rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q 1 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(2), AKT1(1), AKT3(2), APAF1(1), ATM(7), BAX(1), BCL2L1(2), BID(1), BIRC3(3), CAPN1(2), CAPN2(2), CASP10(4), CASP6(1), CASP7(2), CASP8(1), CASP9(1), CFLAR(1), CHP(2), CHUK(2), CSF2RB(5), DFFA(1), DFFB(2), FADD(1), FAS(1), FASLG(1), IKBKB(3), IL1B(1), IL1RAP(2), IRAK1(4), IRAK2(1), IRAK3(3), MAP3K14(1), NFKB1(2), NFKB2(2), NTRK1(3), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKACA(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), RELA(3), TNFRSF10A(1), TNFRSF10B(1), TNFRSF10D(1), TNFRSF1A(2), TP53(119), TRADD(1) 22576808 267 147 219 57 74 68 35 30 60 0 <1.00e-15 <1.93e-13 2 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(3), TP53(119) 2739598 127 118 90 9 24 22 21 14 46 0 2.55e-15 1.93e-13 3 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(1), GAB1(2), GADD45A(1), GCK(1), JUN(2), MAP2K5(2), MAP3K1(3), MAP3K11(2), MAP3K12(2), MAP3K13(5), MAP3K4(4), MAP3K5(3), MAP3K7(3), MAP3K9(4), MAPK10(1), MAPK7(1), MAPK8(2), MAPK9(1), MYEF2(3), NFATC3(3), NR2C2(1), PAPPA(8), SHC1(1), TP53(119), TRAF6(1), ZAK(1) 13764918 186 133 149 32 41 46 33 19 47 0 2.78e-15 1.93e-13 4 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(7), ATR(11), CDC25C(1), CHEK1(4), CHEK2(3), TP53(119) 4293716 145 124 108 8 29 26 25 18 47 0 2.89e-15 1.93e-13 5 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(2), BID(1), BIRC3(3), BNIP3L(1), CASP1(2), CASP10(4), CASP2(1), CASP4(3), CASP6(1), CASP7(2), CASP8(1), CASP9(1), CHUK(2), DFFA(1), DFFB(2), FADD(1), FAS(1), FASLG(1), GZMB(1), IKBKB(3), IRF1(1), IRF3(1), IRF4(3), IRF6(5), JUN(2), LTA(3), MAP3K1(3), MAPK10(1), MDM2(1), MYC(1), NFKB1(2), NFKBIB(1), PLEKHG5(1), PRF1(2), RELA(3), TNFRSF10B(1), TNFRSF1A(2), TNFRSF1B(1), TNFRSF21(3), TP53(119), TRADD(1), TRAF1(4), TRAF3(1) 15688386 199 135 162 41 39 46 33 23 58 0 3.89e-15 1.93e-13 6 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(7), CCNA1(1), CCNB1(1), CCND1(1), CCND2(3), CCND3(1), CCNE2(2), CDK2(1), CDK7(1), CDKN2A(23), CDKN2C(1), CDKN2D(1), CREB3(2), CREB3L3(1), CREB3L4(2), E2F1(3), GADD45A(1), GBA2(2), MCM2(1), MCM3(1), MCM4(4), MCM5(6), MCM6(2), MCM7(3), MDM2(1), MYC(1), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), POLA2(3), POLE2(2), PRIM1(2), RB1(7), RBL1(6), TFDP2(1), TNXB(16), TP53(119), WEE1(2) 20927638 235 137 195 36 45 63 39 20 68 0 4.00e-15 1.93e-13 7 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(23), E2F1(3), MDM2(1), MYC(1), PIK3CA(21), PIK3R1(1), POLR1A(4), POLR1B(4), POLR1C(1), POLR1D(1), RAC1(2), RB1(7), TBX2(3), TP53(119), TWIST1(1) 5437544 194 133 143 19 44 41 30 17 62 0 4.00e-15 1.93e-13 8 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(7), BRCA1(6), CHEK1(4), CHEK2(3), GADD45A(1), JUN(2), MAPK8(2), MDM2(1), MRE11A(2), NFKB1(2), RAD50(3), RAD51(1), RBBP8(1), RELA(3), TP53(119) 8101670 159 122 122 16 30 35 24 21 49 0 4.00e-15 1.93e-13 9 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(119), WT1(4) 1894810 128 122 91 11 25 21 24 15 43 0 4.33e-15 1.93e-13 10 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(7), CDC25B(3), CDC25C(1), CDK2(1), CHEK1(4), RB1(7), TP53(119), WEE1(2) 4759720 144 124 107 10 27 30 22 14 51 0 4.77e-15 1.93e-13 11 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(3), JAK2(3), LIN7A(2), NFKB1(2), RB1(7), RELA(3), TNFRSF1A(2), TNFRSF1B(1), TP53(119), USH1C(5), WT1(4) 5076382 156 126 119 14 29 31 29 16 51 0 5.11e-15 1.93e-13 12 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(7), BUB1(4), BUB1B(5), BUB3(1), CCNA1(1), CCNB1(1), CCNB3(9), CCND2(3), CCND3(1), CCNE2(2), CDAN1(3), CDC25B(3), CDC25C(1), CDC6(4), CDC7(1), CDH1(4), CDK2(1), CDKN2A(23), CHEK1(4), CHEK2(3), DTX4(2), E2F1(3), EP300(5), ESPL1(3), GADD45A(1), GSK3B(1), HDAC1(2), HDAC3(1), HDAC4(5), HDAC5(1), MAD1L1(5), MAD2L1(2), MCM2(1), MCM3(1), MCM4(4), MCM5(6), MCM6(2), MCM7(3), MDM2(1), MPEG1(5), MPL(3), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), PLK1(1), PRKDC(15), PTTG1(1), PTTG2(2), RB1(7), RBL1(6), SKP2(1), SMAD4(2), TBC1D8(2), TGFB1(1), TP53(119), WEE1(2) 30149462 303 151 261 58 58 87 55 24 79 0 5.33e-15 1.93e-13 13 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(7), BAX(1), BCL2L1(2), BID(1), CASP6(1), CASP7(2), CASP9(1), PRKCA(5), PTK2(3), PXN(3), STAT1(2), TLN1(8), TP53(119) 7458200 157 122 119 19 32 37 26 17 45 0 5.33e-15 1.93e-13 14 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(2), BID(1), BIRC3(3), CASP2(1), CASP6(1), CASP7(2), CASP8(1), CASP9(1), FADD(1), FAS(1), FASLG(1), GZMB(1), JUN(2), MAP3K1(3), MAP3K14(1), MAPK10(1), MCL1(2), MDM2(1), MYC(1), NFKB1(2), PARP1(3), PRF1(2), RELA(3), TNFRSF1A(2), TNFRSF1B(1), TP53(119), TRADD(1), TRAF1(4) 10250308 167 128 130 34 34 36 25 21 51 0 5.44e-15 1.93e-13 15 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(3), HRAS(2), PAX3(3), RARA(1), RB1(7), SIRT1(1), SP100(1), TNFRSF1A(2), TNFRSF1B(1), TP53(119) 5235158 152 125 115 17 30 32 22 17 51 0 5.66e-15 1.93e-13 16 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 CCND1(1), CDK2(1), CDKN2A(23), CFL1(3), E2F1(3), MDM2(1), PRB1(2), TP53(119) 2182280 153 125 113 15 25 33 25 14 56 0 5.66e-15 1.93e-13 17 