRIM1(2), RFC1(15), RFC2(4), RFC3(4), RFC4(4), RFC5(7), RPA1(6), RPA2(2), RPA3(4), RPA4(6), RPS27A(3), UBB(3), UBC(5) 17156137 229 61 222 57 82 90 21 9 27 0 0.42 0.63 408 AKAPCENTROSOMEPATHWAY Protein Kinase A at the Centrosome AKAP9, ARHA, CDC2, MAP2, PCNT1, PCNT2, PPP1CA, PPP2CA, PRKACB, PRKACG, PRKAG1, PRKAR2A, PRKAR2B, PRKCE, PRKCL1 10 AKAP9(57), MAP2(27), PPP1CA(6), PPP2CA(6), PRKACB(2), PRKACG(6), PRKAG1(2), PRKAR2A(4), PRKAR2B(5), PRKCE(11) 6468057 126 41 121 36 23 46 24 6 24 3 0.42 0.63 409 NOS1PATHWAY Glutamate stimulates NMDA-mediates calcium influx, which promotes nitric oxide synthesis from arginine by neuronal nitric oxide synthase, activating guanylate cyclase. CALM1, CALM2, CALM3, DLG4, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, NOS1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, SYT1 21 CALM2(3), CALM3(1), DLG4(13), GRIN1(5), GRIN2A(25), GRIN2B(23), GRIN2C(6), GRIN2D(8), NOS1(21), PPP3CA(4), PPP3CB(7), PPP3CC(6), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PRKCA(10), SYT1(4) 8559307 165 49 160 69 35 74 31 6 17 2 0.42 0.63 410 CK1PATHWAY Caseine kinase 1 (CK1) and cdk5 phosphorylate DARPP32 in the dopamine signaling pathway. CDK5, CDK5R1, CSNK1D, DRD1, DRD2, GRM1, PLCB1, PPP1CA, PPP1R1B, PPP2CA, PPP3CA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 17 CDK5(1), CDK5R1(5), DRD1(6), DRD2(10), GRM1(22), PLCB1(6), PPP1CA(6), PPP1R1B(4), PPP2CA(6), PPP3CA(4), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5) 5410482 99 36 97 37 25 42 13 4 13 2 0.43 0.64 411 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_NEOLACTOSERIES ABO, B3GNT1, FUT1, FUT2, FUT9, GCNT2, ST8SIA1 7 B3GNT1(7), FUT1(5), FUT2(3), FUT9(12), GCNT2(17), ST8SIA1(4) 2126144 48 25 45 10 12 24 5 3 4 0 0.43 0.65 412 PARKINPATHWAY In Parkinson's disease, dopaminergic neurons contain Lewy bodies consisting of alpha-synuclein and parkin, an E3 ubiquitin ligase that targets glycosylated alpha-synuclein. GPR37, PARK2, PNUTL1, SNCA, SNCAIP, UBE2E2, UBE2F, UBE2G1, UBE2G2, UBE2L3, UBE2L6, UBL1 10 GPR37(9), PARK2(6), SNCA(2), SNCAIP(12), UBE2E2(3), UBE2F(1), UBE2G1(2), UBE2L3(4), UBE2L6(1) 2165818 40 24 40 13 13 17 4 4 2 0 0.44 0.66 413 PLCDPATHWAY Phospholipase C (PLC-d1) hydrolyzes the membrane lipid PIP2 to DAG and IP3, which induce calcium influx and activates protein kinase C. ADRA1B, PLCD1, PRKCA, PRKCB1, TGM2 4 ADRA1B(7), PLCD1(5), PRKCA(10), TGM2(9) 1769078 31 22 31 20 10 11 5 3 2 0 0.44 0.66 414 METHIONINEPATHWAY Catabolic Pathways for Methionine, Isoleucine, Threonine and Valine BCKDHB, BCKDK, CBS, CTH, MUT 5 BCKDHB(3), BCKDK(6), CBS(13), CTH(5), MUT(7) 1579551 34 21 33 7 8 16 4 1 5 0 0.44 0.66 415 HSA00650_BUTANOATE_METABOLISM Genes involved in butanoate metabolism AACS, AADAC, ABAT, ACADS, ACAT1, ACAT2, ACSM1, AKR1B10, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH5A1, ALDH7A1, ALDH9A1, BDH1, BDH2, DDHD1, ECHS1, EHHADH, GAD1, GAD2, HADH, HADHA, HMGCL, HMGCS1, HMGCS2, HSD17B10, HSD17B4, HSD3B7, ILVBL, L2HGDH, OXCT1, OXCT2, PDHA1, PDHA2, PDHB, PLA1A, PPME1, PRDX6, RDH11, RDH12, RDH13, RDH14 45 AACS(9), AADAC(5), ABAT(9), ACADS(5), ACAT1(6), ACAT2(5), ACSM1(12), AKR1B10(4), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH5A1(9), ALDH7A1(2), ALDH9A1(4), BDH1(6), BDH2(6), DDHD1(14), ECHS1(3), EHHADH(9), GAD1(8), GAD2(12), HADH(1), HADHA(7), HMGCL(3), HMGCS1(4), HMGCS2(8), HSD17B10(4), HSD17B4(10), HSD3B7(3), ILVBL(7), L2HGDH(3), OXCT1(10), OXCT2(2), PDHA1(4), PDHA2(10), PDHB(7), PLA1A(5), PPME1(1), PRDX6(2), RDH11(3), RDH12(6), RDH13(5), RDH14(3) 13856981 253 56 244 64 65 113 33 15 23 4 0.45 0.66 416 HSA00271_METHIONINE_METABOLISM Genes involved in methionine metabolism AHCY, AMD1, BHMT, CBS, CTH, DNMT1, DNMT3A, DNMT3B, KIAA0828, MARS, MARS2, MAT1A, MAT2B, MTAP, MTFMT, MTR, SRM, TAT 17 AHCY(4), AMD1(3), BHMT(2), CBS(13), CTH(5), DNMT1(15), DNMT3A(13), DNMT3B(15), MARS(12), MARS2(7), MAT1A(2), MAT2B(12), MTAP(4), MTFMT(1), MTR(13), SRM(1), TAT(9) 6919050 131 42 121 53 32 62 17 3 17 0 0.45 0.66 417 HSA00380_TRYPTOPHAN_METABOLISM Genes involved in tryptophan metabolism AADAT, AANAT, ABP1, ACAT1, ACAT2, ACMSD, AFMID, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, AOC2, AOC3, AOX1, ASMT, CARM1, CAT, CYP1A1, CYP1A2, CYP1B1, DDC, ECHS1, EHHADH, GCDH, HAAO, HADH, HADHA, HEMK1, HSD17B10, HSD17B4, INDO, INDOL1, INMT, KMO, KYNU, LCMT1, LCMT2, LNX1, MAOA, MAOB, METTL2B, METTL6, NFX1, OGDH, OGDHL, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, TDO2, TPH1, TPH2, WARS, WARS2, WBSCR22 58 AADAT(6), AANAT(4), ABP1(12), ACAT1(6), ACAT2(5), ACMSD(8), AFMID(6), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH7A1(2), ALDH9A1(4), AOC2(6), AOC3(14), AOX1(19), ASMT(3), CARM1(6), CAT(5), CYP1A1(9), CYP1A2(6), CYP1B1(3), DDC(11), ECHS1(3), EHHADH(9), GCDH(5), HAAO(4), HADH(1), HADHA(7), HEMK1(2), HSD17B10(4), HSD17B4(10), INMT(4), KMO(11), KYNU(5), LCMT1(4), LCMT2(13), LNX1(9), MAOA(14), MAOB(7), METTL2B(3), METTL6(2), NFX1(14), OGDH(11), OGDHL(18), PRMT3(10), PRMT5(11), PRMT6(6), PRMT7(4), PRMT8(9), TDO2(3), TPH1(14), TPH2(9), WARS(6), WARS2(5), WBSCR22(9) 20922060 398 70 387 99 95 166 60 25 43 9 0.45 0.67 418 HSA05120_EPITHELIAL_CELL_SIGNALING_IN_HELICOBACTER_PYLORI_INFECTION Genes involved in epithelial cell signaling in Helicobacter pylori infection ADAM10, ADAM17, ATP6AP1, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E1, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, CASP3, CCL5, CDC42, CHUK, CSK, CXCL1, EGFR, F11R, GIT1, HBEGF, IGSF5, IKBKB, IKBKG, IL8, IL8RA, IL8RB, JAM2, JAM3, JUN, LYN, MAP2K4, MAP3K14, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK8, MAPK9, MET, NFKB1, NFKB2, NFKBIA, NOD1, PAK1, PLCG1, PLCG2, PTPN11, PTPRZ1, RAC1, RELA, SRC, TCIRG1, TJP1 63 ADAM10(4), ADAM17(11), ATP6AP1(7), ATP6V0A1(5), ATP6V0A2(11), ATP6V0A4(14), ATP6V0B(2), ATP6V0C(2), ATP6V0D1(3), ATP6V0D2(10), ATP6V1A(7), ATP6V1B1(15), ATP6V1B2(7), ATP6V1C1(3), ATP6V1C2(9), ATP6V1D(4), ATP6V1E1(3), ATP6V1E2(4), ATP6V1F(2), ATP6V1G1(1), ATP6V1G2(4), ATP6V1G3(2), ATP6V1H(5), CASP3(4), CCL5(4), CDC42(5), CHUK(11), CSK(1), CXCL1(1), EGFR(20), F11R(2), GIT1(9), HBEGF(3), IGSF5(9), IKBKB(15), IL8(3), JAM2(9), JAM3(3), JUN(1), LYN(7), MAP2K4(6), MAP3K14(12), MAPK10(9), MAPK13(2), MAPK14(6), MAPK8(7), MAPK9(7), MET(10), NFKB1(12), NFKB2(10), NFKBIA(3), NOD1(9), PAK1(3), PLCG1(12), PLCG2(27), PTPN11(8), PTPRZ1(43), RELA(6), SRC(2), TCIRG1(8), TJP1(33) 23868691 477 75 468 154 118 205 63 23 64 4 0.47 0.69 419 NUCLEOTIDE_METABOLISM ADSL, ADSS, DHFR, HPRT1, IMPDH1, MTHFD2, NME2, OAZ1, POLA, POLB, POLD1, POLG, PRPS2, RRM1, SAT, SRM 13 ADSL(7), ADSS(8), DHFR(3), HPRT1(2), IMPDH1(5), MTHFD2(3), POLB(4), POLD1(15), POLG(7), PRPS2(10), RRM1(4), SRM(1) 4120599 69 33 68 22 16 31 11 5 6 0 0.47 0.69 420 GLYCOLYSIS_AND_GLUCONEOGENESIS Genes involved in glycolysis and gluconeogenesis ALDOA, ALDOB, ALDOC, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GAPDHS, GAPDS, GCK, GOT1, GOT2, GPI, HK1, HK2, HK3, LDHA, LDHAL6B, LDHB, LDHC, MDH1, MDH2, PC, PCK1, PDHA1, PDHA2, PDHB, PDHX, PFKL, PFKM, PFKP, PGAM1, PGAM2, PGK1, PGK2, PKLR, PKM2, TNFAIP1, TPI1 42 ALDOA(6), ALDOB(9), ALDOC(4), DLAT(2), DLD(7), ENO1(5), ENO2(3), ENO3(4), FBP1(4), G6PC(6), GAPDH(2), GAPDHS(10), GCK(5), GOT1(6), GOT2(5), GPI(9), HK1(13), HK2(8), HK3(12), LDHA(6), LDHAL6B(2), LDHB(2), LDHC(3), MDH1(2), MDH2(5), PC(8), PCK1(15), PDHA1(4), PDHA2(10), PDHB(7), PDHX(8), PFKM(7), PFKP(11), PGAM1(2), PGAM2(2), PGK1(6), PGK2(5), PKLR(10), PKM2(5), TNFAIP1(3), TPI1(1) 13872277 244 57 239 81 69 102 30 16 25 2 0.47 0.69 421 CYTOKINEPATHWAY Intercellular signaling in the immune system occurs via secretion of cytokines, which promote antigen-dependent B and T cell response. IFNA1, IFNB1, IFNG, IL10, IL12A, IL12B, IL13, IL14, IL15, IL16, IL17, IL18, IL1A, IL2, IL3, IL4, IL5, IL6, IL8, IL9, LTA, TNF 20 IFNB1(4), IFNG(5), IL10(4), IL12A(7), IL12B(3), IL15(1), IL16(17), IL18(1), IL1A(1), IL2(4), IL5(2), IL6(2), IL8(3), LTA(3), TNF(1) 3594321 58 28 56 22 16 25 7 2 8 0 0.48 0.70 422 HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - lactoseries ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 10 B3GALT1(10), B3GALT2(8), B3GALT5(6), B3GNT5(6), FUT1(5), FUT2(3), FUT3(9), ST3GAL3(6), ST3GAL4(4) 2575225 57 26 54 16 12 28 7 3 7 0 0.48 0.70 423 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 AHCY(4), BHMT(2), CBS(13), CTH(5), DNMT1(15), DNMT3A(13), DNMT3B(15), MARS(12), MARS2(7), MAT1A(2), MAT2B(12), MTR(13) 5873186 113 38 104 44 26 55 14 2 16 0 0.48 0.70 424 KREBS_TCA_CYCLE ACO2, CGI_48, CS, DLAT, DLD, DLST, DLST, DLSTP, FH, IDH2, IDH3A, IDH3B, IDH3G, KIAA1348, MDH1, MDH2, OGDH, PC, PDHA1, PDHA2, PDHB, PDHX, PDK1, PDK2, PDK3, PDK4, PDP2, PPM2C, SDHA, SDHA, SDHAL2, SDHB, SDHC, SDHD, SUCLA2, SUCLG1, SUCLG2, WDR50 30 ACO2(8), CS(5), DLAT(2), DLD(7), DLST(10), FH(11), IDH2(7), IDH3A(5), IDH3B(5), IDH3G(9), MDH1(2), MDH2(5), OGDH(11), PC(8), PDHA1(4), PDHA2(10), PDHB(7), PDHX(8), PDK1(7), PDK2(5), PDK3(10), PDK4(7), PDP2(7), SDHA(12), SDHB(1), SDHC(6), SDHD(1), SUCLA2(5), SUCLG1(1), SUCLG2(14) 9849668 200 51 195 66 57 86 24 13 20 0 0.48 0.70 425 UREACYCLEPATHWAY Ammonia released from amino acid deamination is used to produce carbamoyl phosphate, which is used to convert ornithine to citrulline, from which urea is eventually formed. ARG1, ASL, ASS, CPS1, GLS, GLUD1, GOT1 6 ARG1(5), ASL(4), CPS1(24), GLS(10), GLUD1(4), GOT1(6) 2621352 53 24 51 13 12 20 7 2 8 4 0.49 0.71 426 HSA00531_GLYCOSAMINOGLYCAN_DEGRADATION Genes involved in glycosaminoglycan degradation ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, HGSNAT, HPSE, HPSE2, HYAL1, HYAL2, IDS, IDUA, LCT, NAGLU, SPAM1 16 ARSB(6), GLB1(9), GNS(2), GUSB(5), HEXA(3), HEXB(4), HGSNAT(9), HPSE(4), HPSE2(5), HYAL1(4), HYAL2(1), IDS(6), LCT(30), NAGLU(3), SPAM1(12) 6792858 103 41 101 51 28 45 12 8 10 0 0.49 0.71 427 HSA00240_PYRIMIDINE_METABOLISM Genes involved in pyrimidine metabolism AICDA, AK3, CAD, CANT1, CDA, CMPK, CTPS, CTPS2, DCK, DCTD, DHODH, DPYD, DPYS, DTYMK, DUT, ECGF1, ENTPD1, ENTPD3, ENTPD4, ENTPD5, ENTPD6, ENTPD8, ITPA, NME1, NME2, NME4, NME6, NME7, NP, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT2, PNPT1, POLA1, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, PRIM1, PRIM2, RFC5, RRM1, RRM2, RRM2B, TK1, TK2, TXNRD1, TXNRD2, TYMS, UCK1, UCK2, UMPS, UPB1, UPP1, UPP2, UPRT, ZNRD1 83 AICDA(3), CAD(38), CANT1(5), CDA(1), CTPS(10), CTPS2(10), DCK(4), DCTD(5), DHODH(3), DPYD(16), DPYS(3), DUT(1), ENTPD1(6), ENTPD3(8), ENTPD4(4), ENTPD5(2), ENTPD6(15), ITPA(1), NME6(2), NME7(4), NT5C(1), NT5C1A(2), NT5C1B(10), NT5C2(7), NT5C3(8), NT5E(6), NT5M(4), NUDT2(3), PNPT1(9), POLA1(26), POLD1(15), POLD2(6), POLD3(6), POLD4(1), POLE(1), POLE2(4), POLE3(2), POLR1A(15), POLR1B(16), POLR1C(4), POLR1D(2), POLR2A(25), POLR2B(20), POLR2C(5), POLR2D(3), POLR2E(1), POLR2F(2), POLR2H(3), POLR2K(2), POLR3A(9), POLR3B(7), POLR3G(2), POLR3GL(2), POLR3H(3), PRIM1(2), PRIM2(7), RFC5(7), RRM1(4), RRM2(5), RRM2B(5), TK1(2), TK2(7), TXNRD1(10), TXNRD2(4), TYMS(1), UCK1(5), UCK2(6), UMPS(7), UPB1(9), UPP1(4), UPP2(7), UPRT(6), ZNRD1(1) 27818405 472 81 461 144 110 192 71 32 65 2 0.49 0.71 428 RABPATHWAY Rab family GTPases regulate vesicle transport, endocytosis and exocytosis, and vesicle docking via interactions with the rabphilins. ACTA1, MEL, RAB11A, RAB1A, RAB2, RAB27A, RAB3A, RAB4A, RAB5A, RAB6A, RAB7, RAB9A 9 ACTA1(4), RAB11A(1), RAB1A(3), RAB27A(3), RAB3A(5), RAB4A(5), RAB5A(2), RAB6A(2), RAB9A(7) 1537248 32 18 28 8 9 14 3 0 6 0 0.49 0.71 429 ST_WNT_CA2_CYCLIC_GMP_PATHWAY Some Wnt glycoprotein/Frizzled receptor interactions increase intracellular calcium and decrease cGMP. BF, CAMK2A, CAMK2B, CAMK2D, CAMK2G, DAG1, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, NFAT5, PDE6A, PDE6B, PDE6C, PDE6D, PDE6G, PDE6H, SLC6A13, TF 18 CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), DAG1(7), ITPKB(6), ITPR1(31), ITPR2(38), ITPR3(23), NFAT5(13), PDE6A(13), PDE6B(6), PDE6C(14), PDE6D(1), SLC6A13(10), TF(15) 