rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q 1 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(6), ATR(12), CDC25C(1), CHEK1(4), CHEK2(3), TP53(115) 4293716 141 122 107 5 26 27 24 18 46 0 <1.00e-15 <2.08e-13 2 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 19 ABL1(2), ATM(6), BRCA1(6), CHEK1(4), CHEK2(3), GADD45A(1), JUN(3), MAPK8(2), MDM2(1), NFKB1(2), RAD50(2), RAD51(1), RBBP8(1), RELA(2), TP53(115) 8101670 151 117 116 10 26 33 23 21 48 0 2.55e-15 2.08e-13 3 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 25 ABL1(2), ATM(6), ATR(12), CDKN2A(22), E2F1(2), HDAC1(2), RB1(7), SKP2(1), TGFB1(1), TGFB2(2), TP53(115) 8079954 172 131 135 12 29 36 30 16 61 0 2.89e-15 2.08e-13 4 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 38 AKT1(1), ATF2(2), CDC42(1), DLD(2), DUSP10(3), DUSP4(2), GAB1(2), GADD45A(1), GCK(1), JUN(3), MAP2K5(1), MAP3K1(2), MAP3K11(2), MAP3K12(3), MAP3K13(5), MAP3K4(4), MAP3K5(3), MAP3K7(2), MAP3K9(3), MAPK10(1), MAPK7(1), MAPK8(2), MAPK9(1), MYEF2(3), NFATC3(2), NR2C2(1), PAPPA(8), SHC1(1), TP53(115), TRAF6(1) 13764918 179 131 144 25 35 44 34 20 46 0 3.11e-15 2.08e-13 5 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 110 ABL1(2), ANAPC1(4), ANAPC4(3), ANAPC5(4), ATM(6), ATR(12), BUB1(3), BUB1B(6), BUB3(2), CCNB1(1), CCNB3(9), CCND2(3), CCND3(1), CCNE2(2), CDC25B(1), CDC25C(1), CDC27(2), CDC6(4), CDC7(1), CDK7(1), CDKN2A(22), CDKN2C(1), CHEK1(4), CHEK2(3), CREBBP(12), CUL1(2), DBF4(4), E2F1(2), EP300(6), ESPL1(2), GADD45A(1), GADD45G(1), HDAC1(2), MAD1L1(5), MAD2L1(2), MCM2(1), MCM3(1), MCM4(3), MCM5(6), MCM6(1), MCM7(3), MDM2(1), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), PKMYT1(1), PLK1(1), PRKDC(11), PTTG1(1), PTTG2(2), RB1(7), RBL1(5), RBL2(5), RBX1(1), SFN(2), SKP1(1), SKP2(1), SMAD2(1), SMAD4(2), SMC1A(2), SMC1B(4), TGFB1(1), TGFB2(2), TP53(115), WEE1(2), YWHAB(1), YWHAQ(1) 37187582 326 157 288 50 66 90 62 31 77 0 3.66e-15 2.08e-13 6 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 41 APAF1(1), BAK1(1), BAX(1), BCL2L1(1), BIRC3(3), CASP2(1), CASP7(2), CASP8(1), CASP9(2), FADD(1), FAS(1), FASLG(1), GZMB(1), JUN(3), MAP3K1(2), MAP3K14(1), MAPK10(1), MCL1(2), MDM2(1), MYC(1), NFKB1(2), PARP1(3), PRF1(1), RELA(2), TNFRSF1A(2), TNFRSF1B(1), TP53(115), TRADD(1), TRAF1(4) 10250308 159 121 124 24 30 32 26 21 50 0 4.00e-15 2.08e-13 7 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(6), ATR(12), BRCA1(6), BRCA2(7), CHEK1(4), CHEK2(3), FANCC(2), FANCF(3), FANCG(1), RAD1(1), RAD17(2), RAD50(2), RAD51(1), RAD9A(1), TP53(115), TREX1(1) 11853198 167 124 133 14 31 36 29 21 50 0 4.77e-15 2.08e-13 8 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(2), ATM(6), BUB1(3), BUB1B(6), BUB3(2), CCNB1(1), CCNB3(9), CCND2(3), CCND3(1), CCNE2(2), CDAN1(3), CDC25B(1), CDC25C(1), CDC6(4), CDC7(1), CDH1(3), CDKN2A(22), CHEK1(4), CHEK2(3), DTX4(1), E2F1(2), EP300(6), ESPL1(2), GADD45A(1), HDAC1(2), HDAC3(1), HDAC4(4), HDAC5(1), MAD1L1(5), MAD2L1(2), MCM2(1), MCM3(1), MCM4(3), MCM5(6), MCM6(1), MCM7(3), MDM2(1), MPEG1(4), MPL(2), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), PLK1(1), PRKDC(11), PTTG1(1), PTTG2(2), RB1(7), RBL1(5), SKP2(1), SMAD4(2), TBC1D8(1), TGFB1(1), TP53(115), WEE1(2) 30149462 279 152 241 42 51 76 54 24 74 0 4.88e-15 2.08e-13 9 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 80 AIFM1(1), AKT1(1), AKT3(2), APAF1(1), ATM(6), BAX(1), BCL2L1(1), BIRC3(3), CAPN1(2), CAPN2(2), CASP10(3), CASP7(2), CASP8(1), CASP9(2), CFLAR(1), CHP(2), CHUK(2), CSF2RB(5), DFFB(2), FADD(1), FAS(1), FASLG(1), IKBKB(2), IL1B(1), IL1RAP(2), IRAK1(3), IRAK3(3), MAP3K14(1), NFKB1(2), NFKB2(2), NTRK1(3), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PPP3CA(2), PPP3CB(4), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), RELA(2), TNFRSF10A(1), TNFRSF10B(1), TNFRSF1A(2), TP53(115), TRADD(1) 22576808 246 143 201 44 65 57 34 30 60 0 4.88e-15 2.08e-13 10 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 22 ATM(6), ATR(12), BRCA1(6), CCNB1(1), CDC25B(1), CDC25C(1), CHEK1(4), CHEK2(3), EP300(6), GADD45A(1), MDM2(1), PRKDC(11), RPS6KA1(2), TP53(115), WEE1(2), YWHAQ(1) 11595276 173 129 138 11 32 38 32 22 49 0 5.00e-15 2.08e-13 11 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 65 ATM(6), CCNB1(1), CCND2(3), CCND3(1), CCNE2(2), CDK7(1), CDKN2A(22), CDKN2C(1), CREB3(2), CREB3L3(1), CREB3L4(2), E2F1(2), GADD45A(1), MCM2(1), MCM3(1), MCM4(3), MCM5(6), MCM6(1), MCM7(3), MDM2(1), MYC(1), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), POLE2(2), PRIM1(2), RB1(7), RBL1(5), TFDP2(2), TNXB(15), TP53(115), WEE1(2) 20927638 216 135 179 22 38 54 37 20 67 0 5.11e-15 2.08e-13 12 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 16 ABL1(2), CDKN2A(22), E2F1(2), MDM2(1), MYC(1), PIK3CA(20), PIK3R1(1), POLR1A(2), POLR1B(2), POLR1D(1), RAC1(1), RB1(7), TBX2(3), TP53(115) 5437544 180 129 132 13 39 35 29 17 60 0 5.11e-15 2.08e-13 13 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(12), DAXX(2), HRAS(1), PAX3(2), RARA(1), RB1(7), SP100(1), TNFRSF1A(2), TNFRSF1B(1), TP53(115) 5235158 144 120 110 14 26 29 22 17 50 0 6.22e-15 2.08e-13 14 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 19 ABCB1(15), AKT1(1), ATM(6), BAX(1), CPB2(2), CSNK1A1(2), FHL2(1), GADD45A(1), HIF1A(1), IGFBP3(1), MAPK8(2), MDM2(1), NFKBIB(1), TP53(115) 5676064 150 123 116 7 26 33 28 17 44 2 6.33e-15 2.08e-13 15 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 64 APAF1(1), ATM(6), ATR(12), BAI1(8), BAX(1), CASP8(1), CASP9(2), CCNB1(1), CCNB3(9), CCND2(3), CCND3(1), CCNE2(2), CCNG1(1), CD82(1), CDKN2A(22), CHEK1(4), CHEK2(3), DDB2(3), EI24(1), FAS(1), GADD45A(1), GADD45G(1), GTSE1(2), IGF1(3), IGFBP3(1), LRDD(1), MDM2(1), PPM1D(1), PTEN(13), RFWD2(4), RRM2B(2), SERPINB5(2), SESN1(3), SESN2(2), SESN3(2), SFN(2), SIAH1(1), STEAP3(2), THBS1(1), TNFRSF10B(1), TP53(115), TSC2(5) 17798932 249 141 212 22 42 62 47 26 72 0 6.44e-15 2.08e-13 16 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 59 ALG2(2), BAK1(1), BAX(1), BTK(4), CAD(8), CASP10(3), CASP8(1), CASP8AP2(5), CDK2AP1(1), CSNK1A1(2), DAXX(2), EGFR(6), EPHB2(4), FADD(1), FAF1(1), FAIM2(1), MAP3K1(2), MAP3K5(3), MAPK1(1), MAPK10(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(3), MAPK9(1), MET(3), NFAT5(2), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(4), NR0B2(1), PFN2(1), PTPN13(3), RALBP1(1), ROCK1(5), SMPD1(3), TNFRSF6B(1), TP53(115) 20303748 203 134 168 28 41 51 38 20 53 0 6.55e-15 2.08e-13 17 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(2), MYC(1), SP1(1), SP3(1), TP53(115), WT1(4) 1894810 124 118 90 8 22 21 24 15 42 0 6.88e-15 2.08e-13 18 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 18 IFNG(1), IFNGR1(3), IFNGR2(1), IKBKB(2), JAK2(3), LIN7A(2), NFKB1(2), RB1(7), RELA(2), TNFRSF1A(2), TNFRSF1B(1), TP53(115), USH1C(5), WT1(4) 5076382 150 121 116 9 26 28 30 16 50 0 6.99e-15 2.08e-13 19 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 66 APAF1(1), BAK1(1), BAX(1), BCL2L1(1), BIRC3(3), CASP1(1), CASP10(3), CASP2(1), CASP4(3), CASP7(2), CASP8(1), CASP9(2), CHUK(2), DFFB(2), FADD(1), FAS(1), FASLG(1), GZMB(1), IKBKB(2), IRF1(1), IRF3(1), IRF4(2), IRF6(5), JUN(3), LTA(2), MAP3K1(2), MAPK10(1), MDM2(1), MYC(1), NFKB1(2), NFKBIB(1), PRF1(1), RELA(2), TNFRSF10B(1), TNFRSF1A(2), TNFRSF1B(1), TNFRSF21(3), TP53(115), TRADD(1), TRAF1(4), TRAF3(1) 15688386 183 127 148 27 33 36 34 23 57 0 7.11e-15 2.08e-13 20 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(1), APAF1(1), ATM(6), BAX(1), BCL2L1(1), CASP7(2), CASP9(2), PRKCA(4), PTK2(4), PXN(3), STAT1(2), TLN1(3), TP53(115) 7458200 145 118 111 13 29 29 26 17 44 0 7.22e-15 2.08e-13 21 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(1), CDKN2A(22), CFL1(2), E2F1(2), MDM2(1), PRB1(2), TP53(115) 2182280 145 122 108 9 22 30 26 14 53 0 7.66e-15 2.08e-13 22 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(1), ATM(6), BAX(1), E2F1(2), GADD45A(1), MDM2(1), RB1(7), TP53(115) 4951604 134 118 100 5 23 27 21 15 48 0 7.66e-15 2.08e-13 23 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(6), CDC25B(1), CDC25C(1), CHEK1(4), RB1(7), TP53(115), WEE1(2) 4759720 136 119 102 5 24 28 21 14 49 0 7.77e-15 2.08e-13 24 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(2), MAP3K14(1), NFKB1(2), RELA(2), TP53(115) 2739598 122 113 88 4 21 21 21 14 45 0 8.55e-15 2.19e-13 25 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(1), EGFR(6), MYC(1), POLR2A(1), PRKCA(4), RB1(7), TEP1(3), TERF1(2), TERT(3), TNKS(7), TP53(115), XRCC5(1) 7681590 151 123 116 11 27 32 25 16 51 0 9.77e-15 2.41e-13 26 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 12 CREB1(1), FOS(1), JUN(3), KEAP1(17), MAPK1(1), MAPK14(1), MAPK8(2), NFE2L2(21), PRKCA(4) 2383598 51 48 40 2 14 12 18 3 4 0 5.51e-14 1.30e-12 27 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 247 ACVR1B(3), ACVR1C(3), AKT1(1), AKT3(2), ARRB1(2), ATF2(2), BDNF(1), BRAF(7), CACNA1A(7), CACNA1B(1), CACNA1C(12), CACNA1D(3), CACNA1E(14), CACNA1F(8), CACNA1G(5), CACNA1H(5), CACNA1I(8), CACNA1S(5), CACNA2D1(8), CACNA2D2(3), CACNA2D3(1), CACNA2D4(6), CACNB2(2), CACNB3(2), CACNB4(1), CACNG3(2), CACNG4(2), CACNG6(1), CACNG7(4), CD14(1), CDC25B(1), CDC42(1), CHP(2), CHUK(2), DAXX(2), DUSP10(3), DUSP16(1), DUSP4(2), DUSP5(4), DUSP6(1), DUSP7(1), DUSP9(2), EGF(6), EGFR(6), FAS(1), FASLG(1), FGF10(2), FGF12(3), FGF14(1), FGF2(2), FGF23(1), FGF3(1), FGF5(2), FGF6(2), FGF8(1), FGFR1(1), FGFR2(3), FGFR3(2), FGFR4(1), FLNA(8), FLNB(3), FLNC(11), FOS(1), GADD45A(1), GADD45G(1), GNA12(1), GNG12(1), HRAS(1), IKBKB(2), IL1B(1), IL1R2(3), JUN(3), KRAS(1), MAP2K1(2), MAP2K3(2), MAP2K5(1), MAP2K6(2), MAP3K1(2), MAP3K12(3), MAP3K13(5), MAP3K14(1), MAP3K4(4), MAP3K5(3), MAP3K6(1), MAP3K7(2), MAP4K1(2), MAP4K2(1), MAP4K3(5), MAP4K4(5), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(1), MAPK7(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(3), MAPK9(1), MAPKAPK2(1), MAPKAPK5(3), MAPT(4), MEF2C(3), MKNK2(1), MOS(4), MRAS(2), MYC(1), NF1(20), NFATC2(4), NFATC4(1), NFKB1(2), NFKB2(2), NLK(2), NR4A1(4), NTF3(3), NTRK1(3), NTRK2(1), PAK1(1), PDGFB(1), PDGFRA(8), PDGFRB(4), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(5), PPM1A(2), PPM1B(1), PPP3CA(2), PPP3CB(4), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKACB(2), PRKACG(1), PRKCA(4), PRKCG(8), PRKX(1), PTPN5(1), PTPRR(7), RAC1(1), RAF1(1), RAP1B(1), RAPGEF2(5), RASA1(5), RASA2(3), RASGRF1(5), RASGRF2(4), RASGRP1(1), RASGRP3(6), RASGRP4(4), RPS6KA1(2), RPS6KA2(3), RPS6KA3(1), RPS6KA4(1), RPS6KA5(4), RPS6KA6(4), RRAS2(2), SOS1(6), SOS2(5), SRF(2), STK3(2), STK4(2), TAOK1(6), TAOK2(5), TAOK3(3), TGFB1(1), TGFB2(2), TGFBR2(3), TNFRSF1A(2), TP53(115), TRAF6(1) 79663722 615 171 576 141 129 194 115 61 116 0 4.80e-13 1.09e-11 28 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 144 APC(9), APC2(2), CAMK2B(2), CAMK2D(1), CCND2(3), CCND3(1), CHD8(8), CHP(2), CREBBP(12), CSNK1A1(2), CSNK1A1L(5), CSNK2A1(2), CTBP1(1), CTNNB1(3), CUL1(2), DAAM1(1), DAAM2(5), DKK1(3), DKK2(1), DVL1(3), DVL3(2), EP300(6), FZD1(1), FZD10(1), FZD3(4), FZD4(1), FZD6(2), FZD7(1), FZD9(2), JUN(3), LEF1(3), LRP5(6), LRP6(3), MAP3K7(2), MAPK10(1), MAPK8(2), MAPK9(1), MYC(1), NFAT5(2), NFATC2(4), NFATC3(2), NFATC4(1), NKD1(1), NKD2(2), NLK(2), PLCB1(6), PLCB2(5), PLCB3(3), PLCB4(4), PORCN(2), PPARD(1), PPP2R1A(5), PPP2R1B(2), PPP2R2A(1), PPP2R2B(1), PPP2R2C(1), PPP3CA(2), PPP3CB(4), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRICKLE1(5), PRICKLE2(1), PRKACB(2), PRKACG(1), PRKCA(4), PRKCG(8), PRKX(1), PSEN1(1), RAC1(1), RBX1(1), ROCK1(5), ROCK2(3), RUVBL1(2), SENP2(3), SFRP1(1), SFRP4(3), SFRP5(1), SIAH1(1), SKP1(1), SMAD2(1), SMAD4(2), TBL1XR1(2), TBL1Y(2), TCF7(1), TP53(115), VANGL1(1), VANGL2(1), WIF1(3), WNT10B(2), WNT11(1), WNT2(3), WNT2B(2), WNT3(2), WNT3A(1), WNT6(2), WNT7A(2), WNT7B(1), WNT9A(1), WNT9B(1) 44570488 358 155 322 83 87 101 61 39 70 0 2.31e-11 5.08e-10 29 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 237 ADCYAP1R1(7), ADORA1(3), ADORA2A(5), ADRA1A(2), ADRA1B(3), ADRA2B(4), ADRA2C(2), ADRB2(3), AGTR1(2), AGTR2(3), AVPR1A(3), AVPR1B(2), AVPR2(1), BDKRB1(1), BDKRB2(2), C3AR1(1), C5AR1(1), CALCR(5), CALCRL(3), CCKAR(2), CCKBR(1), CHRM2(6), CHRM3(4), CHRM4(1), CHRM5(2), CNR1(2), CNR2(2), CRHR1(2), CRHR2(2), CTSG(3), CYSLTR1(2), CYSLTR2(1), DRD1(1), DRD2(2), DRD3(5), DRD4(1), DRD5(3), EDNRA(1), EDNRB(3), F2R(2), F2RL1(3), F2RL2(1), F2RL3(1), FPR1(1), FSHB(1), FSHR(11), GABBR1(1), GABBR2(2), GABRA1(6), GABRA2(8), GABRA3(4), GABRA4(3), GABRA5(4), GABRA6(7), GABRB1(3), GABRB2(5), GABRB3(10), GABRD(2), GABRE(4), GABRG1(10), GABRG2(4), GABRG3(8), GABRP(1), GABRQ(5), GABRR1(2), GABRR2(2), GALR1(3), GH2(2), GHR(2), GHRHR(3), GHSR(2), GLP1R(1), GLP2R(3), GLRA1(2), GLRA2(4), GLRA3(3), GLRB(3), GPR156(1), GPR35(1), GPR50(4), GPR63(2), GPR83(2), GRIA1(6), GRIA2(3), GRIA3(8), GRIA4(7), GRID1(10), GRID2(12), GRIK1(4), GRIK2(8), GRIK3(7), GRIK4(3), GRIK5(1), GRIN1(1), GRIN2A(13), GRIN2B(15), GRIN2C(2), GRIN2D(2), GRIN3A(7), GRIN3B(4), GRM1(10), GRM2(2), GRM3(12), GRM4(1), GRM5(11), GRM6(4), GRM7(8), GRM8(8), GRPR(2), GZMA(4), HCRTR2(3), HRH1(3), HRH2(1), HRH3(1), HRH4(3), HTR1A(5), HTR1B(3), HTR1E(4), HTR1F(2), HTR2A(1), HTR2B(1), HTR2C(2), HTR4(3), HTR5A(3), HTR6(1), HTR7(3), LEPR(10), LHB(1), LHCGR(7), LTB4R2(1), MAS1(3), MC2R(2), MC3R(2), MC4R(1), MC5R(3), MCHR1(2), MCHR2(3), MTNR1A(1), MTNR1B(9), NMBR(2), NMUR2(1), NPBWR1(1), NPFFR2(7), NPY1R(3), NPY2R(2), NPY5R(2), NTSR1(3), NTSR2(2), OPRD1(1), OPRM1(2), OXTR(1), P2RX2(1), P2RX3(4), P2RX4(1), P2RX7(1), P2RY1(2), P2RY10(2), P2RY13(1), P2RY14(3), P2RY2(1), P2RY4(1), P2RY6(1), PARD3(5), PPYR1(3), PRL(1), PRLHR(1), PRLR(5), PRSS1(3), PRSS3(2), PTAFR(3), PTGDR(5), PTGER2(2), PTGER3(5), PTGER4(2), PTGFR(2), PTGIR(1), PTH2R(3), RXFP1(7), SSTR1(1), SSTR2(2), SSTR3(1), SSTR4(2), SSTR5(1), TAAR1(4), TAAR2(2), TAAR5(5), TAAR6(4), TAAR8(2), TAAR9(2), TACR1(2), TACR3(3), TBXA2R(2), THRA(1), THRB(1), TRHR(1), TRPV1(2), TSHR(1) 60667562 641 165 639 205 173 222 137 39 70 0 4.11e-10 8.73e-09 30 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 37 ACTA1(1), ACTN2(6), ACTN3(2), ACTN4(4), DES(2), DMD(21), FAM48A(1), MYBPC1(8), MYBPC3(3), MYH3(4), MYH6(11), MYH7(8), MYH8(20), MYL1(3), MYL2(1), MYL3(2), MYOM1(9), NEB(20), TNNI2(1), TNNI3(1), TNNT1(1), TNNT2(2), TNNT3(3), TPM3(1), TTN(249), VIM(4) 37572952 388 142 386 128 104 115 98 28 37 6 3.09e-09 6.31e-08 31 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(1), AKT1(1), AKT3(2), BTK(4), CDKN2A(22), GSK3A(3), IARS(3), INPP5D(5), PDK1(1), PIK3CA(20), PPP1R13B(4), PTEN(13), RPS6KA1(2), RPS6KA2(3), RPS6KA3(1), RPS6KB1(1), SFN(2), SHC1(1), SOS1(6), SOS2(5), TEC(2), YWHAB(1), YWHAQ(1) 9741584 104 77 90 10 22 23 26 4 29 0 3.18e-09 6.31e-08 32 C21_STEROID_HORMONE_METABOLISM AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 AKR1C4(1), AKR1D1(4), CYP11A1(2), CYP11B1(11), CYP11B2(6), CYP17A1(1), CYP21A2(2), HSD11B1(3), HSD11B2(1), HSD3B1(4), HSD3B2(3) 2426318 38 35 38 3 8 16 6 6 2 0 8.97e-08 1.67e-06 33 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(1), AKR1D1(4), CYP11A1(2), CYP11B1(11), CYP11B2(6), CYP17A1(1), CYP21A2(2), HSD11B1(3), HSD11B2(1), HSD3B1(4), HSD3B2(3) 2426318 38 35 38 3 8 16 6 6 2 0 8.97e-08 1.67e-06 34 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(1), AKT3(2), BCR(1), BTK(4), CD19(2), CDKN2A(22), FLOT1(1), GAB1(2), ITPR1(4), ITPR2(11), ITPR3(1), LYN(1), NR0B2(1), PDK1(1), PHF11(1), PIK3CA(20), PITX2(3), PLCG2(3), PPP1R13B(4), PREX1(12), PTEN(13), PTPRC(3), RPS6KA1(2), RPS6KA2(3), RPS6KA3(1), RPS6KB1(1), SYK(1), TEC(2), VAV1(7) 15074642 130 92 116 28 32 34 26 8 30 0 1.50e-07 2.72e-06 35 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 135 ACTB(1), COL11A1(31), COL11A2(10), COL17A1(4), COL1A1(8), COL1A2(12), COL2A1(8), COL3A1(10), COL4A1(6), COL4A2(6), COL4A4(9), COL4A6(6), COL5A1(5), COL5A2(11), COL5A3(11), COL6A3(10), COL6A6(19), COMP(1), DES(2), DSC1(5), DSC2(1), DSC3(6), DSG1(8), DSG2(2), DSG3(3), DSG4(5), FN1(16), GJA1(4), GJA10(5), GJA8(3), GJA9(1), GJB2(1), GJB4(1), GJC1(2), GJC2(1), GJC3(1), GJD2(2), GJD4(2), IBSP(4), INA(2), ITGA6(3), ITGB4(6), KRT1(1), KRT10(1), KRT12(3), KRT13(2), KRT14(1), KRT16(3), KRT17(2), KRT18(2), KRT2(4), KRT20(2), KRT23(2), KRT24(3), KRT27(2), KRT28(1), KRT3(2), KRT31(1), KRT32(2), KRT33A(1), KRT35(1), KRT36(2), KRT37(2), KRT4(1), KRT5(1), KRT6A(1), KRT6B(2), KRT71(2), KRT72(2), KRT73(6), KRT75(1), KRT76(2), KRT77(3), KRT79(3), KRT81(3), KRT82(1), KRT84(1), KRT85(1), KRT9(1), LAMA1(12), LAMA2(18), LAMA3(7), LAMA4(13), LAMA5(6), LAMB1(5), LAMB2(2), LAMB3(1), LAMB4(3), LAMC1(8), LAMC2(2), LAMC3(1), NES(11), PRPH(2), RELN(24), THBS1(1), THBS2(12), THBS3(3), THBS4(1), TNC(11), TNN(14), TNR(16), TNXB(15), VIM(4), VWF(15) 67804472 532 160 531 151 136 189 118 33 56 0 7.29e-07 0.000013 36 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(1), AKT1(1), BDKRB2(2), CHRNA1(1), FLT1(8), FLT4(3), KDR(12), NOS3(1), PDE2A(2), PDE3A(4), PDE3B(3), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PRKG1(4), PRKG2(3), RYR2(84), SLC7A1(4), SYT1(3) 11156150 144 81 142 47 40 46 27 13 18 0 9.92e-07 0.000017 37 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(6), GABRA2(8), GABRA3(4), GABRA4(3), GABRA5(4), GABRA6(7), PRKCE(3) 2131728 35 31 35 6 10 11 8 1 5 0 1.16e-06 0.000019 38 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 63 AKT1(1), AKT3(2), BCL2L1(1), CDC42(1), CDKN2A(22), CREB1(1), CREB3(2), CREB5(3), ERBB4(9), F2RL2(1), GAB1(2), GADD45A(1), GSK3A(3), IGF1(3), INPPL1(3), IRS1(3), IRS2(2), IRS4(2), MET(3), MYC(1), NOLC1(2), PAK1(1), PAK3(1), PAK4(1), PAK7(4), PARD3(5), PARD6A(1), PDK1(1), PIK3CA(20), PIK3CD(3), PPP1R13B(4), PREX1(12), PTEN(13), PTK2(4), PTPN1(1), RPS6KA1(2), RPS6KA2(3), RPS6KA3(1), RPS6KB1(1), SFN(2), SHC1(1), SLC2A4(2), SOS1(6), SOS2(5), TSC1(5), TSC2(5), YWHAB(1), YWHAQ(1) 20981038 174 107 160 35 38 50 41 10 35 0 1.20e-06 0.000020 39 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 163 ADORA1(3), ADORA2A(5), ADRA1A(2), ADRA1B(3), ADRA1D(2), ADRA2C(2), ADRB2(3), AGTR1(2), AGTR2(3), AVPR1A(3), AVPR1B(2), AVPR2(1), BDKRB1(1), BDKRB2(2), C3AR1(1), CCBP2(3), CCKAR(2), CCKBR(1), CCR1(2), CCR10(1), CCR3(1), CCR4(3), CCR6(2), CCR8(1), CCRL1(2), CCRL2(1), CHML(1), CHRM2(6), CHRM3(4), CHRM4(1), CHRM5(2), CNR1(2), CNR2(2), CX3CR1(3), CXCR3(1), CXCR4(5), DRD1(1), DRD2(2), DRD3(5), DRD4(1), DRD5(3), EDNRA(1), EDNRB(3), F2R(2), F2RL1(3), F2RL2(1), F2RL3(1), FPR1(1), FSHR(11), GALR1(3), GALT(1), GHSR(2), GPR17(3), GPR174(4), GPR27(1), GPR35(1), GPR37(2), GPR37L1(2), GPR50(4), GPR6(2), GPR63(2), GPR77(3), GPR83(2), GPR85(2), GPR87(4), GRPR(2), HCRTR2(3), HRH1(3), HRH2(1), HRH3(1), HTR1A(5), HTR1B(3), HTR1E(4), HTR1F(2), HTR2A(1), HTR2B(1), HTR2C(2), HTR4(3), HTR5A(3), HTR6(1), HTR7(3), LHCGR(7), MAS1(3), MC3R(2), MC4R(1), MC5R(3), MTNR1A(1), MTNR1B(9), NMBR(2), NMUR2(1), NPY1R(3), NPY2R(2), NPY5R(2), NTSR1(3), NTSR2(2), OPN1SW(1), OPN3(1), OPRD1(1), OPRM1(2), OR10A5(1), OR11A1(3), OR12D3(4), OR1F1(1), OR1Q1(2), OR2H1(1), OR5V1(1), OR8B8(5), OXTR(1), P2RY1(2), P2RY10(2), P2RY13(1), P2RY14(3), P2RY2(1), P2RY6(1), PPYR1(3), PTAFR(3), PTGDR(5), PTGER2(2), PTGER4(2), PTGFR(2), PTGIR(1), RGR(1), RHO(1), SSTR1(1), SSTR2(2), SSTR3(1), SSTR4(2), SUCNR1(2), TBXA2R(2), TRHR(1) 32937654 298 137 298 101 74 108 65 16 35 0 8.18e-06 0.00013 40 GPCRDB_CLASS_C_METABOTROPIC_GLUTAMATE_PHEROMONE CASR, GABBR1, GPCR5A, GPR51, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GRM1, GRM2, GRM3, GRM4, GRM5, GRM7, GRM8 13 CASR(8), GABBR1(1), GPRC5A(1), GPRC5C(4), GRM1(10), GRM2(2), GRM3(12), GRM4(1), GRM5(11), GRM7(8), GRM8(8) 5627292 66 51 66 29 14 20 15 8 9 0 0.000012 0.00019 41 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 139 ADCY1(7), ADCY2(14), ADCY3(4), ADCY4(3), ADCY5(1), ADCY7(4), ADCY8(13), ADCY9(3), ADRA1A(2), ADRA1B(3), ADRA1D(2), ADRB2(3), ANXA6(4), ARRB1(2), ATP1A4(3), ATP1B2(1), ATP2A2(3), ATP2A3(2), ATP2B1(3), ATP2B2(5), ATP2B3(2), CACNA1A(7), CACNA1B(1), CACNA1C(12), CACNA1D(3), CACNA1E(14), CACNA1S(5), CACNB3(2), CALR(1), CAMK2B(2), CAMK2D(1), CAMK4(3), CASQ1(1), CASQ2(1), CHRM2(6), CHRM3(4), CHRM4(1), CHRM5(2), GJA1(4), GJB2(1), GJB4(1), GNAI3(1), GNAZ(2), GNB1(1), GNB2(2), GNB4(2), GNB5(1), GNG12(1), GNG4(2), GNG5(1), GRK4(1), GRK6(1), ITPR1(4), ITPR2(11), ITPR3(1), KCNB1(1), KCNJ3(7), KCNJ5(2), MIB1(2), NME7(2), PEA15(1), PLCB3(3), PLN(1), PRKACB(2), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PRKCA(4), PRKCD(2), PRKCE(3), PRKCG(8), PRKCQ(4), PRKD1(9), RGS1(3), RGS10(1), RGS11(1), RGS16(1), RGS17(2), RGS18(1), RGS20(1), RGS3(4), RGS5(1), RGS6(4), RGS7(8), RGS9(2), RYR1(24), RYR2(84), RYR3(38), SFN(2), SLC8A1(11), SLC8A3(3), USP5(1), YWHAB(1), YWHAQ(1) 51879168 437 146 434 125 116 160 81 33 47 0 0.000016 0.00024 42 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(2), ASL(3), CPS1(18), GLS(2), GLUD1(4) 2011222 29 28 28 5 9 9 6 1 4 0 0.000017 0.00025 43 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 16 AKT1(1), BCAR1(5), ILK(1), ITGB1(3), MAPK1(1), MAPK3(1), PDK2(1), PDPK1(1), PIK3CA(20), PIK3R1(1), PTEN(13), PTK2(4), SHC1(1), SOS1(6) 5299772 59 49 48 6 23 11 14 3 8 0 0.000021 0.00030 44 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 CCNE2(2), CDKN2A(22), E2F1(2), PRB1(2) 2352092 28 27 25 2 2 10 5 0 11 0 0.000029 0.00040 45 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 130 ACTB(1), ACTN1(2), ACTN2(6), ACTN3(2), ACTN4(4), AKT1(1), AKT3(2), AMOTL1(3), ASH1L(7), CASK(1), CDC42(1), CGN(4), CLDN1(2), CLDN10(4), CLDN16(4), CLDN17(1), CLDN19(1), CLDN2(1), CLDN22(1), CLDN3(1), CLDN6(1), CLDN8(1), CLDN9(3), CSDA(2), CSNK2A1(2), CTNNA2(17), CTNNA3(10), CTNNB1(3), CTTN(2), EPB41(2), EPB41L1(1), EPB41L2(1), EPB41L3(11), EXOC3(2), EXOC4(2), F11R(1), GNAI1(2), GNAI3(1), HCLS1(3), HRAS(1), IGSF5(2), INADL(9), KRAS(1), LLGL1(1), LLGL2(2), MAGI1(5), MAGI2(7), MAGI3(1), MLLT4(1), MPDZ(4), MPP5(2), MRAS(2), MYH1(13), MYH10(1), MYH11(7), MYH13(8), MYH14(4), MYH15(10), MYH2(21), MYH3(4), MYH4(14), MYH6(11), MYH7(8), MYH7B(4), MYH8(20), MYH9(12), MYL2(1), MYLPF(1), PARD3(5), PARD6A(1), PPM1J(1), PPP2R1A(5), PPP2R1B(2), PPP2R2A(1), PPP2R2B(1), PPP2R2C(1), PPP2R3A(2), PPP2R4(1), PRKCA(4), PRKCD(2), PRKCE(3), PRKCG(8), PRKCI(4), PRKCQ(4), PTEN(13), RAB3B(1), RRAS2(2), SPTAN1(2), SYMPK(6), TJAP1(4), TJP1(8), TJP2(3), TJP3(1), VAPA(1), YES1(1) 52815626 380 152 380 111 96 113 74 41 56 0 0.000044 0.00061 46 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 138 ACTA1(1), ADCY1(7), ADCY2(14), ADCY3(4), ADCY4(3), ADCY5(1), ADCY7(4), ADCY8(13), ADCY9(3), ARRB1(2), ATF2(2), ATP2A2(3), ATP2A3(2), CACNB3(2), CAMK2B(2), CAMK2D(1), CNN1(2), CORIN(8), CREB3(2), CRHR1(2), DGKZ(3), FOS(1), GABPA(2), GABPB2(1), GJA1(4), GNB1(1), GNB2(2), GNB4(2), GNB5(1), GNG12(1), GNG4(2), GNG5(1), GRK4(1), GRK6(1), GSTO1(1), GUCY1A3(5), IGFBP3(1), IGFBP6(1), IL1B(1), ITPR1(4), ITPR2(11), ITPR3(1), JUN(3), MIB1(2), MYL2(1), MYLK2(2), NFKB1(2), NOS1(10), NOS3(1), OXTR(1), PDE4B(3), PDE4D(1), PLCB3(3), PLCG1(1), PLCG2(3), PRKACB(2), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PRKCA(4), PRKCD(2), PRKCE(3), PRKCQ(4), PRKD1(9), RAMP2(1), RGS1(3), RGS10(1), RGS11(1), RGS16(1), RGS17(2), RGS18(1), RGS20(1), RGS3(4), RGS5(1), RGS6(4), RGS7(8), RGS9(2), RYR1(24), RYR2(84), RYR3(38), SFN(2), SLC8A1(11), SP1(1), TNXB(15), USP5(1), YWHAB(1), YWHAQ(1) 47658432 396 143 392 114 113 140 75 25 43 0 0.000050 0.00066 47 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 22 CCNB1(1), CCND2(3), CCND3(1), CDK7(1), CDKN2A(22), CDKN2C(1), E2F1(2), RB1(7), RBL1(5) 4296030 43 37 40 4 3 11 9 3 17 0 0.000058 0.00076 48 