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(3), ATM(7), ATR(11), BUB1(4), BUB1B(5), BUB3(1), CCNA1(1), CCNB1(1), CCNB3(9), CCND1(1), CCND2(3), CCND3(1), CCNE2(2), CDC25B(3), CDC25C(1), CDC27(3), CDC6(4), CDC7(1), CDK2(1), CDK7(1), CDKN2A(23), CDKN2C(1), CDKN2D(1), CHEK1(4), CHEK2(3), CREBBP(12), CUL1(3), DBF4(4), E2F1(3), EP300(5), ESPL1(3), GADD45A(1), GADD45G(1), GSK3B(1), HDAC1(2), MAD1L1(5), MAD2L1(2), MCM2(1), MCM3(1), MCM4(4), MCM5(6), MCM6(2), MCM7(3), MDM2(1), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), PKMYT1(1), PLK1(1), PRKDC(15), PTTG1(1), PTTG2(2), RB1(7), RBL1(6), RBL2(5), RBX1(1), SFN(2), SKP1(1), SKP2(1), SMAD2(2), SMAD4(2), SMC1A(2), SMC1B(5), TGFB1(1), TGFB2(1), TP53(119), WEE1(2), YWHAB(2), YWHAE(1), YWHAQ(1) 37187582 349 156 307 66 74 99 62 31 83 0 5.88e-15 1.93e-13 18 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(14), AKT1(1), ATM(7), BAX(1), CPB2(2), CSNK1A1(1), FHL2(2), GADD45A(1), HIF1A(1), IGFBP3(1), MAPK8(2), MDM2(1), NFKBIB(1), TP53(119) 5676064 154 126 117 13 30 32 28 17 45 2 6.22e-15 1.93e-13 19 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(7), BAX(1), CCND1(1), CDK2(1), E2F1(3), GADD45A(1), MDM2(1), RB1(7), TP53(119) 4951604 142 121 105 11 26 29 22 15 50 0 6.55e-15 1.93e-13 20 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(7), ATR(11), BAI1(8), BAX(1), BID(1), CASP8(1), CASP9(1), CCNB1(1), CCNB3(9), CCND1(1), CCND2(3), CCND3(1), CCNE2(2), CCNG1(1), CD82(1), CDK2(1), CDKN2A(23), CHEK1(4), CHEK2(3), DDB2(4), EI24(1), FAS(1), GADD45A(1), GADD45G(1), GTSE1(2), IGF1(2), IGFBP3(1), MDM2(1), PPM1D(1), PTEN(11), RFWD2(4), RPRM(1), RRM2B(2), SERPINB5(2), SERPINE1(2), SESN1(3), SESN2(3), SESN3(2), SFN(2), SIAH1(1), STEAP3(2), THBS1(1), TNFRSF10B(1), TP53(119), TSC2(6) 17798932 258 141 217 37 44 65 45 26 78 0 6.77e-15 1.93e-13 21 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(7), ATR(11), CCNA1(1), CCND1(1), CDK2(1), CDKN2A(23), E2F1(3), GSK3B(1), HDAC1(2), RB1(7), SKP2(1), TGFB1(1), TGFB2(1), TP53(119) 8079954 181 132 141 19 33 37 31 16 64 0 6.88e-15 1.93e-13 22 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(7), ATR(11), BRCA1(6), BRCA2(7), CHEK1(4), CHEK2(3), FANCC(2), FANCE(1), FANCF(3), FANCG(2), MRE11A(2), RAD1(1), RAD17(2), RAD50(3), RAD51(1), RAD9A(1), TP53(119), TREX1(1) 11853198 176 128 139 17 37 37 30 21 51 0 6.88e-15 1.93e-13 23 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(9), IGF1R(1), MYC(1), POLR2A(2), PRKCA(5), RB1(7), TEP1(6), TERF1(2), TERT(5), TNKS(7), TP53(119), XRCC5(1) 7681590 166 125 128 20 32 40 25 16 53 0 7.44e-15 1.99e-13 24 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(7), ATR(11), BRCA1(6), CCNB1(1), CDC25B(3), CDC25C(1), CDKN2D(1), CHEK1(4), CHEK2(3), EP300(5), GADD45A(1), MDM2(1), PRKDC(15), RPS6KA1(4), TP53(119), WEE1(2), YWHAQ(1) 11595276 185 133 146 15 38 42 33 22 50 0 7.77e-15 1.99e-13 25 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(5), CAD(10), CASP10(4), CASP8(1), CASP8AP2(6), CDK2AP1(1), CSNK1A1(1), DAXX(3), DFFA(1), EGFR(9), EPHB2(5), FADD(1), FAF1(1), FAIM2(1), MAP3K1(3), MAP3K5(3), MAPK1(1), MAPK10(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(6), MAPK9(1), MET(3), NFAT5(3), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), NR0B2(1), PTPN13(3), RALBP1(1), ROCK1(5), SMPD1(3), TNFRSF6B(1), TP53(119), TPX2(1), TUFM(1) 20303748 224 139 186 39 50 60 38 20 56 0 9.10e-15 2.24e-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 FOS(1), JUN(2), KEAP1(18), MAPK1(1), MAPK14(1), MAPK8(2), NFE2L2(21), PRKCA(5) 2383598 51 47 40 3 13 13 18 3 4 0 5.71e-14 1.35e-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(3), ATF2(2), ATF4(1), BDNF(1), BRAF(7), CACNA1A(8), CACNA1B(1), CACNA1C(16), CACNA1D(3), CACNA1E(16), CACNA1F(8), CACNA1G(6), CACNA1H(5), CACNA1I(9), CACNA1S(8), CACNA2D1(8), CACNA2D2(5), CACNA2D3(2), CACNA2D4(5), CACNB1(1), CACNB2(2), CACNB3(2), CACNB4(3), CACNG3(2), CACNG4(2), CACNG6(1), CACNG7(4), CD14(1), CDC25B(3), CDC42(1), CHP(2), CHUK(2), CRKL(1), DAXX(3), DUSP10(3), DUSP16(2), DUSP4(1), DUSP5(4), DUSP6(1), DUSP7(1), DUSP9(4), EGF(6), EGFR(9), FAS(1), FASLG(1), FGF10(2), FGF12(2), FGF14(1), FGF2(2), FGF23(1), FGF3(1), FGF5(3), FGF6(2), FGF8(1), FGFR1(3), FGFR2(6), FGFR3(2), FGFR4(1), FLNA(9), FLNB(4), FLNC(13), FOS(1), GADD45A(1), GADD45G(1), GNA12(1), GNG12(1), HRAS(2), IKBKB(3), IL1B(1), IL1R2(3), JUN(2), KRAS(1), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K5(2), MAP2K6(3), MAP3K1(3), MAP3K12(2), MAP3K13(5), MAP3K14(1), MAP3K4(4), MAP3K5(3), MAP3K6(1), MAP3K7(3), MAP4K1(2), MAP4K2(1), MAP4K3(5), MAP4K4(6), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPK7(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(6), MAPK9(1), MAPKAPK2(1), MAPKAPK5(4), MAPT(5), MEF2C(2), MOS(4), MRAS(3), MYC(1), NF1(19), NFATC2(5), NFATC4(2), NFKB1(2), NFKB2(2), NLK(2), NR4A1(4), NTF3(3), NTRK1(3), NTRK2(1), PAK1(3), PAK2(1), PDGFB(1), PDGFRA(8), PDGFRB(5), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PPM1A(2), PPM1B(1), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PPP5C(1), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCG(9), PRKX(1), PTPN5(1), PTPRR(6), RAC1(2), RAF1(1), RAPGEF2(5), RASA1(6), RASA2(3), RASGRF1(5), RASGRF2(4), RASGRP1(1), RASGRP3(8), RASGRP4(4), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KA4(3), RPS6KA5(3), RPS6KA6(3), RRAS2(2), SOS1(6), SOS2(4), SRF(2), STK3(2), STK4(2), TAOK1(6), TAOK2(6), TAOK3(3), TGFB1(1), TGFB2(1), TGFBR2(3), TNFRSF1A(2), TP53(119), TRAF6(1), ZAK(1) 79663722 682 171 640 194 149 240 113 58 122 0 1.29e-13 2.94e-12 