12139049 202 51 199 68 60 85 23 6 26 2 0.50 0.72 430 HSA03320_PPAR_SIGNALING_PATHWAY Genes involved in PPAR signaling pathway ACAA1, ACADL, ACADM, ACOX1, ACOX2, ACOX3, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADIPOQ, ANGPTL4, APOA1, APOA2, APOA5, APOC3, AQP7, CD36, CPT1A, CPT1B, CPT1C, CPT2, CYP27A1, CYP4A11, CYP4A22, CYP7A1, CYP8B1, DBI, EHHADH, FABP1, FABP2, FABP3, FABP4, FABP5, FABP5L1, FABP6, FABP7, FADS2, GK, GK2, HMGCS2, ILK, LOC642956, LPL, ME1, MMP1, NR1H3, OLR1, PCK1, PCK2, PDPK1, PLIN, PLTP, PPARA, PPARD, PPARG, RXRA, RXRB, RXRG, SCD, SCP2, SLC27A1, SLC27A2, SLC27A4, SLC27A5, SLC27A6, SORBS1, UBC, UCP1 65 ACAA1(5), ACADL(7), ACADM(6), ACOX1(4), ACOX2(7), ACOX3(8), ACSL1(13), ACSL3(10), ACSL4(24), ACSL5(18), ACSL6(13), ADIPOQ(3), ANGPTL4(1), APOA2(2), APOA5(2), AQP7(6), CD36(7), CPT1A(10), CPT1C(15), CPT2(7), CYP27A1(8), CYP4A11(5), CYP4A22(8), CYP7A1(12), CYP8B1(8), DBI(3), EHHADH(9), FABP1(5), FABP2(1), FABP3(1), FABP5(3), FABP6(3), FABP7(2), FADS2(2), GK(14), GK2(20), HMGCS2(8), ILK(8), LPL(11), ME1(10), MMP1(2), NR1H3(5), OLR1(1), PCK1(15), PCK2(7), PDPK1(3), PLTP(6), PPARA(2), PPARD(6), PPARG(5), RXRA(1), RXRG(10), SCD(9), SCP2(13), SLC27A1(9), SLC27A2(4), SLC27A4(5), SLC27A5(6), SLC27A6(10), SORBS1(22), UBC(5), UCP1(1) 22612507 456 74 442 121 133 186 64 23 48 2 0.50 0.72 431 HSA00363_BISPHENOL_A_DEGRADATION Genes involved in bisphenol A degradation AKR1B10, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, HSD3B7, PON1, PON2, PON3, RDH11, RDH12, RDH13, RDH14 14 AKR1B10(4), DHRS1(4), DHRS2(3), DHRS3(2), DHRS7(9), DHRSX(4), HSD3B7(3), PON1(12), PON2(8), PON3(1), RDH11(3), RDH12(6), RDH13(5), RDH14(3) 3072823 67 30 65 17 21 25 11 3 7 0 0.50 0.72 432 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3D(3), CD3E(2), CD3G(2) 407734 7 6 7 1 0 4 1 0 2 0 0.51 0.72 433 SELENOAMINO_ACID_METABOLISM AHCY, CBS, CTH, GGT1, MARS, MARS2, MAT1A, MAT2B, PAPSS1, PAPSS2, SCLY, SEPHS1 12 AHCY(4), CBS(13), CTH(5), GGT1(10), MARS(12), MARS2(7), MAT1A(2), MAT2B(12), PAPSS1(6), PAPSS2(6), SCLY(4), SEPHS1(13) 4130398 94 33 88 29 31 39 14 2 8 0 0.51 0.72 434 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 6 FUT1(5), FUT2(3), FUT3(9), FUT6(13), ST3GAL3(6) 1534380 36 20 36 14 4 26 4 1 1 0 0.51 0.72 435 HSA00710_CARBON_FIXATION Genes involved in carbon fixation ALDOA, ALDOB, ALDOC, FBP1, FBP2, GOT1, GOT2, GPT, GPT2, MDH1, MDH2, ME1, ME3, PGK1, PGK2, PKLR, PKM2, RPE, RPIA, TKT, TKTL1, TKTL2, TPI1 22 ALDOA(6), ALDOB(9), ALDOC(4), FBP1(4), GOT1(6), GOT2(5), GPT2(7), MDH1(2), MDH2(5), ME1(10), ME3(7), PGK1(6), PGK2(5), PKLR(10), PKM2(5), RPE(3), RPIA(7), TKT(7), TKTL1(10), TKTL2(12), TPI1(1) 6529241 131 41 128 43 35 57 14 7 16 2 0.51 0.72 436 MONOCYTEPATHWAY Monocytes are a class of immune phagocytes that can develop into macrophages and express LFA-1, CD44, and other surface signaling proteins. CD44, ICAM1, ITGA4, ITGAL, ITGAM, ITGB1, ITGB2, PECAM1, SELE, SELL, SELP 11 CD44(12), ICAM1(3), ITGA4(12), ITGAL(13), ITGAM(24), ITGB1(12), ITGB2(14), SELE(10), SELL(4), SELP(15) 6087091 119 40 114 29 30 50 14 6 17 2 0.52 0.73 437 ONE_CARBON_POOL_BY_FOLATE ALDH1L1, AMT, ATIC, ATP6V0C, SHMT1, DHFR, GART, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 15 ALDH1L1(9), AMT(5), ATIC(9), ATP6V0C(2), DHFR(3), GART(8), MTHFD1(6), MTHFD1L(12), MTHFD2(3), MTHFR(7), MTR(13), SHMT1(6), SHMT2(8), TYMS(1) 6300757 92 37 88 32 23 42 9 3 13 2 0.52 0.73 438 FMLPPATHWAY The fMLP receptor is a G-protein coupled receptor in neutrophils that recognizes formylated bacterial peptides and activates NADPH oxidase. CALM1, CALM2, CALM3, CAMK1, CAMK1G, ELK1, FPR1, GNA15, GNB1, GNGT1, HRAS, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NCF1, NCF2, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKBIA, PAK1, PIK3C2G, PLCB1, PPP3CA, PPP3CB, PPP3CC, RAC1, RAF1, RELA, SYT1 36 CALM2(3), CALM3(1), CAMK1(9), CAMK1G(5), ELK1(2), FPR1(4), GNA15(1), GNB1(3), MAP2K1(2), MAP2K3(8), MAP2K6(9), MAP3K1(31), MAPK1(2), MAPK14(6), MAPK3(4), NCF1(5), NCF2(6), NFATC2(15), NFATC3(12), NFATC4(8), NFKB1(12), NFKBIA(3), PAK1(3), PIK3C2G(22), PLCB1(6), PPP3CA(4), PPP3CB(7), PPP3CC(6), RAF1(7), RELA(6), SYT1(4) 12974832 216 55 212 53 61 65 35 14 37 4 0.52 0.73 439 TERPENOID_BIOSYNTHESIS FDFT1, FDPS, FDPS, LOC402397, IDI1, SQLE 4 FDFT1(3), FDPS(7), IDI1(4), SQLE(6) 1130709 20 14 20 6 5 5 5 3 2 0 0.52 0.73 440 HSA00310_LYSINE_DEGRADATION Genes involved in lysine degradation AADAT, AASDHPPT, AASS, ACAT1, ACAT2, AKR1B10, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, BBOX1, DLST, DOT1L, ECHS1, EHHADH, EHMT1, EHMT2, GCDH, HADH, HADHA, HSD17B10, HSD17B4, HSD3B7, NSD1, OGDH, OGDHL, PIPOX, PLOD1, PLOD2, PLOD3, RDH11, RDH12, RDH13, RDH14, SETD1A, SETD7, SETDB1, SHMT1, SHMT2, SPCS1, SPCS3, SUV39H1, SUV39H2, TMLHE 47 AADAT(6), AASDHPPT(4), AASS(6), ACAT1(6), ACAT2(5), AKR1B10(4), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH7A1(2), ALDH9A1(4), BBOX1(4), DLST(10), DOT1L(8), ECHS1(3), EHHADH(9), EHMT2(6), GCDH(5), HADH(1), HADHA(7), HSD17B10(4), HSD17B4(10), HSD3B7(3), NSD1(36), OGDH(11), OGDHL(18), PIPOX(6), PLOD1(4), PLOD2(16), PLOD3(11), RDH11(3), RDH12(6), RDH13(5), RDH14(3), SETD1A(12), SETD7(6), SETDB1(19), SHMT1(6), SHMT2(8), SPCS1(1), SPCS3(3), SUV39H1(10), SUV39H2(6), TMLHE(5) 19491406 319 68 305 82 78 134 49 19 35 4 0.52 0.73 441 GLYCOSPHINGOLIPID_METABOLISM ARSA, ARSB, ARSD, ARSE, ASAH1, GAL3ST1, GALC, GBA, GBAP, GLA, GLB1, LCT, NEU1, NEU2, NEU3, NEU4, PPAP2A, PPAP2B, PPAP2C, SMPD1, SMPD2, SPTLC1, SPTLC2, UGCG 20 ARSB(6), ARSD(9), ARSE(7), ASAH1(9), GAL3ST1(13), GALC(7), GBA(4), GLA(3), GLB1(9), LCT(30), NEU2(5), NEU3(3), PPAP2A(4), PPAP2B(3), SMPD1(12), SMPD2(5), SPTLC1(6), SPTLC2(6), UGCG(5) 7860710 146 43 145 44 43 68 12 9 14 0 0.52 0.73 442 TCRAPATHWAY The kinases Lck and Fyn phosphorylate and activate the T cell receptor, which recognizes antigen-bound MHCII and leads to T cell activation. CD3D, CD3E, CD3G, CD3Z, CD4, FYN, HLA-DRA, HLA-DRB1, LCK, PTPRC, TRA@, TRB@, ZAP70 10 CD3D(3), CD3E(2), CD3G(2), CD4(8), FYN(7), HLA-DRB1(1), LCK(5), PTPRC(15), ZAP70(10) 3184675 53 27 53 15 11 25 5 2 10 0 0.53 0.73 443 PROPANOATE_METABOLISM ABAT, ACACA, ACADL, ACADM, ACADSB, ACAS2, ACAS2L, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH9A1, ECHS1, EHHADH, HADHA, LDHA, LDHB, LDHC, MCEE, MLYCD, MUT, PCCA, PCCB, SDS, SUCLA2, SUCLG1, SUCLG2 31 ABAT(9), ACACA(27), ACADL(7), ACADM(6), ACADSB(4), ACAT1(6), ACAT2(5), ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH6A1(5), ALDH9A1(4), ECHS1(3), EHHADH(9), HADHA(7), LDHA(6), LDHB(2), LDHC(3), MLYCD(5), MUT(7), PCCA(10), PCCB(8), SDS(3), SUCLA2(5), SUCLG1(1), SUCLG2(14) 11463157 188 50 185 52 49 67 33 15 24 0 0.53 0.73 444 SPPAPATHWAY Thrombin cleaves protease-activated receptors PAR1 and PAR4 to induce calcium influx and activate platelet aggregation, a process inhibited by aspirin. F2, F2R, F2RL3, GNAI1, GNB1, GNGT1, HRAS, ITGA1, ITGB1, MAP2K1, MAPK1, MAPK3, PLA2G4A, PLCB1, PRKCA, PRKCB1, PTGS1, PTK2, RAF1, SRC, SYK, TBXAS1 20 F2(9), F2R(8), GNAI1(4), GNB1(3), ITGA1(20), ITGB1(12), MAP2K1(2), MAPK1(2), MAPK3(4), PLA2G4A(11), PLCB1(6), PRKCA(10), PTGS1(8), PTK2(11), RAF1(7), SRC(2), SYK(6), TBXAS1(6) 8327716 131 44 129 43 34 51 20 7 19 0 0.53 0.73 445 LEPTINPATHWAY Leptin is a peptide secreted by adipose tissue that, in skeletal muscle, promotes fatty acid oxidation, decreases cells' lipid content, and promotes insulin sensitivity. ACACA, CPT1A, LEP, LEPR, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2 10 ACACA(27), CPT1A(10), LEP(2), LEPR(15), PRKAA1(6), PRKAA2(9), PRKAB1(7), PRKAB2(2), PRKAG1(2), PRKAG2(4) 5100499 84 34 82 25 22 33 9 5 15 0 0.53 0.74 446 TRYPTOPHAN_METABOLISM AANAT, ABP1, ACAT1, ACAT2, ACMSD, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, AOC2, AOC3, AOX1, ASMT, CAT, CYP19A1, CYP1A1, CYP1A2, CYP2A6, CYP2A6, CYP2A7, CYP2A7P1, CYP2A13, CYP2B6, CYP2C18, CYP2C19, CYP2C19, CYP2C9, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP3A4, CYP3A5, CYP3A7, CYP4B1, CYP4F8, CYP51A1, DDC, ECHS1, EHHADH, GCDH, HAAO, HADHA, INDO, KMO, KYNU, MAOA, MAOB, SDS, TDO2, TPH1, WARS, WARS2 54 AANAT(4), ABP1(12), ACAT1(6), ACAT2(5), ACMSD(8), ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH9A1(4), AOC2(6), AOC3(14), AOX1(19), ASMT(3), CAT(5), CYP19A1(12), CYP1A1(9), CYP1A2(6), CYP2A13(7), CYP2A6(11), CYP2A7(5), CYP2B6(11), CYP2C18(5), CYP2C19(7), CYP2C8(4), CYP2C9(5), CYP2D6(2), CYP2E1(5), CYP2F1(5), CYP2J2(5), CYP3A4(14), CYP3A5(7), CYP3A7(9), CYP4B1(4), CYP4F8(9), CYP51A1(4), DDC(11), ECHS1(3), EHHADH(9), GCDH(5), HAAO(4), HADHA(7), KMO(11), KYNU(5), MAOA(14), MAOB(7), SDS(3), TDO2(3), TPH1(14), WARS(6), WARS2(5) 19356132 371 67 364 108 101 139 59 22 43 7 0.54 0.74 447 HSA00410_BETA_ALANINE_METABOLISM Genes involved in beta-alanine metabolism ABAT, ABP1, ACADM, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, AOC2, AOC3, CNDP1, DPYD, DPYS, ECHS1, EHHADH, GAD1, GAD2, HADHA, HIBCH, MLYCD, SMS, SRM, UPB1 25 ABAT(9), ABP1(12), ACADM(6), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH7A1(2), ALDH9A1(4), AOC2(6), AOC3(14), CNDP1(6), DPYD(16), DPYS(3), ECHS1(3), EHHADH(9), GAD1(8), GAD2(12), HADHA(7), HIBCH(7), MLYCD(5), SMS(8), SRM(1), UPB1(9) 9239023 164 47 159 46 48 58 26 12 20 0 0.54 0.74 448 HSA00563_GLYCOSYLPHOSPHATIDYLINOSITOL_ANCHOR_BIOSYNTHESIS Genes involved in glycosylphosphatidylinositol(GPI)-anchor biosynthesis GPAA1, GPLD1, PGAP1, PIGA, PIGB, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGU, PIGV, PIGW, PIGX, PIGZ 22 GPAA1(4), GPLD1(10), PGAP1(11), PIGA(8), PIGB(10), PIGC(4), PIGF(4), PIGG(12), PIGH(3), PIGK(6), PIGL(1), PIGN(9), PIGO(15), PIGP(2), PIGS(3), PIGT(10), PIGU(3), PIGV(6), PIGW(8), PIGX(2), PIGZ(6) 8032790 137 45 135 24 37 56 20 8 16 0 0.54 0.74 449 ACE2PATHWAY Angiotensin-converting enzyme 2 (ACE2) digests the blood-pressure regulator angiotensin II (AGT) ultimately to the vasodilator AGT1-7. ACE2, AGT, AGTR1, AGTR2, CMA1, COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6, REN 12 ACE2(19), AGT(7), AGTR2(8), CMA1(1), COL4A1(23), COL4A2(11), COL4A3(24), COL4A4(24), COL4A5(27), COL4A6(35), REN(3) 9026552 182 47 174 50 47 78 16 10 23 8 0.54 0.74 450 BIOGENIC_AMINE_SYNTHESIS AANAT, ACHE, CHAT, COMT, DBH, DDC, DXYS155E, GAD1, GAD2, HDC, MAOA, PAH, PNMT, SLC18A3, TH, TPH1 13 AANAT(4), ACHE(4), CHAT(1), DBH(12), DDC(11), GAD1(8), GAD2(12), HDC(10), MAOA(14), PAH(1), PNMT(3), TPH1(14) 4650223 94 34 93 17 20 32 21 1 18 2 0.55 0.75 451 RNA_TRANSCRIPTION_REACTOME CCNH, CDK7, ERCC3, GTF2A2, GTF2B, GTF2E1, GTF2E2, GTF2F2, GTF2H1, GTF2H2, GTF2H4, ILK, MGC9850, MNAT1, POLR1A, POLR1B, POLR2A, POLR2B, POLR2C, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR3B, POLR3D, POLR3E, POLR3H, POLR3K, TAF12, TAF13, TAF5, TAF6, TAF7, TAF9, TBP, VARS2L 36 CCNH(3), CDK7(6), ERCC3(11), GTF2B(5), GTF2E1(4), GTF2E2(5), GTF2F2(1), GTF2H1(8), GTF2H2(3), GTF2H4(2), ILK(8), MNAT1(2), POLR1A(15), POLR1B(16), POLR2A(25), POLR2B(20), POLR2C(5), POLR2E(1), POLR2F(2), POLR2H(3), POLR2K(2), POLR3B(7), POLR3D(3), POLR3E(5), POLR3H(3), TAF12(1), TAF5(6), TAF6(8), TAF7(3), TAF9(2), TBP(5) 12365860 190 52 183 68 41 81 21 15 32 0 0.56 0.77 452 ACTINYPATHWAY The Arp 2/3 complex localizes to the Y-junction of polymerizing actin fibers that enable lamellipod extension and consequent cell motility. ABI-2, ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, NCK1, NCKAP1, NTRK1, PIR, PSMA7, RAC1, WASF1, WASF2, WASF3, WASL 18 ACTA1(4), ACTR2(7), ACTR3(3), ARPC1A(7), ARPC1B(3), ARPC2(2), ARPC3(2), NCK1(4), NCKAP1(10), NTRK1(11), PIR(4), WASF1(3), WASF2(5), WASF3(9), WASL(8) 5403073 82 35 82 32 27 34 6 3 12 0 0.57 0.78 453 SARSPATHWAY The SARS coronavirus has a 30kb RNA genome containing rep, a large gene encoding viral protease Mpro. ANPEP, CKM, EIF4E, FBL, GPT, LDHA, LDHB, LDHC, MAPK14, NCL 9 ANPEP(13), CKM(3), EIF4E(4), FBL(4), LDHA(6), LDHB(2), LDHC(3), MAPK14(6), NCL(2) 2977223 43 27 43 21 11 15 7 5 3 2 0.58 0.78 454 ARGININECPATHWAY Related catabolic pathways process