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(1), EIF4A1(4), EIF4A2(2), EIF4B(4), EIF4G1(6), EIF4G2(2), EIF4G3(3), PDK2(1), PDPK1(1), PIK3CA(20), PIK3R1(1), PTEN(13), RPS6(1), RPS6KB1(1), TSC1(5), TSC2(5) 7493622 70 57 59 10 18 18 16 5 13 0 0.00012 0.0015 49 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(1), AKT3(2), BPNT1(1), ILK(1), MAPK1(1), MAPK3(1), PDK1(1), PIK3CA(20), PIK3CD(3), PTEN(13), RBL2(5), SHC1(1), SOS1(6) 5509812 56 48 45 6 19 11 14 4 8 0 0.00022 0.0027 50 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(1), PIK3CA(20), PIK3R1(1), PLCB1(6), PLCG1(1), PRKCA(4), VAV1(7) 3448216 40 37 29 6 20 8 7 4 1 0 0.00036 0.0044 51 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 49 AKT1(1), AKT3(2), BRD4(2), CAP1(2), CBL(1), CDC42(1), CDKN2A(22), F2RL2(1), FLOT1(1), GSK3A(3), INPPL1(3), IRS1(3), IRS2(2), IRS4(2), LNPEP(2), MAPK1(1), MAPK3(1), PARD3(5), PARD6A(1), PDK1(1), PIK3CA(20), PIK3CD(3), PIK3R1(1), PPYR1(3), PTEN(13), PTPN1(1), RAF1(1), RPS6KA1(2), RPS6KA2(3), RPS6KA3(1), RPS6KB1(1), SERPINB6(4), SFN(2), SHC1(1), SLC2A4(2), SORBS1(5), SOS1(6), SOS2(5), YWHAB(1), YWHAQ(1) 16118968 133 86 119 21 29 35 32 8 29 0 0.00038 0.0046 52 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(1), EIF4A1(4), EIF4A2(2), EIF4G1(6), EIF4G2(2), EIF4G3(3), GHR(2), IRS1(3), MAPK1(1), MAPK14(1), MAPK3(1), PABPC1(2), PDK2(1), PDPK1(1), PIK3CA(20), PIK3R1(1), PRKCA(4), PTEN(13), RPS6KB1(1) 7576570 69 58 58 13 20 19 16 5 9 0 0.00050 0.0060 53 STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR 10 EPX(4), GBA3(6), LPO(2), MPO(3), PRDX1(1), PRDX6(1), TPO(10), TYR(3) 2635646 30 27 30 7 4 11 12 1 2 0 0.00079 0.0090 54 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(1), GABRA1(6), GABRA2(8), GABRA3(4), GABRA4(3), GABRA5(4), GABRA6(7), GPHN(1), NSF(2), UBQLN1(1) 3229276 37 31 37 8 8 14 9 1 5 0 0.00079 0.0090 55 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(3), F11(3), F12(1), F13B(7), F5(14), F8(9), F9(4), FGA(5), FGB(3), FGG(1), LPA(11), PLAT(1), PLAU(2), PLG(1), SERPINB2(3), SERPINF2(3), VWF(15) 9480458 86 64 86 19 15 32 24 7 8 0 0.00084 0.0094 56 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 67 ADCY1(7), ADCY8(13), ARAF(3), BRAF(7), CACNA1C(12), CALML6(1), CAMK2B(2), CAMK2D(1), CAMK4(3), CHP(2), CREBBP(12), EP300(6), GRIA1(6), GRIA2(3), GRIN1(1), GRIN2A(13), GRIN2B(15), GRIN2C(2), GRIN2D(2), GRM1(10), GRM5(11), HRAS(1), ITPR1(4), ITPR2(11), ITPR3(1), KRAS(1), MAP2K1(2), MAPK1(1), MAPK3(1), PLCB1(6), PLCB2(5), PLCB3(3), PLCB4(4), PPP3CA(2), PPP3CB(4), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKACB(2), PRKACG(1), PRKCA(4), PRKCG(8), PRKX(1), RAF1(1), RAP1B(1), RPS6KA1(2), RPS6KA2(3), RPS6KA3(1), RPS6KA6(4) 27622752 212 117 210 66 64 62 36 26 24 0 0.00086 0.0094 57 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 26 AKT1(1), APC(9), CD14(1), CTNNB1(3), DVL1(3), FZD1(1), GJA1(4), GNAI1(2), IRAK1(3), LBP(4), LEF1(3), NFKB1(2), PDPK1(1), PIK3CA(20), PIK3R1(1), RELA(2), TLR4(10), TOLLIP(1) 8223600 71 58 60 13 22 16 18 7 8 0 0.00087 0.0094 58 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 17 ACE(4), ACE2(3), AGT(1), AGTR1(2), AGTR2(3), ANPEP(5), CMA1(2), CPA3(4), CTSA(2), CTSG(3), ENPEP(7), LNPEP(2), MAS1(3), MME(8), NLN(2), THOP1(1) 5741924 52 46 52 14 10 21 8 4 9 0 0.0012 0.012 59 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 ADCY1(7), CREM(2), FSHB(1), FSHR(11), GNAS(5), XPO1(2) 2597732 28 26 28 11 7 8 6 5 2 0 0.0014 0.014 60 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(5), CD2(1), CD33(2), CD5(2), IFNA1(1), IFNB1(1), IFNG(1), IL10(1), IL12A(1), IL12B(2), IL4(2), ITGAX(9), TLR2(3), TLR4(10), TLR7(3), TLR9(1) 5001444 45 40 44 14 9 17 9 4 6 0 0.0017 0.017 61 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(1), EIF2B5(1), IGF1(3), INPPL1(3), PDK2(1), PDPK1(1), PIK3CA(20), PIK3R1(1), PTEN(13), RPS6(1), RPS6KB1(1) 5349790 46 42 35 8 15 8 9 4 10 0 0.0023 0.023 62 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 62 AKT1(1), AKT3(2), BLNK(1), BTK(4), CARD11(3), CD19(2), CD22(5), CD81(1), CHP(2), CHUK(2), CR2(9), FCGR2B(2), FOS(1), HRAS(1), IKBKB(2), INPP5D(5), JUN(3), KRAS(1), LILRB3(3), LYN(1), MALT1(1), NFAT5(2), NFATC2(4), NFATC3(2), NFATC4(1), NFKB1(2), NFKB2(2), NFKBIB(1), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PLCG2(3), PPP3CA(2), PPP3CB(4), PPP3CC(2), PPP3R1(1), PPP3R2(3), RAC1(1), RASGRP3(6), SYK(1), VAV1(7), VAV2(3), VAV3(1) 20264588 142 93 130 37 43 34 22 20 23 0 0.0023 0.023 63 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 34 ALDH4A1(3), ARG1(2), ASL(3), CKB(1), CKM(2), CKMT2(1), CPS1(18), DAO(1), EPRS(10), GATM(1), GLUD1(4), GLUD2(7), GOT2(2), LAP3(1), NOS1(10), NOS3(1), OTC(2), P4HA1(2), P4HA2(2), P4HA3(3), PARS2(2), RARS(4), RARS2(2) 9714172 84 63 83 17 20 28 17 5 14 0 0.0025 0.024 64 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 32 ADRA1A(2), ADRA1B(3), ADRA1D(2), ADRA2C(2), ADRB2(3), CHRM2(6), CHRM3(4), CHRM4(1), CHRM5(2), DRD1(1), DRD2(2), DRD3(5), DRD4(1), DRD5(3), HRH1(3), HRH2(1), HTR1A(5), HTR1B(3), HTR1E(4), HTR1F(2), HTR2A(1), HTR2B(1), HTR2C(2), HTR4(3), HTR5A(3), HTR6(1), HTR7(3) 7002876 69 51 69 27 15 25 22 3 4 0 0.0026 0.025 65 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(3), CRHR1(2), CRHR2(2), ELTD1(16), EMR1(9), EMR2(4), GHRHR(3), GLP1R(1), GLP2R(3), GPR64(3), LPHN1(1), LPHN2(6), LPHN3(13) 7428118 78 52 78 22 20 25 15 7 11 0 0.0026 0.025 66 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 DLG4(1), GRIN1(1), GRIN2A(13), GRIN2B(15), GRIN2C(2), GRIN2D(2), NOS1(10), PPP3CA(2), PPP3CB(4), PPP3CC(2), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PRKCA(4), SYT1(3) 6877564 67 51 66 18 23 19 6 10 9 0 0.0026 0.025 67 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 65 AGTR1(2), AGTR2(3), ATP8A1(5), AVPR1A(3), AVPR1B(2), AVPR2(1), BDKRB1(1), BDKRB2(2), C3AR1(1), CCKAR(2), CCKBR(1), CCR1(2), CCR10(1), CCR3(1), CCR4(3), CCR6(2), CCR8(1), CX3CR1(3), CXCR3(1), CXCR4(5), EDNRA(1), EDNRB(3), FPR1(1), FSHR(11), GALR1(3), GALT(1), GHSR(2), GPR77(3), GRPR(2), LHCGR(7), MC2R(2), MC3R(2), MC4R(1), MC5R(3), NMBR(2), NPY1R(3), NPY2R(2), NPY5R(2), NTSR1(3), NTSR2(2), OPRD1(1), OPRM1(2), OXTR(1), PPYR1(3), SSTR1(1), SSTR2(2), SSTR3(1), SSTR4(2), TACR1(2), TACR3(3), TRHR(1), TSHR(1) 13849112 118 75 118 42 27 42 23 6 20 0 0.0031 0.028 68 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(7), AKT1(1), CAMK2B(2), CAMK2D(1), CREB1(1), GNAS(5), HRAS(1), MAPK1(1), MAPK14(1), MAPK3(1), PIK3CA(20), PIK3R1(1), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PRKCA(4), RAC1(1), RPS6KA1(2), RPS6KA5(4), SOS1(6) 7817404 67 55 56 11 24 14 18 6 5 0 0.0037 0.033 69 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 74 AKT1(1), AKT3(2), BTK(4), FCER1A(2), FYN(3), HRAS(1), IL4(2), INPP5D(5), KRAS(1), LCP2(2), LYN(1), MAP2K1(2), MAP2K3(2), MAP2K6(2), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(1), MAPK8(2), MAPK9(1), MS4A2(3), PDK1(1), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(5), PLCG1(1), PLCG2(3), PRKCA(4), PRKCD(2), PRKCE(3), RAC1(1), RAF1(1), SOS1(6), SOS2(5), SYK(1), VAV1(7), VAV2(3), VAV3(1) 19629306 142 94 131 31 42 41 27 13 19 0 0.0044 0.039 70 HSA00940_PHENYLPROPANOID_BIOSYNTHESIS Genes involved in phenylpropanoid biosynthesis EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO 7 EPX(4), GBA3(6), LPO(2), MPO(3), PRDX6(1), TPO(10) 2302786 26 23 26 6 4 9 11 1 1 0 0.0044 0.039 71 SMALL_LIGAND_GPCRS C9orf47, CNR1, CNR2, DNMT1, EDG1, EDG2, EDG5, EDG6, MTNR1A, MTNR1B, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, TBXA2R 14 CNR1(2), CNR2(2), DNMT1(3), MTNR1A(1), MTNR1B(9), PTAFR(3), PTGDR(5), PTGER2(2), PTGER4(2), PTGFR(2), PTGIR(1), TBXA2R(2) 3166976 34 30 34 8 11 16 6 0 1 0 0.0046 0.039 72 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(1), AKR1D1(4), ARSB(1), ARSD(1), ARSE(2), CYP11B1(11), CYP11B2(6), HSD11B1(3), HSD11B2(1), HSD3B1(4), HSD3B2(3), SRD5A1(2), SRD5A2(2), STS(3), SULT1E1(1), SULT2A1(3), UGT1A10(2), UGT1A3(1), UGT1A5(2), UGT1A6(1), UGT1A7(1), UGT1A8(3), UGT1A9(1), UGT2B15(1), UGT2B4(4) 7061616 64 50 64 8 14 22 15 7 6 0 0.0048 0.041 73 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 31 ABAT(2), ADC(1), ALDH4A1(3), ALDH5A1(1), CAD(8), CPS1(18), EARS2(2), EPRS(10), GAD1(4), GAD2(5), GCLC(2), GCLM(1), GFPT2(1), GLS(2), GLUD1(4), GLUD2(7), GLUL(2), GOT2(2), GPT(1), GPT2(2), GSR(2), GSS(2), NADSYN1(6), PPAT(2) 10615030 90 66 89 21 20 34 19 9 8 0 0.0051 0.043 74 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 8 CUL1(2), E2F1(2), FBXW7(10), RB1(7) 2297980 21 21 19 3 1 8 2 1 9 0 0.0056 0.046 75 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 44 AKT1(1), AKT3(2), BRAF(7), CAB39(1), DDIT4(2), EIF4B(4), FIGF(1), HIF1A(1), IGF1(3), MAPK1(1), MAPK3(1), PDPK1(1), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PRKAA2(3), RICTOR(3), RPS6(1), RPS6KA1(2), RPS6KA2(3), RPS6KA3(1), RPS6KA6(4), RPS6KB1(1), STK11(3), TSC1(5), TSC2(5), ULK1(1), ULK2(2), VEGFC(4) 14641212 105 79 93 24 28 28 26 8 15 0 0.0057 0.047 76 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 CD3D(1), CD80(2), CD86(1), HLA-DRA(1), HLA-DRB1(1), ICOS(2), ITK(2), LCK(2), PIK3CA(20), PIK3R1(1), PTPN11(2) 3418312 35 31 24 8 15 9 7 2 2 0 0.0059 0.048 77 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 24 ABAT(2), ALDH4A1(3), ALDH5A1(1), CAD(8), CPS1(18), EPRS(10), GAD1(4), GAD2(5), GCLC(2), GCLM(1), GLS(2), GLUD1(4), GLUL(2), GOT2(2), GPT(1), GPT2(2), GSS(2), NADSYN1(6), PPAT(2) 8890922 77 59 76 16 18 30 18 5 6 0 0.0061 0.048 78 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 21 CSNK2A1(2), FOS(1), HRAS(1), INSR(7), IRS1(3), JUN(3), MAP2K1(2), MAPK3(1), MAPK8(2), PIK3CA(20), PIK3R1(1), PTPN11(2), RAF1(1), RASA1(5), SHC1(1), SLC2A4(2), SOS1(6), SRF(2) 6881836 62 51 50 8 23 16 12 5 6 0 0.0061 0.048 79 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 125 ARAF(3), BRAF(7), CD244(2), CHP(2), FAS(1), FASLG(1), FCGR3A(3), FCGR3B(2), FYN(3), GZMB(1), HLA-A(7), HLA-B(1), HLA-C(1), HLA-G(1), HRAS(1), ICAM1(2), IFNA1(1), IFNA10(3), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNAR1(2), IFNB1(1), IFNG(1), IFNGR1(3), IFNGR2(1), ITGAL(1), ITGB2(3), KIR2DL1(1), KIR2DL3(4), KIR3DL1(6), KIR3DL2(1), KLRC1(1), KLRC3(1), KRAS(1), LCK(2), LCP2(2), MAP2K1(2), MAPK1(1), MAPK3(1), NCR1(5), NCR2(1), NFAT5(2), NFATC2(4), NFATC3(2), NFATC4(1), PAK1(1), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PLCG1(1), PLCG2(3), PPP3CA(2), PPP3CB(4), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRF1(1), PRKCA(4), PRKCG(8), PTPN11(2), RAC1(1), RAF1(1), SH2D1A(1), SHC1(1), SHC2(2), SHC3(2), SHC4(4), SOS1(6), SOS2(5), SYK(1), TNFRSF10A(1), TNFRSF10B(1), TYROBP(3), ULBP1(1), ULBP3(1), VAV1(7), VAV2(3), VAV3(1), ZAP70(2) 30808240 218 113 206 57 58 64 47 22 25 2 0.0062 0.048 80 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 21 ADCY1(7), AKT1(1), BAX(1), BCL2L1(1), CSF2RB(5), IGF1(3), KIT(5), PIK3CA(20), PIK3R1(1), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2) 5621418 52 45 41 7 22 16 8 3 3 0 0.0062 0.048 81 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 92 ADCY1(7), ADCY2(14), ADCY3(4), ADCY4(3), ADCY5(1), ADCY7(4), ADCY8(13), ADCY9(3), DRD1(1), DRD2(2), EGF(6), EGFR(6), GJA1(4), GJD2(2), GNAI1(2), GNAI3(1), GNAS(5), GRM1(10), GRM5(11), GUCY1A2(10), GUCY1A3(5), GUCY1B3(3), GUCY2C(4), GUCY2D(1), GUCY2F(4), HRAS(1), HTR2A(1), HTR2B(1), HTR2C(2), ITPR1(4), ITPR2(11), ITPR3(1), KRAS(1), MAP2K1(2), MAP2K5(1), MAPK1(1), MAPK3(1), MAPK7(1), NPR1(2), NPR2(2), PDGFB(1), PDGFC(1), PDGFD(1), PDGFRA(8), PDGFRB(4), PLCB1(6), PLCB2(5), PLCB3(3), PLCB4(4), PRKACB(2), PRKACG(1), PRKCA(4), PRKCG(8), PRKG1(4), PRKG2(3), PRKX(1), RAF1(1), SOS1(6), SOS2(5), TJP1(8), TUBA1B(1), TUBA3C(5), TUBA3D(2), TUBA3E(3), TUBA8(1), TUBAL3(2), TUBB(1), TUBB1(1), TUBB2A(2), TUBB4(4), TUBB4Q(1), TUBB8(1) 36050340 258 125 257 68 71 76 49 30 32 0 0.0064 0.048 82 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 35 ACTA1(1), DOCK1(3), FOS(1), GAB1(2), HGF(6), HRAS(1), ITGA1(3), ITGB1(3), JUN(3), MAP2K1(2), MAP4K1(2), MAPK1(1), MAPK3(1), MAPK8(2), MET(3), PAK1(1), PIK3CA(20), PIK3R1(1), PTEN(13), PTK2(4), PTPN11(2), PXN(3), RAF1(1), RAP1B(1), RASA1(5), SOS1(6), STAT3(1) 12099016 92 71 80 24 29 23 17 8 15 0 0.0069 0.052 83 GLUCOCORTICOID_MINERALOCORTICOID_METABOLISM CPN2, CYP11A1, CYP11B2, CYP17A1, HSD11B1, HSD11B2, HSD3B1, HSD3B2 8 CPN2(1), CYP11A1(2), CYP11B2(6), CYP17A1(1), HSD11B1(3), HSD11B2(1), HSD3B1(4), HSD3B2(3) 1860812 21 19 21 5 3 9 4 4 1 0 0.0070 0.052 84 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 192 ACTB(1), ACTN1(2), ACTN2(6), ACTN3(2), ACTN4(4), AKT1(1), AKT3(2), ARHGAP5(1), BCAR1(5), BIRC3(3), BRAF(7), CAPN2(2), CAV2(1), CAV3(1), CCND2(3), CCND3(1), CDC42(1), COL11A1(31), COL11A2(10), COL1A1(8), COL1A2(12), COL2A1(8), COL3A1(10), COL4A1(6), COL4A2(6), COL4A4(9), COL4A6(6), COL5A1(5), COL5A2(11), COL5A3(11), COL6A3(10), COL6A6(19), COMP(1), CTNNB1(3), DIAPH1(1), DOCK1(3), EGF(6), EGFR(6), ERBB2(1), FARP2(6), FIGF(1), FLNA(8), FLNB(3), FLNC(11), FLT1(8), FN1(16), FYN(3), GRLF1(11), HGF(6), HRAS(1), IBSP(4), IGF1(3), ILK(1), ITGA1(3), ITGA10(5), ITGA11(3), ITGA2(5), ITGA2B(1), ITGA4(3), ITGA5(1), ITGA6(3), ITGA7(3), ITGA8(8), ITGAV(3), ITGB1(3), ITGB3(3), ITGB4(6), ITGB6(1), ITGB7(1), ITGB8(3), JUN(3), KDR(12), LAMA1(12), LAMA2(18), LAMA3(7), LAMA4(13), LAMA5(6), LAMB1(5), LAMB2(2), LAMB3(1), LAMB4(3), LAMC1(8), LAMC2(2), LAMC3(1), MAP2K1(2), MAPK1(1), MAPK10(1), MAPK3(1), MAPK8(2), MAPK9(1), MET(3), MYL2(1), MYLK(5), MYLK2(2), MYLPF(1), PAK1(1), PAK3(1), PAK4(1), PAK7(4), PARVB(1), PARVG(1), PDGFB(1), PDGFC(1), PDGFD(1), PDGFRA(8), PDGFRB(4), PDPK1(1), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PIP5K1C(1), PRKCA(4), PRKCG(8), PTEN(13), PTK2(4), PXN(3), RAC1(1), RAF1(1), RAP1B(1), RAPGEF1(3), RELN(24), ROCK1(5), ROCK2(3), SHC1(1), SHC2(2), SHC3(2), SHC4(4), SOS1(6), SOS2(5), THBS1(1), THBS2(12), THBS3(3), THBS4(1), TLN1(3), TLN2(11), TNC(11), TNN(14), TNR(16), TNXB(15), VASP(2), VAV1(7), VAV2(3), VAV3(1), VCL(2), VEGFC(4), VWF(15) 101666124 755 167 741 217 196 257 155 56 91 0 0.0080 0.059 85 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 51 ACTA1(1), AGT(1), AKT1(1), CALR(1), CAMK1G(2), CAMK4(3), CREBBP(12), CSNK1A1(2), ELSPBP1(1), FGF2(2), HAND1(1), HAND2(1), HRAS(1), IGF1(3), MAP2K1(2), MAPK1(1), MAPK14(1), MAPK3(1), MAPK8(2), MEF2C(3), MYH2(21), NFATC2(4), NFATC3(2), NFATC4(1), NKX2-5(2), PIK3CA(20), PIK3R1(1), PPP3CA(2), PPP3CB(4), PPP3CC(2), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), RAF1(1), RPS6KB1(1), SYT1(3) 13631774 114 77 103 29 38 32 18 15 11 0 0.0081 0.059 86 HSA00471_D_GLUTAMINE_AND_D_GLUTAMATE_METABOLISM Genes involved in D-glutamine and D-glutamate metabolism GLS, GLS2, GLUD1, GLUD2 4 GLS(2), GLUD1(4), GLUD2(7) 1147388 13 13 13 3 3 4 1 2 3 0 0.0088 0.063 87 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 30 B3GNT6(1), B4GALT5(2), C1GALT1C1(1), GALNT1(1), GALNT10(1), GALNT11(2), GALNT12(3), GALNT13(10), GALNT14(3), GALNT2(2), GALNT3(2), GALNT5(6), GALNT6(2), GALNT8(2), GALNTL1(3), GALNTL4(3), GALNTL5(3), GCNT1(2), GCNT3(2), OGT(2), ST3GAL1(1), ST6GALNAC1(3), WBSCR17(9) 8702954 66 57 64 19 12 25 18 5 6 0 0.0096 0.068 88 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(2), PARK2(10), SNCAIP(3), UBE2E2(1), UBE2G2(1), UBE2L6(1) 1721794 18 18 18 4 3 3 8 1 3 0 0.011 0.074 89 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(1), HLA-A(7), ITGB1(3), KLRC1(1), KLRC3(1), MAP2K1(2), MAPK3(1), PAK1(1), PIK3CA(20), PIK3R1(1), RAC1(1), SYK(1), VAV1(7) 5023516 47 38 36 7 19 7 10 5 4 2 0.012 0.081 90 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(1), HRAS(1), KLK2(1), NTRK1(3), PIK3CA(20), PIK3R1(1), PLCG1(1), PRKCA(4), SHC1(1), SOS1(6) 4212014 39 34 28 6 16 8 10 2 3 0 0.012 0.081 91 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 ARPC1A(2), CDC42(1), PAK1(1), PDGFRA(8), PIK3CA(20), PIK3R1(1), RAC1(1), WASL(2) 3584742 36 32 25 4 18 7 8 3 0 0 0.012 0.083 92 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(6), CYP2C9(2) 537204 8 8 8 3 3 1 3 0 1 0 0.013 0.089 93 EPHA4PATHWAY Eph Kinases and ephrins support platelet aggregation ACTA1, EPHA4, EPHB1, FYN, ITGA1, ITGB1, L1CAM, LYN, RAP1B, SELP 10 ACTA1(1), EPHA4(1), EPHB1(13), FYN(3), ITGA1(3), ITGB1(3), L1CAM(2), LYN(1), RAP1B(1), SELP(8) 4224830 36 34 36 17 13 7 7 1 8 0 0.014 0.090 94 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 16 AKT1(1), CREB1(1), MAP2K1(2), MAP2K3(2), MAP2K6(2), MAP3K1(2), MAPK1(1), MAPK14(1), MAPK3(1), NFKB1(2), PIK3CA(20), PIK3R1(1), RB1(7), RELA(2), SP1(1) 5286778 46 40 35 7 20 12 6 2 6 0 0.014 0.093 95 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(5), AMY2B(3), ENPP1(7), ENPP3(3), G6PC(2), GANAB(5), GBA3(6), GBE1(1), GCK(1), GPI(5), GUSB(2), GYS1(1), GYS2(4), HK1(3), HK2(5), HK3(5), MGAM(3), PYGB(3), PYGM(4), SI(31), UGDH(2), UGT1A10(2), UGT1A3(1), UGT1A5(2), UGT1A6(1), UGT1A7(1), UGT1A8(3), UGT1A9(1), UGT2B15(1), UGT2B4(4), UXS1(3) 15203514 120 78 120 26 30 44 28 8 10 0 0.015 0.098 96 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(1), AKR1D1(4), ARSD(1), ARSE(2), CARM1(1), CYP11B1(11), CYP11B2(6), CYP19A1(4), HSD11B1(3), HSD11B2(1), HSD17B1(1), HSD17B12(1), HSD17B7(1), HSD3B1(4), HSD3B2(3), LCMT1(2), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(4), PRMT8(1), SRD5A1(2), SRD5A2(2), STS(3), SULT1E1(1), SULT2A1(3), UGT1A10(2), UGT1A3(1), UGT1A5(2), UGT1A6(1), UGT1A7(1), UGT1A8(3), UGT1A9(1), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4), UGT2B7(2), WBSCR22(3) 13001654 105 73 105 14 29 33 23 11 9 0 0.016 0.10 97 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 168 ADCY1(7), ADCY2(14), ADCY3(4), ADCY4(3), ADCY7(4), ADCY8(13), ADCY9(3), ADORA2A(5), ADRA1A(2), ADRA1B(3), ADRA1D(2), ADRB2(3), AGTR1(2), ATP2A1(1), ATP2A2(3), ATP2A3(2), ATP2B1(3), ATP2B2(5), ATP2B3(2), ATP2B4(3), AVPR1A(3), AVPR1B(2), BDKRB1(1), BDKRB2(2), BST1(1), CACNA1A(7), CACNA1B(1), CACNA1C(12), CACNA1D(3), CACNA1E(14), CACNA1F(8), CACNA1G(5), CACNA1H(5), CACNA1I(8), CACNA1S(5), CALML6(1), CAMK2B(2), CAMK2D(1), CAMK4(3), CCKAR(2), CCKBR(1), CD38(1), CHP(2), CHRM2(6), CHRM3(4), CHRM5(2), CYSLTR1(2), CYSLTR2(1), DRD1(1), EDNRA(1), EDNRB(3), EGFR(6), ERBB2(1), ERBB3(3), ERBB4(9), F2R(2), GNA14(1), GNAL(1), GNAS(5), GRIN1(1), GRIN2A(13), GRIN2C(2), GRIN2D(2), GRM1(10), GRM5(11), GRPR(2), HRH1(3), HRH2(1), HTR2A(1), HTR2B(1), HTR2C(2), HTR4(3), HTR5A(3), HTR6(1), HTR7(3), ITPKA(1), ITPKB(4), ITPR1(4), ITPR2(11), ITPR3(1), LHCGR(7), LTB4R2(1), MYLK(5), MYLK2(2), NOS1(10), NOS3(1), NTSR1(3), OXTR(1), P2RX2(1), P2RX3(4), P2RX4(1), P2RX7(1), PDE1A(2), PDE1B(1), PDE1C(11), PDGFRA(8), PDGFRB(4), PHKA1(4), PHKA2(2), PHKB(6), PHKG1(2), PHKG2(1), PLCB1(6), PLCB2(5), PLCB3(3), PLCB4(4), PLCD3(1), PLCE1(11), PLCG1(1), PLCG2(3), PLCZ1(4), PLN(1), PPP3CA(2), PPP3CB(4), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKACB(2), PRKACG(1), PRKCA(4), PRKCG(8), PRKX(1), PTAFR(3), PTGER3(5), PTGFR(2), RYR1(24), RYR2(84), RYR3(38), SLC8A1(11), SLC8A3(3), SPHK2(1), TACR1(2), TACR3(3), TBXA2R(2), TNNC1(1), TRHR(1), TRPC1(4), VDAC1(1) 74744692 632 160 628 177 183 211 114 57 67 0 0.018 0.11 98 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 ASNS(3), CA12(2), CA13(1), CA14(1), CA3(2), CA4(1), CA5A(1), CA5B(2), CA6(2), CA7(1), CA9(1), CPS1(18), GLS(2), GLUD1(4), GLUD2(7), GLUL(2) 5640108 50 40 49 4 16 14 10 4 6 0 0.018 0.11 99 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 127 ABL1(2), ABLIM1(2), ABLIM2(2), ABLIM3(1), ARHGEF12(3), CDC42(1), CDK5(1), CFL1(2), CFL2(1), CHP(2), CXCR4(5), DCC(12), DPYSL2(1), DPYSL5(6), EFNA3(1), EFNB1(2), EFNB2(1), EPHA1(3), EPHA2(1), EPHA3(6), EPHA4(1), EPHA5(15), EPHA6(9), EPHA7(7), EPHA8(4), EPHB1(13), EPHB2(4), EPHB3(6), EPHB4(2), EPHB6(3), FYN(3), GNAI1(2), GNAI3(1), HRAS(1), ITGB1(3), KRAS(1), L1CAM(2), LIMK2(2), LRRC4C(18), MAPK1(1), MAPK3(1), MET(3), NCK1(2), NFAT5(2), NFATC2(4), NFATC3(2), NFATC4(1), NGEF(1), NRP1(5), NTN1(2), NTN4(1), NTNG1(1), PAK1(1), PAK3(1), PAK4(1), PAK7(4), PLXNA1(6), PLXNA2(2), PLXNA3(3), PLXNB1(3), PLXNB3(3), PLXNC1(8), PPP3CA(2), PPP3CB(4), PPP3CC(2), PPP3R1(1), PPP3R2(3), PTK2(4), RAC1(1), RASA1(5), RGS3(4), ROBO1(6), ROBO2(6), ROBO3(4), ROCK1(5), ROCK2(3), SEMA3A(3), SEMA3B(1), SEMA3C(5), SEMA3D(2), SEMA3E(3), SEMA3F(3), SEMA3G(1), SEMA4A(1), SEMA4B(1), SEMA4C(2), SEMA4D(1), SEMA4F(5), SEMA5A(7), SEMA5B(4), SEMA6C(5), SEMA6D(6), SEMA7A(1), SLIT1(4), SLIT2(10), SLIT3(8), SRGAP1(2), SRGAP2(4), SRGAP3(3), UNC5B(2), UNC5C(6), UNC5D(12) 54208654 362 140 362 129 94 119 69 30 50 0 0.019 0.12 100 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 86 AGRN(1), CD36(1), CD44(3), CD47(2), COL11A1(31), COL11A2(10), COL1A1(8), COL1A2(12), COL2A1(8), COL3A1(10), COL4A1(6), COL4A2(6), COL4A4(9), COL4A6(6), COL5A1(5), COL5A2(11), COL5A3(11), COL6A3(10), COL6A6(19), DAG1(1), FN1(16), FNDC1(7), FNDC3A(1), GP1BA(2), GP5(3), GP6(2), GP9(1), HMMR(1), HSPG2(7), IBSP(4), ITGA1(3), ITGA10(5), ITGA11(3), ITGA2(5), ITGA2B(1), ITGA4(3), ITGA5(1), ITGA6(3), ITGA7(3), ITGA8(8), ITGAV(3), ITGB1(3), ITGB3(3), ITGB4(6), ITGB6(1), ITGB7(1), ITGB8(3), LAMA1(12), LAMA2(18), LAMA3(7), LAMA4(13), LAMA5(6), LAMB1(5), LAMB2(2), LAMB3(1), LAMB4(3), LAMC1(8), LAMC2(2), LAMC3(1), RELN(24), SDC1(1), SDC2(2), SDC3(1), SV2A(2), SV2B(4), SV2C(3), THBS1(1), THBS2(12), THBS3(3), THBS4(1), TNC(11), TNN(14), TNR(16), TNXB(15), VWF(15) 62294660 472 148 471 136 121 173 103 22 53 0 0.019 0.12 101 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 22 ADCY1(7), AKT1(1), GNAI1(2), GNB1(1), ITGAV(3), ITGB3(3), MAPK1(1), MAPK3(1), PDGFRA(8), PIK3CA(20), PIK3R1(1), PLCB1(6), PRKCA(4), PTK2(4), RAC1(1), SMPD1(3), SMPD2(1) 7352290 67 52 56 14 28 19 13 6 1 0 0.019 0.12 102 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(2), ACOX3(4), FADS2(1), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(5) 2761848 26 24 26 3 6 7 6 3 4 0 0.022 0.13 103 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 74 ARAF(3), BRAF(7), C7orf16(1), CACNA1A(7), CRHR1(2), GNA12(1), GNAI1(2), GNAI3(1), GNAS(5), GNAZ(2), GRIA1(6), GRIA2(3), GRIA3(8), GRID2(12), GRM1(10), GRM5(11), GUCY1A2(10), GUCY1A3(5), GUCY1B3(3), GUCY2C(4), GUCY2D(1), GUCY2F(4), HRAS(1), IGF1(3), ITPR1(4), ITPR2(11), ITPR3(1), KRAS(1), LYN(1), MAP2K1(2), MAPK1(1), MAPK3(1), NOS1(10), NOS3(1), NPR1(2), NPR2(2), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(5), PLCB1(6), PLCB2(5), PLCB3(3), PLCB4(4), PPP2R1A(5), PPP2R1B(2), PPP2R2A(1), PPP2R2B(1), PPP2R2C(1), PRKCA(4), PRKCG(8), PRKG1(4), PRKG2(3), RAF1(1), RYR1(24) 30301296 240 113 240 67 57 82 45 23 33 0 0.022 0.13 104 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 ERBB4(9), NRG2(2), NRG3(5), PRKCA(4), PSEN1(1) 2417774 21 21 21 6 3 8 3 2 5 0 0.023 0.14 105 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 52 ALG6(2), CCKBR(1), CCR3(1), CELSR1(9), CELSR2(5), CELSR3(9), CHRM2(6), CHRM3(4), CXCR3(1), DRD4(1), EDNRA(1), EMR2(4), EMR3(3), F2R(2), FSHR(11), GHRHR(3), GPR116(5), GPR132(1), GPR133(1), GPR143(2), GPR17(3), GPR18(1), GPR55(1), GPR56(1), GPR61(2), GPR77(3), GRM1(10), GRPR(2), HRH4(3), LGR6(2), LPHN2(6), LPHN3(13), LTB4R2(1), NTSR1(3), OR8G2(1), P2RY13(1), PTGFR(2), SMO(1), SSTR2(2), TAAR5(5), TSHR(1), VN1R1(2) 18169350 138 87 138 50 36 48 31 9 14 0 0.026 0.15 106 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 109 