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), BTRC(1), CAMK2B(2), CAMK2D(1), CCND1(1), CCND2(3), CCND3(1), CHD8(13), CHP(2), CREBBP(12), CSNK1A1(1), CSNK1A1L(5), CSNK2A1(2), CTBP1(1), CTNNB1(3), CUL1(3), DAAM1(1), DAAM2(5), DKK1(3), DKK2(1), DKK4(1), DVL1(3), DVL3(3), EP300(5), FZD1(1), FZD10(2), FZD3(4), FZD4(1), FZD6(1), FZD9(3), GSK3B(1), JUN(2), LEF1(3), LRP5(6), LRP6(6), MAP3K7(3), MAPK10(1), MAPK8(2), MAPK9(1), MYC(1), NFAT5(3), NFATC2(5), NFATC3(3), NFATC4(2), NKD1(1), NKD2(2), NLK(2), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PORCN(2), PPARD(2), PPP2R1A(6), PPP2R1B(2), PPP2R2A(1), PPP2R2B(2), PPP2R2C(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRICKLE1(5), PRICKLE2(1), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCG(9), PRKX(1), PSEN1(1), RAC1(2), RBX1(1), ROCK1(5), ROCK2(3), RUVBL1(1), SENP2(3), SFRP1(1), SFRP4(3), SIAH1(1), SKP1(1), SMAD2(2), SMAD4(2), TBL1XR1(2), TBL1Y(2), TCF7(1), TP53(119), VANGL1(1), VANGL2(2), WIF1(4), WNT10B(2), WNT11(2), WNT2(3), WNT2B(2), WNT3(2), WNT3A(1), WNT5A(1), WNT5B(1), WNT6(2), WNT7A(2), WNT7B(1), WNT9A(1), WNT9B(2) 44570488 394 157 354 105 103 119 59 40 73 0 6.11e-13 1.34e-11 29 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(2), ACTN2(6), ACTN3(2), ACTN4(5), DES(2), DMD(20), FAM48A(1), MYBPC1(11), MYBPC3(3), MYH3(5), MYH6(12), MYH7(9), MYH8(22), MYL1(4), MYL2(1), MYL3(2), MYOM1(8), NEB(23), TNNC2(1), TNNI1(1), TNNI2(1), TNNI3(2), TNNT1(1), TNNT2(2), TNNT3(3), TPM3(2), TTN(263), VIM(5) 37572952 419 146 415 152 118 133 95 30 37 6 1.47e-10 3.12e-09 30 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(4), ADORA2A(6), ADORA2B(1), ADRA1A(2), ADRA1B(4), ADRA2B(4), ADRA2C(2), ADRB2(3), AGTR1(3), AGTR2(4), AVPR1A(3), AVPR1B(2), AVPR2(1), BDKRB1(3), BDKRB2(1), C3AR1(1), C5AR1(1), CALCR(6), CALCRL(4), CCKAR(2), CCKBR(1), CHRM2(6), CHRM3(5), CHRM4(1), CHRM5(2), CNR1(3), CNR2(3), CRHR1(4), CRHR2(3), CTSG(4), CYSLTR1(3), CYSLTR2(1), DRD1(1), DRD2(2), DRD3(5), DRD4(1), DRD5(3), EDNRA(2), EDNRB(5), F2R(2), F2RL1(3), F2RL2(1), F2RL3(2), FPR1(1), FSHB(1), FSHR(12), GABBR1(3), GABBR2(3), GABRA1(6), GABRA2(8), GABRA3(5), GABRA4(3), GABRA5(4), GABRA6(7), GABRB1(3), GABRB2(6), GABRB3(11), GABRD(2), GABRE(4), GABRG1(10), GABRG2(5), GABRG3(8), GABRP(2), GABRQ(6), GABRR1(2), GABRR2(2), GALR1(3), GH1(1), GH2(2), GHR(2), GHRHR(3), GHSR(3), GLP1R(1), GLP2R(4), GLRA1(2), GLRA2(5), GLRA3(3), GLRB(3), GPR156(2), GPR35(1), GPR50(4), GPR63(2), GPR83(2), GRIA1(6), GRIA2(3), GRIA3(9), GRIA4(7), GRID1(12), GRID2(12), GRIK1(4), GRIK2(8), GRIK3(7), GRIK4(4), GRIK5(1), GRIN1(1), GRIN2A(13), GRIN2B(17), GRIN2C(2), GRIN2D(3), GRIN3A(8), GRIN3B(4), GRM1(13), GRM2(3), GRM3(13), GRM4(1), GRM5(14), GRM6(4), GRM7(8), GRM8(9), GRPR(2), GZMA(4), HCRTR2(3), HRH1(3), HRH2(2), HRH3(1), HRH4(3), HTR1A(6), HTR1B(3), HTR1D(1), HTR1E(5), HTR1F(2), HTR2A(1), HTR2B(2), HTR2C(3), HTR4(3), HTR5A(3), HTR6(1), HTR7(3), LEPR(10), LHB(1), LHCGR(8), LTB4R2(1), MAS1(3), MC2R(2), MC3R(3), MC4R(1), MC5R(3), MCHR1(2), MCHR2(3), MTNR1A(1), MTNR1B(8), NMBR(2), NMUR2(2), NPBWR1(1), NPFFR2(8), NPY1R(3), NPY2R(2), NPY5R(2), NTSR1(3), NTSR2(3), OPRD1(2), OPRK1(1), OPRM1(2), OXTR(1), P2RX2(1), P2RX3(5), P2RX4(2), P2RX7(1), P2RY1(1), P2RY10(2), P2RY13(1), P2RY14(3), P2RY2(2), P2RY4(1), P2RY6(2), PARD3(5), PPYR1(3), PRL(1), PRLHR(1), PRLR(5), PRSS1(3), PRSS3(1), PTAFR(3), PTGDR(5), PTGER2(1), PTGER3(5), PTGER4(2), PTGFR(2), PTGIR(1), PTH2R(5), RXFP1(7), RXFP2(1), 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(2), THRB(1), TRHR(1), TRPV1(2), TSHR(1) 60667562 711 165 706 257 201 263 135 37 75 0 2.05e-10 4.20e-09 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(5), CDKN2A(23), GSK3A(4), GSK3B(1), IARS(3), INPP5D(6), PDK1(1), PIK3CA(21), PPP1R13B(4), PTEN(11), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KB1(1), SFN(2), SHC1(1), SOS1(6), SOS2(4), TEC(2), YWHAB(2), YWHAE(1), YWHAQ(1) 9741584 110 80 96 16 24 27 24 4 31 0 6.46e-09 1.28e-07 32 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(4), ADORA2A(6), ADORA2B(1), ADRA1A(2), ADRA1B(4), ADRA1D(2), ADRA2C(2), ADRB2(3), AGTR1(3), AGTR2(4), AVPR1A(3), AVPR1B(2), AVPR2(1), BDKRB1(3), BDKRB2(1), C3AR1(1), CCBP2(4), CCKAR(2), CCKBR(1), CCR1(2), CCR10(1), CCR3(1), CCR4(3), CCR6(2), CCR8(3), CCRL1(3), CCRL2(1), CHML(1), CHRM2(6), CHRM3(5), CHRM4(1), CHRM5(2), CMKLR1(1), CNR1(3), CNR2(3), CX3CR1(3), CXCR3(1), CXCR4(6), DRD1(1), DRD2(2), DRD3(5), DRD4(1), DRD5(3), EDNRA(2), EDNRB(5), F2R(2), F2RL1(3), F2RL2(1), F2RL3(2), FPR1(1), FSHR(12), GALR1(3), GALT(1), GHSR(3), GPR17(5), GPR174(4), GPR27(1), GPR35(1), GPR37(2), GPR37L1(2), GPR50(4), GPR6(2), GPR63(2), GPR77(4), GPR83(2), GPR85(2), GPR87(6), GRPR(2), HCRTR2(3), HRH1(3), HRH2(2), HRH3(1), HTR1A(6), HTR1B(3), HTR1D(1), HTR1E(5), HTR1F(2), HTR2A(1), HTR2B(2), HTR2C(3), HTR4(3), HTR5A(3), HTR6(1), HTR7(3), LHCGR(8), MAS1(3), MC3R(3), MC4R(1), MC5R(3), MTNR1A(1), MTNR1B(8), NMBR(2), NMUR2(2), NPY1R(3), NPY2R(2), NPY5R(2), NTSR1(3), NTSR2(3), OPN1SW(1), OPN3(1), OPRD1(2), OPRK1(1), OPRM1(2), OR10A5(2), OR11A1(4), OR12D3(4), OR1F1(1), OR1Q1(3), OR2H1(1), OR5V1(1), OR7A5(1), OR8B8(5), OXTR(1), P2RY1(1), P2RY10(2), P2RY13(1), P2RY14(3), P2RY2(2), P2RY6(2), PPYR1(3), PTAFR(3), PTGDR(5), PTGER2(1), PTGER4(2), PTGFR(2), PTGIR(1), RGR(2), SSTR1(1), SSTR2(2), SSTR3(1), SSTR4(2), SUCNR1(2), TBXA2R(2), TRHR(1) 32937654 340 144 339 123 93 129 64 15 39 0 1.84e-07 3.55e-06 33 