arginine, histidine, glutamine, and proline through glutamate to alpha-ketoglutamate, which feeds into the citric acid cycle. ALDH4A1, ARG1, GLS, GLUD1, OAT, PRODH 6 ALDH4A1(2), ARG1(5), GLS(10), GLUD1(4), OAT(7) 1641930 28 19 26 10 5 13 5 1 4 0 0.58 0.79 455 ST_GA12_PATHWAY G-alpha-12 promotes cell survival and proliferation, is involved in the stress response, and activates JNK. BF, BTK, DLG4, EPHB2, F2, F2RL1, F2RL2, F2RL3, JUN, MAP2K5, MAPK1, MAPK7, MAPK8, MYEF2, PLD1, PLD2, PLD3, PTK2, RAF1, RASAL1, SRC, TEC, VAV1 21 BTK(11), DLG4(13), EPHB2(10), F2(9), F2RL1(3), F2RL2(3), JUN(1), MAP2K5(2), MAPK1(2), MAPK7(17), MAPK8(7), MYEF2(6), PLD1(16), PLD2(7), PLD3(3), PTK2(11), RAF1(7), RASAL1(14), SRC(2), TEC(5), VAV1(16) 9304748 165 48 160 58 43 69 26 5 20 2 0.58 0.79 456 CCR5PATHWAY CCR5 is a G-protein coupled receptor expressed in macrophages that recognizes chemokine ligands and is targeted by the HIV envelope protein GP120. CALM1, CALM2, CALM3, CCL2, CCL4, CCR5, CXCL12, CXCR4, FOS, GNAQ, JUN, MAPK14, MAPK8, PLCG1, PRKCA, PRKCB1, PTK2B, SYT1 16 CALM2(3), CALM3(1), CCL4(1), CXCL12(3), CXCR4(1), FOS(6), JUN(1), MAPK14(6), MAPK8(7), PLCG1(12), PRKCA(10), PTK2B(16), SYT1(4) 4564422 71 33 69 32 20 24 9 8 10 0 0.59 0.79 457 UREA_CYCLE_AND_METABOLISM_OF_AMINO_GROUPS ACY1, ALDH18A1, ARG1, ARG2, ASL, ASS, CKB, CKM, CKMT1, CKMT1B, CKMT1A, CKMT2, CPS1, GAMT, GATM, GLUD1, NAGS, OAT, ODC1, OTC, PYCR1, SMS 16 ACY1(3), ALDH18A1(13), ARG1(5), ARG2(6), ASL(4), CKM(3), CKMT1A(5), CKMT1B(2), CKMT2(5), CPS1(24), GATM(8), GLUD1(4), OAT(7), ODC1(3), OTC(8), SMS(8) 5381563 108 36 104 35 27 46 16 5 10 4 0.59 0.80 458 HSA03010_RIBOSOME Genes involved in ribosome C15orf15, FAU, hCG_1644323, hCG_1984468, hCG_2041321, hCG_21078, hCG_26523, LOC283412, LOC284064, LOC284230, LOC284288, LOC284393, LOC285053, LOC342994, LOC347292, LOC388720, LOC389342, LOC390876, LOC391656, LOC400652, LOC402057, LOC439992, LOC440055, LOC440589, LOC440733, LOC440737, LOC441377, LOC441876, LOC441907, MRPL13, MRPS7, RPL10A, RPL10L, RPL11, RPL12, RPL13, RPL13A, RPL14, RPL18, RPL18A, RPL19, RPL21, RPL22L1, RPL23A, RPL23AP2, RPL24, RPL26, RPL27, RPL27A, RPL28, RPL29, RPL3, RPL30, RPL31, RPL32, RPL34, RPL35, RPL35A, RPL36A, RPL36AL, RPL37, RPL37A, RPL38, RPL39, RPL3L, RPL41, RPL6, RPL7, RPL8, RPL9, RPS10, RPS11, RPS12, RPS13, RPS15A, RPS16, RPS18, RPS2, RPS20, RPS21, RPS23, RPS24, RPS25, RPS26, RPS26P10, RPS27, RPS28, RPS29, RPS3, RPS3A, RPS4Y1, RPS5, RPS6, RPS7, RPS8, RPS9, RPSA, tcag7.23 65 FAU(1), MRPS7(6), RPL10A(1), RPL10L(8), RPL11(4), RPL12(1), RPL14(2), RPL18(4), RPL18A(4), RPL19(4), RPL21(2), RPL22L1(3), RPL23A(3), RPL24(3), RPL27(1), RPL27A(1), RPL28(2), RPL29(3), RPL3(5), RPL30(2), RPL31(1), RPL35(1), RPL35A(2), RPL36A(1), RPL36AL(1), RPL37(3), RPL38(1), RPL39(5), RPL3L(3), RPL6(2), RPL7(2), RPL8(1), RPL9(1), RPS10(2), RPS12(3), RPS13(1), RPS15A(1), RPS18(4), RPS20(3), RPS21(2), RPS24(4), RPS25(1), RPS27(2), RPS29(2), RPS3(2), RPS3A(2), RPS5(1), RPS6(6), RPS7(3), RPS8(5), RPS9(1), RPSA(1) 7508663 130 42 126 38 28 64 21 4 13 0 0.59 0.80 459 BLOOD_CLOTTING_CASCADE F10, F11, F12, F13B, F2, F5, F7, F8, F8A1, F9, FGA, FGB, FGG, LPA, PLG, PLAT, PLAU, PLG, SERPINB2, SERPINE1, SERPINF2, VWF 20 F10(10), F11(10), F12(3), F13B(13), F2(9), F5(46), F7(2), F8(41), F9(11), FGA(30), FGB(6), FGG(12), LPA(14), PLAT(6), PLAU(5), PLG(13), SERPINB2(9), SERPINE1(5), SERPINF2(5), VWF(31) 12089576 281 53 269 73 83 112 44 13 25 4 0.60 0.80 460 RHOPATHWAY RhoA is a G protein whose active form stabilizes actin structures such as focal adhesions and activates Rock1, which phosphorylates myosin light chains. ACTR2, ACTR3, ARHA, ARHGAP1, ARHGAP4, ARHGAP5, ARHGAP6, ARHGEF1, ARHGEF11, ARHGEF5, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, BAIAP2, CFL1, DIAPH1, GSN, LIMK1, MYL2, MYLK, OPHN1, PFN1, PIP5K1A, PIP5K1B, PPP1R12B, ROCK1, SRC, TLN1, VCL 30 ACTR2(7), ACTR3(3), ARHGAP1(2), ARHGAP4(15), ARHGAP5(24), ARHGAP6(13), ARHGEF1(11), ARHGEF11(22), ARHGEF5(11), ARPC1A(7), ARPC1B(3), ARPC2(2), ARPC3(2), BAIAP2(1), CFL1(1), DIAPH1(11), GSN(5), LIMK1(7), MYL2(1), MYLK(17), OPHN1(13), PFN1(1), PIP5K1A(7), PIP5K1B(6), PPP1R12B(18), ROCK1(27), SRC(2), TLN1(28), VCL(14) 16054825 281 63 274 79 89 106 29 18 31 8 0.60 0.80 461 PKCPATHWAY Gq-coupled receptors promote hydrolysis of PIP2 to DAG and IP3, which causes calcium influx and activates protein kinase C. GNAQ, NFKB1, NFKBIA, PLCB1, PRKCA, PRKCB1, RELA 6 NFKB1(12), NFKBIA(3), PLCB1(6), PRKCA(10), RELA(6) 2891900 37 23 37 16 4 13 10 4 6 0 0.60 0.80 462 HSA04612_ANTIGEN_PROCESSING_AND_PRESENTATION Genes involved in antigen processing and presentation B2M, CALR, CANX, CD4, CD74, CD8A, CD8B, CIITA, CREB1, CTSB, CTSL1, CTSS, HLA-A, HLA-A29.1, HLA-B, HLA-C, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-E, HLA-F, HLA-G, HSP90AA1, HSP90AB1, HSPA5, IFI30, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LGMN, LTA, NFYA, NFYB, NFYC, PDIA3, PSME1, PSME2, RFX5, RFXANK, RFXAP, TAP1, TAP2, TAPBP 72 B2M(2), CALR(4), CANX(8), CD4(8), CD74(1), CD8A(3), CD8B(1), CIITA(21), CREB1(5), CTSB(1), CTSL1(7), CTSS(6), HLA-A(5), HLA-B(3), HLA-DMA(4), HLA-DMB(2), HLA-DOA(3), HLA-DOB(4), HLA-DPA1(1), HLA-DPB1(2), HLA-DQA1(2), HLA-DQA2(1), HLA-DQB1(1), HLA-DRB1(1), HLA-DRB5(1), HLA-E(2), HLA-F(3), HLA-G(3), HSP90AA1(7), HSP90AB1(20), HSPA5(8), IFNA10(2), IFNA13(3), IFNA14(3), IFNA16(2), IFNA17(2), IFNA2(1), IFNA21(2), IFNA4(3), IFNA5(2), IFNA6(6), IFNA7(2), IFNA8(2), KIR2DL1(6), KIR2DL3(2), KIR2DL4(3), KIR2DS4(6), KIR3DL1(7), KIR3DL2(7), KIR3DL3(3), KLRC1(2), KLRC2(3), KLRC3(1), KLRC4(3), KLRD1(2), LGMN(8), LTA(3), NFYA(7), NFYB(2), NFYC(1), PDIA3(6), PSME1(2), PSME2(2), RFX5(13), RFXANK(4), RFXAP(1), TAP1(7), TAP2(2), TAPBP(5) 16547882 278 58 272 69 80 119 31 10 36 2 0.61 0.81 463 KREBPATHWAY The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain. ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2 8 ACO2(8), CS(5), FH(11), IDH2(7), MDH1(2), OGDH(11), SDHA(12), SUCLA2(5) 3326163 61 28 60 26 17 30 6 4 4 0 0.61 0.81 464 GPCRDB_CLASS_A_RHODOPSIN_LIKE2 CYSLTR1, CYSLTR2, GPR109B, GPR161, GPR171, GPR18, GPR34, GPR39, GPR41, GPR42, GPR45, GPR65, GPR68, GPR75, GPR81, LYPDC1 13 CYSLTR1(5), CYSLTR2(6), GPR161(3), GPR171(6), GPR18(2), GPR34(6), GPR39(10), GPR45(7), GPR65(10), GPR68(4), GPR75(10) 3491073 69 28 65 31 16 28 18 3 4 0 0.61 0.81 465 ALKALOID_BIOSYNTHESIS_II ABP1, AOC2, AOC3, CES1, ESD 5 ABP1(12), AOC2(6), AOC3(14), CES1(12), ESD(2) 2205970 46 23 43 15 13 16 10 3 4 0 0.61 0.81 466 HSA00670_ONE_CARBON_POOL_BY_FOLATE Genes involved in one carbon pool by folate ALDH1L1, AMT, ATIC, DHFR, FTCD, GART, MTFMT, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 15 ALDH1L1(9), AMT(5), ATIC(9), DHFR(3), GART(8), MTFMT(1), MTHFD1(6), MTHFD1L(12), MTHFD2(3), MTHFR(7), MTR(13), SHMT1(6), SHMT2(8), TYMS(1) 6443201 91 36 87 32 22 42 9 3 13 2 0.62 0.81 467 GLUCONEOGENESIS ACYP1, ACYP2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GCK, GPI, HK1, HK2, HK3, LDHA, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKM, PFKP, PGAM1, PGK1, PGM1, PGM3, PKLR, PKM2, TPI1 53 ACYP1(2), ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH6(9), ADH7(6), ADHFE1(7), AKR1A1(1), ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH3B1(5), ALDH3B2(8), ALDH9A1(4), ALDOA(6), ALDOB(9), ALDOC(4), BPGM(2), DLAT(2), DLD(7), ENO1(5), ENO2(3), ENO3(4), FBP1(4), G6PC(6), GAPDH(2), GCK(5), GPI(9), HK1(13), HK2(8), HK3(12), LDHA(6), LDHB(2), LDHC(3), PDHA1(4), PDHA2(10), PDHB(7), PFKM(7), PFKP(11), PGAM1(2), PGK1(6), PGM1(9), PGM3(6), PKLR(10), PKM2(5), TPI1(1) 16614324 284 61 278 94 83 116 34 16 33 2 0.62 0.81 468 GLYCOLYSIS ACYP1, ACYP2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GCK, GPI, HK1, HK2, HK3, LDHA, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKM, PFKP, PGAM1, PGK1, PGM1, PGM3, PKLR, PKM2, TPI1 53 ACYP1(2), ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH6(9), ADH7(6), ADHFE1(7), AKR1A1(1), ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH3B1(5), ALDH3B2(8), ALDH9A1(4), ALDOA(6), ALDOB(9), ALDOC(4), BPGM(2), DLAT(2), DLD(7), ENO1(5), ENO2(3), ENO3(4), FBP1(4), G6PC(6), GAPDH(2), GCK(5), GPI(9), HK1(13), HK2(8), HK3(12), LDHA(6), LDHB(2), LDHC(3), PDHA1(4), PDHA2(10), PDHB(7), PFKM(7), PFKP(11), PGAM1(2), PGK1(6), PGM1(9), PGM3(6), PKLR(10), PKM2(5), TPI1(1) 16614324 284 61 278 94 83 116 34 16 33 2 0.62 0.81 469 CARBON_FIXATION ALDOA, ALDOB, ALDOC, FBP1, FBP2, GOT1, GOT2, GPT, GPT2, MDH1, MDH2, ME1, ME2, ME3, PGK1, PKLR, PKM2, RPE, RPE, LOC440001, RPIA, TKT, TPI1 20 ALDOA(6), ALDOB(9), ALDOC(4), FBP1(4), GOT1(6), GOT2(5), GPT2(7), MDH1(2), MDH2(5), ME1(10), ME2(7), ME3(7), PGK1(6), PKLR(10), PKM2(5), RPE(3), RPIA(7), TKT(7), TPI1(1) 5828254 111 37 109 37 31 47 13 6 12 2 0.62 0.81 470 HSA00730_THIAMINE_METABOLISM Genes involved in thiamine metabolism LHPP, MTMR1, MTMR2, MTMR6, NFS1, PHPT1, THTPA, TPK1 8 LHPP(2), MTMR1(16), MTMR2(4), MTMR6(8), NFS1(8), PHPT1(2), THTPA(1), TPK1(2) 2210750 43 22 41 18 7 17 8 1 10 0 0.62 0.81 471 CIRCADIANPATHWAY A heterodimer composed of Bmal1 and Clock acts as a transcription factor for proteins that regulate circadian rhythms, such as Per and Cry. ARNTL, CLOCK, CRY1, CRY2, CSNK1E, PER1 6 ARNTL(12), CLOCK(11), CRY1(6), CRY2(4), CSNK1E(10), PER1(15) 2749217 58 24 57 17 16 20 10 2 8 2 0.62 0.81 472 DNA_POLYMERASE POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLS 7 POLB(4), POLD1(15), POLD2(6), POLE(1), POLG(7), POLL(8), POLQ(23) 5901627 64 36 63 15 15 29 9 4 7 0 0.62 0.81 473 HSA00480_GLUTATHIONE_METABOLISM Genes involved in glutathione metabolism ANPEP, G6PD, GCLC, GCLM, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GSR, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, OPLAH, TXNDC12 34 ANPEP(13), G6PD(3), GCLC(8), GCLM(3), GGT1(10), GPX3(4), GPX5(7), GPX6(6), GPX7(1), GSR(5), GSS(5), GSTA1(5), GSTA2(6), GSTA3(3), GSTA4(3), GSTA5(2), GSTK1(5), GSTM1(3), GSTM2(1), GSTM3(4), GSTM4(2), GSTM5(2), GSTO2(2), GSTP1(2), GSTZ1(4), IDH1(4), IDH2(7), MGST1(3), MGST3(1), TXNDC12(5) 7001266 129 43 122 48 49 41 18 11 8 2 0.62 0.81 474 HSA00330_ARGININE_AND_PROLINE_METABOLISM Genes involved in arginine and proline metabolism ALDH4A1, ARG1, ARG2, ASL, ASS1, CKB, CKM, CKMT1A, CKMT1B, CKMT2, CPS1, DAO, EPRS, GAMT, GATM, GLUD1, GLUD2, GOT1, GOT2, LAP3, NOS1, NOS2A, NOS3, OAT, OTC, P4HA1, P4HA2, P4HA3, PARS2, PRODH, PYCR1, PYCR2, PYCRL, RARS, RARS2 31 ALDH4A1(2), ARG1(5), ARG2(6), ASL(4), ASS1(3), CKM(3), CKMT1A(5), CKMT1B(2), CKMT2(5), CPS1(24), DAO(5), EPRS(11), GATM(8), GLUD1(4), GLUD2(9), GOT1(6), GOT2(5), LAP3(7), NOS1(21), NOS3(11), OAT(7), OTC(8), P4HA1(8), P4HA2(10), P4HA3(5), PARS2(4), PYCR2(3), PYCRL(1), RARS(11), RARS2(7) 11471044 210 52 204 79 48 98 32 10 18 4 0.62 0.81 475 EIF2PATHWAY Eukaryotic initiation factor 2 (EIF2) initiates translation by transferring Met-tRNA to the 40S ribosome in a GTP-dependent process. EIF2AK3, EIF2AK4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF5, GSK3B, HRI, PPP1CA, PRKR 9 EIF2AK3(14), EIF2AK4(12), EIF2B5(6), EIF2S1(1), EIF2S2(5), EIF2S3(6), EIF5(3), GSK3B(11), PPP1CA(6) 4058459 64 32 63 16 16 27 5 5 11 0 0.63 0.81 476 HYPERTROPHY_MODEL ADAM10, ANKRD1, ATF3, CYR61, DUSP14, EIF4E, EIF4EBP1, GDF8, HBEGF, IFNG, IFRD1, IL18, IL1A, IL1R1, JUND, MYOG, NR4A3, TCF8, VEGF, WDR1 16 ADAM10(4), ANKRD1(4), ATF3(4), CYR61(3), DUSP14(3), EIF4E(4), HBEGF(3), IFNG(5), IFRD1(10), IL18(1), IL1A(1), IL1R1(5), MYOG(1), NR4A3(10), WDR1(10) 3627542 68 29 67 20 23 24 13 2 6 0 0.63 0.81 477 GPCRPATHWAY G-protein coupled receptors activate adenylyl cyclase, which converts ATP to cAMP, to activate second messenger pathways. ADCY1, CALM1, CALM2, CALM3, CREB1, ELK1, FOS, GNAI1, GNAQ, GNAS, GNB1, GNGT1, HRAS, JUN, MAP2K1, MAPK3, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, RAF1, RPS6KA3, SYT1 34 ADCY1(17), CALM2(3), CALM3(1), CREB1(5), ELK1(2), FOS(6), GNAI1(4), GNAS(25), GNB1(3), JUN(1), MAP2K1(2), MAPK3(4), NFATC2(15), NFATC3(12), NFATC4(8), PLCG1(12), PPP3CA(4), PPP3CB(7), PPP3CC(6), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PRKCA(10), RAF1(7), RPS6KA3(17), SYT1(4) 