ACTN1(2), ACTN2(6), ACTN3(2), ACTN4(4), ARHGAP5(1), BCAR1(5), CDC42(1), CDH5(1), CLDN1(2), CLDN10(4), CLDN16(4), CLDN17(1), CLDN19(1), CLDN2(1), CLDN22(1), CLDN3(1), CLDN6(1), CLDN8(1), CLDN9(3), CTNNA2(17), CTNNA3(10), CTNNB1(3), CTNND1(3), CXCR4(5), CYBB(6), ESAM(4), F11R(1), GNAI1(2), GNAI3(1), GRLF1(11), ICAM1(2), ITGA4(3), ITGAL(1), ITGAM(3), ITGB1(3), ITGB2(3), ITK(2), MAPK13(2), MAPK14(1), MLLT4(1), MMP2(3), MMP9(4), MSN(3), MYL2(1), MYLPF(1), NCF2(2), NCF4(1), NOX1(2), NOX3(5), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PLCG1(1), PLCG2(3), PRKCA(4), PRKCG(8), PTK2(4), PTPN11(2), PXN(3), RAC1(1), RAP1B(1), RAPGEF4(5), RASSF5(1), RHOH(3), ROCK1(5), ROCK2(3), THY1(2), TXK(3), VASP(2), VAV1(7), VAV2(3), VAV3(1), VCAM1(4), VCL(2) 34291522 258 122 247 86 73 86 52 24 23 0 0.026 0.15 107 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(2), FOS(1), HRAS(1), IGF1(3), IRS1(3), JUN(3), MAP2K1(2), MAPK3(1), MAPK8(2), PIK3CA(20), PIK3R1(1), PTPN11(2), RAF1(1), RASA1(5), SHC1(1), SOS1(6), SRF(2) 6671084 56 47 44 6 22 14 11 4 5 0 0.027 0.16 108 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 20 ALDH18A1(3), ARG1(2), ASL(3), CKB(1), CKM(2), CKMT2(1), CPS1(18), GATM(1), GLUD1(4), NAGS(1), ODC1(1), OTC(2), SMS(2) 4693148 41 35 40 6 13 12 9 1 6 0 0.027 0.16 109 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 12 ADCY1(7), ADRB2(3), GNAS(5), PLCE1(11), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2) 3962102 34 31 33 10 13 8 5 4 4 0 0.028 0.16 110 NITROGEN_METABOLISM AMT, ASNS, CA1, CA12, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA8, CA9, CPS1, CTH, GLS, GLS2, GLUD1, GLUL, HAL 21 ASNS(3), CA12(2), CA14(1), CA3(2), CA4(1), CA5A(1), CA5B(2), CA6(2), CA7(1), CA9(1), CPS1(18), GLS(2), GLUD1(4), GLUL(2) 5026186 42 36 41 3 14 12 10 2 4 0 0.031 0.17 111 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(1), CREB1(1), HRAS(1), MAPK1(1), MAPK3(1), MAPK7(1), MEF2A(2), MEF2C(3), MEF2D(2), NTRK1(3), PIK3CA(20), PIK3R1(1), PLCG1(1), RPS6KA1(2), SHC1(1) 5185496 41 38 30 9 19 10 7 3 2 0 0.034 0.19 112 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(2), C1QB(2), C1R(2), C1S(2), C2(1), C3(3), C5(1), C6(14), C7(7), C8A(3), C9(1), MASP1(9), MASP2(1), MBL2(3) 5864922 51 40 51 15 11 19 11 4 6 0 0.034 0.19 113 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 43 ABP1(4), ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH4A1(3), ALDH9A1(2), AMD1(1), AOC2(1), AOC3(3), ARG1(2), ASL(3), CKB(1), CKM(2), CKMT2(1), CPS1(18), DAO(1), GATM(1), GLUD1(4), GOT2(2), NOS1(10), NOS3(1), ODC1(1), OTC(2), P4HA1(2), P4HA2(2), P4HA3(3), RARS(4), SMS(2) 11910336 82 66 81 20 22 28 15 5 12 0 0.039 0.21 114 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 CAMK1G(2), HDAC9(13), MEF2A(2), MEF2C(3), MEF2D(2) 2222864 22 20 22 7 11 3 4 2 2 0 0.043 0.23 115 STEROID_BIOSYNTHESIS CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 9 CYP17A1(1), F13B(7), HSD17B1(1), HSD17B4(1), HSD17B7(1), HSD3B1(4), HSD3B2(3) 2187264 18 18 18 4 6 4 4 3 1 0 0.045 0.24 116 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(1), AKT3(2), IARS(3), IL13RA1(2), IL2RG(1), IL4(2), IL4R(1), INPP5D(5), JAK1(1), JAK2(3), JAK3(7), NR0B2(1), PI3(1), PIK3CA(20), PPP1R13B(4), RPS6KB1(1), SERPINA4(4), SHC1(1), SOS1(6), SOS2(5), STAT6(1), TYK2(5) 10061984 77 59 66 12 18 24 21 4 10 0 0.047 0.25 117 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 23 BCAR1(5), CXCR4(5), GNAI1(2), GNB1(1), HRAS(1), MAP2K1(2), MAPK1(1), MAPK3(1), NFKB1(2), PIK3C2G(6), PIK3CA(20), PIK3R1(1), PLCG1(1), PRKCA(4), PTK2(4), PXN(3), RAF1(1), RELA(2) 7686040 62 50 51 15 25 18 11 5 3 0 0.047 0.25 118 NICOTINATE_AND_NICOTINAMIDE_METABOLISM AOX1, CD38, ENPP1, ENPP3, NADSYN1, NMNAT1, NMNAT2, NNMT, NNT, NP, NT5C, NT5E, NT5M, QPRT 13 AOX1(9), CD38(1), ENPP1(7), ENPP3(3), NADSYN1(6), NMNAT2(2), NNT(7), NT5E(2) 3938428 37 30 37 6 7 16 7 4 3 0 0.047 0.25 119 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(1), CXCR3(1), ETV5(1), IFNG(1), IL12A(1), IL12B(2), IL12RB1(3), IL12RB2(3), IL18R1(2), JAK2(3), JUN(3), MAP2K6(2), MAPK14(1), MAPK8(2), STAT4(4), TYK2(5) 4886634 35 34 34 7 7 12 8 3 5 0 0.050 0.26 120 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 15 AKT1(1), AKT3(2), HRAS(1), MAP2K1(2), NGFR(1), NTRK1(3), PIK3CA(20), PIK3CD(3), SHC1(1), SOS1(6) 4474208 40 34 29 9 17 11 8 2 2 0 0.051 0.26 121 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(2), GNAS(5), GNB1(1), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PRKCA(4) 2534364 20 20 20 6 4 8 3 2 3 0 0.051 0.26 122 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(12), EP300(6), LPL(3), NCOA1(5), NCOA2(9), RXRA(1) 4966378 36 33 35 14 6 14 7 3 6 0 0.055 0.28 123 HSA00780_BIOTIN_METABOLISM Genes involved in biotin metabolism BTD, HLCS, SPCS1, SPCS3 4 BTD(1), HLCS(5), SPCS1(1), SPCS3(2) 845144 9 8 9 1 0 2 2 1 4 0 0.057 0.28 124 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(2), ACTB(1), ARHGEF2(5), CD14(1), CDC42(1), CDH1(3), CLDN1(2), CTNNB1(3), CTTN(2), FYN(3), HCLS1(3), ITGB1(3), KRT18(2), NCK1(2), NCL(1), PRKCA(4), ROCK1(5), ROCK2(3), TLR4(10), TLR5(2), TUBA1B(1), TUBA3C(5), TUBA3D(2), TUBA3E(3), TUBA8(1), TUBAL3(2), TUBB(1), TUBB1(1), TUBB2A(2), TUBB4(4), TUBB4Q(1), TUBB8(1), WAS(4), WASL(2), YWHAQ(1) 14327042 89 68 89 20 16 30 20 11 12 0 0.058 0.28 125 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(2), ACTB(1), ARHGEF2(5), CD14(1), CDC42(1), CDH1(3), CLDN1(2), CTNNB1(3), CTTN(2), FYN(3), HCLS1(3), ITGB1(3), KRT18(2), NCK1(2), NCL(1), PRKCA(4), ROCK1(5), ROCK2(3), TLR4(10), TLR5(2), TUBA1B(1), TUBA3C(5), TUBA3D(2), TUBA3E(3), TUBA8(1), TUBAL3(2), TUBB(1), TUBB1(1), TUBB2A(2), TUBB4(4), TUBB4Q(1), TUBB8(1), WAS(4), WASL(2), YWHAQ(1) 14327042 89 68 89 20 16 30 20 11 12 0 0.058 0.28 126 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(3), C5(1), C6(14), C7(7), C8A(3), C9(1) 3440384 29 25 29 9 7 8 7 3 4 0 0.058 0.28 127 COMPLEMENT_ACTIVATION_CLASSICAL C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C9, DAF, MASP1 13 C1QA(2), C1QB(2), C1R(2), C1S(2), C2(1), C3(3), C5(1), C6(14), C7(7), C8A(3), C8B(2), C9(1), MASP1(9) 5718962 49 38 49 17 12 17 11 4 5 0 0.060 0.29 128 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(2), IFNB1(1), JAK1(1), PTPRU(5), REG1A(11), STAT1(2), STAT2(1), TYK2(5) 3383424 28 25 28 7 2 15 4 4 3 0 0.061 0.29 129 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(2), FOS(1), HRAS(1), JUN(3), KLK2(1), MAP2K1(2), MAPK3(1), MAPK8(2), NGFR(1), PIK3CA(20), PIK3R1(1), PLCG1(1), RAF1(1), SHC1(1), SOS1(6) 5181046 44 38 32 7 20 9 11 3 1 0 0.061 0.29 130 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(6), COL4A2(6), COL4A3(5), COL4A4(9), COL4A5(2), COL4A6(6), F10(3), F11(3), F12(1), F2R(2), F5(14), F8(9), F9(4), FGA(5), FGB(3), FGG(1), KLKB1(4), SERPINC1(5), SERPING1(1) 12073384 89 63 89 21 16 38 20 5 10 0 0.061 0.29 131 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 26 CSNK2A1(2), FOS(1), HRAS(1), JAK1(1), JUN(3), MAP2K1(2), MAP3K1(2), MAPK3(1), MAPK8(2), PDGFRA(8), PIK3CA(20), PIK3R1(1), PLCG1(1), PRKCA(4), RAF1(1), RASA1(5), SHC1(1), SOS1(6), SRF(2), STAT1(2), STAT3(1), STAT5A(2) 9354434 69 56 57 12 29 14 15 5 6 0 0.066 0.31 132 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 10 ALDOA(1), CTSD(1), ESR1(5), GREB1(12), HSPB2(1), MTA1(1), MTA3(2), TUBA8(1) 3050208 24 24 24 10 9 7 6 1 1 0 0.069 0.32 133 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 95 ADCY1(7), ADCY2(14), ADCY3(4), ADCY4(3), ADCY5(1), ADCY7(4), ADCY8(13), ADCY9(3), CACNA1C(12), CACNA1D(3), CACNA1F(8), CACNA1S(5), CALML6(1), CAMK2B(2), CAMK2D(1), CDC42(1), EGFR(6), FSHB(1), GNAS(5), HBEGF(1), HRAS(1), ITPR1(4), ITPR2(11), ITPR3(1), JUN(3), KRAS(1), LHB(1), MAP2K1(2), MAP2K3(2), MAP2K6(2), MAP3K1(2), MAP3K4(4), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(1), MAPK7(1), MAPK8(2), MAPK9(1), MMP14(2), MMP2(3), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(5), PLCB1(6), PLCB2(5), PLCB3(3), PLCB4(4), PLD1(6), PLD2(2), PRKACB(2), PRKACG(1), PRKCA(4), PRKCD(2), PRKX(1), RAF1(1), SOS1(6), SOS2(5) 35211604 211 117 209 59 58 70 40 22 21 0 0.070 0.32 134 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(7), ADCY2(14), ADCY3(4), ADCY4(3), ADCY5(1), ADCY7(4), ADCY8(13), ADCY9(3), AKAP1(2), AKAP11(7), AKAP12(3), AKAP3(6), AKAP5(1), AKAP6(11), AKAP7(2), AKAP8(3), AKAP9(7), ARHGEF1(2), CHMP1B(1), GNA12(1), GNA14(1), GNAI3(1), GNAL(1), GNAZ(2), GNB1(1), GNB2(2), GNB5(1), GNG12(1), GNG4(2), GNG5(1), HRAS(1), ITPR1(4), KCNJ3(7), KRAS(1), PDE1A(2), PDE1B(1), PDE1C(11), PDE4A(1), PDE4B(3), PDE4C(2), PDE4D(1), PDE7B(1), PDE8A(5), PDE8B(2), PLCB3(3), PPP3CA(2), PPP3CC(2), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PRKCA(4), PRKCD(2), PRKCE(3), PRKCG(8), PRKCI(4), PRKCQ(4), PRKD1(9), PRKD3(2), SLC9A1(3), USP5(1) 31769796 205 108 205 45 57 64 39 21 24 0 0.074 0.34 135 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 17 ARSB(1), GNS(1), GUSB(2), HEXA(4), HGSNAT(1), HPSE(3), HPSE2(2), HYAL1(3), IDS(1), IDUA(2), LCT(14), SPAM1(3) 5629962 37 34 37 9 8 8 10 4 7 0 0.075 0.34 136 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 67 A2M(4), BDKRB1(1), BDKRB2(2), C1QA(2), C1QB(2), C1R(2), C1S(2), C2(1), C3(3), C3AR1(1), C4BPA(1), C5(1), C5AR1(1), C6(14), C7(7), C8A(3), C8B(2), C9(1), CD46(2), CFB(1), CFH(4), CFI(2), CPB2(2), CR1(4), CR2(9), F10(3), F11(3), F12(1), F13A1(3), F13B(7), F2R(2), F3(1), F5(14), F8(9), F9(4), FGA(5), FGB(3), FGG(1), KLKB1(4), KNG1(4), MASP1(9), MASP2(1), MBL2(3), PLAT(1), PLAU(2), PLG(1), SERPINA1(1), SERPINA5(1), SERPINC1(5), SERPIND1(1), SERPINF2(3), SERPING1(1), VWF(15) 24590700 182 99 182 58 41 60 45 18 18 0 0.077 0.35 137 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(2), FOS(1), HRAS(1), JAK2(3), JUN(3), MAP2K1(2), MAPK3(1), MPL(2), PIK3CA(20), PIK3R1(1), PLCG1(1), PRKCA(4), RAF1(1), RASA1(5), SHC1(1), SOS1(6), STAT1(2), STAT3(1), STAT5A(2) 8070520 59 49 47 7 23 10 14 4 8 0 0.079 0.36 138 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 13 AKT1(1), GHR(2), HRAS(1), IGF1(3), PIK3CA(20), PIK3R1(1), SHC1(1), SOD2(1) 3592396 30 28 19 6 15 8 5 2 0 0 0.081 0.36 139 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(3), AGT(1), AGTR1(2), AGTR2(3), CMA1(2), COL4A1(6), COL4A2(6), COL4A3(5), COL4A4(9), COL4A5(2), COL4A6(6) 6924734 45 41 45 14 10 22 7 0 6 0 0.082 0.37 140 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(1), BCL2L1(1), CASP9(2), CDC42(1), CHUK(2), H2AFX(1), HRAS(1), MAP2K1(2), MAPK3(1), NFKB1(2), PIK3CA(20), PIK3R1(1), RAC1(1), RAF1(1), RALA(2), RALBP1(1), RALGDS(1), RELA(2) 5225724 43 36 32 7 19 8 7 6 3 0 0.083 0.37 141 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(7), ADRB2(3), CFTR(5), GNAS(5), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2) 3468864 28 25 28 8 9 7 6 3 3 0 0.086 0.37 142 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(3), KHK(1), LCT(14), MPI(1), PYGM(4), TPI1(3), TREH(1) 3613934 27 25 27 9 8 3 9 3 4 0 0.086 0.37 143 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(7), GNAS(5), GNB1(1), PRKAR1A(2) 1804742 15 15 15 5 4 5 3 2 1 0 0.091 0.39 144 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(1), EIF2B1(1), EIF2B2(1), EIF2B3(1), EIF2B5(1), ELAVL1(1), FLT1(8), FLT4(3), HIF1A(1), HRAS(1), KDR(12), NOS3(1), PIK3CA(20), PIK3R1(1), PLCG1(1), PRKCA(4), PTK2(4), PXN(3), SHC1(1), VHL(1) 9270240 67 53 56 19 25 16 10 9 7 0 0.092 0.39 145 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(1), CD3D(1), CD4(1), CXCR3(1), IFNG(1), IL12A(1), IL12B(2), IL12RB1(3), IL12RB2(3), JAK2(3), STAT4(4), TYK2(5) 3830026 26 25 26 7 4 7 7 2 6 0 0.093 0.39 146 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 44 ABCA1(5), ABCA10(8), ABCA12(7), ABCA13(25), ABCA2(6), ABCA3(3), ABCA4(10), ABCA5(4), ABCA6(6), ABCA7(3), ABCA8(5), ABCA9(9), ABCB1(15), ABCB10(4), ABCB11(5), ABCB4(6), ABCB5(6), ABCB6(3), ABCB7(2), ABCB8(1), ABCB9(3), ABCC1(4), ABCC10(5), ABCC11(3), ABCC12(12), ABCC2(4), ABCC3(1), ABCC4(1), ABCC5(4), ABCC6(1), ABCC8(5), ABCC9(9), ABCD1(3), ABCD2(10), ABCD4(1), ABCG1(1), ABCG2(1), ABCG4(1), ABCG5(1), ABCG8(4), CFTR(5), TAP1(2) 32453316 214 114 214 70 48 76 51 14 23 2 0.095 0.40 147 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 34 AKT1(1), APC(9), AR(4), BRAF(7), CCL16(1), DAG1(1), EGFR(6), GNAI1(2), ITPKA(1), ITPKB(4), ITPR1(4), ITPR2(11), ITPR3(1), KCNJ3(7), KCNJ5(2), KCNJ9(2), MAPK1(1), MAPK10(1), MAPK14(1), PHKA2(2), PIK3CA(20), PIK3CD(3), PIK3R1(1), PITX2(3), PTX3(2), RAF1(1) 14631244 98 73 86 19 35 26 22 5 10 0 0.097 0.40 148 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(9), BST1(1), CD38(1), ENPP1(7), ENPP3(3), NADSYN1(6), NMNAT2(2), NNT(7), NT5C1A(2), NT5C1B(1), NT5C2(2), NT5C3(3), NT5E(2), NUDT12(2) 5841960 48 38 48 10 10 20 9 4 5 0 0.097 0.40 149 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(1), CHRNB1(1), CHRNG(4), MUSK(2), PIK3CA(20), PIK3R1(1), PTK2(4), RAPSN(3), TERT(3) 4523692 39 34 28 10 22 10 5 1 1 0 0.10 0.42 150 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(1), CASP9(2), CHUK(2), GHR(2), NFKB1(2), PDPK1(1), PIK3CA(20), PIK3R1(1), RELA(2) 3843198 33 28 22 9 14 7 6 4 2 0 0.10 0.42 151 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(1), IFNGR1(3), JAK1(1), JAK2(3), PLA2G2A(1), PTPRU(5), REG1A(11), STAT1(2) 3103786 27 23 27 5 2 13 8 1 3 0 0.10 0.42 152 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(2), CCR1(2), CCR3(1), CCR4(3), CD4(1), CXCR3(1), CXCR4(5), IFNG(1), IFNGR1(3), IFNGR2(1), IL12A(1), IL12B(2), IL12RB1(3), IL12RB2(3), IL18R1(2), IL4(2), IL4R(1), TGFB1(1), TGFB2(2) 5101124 37 32 37 13 8 12 9 0 8 0 0.10 0.42 153 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(1), E2F1(2), HRAS(1), MAPK1(1), MAPK3(1), NFKB1(2), PAK1(1), PIK3CA(20), PIK3R1(1), RAC1(1), RAF1(1), RB1(7), RELA(2) 5529036 41 36 30 3 16 10 5 4 6 0 0.10 0.42 154 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(2), EGF(6), EGFR(6), FOS(1), HRAS(1), JAK1(1), JUN(3), MAP2K1(2), MAP3K1(2), MAPK3(1), MAPK8(2), PIK3CA(20), PIK3R1(1), PLCG1(1), PRKCA(4), RAF1(1), RASA1(5), SHC1(1), SOS1(6), SRF(2), STAT1(2), STAT3(1), STAT5A(2) 10098296 73 57 60 11 29 17 15 4 8 0 0.11 0.44 155 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 23 IMPA1(1), INPP1(1), INPP4A(5), INPP4B(4), INPP5A(3), INPPL1(3), ITPKA(1), ITPKB(4), OCRL(5), PIK3C2A(4), PIK3C2B(6), PIK3C2G(6), PIK3CA(20), PIK3CB(2), PIK3CG(9), PLCB1(6), PLCB2(5), PLCB3(3), PLCB4(4), PLCG1(1), PLCG2(3) 12318668 96 63 85 24 37 20 21 6 12 0 0.11 0.45 156 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 17 CBL(1), EGF(6), EGFR(6), HRAS(1), MAP2K1(2), MAPK1(1), MAPK3(1), PTPRB(13), RAF1(1), RASA1(5), SHC1(1), SOS1(6) 6589916 44 39 43 7 11 13 8 3 9 0 0.11 0.45 157 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(5), AGT(1), AGTR2(3), EDNRA(1), EDNRB(3), EGF(6), EGFR(6), FOS(1), HRAS(1), JUN(3), MYC(1), NFKB1(2), PLCG1(1), PRKCA(4), RELA(2) 5560898 40 34 38 11 8 13 7 4 8 0 0.12 0.46 158 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 78 ABL1(2), ACTN1(2), AKT1(1), AKT3(2), ARHGEF6(2), ARHGEF7(3), BCAR1(5), BRAF(7), CDC42(1), CDKN2A(22), CSE1L(4), DOCK1(3), EPHB2(4), FYN(3), GRLF1(11), ILK(1), ITGA1(3), ITGA10(5), ITGA11(3), ITGA2(5), ITGA4(3), ITGA5(1), ITGA6(3), ITGA7(3), ITGA8(8), ITGB3BP(1), MAP3K11(2), MAPK1(1), MAPK10(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(3), MAPK9(1), MRAS(2), MYLK(5), MYLK2(2), PAK1(1), PAK3(1), PAK4(1), PAK7(4), PIK3CA(20), PIK3CB(2), PKLR(3), PLCG1(1), PLCG2(3), PTEN(13), PTK2(4), RAF1(1), RALA(2), RHO(1), ROCK1(5), ROCK2(3), SHC1(1), SOS1(6), SOS2(5), TLN1(3), TLN2(11), VASP(2), WAS(4) 33437656 226 115 212 62 54 73 48 10 41 0 0.12 0.46 159 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 19 ADCY1(7), ARHGEF1(2), F2R(2), F2RL3(1), GNA12(1), GNAI1(2), GNB1(1), MAP3K7(2), PIK3CA(20), PIK3R1(1), PLCB1(6), PPP1R12B(4), PRKCA(4), ROCK1(5) 7032780 58 46 47 12 22 19 11 4 2 0 0.12 0.46 160 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 82 ACVR1B(3), ACVRL1(3), AKT1(1), BMPR1A(3), BUB1(3), CDKL2(2), CDS1(2), CLK1(1), CLK2(1), CLK4(2), COL4A3BP(3), CSNK2A1(2), DGKA(3), DGKB(3), DGKD(5), DGKE(3), DGKG(1), DGKZ(3), IMPA1(1), INPP1(1), INPP4A(5), INPP4B(4), INPP5A(3), INPPL1(3), ITPKA(1), ITPKB(4), MOS(4), NEK1(3), OCRL(5), PAK4(1), PIK3C2A(4), PIK3C2B(6), PIK3C2G(6), PIK3CA(20), PIK3CB(2), PIK3CG(9), PIM2(2), PLCB1(6), PLCB2(5), PLCB3(3), PLCB4(4), PLCG1(1), PLCG2(3), PLK3(3), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PRKCA(4), PRKCD(2), PRKCE(3), PRKCG(8), PRKCQ(4), PRKD1(9), PRKG1(4), RAF1(1), RPS6KA1(2), RPS6KA2(3), RPS6KA3(1), RPS6KA4(1), RPS6KB1(1), STK11(3), VRK1(1) 31164596 208 107 196 48 67 58 42 15 26 0 0.12 0.47 161 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 54 ADH1B(1), ADH1C(1), ADH4(2), ADH5(1), ADH7(1), ADHFE1(2), AGPAT3(1), AGPAT6(1), ALDH1B1(2), ALDH2(2), ALDH7A1(1), ALDH9A1(2), CEL(1), DAK(1), DGAT2(2), DGKA(3), DGKB(3), DGKD(5), DGKE(3), DGKG(1), DGKI(7), DGKZ(3), GK(4), GK2(5), GLA(2), GPAM(2), LCT(14), LIPA(2), LIPC(1), LIPF(1), LIPG(2), LPL(3), MGLL(1), PNLIP(9), PNLIPRP1(3), PNLIPRP2(2), PNPLA3(1), PPAP2B(1) 15884364 99 76 99 36 27 37 15 12 8 0 0.13 0.48 162 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 81 ANPEP(5), CD14(1), CD19(2), CD1A(4), CD1B(5), CD1C(5), CD1D(3), CD1E(4), CD2(1), CD22(5), CD33(2), CD34(2), CD36(1), CD37(2), CD38(1), CD3D(1), CD4(1), CD44(3), CD5(2), CD8B(1), CD9(1), CR1(4), CR2(9), CSF1(2), CSF1R(3), CSF3R(5), DNTT(2), EPOR(2), FCER2(1), FCGR1A(1), FLT3(4), GP1BA(2), GP5(3), GP9(1), HLA-DRA(1), HLA-DRB1(1), HLA-DRB5(2), IL11RA(1), IL1B(1), IL1R2(3), IL4(2), IL4R(1), IL5RA(2), IL6R(1), IL7R(2), ITGA1(3), ITGA2(5), ITGA2B(1), ITGA4(3), ITGA5(1), ITGA6(3), ITGAM(3), ITGB3(3), KIT(5), MME(8), MS4A1(2), TFRC(2), TPO(10) 21879404 157 93 157 62 38 68 29 5 17 0 0.13 0.48 163 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(6), ADCY3(4), ADCY9(3), ARF1(1), ARF5(3), ATP6V0A1(4), ATP6V0A2(5), ATP6V0A4(2), ATP6V0D1(1), ATP6V0D2(2), ATP6V1A(3), ATP6V1C1(1), ATP6V1D(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(3), ERO1L(1), GNAS(5), PDIA4(1), PLCG1(1), PLCG2(3), PRKCA(4), SEC61A1(2), SEC61A2(1), TRIM23(2) 10010542 61 52 61 16 12 20 17 6 6 0 0.13 0.48 164 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(1), HEXA(4), LCT(14), SLC33A1(2), ST3GAL1(1), ST3GAL5(2), ST6GALNAC3(3), ST6GALNAC5(2), ST8SIA1(2) 4440388 31 28 31 13 11 5 7 3 5 0 0.14 0.52 165 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(3), AKT1(1), GNAS(5), GNB1(1), NFKB1(2), NOS3(1), PIK3CA(20), PIK3R1(1), RELA(2), SYT1(3) 4937720 39 33 28 10 18 7 8 5 1 0 0.14 0.52 166 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 28 BRAF(7), CPEB1(1), EGFR(6), ERBB2(1), ERBB4(9), ETS1(2), ETV6(4), FMN2(21), KRAS(1), MAP2K1(2), MAPK1(1), MAPK3(1), NOTCH1(10), NOTCH2(6), NOTCH3(4), NOTCH4(3), PIWIL1(5), PIWIL2(3), PIWIL3(3), RAF1(1), SOS1(6), SOS2(5), SPIRE1(1) 14423162 103 70 101 33 21 42 17 7 16 0 0.14 0.52 167 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 23 ALDOA(1), ALDOB(2), FBP2(1), GOT2(2), GPT(1), GPT2(2), MDH1(1), MDH2(1), ME3(1), PGK1(1), PGK2(4), PKLR(3), PKM2(2), RPIA(1), TKT(1), TKTL2(9), TPI1(3) 5308138 36 33 36 17 7 10 10 5 4 0 0.14 0.53 168 LYSINE_BIOSYNTHESIS AADAT, AASDH, AASDHPPT, AASS, KARS 5 AADAT(1), AASDH(5), AASDHPPT(1), AASS(6), KARS(2) 1862592 15 15 15 5 2 5 4 2 2 0 0.15 0.53 169 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(12), EP300(6), FYN(3), IL2RG(1), IL7R(2), JAK1(1), JAK3(7), LCK(2), NMI(1), PIK3CA(20), PIK3R1(1), STAT5A(2) 7626588 58 47 46 14 19 18 13 4 4 0 0.15 0.53 170 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 CDK5(1), CFL1(2), CHN1(2), MAP3K1(2), MYL2(1), MYLK(5), NCF2(2), PAK1(1), PDGFRA(8), PIK3CA(20), PIK3R1(1), PLD1(6), PPP1R12B(4), RAC1(1), RALBP1(1), RPS6KB1(1), TRIO(5), VAV1(7) 9449664 70 54 59 18 22 21 18 7 2 0 0.15 0.55 171 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), DAB1(5), FYN(3), LRP8(1), RELN(24) 3755444 34 25 34 9 7 9 10 7 1 0 0.15 0.55 172 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(1), CREBBP(12), DFFB(2), GZMA(4), GZMB(1), PRF1(1) 2860104 21 20 21 9 6 6 3 2 4 0 0.15 0.55 173 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 69 AKT1(1), AKT3(2), CASP9(2), CDC42(1), CHP(2), HRAS(1), KDR(12), KRAS(1), MAP2K1(2), MAPK1(1), MAPK13(2), MAPK14(1), MAPK3(1), MAPKAPK2(1), NFAT5(2), NFATC2(4), NFATC3(2), NFATC4(1), NOS3(1), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(5), PLCG1(1), PLCG2(3), PPP3CA(2), PPP3CB(4), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKCA(4), PRKCG(8), PTK2(4), PXN(3), RAC1(1), RAF1(1), SHC2(2), SPHK2(1) 19897018 141 85 130 40 49 37 20 19 16 0 0.15 0.55 174 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 13 ACTN1(2), ACTN2(6), ACTN3(2), BCAR1(5), CTNNA2(17), CTNNB1(3), PTK2(4), PXN(3), VCL(2) 5688346 44 36 44 25 12 19 6 6 1 0 0.16 0.55 175 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(1), HRAS(1), IRS1(3), MAP2K1(2), MAPK1(1), MAPK3(1), PIK3CA(20), PIK3R1(1), RAF1(1), SHC1(1), SOS1(6) 5084392 38 34 27 3 17 9 9 2 1 0 0.16 0.55 176 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(3), ARG1(2), GLS(2), GLUD1(4) 1445894 11 11 11 5 1 7 2 0 1 0 0.17 0.58 177 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 25 GHR(2), HRAS(1), INSR(7), IRS1(3), JAK2(3), MAP2K1(2), MAPK1(1), MAPK3(1), PIK3CA(20), PIK3R1(1), PLCG1(1), PRKCA(4), RAF1(1), RPS6KA1(2), SHC1(1), SLC2A4(2), SOS1(6), SRF(2), STAT5A(2) 8934888 62 51 51 10 21 17 16 4 4 0 0.18 0.61 178 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 36 ARSD(1), ARSE(2), B4GALT6(1), CERK(3), ENPP7(4), GAL3ST1(1), GALC(1), GLA(2), LCT(14), NEU1(2), NEU2(2), PPAP2B(1), SGMS1(2), SGMS2(1), SGPP1(2), SMPD1(3), SMPD2(1), SMPD3(3), SMPD4(8), SPHK2(1), SPTLC2(3), UGT8(5) 9827558 63 50 63 18 17 15 14 9 8 0 0.18 0.61 179 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(3), C5(1), C6(14), C7(7), ICAM1(2), ITGA4(3), ITGAL(1), ITGB1(3), ITGB2(3), SELP(8), SELPLG(1), VCAM1(4) 6722882 50 39 50 12 12 13 12 6 7 0 0.18 0.61 180 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), DRD1(1), DRD2(2), GRM1(10), PLCB1(6), PPP1R1B(1), PPP3CA(2), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2) 4232840 31 27 31 8 10 11 4 3 3 0 0.20 0.67 181 O_GLYCAN_BIOSYNTHESIS GALNT1, GALNT10, GALNT2, GALNT3, GALNT4, GALNT6, GALNT7, GALNT8, GALNT9, GCNT1, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, WBSCR17 14 GALNT1(1), GALNT10(1), GALNT2(2), GALNT3(2), GALNT6(2), GALNT8(2), GCNT1(2), ST3GAL1(1), ST3GAL4(2), WBSCR17(9) 3854234 24 23 23 10 4 7 8 2 3 0 0.20 0.67 182 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(7), CD3D(1), CD4(1), CREBBP(12), GNAS(5), GNB1(1), HLA-DRA(1), HLA-DRB1(1), LCK(2), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PTPRC(3), ZAP70(2) 6185678 44 37 44 18 11 17 5 5 6 0 0.20 0.67 183 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(7), CD3D(1), CD4(1), CREBBP(12), GNAS(5), GNB1(1), HLA-DRA(1), HLA-DRB1(1), LCK(2), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PTPRC(3), ZAP70(2) 6185678 44 37 44 18 11 17 5 5 6 0 0.20 0.67 184 HSA00520_NUCLEOTIDE_SUGARS_METABOLISM Genes involved in nucleotide sugars metabolism GALE, GALT, TGDS, UGDH, UGP2, UXS1 6 GALT(1), TGDS(1), UGDH(2), UGP2(4), UXS1(3) 1352088 11 10 11 0 0 4 4 1 2 0 0.20 0.67 185 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(1), CSF1R(3), EGF(6), EGFR(6), MET(3), PDGFRA(8), PRKCA(4), SH3GLB1(1), SH3KBP1(4) 5214866 36 32 35 6 10 12 6 3 5 0 0.20 0.67 186 GLYCOSAMINOGLYCAN_DEGRADATION ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, IDS, IDUA, LCT, NAGLU 11 ARSB(1), GNS(1), GUSB(2), HEXA(4), IDS(1), IDUA(2), LCT(14) 3961034 25 23 25 5 6 4 6 4 5 0 0.21 0.68 187 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 ALDH6A1(1), TPI1(3) 435032 4 4 4 1 1 1 2 0 0 0 0.21 0.68 188 HSA00791_ATRAZINE_DEGRADATION Genes involved in atrazine degradation ADAR, APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3F, APOBEC3G, APOBEC4 9 ADAR(4), APOBEC1(6), APOBEC2(1), APOBEC3F(1), APOBEC4(3) 1962984 15 