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(2), AKT1(1), BDKRB2(1), CHRNA1(2), FLT1(9), FLT4(3), KDR(11), NOS3(1), PDE2A(3), PDE3A(5), PDE3B(3), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKG1(5), PRKG2(5), RYR2(88), SLC7A1(5), SYT1(3), TNNI1(1) 11156150 158 87 156 57 50 49 27 12 20 0 2.22e-07 4.15e-06 34 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(15), COL2A1(8), COL3A1(10), COL4A1(11), COL4A2(9), COL4A4(9), COL4A6(9), COL5A1(5), COL5A2(12), COL5A3(11), COL6A3(12), COL6A6(20), COMP(2), DES(2), DSC1(4), DSC2(1), DSC3(7), DSG1(8), DSG2(2), DSG3(2), DSG4(5), FN1(17), GJA1(4), GJA10(5), GJA8(2), GJB2(1), GJB4(1), GJB5(1), GJC1(2), GJC2(1), GJC3(1), GJD2(2), GJD4(2), IBSP(4), INA(2), ITGA6(6), ITGB4(9), KRT1(1), KRT10(1), KRT12(3), KRT13(2), KRT14(1), KRT16(3), KRT17(2), KRT18(2), KRT2(4), KRT20(3), KRT23(2), KRT24(4), KRT27(3), KRT28(2), KRT3(2), KRT31(1), KRT32(2), KRT33A(1), KRT35(1), KRT36(3), KRT37(2), KRT4(1), KRT5(1), KRT6A(2), KRT6B(4), KRT6C(2), KRT71(2), KRT72(2), KRT73(7), KRT74(1), KRT75(2), KRT76(2), KRT77(3), KRT78(1), KRT79(4), KRT81(3), KRT82(1), KRT83(1), KRT84(1), KRT85(1), KRT86(1), KRT9(1), LAMA1(14), LAMA2(17), LAMA3(7), LAMA4(15), LAMA5(7), LAMB1(6), LAMB2(4), LAMB3(1), LAMB4(3), LAMC1(8), LAMC2(4), LAMC3(1), NES(11), PRPH(2), RELN(26), THBS1(1), THBS2(12), THBS3(4), TNC(16), TNN(15), TNR(18), TNXB(16), VIM(5), VWF(16) 67804472 595 159 593 191 163 229 113 33 57 0 2.49e-07 4.52e-06 35 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(5), GABRA4(3), GABRA5(4), GABRA6(7), PRKCE(5) 2131728 38 35 38 7 11 14 8 1 4 0 2.73e-07 4.80e-06 36 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(3), GPRC5A(1), GPRC5C(4), GPRC5D(1), GRM1(13), GRM2(3), GRM3(13), GRM4(1), GRM5(14), GRM7(8), GRM8(9) 5627292 78 60 77 40 20 26 15 8 9 0 5.14e-07 8.72e-06 37 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(1), HSD11B1(3), HSD11B2(1), HSD3B1(4), HSD3B2(5) 2426318 39 36 38 3 8 18 6 5 2 0 5.38e-07 8.72e-06 38 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(1), HSD11B1(3), HSD11B2(1), HSD3B1(4), HSD3B2(5) 2426318 39 36 38 3 8 18 6 5 2 0 5.38e-07 8.72e-06 39 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(5), AKT1(1), AKT3(2), AMOTL1(2), ASH1L(10), CASK(1), CDC42(1), CGN(5), CLDN1(2), CLDN10(4), CLDN16(4), CLDN17(1), CLDN19(1), CLDN2(1), CLDN22(1), CLDN3(1), CLDN6(1), CLDN8(2), CLDN9(3), CSDA(2), CSNK2A1(2), CTNNA2(17), CTNNA3(11), CTNNB1(3), CTTN(4), EPB41(2), EPB41L1(4), EPB41L2(1), EPB41L3(12), EXOC3(2), EXOC4(2), F11R(1), GNAI1(2), GNAI3(1), HCLS1(3), HRAS(2), IGSF5(1), INADL(9), KRAS(1), LLGL1(1), LLGL2(2), MAGI1(5), MAGI2(7), MAGI3(2), MLLT4(3), MPDZ(4), MPP5(2), MRAS(3), MYH1(13), MYH10(3), MYH11(8), MYH13(10), MYH14(4), MYH15(11), MYH2(22), MYH3(5), MYH4(14), MYH6(12), MYH7(9), MYH7B(4), MYH8(22), MYH9(14), MYL2(1), MYLPF(1), PARD3(5), PARD6A(2), PPM1J(1), PPP2R1A(6), PPP2R1B(2), PPP2R2A(1), PPP2R2B(2), PPP2R2C(2), PPP2R3A(2), PPP2R4(1), PRKCA(5), PRKCD(2), PRKCE(5), PRKCG(9), PRKCH(1), PRKCI(4), PRKCQ(4), PTEN(11), RAB13(1), RAB3B(1), RRAS2(2), SPTAN1(2), SYMPK(6), TJAP1(3), TJP1(9), TJP2(5), TJP3(2), VAPA(1), YES1(1), ZAK(1) 52815626 422 155 422 146 108 145 70 40 59 0 1.11e-06 0.000018 40 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(5), CD19(2), CDKN2A(23), FLOT1(2), GAB1(2), ITPR1(5), ITPR2(11), ITPR3(3), LYN(1), NR0B2(1), PDK1(1), PHF11(2), PIK3CA(21), PITX2(3), PLCG2(3), PPP1R13B(4), PREX1(12), PTEN(11), PTPRC(3), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KB1(1), SYK(1), TEC(2), VAV1(7) 15074642 137 93 123 39 36 38 24 8 31 0 2.70e-06 0.000042 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(8), ADCY2(16), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), ADRA1A(2), ADRA1B(4), ADRA1D(2), ADRB2(3), ANXA6(6), ARRB1(3), ATP1A4(4), ATP1B2(1), ATP2A2(6), ATP2A3(2), ATP2B1(4), ATP2B2(6), ATP2B3(3), CACNA1A(8), CACNA1B(1), CACNA1C(16), CACNA1D(3), CACNA1E(16), CACNA1S(8), CACNB1(1), CACNB3(2), CALR(1), CAMK2B(2), CAMK2D(1), CAMK4(3), CASQ1(1), CASQ2(1), CHRM2(6), CHRM3(5), CHRM4(1), CHRM5(2), GJA1(4), GJB2(1), GJB4(1), GJB5(1), GNAI3(1), GNAZ(2), GNB1(1), GNB2(3), GNB3(2), GNB4(2), GNB5(1), GNG12(1), GNG3(1), GNG4(2), GNG5(1), GRK4(1), GRK5(2), GRK6(1), ITPR1(5), ITPR2(11), ITPR3(3), KCNB1(1), KCNJ3(8), KCNJ5(2), MIB1(2), NME7(2), PEA15(1), PLCB3(4), PLN(1), PRKACA(1), PRKACB(2), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), PRKCD(2), PRKCE(5), PRKCG(9), PRKCH(1), PRKCQ(4), PRKD1(9), RGS1(2), RGS10(1), RGS11(1), RGS16(1), RGS17(2), RGS18(1), RGS20(1), RGS3(4), RGS5(2), RGS6(4), RGS7(8), RGS9(2), RYR1(29), RYR2(88), RYR3(43), SFN(2), SLC8A1(13), SLC8A3(3), USP5(3), YWHAB(2), YWHAQ(1) 51879168 507 147 504 159 154 189 80 33 51 0 3.13e-06 0.000047 42 SA_REG_CASCADE_OF_CYCLIN_EXPR Expression of cyclins regulates progression through the cell cycle by activating cyclin-dependent kinases. CCNA1, CCNA2, CCND1, CCNE1, CCNE2, CDK2, CDK4, CDKN1B, CDKN2A, E2F1, E2F2, E2F4, PRB1 13 CCNA1(1), CCND1(1), CCNE2(2), CDK2(1), CDKN2A(23), E2F1(3), PRB1(2) 2352092 33 31 30 6 3 12 5 0 13 0 4.68e-06 0.000069 43 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 CCNA1(1), CCNB1(1), CCND1(1), CCND2(3), CCND3(1), CDK2(1), CDK7(1), CDKN2A(23), CDKN2C(1), CDKN2D(1), E2F1(3), RB1(7), RBL1(6) 4296030 50 42 47 7 5 14 9 3 19 0 9.41e-06 0.00013 44 