11446188 204 52 197 60 57 79 23 14 29 2 0.63 0.81 478 HSA00400_PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS Genes involved in phenylalanine, tyrosine and tryptophan biosynthesis FARS2, FARSA, FARSB, GOT1, GOT2, PAH, TAT, YARS, YARS2 9 FARS2(2), FARSA(6), FARSB(7), GOT1(6), GOT2(5), PAH(1), TAT(9), YARS(8), YARS2(3) 3071867 47 25 46 14 14 17 9 4 3 0 0.63 0.81 479 S1PPATHWAY At low cholesterol concentrations, sterol-regulatory element binding proteins (SREBPs) act as transcription factors to promote cholesterol uptake and biosynthesis. EPLIN, HMGCS1, LDLR, MBTPS1, MBTPS2, SCAP, SREBF1, SREBF2 7 HMGCS1(4), LDLR(12), MBTPS1(13), MBTPS2(15), SCAP(16), SREBF1(6), SREBF2(10) 3548194 76 30 75 20 21 34 7 4 10 0 0.63 0.81 480 HSA04742_TASTE_TRANSDUCTION Genes involved in taste transduction ACCN1, ADCY4, ADCY6, ADCY8, CACNA1A, CACNA1B, GNAS, GNAT3, GNB1, GNB3, GNG13, GNG3, GRM4, ITPR3, KCNB1, PDE1A, PLCB2, PRKACA, PRKACB, PRKACG, PRKX, PRKY, SCNN1A, SCNN1B, SCNN1G, TAS1R1, TAS1R2, TAS1R3, TAS2R1, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R3, TAS2R38, TAS2R39, TAS2R4, TAS2R40, TAS2R41, TAS2R42, TAS2R43, TAS2R44, TAS2R45, TAS2R46, TAS2R48, TAS2R49, TAS2R5, TAS2R50, TAS2R60, TAS2R7, TAS2R8, TAS2R9, TRPM5 46 ACCN1(4), ADCY4(8), ADCY6(16), ADCY8(16), CACNA1A(19), CACNA1B(1), GNAS(25), GNAT3(7), GNB1(3), GNB3(4), GNG13(2), GNG3(3), GRM4(16), ITPR3(23), KCNB1(17), PDE1A(12), PLCB2(9), PRKACA(4), PRKACB(2), PRKACG(6), PRKX(4), SCNN1A(5), SCNN1B(6), SCNN1G(13), TAS1R1(11), TAS1R2(12), TAS2R1(4), TAS2R10(6), TAS2R13(4), TAS2R14(6), TAS2R16(3), TAS2R3(2), TAS2R38(4), TAS2R39(10), TAS2R4(3), TAS2R40(4), TAS2R41(2), TAS2R42(5), TAS2R46(1), TAS2R5(5), TAS2R50(4), TAS2R60(7), TAS2R7(4), TAS2R8(6), TAS2R9(1) 18971820 329 60 322 123 91 141 42 17 38 0 0.64 0.82 481 HSP27PATHWAY Hsp27 oligomers have molecular chaperone activity and protect heat-stressed cells against apoptosis. ACTA1, APAF1, BCL2, CASP3, CASP9, CYCS, DAXX, FAS, FASLG, HSPB1, HSPB2, IL1A, MAPKAPK2, MAPKAPK3, TNF, TNFRSF6 14 ACTA1(4), APAF1(19), CASP3(4), CASP9(3), CYCS(3), DAXX(11), FAS(7), FASLG(6), HSPB2(1), IL1A(1), MAPKAPK2(6), MAPKAPK3(4), TNF(1) 3808943 70 30 69 20 19 25 11 5 10 0 0.64 0.82 482 PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS ENO1, ENO2, ENO3, FARS2, FARSLB, GOT1, GOT2, PAH, TAT, YARS 9 ENO1(5), ENO2(3), ENO3(4), FARS2(2), GOT1(6), GOT2(5), PAH(1), TAT(9), YARS(8) 2926077 43 23 42 14 9 19 6 4 5 0 0.66 0.84 483 HSA00785_LIPOIC_ACID_METABOLISM Genes involved in lipoic acid metabolism LIAS, LIPT1, LOC387787 2 LIAS(7), LIPT1(5) 529863 12 9 12 3 2 7 2 0 1 0 0.66 0.84 484 HSA04740_OLFACTORY_TRANSDUCTION Genes involved in olfactory transduction ADCY3, ADRBK2, ARRB2, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CLCA1, CLCA2, CLCA4, CNGA3, CNGA4, CNGB1, GNAL, GUCA1A, GUCA1B, GUCA1C, PDC, PDE1C, PRKACA, PRKACB, PRKACG, PRKG1, PRKG2, PRKX, PRKY 30 ADCY3(8), ADRBK2(10), ARRB2(3), CALM2(3), CALM3(1), CALML6(4), CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), CLCA1(20), CLCA2(13), CLCA4(16), CNGA3(13), CNGA4(11), CNGB1(14), GNAL(6), GUCA1A(5), GUCA1B(3), GUCA1C(3), PDE1C(14), PRKACA(4), PRKACB(2), PRKACG(6), PRKG1(9), PRKG2(10), PRKX(4) 10456011 207 51 204 85 54 85 31 7 28 2 0.66 0.84 485 HSA00910_NITROGEN_METABOLISM Genes involved in nitrogen metabolism AMT, ASNS, ASRGL1, CA1, CA12, CA13, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA8, CA9, CPS1, CTH, GLS, GLS2, GLUD1, GLUD2, GLUL, HAL 24 AMT(5), ASNS(9), ASRGL1(2), CA1(4), CA12(3), CA13(2), CA14(4), CA2(5), CA3(4), CA4(1), CA5A(5), CA5B(5), CA6(2), CA7(5), CA8(5), CA9(8), CPS1(24), CTH(5), GLS(10), GLS2(9), GLUD1(4), GLUD2(9), GLUL(6), HAL(6) 7353074 142 41 136 47 46 55 16 4 17 4 0.66 0.84 486 UCALPAINPATHWAY Calpains promote formation of integrin adhesion clusters which recruit Rac to enable the formation of mature focal adhesions that do not contain calpain. ACTA1, ACTN1, ACTN2, ACTN3, ARHA, CAPN1, CAPNS1, CAPNS2, ITGA1, ITGB1, ITGB3, PTK2, PXN, RAC1, SPTAN1, SRC, TLN1, VIL2 16 ACTA1(4), ACTN1(13), ACTN2(9), ACTN3(10), CAPN1(4), CAPNS1(3), CAPNS2(6), ITGA1(20), ITGB1(12), ITGB3(16), PTK2(11), PXN(6), SPTAN1(29), SRC(2), TLN1(28) 9938815 173 48 169 72 60 70 13 6 24 0 0.66 0.84 487 HSA00220_UREA_CYCLE_AND_METABOLISM_OF_AMINO_GROUPS Genes involved in urea cycle and metabolism of amino groups ABP1, ACY1, ADC, AGMAT, ALDH18A1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, AMD1, AOC2, AOC3, ARG1, ARG2, ASL, ASS1, CPS1, GATM, MAOA, MAOB, NAGS, ODC1, OTC, SAT1, SAT2, SMS, SRM 29 ABP1(12), ACY1(3), ADC(8), AGMAT(3), ALDH18A1(13), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH7A1(2), ALDH9A1(4), AMD1(3), AOC2(6), AOC3(14), ARG1(5), ARG2(6), ASL(4), ASS1(3), CPS1(24), GATM(8), MAOA(14), MAOB(7), ODC1(3), OTC(8), SAT1(12), SMS(8), SRM(1) 10010037 188 48 180 66 56 76 23 8 21 4 0.66 0.84 488 HSA00660_C5_BRANCHED_DIBASIC_ACID_METABOLISM Genes involved in C5-branched dibasic acid metabolism ILVBL, SUCLA2 2 ILVBL(7), SUCLA2(5) 754762 12 10 11 2 2 9 0 0 1 0 0.66 0.84 489 HSA00300_LYSINE_BIOSYNTHESIS Genes involved in lysine biosynthesis AADAT, AASDHPPT, AASS, KARS 4 AADAT(6), AASDHPPT(4), AASS(6), KARS(7) 1653641 23 16 22 10 7 7 6 2 1 0 0.67 0.84 490 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 ADCY1(17), CREM(5), FHL5(6), FSHR(17), GNAS(25), XPO1(15) 3133290 85 28 81 18 24 42 11 3 5 0 0.67 0.84 491 CCR3PATHWAY CCR3 is a G-protein coupled receptor that recruits eosinophils to inflammation sites via chemokine ligands. ARHA, CCL11, CCR3, CFL1, GNAQ, GNAS, GNB1, GNGT1, HRAS, LIMK1, MAP2K1, MAPK1, MAPK3, MYL2, NOX1, PIK3C2G, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2, RAF1, ROCK2 21 CCR3(5), CFL1(1), GNAS(25), GNB1(3), LIMK1(7), MAP2K1(2), MAPK1(2), MAPK3(4), MYL2(1), NOX1(11), PIK3C2G(22), PLCB1(6), PPP1R12B(18), PRKCA(10), PTK2(11), RAF1(7), ROCK2(15) 8758155 150 44 147 41 40 52 21 8 25 4 0.67 0.84 492 NOTCHPATHWAY Proteolysis and Signaling Pathway of Notch ADAM17, DLL1, FURIN, NOTCH1, PSEN1, RBPSUH 4 ADAM17(11), DLL1(8), FURIN(5), PSEN1(4) 1751631 28 18 28 20 6 16 1 2 3 0 0.67 0.84 493 ST_G_ALPHA_S_PATHWAY The G-alpha-s protein activates adenylyl cyclases, which catalyze cAMP formation. ASAH1, BF, BFAR, BRAF, CAMP, CREB1, CREB3, CREB5, EPAC, GAS, GRF2, MAPK1, RAF1, SNX13, SRC, TERF2IP 12 ASAH1(9), BFAR(9), BRAF(12), CAMP(1), CREB1(5), CREB3(2), CREB5(6), MAPK1(2), RAF1(7), SNX13(12), SRC(2), TERF2IP(4) 3966205 71 30 71 14 11 28 14 6 12 0 0.67 0.84 494 TH1TH2PATHWAY Helper T subtype Th1 produces pro-inflammatory cytokines that stimulate phagocytosis, while Th2 cells promote antibody production and activate eosinophils. CD28, CD86, HLA-DRA, HLA-DRB1, IFNG, IFNGR1, IFNGR2, IL12A, IL12B, IL12RB1, IL12RB2, IL18, IL18R1, IL2, IL2RA, IL4, IL4R, TNFRSF5, TNFSF5 17 CD28(6), CD86(6), HLA-DRB1(1), IFNG(5), IFNGR1(6), IFNGR2(4), IL12A(7), IL12B(3), IL12RB1(16), IL12RB2(11), IL18(1), IL18R1(5), IL2(4), IL2RA(3), IL4R(6) 4512559 84 33 82 19 20 35 9 8 12 0 0.68 0.84 495 FXRPATHWAY The nuclear receptor transcription factors FXR and LXR are activated by cholesterol metabolites and regulate cholesterol homeostasis. FABP6, LDLR, NR0B2, NR1H3, NR1H4, RXRA 6 FABP6(3), LDLR(12), NR0B2(2), NR1H3(5), NR1H4(8), RXRA(1) 1845319 31 21 31 11 8 16 4 0 3 0 0.68 0.84 496 VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS BCAT1, IARS, LARS, LARS2, PDHA1, PDHA2, PDHB 7 BCAT1(9), IARS(13), LARS(23), LARS2(9), PDHA1(4), PDHA2(10), PDHB(7) 3562056 75 27 75 14 15 34 11 4 11 0 0.68 0.85 497 PORPHYRIN_AND_CHLOROPHYLL_METABOLISM ALAD, BLVRA, BLVRB, CP, CPOX, EPRS, FECH, GUSB, HCCS, HMBS, HMOX1, HMOX2, PPOX, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4, UROD, UROS 26 ALAD(3), BLVRA(2), BLVRB(1), CP(12), CPOX(8), EPRS(11), FECH(5), GUSB(5), HCCS(2), HMBS(7), HMOX1(3), HMOX2(5), UGT1A1(6), UGT1A10(8), UGT1A3(4), UGT1A4(4), UGT1A5(7), UGT1A6(5), UGT1A7(9), UGT1A8(4), UGT1A9(4), UGT2B15(9), UGT2B4(10), UROD(2), UROS(3) 9137926 139 43 133 39 42 57 17 7 16 0 0.68 0.85 498 HSA04710_CIRCADIAN_RHYTHM Genes involved in circadian rhythm ARNTL, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, NPAS2, NR1D1, PER1, PER2, PER3 11 ARNTL(12), CLOCK(11), CRY1(6), CRY2(4), CSNK1E(10), NPAS2(10), NR1D1(3), PER1(15), PER2(8), PER3(16) 5595468 95 35 91 27 28 33 14 3 15 2 0.69 0.85 499 ARAPPATHWAY ADP-ribosylation factors (ARFs), members of the Ras superfamily, regulate eukaryotic vesicular trafficking and activate phospholipase D's. ARF1, ARFGAP1, ARFGAP3, ARFGEF2, BIG1, CENTD1, CENTD2, CLTA, CLTB, COP, COPA, DDEF1, DDEF2, GBF1, GPLD1, KDELR1, KDELR2, KDELR3, PSCD1, PSCD2, PSCD3, PSCD4 12 ARF1(4), ARFGAP1(3), ARFGAP3(6), ARFGEF2(30), CLTA(1), CLTB(5), COPA(14), GBF1(23), GPLD1(10), KDELR1(3), KDELR2(2), KDELR3(4) 5507994 105 35 105 25 20 50 14 5 14 2 0.70 0.86 500 GLUTATHIONE_METABOLISM ANPEP, G6PD, GCLC, GCLM, GGT1, GPX1, GPX2, GPX3, GPX4, GPX5, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, PGD 29 ANPEP(13), G6PD(3), GCLC(8), GCLM(3), GGT1(10), GPX3(4), GPX5(7), GSS(5), GSTA1(5), GSTA2(6), GSTA3(3), GSTA4(3), GSTM1(3), GSTM2(1), GSTM3(4), GSTM4(2), GSTM5(2), GSTO2(2), GSTP1(2), GSTZ1(4), IDH1(4), IDH2(7), MGST1(3), MGST3(1), PGD(4) 6272794 109 40 104 41 41 36 14 11 5 2 0.70 0.86 501 DNAFRAGMENTPATHWAY DNA fragmentation during apoptosis is effected by DFF, a caspase-activated DNAse, and by endonuclease G. CASP3, CASP7, DFFA, DFFB, ENDOG, GZMB, HMGB1, HMGB2, TOP2A, TOP2B 9 CASP3(4), CASP7(4), DFFA(1), DFFB(3), GZMB(2), HMGB1(2), HMGB2(3), TOP2A(15), TOP2B(21) 3519275 55 27 55 21 5 17 13 7 13 0 0.70 0.86 502 HSA00450_SELENOAMINO_ACID_METABOLISM Genes involved in selenoamino acid metabolism AHCY, CARM1, CBS, CTH, GGT1, GGTL3, GGTL4, HEMK1, KIAA0828, LCMT1, LCMT2, MARS, MARS2, MAT1A, MAT2B, METTL2B, METTL6, PAPSS1, PAPSS2, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, SCLY, SEPHS1, SEPHS2, WBSCR22 26 AHCY(4), CARM1(6), CBS(13), CTH(5), GGT1(10), HEMK1(2), LCMT1(4), LCMT2(13), MARS(12), MARS2(7), MAT1A(2), MAT2B(12), METTL2B(3), METTL6(2), PAPSS1(6), PAPSS2(6), PRMT3(10), PRMT5(11), PRMT6(6), PRMT7(4), PRMT8(9), SCLY(4), SEPHS1(13), SEPHS2(4), WBSCR22(9) 8352572 177 41 169 45 53 71 23 7 19 4 0.70 0.86 503 RARRXRPATHWAY RXR and RAR suppress transcription in the absence of ligand and, on binding trans- or 9-cis-retinoic acid, are ubiquitinated to allow transcription to proceed. ERCC3, GTF2A1, GTF2B, GTF2E1, GTF2F1, HDAC3, NCOA1, NCOA2, NCOA3, NCOR2, PCAF, POLR2A, RARA, RXRA, TBP 14 ERCC3(11), GTF2A1(5), GTF2B(5), GTF2E1(4), GTF2F1(6), HDAC3(10), NCOA1(17), NCOA2(16), NCOA3(8), NCOR2(24), POLR2A(25), RARA(3), RXRA(1), TBP(5) 8039721 140 41 137 55 27 68 23 7 15 0 0.70 0.86 504 HSA00460_CYANOAMINO_ACID_METABOLISM Genes involved in cyanoamino acid metabolism ASRGL1, GBA, GBA3, GGT1, GGTL3, GGTL4, SHMT1, SHMT2 6 ASRGL1(2), GBA(4), GBA3(9), GGT1(10), SHMT1(6), SHMT2(8) 1968643 39 20 36 13 12 14 4 1 6 2 0.70 0.86 505 GPCRDB_CLASS_B_SECRETIN_LIKE ADCYAP1R1, CALCR, CALCRL, CD97, CRHR1, CRHR2, ELTD1, EMR1, EMR2, GCGR, GHRHR, GIPR, GLP1R, GLP2R, GPR64, LPHN1, LPHN2, LPHN3, PTHR1, PTHR2, SCTR, VIPR1, VIPR2 20 ADCYAP1R1(7), CALCR(5), CALCRL(9), CD97(8), CRHR1(2), CRHR2(2), ELTD1(12), EMR1(22), EMR2(5), GHRHR(2), GIPR(4), GLP1R(8), GLP2R(17), GPR64(10), LPHN1(16), LPHN2(30), LPHN3(29), SCTR(4), VIPR1(3) 9426160 195 48 190 57 43 93 23 14 20 2 0.71 0.86 506 FEEDERPATHWAY Sugars such as mannose, galactose, and fructose are enzymatically converted to glucose via feeder pathways that lead to glycolysis. HK1, KHK, LCT, MPI, PGM1, PYGL, PYGM, TPI1, TREH 9 HK1(13), KHK(1), LCT(30), MPI(5), PGM1(9), PYGL(9), PYGM(10), TPI1(1), TREH(4) 4675557 82 30 82 33 19 36 11 8 8 0 0.71 0.86 507 GLYCEROPHOSPHOLIPID_METABOLISM