14 15 4 5 3 3 1 3 0 0.21 0.69 189 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(1), LDLR(3), NR0B2(1), NR1H3(2), NR1H4(2), RXRA(1) 1464406 10 10 10 3 2 3 2 1 2 0 0.21 0.69 190 HSA00750_VITAMIN_B6_METABOLISM Genes involved in vitamin B6 metabolism AOX1, PDXK, PDXP, PNPO, PSAT1 5 AOX1(9), PDXP(1), PSAT1(1) 1306342 11 10 11 2 1 4 2 3 1 0 0.22 0.72 191 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(2), CR1(4), CR2(9), FCGR2B(2), HLA-DRA(1), HLA-DRB1(1), ICAM1(2), ITGAL(1), ITGB2(3), PTPRC(3) 4122124 28 26 28 13 7 9 4 5 3 0 0.22 0.72 192 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(1), CD3D(1), GZMB(1), HLA-A(7), ICAM1(2), ITGAL(1), ITGB2(3), PRF1(1) 2341056 17 15 17 6 1 4 3 3 4 2 0.23 0.72 193 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 AKT1(1), AKT3(2), ARHGAP1(1), ARHGAP4(1), ARHGEF11(7), BTK(4), CDC42(1), CFL1(2), CFL2(1), GDI1(1), GDI2(1), INPPL1(3), ITPR1(4), ITPR2(11), ITPR3(1), MYLK(5), MYLK2(2), PAK1(1), PAK3(1), PAK4(1), PAK7(4), PDK1(1), PIK3CA(20), PIK3CD(3), PIK3CG(9), PIK3R1(1), PITX2(3), PPP1R13B(4), PTEN(13), RACGAP1(1), RHO(1), ROCK1(5), ROCK2(3), WASL(2) 19220618 121 81 109 36 32 30 27 10 22 0 0.23 0.72 194 HSA00680_METHANE_METABOLISM Genes involved in methane metabolism ADH5, CAT, EPX, LPO, MPO, MTHFR, PRDX6, SHMT1, SHMT2, TPO 10 ADH5(1), EPX(4), LPO(2), MPO(3), MTHFR(1), PRDX6(1), TPO(10) 3156652 22 21 22 9 3 9 8 2 0 0 0.23 0.72 195 N_GLYCAN_DEGRADATION AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 13 AGA(2), FUCA1(1), HEXA(4), LCT(14), MAN2C1(5), MANBA(2), NEU1(2), NEU2(2) 4555198 32 26 32 9 9 6 10 3 4 0 0.23 0.72 196 METHANE_METABOLISM ADH5, ATP6V0C, SHMT1, CAT, EPX, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, SHMT1, SHMT2, TPO 13 ADH5(1), EPX(4), LPO(2), MPO(3), PRDX1(1), PRDX6(1), TPO(10) 3214324 22 21 22 10 3 8 9 2 0 0 0.23 0.74 197 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 CMBL(1) 134924 1 1 1 0 0 0 1 0 0 0 0.25 0.78 198 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(12), GNA12(1), PRKACB(2), PRKACG(1), PRKAR2B(2) 2728562 18 18 18 5 4 8 3 2 1 0 0.25 0.79 199 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(2), C1QB(2), C1R(2), C1S(2), C2(1), C3(3), C5(1), C6(14), C7(7), C8A(3), C9(1) 4840888 38 29 38 13 9 13 8 3 5 0 0.26 0.79 200 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(9), CDH1(3), CREBBP(12), EP300(6), MAP2K1(2), MAP3K7(2), MAPK3(1), TGFB1(1), TGFB2(2), TGFBR2(3) 6897500 41 38 40 11 6 16 10 3 6 0 0.26 0.79 201 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 46 AKT1(1), AKT3(2), BCR(1), BLNK(1), BTK(4), CD19(2), CD22(5), CD81(1), CR2(9), DAG1(1), FLOT1(1), GSK3A(3), INPP5D(5), ITPR1(4), ITPR2(11), ITPR3(1), LYN(1), MAP4K1(2), MAPK1(1), MAPK3(1), NFATC2(4), NR0B2(1), PDK1(1), PIK3CA(20), PIK3CD(3), PIK3R1(1), PLCG2(3), PPP1R13B(4), PPP3CA(2), PPP3CB(4), PPP3CC(2), PTPRC(3), RAF1(1), SHC1(1), SOS1(6), SOS2(5), SYK(1), VAV1(7) 20172206 126 81 115 35 39 33 23 12 19 0 0.26 0.79 202 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 CKS1B(1), CUL1(2), E2F1(2), RB1(7), RBX1(1), SKP2(1), UBE2M(1) 2348354 15 14 15 1 2 6 0 1 6 0 0.26 0.81 203 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 CD86(1), HLA-DRA(1), HLA-DRB1(1), IFNG(1), IFNGR1(3), IFNGR2(1), IL12A(1), IL12B(2), IL12RB1(3), IL12RB2(3), IL18R1(2), IL4(2), IL4R(1) 3417422 22 20 22 8 3 7 6 0 6 0 0.27 0.81 204 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 142 ADCY1(7), ADCY2(14), ADCY3(4), ADCY4(3), ADCY5(1), ADCY7(4), ADCY8(13), ADCY9(3), ADSL(1), ADSS(1), ADSSL1(1), AK5(3), AK7(1), AMPD1(4), AMPD2(1), AMPD3(6), CANT1(1), DCK(1), ENPP1(7), ENPP3(3), ENTPD1(1), ENTPD2(1), ENTPD3(1), ENTPD6(3), GART(1), GDA(6), GUCY1A2(10), GUCY1A3(5), GUCY1B3(3), GUCY2C(4), GUCY2D(1), GUCY2F(4), GUK1(2), HPRT1(1), IMPDH1(1), NME4(1), NME7(2), NPR1(2), NPR2(2), NT5C1A(2), NT5C1B(1), NT5C2(2), NT5C3(3), NT5E(2), NUDT9(2), PAPSS2(1), PDE10A(5), PDE11A(8), PDE1A(2), PDE1C(11), PDE2A(2), PDE3B(3), PDE4A(1), PDE4B(3), PDE4C(2), PDE4D(1), PDE5A(4), PDE6H(2), PDE7B(1), PDE8A(5), PDE8B(2), PDE9A(2), PFAS(4), PKLR(3), PKM2(2), PNPT1(2), POLA1(4), POLD1(2), POLD3(1), POLE2(2), POLE4(1), POLR1A(2), POLR1B(2), POLR1D(1), POLR2A(1), POLR2B(2), POLR2D(1), POLR2E(1), POLR3A(1), POLR3B(2), POLR3G(1), POLR3H(1), PPAT(2), PRIM1(2), PRIM2(10), PRPS1(1), PRPS1L1(1), PRPS2(1), RFC5(1), RRM1(1), RRM2B(2), XDH(8) 44705590 262 122 262 92 70 90 44 20 38 0 0.27 0.81 205 SA_DIACYLGLYCEROL_SIGNALING DAG (diacylglycerol) signaling activity ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP 10 ESR1(5), ESR2(1), ITPKA(1), PDE1A(2), PDE1B(1), PLCB1(6), PLCB2(5), PRL(1), VIP(1) 3042376 23 21 23 8 10 7 3 2 1 0 0.27 0.81 206 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 2 FAH(1), GSTZ1(2) 353152 3 3 3 1 1 0 0 1 1 0 0.27 0.81 207 NUCLEOTIDE_GPCRS ADORA1, ADORA2A, ADORA2B, ADORA3, GPR23, LTB4R, P2RY1, P2RY2, P2RY5, P2RY6 8 ADORA1(3), ADORA2A(5), P2RY1(2), P2RY2(1), P2RY6(1) 1601110 12 11 12 4 5 5 1 0 1 0 0.27 0.81 208 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 CD3D(1), FOS(1), FYN(3), HRAS(1), JUN(3), LCK(2), MAP2K1(2), MAP3K1(2), MAPK3(1), MAPK8(2), NFATC2(4), NFATC3(2), NFATC4(1), NFKB1(2), PIK3CA(20), PIK3R1(1), PLCG1(1), PPP3CA(2), PPP3CB(4), PPP3CC(2), PRKCA(4), RAC1(1), RAF1(1), RASA1(5), RELA(2), SHC1(1), SOS1(6), SYT1(3), VAV1(7), ZAP70(2) 12961782 89 63 77 12 32 19 16 13 9 0 0.28 0.82 209 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 89 ACVR1B(3), ACVR1C(3), ACVR2A(3), ACVRL1(3), AMHR2(4), BMP4(1), BMP5(5), BMPR1A(3), CHRD(3), COMP(1), CREBBP(12), CUL1(2), DCN(1), EP300(6), GDF5(4), GDF6(2), ID2(1), ID4(1), IFNG(1), INHBA(4), INHBC(1), LEFTY2(2), LTBP1(10), MAPK1(1), MAPK3(1), MYC(1), NODAL(3), PITX2(3), PPP2R1A(5), PPP2R1B(2), PPP2R2A(1), PPP2R2B(1), PPP2R2C(1), RBL1(5), RBL2(5), RBX1(1), ROCK1(5), ROCK2(3), RPS6KB1(1), SKP1(1), SMAD1(3), SMAD2(1), SMAD4(2), SMAD7(2), SMURF1(2), SP1(1), TGFB1(1), TGFB2(2), TGFBR2(3), THBS1(1), THBS2(12), THBS3(3), THBS4(1), ZFYVE16(3), ZFYVE9(5) 27101212 158 98 156 44 26 55 38 17 22 0 0.28 0.82 210 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 CD4(1), CD80(2), HLA-DRA(1), HLA-DRB1(1), IL10(1), IL4(2) 1077612 8 8 8 3 0 3 2 1 2 0 0.28 0.82 211 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 33 AARS(1), AARS2(5), ABAT(2), ACY3(2), ADSL(1), ADSS(1), ADSSL1(1), AGXT2(1), ASL(3), ASNS(3), CAD(8), DARS(1), DARS2(5), DDO(2), DLAT(1), DLD(2), GAD1(4), GAD2(5), GOT2(2), GPT(1), GPT2(2), NARS(2), NARS2(2), PC(2), PDHA1(2), PDHA2(5) 10270600 66 53 66 21 13 29 11 6 7 0 0.28 0.82 212 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 44 ADH1B(1), ADH1C(1), ADH4(2), ADH7(1), ADHFE1(2), AGPAT3(1), ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH9A1(2), CEL(1), DGKA(3), DGKB(3), DGKD(5), DGKE(3), DGKG(1), DGKZ(3), GK(4), GLA(2), LCT(14), LIPC(1), LIPF(1), LIPG(2), LPL(3), PNLIP(9), PNLIPRP1(3), PNLIPRP2(2), PPAP2B(1) 13024438 77 62 77 31 20 29 13 8 7 0 0.28 0.82 213 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 47 IMPA1(1), INPP1(1), INPP4A(5), INPP4B(4), INPP5A(3), INPP5B(5), INPP5E(2), INPPL1(3), ITPK1(1), ITPKA(1), ITPKB(4), OCRL(5), PI4KA(4), PI4KB(1), PIK3C3(3), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIP4K2A(2), PIP4K2B(2), PIP4K2C(3), PIP5K1A(3), PIP5K1B(2), PIP5K1C(1), PLCB1(6), PLCB2(5), PLCB3(3), PLCB4(4), PLCD3(1), PLCE1(11), PLCG1(1), PLCG2(3), PLCZ1(4), PTEN(13), SYNJ1(2), SYNJ2(3) 20365336 146 83 134 35 50 34 28 12 22 0 0.28 0.82 214 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(1), ALOX15(2), CYP4F2(3), CYP4F3(2), EPX(4), GGT1(1), LPO(2), LTA4H(2), MPO(3), PLA2G2A(1), PLA2G2E(2), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(5), PRDX1(1), PRDX6(1), PTGS1(2), TBXAS1(2), TPO(10) 7586538 54 43 54 24 11 19 17 3 4 0 0.29 0.83 215 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 GUSB(2), UGDH(2), UGP2(4), UGT1A10(2), UGT1A3(1), UGT1A5(2), UGT1A6(1), UGT1A7(1), UGT1A8(3), UGT1A9(1), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4), UGT2B7(2) 6739792 43 39 43 9 10 12 15 3 3 0 0.30 0.85 216 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 14 APC(9), CREBBP(12), CTNNB1(3), DVL1(3), EP300(6), FZD1(1), HDAC1(2), LEF1(3), PITX2(3), TRRAP(11) 8810288 53 46 52 12 9 16 17 3 8 0 0.30 0.85 217 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(2), GOT2(2), TAT(1), TYR(3) 1255434 8 8 8 2 2 4 0 1 1 0 0.30 0.85 218 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 AKT1(1), APC(9), CAV3(1), DAG1(1), DLG4(1), EPHB2(4), GNAI1(2), ITPR1(4), ITPR2(11), ITPR3(1), KCNJ3(7), KCNJ5(2), KCNJ9(2), MAPK1(1), PITX2(3), PTX3(2), RAC1(1), RHO(1), RYR1(24) 12603824 78 60 78 20 16 29 16 6 11 0 0.30 0.85 219 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(1), IFNG(1), IL12A(1), IL12B(2) 802958 5 5 5 1 0 1 2 0 2 0 0.30 0.85 220 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 6 DBH(1), GAD1(4), HDC(3), PNMT(2), TH(1), TPH1(1) 1656468 12 11 12 2 2 6 2 1 1 0 0.31 0.87 221 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 NFYB(1), RB1(7), SP1(1), SP3(1) 1794596 10 10 10 1 1 3 0 0 6 0 0.31 0.87 222 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(1), JAK2(3), JAK3(7), PIAS1(2), PIAS3(2), PTPRU(5), REG1A(11) 3829492 31 24 31 5 1 17 8 2 3 0 0.31 0.87 223 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 109 A4GNT(5), ALG1(1), ALG13(6), ALG2(2), ALG6(2), B3GALT6(1), B3GNT2(1), B3GNT6(1), B3GNT7(1), B4GALT1(1), B4GALT3(1), B4GALT4(1), B4GALT5(2), C1GALT1C1(1), CHPF(1), CHST1(2), CHST12(1), CHST2(3), CHST3(2), CHST4(2), CHST6(3), DDOST(1), EXT1(2), EXT2(1), EXTL1(1), EXTL3(1), FUT8(2), GALNT1(1), GALNT10(1), GALNT11(2), GALNT12(3), GALNT13(10), GALNT14(3), GALNT2(2), GALNT3(2), GALNT5(6), GALNT6(2), GALNT8(2), GALNTL1(3), GALNTL4(3), GALNTL5(3), GANAB(5), GCNT1(2), GCNT3(2), HS3ST2(1), HS3ST5(4), HS6ST1(2), HS6ST3(2), MAN1A1(3), MAN1A2(3), MAN1C1(3), MAN2A1(3), MGAT1(1), MGAT2(2), MGAT3(4), MGAT4A(2), MGAT4B(1), MGAT5(3), MGAT5B(4), NDST1(2), NDST2(1), NDST3(4), NDST4(11), OGT(2), RPN1(1), ST3GAL1(1), ST3GAL4(2), ST6GAL1(1), ST6GALNAC1(3), STT3B(1), WBSCR17(9), XYLT1(2) 30285098 178 107 176 62 38 68 35 20 17 0 0.32 0.88 224 HSA00300_LYSINE_BIOSYNTHESIS Genes involved in lysine biosynthesis AADAT, AASDHPPT, AASS, KARS 4 AADAT(1), AASDHPPT(1), AASS(6), KARS(2) 1265758 10 10 10 3 2 4 3 0 1 0 0.32 0.89 225 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(1), CAPN1(2), CAPN2(2), CAPNS2(1), CXCR3(1), EGF(6), EGFR(6), HRAS(1), ITGA1(3), ITGB1(3), MAPK1(1), MAPK3(1), MYL2(1), MYLK(5), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PTK2(4), PXN(3), TLN1(3) 8846956 52 46 51 13 15 16 7 7 7 0 0.33 0.90 226 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 28 ANXA4(1), ANXA5(2), ANXA6(4), CYP11A1(2), EDNRA(1), EDNRB(3), HSD11B1(3), HSD11B2(1), PLA2G4A(5), PRL(1), PTGDR(5), PTGER2(2), PTGER4(2), PTGFR(2), PTGIR(1), PTGS1(2), TBXAS1(2) 5652568 39 33 39 15 8 14 8 3 6 0 0.33 0.90 227 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(7), AP2A1(2), AP2M1(1), DNM1(1), EPN1(2), EPS15(4), PICALM(4), PPP3CA(2), PPP3CB(4), PPP3CC(2), SYNJ1(2), SYNJ2(3), SYT1(3) 6051110 37 34 37 9 11 8 6 5 7 0 0.33 0.90 228 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 15 AGA(2), FUCA1(1), HEXA(4), LCT(14), MAN2B1(1), MAN2B2(3), MAN2C1(5), MANBA(2), NEU1(2), NEU2(2) 5600236 36 29 36 11 9 8 11 4 4 0 0.34 0.92 229 HSA00660_C5_BRANCHED_DIBASIC_ACID_METABOLISM Genes involved in C5-branched dibasic acid metabolism ILVBL, SUCLA2 2 ILVBL(2), SUCLA2(2) 579390 4 4 4 0 1 1 1 1 0 0 0.34 0.92 230 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(1), CFL1(2), GNAS(5), GNB1(1), HRAS(1), MAP2K1(2), MAPK1(1), MAPK3(1), MYL2(1), NOX1(2), PIK3C2G(6), PLCB1(6), PPP1R12B(4), PRKCA(4), PTK2(4), RAF1(1), ROCK2(3) 6923488 45 39 45 14 12 18 8 3 4 0 0.35 0.93 231 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(1) 192952 1 1 1 0 0 0 0 0 1 0 0.35 0.93 232 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 29 BRAF(7), CREB1(1), CREB3(2), CREB5(3), DUSP4(2), DUSP6(1), DUSP9(2), EEF2K(3), MAP2K1(2), MAPK1(1), MAPK3(1), MKNK2(1), MOS(4), NFKB1(2), RPS6KA1(2), RPS6KA2(3), RPS6KA3(1), SHC1(1), SOS1(6), SOS2(5), TRAF3(1) 8109146 51 42 50 11 8 13 17 3 10 0 0.35 0.93 233 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 22 APC(9), CREBBP(12), CSNK1A1(2), CSNK2A1(2), CTBP1(1), CTNNB1(3), DVL1(3), FZD1(1), HDAC1(2), MAP3K7(2), MYC(1), NLK(2), PPARD(1), TLE1(4), WIF1(3) 7875610 48 41 48 10 11 14 11 5 7 0 0.35 0.93 234 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 25 ATM(6), CCND2(3), DAZL(1), DMC1(1), EGR1(2), ESR2(1), FSHR(11), INHA(3), LHCGR(7), MLH1(1), MSH5(2), NCOR1(5), NRIP1(3), PGR(3), PRLR(5), PTGER2(2), SMPD1(3), VDR(3), ZP2(2) 9486510 64 47 64 24 20 20 8 7 9 0 0.35 0.93 235 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 75 ACP1(1), ACTB(1), ACTN1(2), ACTN2(6), ACTN3(2), ACTN4(4), ACVR1B(3), ACVR1C(3), CDC42(1), CDH1(3), CREBBP(12), CSNK2A1(2), CTNNA2(17), CTNNA3(10), CTNNB1(3), CTNND1(3), EGFR(6), EP300(6), ERBB2(1), FARP2(6), FER(2), FGFR1(1), FYN(3), INSR(7), IQGAP1(6), LEF1(3), LMO7(6), MAP3K7(2), MAPK1(1), MAPK3(1), MET(3), MLLT4(1), NLK(2), PARD3(5), PTPN1(1), PTPRB(13), PTPRF(6), PTPRJ(2), PTPRM(6), PVRL1(2), PVRL3(2), PVRL4(5), RAC1(1), SMAD2(1), SMAD4(2), SNAI1(3), SNAI2(2), SORBS1(5), SSX2IP(1), TCF7(1), TGFBR2(3), TJP1(8), VCL(2), WAS(4), WASF3(1), WASL(2), YES1(1) 32265170 209 107 207 65 39 71 53 21 25 0 0.36 0.94 236 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 129 ALCAM(3), CADM1(2), CADM3(3), CD2(1), CD22(5), CD226(3), CD276(1), CD34(2), CD4(1), CD40(1), CD40LG(2), CD58(1), CD6(1), CD80(2), CD86(1), CD8B(1), CDH1(3), CDH2(9), CDH3(1), CDH4(6), CDH5(1), CLDN1(2), CLDN10(4), CLDN16(4), CLDN17(1), CLDN19(1), CLDN2(1), CLDN22(1), CLDN3(1), CLDN6(1), CLDN8(1), CLDN9(3), CNTN1(9), CNTN2(1), CNTNAP1(3), CNTNAP2(23), ESAM(4), F11R(1), GLG1(3), HLA-A(7), HLA-B(1), HLA-C(1), HLA-DMA(1), HLA-DMB(1), HLA-DPA1(1), HLA-DQA2(1), HLA-DRA(1), HLA-DRB1(1), HLA-DRB5(2), HLA-G(1), ICAM1(2), ICAM3(2), ICOS(2), ITGA4(3), ITGA6(3), ITGA8(8), ITGAL(1), ITGAM(3), ITGAV(3), ITGB1(3), ITGB2(3), ITGB7(1), ITGB8(3), L1CAM(2), MADCAM1(1), MAG(4), NCAM1(2), NCAM2(10), NEGR1(2), NEO1(3), NFASC(5), NLGN1(7), NLGN2(1), NLGN3(4), NRCAM(3), NRXN1(15), NRXN2(7), NRXN3(7), PTPRC(3), PTPRF(6), PTPRM(6), PVRL1(2), PVRL3(2), SDC1(1), SDC2(2), SDC3(1), SELE(4), SELL(2), SELP(8), SELPLG(1), SIGLEC1(7), VCAM1(4), VCAN(15) 40778020 306 120 305 112 78 111 65 20 30 2 0.36 0.94 237 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(12), EP300(6), ESR1(5), MAPK1(1), MAPK3(1) 4039354 25 24 24 6 5 9 6 2 3 0 0.36 0.94 238 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(7), GNAS(5), GNB1(1), PRKAA2(3), PRKACB(2), PRKACG(1), PRKAG2(4), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2) 4084922 28 24 28 7 8 9 5 3 3 0 0.36 0.94 239 INOSITOL_METABOLISM ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 5 ALDH6A1(1), ALDOA(1), ALDOB(2), TPI1(3) 1036850 7 7 7 3 2 2 3 0 0 0 0.37 0.94 240 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 29 AGA(2), ARSB(1), FUCA1(1), GNS(1), GUSB(2), HEXA(4), HGSNAT(1), HPSE(3), HPSE2(2), HYAL1(3), IDS(1), IDUA(2), LCT(14), MAN2B1(1), MAN2B2(3), MAN2C1(5), MANBA(2), NEU1(2), NEU2(2), SPAM1(3) 9523534 55 44 55 15 11 14 17 5 8 0 0.37 0.94 241 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 7 FUT3(3), FUT5(4), FUT6(2) 1397656 9 8 9 2 2 3 3 1 0 0 0.37 0.94 242 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 9 ALDOB(2), GPI(5), HK1(3), PFKL(2), PGK1(1), PKLR(3), TPI1(3) 2381818 19 15 19 4 6 5 5 0 3 0 0.37 0.94 243 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 31 ABP1(4), ADH1B(1), ADH1C(1), ADH4(2), ADH7(1), ADHFE1(2), ALDH3B2(1), AOC2(1), AOC3(3), AOX1(9), DBH(1), DCT(1), DDC(2), FAH(1), GOT2(2), GSTZ1(2), HPD(1), PNMT(2), TAT(1), TH(1), TPO(10), TYR(3) 8331112 52 44 52 15 14 22 6 8 2 0 0.37 0.94 244 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(6), EGFR(6), ERBB3(3), NRG1(3), UBE2D1(1) 2762204 19 17 18 4 6 6 3 1 3 0 0.38 0.95 245 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 27 AKT1(1), AKT3(2), GSK3A(3), IL4R(1), IRS1(3), IRS2(2), JAK1(1), JAK3(7), MAP4K1(2), MAPK1(1), MAPK3(1), PDK1(1), PIK3CA(20), PIK3CD(3), PIK3R1(1), PPP1R13B(4), RAF1(1), SHC1(1), SOS1(6), SOS2(5), STAT6(1) 10077114 67 51 56 16 21 20 15 4 7 0 0.38 0.95 246 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 203 ACTN1(2), ACTN2(6), ACTN3(2), ACTN4(4), APC(9), APC2(2), ARAF(3), ARHGEF1(2), ARHGEF12(3), ARHGEF4(3), ARHGEF6(2), ARHGEF7(3), ARPC1A(2), BCAR1(5), BDKRB1(1), BDKRB2(2), BRAF(7), CD14(1), CDC42(1), CFL1(2), CFL2(1), CHRM2(6), CHRM3(4), CHRM4(1), CHRM5(2), CYFIP1(4), CYFIP2(6), DIAPH1(1), DIAPH2(1), DIAPH3(5), DOCK1(3), EGF(6), EGFR(6), F2R(2), FGD1(3), FGD3(2), FGF10(2), FGF12(3), FGF14(1), FGF2(2), FGF23(1), FGF3(1), FGF5(2), FGF6(2), FGF8(1), FGFR1(1), FGFR2(3), FGFR3(2), FGFR4(1), FN1(16), GIT1(1), GNA12(1), GNG12(1), GRLF1(11), GSN(2), HRAS(1), IQGAP1(6), IQGAP2(6), IQGAP3(9), ITGA1(3), ITGA10(5), ITGA11(3), ITGA2(5), ITGA2B(1), ITGA4(3), ITGA5(1), ITGA6(3), ITGA7(3), ITGA8(8), ITGAD(6), ITGAE(3), ITGAL(1), ITGAM(3), ITGAV(3), ITGAX(9), ITGB1(3), ITGB2(3), ITGB3(3), ITGB4(6), ITGB6(1), ITGB7(1), ITGB8(3), KRAS(1), LIMK2(2), MAP2K1(2), MAPK1(1), MAPK3(1), MOS(4), MRAS(2), MSN(3), MYH10(1), MYH14(4), MYH9(12), MYL2(1), MYLK(5), MYLK2(2), MYLPF(1), NCKAP1(4), NCKAP1L(8), PAK1(1), PAK3(1), PAK4(1), PAK7(4), PDGFB(1), PDGFRA(8), PDGFRB(4), PFN2(1), PFN3(1), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PIP4K2A(2), PIP4K2B(2), PIP4K2C(3), PIP5K1A(3), PIP5K1B(2), PIP5K1C(1), PPP1R12B(4), PTK2(4), PXN(3), RAC1(1), RAF1(1), RDX(1), ROCK1(5), ROCK2(3), RRAS2(2), SCIN(1), SLC9A1(3), SOS1(6), SOS2(5), SSH1(1), SSH2(6), TIAM1(8), TIAM2(3), VAV1(7), VAV2(3), VAV3(1), VCL(2), WAS(4), WASL(2) 76078980 478 147 465 136 105 163 100 48 62 0 0.38 0.95 247 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(3) 455858 3 3 3 0 0 2 1 0 0 0 0.39 0.95 248 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 35 ACTG2(6), AKT1(1), CDC42(1), CFL1(2), CFL2(1), FLNA(8), FLNC(11), FSCN3(1), GDI1(1), GDI2(1), MYH2(21), MYLK(5), MYLK2(2), PAK1(1), PAK3(1), PAK4(1), PAK7(4), PFN2(1), RHO(1), ROCK1(5), ROCK2(3), VASP(2), WASL(2) 13114684 82 62 82 31 17 35 16 5 9 0 0.39 0.95 249 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 73 CALML6(1), CDS1(2), DGKA(3), DGKB(3), DGKD(5), DGKE(3), DGKG(1), DGKI(7), DGKZ(3), IMPA1(1), INPP1(1), INPP4A(5), INPP4B(4), INPP5A(3), INPP5B(5), INPP5D(5), INPP5E(2), INPPL1(3), ITPK1(1), ITPKA(1), ITPKB(4), ITPR1(4), ITPR2(11), ITPR3(1), OCRL(5), PI4KA(4), PI4KB(1), PIK3C2A(4), PIK3C2B(6), PIK3C2G(6), PIK3C3(3), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PIP4K2A(2), PIP4K2B(2), PIP4K2C(3), PIP5K1A(3), PIP5K1B(2), PIP5K1C(1), PLCB1(6), PLCB2(5), PLCB3(3), PLCB4(4), PLCD3(1), PLCE1(11), PLCG1(1), PLCG2(3), PLCZ1(4), PRKCA(4), PRKCG(8), PTEN(13), SYNJ1(2), SYNJ2(3) 34411672 231 109 219 56 75 59 45 17 35 0 0.39 0.95 250 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(1), ADCY1(7), CAP1(2), CCNB1(1), CDC25C(1), GNAI1(2), GNAS(5), GNB1(1), HRAS(1), MAPK1(1), MAPK3(1), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), RPS6KA1(2) 5515508 33 30 33 12 7 11 7 6 2 0 0.39 0.95 251 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 IFNA1(1), IFNB1(1), IFNG(1), IL10(1), IL12A(1), IL12B(2), IL16(5), IL4(2), LTA(2) 2643656 16 16 16 4 3 4 5 3 1 0 0.39 0.95 252 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(4), ALDH3B2(1), AOC2(1), AOC3(3), DDC(2), EPX(4), GOT2(2), HPD(1), LPO(2), MPO(3), PRDX1(1), PRDX6(1), TAT(1), TPO(10) 5946980 36 33 36 17 10 11 11 4 0 0 0.39 0.95 253 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(4), ADRBK2(1), CALML6(1), CAMK2B(2), CAMK2D(1), CLCA1(4), CLCA2(4), CLCA4(2), CNGA3(3), CNGA4(4), CNGB1(4), GNAL(1), GUCA1A(2), PDE1C(11), PRKACB(2), PRKACG(1), PRKG1(4), PRKG2(3), PRKX(1) 8251724 55 43 55 12 20 16 5 5 9 0 0.39 0.95 254 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 BLVRA(2), CP(2), CPOX(2), EARS2(2), EPRS(10), FECH(2), FTH1(2), FTMT(4), GUSB(2), MMAB(1), PPOX(1), UGT1A10(2), UGT1A3(1), UGT1A5(2), UGT1A6(1), UGT1A7(1), UGT1A8(3), UGT1A9(1), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4), UGT2B7(2), UROD(1) 10816526 66 54 66 14 14 22 19 5 6 0 0.39 0.95 255 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(7), ASH2L(2), CARM1(1), CTCFL(2), DOT1L(4), EED(2), EHMT2(1), EZH1(3), EZH2(4), FBXO11(4), HSF4(1), JMJD6(1), KDM6A(3), MEN1(2), MLL(4), MLL2(34), MLL3(20), MLL4(5), MLL5(3), NSD1(8), OGT(2), PRDM2(4), PRDM9(9), PRMT5(1), PRMT6(2), PRMT7(4), PRMT8(1), RBBP5(1), SATB1(2), SETD1A(6), SETD2(4), SETD8(1), SETDB1(3), SMYD3(1), STK38(4), SUV39H1(1), SUV39H2(2), SUV420H1(1), SUZ12(3), WHSC1(1), WHSC1L1(12) 32840110 176 101 176 42 26 52 39 12 45 2 0.40 0.97 256 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 ALOX15(2), CYP1A2(1), CYP2C19(6), CYP2C8(2), CYP2C9(2), CYP2J2(1), CYP3A4(1), CYP3A43(3), CYP3A7(1), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(5), RDH11(1), RDH12(2), RDH13(1) 6442710 42 35 42 13 14 10 8 4 6 0 0.40 0.97 257 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 99 AKT1(1), AKT3(2), CASP8(1), CCL3(2), CD14(1), CD40(1), CD80(2), CD86(1), CHUK(2), FADD(1), FOS(1), IFNA1(1), IFNA10(3), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNAR1(2), IFNB1(1), IKBKB(2), IKBKE(3), IL12A(1), IL12B(2), IL1B(1), IRAK1(3), IRF3(1), JUN(3), LBP(4), MAP2K1(2), MAP2K3(2), MAP2K6(2), MAP3K7(2), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(1), MAPK8(2), MAPK9(1), NFKB1(2), NFKB2(2), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), RAC1(1), RELA(2), STAT1(2), TBK1(2), TLR1(2), TLR2(3), TLR3(2), TLR4(10), TLR5(2), TLR7(3), TLR8(1), TLR9(1), TOLLIP(1), TRAF3(1), TRAF6(1) 24430500 147 89 134 40 42 41 31 17 16 0 0.41 0.97 258 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 29 ATG12(1), ATG3(1), ATG7(4), BECN1(1), IFNA1(1), IFNA10(3), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNG(1), PIK3C3(3), PIK3R4(5), PRKAA2(3), ULK1(1), ULK2(2) 5718962 34 30 33 9 10 8 12 1 3 0 0.41 0.97 259 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 GLUL(2), PGLYRP2(1) 506410 3 3 3 0 0 1 1 1 0 0 0.41 0.97 260 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 IL6R(1), JAK1(1), JAK2(3), JAK3(7), PIAS3(2), PTPRU(5), REG1A(11), STAT3(1) 4228924 31 25 31 5 2 17 7 2 3 0 0.41 0.97 261 IRINOTECAN_PATHWAY_PHARMGKB ABCC1, ABCC2, ABCG2, BCHE, CES1, CES2, CES4, CYP3A4, CYP3A5, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6 17 ABCC1(4), ABCC2(4), ABCG2(1), BCHE(9), CES1(2), CES2(1), CYP3A4(1), UGT1A10(2), UGT1A3(1), UGT1A5(2), UGT1A6(1), UGT1A7(1), UGT1A8(3), UGT1A9(1) 6087244 33 33 33 9 7 15 8 2 1 0 0.42 0.98 262 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(4), AGT(1), AGTR1(2), AGTR2(3), BDKRB2(2), KNG1(4), NOS3(1) 2766476 17 16 17 10 3 6 4 2 2 0 0.42 0.98 263 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 39 AKT1(1), AKT3(2), BCR(1), BLNK(1), BTK(4), CD19(2), DAG1(1), EPHB2(4), ITPKA(1), ITPKB(4), LYN(1), MAP2K1(2), MAPK1(1), NFAT5(2), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(4), PI3(1), PIK3CA(20), PIK3CD(3), PIK3R1(1), PLCG2(3), PPP1R13B(4), RAF1(1), SERPINA4(4), SHC1(1), SOS1(6), SOS2(5), SYK(1), VAV1(7) 14332916 94 64 83 22 29 24 20 9 12 0 0.42 0.98 264 HSA00232_CAFFEINE_METABOLISM Genes involved in caffeine metabolism CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH 7 CYP1A2(1), CYP2A13(1), CYP2A6(4), NAT2(1), XDH(8) 2131550 15 13 15 6 4 6 2 1 2 0 0.42 0.98 265 