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(2), CDC42(1), CDK2(1), CDKN2A(23), CREB3(2), CREB5(3), EBP(1), ERBB4(9), F2RL2(1), GAB1(2), GADD45A(1), GSK3A(4), GSK3B(1), IGF1(2), INPPL1(3), IRS1(4), IRS2(2), IRS4(3), MET(3), MYC(1), NOLC1(2), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PARD3(5), PARD6A(2), PDK1(1), PIK3CA(21), PIK3CD(3), PPP1R13B(4), PREX1(12), PTEN(11), PTK2(3), PTPN1(1), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KB1(1), SFN(2), SHC1(1), SLC2A4(2), SOS1(6), SOS2(4), TSC1(6), TSC2(6), YWHAB(2), YWHAE(1), YWHAQ(1) 20981038 190 108 176 47 42 62 39 10 37 0 0.000019 0.00026 45 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(2), CPS1(20), GLS(2), GLUD1(3), GOT1(2) 2011222 31 29 29 5 10 11 5 1 4 0 0.000022 0.00030 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(2), ADCY1(8), ADCY2(16), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), ARRB1(3), ATF2(2), ATF4(1), ATP2A2(6), ATP2A3(2), CACNB3(2), CALCA(1), CAMK2B(2), CAMK2D(1), CNN1(1), CNN2(1), CORIN(6), CREB3(2), CRHR1(4), DGKZ(3), FOS(1), GABPA(2), GABPB2(1), GBA2(2), GJA1(4), GNB1(1), GNB2(3), GNB3(2), GNB4(2), GNB5(1), GNG12(1), GNG3(1), GNG4(2), GNG5(1), GRK4(1), GRK5(2), GRK6(1), GSTO1(1), GUCA2B(1), GUCY1A3(6), IGFBP3(1), IGFBP6(1), IL1B(1), ITPR1(5), ITPR2(11), ITPR3(3), JUN(2), MIB1(2), MYL2(1), MYLK2(2), NFKB1(2), NOS1(10), NOS3(1), OXTR(1), PDE4B(3), PDE4D(1), PLCB3(4), PLCG1(2), PLCG2(3), PRKACA(1), PRKACB(2), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), PRKCD(2), PRKCE(5), PRKCH(1), PRKCQ(4), PRKD1(9), RAMP2(1), RGS1(2), RGS10(1), RGS11(1), RGS16(1), RGS17(2), RGS18(1), RGS20(1), RGS3(4), RGS5(2), RGS6(4), RGS7(8), RGS9(2), RYR1(29), RYR2(88), RYR3(43), SFN(2), SLC8A1(13), SP1(1), TNXB(16), USP5(3), YWHAB(2), YWHAQ(1) 47658432 452 144 449 149 144 168 73 24 43 0 0.000023 0.00031 47 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(5), AKT1(1), AKT3(2), BCAR1(5), BIRC3(3), BRAF(7), CAPN2(2), CAV2(1), CAV3(1), CCND1(1), CCND2(3), CCND3(1), CDC42(1), COL11A1(31), COL11A2(10), COL1A1(8), COL1A2(15), COL2A1(8), COL3A1(10), COL4A1(11), COL4A2(9), COL4A4(9), COL4A6(9), COL5A1(5), COL5A2(12), COL5A3(11), COL6A3(12), COL6A6(20), COMP(2), CRKL(1), CTNNB1(3), DIAPH1(1), DOCK1(3), EGF(6), EGFR(9), ERBB2(3), FARP2(6), FIGF(1), FLNA(9), FLNB(4), FLNC(13), FLT1(9), FN1(17), FYN(4), GRLF1(11), GSK3B(1), HGF(6), HRAS(2), IBSP(4), IGF1(2), IGF1R(1), ILK(1), ITGA1(4), ITGA10(6), ITGA11(3), ITGA2(5), ITGA2B(1), ITGA3(2), ITGA4(5), ITGA5(1), ITGA6(6), ITGA7(3), ITGA8(9), ITGA9(1), ITGAV(3), ITGB1(4), ITGB3(3), ITGB4(9), ITGB5(2), ITGB6(2), ITGB7(1), ITGB8(3), JUN(2), KDR(11), LAMA1(14), LAMA2(17), LAMA3(7), LAMA4(15), LAMA5(7), LAMB1(6), LAMB2(4), LAMB3(1), LAMB4(3), LAMC1(8), LAMC2(4), LAMC3(1), MAP2K1(2), MAPK1(1), MAPK10(1), MAPK3(2), MAPK8(2), MAPK9(1), MET(3), MYL2(1), MYLK(7), MYLK2(2), MYLPF(1), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PARVB(1), PARVG(1), PDGFB(1), PDGFC(1), PDGFD(1), PDGFRA(8), PDGFRB(5), PDPK1(1), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PIP5K1C(2), PPP1CA(1), PPP1CB(1), PPP1CC(1), PRKCA(5), PRKCG(9), PTEN(11), PTK2(3), PXN(3), RAC1(2), RAF1(1), RAPGEF1(3), RELN(26), ROCK1(5), ROCK2(3), SHC1(1), SHC2(3), SHC3(3), SHC4(4), SOS1(6), SOS2(4), THBS1(1), THBS2(12), THBS3(4), TLN1(8), TLN2(11), TNC(16), TNN(15), TNR(18), TNXB(16), VASP(2), VAV1(7), VAV2(4), VAV3(1), VCL(2), VEGFC(4), VWF(16) 101666124 850 169 834 275 231 318 152 56 93 0 0.000032 0.00041 48 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(4), MAPK1(1), MAPK3(2), PDK2(2), PDPK1(1), PIK3CA(21), PIK3R1(1), PTEN(11), PTK2(3), SHC1(1), SOS1(6) 5299772 60 49 49 7 23 12 13 3 9 0 0.000056 0.00071 49 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(3), EIF4A2(3), EIF4B(6), EIF4G1(8), EIF4G2(4), EIF4G3(3), PDK2(2), PDPK1(1), PIK3CA(21), PIK3R1(1), PTEN(11), RPS6(1), RPS6KB1(1), TSC1(6), TSC2(6) 7493622 78 61 66 15 20 25 15 4 14 0 0.000068 0.00086 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(21), PIK3R1(1), PLCB1(7), PLCG1(2), PRKCA(5), VAV1(7) 3448216 44 40 33 8 20 11 8 4 1 0 0.00033 0.0041 51 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(8), ADCY8(13), ARAF(3), ATF4(1), BRAF(7), CACNA1C(16), CAMK2B(2), CAMK2D(1), CAMK4(3), CHP(2), CREBBP(12), EP300(5), GRIA1(6), GRIA2(3), GRIN1(1), GRIN2A(13), GRIN2B(17), GRIN2C(2), GRIN2D(3), GRM1(13), GRM5(14), HRAS(2), ITPR1(5), ITPR2(11), ITPR3(3), KRAS(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PPP1CA(1), PPP1CB(1), PPP1CC(1), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCG(9), PRKX(1), RAF1(1), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KA6(3) 27622752 240 123 237 79 75 81 36 25 23 0 0.00038 0.0045 52 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), GABARAP(1), GABRA1(6), GABRA2(8), GABRA3(5), GABRA4(3), GABRA5(4), GABRA6(7), GPHN(1), NSF(2), UBQLN1(2) 3229276 40 35 40 8 9 17 9 1 4 0 0.00046 0.0055 53 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(2), PDK1(1), PIK3CA(21), PIK3CD(3), PTEN(11), RBL2(5), SHC1(1), SOS1(6) 5509812 56 48 45 7 20 11 12 4 9 0 0.00069 0.0080 54 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(3), ADC(1), ALDH4A1(3), ALDH5A1(1), CAD(10), CPS1(20), EARS2(2), EPRS(11), GAD1(5), GAD2(5), GCLC(2), GCLM(1), GFPT2(1), GLS(2), GLUD1(3), GLUD2(7), GLUL(1), GOT1(2), GOT2(3), GPT(1), GPT2(2), GSR(2), GSS(2), NADSYN1(10), PPAT(1) 10615030 101 73 98 30 22 42 19 8 10 0 0.00073 0.0083 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(4), F12(1), F13B(7), F5(15), F8(10), F9(4), FGA(5), FGB(3), FGG(1), LPA(11), PLAT(1), PLAU(2), PLG(2), SERPINB2(3), SERPINE1(2), SERPINF2(3), VWF(16) 