ACHE, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPS, CDIPT, CDS1, CDS2, CHAT, CHKA, CHKB, CHKB, CPT1B, CLC, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKQ, DGKZ, ETNK1, GNPAT, GPD1, GPD2, LCAT, LGALS13, LYPLA1, LYPLA2, LYPLA2, LYPLA2P1, LOC388499, LYPLA3, PAFAH1B1, PAFAH2, PCYT1A, PCYT1B, PEMT, PISD, PLA2G1B, PLA2G2A, PLA2G2E, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCB2, PLCG1, PLCG2, PPAP2A, PPAP2B, PPAP2C 47 ACHE(4), AGPAT1(2), AGPAT2(1), AGPAT3(6), AGPAT4(4), AGPS(10), CDIPT(1), CDS1(3), CDS2(2), CHAT(1), CHKA(8), DGKA(15), DGKB(17), DGKD(21), DGKE(4), DGKG(13), DGKH(11), DGKZ(9), ETNK1(9), GNPAT(11), GPD1(6), GPD2(5), LCAT(2), LGALS13(2), LYPLA1(2), LYPLA2(5), PAFAH1B1(1), PAFAH2(6), PCYT1A(7), PCYT1B(4), PEMT(2), PISD(5), PLA2G1B(1), PLA2G2E(3), PLA2G3(5), PLA2G4A(11), PLA2G5(2), PLA2G6(6), PLCB2(9), PLCG1(12), PLCG2(27), PPAP2A(4), PPAP2B(3) 16172413 282 62 278 93 74 108 44 21 31 4 0.71 0.87 508 GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM ACO1, ACO2, CS, GRHPR, HAO1, HAO2, HYI, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 12 ACO1(13), ACO2(8), CS(5), GRHPR(4), HAO1(2), HAO2(7), HYI(2), MDH1(2), MDH2(5), MTHFD1(6), MTHFD1L(12), MTHFD2(3) 4485313 69 33 68 28 24 26 9 5 5 0 0.72 0.87 509 NUCLEOTIDE_GPCRS ADORA1, ADORA2A, ADORA2B, ADORA3, GPR23, LTB4R, P2RY1, P2RY2, P2RY5, P2RY6 8 ADORA1(6), ADORA2A(5), ADORA2B(2), ADORA3(5), LTB4R(3), P2RY1(2), P2RY2(6), P2RY6(3) 2001147 32 21 32 14 9 9 10 4 0 0 0.72 0.87 510 HSA00340_HISTIDINE_METABOLISM Genes involved in histidine metabolism ABP1, ACY3, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH7A1, ALDH9A1, AMDHD1, AOC2, AOC3, ASPA, CARM1, CNDP1, DDC, FTCD, HAL, HARS, HARS2, HDC, HEMK1, HNMT, LCMT1, LCMT2, MAOA, MAOB, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, PRPS1, PRPS2, UROC1, WBSCR22 40 ABP1(12), ACY3(4), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH3B1(5), ALDH3B2(8), ALDH7A1(2), ALDH9A1(4), AMDHD1(9), AOC2(6), AOC3(14), ASPA(5), CARM1(6), CNDP1(6), DDC(11), HAL(6), HARS(4), HARS2(8), HDC(10), HEMK1(2), HNMT(5), LCMT1(4), LCMT2(13), MAOA(14), MAOB(7), METTL2B(3), METTL6(2), PRMT3(10), PRMT5(11), PRMT6(6), PRMT7(4), PRMT8(9), PRPS1(3), PRPS2(10), UROC1(14), WBSCR22(9) 13349823 263 53 257 73 72 99 37 15 36 4 0.72 0.87 511 HSA00510_N_GLYCAN_BIOSYNTHESIS Genes involved in N-glycan biosynthesis ALG1, ALG10, ALG10B, ALG11, ALG12, ALG13, ALG14, ALG2, ALG3, ALG5, ALG6, ALG8, ALG9, B4GALT1, B4GALT2, B4GALT3, DAD1, DDOST, DHDDS, DOLPP1, DPAGT1, DPM1, FUT8, GANAB, GCS1, MAN1A1, MAN1A2, MAN1B1, MAN1C1, MAN2A1, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT5, MGAT5B, RFT1, RPN1, RPN2, ST6GAL1, STT3B 41 ALG1(2), ALG10(9), ALG10B(8), ALG11(6), ALG12(1), ALG13(17), ALG14(2), ALG2(2), ALG3(5), ALG5(4), ALG6(5), ALG8(8), ALG9(6), B4GALT1(2), B4GALT2(5), B4GALT3(8), DAD1(1), DDOST(3), DHDDS(8), DOLPP1(1), DPAGT1(4), DPM1(2), FUT8(13), GANAB(13), MAN1A1(11), MAN1A2(9), MAN1B1(4), MAN1C1(7), MAN2A1(23), MGAT1(3), MGAT2(2), MGAT3(4), MGAT4A(4), MGAT4B(7), MGAT5(9), MGAT5B(7), RFT1(6), RPN1(6), RPN2(9), ST6GAL1(10), STT3B(6) 14360076 262 58 245 64 65 109 41 9 34 4 0.73 0.88 512 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(5) 259076 5 3 5 2 1 3 0 1 0 0 0.73 0.88 513 RANPATHWAY RanGEF (aka RCC1) and RanGFP regulate the GTP- or GDP-bound state of Ran, creating a Ran gradient across the nuclear membrane that is used in nuclear import. CHC1, RAN, RANBP1, RANBP2, RANGAP1 4 RAN(1), RANBP2(37), RANGAP1(5) 2882340 43 23 43 7 9 14 9 1 10 0 0.73 0.88 514 KERATAN_SULFATE_BIOSYNTHESIS B3GNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT5, FUT8, SIAT4A, SIAT4B, SIAT6, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 10 B3GNT1(7), B4GALT1(2), B4GALT2(5), B4GALT3(8), B4GALT5(2), FUT8(13), ST3GAL1(2), ST3GAL2(4), ST3GAL3(6), ST3GAL4(4) 2606056 53 25 48 17 15 25 9 0 4 0 0.73 0.88 515 PROTEASOMEPATHWAY Ubiquitinated proteins are targeted for proteolytic degradation by the proteasome, where they are unfolded and degraded to small peptides in an ATP-dependent process. PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMC3, PSMD14, RPN1, RPN2, UBE1, UBE2A, UBE3A 20 PSMA1(5), PSMA2(5), PSMA3(5), PSMA4(2), PSMA5(1), PSMA6(2), PSMB1(2), PSMB2(2), PSMB3(4), PSMB4(3), PSMB5(4), PSMB6(3), PSMB7(1), PSMC3(1), PSMD14(3), RPN1(6), RPN2(9), UBE2A(4), UBE3A(13) 4635883 75 30 71 24 14 32 11 3 15 0 0.74 0.88 516 HSA00860_PORPHYRIN_AND_CHLOROPHYLL_METABOLISM Genes involved in porphyrin and chlorophyll metabolism ALAD, ALAS1, ALAS2, BLVRA, BLVRB, COX10, COX15, CP, CPOX, EARS2, EPRS, FECH, FTH1, FTMT, GUSB, HCCS, HMBS, HMOX1, HMOX2, MMAB, PPOX, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, UROD, UROS 41 ALAD(3), ALAS1(12), ALAS2(11), BLVRA(2), BLVRB(1), COX10(5), COX15(4), CP(12), CPOX(8), EARS2(4), EPRS(11), FECH(5), FTH1(2), FTMT(7), GUSB(5), HCCS(2), HMBS(7), HMOX1(3), HMOX2(5), MMAB(2), UGT1A1(6), UGT1A10(8), UGT1A3(4), UGT1A4(4), UGT1A5(7), UGT1A6(5), UGT1A7(9), UGT1A8(4), UGT1A9(4), UGT2A1(9), UGT2A3(5), UGT2B10(14), UGT2B11(22), UGT2B15(9), UGT2B17(4), UGT2B28(14), UGT2B4(10), UGT2B7(10), UROD(2), UROS(3) 13992494 264 53 254 65 79 107 38 13 27 0 0.74 0.88 517 LYSINE_BIOSYNTHESIS AADAT, AASDH, AASDHPPT, AASS, KARS 5 AADAT(6), AASDH(11), AASDHPPT(4), AASS(6), KARS(7) 2455008 34 22 33 16 12 9 8 2 3 0 0.74 0.88 518 BETA_ALANINE_METABOLISM ABAT, ABP1, ACADL, ACADM, ACADSB, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, AOC2, AOC3, CNDP1, DPYD, DPYS, ECHS1, EHHADH, GAD1, GAD2, HADHA, MLYCD, SDS, SMS, UPB1 27 ABAT(9), ABP1(12), ACADL(7), ACADM(6), ACADSB(4), ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH9A1(4), AOC2(6), AOC3(14), CNDP1(6), DPYD(16), DPYS(3), ECHS1(3), EHHADH(9), GAD1(8), GAD2(12), HADHA(7), MLYCD(5), SDS(3), SMS(8), UPB1(9) 10047799 183 49 178 64 52 63 29 15 24 0 0.74 0.88 519 HSA00051_FRUCTOSE_AND_MANNOSE_METABOLISM Genes involved in fructose and mannose metabolism AKR1B1, AKR1B10, ALDOA, ALDOB, ALDOC, FBP1, FBP2, FPGT, FUK, GMDS, GMPPA, GMPPB, HK1, HK2, HK3, HSD3B7, KHK, LHPP, MPI, MTMR1, MTMR2, MTMR6, PFKFB1, PFKFB2, PFKFB3, PFKFB4, PFKL, PFKM, PFKP, PGM2, PHPT1, PMM1, PMM2, RDH11, RDH12, RDH13, RDH14, SORD, TPI1, TSTA3, UGCGL1, UGCGL2 39 AKR1B1(2), AKR1B10(4), ALDOA(6), ALDOB(9), ALDOC(4), FBP1(4), FPGT(5), FUK(8), GMDS(3), GMPPA(9), GMPPB(3), HK1(13), HK2(8), HK3(12), HSD3B7(3), KHK(1), LHPP(2), MPI(5), MTMR1(16), MTMR2(4), MTMR6(8), PFKFB1(9), PFKFB2(1), PFKFB3(7), PFKFB4(4), PFKM(7), PFKP(11), PGM2(6), PHPT1(2), PMM1(1), PMM2(6), RDH11(3), RDH12(6), RDH13(5), RDH14(3), SORD(3), TPI1(1), TSTA3(4) 12021700 208 55 202 71 56 86 25 14 25 2 0.74 0.88 520 HSA00030_PENTOSE_PHOSPHATE_PATHWAY Genes involved in pentose phosphate pathway ALDOA, ALDOB, ALDOC, DERA, FBP1, FBP2, G6PD, GPI, H6PD, PFKL, PFKM, PFKP, PGD, PGLS, PGM1, PGM3, PRPS1, PRPS1L1, PRPS2, RBKS, RPE, RPIA, TALDO1, TKT, TKTL1, TKTL2 25 ALDOA(6), ALDOB(9), ALDOC(4), DERA(9), FBP1(4), G6PD(3), GPI(9), H6PD(5), PFKM(7), PFKP(11), PGD(4), PGLS(1), PGM1(9), PGM3(6), PRPS1(3), PRPS1L1(5), PRPS2(10), RBKS(1), RPE(3), RPIA(7), TALDO1(6), TKT(7), TKTL1(10), TKTL2(12) 7865729 151 45 143 50 40 67 17 8 17 2 0.75 0.88 521 CACAMPATHWAY Calcium functions as a second messenger activating the calcium/calmodulin-dependent kinases, which phosphorylate targets such as CREB. CALM1, CALM2, CALM3, CAMK1, CAMK1G, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CAMKK1, CAMKK2, CREB1, SYT1 14 CALM2(3), CALM3(1), CAMK1(9), CAMK1G(5), CAMK2A(8), CAMK2B(2), CAMK2D(7), CAMK2G(8), CAMK4(5), CAMKK1(8), CAMKK2(6), CREB1(5), SYT1(4) 3825434 71 30 69 11 16 31 7 4 13 0 0.75 0.88 522 HSA00100_BIOSYNTHESIS_OF_STEROIDS Genes involved in biosynthesis of steroids CYP27B1, CYP51A1, DHCR24, DHCR7, EBP, FDFT1, FDPS, GGCX, GGPS1, HMGCR, HSD17B7, IDI1, IDI2, LSS, MVD, MVK, NQO1, NSDHL, PMVK, SC4MOL, SC5DL, SQLE, TM7SF2, VKORC1 24 CYP27B1(9), CYP51A1(4), DHCR24(6), DHCR7(4), FDFT1(3), FDPS(7), GGCX(10), GGPS1(2), HMGCR(15), HSD17B7(4), IDI1(4), IDI2(2), MVD(3), MVK(7), NQO1(3), NSDHL(9), PMVK(2), SC4MOL(3), SC5DL(3), SQLE(6), TM7SF2(3), VKORC1(3) 6305059 112 34 111 49 31 42 17 8 14 0 0.75 0.89 523 1_AND_2_METHYLNAPHTHALENE_DEGRADATION ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 7 ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH6(9), ADH7(6), ADHFE1(7) 2015487 42 21 41 7 11 15 10 0 6 0 0.75 0.89 524 N_GLYCAN_BIOSYNTHESIS ALG3, ALG5, B4GALT1, B4GALT2, B4GALT3, B4GALT5, DDOST, DPAGT1, DPM1, FUT8, GCS1, MAN1A1, MAN1B1, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT5, RPN1, RPN2, ST6GAL1 21 ALG3(5), ALG5(4), B4GALT1(2), B4GALT2(5), B4GALT3(8), B4GALT5(2), DDOST(3), DPAGT1(4), DPM1(2), FUT8(13), MAN1A1(11), MAN1B1(4), MGAT1(3), MGAT2(2), MGAT3(4), MGAT4A(4), MGAT4B(7), MGAT5(9), RPN1(6), RPN2(9), ST6GAL1(10) 6557682 117 37 109 31 36 46 20 2 13 0 0.76 0.89 525 HSA00900_TERPENOID_BIOSYNTHESIS Genes involved in terpenoid biosynthesis FDFT1, FDPS, GGPS1, IDI1, IDI2, SQLE 6 FDFT1(3), FDPS(7), GGPS1(2), IDI1(4), IDI2(2), SQLE(6) 1516694 24 16 24 10 6 8 5 3 2 0 0.76 0.89 526 HSA00010_GLYCOLYSIS_AND_GLUCONEOGENESIS Genes involved in glycolysis and gluconeogenesis ACSS1, ACSS2, ACYP1, ACYP2, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH7A1, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, G6PC2, GALM, GAPDH, GAPDHS, GCK, GPI, HK1, HK2, HK3, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKL, PFKM, PFKP, PGAM1, PGAM2, PGAM4, PGK1, PGK2, PGM1, PGM3, PKLR, PKM2, TPI1 62 ACSS1(4), ACSS2(11), ACYP1(2), ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH5(3), ADH6(9), ADH7(6), ADHFE1(7), AKR1A1(1), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH3B1(5), ALDH3B2(8), ALDH7A1(2), ALDH9A1(4), ALDOA(6), ALDOB(9), ALDOC(4), BPGM(2), DLAT(2), DLD(7), ENO1(5), ENO2(3), ENO3(4), FBP1(4), G6PC(6), G6PC2(9), GAPDH(2), GAPDHS(10), GCK(5), GPI(9), HK1(13), HK2(8), HK3(12), LDHA(6), LDHAL6A(8), LDHAL6B(2), LDHB(2), LDHC(3), PDHA1(4), PDHA2(10), PDHB(7), PFKM(7), PFKP(11), PGAM1(2), PGAM2(2), PGK1(6), PGK2(5), PGM1(9), PGM3(6), PKLR(10), PKM2(5), TPI1(1) 19211776 325 62 318 106 97 131 42 20 31 4 0.76 0.89 527 NITROGEN_METABOLISM AMT, ASNS, CA1, CA12, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA8, CA9, CPS1, CTH, GLS, GLS2, GLUD1, GLUL, HAL 21 AMT(5), ASNS(9), CA1(4), CA12(3), CA14(4), CA2(5), CA3(4), CA4(1), CA5A(5), CA5B(5), CA6(2), CA7(5), CA8(5), CA9(8), CPS1(24), CTH(5), GLS(10), GLS2(9), GLUD1(4), GLUL(6), HAL(6) 6613130 129 39 123 36 42 47 15 4 17 4 0.76 0.89 528 SALMONELLAPATHWAY Salmonella induces membrane ruffling in infected cells via bacterial proteins including SipA, SipC, and SopE, which alter actin structure. ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, RAC1, WASF1, WASL 12 ACTA1(4), ACTR2(7), ACTR3(3), ARPC1A(7), ARPC1B(3), ARPC2(2), ARPC3(2), CDC42(5), WASF1(3), WASL(8) 2884252 44 23 44 13 15 18 2 0 9 0 0.76 0.89 529 SA_MMP_CYTOKINE_CONNECTION Cytokines can induce activation of matrix metalloproteinases, which degrade extracellular matrix. ACE, CD44, CSF1, FCGR3A, IL1B, IL6R, SELL, SPN, TGFB1, TGFB2, TNF, TNFRSF1A, TNFRSF1B, TNFRSF8, TNFSF8 15 ACE(14), CD44(12), CSF1(5), FCGR3A(2), IL1B(2), IL6R(12), SELL(4), SPN(4), TGFB1(4), TGFB2(6), TNF(1), TNFRSF1A(6), TNFRSF1B(3), TNFRSF8(8), TNFSF8(1) 4599794 84 30 81 21 26 28 16 4 10 0 0.76 0.89 530 TSP1PATHWAY Thrombospondin-1 (TSP-1) inhibits angiogenesis by inducing caspase-dependent apoptosis in microvascular endothelial cells. CASP3, CD36, FOS, FYN, JUN, MAPK14, THBS1 7 CASP3(4), CD36(7), FOS(6), FYN(7), JUN(1), MAPK14(6), THBS1(12) 2603188 43 22 43 11 12 18 4 4 5 0 0.76 0.89 531 HSA00632_BENZOATE_DEGRADATION_VIA_COA_LIGATION Genes involved in benzoate degradation via CoA ligation ACAT1, ACAT2, ACOT11, ACYP1, ACYP2, ARD1A, CARKL, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ECHS1, EHHADH, ESCO1, ESCO2, FN3K, GCDH, HADHA, ITGB1BP3, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1, YOD1 24 ACAT1(6), ACAT2(5), ACOT11(6), ACYP1(2), DHRS1(4), DHRS2(3), DHRS3(2), DHRS7(9), DHRSX(4), ECHS1(3), EHHADH(9), ESCO1(11), ESCO2(6), GCDH(5), HADHA(7), ITGB1BP3(1), NAT6(2), PNPLA3(6), SH3GLB1(8), YOD1(2) 8986878 101 39 101 38 27 46 13 4 11 0 0.77 0.89 532 HSA00980_METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450 Genes involved in metabolism of xenobiotics by cytochrome P450 ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AKR1C1, AKR1C2, AKR1C3, AKR1C4, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, CYP1A1, CYP1A2, CYP1B1, CYP2B6, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2E1, CYP2F1, CYP2S1, CYP3A4, CYP3A43, CYP3A5, CYP3A7, DHDH, EPHX1, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, MGST1, MGST2, MGST3, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7 69 ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH5(3), ADH6(9), ADH7(6), ADHFE1(7), AKR1C1(5), AKR1C2(3), AKR1C3(3), AKR1C4(5), ALDH3A1(6), ALDH3B1(5), ALDH3B2(8), CYP1A1(9), CYP1A2(6), CYP1B1(3), CYP2B6(11), CYP2C18(5), CYP2C19(7), CYP2C8(4), CYP2C9(5), CYP2E1(5), CYP2F1(5), CYP2S1(8), CYP3A4(14), CYP3A43(5), CYP3A5(7), CYP3A7(9), DHDH(3), EPHX1(2), GSTA1(5), GSTA2(6), GSTA3(3), GSTA4(3), GSTA5(2), GSTK1(5), GSTM1(3), GSTM2(1), GSTM3(4), GSTM4(2), GSTM5(2), GSTO2(2), GSTP1(2), GSTZ1(4), MGST1(3), MGST3(1), UGT1A1(6), UGT1A10(8), UGT1A3(4), UGT1A4(4), UGT1A5(7), UGT1A6(5), UGT1A7(9), UGT1A8(4), UGT1A9(4), UGT2A1(9), UGT2A3(5), UGT2B10(14), UGT2B11(22), UGT2B15(9), UGT2B17(4), UGT2B28(14), UGT2B4(10), UGT2B7(10) 19472525 384 66 369 86 106 161 61 20 36 0 0.78 0.90 533 BILE_ACID_BIOSYNTHESIS ACAA1, ACAA2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1C4, AKR1D1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, BAAT, CEL, CYP27A1, CYP7A1, HADHB, SOAT2, SRD5A1, SRD5A2 27 ACAA1(5), ACAA2(2), ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH6(9), ADH7(6), ADHFE1(7), AKR1C4(5), AKR1D1(8), ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH9A1(4), BAAT(7), CEL(6), CYP27A1(8), CYP7A1(12), HADHB(5), SOAT2(8), SRD5A1(4), SRD5A2(4) 8060036 152 42 147 43 47 55 25 8 17 0 0.78 0.90 534 HSA00720_REDUCTIVE_CARBOXYLATE_CYCLE Genes involved in reductive carboxylate cycle (CO2 fixation) ACLY, ACO1, ACO2, ACSS1, ACSS2, FH, IDH1, IDH2, LOC441996, MDH1, MDH2, SUCLA2 11 ACLY(9), ACO1(13), ACO2(8), ACSS1(4), ACSS2(11), FH(11), IDH1(4), IDH2(7), MDH1(2), MDH2(5), SUCLA2(5) 4691092 79 32 78 36 22 35 6 7 7 2 0.79 0.91 535 FATTY_ACID_BIOSYNTHESIS_PATH_2 ACAA1, ACAA2, ACAT1, ACAT2, ECHS1, EHHADH, HADHA, HADHB, SDS 9 ACAA1(5), ACAA2(2), ACAT1(6), ACAT2(5), ECHS1(3), EHHADH(9), HADHA(7), HADHB(5), SDS(3) 2850075 45 22 45 13 10 20 8 5 2 0 0.79 0.91 536 BOTULINPATHWAY Blockade of Neurotransmitter Relase by Botulinum Toxin CHRM1, CHRNA1, SNAP25, STX1A, VAMP2 5 CHRM1(6), CHRNA1(6), SNAP25(7), STX1A(2) 1149112 21 17 20 7 8 7 4 1 1 0 0.79 0.91 537 BETAOXIDATIONPATHWAY Beta-Oxidation of Fatty Acids ACADL, ACADM, ACADS, ACAT1, ECHS1, HADHA 6 ACADL(7), ACADM(6), ACADS(5), ACAT1(6), ECHS1(3), HADHA(7) 1813293 34 18 33 14 3 20 5 3 3 0 0.80 0.91 538 HSA00062_FATTY_ACID_ELONGATION_IN_MITOCHONDRIA Genes involved in fatty acid elongation in mitochondria ACAA2, ECHS1, HADH, HADHA, HADHB, HSD17B10, HSD17B4, MECR, PPT1, PPT2 10 ACAA2(2), ECHS1(3), HADH(1), HADHA(7), HADHB(5), HSD17B10(4), HSD17B4(10), MECR(6), PPT1(6), PPT2(3) 2893812 47 23 45 11 6 24 7 6 4 0 0.80 0.91 539 HSA04614_RENIN_ANGIOTENSIN_SYSTEM Genes involved in renin-angiotensin system ACE, ACE2, AGT, AGTR1, AGTR2, ANPEP, CMA1, CPA3, CTSA, CTSG, ENPEP, LNPEP, MAS1, MME, NLN, REN, THOP1 16 ACE(14), ACE2(19), AGT(7), AGTR2(8), ANPEP(13), CMA1(1), CPA3(5), CTSA(7), CTSG(3), ENPEP(13), LNPEP(9), MAS1(2), MME(8), NLN(4), REN(3) 7026122 116 38 112 47 36 38 18 6 14 4 0.80 0.91 540 ERYTHPATHWAY Erythropoietin selectively stimulates erythrocyte differentiation from CFU-GEMM cells in bone marrow. CCL3, CSF2, CSF3, EPO, FLT3, IGF1, IL11, IL1A, IL3, IL6, IL9, KITLG, TGFB1, TGFB2, TGFB3 14 CCL3(1), CSF3(1), EPO(2), FLT3(9), IGF1(3), IL1A(1), IL6(2), KITLG(2), TGFB1(4), TGFB2(6), TGFB3(9) 2884730 40 22 40 13 10 18 4 1 7 0 0.80 0.91 541 HSA00620_PYRUVATE_METABOLISM Genes involved in pyruvate metabolism ACACA, ACACB, ACAT1, ACAT2, ACOT12, ACSS1, ACSS2, ACYP1, ACYP2, AKR1B1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, DLAT, DLD, GLO1, GRHPR, HAGH, HAGHL, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, LDHD, MDH1, MDH2, ME1, ME2, ME3, PC, PCK1, PCK2, PDHA1, PDHA2, PDHB, PKLR, PKM2 41 ACACA(27), ACACB(31), ACAT1(6), ACAT2(5), ACOT12(10), ACSS1(4), ACSS2(11), ACYP1(2), AKR1B1(2), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH7A1(2), ALDH9A1(4), DLAT(2), DLD(7), GRHPR(4), HAGH(2), LDHA(6), LDHAL6A(8), LDHAL6B(2), LDHB(2), LDHC(3), LDHD(3), MDH1(2), MDH2(5), ME1(10), ME2(7), ME3(7), PC(8), PCK1(15), PCK2(7), PDHA1(4), PDHA2(10), PDHB(7), PKLR(10), PKM2(5) 15880833 257 60 249 91 70 107 30 11 35 4 0.81 0.91 542 IL12PATHWAY IL12 and Stat4 Dependent Signaling Pathway in Th1 Development CCR5, CD3D, CD3E, CD3G, CD3Z, CXCR3, ETV5, IFNG, IL12A, IL12B, IL12RB1, IL12RB2, IL18, IL18R1, JAK2, JUN, MAP2K6, MAPK14, MAPK8, STAT4, TRA@, TRB@, TYK2 19 CD3D(3), CD3E(2), CD3G(2), CXCR3(5), ETV5(10), IFNG(5), IL12A(7), IL12B(3), IL12RB1(16), IL12RB2(11), IL18(1), IL18R1(5), JAK2(21), JUN(1), MAP2K6(9), MAPK14(6), MAPK8(7), STAT4(9), TYK2(7) 6381539 130 36 127 25 26 50 17 14 17 6 0.81 0.91 543 EICOSANOID_SYNTHESIS ALOX12, ALOX15, ALOX15B, ALOX5, ALOX5AP, DPEP1, GGT1, IPLA2(GAMMA), LTA4H, LTC4S, PLA2G2A, PLA2G6, PTGDS, PTGES, PTGIS, PTGS1, PTGS2, TBXAS1 15 ALOX12(6), ALOX15(12), ALOX15B(12), ALOX5(7), ALOX5AP(4), GGT1(10), LTA4H(6), PLA2G6(6), PTGDS(6), PTGES(2), PTGIS(8), PTGS1(8), PTGS2(7), TBXAS1(6) 4640424 100 32 98 26 27 47 13 3 10 0 0.81 0.91 544 HSA00903_LIMONENE_AND_PINENE_DEGRADATION Genes involved in limonene and pinene degradation ACOT11, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, ARD1A, CYP2C19, CYP2C9, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ECHS1, EHHADH, ESCO1, ESCO2, HADHA, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1, YOD1 26 ACOT11(6), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH7A1(2), ALDH9A1(4), CYP2C19(7), CYP2C9(5), DHRS1(4), DHRS2(3), DHRS3(2), DHRS7(9), DHRSX(4), ECHS1(3), EHHADH(9), ESCO1(11), ESCO2(6), HADHA(7), NAT6(2), PNPLA3(6), SH3GLB1(8), YOD1(2) 10656293 117 40 116 47 40 48 11 6 12 0 0.81 0.91 545 PENTOSE_AND_GLUCURONATE_INTERCONVERSIONS AKR1B1, DCXR, GUSB, RPE, RPE, LOC440001, UCHL1, UCHL3, UGDH, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4 18 AKR1B1(2), GUSB(5), RPE(3), UCHL1(5), UCHL3(1), UGDH(3), UGT1A1(6), UGT1A10(8), UGT1A3(4), UGT1A4(4), UGT1A5(7), UGT1A6(5), UGT1A7(9), UGT1A8(4), UGT1A9(4), UGT2B15(9), UGT2B4(10) 5675055 89 33 85 16 31 32 12 5 9 0 0.82 0.92 546 HSA04140_REGULATION_OF_AUTOPHAGY Genes involved in regulation of autophagy ATG12, ATG3, ATG5, ATG7, BECN1, GABARAP, GABARAPL1, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNG, INS, LOC441925, PIK3C3, PIK3R4, PRKAA1, PRKAA2, ULK1, ULK2, ULK3 27 ATG12(1), ATG3(4), ATG5(3), ATG7(6), GABARAP(2), GABARAPL1(2), IFNA10(2), IFNA13(3), IFNA14(3), IFNA16(2), IFNA17(2), IFNA2(1), IFNA21(2), IFNA4(3), IFNA5(2), IFNA6(6), IFNA7(2), IFNA8(2), IFNG(5), PIK3C3(11), PIK3R4(25), PRKAA1(6), PRKAA2(9), ULK2(10), ULK3(5) 6746014 119 37 118 37 32 49 19 7 12 0 0.82 0.92 547 HSA00750_VITAMIN_B6_METABOLISM Genes involved in vitamin B6 metabolism AOX1, PDXK, PDXP, PNPO, PSAT1 5 AOX1(19), PDXK(3), PDXP(1), PNPO(4), PSAT1(5) 1614923 32 18 32 11 10 12 5 1 4 0 0.82 0.93 548 HSA03022_BASAL_TRANSCRIPTION_FACTORS Genes involved in basal transcription factors GTF2A1, GTF2A1L, GTF2A2, GTF2B, GTF2E1, GTF2E2, GTF2F1, GTF2F2, GTF2H1, GTF2H2, GTF2H3, GTF2H4, GTF2I, GTF2IRD1, LOC391764, STON1, TAF1, TAF10, TAF12, TAF13, TAF1L, TAF2, TAF4, TAF4B, TAF5, TAF5L, TAF6, TAF6L, TAF7, TAF7L, TAF9, TAF9B, TBPL1, TBPL2 31 GTF2A1(5), GTF2A1L(2), GTF2B(5), GTF2E1(4), GTF2E2(5), GTF2F1(6), GTF2F2(1), GTF2H1(8), GTF2H2(3), GTF2H3(3), GTF2H4(2), GTF2I(5), GTF2IRD1(15), STON1(2), TAF1(40), TAF10(1), TAF12(1), TAF1L(41), TAF2(17), TAF4(7), TAF4B(11), TAF5(6), TAF5L(4), TAF6(8), TAF6L(8), TAF7(3), TAF7L(10), TAF9(2), TBPL1(4), TBPL2(4) 12706674 233 48 229 66 58 101 34 11 27 2 0.83 0.93 549 HSA00120_BILE_ACID_BIOSYNTHESIS Genes involved in bile acid biosynthesis ACAA1, ACAA2, ACAD8, ACAD9, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AKR1B10, AKR1C4, AKR1D1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, BAAT, CEL, CYP27A1, CYP7A1, HADHB, HSD3B7, LIPA, RDH11, RDH12, RDH13, RDH14, SLC27A5, SOAT1, SOAT2, SRD5A1, SRD5A2 38 ACAA1(5), ACAA2(2), ACAD8(7), ACAD9(10), ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH5(3), ADH6(9), ADH7(6), ADHFE1(7), AKR1B10(4), AKR1C4(5), AKR1D1(8), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH7A1(2), ALDH9A1(4), BAAT(7), CEL(6), CYP27A1(8), CYP7A1(12), HADHB(5), HSD3B7(3), LIPA(6), RDH11(3), RDH12(6), RDH13(5), RDH14(3), SLC27A5(6), SOAT1(10), SOAT2(8), SRD5A1(4), SRD5A2(4) 10858009 205 48 200 50 60 80 31 10 22 2 0.83 0.93 550 NICOTINATE_AND_NICOTINAMIDE_METABOLISM AOX1, CD38, ENPP1, ENPP3, NADSYN1, NMNAT1, NMNAT2, NNMT, NNT, NP, NT5C, NT5E, NT5M, QPRT 13 AOX1(19), CD38(7), ENPP1(11), ENPP3(16), NADSYN1(12), NMNAT1(4), NMNAT2(2), NNMT(7), NNT(9), NT5C(1), NT5E(6), NT5M(4) 5019239 98 34 94 20 22 43 20 7 6 0 0.83 0.93 551 FRUCTOSE_AND_MANNOSE_METABOLISM AKR1B1, ALDOA, ALDOB, ALDOC, FBP1, FBP2, FPGT, GCK, GMDS, GMPPA, GMPPB, HK1, HK2, HK3, KHK, MPI, PFKFB1, PFKFB3, PFKFB4, PFKM, PFKP, PMM1, PMM2, SORD, TPI1 25 AKR1B1(2), ALDOA(6), ALDOB(9), ALDOC(4), FBP1(4), FPGT(5), GCK(5), GMDS(3), GMPPA(9), GMPPB(3), HK1(13), HK2(8), HK3(12), KHK(1), MPI(5), PFKFB1(9), PFKFB3(7), PFKFB4(4), PFKM(7), PFKP(11), PMM1(1), PMM2(6), SORD(3), TPI1(1) 8193876 138 43 135 46 39 60 14 11 12 2 0.83 0.93 552 CIRCADIAN_EXERCISE ARNTL, AZIN1, BTG1, C10orf110, C1orf1, CBX3, CEBPB, CLDN5, CLOCK, CRY1, CRY2, DAZAP2, DAZAP2, LOC401029, DNAJA1, EIF4G2, ETV6, G0S2, GENX_3414, GFRA1, GSTM3, GSTP1, HERPUD1, HLA_DMA, HSPA8, IDI1, KLF9, MAP3K7IP2, MYF6, NCKAP1, NCOA4, NR1D2, OAZIN, PER1, PER2, PIGF, PPP1R3C, PPP2CB, PSMA4, PURA, SF3A3, SUMO3, TOB1, TUBB3, UCP3, UGP2, VAPA, ZFR 37 ARNTL(12), AZIN1(3), CBX3(5), CLOCK(11), CRY1(6), CRY2(4), DAZAP2(2), DNAJA1(1), EIF4G2(8), ETV6(9), GFRA1(6), GSTM3(4), GSTP1(2), HERPUD1(1), HSPA8(10), IDI1(4), KLF9(3), MYF6(8), NCKAP1(10), NCOA4(12), NR1D2(5), PER1(15), PER2(8), PIGF(4), PPP1R3C(3), PPP2CB(2), PSMA4(2), SF3A3(6), SUMO3(3), TOB1(2), UCP3(1), UGP2(8), VAPA(5), ZFR(13) 12390477 198 49 193 60 49 84 26 10 26 3 0.84 0.94 553 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(7), CYP2C9(5) 721302 12 8 12 4 5 6 0 0 1 0 0.84 0.94 554 ARGININE_AND_PROLINE_METABOLISM ABP1, AGMAT, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH4A1, ALDH9A1, AMD1, AOC2, AOC3, ARG1, ARG2, ASL, ASS, CKB, CKM, CKMT1, CKMT1B, CKMT1A, CKMT2, CPS1, DAO, GAMT, GATM, GLUD1, GOT1, GOT2, MAOA, MAOB, NOS1, NOS2A, NOS3, OAT, ODC1, OTC, P4HA1, P4HA2, P4HA3, P4HB, PYCR1, RARS, SAT, SMS 40 ABP1(12), AGMAT(3), ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH4A1(2), ALDH9A1(4), AMD1(3), AOC2(6), AOC3(14), ARG1(5), ARG2(6), ASL(4), CKM(3), CKMT1A(5), CKMT1B(2), CKMT2(5), CPS1(24), DAO(5), GATM(8), GLUD1(4), GOT1(6), GOT2(5), MAOA(14), MAOB(7), NOS1(21), NOS3(11), OAT(7), ODC1(3), OTC(8), P4HA1(8), P4HA2(10), P4HA3(5), P4HB(1), RARS(11), SMS(8) 14375611 272 54 264 88 70 117 35 17 29 4 0.85 0.94 555 HSA00600_SPHINGOLIPID_METABOLISM Genes involved in sphingolipid metabolism ARSA, ARSD, ARSE, ASAH1, ASAH3L, B4GALT6, CERK, DEGS1, DEGS2, ENPP7, FVT1, GAL3ST1, GALC, GBA, GLA, GLB1, LCT, NEU1, NEU2, NEU3, NEU4, PHCA, PPAP2A, PPAP2B, PPAP2C, SGMS1, SGMS2, SGPP1, SGPP2, SMPD1, SMPD2, SMPD3, SMPD4, SPHK1, SPHK2, SPTLC1, SPTLC2, UGCG, UGT8 33 ARSD(9), ARSE(7), ASAH1(9), B4GALT6(5), CERK(8), DEGS1(5), DEGS2(4), ENPP7(3), GAL3ST1(13), GALC(7), GBA(4), GLA(3), GLB1(9), LCT(30), NEU2(5), NEU3(3), PPAP2A(4), PPAP2B(3), SGMS1(3), SGMS2(6), SGPP1(2), SGPP2(3), SMPD1(12), SMPD2(5), SMPD3(6), SMPD4(16), SPHK1(2), SPHK2(1), SPTLC1(6), SPTLC2(6), UGCG(5), UGT8(12) 11178269 216 50 213 62 70 88 18 12 28 0 0.85 0.94 556 MCALPAINPATHWAY In integrin-mediated