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(2), F13A1(3), F2R(2), FGA(5), FGB(3), FGG(1), PLAT(1), PLAU(2), PLG(1), SERPINB2(3) 3573172 23 21 23 7 3 10 8 0 2 0 0.42 0.98 266 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 32 GORASP1(1), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(3), MAPK9(1), MAPKAPK5(3), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(4), PIK3CA(20), PIK3CD(3), PIK3R1(1), SYT1(3), TRAF3(1), TRAF5(2), TRAF6(1) 9355680 59 48 48 11 24 17 7 7 4 0 0.42 0.98 267 GPCRDB_CLASS_A_RHODOPSIN_LIKE2 CYSLTR1, CYSLTR2, GPR109B, GPR161, GPR171, GPR18, GPR34, GPR39, GPR41, GPR42, GPR45, GPR65, GPR68, GPR75, GPR81, LYPDC1 13 CYSLTR1(2), CYSLTR2(1), GPR109B(2), GPR161(1), GPR171(2), GPR18(1), GPR34(1), GPR39(1), GPR45(4), GPR65(1), GPR68(1), GPR75(2) 2642232 19 16 19 6 7 7 4 0 1 0 0.43 0.99 268 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 8 CARS(5), GOT2(2), LDHB(2), LDHC(1) 1840164 10 10 10 2 0 3 3 2 2 0 0.43 0.99 269 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 37 BTK(4), FCER1A(2), FOS(1), HRAS(1), JUN(3), LYN(1), MAP2K1(2), MAP3K1(2), MAPK1(1), MAPK3(1), MAPK8(2), NFATC2(4), NFATC3(2), NFATC4(1), PIK3CA(20), PIK3R1(1), PLA2G4A(5), PLCG1(1), PPP3CA(2), PPP3CB(4), PPP3CC(2), RAF1(1), SHC1(1), SOS1(6), SYK(1), SYT1(3), VAV1(7) 11633724 81 58 69 20 30 17 16 11 7 0 0.43 0.99 270 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 56 BMP4(1), BMP5(5), CSNK1A1(2), CSNK1A1L(5), CSNK1G1(2), DHH(1), GLI1(1), GLI2(4), GLI3(6), HHIP(1), IHH(1), LRP2(37), PRKACB(2), PRKACG(1), PRKX(1), PTCH1(4), PTCH2(5), SMO(1), STK36(2), SUFU(2), WNT10B(2), WNT11(1), WNT2(3), WNT2B(2), WNT3(2), WNT3A(1), WNT6(2), WNT7A(2), WNT7B(1), WNT9A(1), WNT9B(1) 16809964 102 73 101 39 30 26 21 14 11 0 0.44 0.99 271 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 85 ABL1(2), ABL2(5), AKT1(1), AKT3(2), ARAF(3), AREG(2), BRAF(7), CAMK2B(2), CAMK2D(1), CBL(1), CBLB(4), EGF(6), EGFR(6), ERBB2(1), ERBB3(3), ERBB4(9), EREG(1), GAB1(2), HBEGF(1), HRAS(1), JUN(3), KRAS(1), MAP2K1(2), MAPK1(1), MAPK10(1), MAPK3(1), MAPK8(2), MAPK9(1), MYC(1), NCK1(2), NRG1(3), NRG2(2), NRG3(5), PAK1(1), PAK3(1), PAK4(1), PAK7(4), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PLCG1(1), PLCG2(3), PRKCA(4), PRKCG(8), PTK2(4), RAF1(1), RPS6KB1(1), SHC1(1), SHC2(2), SHC3(2), SHC4(4), SOS1(6), SOS2(5), STAT5A(2), TGFA(1) 28169390 179 99 166 55 53 57 35 12 22 0 0.44 0.99 272 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(1), CREB1(1), CREBBP(12), EP300(6), NCOA3(4), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), RARA(1), RXRA(1) 5467804 34 29 33 10 7 14 4 5 4 0 0.44 0.99 273 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(3), F2R(2), F3(1), F5(14), FGA(5), FGB(3), FGG(1), SERPINC1(5) 4394464 34 25 34 7 3 13 13 3 2 0 0.44 1.00 274 HSA00430_TAURINE_AND_HYPOTAURINE_METABOLISM Genes involved in taurine and hypotaurine metabolism BAAT, CDO1, CSAD, GAD1, GAD2, GGT1, GGTL3, GGTL4 6 BAAT(2), CSAD(1), GAD1(4), GAD2(5), GGT1(1) 1577970 13 10 13 8 4 6 2 1 0 0 0.44 1.00 275 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 24 ATF2(2), BCR(1), BLNK(1), FOS(1), HRAS(1), JUN(3), LYN(1), MAP2K1(2), MAP3K1(2), MAPK1(1), MAPK3(1), MAPK8IP3(3), PAPPA(8), RAC1(1), RPS6KA1(2), RPS6KA3(1), SHC1(1), SOS1(6), SYK(1), VAV1(7), VAV2(3), VAV3(1) 8747988 50 44 49 10 10 14 16 6 4 0 0.45 1.00 276 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 BRAF(7), CREB1(1), CREB3(2), CREB5(3), MAPK1(1), RAF1(1), SNX13(4) 3132622 19 18 19 6 5 3 8 0 3 0 0.45 1.00 277 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(1), CHIA(5), CHIT1(4), CMAS(2), CTBS(4), CYB5R1(1), GFPT2(1), GNE(2), GNPDA2(3), HEXA(4), HK1(3), HK2(5), HK3(5), MTMR1(1), MTMR2(1), MTMR6(4), UAP1(1) 7756350 47 38 47 13 11 16 9 3 8 0 0.45 1.00 278 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(6), COL4A2(6), COL4A3(5), COL4A4(9), COL4A5(2), COL4A6(6), SLC23A1(1), SLC23A2(2), SLC2A3(2) 6862612 39 35 39 10 12 17 4 1 5 0 0.45 1.00 279 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP1(1), ACPT(1), ENPP1(7), ENPP3(3), FLAD1(1), TYR(3) 2593104 16 15 16 5 3 9 2 0 2 0 0.46 1.00 280 HSA00730_THIAMINE_METABOLISM Genes involved in thiamine metabolism LHPP, MTMR1, MTMR2, MTMR6, NFS1, PHPT1, THTPA, TPK1 8 MTMR1(1), MTMR2(1), MTMR6(4), NFS1(2), TPK1(3) 1721082 11 11 11 1 1 4 5 0 1 0 0.47 1.00 281 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 B4GALT1(1), FBP2(1), G6PC(2), GALK2(1), GALT(1), GANAB(5), GCK(1), GLA(2), HK1(3), HK2(5), HK3(5), LCT(14), MGAM(3), PFKM(4), PFKP(2) 8911570 50 45 50 20 17 17 6 7 3 0 0.47 1.00 282 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(1), ACP6(2), ACPT(1), ENPP1(7), ENPP3(3), FLAD1(1), MTMR1(1), MTMR2(1), MTMR6(4), TYR(3) 4031522 24 22 24 7 4 10 5 0 5 0 0.47 1.00 283 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(2), FOS(1), HRAS(1), JUN(3), MAP2K1(2), MAPK1(1), MAPK3(1), MYC(1), NFKB1(2), PLCB1(6), PRKCA(4), RAF1(1), RELA(2) 4191188 27 23 26 7 9 7 3 6 2 0 0.47 1.00 284 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(2), GSS(2), NFKB1(2), NOX1(2), RELA(2), XDH(8) 2705600 18 14 18 2 4 5 2 4 3 0 0.47 1.00 285 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALT(1), TGDS(1), UGDH(2), UXS1(3) 1073162 7 6 7 0 0 3 2 1 1 0 0.48 1.00 286 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(2), ABP1(4), ACADL(2), ACADM(1), ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH9A1(2), AOC2(1), AOC3(3), CNDP1(3), DPYD(7), DPYS(4), GAD1(4), GAD2(5), HADHA(2), MLYCD(1), SDS(2), SMS(2) 7843214 51 40 51 17 14 20 8 5 4 0 0.49 1.00 287 ALKALOID_BIOSYNTHESIS_II ABP1, AOC2, AOC3, CES1, ESD 5 ABP1(4), AOC2(1), AOC3(3), CES1(2) 1611612 10 9 10 5 4 2 2 2 0 0 0.49 1.00 288 BETAOXIDATIONPATHWAY Beta-Oxidation of Fatty Acids ACADL, ACADM, ACADS, ACAT1, ECHS1, HADHA 6 ACADL(2), ACADM(1), ACADS(2), ACAT1(1), HADHA(2) 1468678 8 8 8 1 2 2 1 1 2 0 0.49 1.00 289 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 CD3D(1), IFNG(1), IL4(2), TGFB1(1), TGFB2(2), TGFBR2(3), TGFBR3(6) 2875946 16 16 16 7 0 7 6 0 3 0 0.49 1.00 290 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 30 ABP1(4), ADC(1), ALDH18A1(3), ALDH1B1(2), ALDH2(2), ALDH7A1(1), ALDH9A1(2), AMD1(1), AOC2(1), AOC3(3), ARG1(2), ASL(3), CPS1(18), GATM(1), NAGS(1), ODC1(1), OTC(2), SMS(2) 8031894 50 40 49 9 18 15 10 3 4 0 0.49 1.00 291 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 73 B2M(1), CALR(1), CANX(1), CD4(1), CD8B(1), CIITA(3), CREB1(1), CTSL1(1), CTSS(2), HLA-A(7), HLA-B(1), HLA-C(1), HLA-DMA(1), HLA-DMB(1), HLA-DPA1(1), HLA-DQA2(1), HLA-DRA(1), HLA-DRB1(1), HLA-DRB5(2), HLA-G(1), HSP90AB1(2), HSPA5(3), IFNA1(1), IFNA10(3), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), KIR2DL1(1), KIR2DL3(4), KIR2DS4(5), KIR3DL1(6), KIR3DL2(1), KIR3DL3(1), KLRC1(1), KLRC3(1), LTA(2), NFYB(1), PSME2(1), TAP1(2), TAPBP(3) 12697808 76 51 74 31 8 22 22 8 14 2 0.50 1.00 292 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(2), ABP1(4), ACADM(1), ALDH1B1(2), ALDH2(2), ALDH7A1(1), ALDH9A1(2), AOC2(1), AOC3(3), CNDP1(3), DPYD(7), DPYS(4), GAD1(4), GAD2(5), HADHA(2), HIBCH(1), MLYCD(1), SMS(2) 7313308 47 37 47 16 15 17 6 5 4 0 0.50 1.00 293 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 HRAS(1), MMP14(2), MMP2(3), MMP9(4), RECK(3), TIMP2(1) 2030980 14 11 14 3 2 6 3 2 1 0 0.50 1.00 294 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(1), CARS(5), DARS(1), EPRS(10), FARS2(1), HARS(2), IARS(3), KARS(2), LARS2(3), MARS(1), NARS(2), RARS(4), SARS(2), TARS(3), WARS(3), WARS2(1), YARS(1) 8565716 45 42 45 12 6 15 17 2 5 0 0.51 1.00 295 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(1), DIAPH1(1), FYN(3), GSN(2), HRAS(1), ITGA1(3), ITGB1(3), MAP2K1(2), MAPK1(1), MAPK3(1), MYL2(1), MYLK(5), PIK3CA(20), PIK3R1(1), PTK2(4), PXN(3), RAF1(1), ROCK1(5), SHC1(1), TLN1(3) 10127488 62 52 51 12 23 15 12 9 3 0 0.51 1.00 296 BIOGENIC_AMINE_SYNTHESIS AANAT, ACHE, CHAT, COMT, DBH, DDC, DXYS155E, GAD1, GAD2, HDC, MAOA, PAH, PNMT, SLC18A3, TH, TPH1 15 ACHE(2), CHAT(2), DBH(1), DDC(2), GAD1(4), GAD2(5), HDC(3), PAH(1), PNMT(2), TH(1), TPH1(1) 3978300 24 22 24 9 8 10 4 1 1 0 0.51 1.00 297 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(1), CSF1(2), LDLR(3), LPL(3) 1424534 9 9 9 2 5 3 1 0 0 0 0.52 1.00 298 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 RANBP2(11), RANGAP1(4) 2248318 15 13 15 5 2 6 3 2 2 0 0.52 1.00 299 ACETYLCHOLINE_SYNTHESIS ACHE, CHAT, CHKA, PCYT1A, PDHA1, PDHA2, PEMT, SLC18A3 8 ACHE(2), CHAT(2), CHKA(2), PDHA1(2), PDHA2(5) 1926672 13 12 13 2 3 6 3 1 0 0 0.52 1.00 300 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 43 ALDOA(1), ALDOB(2), DLAT(1), DLD(2), ENO2(1), ENO3(1), FBP2(1), G6PC(2), GAPDH(2), GAPDHS(1), GCK(1), GOT2(2), GPI(5), HK1(3), HK2(5), HK3(5), LDHAL6B(1), LDHB(2), LDHC(1), MDH1(1), MDH2(1), PC(2), PCK1(1), PDHA1(2), PDHA2(5), PFKL(2), PFKM(4), PFKP(2), PGAM2(1), PGK1(1), PGK2(4), PKLR(3), PKM2(2), TPI1(3) 11286268 73 54 73 25 19 28 13 6 7 0 0.52 1.00 301 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 ATP6V0A1(4), ATP6V0A4(2), ATP6V0D1(1), ATP6V1A(3), ATP6V1B1(2), ATP6V1C1(1), ATP6V1D(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(3), FDXR(2) 4317924 21 20 21 7 5 3 7 1 5 0 0.52 1.00 302 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(2), CSF1R(3), E2F1(2), ETS1(2), ETV3(2), FOS(1), HDAC5(1), HRAS(1), JUN(3), NCOR2(6), RBL1(5), RBL2(5), SIN3A(5), SIN3B(3) 7269342 41 36 40 9 7 15 8 7 4 0 0.53 1.00 303 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(15), ABCB11(5), ABCB4(6), ABCC1(4), ABCC3(1) 3890190 31 22 31 8 10 9 8 2 0 2 0.54 1.00 304 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 146 AKT1(1), AKT3(2), BCL2L1(1), CBL(1), CBLB(4), CCND2(3), CCND3(1), CNTFR(1), CREBBP(12), CSF2RB(5), CSF3R(5), EP300(6), EPOR(2), GH2(2), GHR(2), IFNA1(1), IFNA10(3), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNAR1(2), IFNB1(1), IFNG(1), IFNGR1(3), IFNGR2(1), IL10(1), IL11RA(1), IL12A(1), IL12B(2), IL12RB1(3), IL12RB2(3), IL13RA1(2), IL13RA2(1), IL20RA(1), IL21(1), IL21R(1), IL22(1), IL22RA2(1), IL23R(1), IL28B(1), IL2RB(2), IL2RG(1), IL4(2), IL4R(1), IL5RA(2), IL6R(1), IL7R(2), JAK1(1), JAK2(3), JAK3(7), LEPR(10), LIFR(2), MPL(2), MYC(1), OSMR(2), PIAS1(2), PIAS3(2), PIAS4(2), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PIM1(2), PRL(1), PRLR(5), PTPN11(2), SOCS2(1), SOCS5(3), SOS1(6), SOS2(5), SPRED1(1), SPRED2(1), STAM(1), STAM2(2), STAT1(2), STAT2(1), STAT3(1), STAT4(4), STAT5A(2), STAT6(1), TPO(10), TYK2(5) 38399228 232 115 219 85 57 79 53 21 22 0 0.54 1.00 305 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 131 ACACA(1), ACACB(8), AKT1(1), AKT3(2), ARAF(3), BRAF(7), CALML6(1), CBL(1), CBLB(4), EXOC7(1), FBP2(1), FLOT1(1), G6PC(2), G6PC2(1), GCK(1), GYS1(1), GYS2(4), HRAS(1), IKBKB(2), INPP5D(5), INSR(7), IRS1(3), IRS2(2), IRS4(2), KRAS(1), LIPE(1), MAP2K1(2), MAPK1(1), MAPK10(1), MAPK3(1), MAPK8(2), MAPK9(1), MKNK2(1), PCK1(1), PCK2(1), PDE3A(4), PDE3B(3), PDPK1(1), PFKL(2), PFKM(4), PFKP(2), PHKA1(4), PHKA2(2), PHKB(6), PHKG1(2), PHKG2(1), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PKLR(3), PKM2(2), PPARGC1A(5), PPP1R3A(12), PPP1R3C(2), PPP1R3D(2), PRKAA2(3), PRKACB(2), PRKACG(1), PRKAG2(4), PRKAG3(2), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PRKCI(4), PRKX(1), PTPN1(1), PTPRF(6), PYGB(3), PYGM(4), RAF1(1), RAPGEF1(3), RPS6(1), RPS6KB1(1), SHC1(1), SHC2(2), SHC3(2), SHC4(4), SLC2A4(2), SOCS2(1), SORBS1(5), SOS1(6), SOS2(5), SREBF1(2), TRIP10(2), TSC1(5), TSC2(5) 44062120 258 120 247 82 70 86 54 17 31 0 0.55 1.00 306 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 BLVRA(2), CP(2), CPOX(2), EPRS(10), FECH(2), GUSB(2), PPOX(1), UGT1A10(2), UGT1A3(1), UGT1A5(2), UGT1A6(1), UGT1A7(1), UGT1A8(3), UGT1A9(1), UGT2B15(1), UGT2B4(4), UROD(1) 7022990 38 35 38 9 6 14 13 2 3 0 0.55 1.00 307 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(3), DYRK1B(1), GLI2(4), GLI3(6), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), SMO(1), SUFU(2) 4465486 25 23 25 12 4 11 4 3 3 0 0.55 1.00 308 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 43 CEBPA(1), CHUK(2), DAXX(2), EGF(6), EGFR(6), ETS1(2), FOS(1), HOXA7(2), HRAS(1), IKBKB(2), JUN(3), MAP2K1(2), MAP2K3(2), MAP2K6(2), MAP3K1(2), MAP3K14(1), MAP3K5(3), MAPK1(1), MAPK13(2), MAPK14(1), MAPK3(1), MAPK8(2), NFKB1(2), PRKCA(4), PRKCD(2), PRKCE(3), PRKCG(8), PRKCQ(4), RAF1(1), RELA(2), SP1(1), TNFRSF1A(2), TNFRSF1B(1) 13433838 77 60 75 17 23 24 14 6 10 0 0.55 1.00 309 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(1), CD4(1), HLA-DRA(1), HLA-DRB1(1), IL1B(1), IL4(2), IL5RA(2) 1438952 9 8 9 2 1 4 1 0 3 0 0.55 1.00 310 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 16 GATA3(5), IL4(2), MAF(1), MAP2K3(2), MAPK14(1), NFATC2(4), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2) 3260782 23 19 23 6 10 7 3 1 2 0 0.56 1.00 311 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 CDC25B(1), CDK7(1), CHEK1(4), NEK1(3), WEE1(2) 1979716 11 11 11 1 3 5 2 0 1 0 0.56 1.00 312 CYANOAMINO_ACID_METABOLISM ATP6V0C, SHMT1, GBA3, GGT1, SHMT1, SHMT2 5 GBA3(6), GGT1(1) 1181208 7 6 7 4 1 2 3 0 1 0 0.56 1.00 313 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 49 ACOX1(2), APOA2(1), CD36(1), CREBBP(12), EP300(6), HSD17B4(1), JUN(3), LPL(3), MAPK1(1), MAPK3(1), MYC(1), NCOA1(5), NCOR1(5), NCOR2(6), NR0B2(1), NR1H3(2), NRIP1(3), PIK3CA(20), PIK3R1(1), PPARA(1), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PRKCA(4), RB1(7), RELA(2), RXRA(1), SP1(1), STAT5A(2) 16962866 101 70 88 35 30 30 17 9 15 0 0.56 1.00 314 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 80 AGL(5), AMY2B(3), ASCC3(9), ATP13A2(1), DDX18(2), DDX19A(1), DDX23(3), DDX4(1), DDX41(2), DDX50(1), DDX52(1), DDX54(3), DDX55(1), DDX56(1), ENPP1(7), ENPP3(3), ENTPD7(1), ERCC3(1), G6PC(2), G6PC2(1), GANC(3), GBA3(6), GBE1(1), GCK(1), GPI(5), GUSB(2), GYS1(1), GYS2(4), HK1(3), HK2(5), HK3(5), IFIH1(3), MGAM(3), NUDT8(1), PYGB(3), PYGM(4), RAD54L(1), SETX(10), SI(31), SKIV2L2(2), SMARCA2(2), TREH(1), UGDH(2), UGP2(4), UGT1A10(2), UGT1A3(1), UGT1A5(2), UGT1A6(1), UGT1A7(1), UGT1A8(3), UGT1A9(1), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4), UGT2B7(2), UXS1(3) 33165672 190 102 190 50 51 64 47 12 16 0 0.57 1.00 315 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 29 EGFR(6), GNAS(5), GNB1(1), HRAS(1), ITGB1(3), KLK2(1), MAP2K1(2), MAPK1(1), MAPK3(1), MKNK2(1), MYC(1), NGFR(1), PDGFRA(8), PTPRR(7), RAF1(1), RPS6KA1(2), RPS6KA5(4), SHC1(1), SOS1(6), STAT3(1) 9071948 54 45 53 12 16 12 19 5 2 0 0.57 1.00 316 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 40 ALK(5), AR(4), ESR1(5), ESR2(1), HNF4A(2), NR0B1(4), NR1H3(2), NR1I2(1), NR1I3(1), NR2C2(1), NR2E1(3), NR2F6(1), NR4A1(4), NR4A2(3), NR5A2(4), PGR(3), PPARA(1), PPARD(1), RARA(1), RARB(2), RARG(1), ROR1(3), RORA(2), RORC(2), RXRA(1), RXRG(4), THRA(1), THRB(1), VDR(3) 11522474 67 52 67 21 19 20 14 4 10 0 0.57 1.00 317 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 ATP6V0A1(4), ATP6V0A4(2), ATP6V0D1(1), ATP6V1A(3), ATP6V1B1(2), ATP6V1C1(1), ATP6V1D(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(3) 4058222 19 18 19 7 4 2 7 1 5 0 0.58 1.00 318 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 ATP6V0A1(4), ATP6V0A4(2), ATP6V0D1(1), ATP6V1A(3), ATP6V1B1(2), ATP6V1C1(1), ATP6V1D(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(3) 4058222 19 18 19 7 4 2 7 1 5 0 0.58 1.00 319 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 ATP6V0A1(4), ATP6V0A4(2), ATP6V0D1(1), ATP6V1A(3), ATP6V1B1(2), ATP6V1C1(1), ATP6V1D(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(3) 4058222 19 18 19 7 4 2 7 1 5 0 0.58 1.00 320 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 22 BTK(4), DLG4(1), EPHB2(4), F2RL1(3), F2RL2(1), F2RL3(1), JUN(3), MAP2K5(1), MAPK1(1), MAPK7(1), MAPK8(2), MYEF2(3), PLD1(6), PLD2(2), PLD3(1), PTK2(4), RAF1(1), RASAL1(3), TEC(2), VAV1(7) 7510888 51 37 50 16 13 17 11 4 6 0 0.58 1.00 321 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 CXCR4(5), FOS(1), JUN(3), MAPK14(1), MAPK8(2), PLCG1(1), PRKCA(4), SYT1(3) 3539708 20 19 19 8 7 5 4 3 1 0 0.59 1.00 322 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 5 CDK5(1), GRIA2(3), PPP1R1B(1) 1061414 5 5 5 5 0 2 1 0 2 0 0.59 1.00 323 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 33 AGT(1), AGTR1(2), ATF2(2), EGFR(6), HRAS(1), JUN(3), MAP2K1(2), MAP3K1(2), MAPK1(1), MAPK3(1), MAPK8(2), MEF2A(2), MEF2C(3), MEF2D(2), PAK1(1), PRKCA(4), PTK2(4), RAC1(1), RAF1(1), SHC1(1), SOS1(6), SYT1(3) 9123746 51 46 49 18 16 13 12 6 4 0 0.59 1.00 324 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(1), GTF2B(1), GTF2E1(1), GTF2F1(1), GTF2H4(1), GTF2I(1), GTF2IRD1(4), TAF1(10), TAF1L(16), TAF2(6), TAF4(1), TAF4B(4), TAF5L(1), TAF6L(1), TAF7L(1), TAF9(2), TBPL2(1) 9710434 53 46 53 13 15 16 10 6 6 0 0.59 1.00 325 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 15 CHUK(2), CREBBP(12), EP300(6), FADD(1), HDAC3(1), IKBKB(2), NFKB1(2), RELA(2), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TRAF6(1) 6117860 33 28 32 9 7 9 6 4 7 0 0.60 1.00 326 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 246 ACVR1B(3), ACVR2A(3), AMHR2(4), BMPR1A(3), CCL14(2), CCL16(1), CCL20(1), CCL26(2), CCL3(2), CCR1(2), CCR3(1), CCR4(3), CCR6(2), CCR8(1), CD27(1), CD40(1), CD40LG(2), CNTFR(1), CSF1(2), CSF1R(3), CSF2RB(5), CSF3R(5), CX3CR1(3), CXCL5(2), CXCR3(1), CXCR4(5), EDA2R(1), EGF(6), EGFR(6), EPOR(2), FAS(1), FASLG(1), FLT1(8), FLT3(4), FLT4(3), GDF5(4), GH2(2), GHR(2), HGF(6), IFNA1(1), IFNA10(3), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNAR1(2), IFNB1(1), IFNG(1), IFNGR1(3), IFNGR2(1), IL10(1), IL11RA(1), IL12A(1), IL12B(2), IL12RB1(3), IL12RB2(3), IL13RA1(2), IL17A(1), IL17RA(3), IL18R1(2), IL18RAP(2), IL1B(1), IL1R2(3), IL1RAP(2), IL20RA(1), IL21(1), IL21R(1), IL22(1), IL22RA2(1), IL23R(1), IL28B(1), IL2RB(2), IL2RG(1), IL4(2), IL4R(1), IL5RA(2), IL6R(1), IL7R(2), INHBA(4), INHBC(1), KDR(12), KIT(5), LEPR(10), LIFR(2), LTA(2), LTBR(1), MET(3), MPL(2), NGFR(1), OSMR(2), PDGFB(1), PDGFC(1), PDGFRA(8), PDGFRB(4), PF4(1), PLEKHO2(3), PRL(1), PRLR(5), TGFB1(1), TGFB2(2), TGFBR2(3), TNFRSF10A(1), TNFRSF10B(1), TNFRSF11A(1), TNFRSF11B(1), TNFRSF13B(1), TNFRSF18(1), TNFRSF19(1), TNFRSF1A(2), TNFRSF1B(1), TNFRSF21(3), TNFRSF6B(1), TNFRSF9(1), TNFSF11(1), TNFSF13(1), TNFSF14(1), TNFSF18(1), TPO(10), VEGFC(4), XCL1(1), XCR1(1) 47276444 282 124 280 111 74 99 56 19 34 0 0.60 1.00 327 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 CD4(1), HLA-DRA(1), HLA-DRB1(1) 650412 3 3 3 2 0 1 0 0 2 0 0.60 1.00 328 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 21 ALDOA(1), ALDOB(2), FBP2(1), GOT2(2), GPT(1), GPT2(2), MDH1(1), MDH2(1), ME2(2), ME3(1), PGK1(1), PKLR(3), PKM2(2), RPIA(1), TKT(1), TPI1(3) 4743700 25 24 25 13 5 7 6 3 4 0 0.60 1.00 329 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(1), BCR(1), FOS(1), HRAS(1), JAK2(3), JUN(3), MAP2K1(2), MAP3K1(2), MAPK3(1), MAPK8(2), MYC(1), PIK3CA(20), PIK3R1(1), RAF1(1), SOS1(6), STAT1(2), STAT5A(2) 7564110 50 40 38 7 20 11 13 4 2 0 0.60 1.00 330 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 17 CARS(5), GOT2(2), LDHAL6B(1), LDHB(2), LDHC(1), SDS(2), SULT1B1(4), SULT1C2(3), SULT1C4(1) 3393748 21 18 21 4 2 9 6 2 2 0 0.61 1.00 331 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 21 AARS(1), ABAT(2), ADSL(1), ADSS(1), AGXT2(1), ASL(3), ASNS(3), CAD(8), DARS(1), DDO(2), GAD1(4), GAD2(5), GOT2(2), GPT(1), GPT2(2), NARS(2), PC(2) 7056632 41 34 41 16 7 20 8 3 3 0 0.62 1.00 332 GANGLIOSIDE_BIOSYNTHESIS B3GALT4, GALGT, SIAT4A, SIAT4B, SIAT7B, SIAT7D, SIAT9, ST3GAL1, ST3GAL2, ST3GAL4, ST3GAL5, ST6GALNAC2, ST6GALNAC4, ST8SIA1 8 B3GALT4(1), ST3GAL1(1), ST3GAL4(2), ST3GAL5(2), ST8SIA1(2) 1506770 8 8 8 6 2 2 3 0 1 0 0.62 1.00 333 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 30 AKT1(1), CABIN1(1), CAMK1G(2), HDAC5(1), IGF1(3), INSR(7), MAP2K6(2), MAPK14(1), MAPK7(1), MEF2A(2), MEF2C(3), MEF2D(2), NFATC2(4), PIK3CA(20), PIK3R1(1), PPP3CA(2), PPP3CB(4), PPP3CC(2), SYT1(3) 9507870 62 46 51 15 23 16 11 8 4 0 0.62 1.00 334 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 21 CHUK(2), FADD(1), IKBKB(2), IRAK1(3), MAP3K1(2), MAP3K14(1), MAP3K7(2), NFKB1(2), RELA(2), TLR4(10), TNFAIP3(3), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TRAF6(1) 6703836 35 29 35 14 8 8 7 5 7 0 0.62 1.00 335 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 ACAA2(1), ACAD8(2), ACAD9(3), ADH1B(1), ADH1C(1), ADH4(2), ADH5(1), ADH7(1), ADHFE1(2), AKR1C4(1), AKR1D1(4), ALDH1B1(2), ALDH2(2), ALDH7A1(1), ALDH9A1(2), BAAT(2), CEL(1), CYP27A1(1), CYP7A1(3), HADHB(2), LIPA(2), RDH11(1), RDH12(2), RDH13(1), SLC27A5(4), SOAT2(1), SRD5A1(2), SRD5A2(2) 8668778 50 42 50 12 12 19 6 7 6 0 0.63 1.00 336 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 32 APC(9), ATF2(2), BMP10(1), BMP4(1), BMP5(5), BMPR1A(3), CHRD(3), CTNNB1(3), DVL1(3), FZD1(1), MAP3K7(2), MEF2C(3), MYL2(1), NKX2-5(2), RFC1(1), TGFB1(1), TGFB2(2), TGFBR2(3), TGFBR3(6) 9785906 52 44 52 14 10 15 14 6 7 0 0.63 1.00 337 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 9 CUL1(2), E2F1(2), RB1(7), SKP2(1) 2358678 12 11 12 1 1 6 0 0 5 0 0.63 1.00 338 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(3), PRKCA(4) 1368286 7 7 7 1 2 1 3 0 1 0 0.63 1.00 339 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 29 CD4(1), CSF1(2), HLA-DRA(1), HLA-DRB1(1), IFNA1(1), IFNB1(1), IFNG(1), IL10(1), IL12A(1), IL12B(2), IL4(2), LTA(2), TGFB1(1), TGFB2(2) 3596846 19 18 19 6 2 6 5 3 3 0 0.64 1.00 340 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 92 AKT1(1), AKT3(2), CARD11(3), CBL(1), CBLB(4), CD3D(1), CD4(1), CD40LG(2), CD8B(1), CDC42(1), CHP(2), CHUK(2), FOS(1), FYN(3), HRAS(1), ICOS(2), IFNG(1), IKBKB(2), IL10(1), IL4(2), ITK(2), JUN(3), KRAS(1), LCK(2), LCP2(2), MALT1(1), MAP3K14(1), NCK1(2), NFAT5(2), NFATC2(4), NFATC3(2), NFATC4(1), NFKB1(2), NFKB2(2), NFKBIB(1), PAK1(1), PAK3(1), PAK4(1), PAK7(4), PDK1(1), PIK3CA(20), PIK3CB(2), PIK3CD(3), PIK3CG(9), PIK3R1(1), PIK3R2(3), PIK3R3(2), PIK3R5(2), PLCG1(1), PPP3CA(2), PPP3CB(4), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKCQ(4), PTPRC(3), RASGRP1(1), SOS1(6), SOS2(5), TEC(2), VAV1(7), VAV2(3), VAV3(1), ZAP70(2) 27660132 159 92 147 45 44 43 32 20 20 0 0.64 1.00 341 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 32 AKT1(1), DAG1(1), DGKA(3), ETFA(2), GCA(1), ITPKA(1), ITPKB(4), ITPR1(4), ITPR2(11), ITPR3(1), MAP2K1(2), MAPK1(1), MAPK3(1), NR1I3(1), PAK1(1), PDE3A(4), PDE3B(3), PI3(1), PIK3C2G(6), PIK3CA(20), PIK3CD(3), PIK3R1(1), RIPK3(1), SGCB(1), VASP(2) 13431346 77 59 66 20 32 19 15 3 8 0 0.64 1.00 342 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(2), PLCB1(6), PRKCA(4), RELA(2) 2235858 14 11 14 4 5 4 1 2 2 0 0.64 1.00 343 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(1), ACO2(3), FH(2), IDH1(2), MDH1(1), MDH2(1), SUCLA2(2) 2378792 12 12 12 3 2 6 1 2 1 0 0.64 1.00 344 GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM ACO1, ACO2, CS, GRHPR, HAO1, HAO2, HYI, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 12 ACO1(1), ACO2(3), GRHPR(1), HAO1(5), MDH1(1), MDH2(1), MTHFD1(3), MTHFD1L(2), MTHFD2(3) 3428992 20 18 20 2 6 6 5 2 1 0 0.65 1.00 345 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 30 AGPAT3(1), AGPAT6(1), ENPP2(6), ENPP6(1), PAFAH1B1(1), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(5), PLD1(6), PLD2(2), PPAP2B(1) 6299776 38 31 38 18 7 17 8 1 5 0 0.65 1.00 346 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT2(2), TAT(1) 702744 3 3 3 2 1 1 0 1 0 0 0.65 1.00 347 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 16 B3GNT2(1), B3GNT7(1), B4GALT1(1), B4GALT3(1), B4GALT4(1), CHST1(2), CHST2(3), CHST4(2), CHST6(3), FUT8(2), ST3GAL1(1), ST3GAL4(2) 