9480458 93 69 92 24 19 37 23 6 8 0 0.00074 0.0083 56 STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR 10 EPX(5), GBA3(6), LPO(2), MPO(3), PRDX1(1), PRDX6(1), TPO(11), TYR(3) 2635646 32 29 32 8 5 12 12 1 2 0 0.00084 0.0092 57 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(3), AGTR2(4), ATP8A1(6), AVPR1A(3), AVPR1B(2), AVPR2(1), BDKRB1(3), BDKRB2(1), C3AR1(1), CCKAR(2), CCKBR(1), CCR1(2), CCR10(1), CCR3(1), CCR4(3), CCR6(2), CCR8(3), CX3CR1(3), CXCR3(1), CXCR4(6), EDNRA(2), EDNRB(5), FPR1(1), FSHR(12), GALR1(3), GALT(1), GHSR(3), GPR77(4), GRPR(2), LHCGR(8), MC2R(2), MC3R(3), MC4R(1), MC5R(3), NMBR(2), NPY1R(3), NPY2R(2), NPY5R(2), NTSR1(3), NTSR2(3), OPRD1(2), OPRK1(1), OPRM1(2), OXTR(1), PPYR1(3), SSTR1(1), SSTR2(2), SSTR3(1), SSTR4(2), TACR1(2), TACR3(3), TRHR(1), TSHR(1) 13849112 136 82 135 56 36 51 23 5 21 0 0.00089 0.0094 58 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(8), ADCY2(16), ADCY3(5), ADCY4(4), ADCY7(4), ADCY8(13), ADCY9(4), ADORA2A(6), ADORA2B(1), ADRA1A(2), ADRA1B(4), ADRA1D(2), ADRB2(3), AGTR1(3), ATP2A1(2), ATP2A2(6), ATP2A3(2), ATP2B1(4), ATP2B2(6), ATP2B3(3), ATP2B4(5), AVPR1A(3), AVPR1B(2), BDKRB1(3), BDKRB2(1), BST1(1), CACNA1A(8), CACNA1B(1), CACNA1C(16), CACNA1D(3), CACNA1E(16), CACNA1F(8), CACNA1G(6), CACNA1H(5), CACNA1I(9), CACNA1S(8), CAMK2B(2), CAMK2D(1), CAMK4(3), CCKAR(2), CCKBR(1), CD38(1), CHP(2), CHRM2(6), CHRM3(5), CHRM5(2), CYSLTR1(3), CYSLTR2(1), DRD1(1), EDNRA(2), EDNRB(5), EGFR(9), ERBB2(3), ERBB3(3), ERBB4(9), F2R(2), GNA14(1), GNA15(1), GNAL(2), GNAS(4), GRIN1(1), GRIN2A(13), GRIN2C(2), GRIN2D(3), GRM1(13), GRM5(14), GRPR(2), HRH1(3), HRH2(2), HTR2A(1), HTR2B(2), HTR2C(3), HTR4(3), HTR5A(3), HTR6(1), HTR7(3), ITPKA(1), ITPKB(3), ITPR1(5), ITPR2(11), ITPR3(3), LHCGR(8), LTB4R2(1), MYLK(7), MYLK2(2), NOS1(10), NOS3(1), NTSR1(3), OXTR(1), P2RX2(1), P2RX3(5), P2RX4(2), P2RX7(1), PDE1A(2), PDE1B(1), PDE1C(12), PDGFRA(8), PDGFRB(5), PHKA1(4), PHKA2(4), PHKB(6), PHKG1(2), PHKG2(1), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PLCD3(2), PLCE1(10), PLCG1(2), PLCG2(3), PLCZ1(3), PLN(1), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCG(9), PRKX(1), PTAFR(3), PTGER3(5), PTGFR(2), RYR1(29), RYR2(88), RYR3(43), SLC8A1(13), SLC8A3(3), SPHK2(1), TACR1(2), TACR3(3), TBXA2R(2), TNNC1(1), TNNC2(1), TRHR(1), TRPC1(5), VDAC1(1), VDAC2(1) 74744692 720 161 715 231 228 252 114 55 71 0 0.00089 0.0094 59 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), CCND1(1), CD14(1), CTNNB1(3), DVL1(3), FZD1(1), GJA1(4), GNAI1(2), GSK3B(1), IRAK1(4), LBP(5), LEF1(3), NFKB1(2), PDPK1(1), PIK3CA(21), PIK3R1(1), RELA(3), TLR4(10), TOLLIP(1) 8223600 77 61 66 15 22 20 19 7 9 0 0.00095 0.0099 60 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(3), EIF4A2(3), EIF4G1(8), EIF4G2(4), EIF4G3(3), GHR(2), IRS1(4), MAPK1(1), MAPK14(1), MAPK3(2), PABPC1(1), PDK2(2), PDPK1(1), PIK3CA(21), PIK3R1(1), PRKCA(5), PTEN(11), RPS6KB1(1) 7576570 75 59 64 19 22 24 15 4 10 0 0.0015 0.015 61 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), BID(1), BRAF(7), CD244(1), CHP(2), FAS(1), FASLG(1), FCGR3A(3), FCGR3B(2), FYN(4), GZMB(1), HLA-A(7), HLA-B(1), HLA-C(1), HLA-G(1), HRAS(2), ICAM1(2), IFNA1(1), IFNA10(1), 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(3), KIR2DL3(4), KIR3DL1(6), KIR3DL2(1), KLRC1(1), KLRC3(1), KRAS(1), LAT(1), LCK(2), LCP2(2), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), NCR1(5), NCR2(1), NFAT5(3), NFATC2(5), NFATC3(3), NFATC4(2), PAK1(3), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLCG1(2), PLCG2(3), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRF1(2), PRKCA(5), PRKCG(9), PTPN11(3), RAC1(2), RAF1(1), SH2D1A(1), SH3BP2(2), SHC1(1), SHC2(3), SHC3(3), SHC4(4), SOS1(6), SOS2(4), SYK(1), TNFRSF10A(1), TNFRSF10B(1), TNFRSF10D(1), TYROBP(3), ULBP1(1), ULBP3(1), VAV1(7), VAV2(4), VAV3(1), ZAP70(3) 30808240 245 119 234 69 69 81 47 22 24 2 0.0016 0.017 62 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(1), CBL(4), CDC42(1), CDKN2A(23), F2RL2(1), FLOT1(2), GSK3A(4), GSK3B(1), INPPL1(3), IRS1(4), IRS2(2), IRS4(3), LNPEP(2), MAPK1(1), MAPK3(2), PARD3(5), PARD6A(2), PDK1(1), PIK3CA(21), PIK3CD(3), PIK3R1(1), PPYR1(3), PTEN(11), PTPN1(1), RAF1(1), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KB1(1), SERPINB6(4), SFN(2), SHC1(1), SLC2A4(2), SORBS1(5), SOS1(6), SOS2(4), YWHAB(2), YWHAE(1), YWHAQ(1) 16118968 144 87 130 29 34 41 31 8 30 0 0.0019 0.019 63 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 CDK2(1), CUL1(3), E2F1(3), FBXW7(10), RB1(7) 2297980 24 24 22 3 2 9 2 1 10 0 0.0019 0.019 64 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(6), CALCRL(4), CRHR1(4), CRHR2(3), ELTD1(15), EMR1(9), EMR2(5), GHRHR(3), GLP1R(1), GLP2R(4), GPR64(3), LPHN1(4), LPHN2(6), LPHN3(13) 7428118 87 56 87 29 22 30 15 7 13 0 0.0021 0.020 65 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(4), KLRC1(1), KLRC3(1), LAT(1), MAP2K1(2), MAPK3(2), PAK1(3), PIK3CA(21), PIK3R1(1), RAC1(2), SYK(1), VAV1(7) 5023516 54 44 43 9 22 9 11 5 5 2 0.0022 0.021 66 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(3), ALDH4A1(3), ALDH5A1(1), CAD(10), CPS1(20), EPRS(11), GAD1(5), GAD2(5), GCLC(2), GCLM(1), GLS(2), GLUD1(3), GLUL(1), GOT1(2), GOT2(3), GPT(1), GPT2(2), GSS(2), NADSYN1(10), PPAT(1) 8890922 88 65 85 24 20 39 18 4 7 0 0.0023 0.021 67 