cell migration, calpains digest links between the actin cytoskeleton and focal adhesion proteins. ACTA1, CAPN1, CAPN2, CAPNS1, CAPNS2, CXCR3, EGF, EGFR, HRAS, ITGA1, ITGB1, MAPK1, MAPK3, MYL2, MYLK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTK2, PXN, TLN1, VIL2 24 ACTA1(4), CAPN1(4), CAPN2(6), CAPNS1(3), CAPNS2(6), CXCR3(5), EGF(24), EGFR(20), ITGA1(20), ITGB1(12), MAPK1(2), MAPK3(4), MYL2(1), MYLK(17), PRKACB(2), PRKACG(6), PRKAR1A(4), PRKAR1B(8), PRKAR2A(4), PRKAR2B(5), PTK2(11), PXN(6), TLN1(28) 11430892 202 47 195 63 56 84 23 7 30 2 0.85 0.94 557 HSA00791_ATRAZINE_DEGRADATION Genes involved in atrazine degradation ADAR, APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3F, APOBEC3G, APOBEC4 9 ADAR(6), APOBEC1(7), APOBEC2(5), APOBEC3A(2), APOBEC3B(8), APOBEC3C(5), APOBEC3F(6), APOBEC3G(4), APOBEC4(4) 2589565 47 24 47 18 12 22 9 1 1 2 0.85 0.95 558 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALE(2), GALT(2), TGDS(3), UGDH(3), UXS1(5) 1422050 15 13 15 9 5 4 4 1 1 0 0.86 0.95 559 MEF2DPATHWAY Mef2 transcription factors promote calcium-induced apoptosis in T cells and are regulated by MAP kinases and histone deacetylases. CABIN1, CALM1, CALM2, CALM3, CAPN2, CAPNS1, CAPNS2, EP300, HDAC1, HDAC2, MEF2D, NFATC1, NFATC2, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, SYT1, TRA@, TRB@ 18 CABIN1(15), CALM2(3), CALM3(1), CAPN2(6), CAPNS1(3), CAPNS2(6), EP300(29), HDAC1(4), HDAC2(5), MEF2D(7), NFATC2(15), PPP3CA(4), PPP3CB(7), PPP3CC(6), PRKCA(10), SYT1(4) 8113333 125 37 123 44 29 45 20 7 22 2 0.86 0.95 560 HSA00626_NAPHTHALENE_AND_ANTHRACENE_DEGRADATION Genes involved in naphthalene and anthracene degradation CARM1, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, HEMK1, LCMT1, LCMT2, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, WBSCR22 18 CARM1(6), DHRS1(4), DHRS2(3), DHRS3(2), DHRS7(9), DHRSX(4), HEMK1(2), LCMT1(4), LCMT2(13), METTL2B(3), METTL6(2), PRMT3(10), PRMT5(11), PRMT6(6), PRMT7(4), PRMT8(9), WBSCR22(9) 5012547 101 30 99 23 27 41 10 5 14 4 0.87 0.96 561 REELINPATHWAY Reelin is secreted by neurons and recognized by receptors including cadherin related neuronal receptors, which promote phosphorylation of Dab1. CDK5, CDK5R1, DAB1, FYN, LRP8, RELN, VLDLR 7 CDK5(1), CDK5R1(5), DAB1(7), FYN(7), LRP8(3), RELN(48), VLDLR(6) 4995100 77 31 75 35 22 27 16 3 7 2 0.87 0.96 562 ACETAMINOPHENPATHWAY Acetaminophen selectively inhibits Cox-3, which is localized to the brain, and yields the toxic metabolite NAPQI when processed by CAR in the liver. CYP1A2, CYP2E1, CYP3A, NR1I3, PTGS1, PTGS2 5 CYP1A2(6), CYP2E1(5), NR1I3(7), PTGS1(8), PTGS2(7) 1873760 33 18 32 8 9 12 3 2 7 0 0.88 0.96 563 PENTOSE_PHOSPHATE_PATHWAY ALDOA, ALDOB, ALDOC, FBP1, FBP2, G6PD, GPI, H6PD, PFKM, PFKP, PGD, PGLS, PGM1, PGM3, PRPS1, PRPS1L1, PRPS2, RBKS, RPE, RPE, LOC440001, RPIA, TAL1, TALDO1, TALDO1, HSUP1, TKT 23 ALDOA(6), ALDOB(9), ALDOC(4), FBP1(4), G6PD(3), GPI(9), H6PD(5), PFKM(7), PFKP(11), PGD(4), PGLS(1), PGM1(9), PGM3(6), PRPS1(3), PRPS1L1(5), PRPS2(10), RBKS(1), RPE(3), RPIA(7), TAL1(1), TALDO1(6), TKT(7) 6914987 121 38 116 42 34 53 15 7 10 2 0.88 0.96 564 HSA00440_AMINOPHOSPHONATE_METABOLISM Genes involved in aminophosphonate metabolism CARM1, CHPT1, HEMK1, LCMT1, LCMT2, METTL2B, METTL6, PCYT1A, PCYT1B, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, WBSCR22 16 CARM1(6), HEMK1(2), LCMT1(4), LCMT2(13), METTL2B(3), METTL6(2), PCYT1A(7), PCYT1B(4), PRMT3(10), PRMT5(11), PRMT6(6), PRMT7(4), PRMT8(9), WBSCR22(9) 4773069 90 29 88 21 24 36 10 5 11 4 0.88 0.96 565 CDK5PATHWAY Cdk5, a regulatory kinase implicated in neuronal development, represses Mek1, which downregulates the MAP kinase pathway. CDK5, CDK5R1, DPM2, EGR1, HRAS, KLK2, MAP2K1, MAP2K2, MAPK1, MAPK3, NGFB, NGFR, RAF1 11 CDK5(1), CDK5R1(5), DPM2(4), EGR1(8), KLK2(2), MAP2K1(2), MAPK1(2), MAPK3(4), NGFR(4), RAF1(7) 2632824 39 23 39 16 12 15 6 3 3 0 0.88 0.96 566 GLYCOSAMINOGLYCAN_DEGRADATION ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, IDS, IDUA, LCT, NAGLU 10 ARSB(6), GLB1(9), GNS(2), GUSB(5), HEXA(3), HEXB(4), IDS(6), LCT(30), NAGLU(3) 4640424 68 31 68 29 20 30 8 5 5 0 0.88 0.96 567 HSA05110_CHOLERA_INFECTION Genes involved in cholera - infection ACTG1, ACTG2, ADCY3, ADCY9, AK1, ARF1, ARF3, ARF4, ARF5, ARF6, ARL4D, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E1, ATP6V1A, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ERO1L, GNAS, PDIA4, PLCG1, PLCG2, PRKCA, SEC61A1, SEC61A2, SEC61B, SEC61G, TRIM23 41 ACTG2(1), ADCY3(8), ADCY9(25), AK1(2), ARF1(4), ARF3(2), ARF4(3), ARF5(5), ARF6(2), ARL4D(1), ATP6V0A1(5), ATP6V0A2(11), ATP6V0A4(14), ATP6V0B(2), ATP6V0C(2), ATP6V0D1(3), ATP6V0D2(10), ATP6V1A(7), ATP6V1C1(3), ATP6V1C2(9), ATP6V1D(4), ATP6V1E1(3), ATP6V1E2(4), ATP6V1F(2), ATP6V1G1(1), ATP6V1G2(4), ATP6V1G3(2), ATP6V1H(5), ERO1L(6), GNAS(25), PDIA4(4), PLCG1(12), PLCG2(27), PRKCA(10), SEC61A1(3), SEC61A2(6), SEC61B(1), SEC61G(3), TRIM23(12) 12614420 253 53 247 72 73 112 24 11 31 2 0.88 0.96 568 ETCPATHWAY Energy is extracted from carbohydrates via oxidation and transferred to the mitochondrial electron transport chain, which couples ATP synthesis to the reduction of oxygen to water. ATP5A1, CYCS, GPD2, MTCO1, NDUFA1, SDHA, SDHB, SDHC, SDHD, UQCRC1 9 ATP5A1(11), CYCS(3), GPD2(5), NDUFA1(1), SDHA(12), SDHB(1), SDHC(6), SDHD(1), UQCRC1(6) 2329533 46 20 46 9 10 24 6 3 3 0 0.89 0.96 569 EOSINOPHILSPATHWAY Recruitment of eosinophils in the inflammatory response observed in asthma occurs via the chemoattractant eotaxin binding to the CCR3 receptor. CCL11, CCL5, CCR3, CSF2, HLA-DRA, HLA-DRB1, IL3, IL5 8 CCL5(4), CCR3(5), HLA-DRB1(1), IL5(2) 1083387 12 9 12 2 2 4 2 0 4 0 0.89 0.96 570 HSA00920_SULFUR_METABOLISM Genes involved in sulfur metabolism BPNT1, CHST11, CHST12, CHST13, PAPSS1, PAPSS2, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SULT2B1, SUOX 11 BPNT1(1), CHST11(9), CHST12(5), PAPSS1(6), PAPSS2(6), SULT1A1(8), SULT1A2(2), SULT1E1(13), SULT2A1(7), SULT2B1(4), SUOX(4) 3175354 65 26 61 26 19 32 8 2 4 0 0.90 0.97 571 HSA00780_BIOTIN_METABOLISM Genes involved in biotin metabolism BTD, HLCS, SPCS1, SPCS3 4 BTD(8), HLCS(5), SPCS1(1), SPCS3(3) 1059965 17 11 17 13 6 5 4 0 2 0 0.90 0.97 572 HSA00290_VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS Genes involved in valine, leucine and isoleucine biosynthesis BCAT1, BCAT2, IARS, IARS2, ILVBL, LARS, LARS2, PDHA1, PDHA2, PDHB, VARS, VARS2 12 BCAT1(9), BCAT2(6), IARS(13), IARS2(21), ILVBL(7), LARS(23), LARS2(9), PDHA1(4), PDHA2(10), PDHB(7), VARS(8), VARS2(5) 6538801 122 34 121 25 31 55 15 6 15 0 0.91 0.97 573 CDMACPATHWAY Cadmium 2+ promotes cell proliferation in cultured macrophages by entering the cell via calcium channels and activating the MAP kinase pathway. CUZD1, FOS, HRAS, JUN, MAP2K1, MAPK1, MAPK3, MYC, NFKB1, NFKBIA, PLCB1, PRKCA, PRKCB1, RAF1, RELA, TNF 15 CUZD1(6), FOS(6), JUN(1), MAP2K1(2), MAPK1(2), MAPK3(4), MYC(7), NFKB1(12), NFKBIA(3), PLCB1(6), PRKCA(10), RAF1(7), RELA(6), TNF(1) 5383714 73 31 73 20 12 27 18 9 7 0 0.91 0.97 574 CALCINEURINPATHWAY Increased intracellular calcium activates the phosphatase calcineurin in differentiating keratinocytes. CALM1, CALM2, CALM3, CDKN1A, GNAQ, MARCKS, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, SP1, SP3, SYT1 17 CALM2(3), CALM3(1), CDKN1A(1), NFATC2(15), NFATC3(12), NFATC4(8), PLCG1(12), PPP3CA(4), PPP3CB(7), PPP3CC(6), PRKCA(10), SP1(6), SP3(12), SYT1(4) 6970913 101 36 97 42 30 36 16 5 14 0 0.91 0.97 575 FOLATE_BIOSYNTHESIS ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, DHFR, FPGS, GCH1, GGH, SPR 9 ALPI(3), ALPL(3), ALPP(4), ALPPL2(5), DHFR(3), FPGS(3), GCH1(2), GGH(3), SPR(2) 2019311 28 19 28 10 8 15 2 3 0 0 0.91 0.97 576 INOSITOL_METABOLISM ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 5 ALDH6A1(5), ALDOA(6), ALDOB(9), ALDOC(4), TPI1(1) 1383093 25 14 24 6 7 9 3 2 2 2 0.91 0.97 577 PYRUVATE_METABOLISM ACACA, ACAS2, ACAS2L, ACAT1, ACAT2, ACYP1, ACYP2, ADH5, AKR1B1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, CACH_1, DLAT, DLD, GLO1, GRHPR, HAGH, HAGHL, LDHA, LDHB, LDHC, LDHD, MDH1, MDH2, ME1, ME2, ME3, PC, PCK1, PDHA1, PDHA2, PDHB, PKLR, PKM2 36 ACACA(27), ACAT1(6), ACAT2(5), ACYP1(2), ADH5(3), AKR1B1(2), ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH9A1(4), DLAT(2), DLD(7), GRHPR(4), HAGH(2), LDHA(6), LDHB(2), LDHC(3), LDHD(3), MDH1(2), MDH2(5), ME1(10), ME2(7), ME3(7), PC(8), PCK1(15), PDHA1(4), PDHA2(10), PDHB(7), PKLR(10), PKM2(5) 12406490 200 51 197 71 52 82 25 10 31 0 0.92 0.97 578 MALATEXPATHWAY The tricarboxylate transfer pathway shuttles acetyl groups of acetyl-CoA between mitochondria and the cytoplasm. ACLY, CS, MDH1, ME1, PC, PDHA1, SLC25A1, SLC25A11 8 ACLY(9), CS(5), MDH1(2), ME1(10), PC(8), PDHA1(4), SLC25A1(2), SLC25A11(2) 3162448 42 22 42 27 7 21 6 3 5 0 0.92 0.97 579 PROTEASOME PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB10, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMB8, PSMB9 17 PSMA1(5), PSMA2(5), PSMA3(5), PSMA4(2), PSMA5(1), PSMA6(2), PSMB1(2), PSMB10(3), PSMB2(2), PSMB3(4), PSMB4(3), PSMB5(4), PSMB6(3), PSMB7(1), PSMB8(3), PSMB9(1) 3051313 46 22 43 12 9 20 7 2 8 0 0.92 0.97 580 STEROID_BIOSYNTHESIS CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 9 CYP17A1(3), F13B(13), HSD17B1(3), HSD17B2(3), HSD17B3(6), HSD17B4(10), HSD17B7(4), HSD3B1(1), HSD3B2(5) 2838125 48 23 45 20 13 23 5 1 6 0 0.92 0.97 581 HSA04130_SNARE_INTERACTIONS_IN_VESICULAR_TRANSPORT Genes involved in SNARE interactions in vesicular transport BET1, BET1L, BNIP1, C1orf142, GOSR1, GOSR2, SEC22B, SNAP23, SNAP25, SNAP29, STX10, STX11, STX12, STX16, STX17, STX18, STX19, STX2, STX3, STX4, STX5, STX6, STX7, STX8, TSNARE1, USE1, VAMP1, VAMP2, VAMP3, VAMP4, VAMP5, VAMP7, VAMP8, VTI1A, VTI1B, YKT6 35 BET1(2), BNIP1(7), GOSR1(1), SEC22B(1), SNAP23(2), SNAP25(7), SNAP29(2), STX10(1), STX11(3), STX12(3), STX16(1), STX17(3), STX18(2), STX3(8), STX4(6), STX5(6), STX6(4), STX7(4), STX8(4), TSNARE1(5), USE1(4), VAMP1(1), VAMP4(2), VAMP8(1), VTI1B(9), YKT6(6) 5730264 95 33 92 31 26 40 13 3 11 2 0.92 0.97 582 HSA00760_NICOTINATE_AND_NICOTINAMIDE_METABOLISM Genes involved in nicotinate and nicotinamide metabolism AOX1, BST1, C9orf95, CD38, ENPP1, ENPP3, NADK, NADSYN1, NMNAT1, NMNAT2, NMNAT3, NNMT, NNT, NP, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT12, PBEF1, QPRT 22 AOX1(19), BST1(5), CD38(7), ENPP1(11), ENPP3(16), NADK(4), NADSYN1(12), NMNAT1(4), NMNAT2(2), NMNAT3(2), NNMT(7), NNT(9), NT5C(1), NT5C1A(2), NT5C1B(10), NT5C2(7), NT5C3(8), NT5E(6), NT5M(4), NUDT12(2) 7422623 138 39 132 36 35 54 31 12 6 0 0.93 0.97 583 BENZOATE_DEGRADATION_VIA_COA_LIGATION ACAT1, ACAT2, ACYP1, ACYP2, ECHS1, EHHADH, GCDH, HADHA, SDHB, SDS 10 ACAT1(6), ACAT2(5), ACYP1(2), ECHS1(3), EHHADH(9), GCDH(5), HADHA(7), SDHB(1), SDS(3) 2646208 41 21 41 15 9 20 6 4 2 0 0.93 0.97 584 HSA00561_GLYCEROLIPID_METABOLISM Genes involved in glycerolipid metabolism ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AGK, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, AKR1A1, AKR1B1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, CEL, DAK, DGAT1, DGAT2, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKI, DGKQ, DGKZ, GK, GK2, GLA, GLB1, GPAM, LCT, LIPA, LIPC, LIPF, LIPG, LPL, LYCAT, MGLL, PNLIP, PNLIPRP1, PNLIPRP2, PNPLA3, PPAP2A, PPAP2B, PPAP2C, UGCGL1, UGCGL2 52 ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH5(3), ADH6(9), ADH7(6), ADHFE1(7), AGK(4), AGPAT1(2), AGPAT2(1), AGPAT3(6), AGPAT4(4), AGPAT6(8), AKR1A1(1), AKR1B1(2), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH7A1(2), ALDH9A1(4), CEL(6), DAK(8), DGAT2(4), DGKA(15), DGKB(17), DGKD(21), DGKE(4), DGKG(13), DGKH(11), DGKI(21), DGKZ(9), GK(14), GK2(20), GLA(3), GLB1(9), GPAM(7), LCT(30), LIPA(6), LIPC(8), LIPF(7), LIPG(6), LPL(11), MGLL(6), PNLIP(3), PNLIPRP1(4), PNLIPRP2(8), PNPLA3(6), PPAP2A(4), PPAP2B(3) 19553307 380 62 370 108 106 157 58 23 34 2 0.93 0.97 585 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 