3427212 20 18 20 10 8 6 4 2 0 0 0.65 1.00 348 HSA00900_TERPENOID_BIOSYNTHESIS Genes involved in terpenoid biosynthesis FDFT1, FDPS, GGPS1, IDI1, IDI2, SQLE 6 FDPS(1), GGPS1(2), IDI1(1), IDI2(2), SQLE(2) 1174622 8 7 8 0 3 2 1 2 0 0 0.65 1.00 349 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 42 AKT1(1), BRAF(7), CREB1(1), CREB3(2), CREB5(3), CREBBP(12), DAG1(1), EGR1(2), EGR2(6), EGR3(1), FRS2(3), JUN(3), MAP1B(3), MAPK1(1), MAPK10(1), MAPK3(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(3), MAPK9(1), NTRK1(3), OPN1LW(2), PIK3C2G(6), PIK3CA(20), PIK3CD(3), PIK3R1(1), PTPN11(2), RPS6KA3(1), SHC1(1), TH(1) 14262962 96 63 84 29 37 29 18 6 6 0 0.66 1.00 350 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(2), CLOCK(5), CRY1(1), CRY2(2), PER1(4) 2337496 14 12 14 3 0 5 7 1 1 0 0.66 1.00 351 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(1), LDLR(3), MBTPS1(3), MBTPS2(3), SCAP(4), SREBF1(2), SREBF2(2) 3331092 18 17 18 3 5 5 4 4 0 0 0.66 1.00 352 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 23 UBE2A(1), UBE2C(1), UBE2D1(1), UBE2D2(1), UBE2E3(1), UBE2G2(1), UBE2J1(2), UBE2L6(1), UBE2M(1), UBE3A(5) 2847644 15 15 15 4 4 6 2 1 2 0 0.66 1.00 353 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(3), DLAT(1), DLD(2), DLST(1), FH(2), IDH3A(1), IDH3B(3), IDH3G(1), MDH1(1), MDH2(1), OGDH(3), PC(2), PDHA1(2), PDHA2(5), PDK1(1), PDK2(1), PDK3(2), PDK4(2), PDP2(4), SDHA(1), SUCLA2(2), SUCLG2(1) 7678564 42 37 42 12 5 17 7 8 5 0 0.66 1.00 354 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 32 B4GALT1(1), G6PC(2), G6PC2(1), GALK2(1), GALT(1), GANC(3), GCK(1), GLA(2), HK1(3), HK2(5), HK3(5), LCT(14), MGAM(3), PFKL(2), PFKM(4), PFKP(2), RDH11(1), RDH12(2), RDH13(1), UGP2(4) 10583880 58 49 58 21 22 14 8 9 5 0 0.66 1.00 355 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 112 ATP12A(4), ATP4A(6), ATP5A1(2), ATP5B(1), ATP5C1(3), ATP5G2(2), ATP5G3(1), ATP5L(1), ATP6V0A1(4), ATP6V0A2(5), ATP6V0A4(2), ATP6V0D1(1), ATP6V0D2(2), ATP6V1A(3), ATP6V1B1(2), ATP6V1C1(1), ATP6V1D(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(3), COX4I1(1), COX4I2(1), COX6B1(1), COX7B2(2), CYC1(4), NDUFA13(2), NDUFA7(1), NDUFAB1(1), NDUFB5(2), NDUFB8(1), NDUFS1(3), NDUFS6(1), NDUFS8(1), NDUFV1(2), NDUFV2(2), SDHA(1), UQCRB(1), UQCRC2(1) 15113624 74 59 74 21 12 24 22 7 9 0 0.68 1.00 356 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 36 ANPEP(5), GCLC(2), GCLM(1), GGT1(1), GPX5(1), GPX6(2), GSR(2), GSS(2), GSTA2(1), GSTA4(1), GSTA5(1), GSTM3(1), GSTM4(3), GSTM5(2), GSTZ1(2), IDH1(2), MGST1(1), OPLAH(3) 6086710 33 30 33 10 7 15 7 3 1 0 0.68 1.00 357 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(1), ACPT(1), ALPL(3), ALPP(2), ALPPL2(1), CYP19A1(4), CYP1A1(7), CYP1A2(1), CYP2A13(1), CYP2A6(4), CYP2B6(3), CYP2C19(6), CYP2C8(2), CYP2C9(2), CYP2D6(3), CYP2F1(3), CYP2J2(1), CYP3A4(1), CYP3A7(1), CYP4B1(2), CYP4F8(1), PON1(4) 7937020 54 38 54 26 16 15 15 4 4 0 0.68 1.00 358 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 99 ADCY1(7), ADCY2(14), ADCY3(4), ADCY4(3), ADCY5(1), ADCY7(4), ADCY8(13), ADCY9(3), CALML6(1), CAMK2B(2), CAMK2D(1), CREB1(1), CREB3(2), CREB3L2(2), CREB3L3(1), CREB3L4(2), CREBBP(12), CTNNB1(3), DCT(1), DVL1(3), DVL3(2), EDNRB(3), EP300(6), FZD1(1), FZD10(1), FZD3(4), FZD4(1), FZD6(2), FZD7(1), FZD9(2), GNAI1(2), GNAI3(1), GNAS(5), HRAS(1), KIT(5), KRAS(1), LEF1(3), MAP2K1(2), MAPK1(1), MAPK3(1), PLCB1(6), PLCB2(5), PLCB3(3), PLCB4(4), POMC(1), PRKACB(2), PRKACG(1), PRKCA(4), PRKCG(8), PRKX(1), RAF1(1), TCF7(1), TYR(3), TYRP1(2), WNT10B(2), WNT11(1), WNT2(3), WNT2B(2), WNT3(2), WNT3A(1), WNT6(2), WNT7A(2), WNT7B(1), WNT9A(1), WNT9B(1) 29895100 185 97 184 58 52 62 32 22 17 0 0.68 1.00 359 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3D(1) 303668 1 1 1 0 0 1 0 0 0 0 0.68 1.00 360 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 19 EXT1(2), EXT2(1), EXTL1(1), EXTL3(1), HS3ST2(1), HS3ST5(4), HS6ST1(2), HS6ST3(2), NDST1(2), NDST2(1), NDST3(4), NDST4(11) 5722344 32 28 32 13 2 15 7 6 2 0 0.68 1.00 361 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 10 ANPEP(5), CKM(2), FBL(1), GPT(1), LDHB(2), LDHC(1), MAPK14(1), NCL(1) 2415104 14 12 14 4 2 7 2 1 2 0 0.70 1.00 362 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 34 AKT1(1), AKT3(2), BRAF(7), DAG1(1), DRD2(2), EGFR(6), EPHB2(4), ITPKA(1), ITPKB(4), ITPR1(4), ITPR2(11), ITPR3(1), KCNJ3(7), KCNJ5(2), KCNJ9(2), MAPK1(1), PI3(1), PIK3CB(2), PITX2(3), PLCB1(6), PLCB2(5), PLCB3(3), PLCB4(4), RAF1(1), RGS20(1), SHC1(1), SOS1(6), SOS2(5), STAT3(1) 16020534 95 66 94 21 24 31 21 5 14 0 0.70 1.00 363 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 53 ABP1(4), ACAT1(1), ACMSD(1), ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH9A1(2), AOC2(1), AOC3(3), AOX1(9), CYP19A1(4), CYP1A1(7), CYP1A2(1), CYP2A13(1), CYP2A6(4), CYP2B6(3), CYP2C19(6), CYP2C8(2), CYP2C9(2), CYP2D6(3), CYP2F1(3), CYP2J2(1), CYP3A4(1), CYP3A7(1), CYP4B1(2), CYP4F8(1), DDC(2), GCDH(1), HADHA(2), KMO(2), KYNU(3), SDS(2), TDO2(1), TPH1(1), WARS(3), WARS2(1) 14696748 87 63 87 39 23 29 21 8 6 0 0.70 1.00 364 AMINOSUGARS_METABOLISM CMAS, CYB5R3, GCK, GFPT1, GNE, GNPDA1, GNPDA2, HEXA, HEXB, HK1, HK2, HK3, PGM3, RENBP, UAP1 15 CMAS(2), GCK(1), GNE(2), GNPDA2(3), HEXA(4), HK1(3), HK2(5), HK3(5), UAP1(1) 4584390 26 22 26 7 7 9 3 3 4 0 0.70 1.00 365 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(4), CD44(3), CSF1(2), FCGR3A(3), IL1B(1), IL6R(1), SELL(2), TGFB1(1), TGFB2(2), TNFRSF1A(2), TNFRSF1B(1) 3779118 22 18 22 8 6 6 5 2 3 0 0.70 1.00 366 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 12 CDK5(1), EGR1(2), HRAS(1), KLK2(1), MAP2K1(2), MAPK1(1), MAPK3(1), NGFR(1), RAF1(1) 2270034 11 11 11 3 2 6 2 1 0 0 0.71 1.00 367 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(1), ACO2(3), GRHPR(1), HAO1(5), MDH1(1), MDH2(1), MTHFD1(3), MTHFD1L(2), MTHFD2(3) 3592396 20 18 20 2 6 6 5 2 1 0 0.72 1.00 368 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(1), GTF2A1(1), GTF2B(1), GTF2E1(1), GTF2F1(1), HDAC3(1), NCOA1(5), NCOA2(9), NCOA3(4), NCOR2(6), POLR2A(1), RARA(1), RXRA(1), TBP(1) 6895008 34 30 34 13 8 12 5 2 7 0 0.72 1.00 369 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 15 CCL3(2), FLT3(4), IGF1(3), TGFB1(1), TGFB2(2) 2290504 12 12 12 9 2 6 4 0 0 0 0.72 1.00 370 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 CCR3(1), HLA-DRA(1), HLA-DRB1(1) 817376 3 3 3 0 0 1 0 0 2 0 0.72 1.00 371 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 ADH1B(1), ADH1C(1), ADH4(2), ADH5(1), ADH7(1), ADHFE1(2), AKR1C2(1), AKR1C3(1), AKR1C4(1), ALDH3B2(1), CYP1A1(7), CYP1A2(1), CYP2B6(3), CYP2C19(6), CYP2C8(2), CYP2C9(2), CYP2F1(3), CYP2S1(1), CYP3A4(1), CYP3A43(3), CYP3A7(1), GSTA2(1), GSTA4(1), GSTA5(1), GSTM3(1), GSTM4(3), GSTM5(2), GSTZ1(2), MGST1(1), UGT1A10(2), UGT1A3(1), UGT1A5(2), UGT1A6(1), UGT1A7(1), UGT1A8(3), UGT1A9(1), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4), UGT2B7(2) 14907500 89 63 89 33 24 25 26 8 6 0 0.73 1.00 372 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(7), CREB1(1), FOS(1), GNAI1(2), GNAS(5), GNB1(1), HRAS(1), JUN(3), MAP2K1(2), MAPK3(1), NFATC2(4), NFATC3(2), NFATC4(1), PLCG1(1), PPP3CA(2), PPP3CB(4), PPP3CC(2), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), PRKCA(4), RAF1(1), RPS6KA3(1), SYT1(3) 9434534 57 43 56 14 18 17 7 10 5 0 0.73 1.00 373 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 ADH1B(1), ADH1C(1), ADH4(2), ADH7(1), ADHFE1(2), ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH3B2(1), ALDH9A1(2), ALDOA(1), ALDOB(2), BPGM(1), DLAT(1), DLD(2), ENO2(1), ENO3(1), FBP2(1), G6PC(2), GAPDH(2), GCK(1), GPI(5), HK1(3), HK2(5), HK3(5), LDHB(2), LDHC(1), PDHA1(2), PDHA2(5), PFKM(4), PFKP(2), PGK1(1), PKLR(3), PKM2(2), TPI1(3) 12973530 74 59 74 19 20 31 14 6 3 0 0.73 1.00 374 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 ADH1B(1), ADH1C(1), ADH4(2), ADH7(1), ADHFE1(2), ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH3B2(1), ALDH9A1(2), ALDOA(1), ALDOB(2), BPGM(1), DLAT(1), DLD(2), ENO2(1), ENO3(1), FBP2(1), G6PC(2), GAPDH(2), GCK(1), GPI(5), HK1(3), HK2(5), HK3(5), LDHB(2), LDHC(1), PDHA1(2), PDHA2(5), PFKM(4), PFKP(2), PGK1(1), PKLR(3), PKM2(2), TPI1(3) 12973530 74 59 74 19 20 31 14 6 3 0 0.73 1.00 375 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 22 CHUK(2), CREBBP(12), EP300(6), IKBKB(2), IL1B(1), MAP2K3(2), MAP2K6(2), MAP3K14(1), MAP3K7(2), MAPK14(1), NFKB1(2), RELA(2), TGFBR2(3), TLR2(3) 8069630 41 36 40 11 10 12 8 3 8 0 0.73 1.00 376 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(1), CPT1A(3), LEPR(10), PRKAA2(3), PRKAG2(4) 3886986 21 20 21 6 8 5 6 1 1 0 0.74 1.00 377 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 26 ALDOA(1), ALDOB(2), DERA(1), FBP2(1), GPI(5), H6PD(2), PFKL(2), PFKM(4), PFKP(2), PRPS1(1), PRPS1L1(1), PRPS2(1), RBKS(1), RPIA(1), TALDO1(1), TKT(1), TKTL2(9) 6647588 36 31 36 14 9 10 8 4 5 0 0.74 1.00 378 HSA00363_BISPHENOL_A_DEGRADATION Genes involved in bisphenol A degradation AKR1B10, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, HSD3B7, PON1, PON2, PON3, RDH11, RDH12, RDH13, RDH14 13 DHRS2(1), PON1(4), PON2(1), PON3(1), RDH11(1), RDH12(2), RDH13(1) 2268076 11 11 11 3 3 3 1 2 2 0 0.74 1.00 379 GLOBOSIDE_METABOLISM A4GALT, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, ST8SIA1 13 FUT9(1), GBGT1(2), GLA(2), HEXA(4), ST3GAL1(1), ST3GAL4(2), ST8SIA1(2) 2748498 14 12 14 5 2 5 4 2 1 0 0.74 1.00 380 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 40 ARNTL(2), AZIN1(1), BTG1(1), CLOCK(5), CRY1(1), CRY2(2), EIF4G2(2), ETV6(4), GSTM3(1), HERPUD1(1), HSPA8(3), IDI1(1), KLF9(1), MYF6(1), NCKAP1(4), PER1(4), PER2(2), PIGF(1), PPP1R3C(2), PSMA4(1), PURA(1), SF3A3(2), UCP3(3), UGP2(4), VAPA(1), ZFR(4) 9949310 55 43 55 13 7 18 17 4 9 0 0.74 1.00 381 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 43 CBL(1), CD3D(1), DAG1(1), EPHB2(4), FBXW7(10), ITK(2), ITPKA(1), ITPKB(4), LCK(2), LCP2(2), MAPK1(1), NCK1(2), NFAT5(2), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(4), PAK1(1), PAK3(1), PAK4(1), PAK7(4), PLCG1(1), PTPRC(3), RAF1(1), RASGRP1(1), RASGRP3(6), RASGRP4(4), SOS1(6), SOS2(5), VAV1(7), ZAP70(2) 15279876 86 62 84 31 21 25 20 6 14 0 0.74 1.00 382 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(1), JAK2(3), JAK3(7), MAPK1(1), MAPK3(1), STAT3(1), TYK2(5) 3262918 19 16 19 3 2 10 5 1 1 0 0.74 1.00 383 SULFUR_METABOLISM BPNT1, PAPSS1, PAPSS2, SULT1A2, SULT1A3, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SUOX 7 BPNT1(1), PAPSS2(1), SULT1A2(2), SULT1E1(1), SULT2A1(3) 1626208 8 8 8 3 2 3 2 0 1 0 0.74 1.00 384 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 ACAA2(1), ADH1B(1), ADH1C(1), ADH4(2), ADH7(1), ADHFE1(2), AKR1C4(1), AKR1D1(4), ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH9A1(2), BAAT(2), CEL(1), CYP27A1(1), CYP7A1(3), HADHB(2), SOAT2(1), SRD5A1(2), SRD5A2(2) 6312592 35 30 35 8 7 15 6 4 3 0 0.74 1.00 385 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 21 F2R(2), F2RL3(1), GNAI1(2), GNB1(1), HRAS(1), ITGA1(3), ITGB1(3), MAP2K1(2), MAPK1(1), MAPK3(1), PLA2G4A(5), PLCB1(6), PRKCA(4), PTGS1(2), PTK2(4), RAF1(1), SYK(1), TBXAS1(2) 6603266 42 32 42 12 13 15 7 3 4 0 0.75 1.00 386 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(1), BTK(4), FOS(1), HRAS(1), JUN(3), LYN(1), MAP2K1(2), MAP3K1(2), MAPK14(1), MAPK3(1), MAPK8(2), NFATC2(4), NFATC3(2), NFATC4(1), PLCG1(1), PPP3CA(2), PPP3CB(4), PPP3CC(2), PRKCA(4), RAC1(1), RAF1(1), SHC1(1), SOS1(6), SYK(1), SYT1(3), VAV1(7) 10354616 59 46 58 12 18 12 12 10 7 0 0.75 1.00 387 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 27 ABP1(4), ALDH3B2(1), AOC2(1), AOC3(3), DDC(2), EPX(4), ESCO1(1), GOT2(2), HPD(1), LPO(2), MPO(3), MYST3(9), MYST4(3), PNPLA3(1), PRDX6(1), SH3GLB1(1), TAT(1), TPO(10) 9222714 50 42 50 23 12 17 13 5 3 0 0.75 1.00 388 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(3), ICAM1(2), ITGA4(3), ITGAL(1), ITGAM(3), ITGB1(3), ITGB2(3), SELE(4), SELL(2), SELP(8) 4718780 32 23 32 7 8 9 9 2 4 0 0.75 1.00 389 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 BCAT2(2), COASY(2), DPYD(7), DPYS(4), ENPP1(7), ENPP3(3), ILVBL(2), PANK3(1), PPCS(1), VNN1(2) 4731952 31 23 31 9 10 9 7 2 3 0 0.76 1.00 390 METHIONINEPATHWAY Catabolic Pathways for Methionine, Isoleucine, Threonine and Valine BCKDHB, BCKDK, CBS, CTH, MUT 5 BCKDHB(2), CBS(4), MUT(1) 1333932 7 6 7 0 0 5 0 0 2 0 0.76 1.00 391 1_AND_2_METHYLNAPHTHALENE_DEGRADATION ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 7 ADH1B(1), ADH1C(1), ADH4(2), ADH7(1), ADHFE1(2) 1501074 7 7 7 2 3 4 0 0 0 0 0.76 1.00 392 HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - lactoseries ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 10 B3GALT1(2), B3GALT2(2), FUT3(3), ST3GAL4(2) 1955330 9 9 9 4 3 0 5 1 0 0 0.76 1.00 393 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(1), CREM(2), FOS(1), JUN(3), MAPK3(1), POLR2A(1), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2) 3384492 17 16 16 5 5 6 1 2 3 0 0.76 1.00 394 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 93 ANK2(19), B3GALT4(1), CDR1(2), DGKI(7), MRPL19(1), PIGK(1), RPL14(1), RPL19(1), RPL32(1), RPL37(1), RPL3L(1), RPL4(1), RPL5(1), RPL7(1), RPL8(2), RPLP0(2), RPS11(1), RPS18(1), RPS2(1), RPS21(1), RPS26(1), RPS6(1), RPS6KA1(2), RPS6KA2(3), RPS6KA3(1), RPS6KA6(4), RPS6KB1(1), RPS8(1), SLC36A2(2), TBC1D10C(1), TSPAN9(1), UBB(1), UBC(1) 14395750 67 58 67 31 15 15 24 11 2 0 0.76 1.00 395 SA_FAS_SIGNALING The TNF-type receptor Fas induces apoptosis on ligand binding. BCL2, CASP3, CASP8, CFL1, CFLAR, P11, PDE6D, TNFRSF6, TNFSF6 6 CASP8(1), CFL1(2), CFLAR(1) 1038452 4 4 4 1 0 3 0 0 1 0 0.76 1.00 396 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(3), FH(2), MDH1(1), OGDH(3), SDHA(1), SUCLA2(2) 2517098 12 12 12 6 1 5 2 3 1 0 0.76 1.00 397 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(1), CAPN1(2), CAPNS2(1), CDK5(1), CSNK1A1(2), MAPT(4) 2580466 11 11 11 1 1 5 0 1 4 0 0.77 1.00 398 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 30 AKT1(1), AKT3(2), APC(9), CSNK1A1(2), CTNNB1(3), DACT1(3), DKK1(3), DKK2(1), DVL1(3), FSTL1(2), GSK3A(3), LRP1(10), MVP(2), NKD1(1), NKD2(2), PSEN1(1), SENP2(3), SFRP1(1), WIF1(3) 10938100 55 46 55 15 15 16 13 2 9 0 0.77 1.00 399 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 110 ADCY1(7), ADCY2(14), ADCY3(4), ADCY4(3), ADCY5(1), ADCY7(4), ADCY8(13), ADSL(1), ADSS(1), AK5(3), AMPD1(4), AMPD2(1), AMPD3(6), ATP5A1(2), ATP5B(1), ATP5C1(3), ATP5G2(2), ATP5G3(1), CANT1(1), DCK(1), ENPP1(7), ENPP3(3), ENTPD1(1), ENTPD2(1), GART(1), GDA(6), GUCY1A2(10), GUCY1A3(5), GUCY1B3(3), GUCY2C(4), GUCY2D(1), GUCY2F(4), GUK1(2), HPRT1(1), IMPDH1(1), NPR1(2), NPR2(2), NT5E(2), PAPSS2(1), PDE1A(2), PDE4A(1), PDE4B(3), PDE4C(2), PDE4D(1), PDE5A(4), PDE6B(3), PDE7B(1), PDE8A(5), PDE9A(2), PFAS(4), PKLR(3), PKM2(2), POLB(1), POLD1(2), POLG(1), POLL(1), POLQ(12), POLR1B(2), POLR2A(1), POLR2B(2), POLR2D(1), POLR2E(1), PPAT(2), PRPS1(1), PRPS1L1(1), PRPS2(1), RRM1(1) 35177072 193 105 193 60 50 67 34 19 23 0 0.77 1.00 400 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(1), EGF(6), EGFR(6), TF(5), TFRC(2) 3479188 20 17 19 2 8 8 2 0 2 0 0.78 1.00 401 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(2), IKBKAP(2), IKBKB(2), LTA(2), MAP3K1(2), MAP3K14(1), NFKB1(2), RELA(2), TANK(4), TNFAIP3(3), TNFRSF1B(1), TRAF1(4), TRAF3(1) 6090804 28 24 28 10 5 4 6 5 8 0 0.78 1.00 402 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(1), AARS2(5), CARS(5), DARS(1), DARS2(5), EARS2(2), EPRS(10), FARS2(1), FARSA(2), HARS(2), HARS2(2), IARS(3), IARS2(3), KARS(2), LARS2(3), MARS(1), NARS(2), NARS2(2), PARS2(2), RARS(4), RARS2(2), SARS(2), SARS2(2), TARS(3), TARS2(2), VARS(3), VARS2(1), WARS(3), WARS2(1), YARS(1) 14615580 78 58 78 23 9 30 24 5 10 0 0.78 1.00 403 SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES ACAT1, ACAT2, BDH, HMGCL, OXCT1 4 ACAT1(1), HMGCL(1), OXCT1(2) 901926 4 4 4 3 3 1 0 0 0 0 0.78 1.00 404 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(1), ALDOB(2), FBP2(1), GPI(5), H6PD(2), PFKM(4), PFKP(2), PRPS1(1), PRPS1L1(1), PRPS2(1), RBKS(1), RPIA(1), TAL1(2), TALDO1(1), TKT(1) 5552176 26 25 26 12 6 8 4 3 5 0 0.78 1.00 405 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 31 CD14(1), CHUK(2), FOS(1), IKBKB(2), IRAK1(3), JUN(3), MAP2K3(2), MAP2K6(2), MAP3K1(2), MAP3K14(1), MAP3K7(2), MAPK14(1), MAPK8(2), NFKB1(2), PPARA(1), RELA(2), TLR2(3), TLR3(2), TLR4(10), TLR7(3), TLR9(1), TOLLIP(1), TRAF6(1) 9909082 50 41 49 16 16 11 9 6 8 0 0.78 1.00 406 IFNGPATHWAY IFN gamma signaling pathway IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 6 IFNG(1), IFNGR1(3), IFNGR2(1), JAK1(1), JAK2(3), STAT1(2) 2203818 11 10 11 2 2 3 5 0 1 0 0.78 1.00 407 STREPTOMYCIN_BIOSYNTHESIS GCK, HK1, HK2, HK3, IMPA1, PGM1, PGM3, TGDS 8 GCK(1), HK1(3), HK2(5), HK3(5), IMPA1(1), TGDS(1) 2756330 16 14 16 4 6 6 1 2 1 0 0.79 1.00 408 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(3), ICAM1(2), ITGAL(1), ITGAM(3), ITGB2(3), SELE(4), SELL(2) 3233726 18 16 18 5 5 5 5 2 1 0 0.79 1.00 409 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(6), EGFR(6), MAP2K1(2), MAP3K1(2), MAPK14(1), NCOR2(6), RARA(1), RXRA(1), THRA(1), THRB(1) 4792828 27 23 26 9 12 8 4 0 3 0 0.79 1.00 410 HSA00625_TETRACHLOROETHENE_DEGRADATION Genes involved in tetrachloroethene degradation AKR1B10, EPHX2, HSD3B7, RDH11, RDH12, RDH13, RDH14 7 EPHX2(2), RDH11(1), RDH12(2), RDH13(1) 1309724 6 6 6 2 3 0 0 2 1 0 0.79 1.00 411 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 14 CSF2RB(5), FOS(1), HRAS(1), JAK2(3), MAP2K1(2), MAPK3(1), RAF1(1), SHC1(1), SOS1(6), STAT5A(2) 4575846 23 22 23 2 6 7 6 1 3 0 0.79 1.00 412 PANTOTHENATE_AND_COA_BIOSYNTHESIS BCAT1, COASY, DPYD, DPYS, ENPP1, ENPP3, PANK1, PANK2, PANK3, PANK4, PPCS, UPB1 12 COASY(2), DPYD(7), DPYS(4), ENPP1(7), ENPP3(3), PANK3(1), PPCS(1) 3808488 25 18 25 8 7 9 4 2 3 0 0.80 1.00 413 TERPENOID_BIOSYNTHESIS FDFT1, FDPS, FDPS, LOC402397, IDI1, SQLE 4 FDPS(1), IDI1(1), SQLE(2) 887152 4 4 4 0 2 1 0 1 0 0 0.80 1.00 414 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(2), IL13RA2(1), IL4R(1), JAK1(1), JAK2(3), TYK2(5) 2816850 13 12 13 5 1 4 5 1 2 0 0.80 1.00 415 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(2), IL13RA2(1), IL4R(1), JAK1(1), JAK2(3), TYK2(5) 2816850 13 12 13 5 1 4 5 1 2 0 0.80 1.00 416 NOTCHPATHWAY Proteolysis and Signaling Pathway of Notch ADAM17, DLL1, FURIN, NOTCH1, PSEN1, RBPSUH 5 DLL1(1), FURIN(1), NOTCH1(10), PSEN1(1) 2659320 13 11 13 6 2 6 0 1 4 0 0.80 1.00 417 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 55 ABP1(4), ADH1B(1), ADH1C(1), ADH4(2), ADH5(1), ADH7(1), ADHFE1(2), ALDH3B2(1), AOC2(1), AOC3(3), AOX1(9), CARM1(1), DBH(1), DCT(1), DDC(2), ECH1(1), ESCO1(1), FAH(1), GOT2(2), GSTZ1(2), HPD(1), LCMT1(2), MYST3(9), MYST4(3), PNMT(2), PNPLA3(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(4), PRMT8(1), SH3GLB1(1), TAT(1), TH(1), TPO(10), TYR(3), TYRP1(2), WBSCR22(3) 15827048 87 63 87 24 23 34 11 11 8 0 0.80 1.00 418 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(1), RAB11A(1), RAB4A(3) 1158068 5 5 5 9 3 2 0 0 0 0 0.81 1.00 419 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 21 B3GNT2(1), B3GNT3(4), B3GNT4(1), B4GALT1(1), B4GALT3(1), B4GALT4(1), FUT3(3), FUT5(4), FUT6(2), FUT9(1), GCNT2(1), ST8SIA1(2) 4446796 22 19 22 12 7 6 6 2 1 0 0.81 1.00 420 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 63 ACSS1(3), ADH1B(1), ADH1C(1), ADH4(2), ADH5(1), ADH7(1), ADHFE1(2), ALDH1B1(2), ALDH2(2), ALDH3B2(1), ALDH7A1(1), ALDH9A1(2), ALDOA(1), ALDOB(2), BPGM(1), DLAT(1), DLD(2), ENO2(1), ENO3(1), FBP2(1), G6PC(2), G6PC2(1), GAPDH(2), GAPDHS(1), GCK(1), GPI(5), HK1(3), HK2(5), HK3(5), LDHAL6B(1), LDHB(2), LDHC(1), PDHA1(2), PDHA2(5), PFKL(2), PFKM(4), PFKP(2), PGAM2(1), PGK1(1), PGK2(4), PKLR(3), PKM2(2), TPI1(3) 15403764 87 64 87 27 25 33 15 8 6 0 0.81 1.00 421 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(4), ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH3B2(1), ALDH9A1(2), AOC2(1), AOC3(3), CNDP1(3), DDC(2), HARS(2), HDC(3), HNMT(2), PRPS1(1), PRPS2(1) 6575498 31 30 31 14 10 11 6 3 1 0 0.81 1.00 422 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 34 AKT1(1), AKT3(2), ARHGEF11(7), CDC42(1), DLG4(1), LPA(11), MAP3K1(2), MAP3K5(3), MAPK8(2), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(4), PDK1(1), PHKA2(2), PI3(1), PIK3CB(2), PLD1(6), PLD2(2), PLD3(1), PTK2(4), RDX(1), ROCK1(5), ROCK2(3), SERPINA4(4), SRF(2), TBXA2R(2) 13379548 76 54 75 27 11 31 18 9 7 0 0.82 1.00 423 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 25 APC(9), CERK(3), CREB1(1), CREB3(2), CREB5(3), DAG1(1), EPHB2(4), FOS(1), ITPKA(1), ITPKB(4), JUN(3), MAPK1(1), MAPK10(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(3), MAPK9(1) 7865998 42 34 41 11 12 12 10 2 6 0 0.82 1.00 424 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(1), ABP1(4), AOC2(1), AOC3(3), CES1(2), CES7(1), DDHD1(4), ESCO1(1), LIPA(2), MYST3(9), MYST4(3), PLA1A(5), PNPLA3(1), PRDX6(1), SH3GLB1(1) 6849084 39 31 39 17 11 14 7 4 3 0 0.82 1.00 425 UBIQUINONE_BIOSYNTHESIS NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 14 NDUFB5(2), NDUFS1(3), NDUFV1(2), NDUFV2(2) 1823966 9 8 9 2 4 2 2 1 0 0 0.82 1.00 426 HSA00460_CYANOAMINO_ACID_METABOLISM Genes involved in cyanoamino acid metabolism ASRGL1, GBA, GBA3, GGT1, GGTL3, GGTL4, SHMT1, SHMT2 6 GBA3(6), GGT1(1) 1569604 7 6 7 4 1 2 3 0 1 0 0.82 1.00 427 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(3), LPL(3), RXRA(1) 1557322 7 7 7 3 2 4 0 1 0 0 0.83 1.00 428 VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS BCAT1, IARS, LARS, LARS2, PDHA1, PDHA2, PDHB 7 IARS(3), LARS2(3), PDHA1(2), PDHA2(5) 2688156 13 12 13 2 1 6 4 1 1 0 0.83 1.00 429 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 CD3D(1), CD4(1) 675510 2 2 2 2 0 1 0 0 1 0 0.83 1.00 430 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 58 APC(9), CCND2(3), CCND3(1), CTNNB1(3), DVL1(3), DVL3(2), FZD1(1), FZD10(1), FZD3(4), FZD6(2), FZD7(1), FZD9(2), JUN(3), LDLR(3), MAPK10(1), MAPK9(1), MYC(1), PAFAH1B1(1), PLAU(2), PPP2R5C(5), PRKCA(4), PRKCD(2), PRKCE(3), PRKCG(8), PRKCI(4), PRKCQ(4), PRKD1(9), RAC1(1), SFRP4(3), TCF7(1), WNT10B(2), WNT11(1), WNT2(3), WNT2B(2), WNT3(2), WNT6(2), WNT7A(2), WNT7B(1) 16330076 103 64 102 26 32 32 22 10 7 0 0.83 1.00 431 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 GUSB(2), UGDH(2), UGT1A10(2), UGT1A3(1), UGT1A5(2), UGT1A6(1), UGT1A7(1), UGT1A8(3), UGT1A9(1), UGT2B15(1), UGT2B4(4) 4394820 20 19 20 4 4 6 8 1 1 0 0.83 1.00 432 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 IFNA1(1), IFNAR1(2), IFNB1(1), JAK1(1), STAT1(2), STAT2(1), TYK2(5) 2905494 13 13 13 5 3 5 1 3 1 0 0.84 1.00 433 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 30 ANPEP(5), GCLC(2), GCLM(1), GGT1(1), GPX5(1), GSS(2), GSTA2(1), GSTA4(1), GSTM3(1), GSTM4(3), GSTM5(2), GSTZ1(2), IDH1(2), MGST1(1) 4947866 25 23 25 8 7 12 4 2 0 0 0.84 1.00 434 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 65 ADAM10(4), ATP6V0A1(4), ATP6V0A2(5), ATP6V0A4(2), ATP6V0D1(1), ATP6V0D2(2), ATP6V1A(3), ATP6V1B1(2), ATP6V1C1(1), ATP6V1D(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(3), CDC42(1), CHUK(2), EGFR(6), F11R(1), GIT1(1), HBEGF(1), IGSF5(2), IKBKB(2), JUN(3), LYN(1), MAP3K14(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK8(2), MAPK9(1), MET(3), NFKB1(2), NFKB2(2), NOD1(4), PAK1(1), PLCG1(1), PLCG2(3), PTPN11(2), PTPRZ1(8), RAC1(1), RELA(2), TJP1(8) 19090856 95 65 93 19 27 22 19 10 17 0 0.85 1.00 435 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 