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(8), ADCY2(16), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), DRD1(1), DRD2(2), EGF(6), EGFR(9), GJA1(4), GJD2(2), GNAI1(2), GNAI3(1), GNAS(4), GRM1(13), GRM5(14), GUCY1A2(10), GUCY1A3(6), GUCY1B3(3), GUCY2C(4), GUCY2D(1), GUCY2F(8), HRAS(2), HTR2A(1), HTR2B(2), HTR2C(3), ITPR1(5), ITPR2(11), ITPR3(3), KRAS(1), MAP2K1(2), MAP2K2(2), MAP2K5(2), MAPK1(1), MAPK3(2), MAPK7(1), NPR1(2), NPR2(5), PDGFB(1), PDGFC(1), PDGFD(1), PDGFRA(8), PDGFRB(5), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCG(9), PRKG1(5), PRKG2(5), PRKX(1), RAF1(1), SOS1(6), SOS2(4), TJP1(9), TUBA1B(1), TUBA3C(5), TUBA3D(4), TUBA3E(3), TUBA8(1), TUBAL3(2), TUBB(1), TUBB1(1), TUBB2A(1), TUBB4(4), TUBB4Q(2), TUBB8(2) 36050340 304 129 301 99 97 99 47 29 32 0 0.0023 0.021 68 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(2), ARHGEF12(3), CDC42(1), CDK5(2), CFL1(3), CFL2(1), CHP(2), CXCR4(6), DCC(12), DPYSL2(2), DPYSL5(5), EFNA1(1), EFNA3(1), EFNB1(2), EFNB2(1), EPHA1(4), EPHA2(1), EPHA3(6), EPHA4(1), EPHA5(16), EPHA6(10), EPHA7(7), EPHA8(3), EPHB1(17), EPHB2(5), EPHB3(9), EPHB4(2), EPHB6(4), FES(1), FYN(4), GNAI1(2), GNAI3(1), GSK3B(1), HRAS(2), ITGB1(4), KRAS(1), L1CAM(2), LIMK1(1), LIMK2(1), LRRC4C(18), MAPK1(1), MAPK3(2), MET(3), NCK1(3), NFAT5(3), NFATC2(5), NFATC3(3), NFATC4(2), NGEF(1), NRP1(4), NTN1(2), NTN4(1), NTNG1(1), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PLXNA1(10), PLXNA2(6), PLXNA3(3), PLXNB1(4), PLXNB3(3), PLXNC1(9), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PTK2(3), RAC1(2), RASA1(6), RGS3(4), ROBO1(7), ROBO2(6), ROBO3(5), ROCK1(5), ROCK2(3), SEMA3A(3), SEMA3B(1), SEMA3C(5), SEMA3D(2), SEMA3E(3), SEMA3F(3), SEMA3G(1), SEMA4A(2), SEMA4B(1), SEMA4C(2), SEMA4D(1), SEMA4F(5), SEMA4G(1), SEMA5A(7), SEMA5B(4), SEMA6C(4), SEMA6D(6), SEMA7A(1), SLIT1(4), SLIT2(9), SLIT3(11), SRGAP1(2), SRGAP2(5), SRGAP3(3), UNC5B(2), UNC5C(6), UNC5D(12) 54208654 413 143 413 159 116 147 63 31 56 0 0.0028 0.025 69 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(17), GRIN2C(2), GRIN2D(3), NOS1(10), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), SYT1(3) 6877564 74 54 73 25 24 25 6 10 9 0 0.0029 0.026 70 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(5), CARD11(3), CD19(2), CD22(5), CD79A(1), CD81(1), CHP(2), CHUK(2), CR2(9), FCGR2B(2), FOS(1), GSK3B(1), HRAS(2), IKBKB(3), INPP5D(6), JUN(2), KRAS(1), LILRB3(3), LYN(1), MALT1(2), NFAT5(3), NFATC2(5), NFATC3(3), NFATC4(2), NFKB1(2), NFKB2(2), NFKBIB(1), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLCG2(3), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), RAC1(2), RASGRP3(8), SYK(1), VAV1(7), VAV2(4), VAV3(1) 20264588 159 97 148 47 49 45 23 20 22 0 0.0029 0.026 71 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(8), CRHR1(4), GNA12(1), GNA13(1), GNAI1(2), GNAI3(1), GNAS(4), GNAZ(2), GRIA1(6), GRIA2(3), GRIA3(9), GRID2(12), GRM1(13), GRM5(14), GUCY1A2(10), GUCY1A3(6), GUCY1B3(3), GUCY2C(4), GUCY2D(1), GUCY2F(8), HRAS(2), IGF1(2), IGF1R(1), ITPR1(5), ITPR2(11), ITPR3(3), KRAS(1), LYN(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), NOS1(10), NOS3(1), NPR1(2), NPR2(5), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PPP2R1A(6), PPP2R1B(2), PPP2R2A(1), PPP2R2B(2), PPP2R2C(2), PRKCA(5), PRKCG(9), PRKG1(5), PRKG2(5), RAF1(1), RYR1(29) 30301296 281 121 278 87 73 106 45 22 35 0 0.0030 0.026 72 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 ADCY1(8), CREM(2), FSHB(1), FSHR(12), GNAS(4), XPO1(2) 2597732 29 26 29 12 9 8 6 4 2 0 0.0033 0.028 73 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(4), ADRA1D(2), ADRA2C(2), ADRB2(3), CHRM2(6), CHRM3(5), CHRM4(1), CHRM5(2), DRD1(1), DRD2(2), DRD3(5), DRD4(1), DRD5(3), HRH1(3), HRH2(2), HTR1A(6), HTR1B(3), HTR1D(1), HTR1E(5), HTR1F(2), HTR2A(1), HTR2B(2), HTR2C(3), HTR4(3), HTR5A(3), HTR6(1), HTR7(3) 7002876 77 55 77 33 20 27 21 3 6 0 0.0033 0.028 74 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(2), ASS1(4), CKB(1), CKM(2), CKMT2(1), CPS1(20), DAO(1), EPRS(11), GATM(1), GLUD1(3), GLUD2(7), GOT1(2), GOT2(3), LAP3(1), NOS1(10), NOS3(1), OTC(2), P4HA1(2), P4HA2(3), P4HA3(3), PARS2(1), RARS(4), RARS2(2) 9714172 92 66 88 22 25 32 16 5 14 0 0.0034 0.028 75 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(3), AGTR2(4), ANPEP(5), CMA1(4), CPA3(4), CTSA(2), CTSG(4), ENPEP(7), LNPEP(2), MAS1(3), MME(6), NLN(2), THOP1(1) 5741924 55 46 55 22 11 23 8 4 9 0 0.0037 0.030 76 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(3), C1GALT1C1(1), GALNT1(1), GALNT10(2), GALNT11(2), GALNT12(3), GALNT13(11), GALNT14(4), GALNT2(4), GALNT3(2), GALNT5(6), GALNT6(2), GALNT7(1), GALNT8(2), GALNTL1(3), GALNTL2(1), GALNTL4(4), GALNTL5(3), GCNT1(3), GCNT3(3), OGT(2), ST3GAL1(1), ST3GAL2(2), ST6GALNAC1(6), WBSCR17(9) 8702954 82 65 79 26 13 39 17 5 8 0 0.0038 0.031 77 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(3), IFNA1(1), IFNB1(1), IFNG(1), IL10(1), IL12A(1), IL12B(3), IL4(2), ITGAX(9), TLR2(3), TLR4(10), TLR7(3), TLR9(1) 5001444 47 42 45 17 10 18 8 4 7 0 0.0040 0.032 78 CDC42RACPATHWAY PI3 kinase stimulates cell migration by activating cdc42, which activates ARP2/3, which in turn promotes formation of new actin fibers. ACTR2, ACTR3, ARHA, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, PAK1, PDGFRA, PIK3CA, PIK3R1, RAC1, WASL 14 ACTR2(1), ARPC1A(2), ARPC1B(1), CDC42(1), PAK1(3), PDGFRA(8), PIK3CA(21), PIK3R1(1), RAC1(2), WASL(2) 3584742 42 37 31 8 20 10 9 3 0 0 0.0041 0.032 79 HSA00940_PHENYLPROPANOID_BIOSYNTHESIS