ALDH6A1(5), TPI1(1) 575512 6 5 6 2 3 1 1 0 1 0 0.93 0.97 586 SA_PROGRAMMED_CELL_DEATH Programmed cell death, or apoptosis, eliminates damaged or unneeded cells. APAF1, BAD, BAK1, BAX, BCL10, BCL2, BCL2L1, BCL2L11, BID, CASP8AP2, CASP9, CES1 12 APAF1(19), BAD(2), BAK1(4), BAX(4), BCL10(2), BCL2L1(3), BCL2L11(4), BID(3), CASP8AP2(18), CASP9(3), CES1(12) 3983652 74 27 73 22 18 26 18 4 8 0 0.93 0.97 587 LYSINE_DEGRADATION AADAT, AASDH, AASDHPPT, AASS, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ATP6V0C, SHMT1, BAT8, BBOX1, DLST, DLSTP, DOT1L, ECHS1, EHHADH, EHMT1, EHMT2, GCDH, HADHA, PLOD1, PLOD2, PLOD3, SDS, SHMT1, SHMT2, TMLHE 31 AADAT(6), AASDH(11), AASDHPPT(4), AASS(6), ACAT1(6), ACAT2(5), ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH9A1(4), ATP6V0C(2), BBOX1(4), DLST(10), DOT1L(8), ECHS1(3), EHHADH(9), EHMT2(6), GCDH(5), HADHA(7), PLOD1(4), PLOD2(16), PLOD3(11), SDS(3), SHMT1(6), SHMT2(8), TMLHE(5) 12013813 181 46 178 53 53 61 29 14 20 4 0.93 0.97 588 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(14), AGT(7), AGTR2(8), BDKRB2(9), KNG1(8), NOS3(11), REN(3) 3061590 60 24 57 21 19 28 6 2 5 0 0.94 0.97 589 GLYCEROLIPID_METABOLISM ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AKR1A1, AKR1B1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, CEL, DGAT1, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKQ, DGKZ, GK, GLA, GLB1, LCT, LIPC, LIPF, LIPG, LPL, PNLIP, PNLIPRP1, PNLIPRP2, PPAP2A, PPAP2B, PPAP2C 42 ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH6(9), ADH7(6), ADHFE1(7), AGPAT1(2), AGPAT2(1), AGPAT3(6), AGPAT4(4), AKR1A1(1), AKR1B1(2), ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH9A1(4), CEL(6), DGKA(15), DGKB(17), DGKD(21), DGKE(4), DGKG(13), DGKH(11), DGKZ(9), GK(14), GLA(3), GLB1(9), LCT(30), LIPC(8), LIPF(7), LIPG(6), LPL(11), PNLIP(3), PNLIPRP1(4), PNLIPRP2(8), PPAP2A(4), PPAP2B(3) 15873185 300 56 295 89 83 120 49 17 29 2 0.94 0.97 590 HISTIDINE_METABOLISM ABP1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, AOC2, AOC3, ASPA, CNDP1, DDC, HAL, HARS, HARSL, HDC, HNMT, MAOA, MAOB, PRPS1, PRPS2 24 ABP1(12), ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH3B1(5), ALDH3B2(8), ALDH9A1(4), AOC2(6), AOC3(14), ASPA(5), CNDP1(6), DDC(11), HAL(6), HARS(4), HDC(10), HNMT(5), MAOA(14), MAOB(7), PRPS1(3), PRPS2(10) 8577710 162 38 158 55 44 63 21 10 24 0 0.94 0.97 591 HSA01040_POLYUNSATURATED_FATTY_ACID_BIOSYNTHESIS Genes involved in polyunsaturated fatty acid biosynthesis ACAA1, ACOX1, ACOX3, ELOVL2, ELOVL5, ELOVL6, FADS1, FADS2, FASN, GPSN2, HADHA, HSD17B12, PECR, SCD 12 ACAA1(5), ACOX1(4), ACOX3(8), ELOVL2(5), ELOVL5(4), ELOVL6(3), FADS1(5), FADS2(2), HADHA(7), HSD17B12(4), PECR(5), SCD(9) 3716450 61 24 61 18 16 27 8 4 6 0 0.94 0.97 592 HSA00040_PENTOSE_AND_GLUCURONATE_INTERCONVERSIONS Genes involved in pentose and glucuronate interconversions AKR1B1, DCXR, GUSB, RPE, UGDH, UGP2, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, XYLB 25 AKR1B1(2), GUSB(5), RPE(3), UGDH(3), UGP2(8), UGT1A1(6), UGT1A10(8), UGT1A3(4), UGT1A4(4), UGT1A5(7), UGT1A6(5), UGT1A7(9), UGT1A8(4), UGT1A9(4), UGT2A1(9), UGT2A3(5), UGT2B10(14), UGT2B11(22), UGT2B15(9), UGT2B17(4), UGT2B28(14), UGT2B4(10), UGT2B7(10), XYLB(9) 8802370 178 39 169 36 59 64 30 8 17 0 0.94 0.97 593 ACETYLCHOLINE_SYNTHESIS ACHE, CHAT, CHKA, PCYT1A, PDHA1, PDHA2, PEMT, SLC18A3 8 ACHE(4), CHAT(1), CHKA(8), PCYT1A(7), PDHA1(4), PDHA2(10), PEMT(2) 2379723 36 19 36 13 12 11 6 3 4 0 0.94 0.97 594 HSA00520_NUCLEOTIDE_SUGARS_METABOLISM Genes involved in nucleotide sugars metabolism GALE, GALT, TGDS, UGDH, UGP2, UXS1 6 GALE(2), GALT(2), TGDS(3), UGDH(3), UGP2(8), UXS1(5) 1796563 23 15 22 10 9 7 5 1 1 0 0.94 0.97 595 ST_PAC1_RECEPTOR_PATHWAY The signaling peptide PACAP binds to its receptor, PAC1R, which activates adenylyl cyclase and phospholipase C. ASAH1, CAMP, DAG1, GAS, GNAQ, ITPKA, ITPKB, PACAP 5 ASAH1(9), CAMP(1), DAG1(7), ITPKB(6) 1846275 23 18 23 13 8 11 1 0 3 0 0.94 0.97 596 EEA1PATHWAY The FYVE-finger proteins EEA1 and HRS are localized to endosome membranes and regulate sorting and ubiquitination in the vesicle transport system. EEA1, EGF, EGFR, HGS, RAB5A, TF, TFRC 7 EEA1(20), EGF(24), EGFR(20), RAB5A(2), TF(15), TFRC(6) 4485074 87 28 84 20 25 32 12 5 13 0 0.94 0.97 597 1_2_DICHLOROETHANE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH9A1(4) 2683253 36 19 35 16 14 12 2 3 5 0 0.95 0.98 598 ASCORBATE_AND_ALDARATE_METABOLISM ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH9A1(4) 2683253 36 19 35 16 14 12 2 3 5 0 0.95 0.98 599 HSA00603_GLYCOSPHINGOLIPID_BIOSYNTHESIS_GLOBOSERIES Genes involved in glycosphingolipid biosynthesis - globoseries A4GALT, B3GALNT1, B3GALT5, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, ST3GAL1, ST3GAL2, ST8SIA1 14 B3GALNT1(5), B3GALT5(6), FUT1(5), FUT2(3), FUT9(12), GBGT1(6), GLA(3), HEXA(3), HEXB(4), NAGA(3), ST3GAL1(2), ST3GAL2(4), ST8SIA1(4) 3554408 60 25 57 19 16 28 7 3 6 0 0.95 0.98 600 LIMONENE_AND_PINENE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ECHS1, EHHADH, HADHA, SDS 12 ALDH1A1(6), ALDH1A2(9), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH9A1(4), ECHS1(3), EHHADH(9), HADHA(7), SDS(3) 4060849 58 25 57 27 20 21 5 7 5 0 0.95 0.98 601 CBLPATHWAY Activated EGF receptors undergo endocytosis into clathrin-coated vesicles, where they are recycled to the membrane or ubiquitinated by Cbl. CBL, CSF1R, EGF, EGFR, GRB2, MET, PDGFRA, PRKCA, PRKCB1, SH3GLB1, SH3GLB2, SH3KBP1, SRC 12 CBL(10), CSF1R(7), EGF(24), EGFR(20), GRB2(3), MET(10), PDGFRA(29), PRKCA(10), SH3GLB1(8), SH3GLB2(3), SH3KBP1(10), SRC(2) 6861212 136 35 131 48 40 51 23 6 14 2 0.96 0.98 602 SULFUR_METABOLISM BPNT1, PAPSS1, PAPSS2, SULT1A2, SULT1A3, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SUOX 7 BPNT1(1), PAPSS1(6), PAPSS2(6), SULT1A2(2), SULT1E1(13), SULT2A1(7), SUOX(4) 2179680 39 19 36 14 10 19 6 2 2 0 0.96 0.99 603 DCPATHWAY Dendritic cells internalize and present antigen, after which they migrate to lymphocyte-rich tissues and induce T and B cell differentiation. ANPEP, CD2, CD33, CD5, CD7, CSF2, IFNA1, IFNB1, IFNG, IL10, IL12A, IL12B, IL13, IL3, IL4, IL5, ITGAX, TLR2, TLR4, TLR7, TLR9, TNFRSF5 21 ANPEP(13), CD2(4), CD33(11), CD5(7), IFNB1(4), IFNG(5), IL10(4), IL12A(7), IL12B(3), IL5(2), ITGAX(9), TLR2(12), TLR4(14), TLR7(15), TLR9(7) 6604765 117 35 114 44 34 47 15 8 11 2 0.97 0.99 604 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ2(1), COQ3(4), COQ5(4), COQ6(3), COQ7(3), NDUFA13(1) 1409144 16 13 16 5 2 9 3 1 1 0 0.97 0.99 605 HSA00642_ETHYLBENZENE_DEGRADATION Genes involved in ethylbenzene degradation ARD1A, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ESCO1, ESCO2, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1 12 DHRS1(4), DHRS2(3), DHRS3(2), DHRS7(9), DHRSX(4), ESCO1(11), ESCO2(6), NAT6(2), PNPLA3(6), SH3GLB1(8) 5790253 55 26 55 21 17 24 6 0 8 0 0.98 0.99 606 CAPROLACTAM_DEGRADATION AKR1A1, ECHS1, EHHADH, HADHA, SDS 5 AKR1A1(1), ECHS1(3), EHHADH(9), HADHA(7), SDS(3) 1618986 23 13 23 14 6 10 3 4 0 0 0.98 1.00 607 HSA00960_ALKALOID_BIOSYNTHESIS_II Genes involved in alkaloid biosynthesis II AADAC, ABP1, AOC2, AOC3, ARD1A, CES1, CES7, DDHD1, ESCO1, ESCO2, LIPA, LYCAT, MYST3, MYST4, NAT5, NAT6, PLA1A, PNPLA3, PPME1, PRDX6, SH3GLB1 18 AADAC(5), ABP1(12), AOC2(6), AOC3(14), CES1(12), DDHD1(14), ESCO1(11), ESCO2(6), LIPA(6), NAT6(2), PLA1A(5), PNPLA3(6), PPME1(1), PRDX6(2), SH3GLB1(8) 8989268 110 34 107 41 31 38 21 5 13 2 0.98 1.00 608 HSA00790_FOLATE_BIOSYNTHESIS Genes involved in folate biosynthesis ALPI, ALPL, ALPP, ALPPL2, ASCC3, ASCC3L1, ATP13A2, DDX18, DDX19A, DDX23, DDX4, DDX41, DDX47, DDX50, DDX51, DDX52, DDX54, DDX55, DDX56, DHFR, DHX58, ENTPD7, EP400, ERCC2, ERCC3, FPGS, GCH1, GGH, IFIH1, MOV10L1, NUDT5, NUDT8, PTS, QDPR, RAD54B, RAD54L, RUVBL2, SETX, SKIV2L2, SMARCA2, SMARCA5, SPR 40 ALPI(3), ALPL(3), ALPP(4), ALPPL2(5), ASCC3(25), ATP13A2(6), DDX18(14), DDX19A(1), DDX23(12), DDX4(18), DDX41(2), DDX47(8), DDX50(11), DDX52(7), DDX54(8), DDX55(5), DDX56(6), DHFR(3), DHX58(5), ENTPD7(7), ERCC2(4), ERCC3(11), FPGS(3), GCH1(2), GGH(3), IFIH1(5), NUDT5(1), NUDT8(1), PTS(2), QDPR(1), RAD54B(14), RAD54L(5), RUVBL2(6), SETX(41), SKIV2L2(20), SMARCA2(24), SMARCA5(19), SPR(2) 21254270 317 59 305 94 78 120 58 17 37 7 0.98 1.00 609 HSA00641_3_CHLOROACRYLIC_ACID_DEGRADATION Genes involved in 3-chloroacrylic acid degradation ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1 15 ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH5(3), ADH6(9), ADH7(6), ADHFE1(7), ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH7A1(2), ALDH9A1(4) 4558447 68 24 66 17 21 25 11 3 8 0 0.99 1.00 610 HSA03050_PROTEASOME Genes involved in proteasome PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMC2, PSMC3, PSMD1, PSMD11, PSMD12, PSMD13, PSMD2, PSMD6 22 PSMA1(5), PSMA2(5), PSMA3(5), PSMA4(2), PSMA5(1), PSMA6(2), PSMB1(2), PSMB2(2), PSMB3(4), PSMB4(3), PSMB5(4), PSMB6(3), PSMB7(1), PSMC2(2), PSMC3(1), PSMD1(14), PSMD11(5), PSMD12(4), PSMD13(1), PSMD2(11), PSMD6(2) 5593078 79 28 74 21 18 33 12 2 14 0 0.99 1.00 611 HSA00930_CAPROLACTAM_DEGRADATION Genes involved in caprolactam degradation AKR1A1, ASAHL, ECHS1, EHHADH, HADH, HADHA, HSD17B10, HSD17B4, NTAN1, SIRT1, SIRT2, SIRT5, SIRT7, VNN2, VNN3 12 AKR1A1(1), ECHS1(3), EHHADH(9), HADH(1), HADHA(7), HSD17B10(4), HSD17B4(10), NTAN1(3), SIRT1(8), SIRT2(7), SIRT5(3), VNN2(10) 3895700 66 22 64 21 15 36 9 4 2 0 0.99 1.00 612 GLOBOSIDE_METABOLISM A4GALT, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, ST8SIA1 13 FUT1(5), FUT2(3), FUT9(12), GBGT1(6), GLA(3), HEXA(3), HEXB(4), NAGA(3), ST3GAL1(2), ST3GAL2(4), ST3GAL4(4), ST8SIA1(4) 3332855 53 22 52 16 14 24 9 3 3 0 0.99 1.00 613 HSA00564_GLYCEROPHOSPHOLIPID_METABOLISM Genes involved in glycerophospholipid metabolism ACHE, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, ARD1A, CDIPT, CDS1, CDS2, CHAT, CHKA, CHKB, CHPT1, CRLS1, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKI, DGKQ, DGKZ, ESCO1, ESCO2, ETNK1, ETNK2, GNPAT, GPAM, GPD1, GPD1L, GPD2, LCAT, LYCAT, LYPLA1, LYPLA2, LYPLA3, MYST3, MYST4, NAT5, NAT6, PCYT1A, PCYT1B, PEMT, PHOSPHO1, PISD, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLD1, PLD2, PNPLA3, PPAP2A, PPAP2B, PPAP2C, PTDSS1, PTDSS2, SH3GLB1 61 ACHE(4), AGPAT1(2), AGPAT2(1), AGPAT3(6), AGPAT4(4), AGPAT6(8), CDIPT(1), CDS1(3), CDS2(2), CHAT(1), CHKA(8), DGKA(15), DGKB(17), DGKD(21), DGKE(4), DGKG(13), DGKH(11), DGKI(21), DGKZ(9), ESCO1(11), ESCO2(6), ETNK1(9), ETNK2(3), GNPAT(11), GPAM(7), GPD1(6), GPD1L(3), GPD2(5), LCAT(2), LYPLA1(2), LYPLA2(5), NAT6(2), PCYT1A(7), PCYT1B(4), PEMT(2), PISD(5), PLA2G10(1), PLA2G12A(1), PLA2G12B(3), PLA2G1B(1), PLA2G2D(2), PLA2G2E(3), PLA2G2F(3), PLA2G3(5), PLA2G4A(11), PLA2G5(2), PLA2G6(6), PLD1(16), PLD2(7), PNPLA3(6), PPAP2A(4), PPAP2B(3), PTDSS1(6), PTDSS2(1), SH3GLB1(8) 21566165 330 60 327 117 87 131 48 20 42 2 1.00 1.00 614 HSA00053_ASCORBATE_AND_ALDARATE_METABOLISM Genes involved in ascorbate and aldarate metabolism ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, MIOX, UGDH 9 ALDH1B1(7), ALDH2(2), ALDH3A1(6), ALDH3A2(2), ALDH7A1(2), ALDH9A1(4), UGDH(3) 2749695 26 16 25 12 11 8 2 2 3 0 1.00 1.00 615 HSA03060_PROTEIN_EXPORT Genes involved in protein export OXA1L, SEC61A2, SRP19, SRP54, SRP68, SRP72, SRP9, SRPR 8 OXA1L(2), SEC61A2(6), SRP19(3), SRP54(6), SRP68(6), SRP72(8), SRP9(3), SRPR(8) 2641667 42 18 41 12 11 17 5 3 6 0 1.00 1.00 616 HSA00624_1_AND_2_METHYLNAPHTHALENE_DEGRADATION Genes involved in 1- and 2-methylnaphthalene degradation ACAD8, ACAD9, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ARD1A, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ESCO1, ESCO2, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1 22 ACAD8(7), ACAD9(10), ADH1A(2), ADH1B(6), ADH1C(7), ADH4(5), ADH5(3), ADH6(9), ADH7(6), ADHFE1(7), DHRS1(4), DHRS2(3), DHRS3(2), DHRS7(9), DHRSX(4), ESCO1(11), ESCO2(6), NAT6(2), PNPLA3(6), SH3GLB1(8) 8769627 117 32 116 32 30 47 18 2 18 2 1.00 1.00