23 ARSB(1), ARSD(1), ARSE(2), GAL3ST1(1), GALC(1), GLA(2), LCT(14), NEU1(2), NEU2(2), PPAP2B(1), SMPD1(3), SMPD2(1), SPTLC2(3) 6640468 34 29 34 12 11 8 7 5 3 0 0.85 1.00 436 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(1), CD4(1), FYN(3), HLA-DRA(1), HLA-DRB1(1), LCK(2), PTPRC(3), ZAP70(2) 2464054 14 11 14 6 2 7 2 1 2 0 0.85 1.00 437 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 ACO1(1), ACO2(3), ACSS1(3), FH(2), IDH1(2), MDH1(1), MDH2(1), SUCLA2(2) 3552346 15 15 15 5 3 6 2 3 1 0 0.86 1.00 438 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(2), FOS(1), HRAS(1), IL2RB(2), IL2RG(1), JAK1(1), JAK3(7), JUN(3), LCK(2), MAP2K1(2), MAPK3(1), MAPK8(2), RAF1(1), SHC1(1), SOS1(6), STAT5A(2), SYK(1) 6428648 36 29 35 9 9 13 9 2 3 0 0.86 1.00 439 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(1), CD3D(1), CD4(1), ICAM1(2), ITGAL(1), ITGB2(3), PTPRC(3), THY1(2) 3034544 14 14 14 9 2 8 1 2 1 0 0.87 1.00 440 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 51 AKR1C3(1), ALOX12B(1), ALOX15(2), ALOX15B(1), CYP2B6(3), CYP2C19(6), CYP2C8(2), CYP2C9(2), CYP2J2(1), CYP4A22(2), CYP4F2(3), CYP4F3(2), DHRS4(1), EPHX2(2), GGT1(1), GPX5(1), GPX6(2), LTA4H(2), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(5), PTGES(1), PTGS1(2), TBXAS1(2) 10638882 59 44 59 28 16 14 20 2 7 0 0.87 1.00 441 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(1), CD34(2), CD3D(1), CD4(1), CD58(1) 1701146 6 6 6 6 1 3 0 0 2 0 0.87 1.00 442 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(3), ICAM1(2), ITGA4(3), ITGAL(1), ITGB1(3), ITGB2(3), SELE(4), SELL(2) 3655764 21 16 21 3 5 6 7 2 1 0 0.88 1.00 443 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(1), ABAT(2), ACADS(2), ACAT1(1), ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH5A1(1), ALDH9A1(2), GAD1(4), GAD2(5), HADHA(2), HMGCL(1), OXCT1(2), PDHA1(2), PDHA2(5), SDS(2) 6966742 38 31 38 16 8 18 4 4 4 0 0.88 1.00 444 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 41 ABP1(4), ACY3(2), ALDH1B1(2), ALDH2(2), ALDH3B2(1), ALDH7A1(1), ALDH9A1(2), AMDHD1(1), AOC2(1), AOC3(3), CARM1(1), CNDP1(3), DDC(2), HARS(2), HARS2(2), HDC(3), HNMT(2), LCMT1(2), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(4), PRMT8(1), PRPS1(1), PRPS2(1), UROC1(1), WBSCR22(3) 10716134 52 45 52 17 22 15 8 4 3 0 0.88 1.00 445 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(1), AASDHPPT(1), AASS(6), ACAT1(1), ALDH1B1(2), ALDH2(2), ALDH7A1(1), ALDH9A1(2), BBOX1(2), DLST(1), DOT1L(4), EHMT2(1), GCDH(1), HADH(1), HADHA(2), HSD17B4(1), NSD1(8), OGDH(3), OGDHL(4), PIPOX(1), PLOD1(4), PLOD2(4), PLOD3(5), RDH11(1), RDH12(2), RDH13(1), SETD1A(6), SETDB1(3), SPCS1(1), SPCS3(2), SUV39H1(1), SUV39H2(2) 15838974 77 58 77 33 9 24 22 8 14 0 0.88 1.00 446 TSP1PATHWAY Thrombospondin-1 (TSP-1) inhibits angiogenesis by inducing caspase-dependent apoptosis in microvascular endothelial cells. CASP3, CD36, FOS, FYN, JUN, MAPK14, THBS1 7 CD36(1), FOS(1), FYN(3), JUN(3), MAPK14(1), THBS1(1) 1984344 10 9 9 1 2 2 4 2 0 0 0.89 1.00 447 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(1), CD3D(1), ICAM1(2), ITGAL(1), ITGB2(3), PTPRC(3), THY1(2) 2883956 13 13 13 8 2 8 1 2 0 0 0.89 1.00 448 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 24 CASP2(1), CHUK(2), CRADD(1), IKBKB(2), JUN(3), LTA(2), MAP2K3(2), MAP2K6(2), MAP3K1(2), MAP3K14(1), MAP4K2(1), MAPK14(1), MAPK8(2), NFKB1(2), RELA(2), TANK(4), TNFRSF1A(2), TRADD(1) 6698318 33 27 32 10 8 9 6 3 7 0 0.89 1.00 449 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 FUT9(1), GBGT1(2), GLA(2), HEXA(4), ST3GAL1(1), ST8SIA1(2) 2913504 12 11 12 5 2 5 2 2 1 0 0.89 1.00 450 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 12 APC(9), CTNNB1(3), DLL1(1), DVL1(3), FZD1(1), NOTCH1(10), PSEN1(1) 5808318 28 24 28 8 6 10 5 1 6 0 0.89 1.00 451 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 PSMA4(1), PSMA5(1), PSMB3(1), PSMB4(1), PSMC3(1), PSMD14(3), RPN1(1), UBE2A(1), UBE3A(5) 3479544 15 15 15 3 4 6 3 0 2 0 0.89 1.00 452 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 52 APAF1(1), ARHGDIB(1), BAG4(1), BIRC3(3), CASP2(1), CASP7(2), CASP8(1), CASP9(2), CFLAR(1), CHUK(2), CRADD(1), DAXX(2), DFFB(2), FADD(1), GSN(2), MAP3K1(2), MAP3K14(1), MAP3K5(3), MAPK8(2), MDM2(1), NFKB1(2), NUMA1(4), PRKCD(2), PRKDC(11), PSEN1(1), PSEN2(2), PTK2(4), RASA1(5), RB1(7), RELA(2), SPTAN1(2), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TRAF1(4) 19149418 82 63 82 26 16 24 11 8 23 0 0.90 1.00 453 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(1), BDH1(3), HMGCL(1), HMGCS1(1), HMGCS2(1), OXCT1(2) 1973842 9 8 9 5 3 4 1 1 0 0 0.90 1.00 454 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 ACADL(2), ACADM(1), ACOX1(2), ACOX3(4), ACSL1(2), ACSL3(1), ACSL6(1), ADIPOQ(1), ANGPTL4(1), APOA2(1), APOA5(3), CD36(1), CPT1A(3), CPT1C(3), CPT2(1), CYP27A1(1), CYP4A22(2), CYP7A1(3), DBI(1), FABP5(1), FABP6(1), FABP7(1), FADS2(1), GK(4), GK2(5), HMGCS2(1), ILK(1), LPL(3), MMP1(3), NR1H3(2), PCK1(1), PCK2(1), PDPK1(1), PLTP(2), PPARA(1), PPARD(1), RXRA(1), RXRG(4), SCD(1), SCP2(1), SLC27A1(1), SLC27A2(2), SLC27A4(1), SLC27A5(4), SLC27A6(3), SORBS1(5), UBC(1), UCP1(2) 17498112 90 65 90 39 24 25 27 6 8 0 0.90 1.00 455 AKAPCENTROSOMEPATHWAY Protein Kinase A at the Centrosome AKAP9, ARHA, CDC2, MAP2, PCNT1, PCNT2, PPP1CA, PPP2CA, PRKACB, PRKACG, PRKAG1, PRKAR2A, PRKAR2B, PRKCE, PRKCL1 10 AKAP9(7), MAP2(8), PRKACB(2), PRKACG(1), PRKAR2B(2), PRKCE(3) 4900162 23 20 23 7 6 3 9 3 2 0 0.90 1.00 456 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(1), ACO2(3), DLD(2), DLST(1), FH(2), IDH1(2), IDH3A(1), IDH3B(3), IDH3G(1), MDH1(1), MDH2(1), PC(2), PCK1(1), SDHA(1), SUCLA2(2), SUCLG2(1) 5541852 25 23 25 8 5 8 3 5 4 0 0.90 1.00 457 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 28 BCAR1(5), HRAS(1), JUN(3), MAP2K1(2), MAP2K3(2), MAP3K1(2), MAPK1(1), MAPK14(1), MAPK3(1), MAPK8(2), PAK1(1), PLCG1(1), PRKCA(4), RAC1(1), RAF1(1), SHC1(1), SOS1(6), SYT1(3) 7794620 38 34 37 11 14 8 9 5 2 0 0.90 1.00 458 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 ALDOA(1), ALDOB(2), FBP2(1), FPGT(2), GCK(1), GMPPA(1), HK1(3), HK2(5), HK3(5), KHK(1), MPI(1), PFKFB1(2), PFKM(4), PFKP(2), PMM1(1), TPI1(3) 6506434 35 28 35 13 12 8 10 3 2 0 0.90 1.00 459 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(1), AADAC(1), ABAT(2), ACADS(2), ACAT1(1), ACSM1(5), ALDH1B1(2), ALDH2(2), ALDH5A1(1), ALDH7A1(1), ALDH9A1(2), BDH1(3), DDHD1(4), GAD1(4), GAD2(5), HADH(1), HADHA(2), HMGCL(1), HMGCS1(1), HMGCS2(1), HSD17B4(1), ILVBL(2), OXCT1(2), PDHA1(2), PDHA2(5), PLA1A(5), PRDX6(1), RDH11(1), RDH12(2), RDH13(1) 11071778 64 45 64 23 16 24 8 10 6 0 0.90 1.00 460 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 AHCY(1), CBS(4), DNMT1(3), DNMT3A(6), DNMT3B(3), MARS(1), MAT1A(1), MTR(4) 4733020 23 19 23 10 3 11 6 1 2 0 0.90 1.00 461 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 ADH1B(1), ADH1C(1), ADH4(2), ADH5(1), ADH7(1), ADHFE1(2), ALDH1B1(2), ALDH2(2), ALDH7A1(1), ALDH9A1(2) 3593286 15 15 15 3 5 8 0 2 0 0 0.90 1.00 462 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(1), HADH(1), HADHA(2), HADHB(2), HSD17B4(1), PPT1(1) 2306524 8 8 8 2 1 0 2 3 2 0 0.91 1.00 463 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 47 APAF1(1), BAX(1), BCL2A1(1), BCL2L1(1), CASP1(1), CASP10(3), CASP2(1), CASP4(3), CASP7(2), CASP8(1), CASP9(2), CD40(1), CD40LG(2), CRADD(1), DAXX(2), DFFB(2), FADD(1), FAS(1), FASLG(1), IKBKE(3), LTA(2), MCL1(2), NFKB1(2), NGFR(1), NTRK1(3), PTPN13(3), SFRS2IP(3), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TRAF1(4), TRAF3(1), TRAF6(1) 12079436 57 43 57 23 12 19 7 7 12 0 0.91 1.00 464 HSA00920_SULFUR_METABOLISM Genes involved in sulfur metabolism BPNT1, CHST11, CHST12, CHST13, PAPSS1, PAPSS2, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SULT2B1, SUOX 12 BPNT1(1), CHST12(1), PAPSS2(1), SULT1A1(1), SULT1A2(2), SULT1E1(1), SULT2A1(3) 2544332 10 10 10 5 2 3 2 2 1 0 0.91 1.00 465 CAPROLACTAM_DEGRADATION AKR1A1, ECHS1, EHHADH, HADHA, SDS 5 HADHA(2), SDS(2) 1318802 4 4 4 5 0 1 1 0 2 0 0.91 1.00 466 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 10 BAG4(1), BIRC3(3), CASP8(1), FADD(1), TNFRSF1A(2), TNFRSF1B(1), TRADD(1) 2346218 10 8 10 4 3 2 0 2 3 0 0.91 1.00 467 PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS ENO1, ENO2, ENO3, FARS2, FARSLB, GOT1, GOT2, PAH, TAT, YARS 9 ENO2(1), ENO3(1), FARS2(1), GOT2(2), PAH(1), TAT(1), YARS(1) 2211650 8 8 8 3 4 1 1 1 1 0 0.91 1.00 468 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 GNB1(1), HTR2C(2), PLCB1(6) 1924358 9 8 9 4 3 4 0 2 0 0 0.91 1.00 469 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 37 AGT(1), AGTR2(3), CAMK2B(2), CAMK2D(1), CDK5(1), FYN(3), GNAI1(2), GNB1(1), HRAS(1), JAK2(3), MAP2K1(2), MAPK1(1), MAPK14(1), MAPK3(1), MAPK8(2), MAPT(4), MYLK(5), PLCG1(1), PRKCA(4), RAF1(1), SHC1(1), SOS1(6), STAT1(2), STAT3(1), STAT5A(2), SYT1(3) 11315994 55 47 55 13 12 18 14 5 6 0 0.91 1.00 470 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(1), PLCG1(1), PRKCA(4) 1819516 6 6 6 3 2 2 1 0 1 0 0.91 1.00 471 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(1), HRAS(1), SHC1(1), SOS1(6) 2388582 9 9 9 1 2 1 4 1 1 0 0.91 1.00 472 HSA00521_STREPTOMYCIN_BIOSYNTHESIS Genes involved in streptomycin biosynthesis GCK, HK1, HK2, HK3, IMPA1, IMPA2, ISYNA1, PGM1, PGM3, TGDS 10 GCK(1), HK1(3), HK2(5), HK3(5), IMPA1(1), TGDS(1) 3175520 16 14 16 4 6 6 1 2 1 0 0.91 1.00 473 FATTY_ACID_BIOSYNTHESIS_PATH_2 ACAA1, ACAA2, ACAT1, ACAT2, ECHS1, EHHADH, HADHA, HADHB, SDS 9 ACAA2(1), ACAT1(1), HADHA(2), HADHB(2), SDS(2) 2252946 8 8 8 7 1 1 2 2 2 0 0.91 1.00 474 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 39 ANAPC1(4), ANAPC4(3), ANAPC5(4), CDC27(2), CUL1(2), CUL3(8), FBXW7(10), ITCH(2), RBX1(1), SKP1(1), SKP2(1), SMURF1(2), UBA1(3), UBE2C(1), UBE2D1(1), UBE2D2(1), UBE2E2(1), UBE2E3(1), VHL(1), WWP1(1) 10982956 50 42 48 12 10 11 9 8 12 0 0.91 1.00 475 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 ALDH1A2(2), BCMO1(1) 1037384 3 3 3 3 0 1 1 0 1 0 0.91 1.00 476 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(1), ARHGAP5(1), ARHGDIB(1), CASP1(1), CASP10(3), CASP8(1), CASP9(2), GZMB(1), JUN(3), PRF1(1) 3454802 15 15 14 8 3 5 3 2 2 0 0.91 1.00 477 KERATAN_SULFATE_BIOSYNTHESIS B3GNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT5, FUT8, SIAT4A, SIAT4B, SIAT6, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 10 B4GALT1(1), B4GALT3(1), B4GALT5(2), FUT8(2), ST3GAL1(1), ST3GAL4(2) 2168218 9 9 9 10 2 4 2 1 0 0 0.91 1.00 478 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(1), BIRC3(3), CASP10(3), CASP7(2), CASP8(1), CASP9(2), DFFB(2), GZMB(1), PRF1(1), SCAP(4), SREBF1(2), SREBF2(2) 5027432 24 21 24 10 5 9 5 3 2 0 0.92 1.00 479 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 22 AKT1(1), AP2A1(2), AP2M1(1), ARF1(1), BTK(4), EEA1(1), GSK3A(3), LYN(1), PDPK1(1), PFKL(2), PFKM(4), PFKP(2), PLCG1(1), PRKCE(3), RAC1(1), RPS6KB1(1), VAV2(3) 6962292 32 27 32 13 8 4 10 3 7 0 0.92 1.00 480 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(1), LCMT1(2), PCYT1B(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(4), PRMT8(1), WBSCR22(3) 3831272 17 16 17 2 7 5 2 1 2 0 0.92 1.00 481 HSA00053_ASCORBATE_AND_ALDARATE_METABOLISM Genes involved in ascorbate and aldarate metabolism ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, MIOX, UGDH 9 ALDH1B1(2), ALDH2(2), ALDH7A1(1), ALDH9A1(2), UGDH(2) 2317560 9 9 9 1 2 6 0 1 0 0 0.92 1.00 482 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 ACAA2(1), ACADL(2), ACADM(1), ACADS(2), ACAT1(1), ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH6A1(1), ALDH9A1(2), AOX1(9), BCKDHB(2), HADHA(2), HADHB(2), HMGCL(1), MCCC1(4), MUT(1), OXCT1(2), PCCA(2), PCCB(6), SDS(2) 9687116 49 39 49 13 6 19 11 8 5 0 0.92 1.00 483 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 57 AADAT(1), ABP1(4), ACAT1(1), ACMSD(1), ALDH1B1(2), ALDH2(2), ALDH7A1(1), ALDH9A1(2), AOC2(1), AOC3(3), AOX1(9), CARM1(1), CYP1A1(7), CYP1A2(1), DDC(2), GCDH(1), HADH(1), HADHA(2), HSD17B4(1), INMT(2), KMO(2), KYNU(3), LCMT1(2), LNX1(2), NFX1(1), OGDH(3), OGDHL(4), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(4), PRMT8(1), TDO2(1), TPH1(1), TPH2(5), WARS(3), WARS2(1), WBSCR22(3) 16210282 86 61 86 31 21 31 15 10 9 0 0.92 1.00 484 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 40 ALDOA(1), ALDOB(2), FBP2(1), FPGT(2), FUK(1), GMPPA(1), HK1(3), HK2(5), HK3(5), KHK(1), MPI(1), MTMR1(1), MTMR2(1), MTMR6(4), PFKFB1(2), PFKL(2), PFKM(4), PFKP(2), PGM2(4), PMM1(1), RDH11(1), RDH12(2), RDH13(1), TPI1(3) 10174124 51 42 51 15 16 10 13 6 6 0 0.92 1.00 485 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(1), CAPN2(2), CAPNS2(1), EP300(6), HDAC1(2), MEF2D(2), NFATC2(4), PPP3CA(2), PPP3CB(4), PPP3CC(2), PRKCA(4), SYT1(3) 6598994 33 26 32 8 10 7 6 6 4 0 0.93 1.00 486 MITOCHONDRIAL_FATTY_ACID_BETAOXIDATION ACADL, ACADM, ACADS, ACADVL, ACSL1, ACSL3, ACSL4, CPT1A, CPT2, DCI, EHHADH, HADHA, HADHSC, MGC5139, PECR, SCP2, SLC25A20 15 ACADL(2), ACADM(1), ACADS(2), ACADVL(1), ACSL1(2), ACSL3(1), CPT1A(3), CPT2(1), DCI(1), HADHA(2), PECR(1), SCP2(1) 4528320 18 18 18 7 4 5 5 1 3 0 0.93 1.00 487 1_2_DICHLOROETHANE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH9A1(2) 2153800 8 8 8 0 1 5 1 1 0 0 0.93 1.00 488 ASCORBATE_AND_ALDARATE_METABOLISM ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH9A1(2) 2153800 8 8 8 0 1 5 1 1 0 0 0.93 1.00 489 HSA05050_DENTATORUBROPALLIDOLUYSIAN_ATROPHY Genes involved in dentatorubropallidoluysian atrophy (DRPLA) ATN1, BAIAP2, CASP1, CASP3, CASP7, CASP8, GAPDH, INS, INSR, ITCH, MAGI1, MAGI2, RERE, WWP1, WWP2 15 ATN1(2), CASP1(1), CASP7(2), CASP8(1), GAPDH(2), INSR(7), ITCH(2), MAGI1(5), MAGI2(7), RERE(2), WWP1(1) 6378808 32 24 32 10 6 11 6 3 6 0 0.93 1.00 490 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(1), IL2RG(1), IL4(2), IL4R(1), IRS1(3), JAK1(1), JAK3(7), RPS6KB1(1), SHC1(1), STAT6(1) 4071928 19 16 19 6 3 9 5 0 2 0 0.93 1.00 491 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 6 DAG1(1), ITPKA(1), ITPKB(4) 1687262 6 6 6 2 4 0 1 0 1 0 0.93 1.00 492 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 CAMK1G(2), CAMK2B(2), CAMK2D(1), CAMK4(3), HDAC5(1), MEF2A(2), MEF2C(3), MEF2D(2), PPARA(1), PPP3CA(2), PPP3CB(4), PPP3CC(2), SLC2A4(2), SYT1(3) 5542920 30 22 30 10 11 5 3 7 4 0 0.93 1.00 493 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 BGN(1), DCN(1), FMOD(1) 967608 3 3 3 2 0 2 1 0 0 0 0.93 1.00 494 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 21 CSNK2A1(2), FOS(1), HRAS(1), IL6R(1), JAK1(1), JAK2(3), JAK3(7), JUN(3), MAP2K1(2), MAPK3(1), PTPN11(2), RAF1(1), SHC1(1), SOS1(6), SRF(2), STAT3(1) 6555740 35 28 34 7 8 12 10 3 2 0 0.93 1.00 495 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(1), AMD1(1), CBS(4), DNMT1(3), DNMT3A(6), DNMT3B(3), MARS(1), MAT1A(1), MTAP(1), MTR(4), TAT(1) 5640642 26 22 26 11 4 12 6 1 3 0 0.93 1.00 496 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 18 ATF2(2), CHUK(2), IFNG(1), IKBKB(2), IL4(2), JUN(3), MAP3K1(2), MAP3K5(3), MAP4K5(1), MAPK14(1), MAPK8(2), NFKB1(2), RELA(2), TNFRSF9(1) 5344806 26 21 25 9 5 6 9 2 4 0 0.93 1.00 497 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(1), FARSA(2), GOT2(2), PAH(1), TAT(1), YARS(1) 2348888 8 8 8 5 4 2 0 1 1 0 0.93 1.00 498 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 34 AKT1(1), BCL2L1(1), CBL(1), CFLAR(1), E2F1(2), FOS(1), HRAS(1), IL2RB(2), IL2RG(1), IRS1(3), JAK1(1), JAK3(7), MAPK1(1), MAPK3(1), MYC(1), NMI(1), PIK3CA(20), PIK3R1(1), RAF1(1), RPS6KB1(1), SHC1(1), SOS1(6), STAT5A(2), SYK(1) 9874728 59 41 48 13 20 19 13 3 4 0 0.93 1.00 499 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 BCAT2(2), IARS(3), IARS2(3), ILVBL(2), LARS2(3), PDHA1(2), PDHA2(5), VARS(3), VARS2(1) 5037400 24 20 24 5 4 10 6 1 3 0 0.93 1.00 500 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 10 CASP7(2), DFFB(2), GZMB(1), TOP2A(2), TOP2B(4) 2721976 11 10 11 5 1 4 4 1 1 0 0.93 1.00 501 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(2), EPOR(2), FOS(1), HRAS(1), JAK2(3), JUN(3), MAP2K1(2), MAPK3(1), MAPK8(2), PLCG1(1), RAF1(1), SHC1(1), SOS1(6), STAT5A(2) 5861184 28 24 27 5 8 7 8 2 3 0 0.94 1.00 502 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 17 CARM1(1), DHRS2(1), LCMT1(2), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(4), PRMT8(1), WBSCR22(3) 3890012 17 16 17 2 8 4 2 1 2 0 0.94 1.00 503 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 28 ARHGDIB(1), BAG4(1), CASP2(1), CASP8(1), CRADD(1), DFFB(2), FADD(1), JUN(3), MADD(3), MAP3K1(2), MAP3K7(2), MAPK8(2), PAK1(1), PRKDC(11), RB1(7), SPTAN1(2), TNFRSF1A(2), TRADD(1) 10863874 44 40 43 16 9 15 5 2 13 0 0.94 1.00 504 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 12 CPO(1), FECH(2), GATA1(2), HBB(2), UROD(1) 2209870 8 8 8 3 2 3 0 1 2 0 0.94 1.00 505 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 92 ACTB(1), CABIN1(1), CAMK2B(2), CAMK4(3), CNR1(2), CREBBP(12), CSNK2A1(2), EGR2(6), EGR3(1), EP300(6), FCER1A(2), FCGR3A(3), FKBP1B(1), FOS(1), GATA3(5), GRLF1(11), GSK3A(3), HRAS(1), ICOS(2), IFNA1(1), IFNB1(1), IFNG(1), IL10(1), IL1B(1), IL4(2), ITK(2), KPNA5(2), MAPK14(1), MAPK8(2), MAPK9(1), MEF2A(2), MEF2D(2), MYF5(3), NFAT5(2), NFATC2(4), NFATC3(2), NFATC4(1), NFKB2(2), NFKBIB(1), NUP214(4), OPRD1(1), P2RX7(1), PAK1(1), PPP3CB(4), PPP3CC(2), PPP3R1(1), PTPRC(3), RELA(2), SFN(2), SLA(1), SP1(1), SP3(1), TGFB1(1), TRPV6(3), VAV1(7), VAV2(3), VAV3(1), XPO5(1) 24820854 139 80 138 44 40 32 30 17 20 0 0.94 1.00 506 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 CHUK(2), EGR2(6), EGR3(1), MAP3K1(2), MYC(1), NFATC2(4), NFKB1(2), PLCG1(1), PPP3CA(2), PPP3CB(4), PPP3CC(2), PRKACB(2), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(2), RELA(2), SYT1(3), VIP(1) 7466566 41 29 41 10 14 8 5 8 6 0 0.94 1.00 507 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(1), ARHGEF1(2), GNA12(1), GNB1(1), MYL2(1), MYLK(5), PLCB1(6), PPP1R12B(4), PRKCA(4), ROCK1(5) 5569976 30 23 30 9 6 13 6 3 2 0 0.94 1.00 508 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 18 MARCKS(1), NFATC2(4), NFATC3(2), NFATC4(1), PLCG1(1), PPP3CA(2), PPP3CB(4), PPP3CC(2), PRKCA(4), SP1(1), SP3(1), SYT1(3) 5691372 26 22 26 5 9 7 2 5 3 0 0.94 1.00 509 BOTULINPATHWAY Blockade of Neurotransmitter Relase by Botulinum Toxin CHRM1, CHRNA1, SNAP25, STX1A, VAMP2 5 CHRNA1(1), SNAP25(1) 869530 2 2 2 3 0 1 1 0 0 0 0.94 1.00 510 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(6), CARM1(1), CREBBP(12), EP300(6), ERCC3(1), ESR1(5), GRIP1(3), GTF2A1(1), GTF2E1(1), GTF2F1(1), HDAC1(2), HDAC3(1), HDAC4(4), HDAC5(1), MEF2C(3), NCOR2(6), NR0B1(4), NRIP1(3), POLR2A(1), TBP(1) 12822586 63 48 62 19 18 17 13 7 8 0 0.94 1.00 511 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 26 ADRBK1(1), AKT1(1), AKT3(2), DAG1(1), ITPKA(1), ITPKB(4), ITPR1(4), ITPR2(11), ITPR3(1), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(4), PDK1(1), PHKA2(2), PIK3CB(2), PITX2(3), PLD1(6), PLD2(2), PLD3(1), VN1R1(2) 12327212 55 45 55 15 11 21 8 6 9 0 0.95 1.00 512 HSA00930_CAPROLACTAM_DEGRADATION Genes involved in caprolactam degradation AKR1A1, ASAHL, ECHS1, EHHADH, HADH, HADHA, HSD17B10, HSD17B4, NTAN1, SIRT1, SIRT2, SIRT5, SIRT7, VNN2, VNN3 13 HADH(1), HADHA(2), HSD17B4(1), SIRT2(2), VNN2(5) 3154338 11 10 11 7 0 3 3 1 4 0 0.95 1.00 513 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 22 ACP1(1), ACP6(2), ACPT(1), ALPL(3), ALPP(2), ALPPL2(1), CMBL(1), CYP3A4(1), CYP3A43(3), CYP3A7(1), DHRS2(1), PON1(4), PON2(1), PON3(1) 4730528 23 18 23 10 6 8 3 2 4 0 0.95 1.00 514 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 35 ACTA1(1), ACTN1(2), ACTN2(6), ACTN3(2), BCAR1(5), BCR(1), CAPN1(2), CAPNS2(1), FYN(3), HRAS(1), ITGA1(3), ITGB1(3), JUN(3), MAP2K1(2), MAPK1(1), MAPK3(1), MAPK8(2), PPP1R12B(4), PTK2(4), PXN(3), RAF1(1), ROCK1(5), SHC1(1), SOS1(6), TLN1(3), VCL(2) 12940422 68 51 67 21 17 22 14 10 5 0 0.95 1.00 515 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 31 CHUK(2), IFNA1(1), IFNB1(1), IKBKB(2), IL1B(1), IL1RAP(2), IRAK1(3), IRAK3(3), JUN(3), MAP2K3(2), MAP2K6(2), MAP3K1(2), MAP3K14(1), MAP3K7(2), MAPK14(1), MAPK8(2), NFKB1(2), RELA(2), TGFB1(1), TGFB2(2), TOLLIP(1), TRAF6(1) 8061264 39 32 38 14 14 10 6 5 4 0 0.95 1.00 516 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(1), FOSL2(1), IFNAR1(2), IFNB1(1), MAPK8(2), NFKB1(2), RELA(2), TNFRSF11A(1), TNFSF11(1), TRAF6(1) 3013540 14 11 14 2 5 4 0 3 2 0 0.95 1.00 517 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 37 ACACA(1), ACAT1(1), ADH5(1), ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH9A1(2), DLAT(1), DLD(2), GRHPR(1), HAGHL(1), LDHB(2), LDHC(1), LDHD(6), MDH1(1), MDH2(1), ME2(2), ME3(1), PC(2), PCK1(1), PDHA1(2), PDHA2(5), PKLR(3), PKM2(2) 9947530 45 39 45 21 10 18 8 5 4 0 0.95 1.00 518 LIMONENE_AND_PINENE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ECHS1, EHHADH, HADHA, SDS 12 ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH9A1(2), HADHA(2), SDS(2) 3292822 12 12 12 5 1 6 2 1 2 0 0.96 1.00 519 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(2), GPD2(2), SDHA(1) 1766116 5 5 5 2 0 2 1 2 0 0 0.96 1.00 520 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(7), EIF2AK4(4), EIF2B5(1), EIF5(1) 3140988 13 13 13 5 7 4 1 0 1 0 0.96 1.00 521 HSA03060_PROTEIN_EXPORT Genes involved in protein export OXA1L, SEC61A2, SRP19, SRP54, SRP68, SRP72, SRP9, SRPR 8 OXA1L(1), SEC61A2(1), SRP54(1), SRP72(1), SRPR(2) 2013536 6 6 6 3 2 2 2 0 0 0 0.96 1.00 522 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(2), ACACA(1), ACADL(2), ACADM(1), ACAT1(1), ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH6A1(1), ALDH9A1(2), HADHA(2), LDHB(2), LDHC(1), MLYCD(1), MUT(1), PCCA(2), PCCB(6), SDS(2), SUCLA2(2), SUCLG2(1) 8878106 36 34 36 11 5 16 7 3 5 0 0.96 1.00 523 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 21 ACAD8(2), ACAD9(3), ADH1B(1), ADH1C(1), ADH4(2), ADH5(1), ADH7(1), ADHFE1(2), DHRS2(1), ESCO1(1), MYST3(9), MYST4(3), PNPLA3(1), SH3GLB1(1) 6562148 29 26 29 11 7 11 4 2 5 0 0.96 1.00 524 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(1), AASDH(5), AASDHPPT(1), AASS(6), ACAT1(1), ALDH1A2(2), ALDH1B1(2), ALDH2(2), ALDH9A1(2), BBOX1(2), DLST(1), DOT1L(4), EHMT2(1), GCDH(1), HADHA(2), PLOD1(4), PLOD2(4), PLOD3(5), SDS(2) 10099720 48 38 48 23 5 17 16 4 6 0 0.96 1.00 525 BENZOATE_DEGRADATION_VIA_COA_LIGATION ACAT1, ACAT2, ACYP1, ACYP2, ECHS1, EHHADH, GCDH, HADHA, SDHB, SDS 10 ACAT1(1), GCDH(1), HADHA(2), SDS(2) 2113928 6 6 6 7 1 1 2 0 2 0 0.96 1.00 526 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 21 APAF1(1), ARHGDIB(1), BIRC3(3), CASP1(1), CASP10(3), CASP2(1), CASP4(3), CASP7(2), CASP8(1), CASP9(2), DFFB(2), GZMB(1), PRF1(1) 5233378 22 19 22 9 3 8 4 2 5 0 0.96 1.00 527 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 47 ACCN1(4), ADCY4(3), ADCY8(13), CACNA1A(7), CACNA1B(1), GNAS(5), GNAT3(1), GNB1(1), GRM4(1), ITPR3(1), KCNB1(1), PDE1A(2), PLCB2(5), PRKACB(2), PRKACG(1), PRKX(1), SCNN1B(1), SCNN1G(1), TAS1R1(2), TAS2R1(3), TAS2R10(3), TAS2R16(4), TAS2R38(2), TAS2R39(1), TAS2R4(1), TAS2R40(2), TAS2R41(5), TAS2R42(1), TAS2R5(1), TAS2R60(7), TAS2R7(1), TAS2R8(1), TAS2R9(3) 15460190 88 57 88 34 23 27 23 8 7 0 0.97 1.00 528 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(6), CDC25B(1), CDC25C(1), CHEK1(4), WEE1(2) 3709342 14 13 14 1 4 6 1 1 2 0 0.97 1.00 529 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 90 AKT1(1), AKT3(2), BCAR1(5), CAPN1(2), CAPN10(3), CAPN11(2), CAPN2(2), CAPN3(6), CAPN5(2), CAPN6(5), CAPN7(1), CAV2(1), CAV3(1), CDC42(1), DOCK1(3), FYN(3), ILK(1), ITGA10(5), ITGA11(3), ITGA2(5), ITGA2B(1), ITGA4(3), ITGA5(1), ITGA6(3), ITGA7(3), ITGA8(8), ITGAD(6), ITGAE(3), ITGAL(1), ITGAM(3), ITGAV(3), ITGAX(9), ITGB1(3), ITGB2(3), ITGB3(3), ITGB4(6), ITGB6(1), ITGB7(1), ITGB8(3), MAP2K1(2), MAP2K3(2), MAP2K6(2), MAPK10(1), MAPK4(1), MAPK6(2), MAPK7(1), MYLK2(2), PAK1(1), PAK3(1), PAK4(1), PDPK1(1), PIK3R2(3), PTK2(4), PXN(3), RAC1(1), RAP1B(1), RAPGEF1(3), RHO(1), ROCK1(5), ROCK2(3), SDCCAG8(5), SHC1(1), SHC3(2), SORBS1(5), SOS1(6), TLN1(3), TNS1(6), VASP(2), VAV2(3), VAV3(1), VCL(2) 36879464 195 104 194 67 45 75 42 13 20 0 0.97 1.00 530 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(2), ACAA2(1), ACADM(1), ACADS(2), ACAT1(1), ALDH1B1(2), ALDH2(2), ALDH6A1(1), ALDH7A1(1), ALDH9A1(2), AOX1(9), AUH(1), BCAT2(2), BCKDHB(2), DBT(1), DLD(2), HADH(1), HADHA(2), HADHB(2), HIBCH(1), HMGCL(1), HMGCS1(1), HMGCS2(1), HSD17B4(1), MCCC1(4), MUT(1), OXCT1(2), PCCA(2), PCCB(6) 11653660 57 43 57 14 11 17 12 10 7 0 0.97 1.00 531 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(1), ARFGAP1(1), ARFGEF2(3), COPA(8), GBF1(4), KDELR2(1) 4367764 18 16 18 9 4 4 6 3 1 0 0.97 1.00 532 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(1), ASPH(3), COPS5(2), CREB1(1), EP300(6), HIF1A(1), JUN(3), NOS3(1), VHL(1) 4582432 19 17 17 8 2 7 6 3 1 0 0.97 1.00 533 HEME_BIOSYNTHESIS ALAD, ALAS1, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, UROS 9 CPOX(2), FECH(2), PPOX(1), UROD(1) 2065156 6 6 6 2 1 3 0 1 1 0 0.97 1.00 534 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 49 ACHE(2), AGPAT3(1), CDS1(2), CHAT(2), CHKA(2), DGKA(3), DGKB(3), DGKD(5), DGKE(3), DGKG(1), DGKZ(3), ETNK1(3), GPD1(1), GPD2(2), LYPLA1(3), PAFAH1B1(1), PCYT1B(1), PISD(1), PLA2G2A(1), PLA2G2E(2), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(5), PLCB2(5), PLCG1(1), PLCG2(3), PPAP2B(1) 13840390 67 51 67 24 17 25 13 5 7 0 0.97 1.00 535 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(1), ARPC1A(2), NCK1(2), NCKAP1(4), NTRK1(3), RAC1(1), WASF3(1), WASL(2) 4129422 16 15 16 11 2 7 2 2 3 0 0.97 1.00 536 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(2), IL1B(1), MST1(1), MST1R(1) 1782314 5 5 5 2 2 2 1 0 0 0 0.97 1.00 537 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 CAMK1G(2), CAMK2B(2), CAMK2D(1), CAMK4(3), CREB1(1), SYT1(3) 3177478 12 11 12 7 5 1 1 4 1 0 0.97 1.00 538 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 37 CAMK1G(2), FPR1(1), GNB1(1), HRAS(1), MAP2K1(2), MAP2K3(2), MAP2K6(2), MAP3K1(2), MAPK1(1), MAPK14(1), MAPK3(1), NCF2(2), NFATC2(4), NFATC3(2), NFATC4(1), NFKB1(2), PAK1(1), PIK3C2G(6), PLCB1(6), PPP3CA(2), PPP3CB(4), PPP3CC(2), RAC1(1), RAF1(1), RELA(2), SYT1(3) 10537956 55 41 55 19 19 16 6 10 4 0 0.97 1.00 539 FOLATE_BIOSYNTHESIS ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, DHFR, FPGS, GCH1, GGH, SPR 9 ALPL(3), ALPP(2), ALPPL2(1), GCH1(1) 1834468 7 6 7 4 3 3 0 1 0 0 0.97 1.00 540 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 35 AKT1(1), CDC42(1), CREB1(1), CREB3(2), CREB5(3), DUSP10(3), EEF2K(3), GADD45A(1), MAP2K3(2), MAP2K6(2), MAP3K4(4), MAP3K5(3), MAP3K7(2), MAPK1(1), MAPK13(2), MAPK14(1), MAPKAPK2(1), MAPKAPK5(3), MKNK2(1), MYEF2(3), NFKB1(2), NR2C2(1), SRF(2), TRAF6(1) 9192632 46 34 46 15 7 15 13 6 5 0 0.97 1.00 541 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 19 CAMK2B(2), CAMK2D(1), DAG1(1), ITPKA(1), ITPKB(4), ITPR1(4), ITPR2(11), ITPR3(1), NFAT5(2), PDE6A(2), PDE6B(3), PDE6H(2), SLC6A13(4), TF(5) 9814920 43 37 43 12 17 9 8 1 8 0 0.97 1.00 542 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ7(1), NDUFA13(2) 1115170 3 3 3 2 0 2 1 0 0 0 0.97 1.00 543 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(1), ARPC1A(2), CDC42(1), RAC1(1), WASL(2) 2180856 7 7 7 6 1 3 2 1 0 0 0.97 1.00 544 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 ALG5(2), B4GALT1(1), B4GALT3(1), B4GALT5(2), DDOST(1), FUT8(2), MAN1A1(3), MGAT1(1), MGAT2(2), MGAT3(4), MGAT4A(2), MGAT4B(1), MGAT5(3), RPN1(1), ST6GAL1(1) 5405504 27 21 27 14 11 9 2 3 2 0 0.98 1.00 545 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(1), BAK1(1), BAX(1), BCL2L1(1), CASP8AP2(5), CASP9(2), CES1(2) 3102540 13 10 13 5 3 2 5 2 1 0 0.98 1.00 546 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(5), APOC2(2), CYP7A1(3), LDLR(3), LIPC(1), LPL(3), LRP1(10), SCARB1(3) 6764356 30 26 30 15 12 11 5 0 2 0 0.98 1.00 547 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 27 ARHGDIB(1), CASP10(3), CASP7(2), CASP8(1), CFLAR(1), DAXX(2), DFFB(2), FADD(1), FAF1(1), JUN(3), MAP3K1(2), MAP3K7(2), MAPK8(2), PAK1(1), PRKDC(11), PTPN13(3), RB1(7), RIPK2(1), SPTAN1(2) 11532976 48 40 47 12 10 19 6 2 11 0 0.98 1.00 548 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 13 ACOX1(2), ACOX3(4), ELOVL5(2), ELOVL6(1), FADS1(1), FADS2(1), HADHA(2), HSD17B12(1), PECR(1), SCD(1) 4036862 16 14 16 4 3 3 4 2 4 0 0.98 1.00 549 HYPERTROPHY_MODEL ADAM10, ANKRD1, ATF3, CYR61, DUSP14, EIF4E, EIF4EBP1, GDF8, HBEGF, IFNG, IFRD1, IL18, IL1A, IL1R1, JUND, MYOG, NR4A3, TCF8, VEGF, WDR1 17 ADAM10(4), HBEGF(1), IFNG(1), NR4A3(2), WDR1(1) 2985950 9 9 9 5 1 3 1 2 2 0 0.98 1.00 550 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_NEOLACTOSERIES ABO, B3GNT1, FUT1, FUT2, FUT9, GCNT2, ST8SIA1 7 FUT9(1), GCNT2(1), ST8SIA1(2) 1700256 4 4 4 3 1 1 1 0 1 0 0.98 1.00 551 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(2), ACACA(1), ACACB(8), ACADM(1), ACAT1(1), ACSS1(3), ALDH1B1(2), ALDH2(2), ALDH6A1(1), ALDH7A1(1), ALDH9A1(2), HADHA(2), HIBCH(1), LDHAL6B(1), LDHB(2), LDHC(1), MLYCD(1), MUT(1), PCCA(2), PCCB(6), SUCLA2(2), SUCLG2(1) 10649918 44 39 44 15 11 17 6 4 6 0 0.98 1.00 552 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 58 ATP12A(4), ATP6V0A1(4), ATP6V0A4(2), ATP6V0D1(1), ATP6V1A(3), ATP6V1B1(2), ATP6V1C1(1), ATP6V1D(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(3), ATP7B(1), COX4I1(1), COX6B1(1), NDUFB5(2), NDUFS1(3), NDUFV1(2), NDUFV2(2), SDHA(1), UQCRB(1) 9402494 37 31 37 12 9 8 11 3 6 0 0.98 1.00 553 SRCRPTPPATHWAY Activation of Src by Protein-tyrosine phosphatase alpha CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CSK, GRB2, PRKCA, PRKCB1, PTPRA, SRC 9 CCNB1(1), CDC25B(1), CDC25C(1), PRKCA(4) 2502858 7 7 7 3 1 3 1 1 1 0 0.98 1.00 554 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 15 CHUK(2), MAP3K14(1), MAPK14(1), MAPK8(2), NFKB1(2), RELA(2), TNFRSF13B(1), TNFSF13(1), TRAF3(1), TRAF5(2), TRAF6(1) 3974740 16 13 16 7 5 3 1 1 6 0 0.98 1.00 555 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 39 ATF2(2), CDC42(1), CREB1(1), DAXX(2), HRAS(1), HSPB2(1), MAP2K6(2), MAP3K1(2), MAP3K5(3), MAP3K7(2), MAP3K9(3), MAPK14(1), MAPKAPK2(1), MAPKAPK5(3), MEF2A(2), MEF2C(3), MEF2D(2), MYC(1), PLA2G4A(5), RAC1(1), RPS6KA5(4), SHC1(1), STAT1(2), TGFB1(1), TGFB2(2), TRADD(1) 9996480 50 37 50 19 12 15 13 5 5 0 0.98 1.00 556 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 19 APAF1(1), BAK1(1), BAX(1), BCL2L1(1), BIRC3(3), CASP7(2), CASP8(1), CASP9(2), DFFB(2) 3689762 14 12 14 5 3 3 3 2 3 0 0.98 1.00 557 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 ACO1(1), ACO2(3), DLD(2), DLST(1), FH(2), IDH1(2), IDH3A(1), IDH3B(3), IDH3G(1), MDH1(1), MDH2(1), OGDH(3), OGDHL(4), PC(2), PCK1(1), PCK2(1), SDHA(1), SUCLA2(2), SUCLG2(1) 8013026 33 29 33 17 7 11 4 6 5 0 0.98 1.00 558 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(1), ACTN1(2), ACTN2(6), ACTN3(2), CAPN1(2), CAPNS2(1), ITGA1(3), ITGB1(3), ITGB3(3), PTK2(4), PXN(3), RAC1(1), SPTAN1(2), TLN1(3) 7784474 36 28 36 17 12 9 4 7 4 0 0.98 1.00 559 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 IL22(1), IL22RA2(1), JAK1(1), JAK2(3), JAK3(7), STAT1(2), STAT3(1), STAT5A(2), TYK2(5) 5072466 23 18 23 8 5 10 5 1 2 0 0.98 1.00 560 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(1), CARM1(1), CBS(4), GGT1(1), LCMT1(2), MARS(1), MAT1A(1), PAPSS2(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(4), PRMT8(1), SEPHS1(3), WBSCR22(3) 6761864 28 25 28 9 10 10 2 1 5 0 0.98 1.00 561 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 25 ACOT11(1), ALDH1B1(2), ALDH2(2), ALDH7A1(1), ALDH9A1(2), CYP2C19(6), CYP2C9(2), DHRS2(1), ESCO1(1), HADHA(2), MYST3(9), MYST4(3), PNPLA3(1), SH3GLB1(1) 8198324 34 29 34 15 8 12 6 2 6 0 0.99 1.00 562 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(4), POLB(1), POLD1(2), POLD3(1), POLE2(2), POLE4(1), POLG(1), POLG2(1), POLI(2), POLK(3), POLL(1), POLQ(12), PRIM1(2), PRIM2(10), REV1(5), REV3L(3), RFC5(1) 11221120 52 38 52 15 13 13 12 4 10 0 0.99 1.00 563 ONE_CARBON_POOL_BY_FOLATE ALDH1L1, AMT, ATIC, ATP6V0C, SHMT1, DHFR, GART, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 15 ALDH1L1(3), GART(1), MTHFD1(3), MTHFD1L(2), MTHFD2(3), MTHFR(1), MTR(4) 4817926 17 16 17 6 3 3 8 2 1 0 0.99 1.00 564 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(2), IKBKAP(2), IKBKB(2), MAP3K1(2), MAP3K14(1), NFKB1(2), RELA(2), TNFAIP3(3), TRAF3(1), TRAF6(1) 4931312 18 14 18 7 5 2 4 2 5 0 0.99 1.00 565 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(1), CDC25B(1), CDC25C(1), CDK7(1), XPO1(2) 2376300 6 6 6 4 0 2 1 3 0 0 0.99 1.00 566 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 15 CD4(1), CSF1(2), IL4(2) 1697764 5 4 5 5 1 2 1 0 1 0 0.99 1.00 567 NUCLEOTIDE_METABOLISM ADSL, ADSS, DHFR, HPRT1, IMPDH1, MTHFD2, NME2, OAZ1, POLA, POLB, POLD1, POLG, PRPS2, RRM1, SAT, SRM 14 ADSL(1), ADSS(1), HPRT1(1), IMPDH1(1), MTHFD2(3), POLB(1), POLD1(2), POLG(1), PRPS2(1), RRM1(1) 3494318 13 11 13 3 3 5 3 1 1 0 0.99 1.00 568 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 85 AICDA(2), CAD(8), CANT1(1), CDA(1), CTPS(2), CTPS2(2), DCK(1), DPYD(7), DPYS(4), ENTPD1(1), ENTPD3(1), ENTPD6(3), NME4(1), NME7(2), NT5C1A(2), NT5C1B(1), NT5C2(2), NT5C3(3), NT5E(2), PNPT1(2), POLA1(4), POLD1(2), POLD3(1), POLE2(2), POLE4(1), POLR1A(2), POLR1B(2), POLR1D(1), POLR2A(1), POLR2B(2), POLR2D(1), POLR2E(1), POLR3A(1), POLR3B(2), POLR3G(1), POLR3H(1), PRIM1(2), PRIM2(10), RFC5(1), RRM1(1), RRM2B(2), TXNRD1(2), TXNRD2(2), UMPS(1), UPP1(3), UPP2(1), UPRT(1) 22105464 99 68 98 37 18 36 18 6 21 0 0.99 1.00 569 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 17 B3GALT6(1), B3GAT1(2), B3GAT2(2), CHPF(1), CHST12(1), CHST3(2), DSE(1), XYLT1(2) 4030810 12 11 12 9 1 4 3 2 2 0 0.99 1.00 570 EICOSANOID_SYNTHESIS ALOX12, ALOX15, ALOX15B, ALOX5, ALOX5AP, DPEP1, GGT1, IPLA2(GAMMA), LTA4H, LTC4S, PLA2G2A, PLA2G6, PTGDS, PTGES, PTGIS, PTGS1, PTGS2, TBXAS1 17 ALOX15(2), ALOX15B(1), GGT1(1), LTA4H(2), PLA2G2A(1), PLA2G6(5), PTGES(1), PTGS1(2), TBXAS1(2) 4144552 17 14 17 6 4 9 4 0 0 0 0.99 1.00 571 SELENOAMINO_ACID_METABOLISM AHCY, CBS, CTH, GGT1, MARS, MARS2, MAT1A, MAT2B, PAPSS1, PAPSS2, SCLY, SEPHS1 12 AHCY(1), CBS(4), GGT1(1), MARS(1), MAT1A(1), PAPSS2(1), SEPHS1(3) 3369540 12 10 12 7 3 6 0 0 3 0 0.99 1.00 572 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 21 BAX(1), CASP8(1), FADD(1), MAP2K1(2), MAP3K1(2), MAPK1(1), MAPK3(1), MAPK8(2), NFKB1(2), NSMAF(2), RAF1(1), RELA(2), SMPD1(3), TNFRSF1A(2), TRADD(1) 5630140 24 18 24 10 8 6 5 2 3 0 0.99 1.00 573 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 64 ACHE(2), AGPAT3(1), AGPAT6(1), CDS1(2), CHAT(2), CHKA(2), CRLS1(1), DGKA(3), DGKB(3), DGKD(5), DGKE(3), DGKG(1), DGKI(7), DGKZ(3), ESCO1(1), ETNK1(3), GPAM(2), GPD1(1), GPD1L(1), GPD2(2), LYPLA1(3), MYST3(9), MYST4(3), PCYT1B(1), PISD(1), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(5), PLD1(6), PLD2(2), PNPLA3(1), PPAP2B(1), PTDSS1(1), SH3GLB1(1) 18095124 94 60 94 38 22 36 17 7 12 0 0.99 1.00 574 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(1), NR1I3(1), PTGS1(2) 1417058 4 3 4 4 1 2 0 1 0 0 0.99 1.00 575 DNA_POLYMERASE POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLS 7 POLB(1), POLD1(2), POLG(1), POLL(1), POLQ(12) 4560360 17 15 17 3 4 6 3 3 1 0 0.99 1.00 576 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 42 ACACA(1), ACACB(8), ACAT1(1), ACOT12(1), ACSS1(3), ALDH1B1(2), ALDH2(2), ALDH7A1(1), ALDH9A1(2), DLAT(1), DLD(2), GRHPR(1), HAGHL(1), LDHAL6B(1), LDHB(2), LDHC(1), LDHD(6), MDH1(1), MDH2(1), ME2(2), ME3(1), PC(2), PCK1(1), PCK2(1), PDHA1(2), PDHA2(5), PKLR(3), PKM2(2) 12575344 57 44 57 27 17 22 8 5 5 0 0.99 1.00 577 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 85 ATF2(2), BRAF(7), CEBPA(1), CHUK(2), CREB1(1), DAXX(2), FOS(1), HRAS(1), IKBKB(2), JUN(3), MAP2K1(2), MAP2K3(2), MAP2K5(1), MAP2K6(2), MAP3K1(2), MAP3K11(2), MAP3K12(3), MAP3K13(5), MAP3K14(1), MAP3K4(4), MAP3K5(3), MAP3K6(1), MAP3K7(2), MAP3K9(3), MAP4K1(2), MAP4K2(1), MAP4K3(5), MAP4K4(5), MAP4K5(1), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(1), MAPK4(1), MAPK6(2), MAPK7(1), MAPK8(2), MAPK9(1), MAPKAPK2(1), MAPKAPK5(3), MEF2A(2), MEF2C(3), MEF2D(2), MKNK2(1), MYC(1), NFKB1(2), PAK1(1), RAC1(1), RAF1(1), RELA(2), RPS6KA1(2), RPS6KA2(3), RPS6KA3(1), RPS6KA4(1), RPS6KA5(4), RPS6KB1(1), SHC1(1), SP1(1), STAT1(2), TGFB1(1), TGFB2(2), TRADD(1) 26589284 122 77 120 42 30 35 26 14 17 0 0.99 1.00 578 PROTEASOME PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB10, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMB8, PSMB9 17 PSMA4(1), PSMA5(1), PSMB3(1), PSMB4(1), PSMB8(2) 2341234 6 6 6 3 2 2 1 0 1 0 0.99 1.00 579 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(1), ALG13(6), ALG2(2), ALG5(2), ALG6(2), B4GALT1(1), B4GALT3(1), DDOST(1), FUT8(2), GANAB(5), MAN1A1(3), MAN1A2(3), MAN1C1(3), MAN2A1(3), MGAT1(1), MGAT2(2), MGAT3(4), MGAT4A(2), MGAT4B(1), MGAT5(3), MGAT5B(4), RPN1(1), ST6GAL1(1), STT3B(1) 11591360 55 39 55 21 18 20 5 6 6 0 0.99 1.00 580 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 BMPR1A(3) 1683524 3 3 3 1 2 0 0 1 0 0 0.99 1.00 581 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 MDH1(1), PC(2), PDHA1(2), SLC25A11(1) 2508910 6 6 6 4 0 3 0 2 1 0 0.99 1.00 582 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 60 B3GALT1(2), B3GALT2(2), B3GALT4(1), B3GNT2(1), B3GNT3(4), B3GNT4(1), B4GALT1(1), B4GALT3(1), B4GALT4(1), B4GALT6(1), FUT3(3), FUT5(4), FUT6(2), FUT9(1), GBGT1(2), GCNT2(1), PIGB(1), PIGF(1), PIGG(4), PIGH(1), PIGK(1), PIGL(2), PIGN(1), PIGO(1), PIGQ(1), PIGX(1), PIGZ(2), ST3GAL1(1), ST3GAL4(2), ST3GAL5(2), ST6GALNAC3(3), ST6GALNAC5(2), ST8SIA1(2) 13400908 56 44 56 31 14 12 17 6 7 0 0.99 1.00 583 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 70 ACACB(8), ACSL1(2), ACSL3(1), ACSL6(1), ADIPOQ(1), ADIPOR2(2), AKT1(1), AKT3(2), CD36(1), CHUK(2), CPT1A(3), CPT1C(3), CPT2(1), G6PC(2), G6PC2(1), IKBKB(2), IRS1(3), IRS2(2), IRS4(2), JAK1(1), JAK2(3), JAK3(7), LEPR(10), MAPK10(1), MAPK8(2), MAPK9(1), NFKB1(2), NFKB2(2), NFKBIB(1), PCK1(1), PCK2(1), POMC(1), PPARA(1), PPARGC1A(5), PRKAA2(3), PRKAG2(4), PRKAG3(2), PRKCQ(4), PTPN11(2), RELA(2), RXRA(1), RXRG(4), SLC2A4(2), STAT3(1), STK11(3), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TYK2(5) 22732024 116 71 115 32 37 40 21 7 11 0 0.99 1.00 584 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 15 ACTA1(1), APAF1(1), CASP9(2), DAXX(2), FAS(1), FASLG(1), HSPB2(1), MAPKAPK2(1) 3068186 10 9 10 9 4 2 2 1 1 0 0.99 1.00 585 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 16 ALDH1L1(3), GART(1), MTHFD1(3), MTHFD1L(2), MTHFD2(3), MTHFR(1), MTR(4) 5119102 17 16 17 6 3 3 8 2 1 0 0.99 1.00 586 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(1), EPOR(2), GRIN1(1), HIF1A(1), JAK2(3), NFKB1(2), RELA(2), SOD2(1) 3452132 13 9 13 1 3 3 3 1 3 0 1.00 1.00 587 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 43 CREBBP(12), CTBP1(1), DLL1(1), DLL3(1), DLL4(1), DTX2(2), DTX3(2), DTX3L(1), DTX4(1), DVL1(3), DVL3(2), EP300(6), HDAC1(2), JAG2(1), LFNG(1), MAML1(2), MAML2(5), MFNG(1), NCOR2(6), NCSTN(3), NOTCH1(10), NOTCH2(6), NOTCH3(4), NOTCH4(3), PSEN1(1), PSEN2(2), PSENEN(1), SNW1(2) 19396660 83 62 82 28 21 25 16 6 15 0 1.00 1.00 588 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 27 BAG4(1), BIRC3(3), CASP8(1), CFLAR(1), FADD(1), JUN(3), MAP3K7(2), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(4), NR2C2(1), RALBP1(1), TNFAIP3(3), TNFRSF1A(2), TNFRSF1B(1), TRADD(1) 7490062 31 23 30 13 6 10 4 7 4 0 1.00 1.00 589 HSA00642_ETHYLBENZENE_DEGRADATION Genes involved in ethylbenzene degradation ARD1A, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ESCO1, ESCO2, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1 11 DHRS2(1), ESCO1(1), MYST3(9), MYST4(3), PNPLA3(1), SH3GLB1(1) 4289088 16 13 16 8 3 6 3 1 3 0 1.00 1.00 590 HSA04710_CIRCADIAN_RHYTHM Genes involved in circadian rhythm ARNTL, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, NPAS2, NR1D1, PER1, PER2, PER3 11 ARNTL(2), CLOCK(5), CRY1(1), CRY2(2), PER1(4), PER2(2), PER3(1) 4651140 17 14 17 9 0 8 7 1 1 0 1.00 1.00 591 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 34 BNIP1(1), GOSR1(1), SEC22B(4), SNAP25(1), STX10(1), STX11(1), STX5(2), STX7(1), TSNARE1(1), USE1(1), YKT6(1) 4427750 15 14 15 9 3 5 4 2 1 0 1.00 1.00 592 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 45 ABP1(4), AGXT2(1), AOC2(1), AOC3(3), CBS(4), CHDH(1), CHKA(2), DAO(1), DLD(2), DMGDH(1), GATM(1), GLDC(4), GNMT(1), PHGDH(2), PIPOX(1), PISD(1), PSAT1(1), PSPH(1), RDH11(1), RDH12(2), RDH13(1), SARDH(4), SARS(2), SARS2(2), SDS(2), TARS(3), TARS2(2) 11695846 51 38 51 18 12 18 12 4 5 0 1.00 1.00 593 CHONDROITIN B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 HS3ST2(1), XYLT1(2) 1890716 3 3 3 3 0 2 1 0 0 0 1.00 1.00 594 HEPARAN_SULFATE_BIOSYNTHESIS B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 HS3ST2(1), XYLT1(2) 1890716 3 3 3 3 0 2 1 0 0 0 1.00 1.00 595 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 23 GPAA1(3), PGAP1(3), PIGB(1), PIGF(1), PIGG(4), PIGH(1), PIGK(1), PIGL(2), PIGN(1), PIGO(1), PIGQ(1), PIGX(1), PIGZ(2) 6629788 22 19 22 15 4 3 5 6 4 0 1.00 1.00 596 BIOSYNTHESIS_OF_STEROIDS DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, IDI1, LSS, MVD, MVK, NQO1, NQO2, PMVK, SC5DL, SQLE, VKORC1 14 DHCR7(2), FDPS(1), IDI1(1), MVD(1), SC5DL(1), SQLE(2) 3072458 8 8 8 4 2 3 2 1 0 0 1.00 1.00 597 CHOLESTEROL_BIOSYNTHESIS C10orf110, CYP51A1, DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, HMGCS1, IDI1, LSS, MVD, MVK, NSDHL, PMVK, SC4MOL, SC5DL, SQLE 15 DHCR7(2), FDPS(1), HMGCS1(1), IDI1(1), MVD(1), NSDHL(1), SC5DL(1), SQLE(2) 3632980 10 10 10 4 2 4 2 2 0 0 1.00 1.00 598 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 37 EEF1A2(1), EEF1B2(1), EEF1D(1), EEF1G(2), EEF2(1), EEF2K(3), EIF2AK3(7), EIF2B1(1), EIF2B2(1), EIF2B3(1), EIF2B5(1), EIF4A1(4), EIF4A2(2), EIF4G1(6), EIF4G3(3), EIF5(1), EIF5B(1), ETF1(1), KIAA0664(1), PABPC1(2), PABPC3(6), PAIP1(1), SLC35A4(1) 12059144 49 41 49 19 9 17 15 3 5 0 1.00 1.00 599 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 PSMA4(1), PSMA5(1), PSMB3(1), PSMB4(1), PSMC2(4), PSMC3(1), PSMD1(2), PSMD11(1), PSMD12(1), PSMD13(1) 4277518 14 13 14 6 5 6 2 0 1 0 1.00 1.00 600 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 37 ABP1(4), AGXT2(1), AOC2(1), AOC3(3), CBS(4), CHDH(1), CHKA(2), DAO(1), DLD(2), DMGDH(1), GATM(1), GLDC(4), PISD(1), PLCB2(5), PLCG1(1), PLCG2(3), PSPH(1), SARDH(4), SARS(2), TARS(3) 11524254 45 36 45 15 12 15 11 3 4 0 1.00 1.00 601 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 ACAA2(1), ACADL(2), ACADM(1), ACADS(2), ACADVL(1), ACAT1(1), ACOX1(2), ACOX3(4), ACSL1(2), ACSL3(1), ACSL6(1), ADH1B(1), ADH1C(1), ADH4(2), ADH5(1), ADH7(1), ADHFE1(2), ALDH1B1(2), ALDH2(2), ALDH7A1(1), ALDH9A1(2), CPT1A(3), CPT1C(3), CPT2(1), CYP4A22(2), DCI(1), GCDH(1), HADH(1), HADHA(2), HADHB(2), HSD17B4(1), PECI(1) 13166660 51 43 51 18 11 18 10 8 4 0 1.00 1.00 602 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), IL10(1), JAK1(1), STAT1(2), STAT3(1), STAT5A(2) 3285880 9 8 9 5 2 4 2 1 0 0 1.00 1.00 603 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 67 RPL10L(3), RPL14(1), RPL19(1), RPL32(1), RPL37(1), RPL3L(1), RPL7(1), RPL8(2), RPS11(1), RPS18(1), RPS2(1), RPS21(1), RPS26(1), RPS6(1), RPS8(1) 6262930 18 18 18 11 4 4 6 3 1 0 1.00 1.00 604 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 ARHGAP1(1), ARHGAP4(1), ARHGAP5(1), ARHGAP6(5), ARHGEF1(2), ARHGEF11(7), ARHGEF5(1), ARPC1A(2), CFL1(2), DIAPH1(1), GSN(2), MYL2(1), MYLK(5), OPHN1(1), PIP5K1A(3), PIP5K1B(2), PPP1R12B(4), ROCK1(5), TLN1(3), VCL(2) 12577124 51 40 50 14 8 20 13 7 3 0 1.00 1.00 605 HSA00061_FATTY_ACID_BIOSYNTHESIS Genes involved in fatty acid biosynthesis ACACA, ACACB, FASN, MCAT, OLAH, OXSM 6 ACACA(1), ACACB(8), MCAT(1), OLAH(1), OXSM(1) 4429352 12 11 12 8 6 4 1 0 1 0 1.00 1.00 606 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 DHCR7(2), FDPS(1), GGPS1(2), HSD17B7(1), IDI1(1), IDI2(2), MVD(1), NSDHL(1), SC5DL(1), SQLE(2), TM7SF2(1) 5284998 15 14 15 5 4 5 4 2 0 0 1.00 1.00 607 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 23 ACAT1(1), ACOT11(1), DHRS2(1), ESCO1(1), GCDH(1), HADHA(2), MYST3(9), MYST4(3), PNPLA3(1), SH3GLB1(1) 6846592 21 18 21 13 4 7 4 1 5 0 1.00 1.00 608 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 32 APAF1(1), BIRC3(3), CASP10(3), CASP7(2), CASP8(1), CASP9(2), CFLAR(1), CHUK(2), DFFB(2), FADD(1), GAS2(2), MAP3K14(1), NFKB1(2), RELA(2), SPTAN1(2), TNFRSF10A(1), TNFRSF10B(1), TRADD(1) 9154184 30 24 30 12 7 8 3 5 7 0 1.00 1.00 609 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 91 CD2BP2(2), CDC40(2), CLK2(1), CLK3(1), CLK4(2), COL2A1(8), CPSF1(3), CPSF2(2), CPSF3(1), CPSF4(1), CSTF2(2), CSTF2T(2), CSTF3(1), DDX1(5), DHX15(2), DHX16(1), DHX38(1), DHX8(1), DHX9(5), DICER1(7), FUS(1), METTL3(1), NCBP1(2), NXF1(1), PAPOLA(1), POLR2A(1), PRPF3(1), PRPF4(2), PRPF4B(5), PRPF8(5), PSKH1(1), PTBP2(1), RBM17(1), RBM5(1), RNPS1(1), SF3A1(1), SF3A2(2), SF3A3(2), SF3B1(2), SF3B2(2), SF3B4(1), SF4(2), SFRS12(1), SFRS14(4), SFRS2(2), SFRS6(1), SFRS8(2), SNRPA(2), SNRPB(3), SNRPD1(1), SNRPD2(1), SNRPN(1), SPOP(1), SRPK1(2), SRRM1(2), SUPT5H(2), XRN2(2) 28537138 114 74 112 30 26 32 33 10 13 0 1.00 1.00 610 RNA_POLYMERASE POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT 14 POLR1B(2), POLR2A(1), POLR2B(2), POLR2D(1), POLR2E(1) 3743518 7 6 7 2 2 1 0 1 3 0 1.00 1.00 611 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 42 CDC6(4), CDC7(1), DIAPH2(1), GMNN(2), MCM10(3), MCM2(1), MCM3(1), MCM4(3), MCM5(6), MCM6(1), MCM7(3), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), POLD1(2), POLD3(1), POLE2(2), PRIM1(2), RFC1(1), RFC4(3), RFC5(1), RPA4(2), UBB(1), UBC(1) 13878660 46 38 46 15 11 13 14 1 7 0 1.00 1.00 612 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 54 CAD(8), CANT1(1), CDA(1), CTPS(2), CTPS2(2), DCK(1), DPYD(7), DPYS(4), ENTPD1(1), NT5E(2), POLB(1), POLD1(2), POLG(1), POLL(1), POLQ(12), POLR1B(2), POLR2A(1), POLR2B(2), POLR2D(1), POLR2E(1), RRM1(1), TXNRD1(2), UMPS(1), UPP1(3) 15680732 60 43 60 12 11 23 11 6 9 0 1.00 1.00 613 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(2), POLR1B(2), POLR1D(1), POLR2A(1), POLR2B(2), POLR2D(1), POLR2E(1), POLR3A(1), POLR3B(2), POLR3G(1), POLR3H(1) 6292478 15 13 15 12 5 4 1 2 3 0 1.00 1.00 614 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 CDK7(1), ERCC3(1), GTF2B(1), GTF2E1(1), GTF2H4(1), ILK(1), POLR1A(2), POLR1B(2), POLR2A(1), POLR2B(2), POLR2E(1), POLR3B(2), POLR3D(1), POLR3E(2), POLR3H(1), TAF9(2), TBP(1) 9538486 23 19 23 14 7 4 3 3 6 0 1.00 1.00 615 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 41 ALPL(3), ALPP(2), ALPPL2(1), ASCC3(9), ATP13A2(1), DDX18(2), DDX19A(1), DDX23(3), DDX4(1), DDX41(2), DDX50(1), DDX52(1), DDX54(3), DDX55(1), DDX56(1), ENTPD7(1), ERCC3(1), GCH1(1), IFIH1(3), NUDT8(1), RAD54L(1), SETX(10), SKIV2L2(2), SMARCA2(2) 17193732 54 37 54 23 14 21 12 3 4 0 1.00 1.00 616 HSA00785_LIPOIC_ACID_METABOLISM Genes involved in lipoic acid metabolism LIAS, LIPT1, LOC387787 2 407442 0 0 0 0 0 0 0 0 0 0 1.00 1.00