Genes involved in phenylpropanoid biosynthesis EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO 7 EPX(5), GBA3(6), LPO(2), MPO(3), PRDX6(1), TPO(11) 2302786 28 25 28 7 5 10 11 1 1 0 0.0042 0.033 80 HSA04810_REGULATION_OF_ACTIN_CYTOSKELETON Genes involved in regulation of actin cytoskeleton ABI2, ACTN1, ACTN2, ACTN3, ACTN4, APC, APC2, ARAF, ARHGEF1, ARHGEF12, ARHGEF4, ARHGEF6, ARHGEF7, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, ARPC5, ARPC5L, BAIAP2, BCAR1, BDKRB1, BDKRB2, BRAF, C3orf10, CD14, CDC42, CFL1, CFL2, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CRK, CRKL, CSK, CYFIP1, CYFIP2, DIAPH1, DIAPH2, DIAPH3, DOCK1, EGF, EGFR, EZR, F2, F2R, FGD1, FGD3, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14, FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FN1, GIT1, GNA12, GNA13, GNG12, GRLF1, GSN, HRAS, INS, IQGAP1, IQGAP2, IQGAP3, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, KRAS, LIMK1, LIMK2, LOC200025, LOC645126, LOC653888, MAP2K1, MAP2K2, MAPK1, MAPK3, MLCK, MOS, MRAS, MRCL3, MRLC2, MSN, MYH10, MYH14, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, NCKAP1, NCKAP1L, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDGFA, PDGFB, PDGFRA, PDGFRB, PFN1, PFN2, PFN3, PFN4, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R12B, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RDX, RHOA, ROCK1, ROCK2, RRAS, RRAS2, SCIN, SLC9A1, SOS1, SOS2, SSH1, SSH2, SSH3, TIAM1, TIAM2, TMSB4X, TMSB4Y, TMSL3, VAV1, VAV2, VAV3, VCL, WAS, WASF1, WASF2, WASL 203 ACTN1(2), ACTN2(6), ACTN3(2), ACTN4(5), APC(9), APC2(2), ARAF(3), ARHGEF1(2), ARHGEF12(3), ARHGEF4(3), ARHGEF6(2), ARHGEF7(3), ARPC1A(2), ARPC1B(1), BCAR1(5), BDKRB1(3), BDKRB2(1), BRAF(7), CD14(1), CDC42(1), CFL1(3), CFL2(1), CHRM2(6), CHRM3(5), CHRM4(1), CHRM5(2), CRKL(1), CYFIP1(6), CYFIP2(7), DIAPH1(1), DIAPH3(5), DOCK1(3), EGF(6), EGFR(9), EZR(1), F2R(2), FGD1(3), FGD3(3), FGF10(2), FGF12(2), FGF14(1), FGF2(2), FGF23(1), FGF3(1), FGF5(3), FGF6(2), FGF8(1), FGFR1(3), FGFR2(6), FGFR3(2), FGFR4(1), FN1(17), GIT1(1), GNA12(1), GNA13(1), GNG12(1), GRLF1(11), GSN(2), HRAS(2), IQGAP1(6), IQGAP2(6), IQGAP3(11), ITGA1(4), ITGA10(6), ITGA11(3), ITGA2(5), ITGA2B(1), ITGA3(2), ITGA4(5), ITGA5(1), ITGA6(6), ITGA7(3), ITGA8(9), ITGA9(1), ITGAD(6), ITGAE(3), ITGAL(1), ITGAM(3), ITGAV(3), ITGAX(9), ITGB1(4), ITGB2(3), ITGB3(3), ITGB4(9), ITGB5(2), ITGB6(2), ITGB7(1), ITGB8(3), KRAS(1), LIMK1(1), LIMK2(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), MOS(4), MRAS(3), MSN(3), MYH10(3), MYH14(4), MYH9(14), MYL2(1), MYLK(7), MYLK2(2), MYLPF(1), NCKAP1(5), NCKAP1L(9), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PDGFB(1), PDGFRA(8), PDGFRB(5), PFN3(1), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PIP4K2A(2), PIP4K2B(3), PIP4K2C(3), PIP5K1A(4), PIP5K1B(1), PIP5K1C(2), PPP1CA(1), PPP1CB(1), PPP1CC(1), PPP1R12B(3), PTK2(3), PXN(3), RAC1(2), RAF1(1), RDX(1), ROCK1(5), ROCK2(3), RRAS2(2), SCIN(1), SLC9A1(3), SOS1(6), SOS2(4), SSH1(1), SSH2(7), TIAM1(9), TIAM2(4), VAV1(7), VAV2(4), VAV3(1), VCL(2), WAS(5), WASL(2) 76078980 548 154 533 166 135 201 98 47 67 0 0.0045 0.034 81 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(8), AKT1(1), BAX(1), BCL2L1(2), CSF2RB(5), IGF1(2), IGF1R(1), KIT(6), PIK3CA(21), PIK3R1(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 5621418 58 50 47 9 25 18 9 3 3 0 0.0047 0.036 82 EPHA4PATHWAY Eph Kinases and ephrins support platelet aggregation ACTA1, EPHA4, EPHB1, FYN, ITGA1, ITGB1, L1CAM, LYN, RAP1B, SELP 10 ACTA1(2), EPHA4(1), EPHB1(17), FYN(4), ITGA1(4), ITGB1(4), L1CAM(2), LYN(1), SELP(8) 4224830 43 38 43 19 16 9 8 1 9 0 0.0056 0.042 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(5) 1860812 23 21 22 5 3 11 4 4 1 0 0.0060 0.045 84 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(2), ARSD(1), ARSE(2), CYP11B1(11), CYP11B2(6), HSD11B1(3), HSD11B2(1), HSD3B1(4), HSD3B2(5), SRD5A1(2), SRD5A2(2), STS(3), SULT1E1(1), SULT2A1(3), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2B15(1), UGT2B4(4) 7061616 67 53 66 10 17 24 13 7 6 0 0.0063 0.046 85 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(3), AGTR2(4), CMA1(4), COL4A1(11), COL4A2(9), COL4A3(5), COL4A4(9), COL4A5(3), COL4A6(9) 6924734 61 52 61 22 15 31 7 0 8 0 0.0071 0.051 86 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(5), FCER1A(1), FYN(4), HRAS(2), IL4(2), INPP5D(6), KRAS(1), LAT(1), LCP2(2), LYN(1), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K6(3), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPK8(2), MAPK9(1), MS4A2(2), PDK1(1), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLCG1(2), PLCG2(3), PRKCA(5), PRKCD(2), PRKCE(5), RAC1(2), RAF1(1), SOS1(6), SOS2(4), SYK(1), VAV1(7), VAV2(4), VAV3(1) 19629306 157 97 146 42 47 51 28 13 18 0 0.0071 0.051 87 NICOTINATE_AND_NICOTINAMIDE_METABOLISM AOX1, CD38, ENPP1, ENPP3, NADSYN1, NMNAT1, NMNAT2, NNMT, NNT, NP, NT5C, NT5E, NT5M, QPRT 13 AOX1(11), CD38(1), ENPP1(7), ENPP3(4), NADSYN1(10), NMNAT1(3), NMNAT2(2), NNMT(1), NNT(7), NT5E(2) 3938428 48 37 46 10 13 20 7 4 4 0 0.0073 0.051 88 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(8), ADCY2(16), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), ADSL(1), ADSS(1), ADSSL1(1), AK5(2), AK7(1), AMPD1(4), AMPD2(1), AMPD3(6), CANT1(3), DCK(1), ENPP1(7), ENPP3(4), ENTPD1(1), ENTPD2(1), ENTPD3(1), ENTPD5(1), ENTPD6(3), GART(2), GDA(6), GUCY1A2(10), GUCY1A3(6), GUCY1B3(3), GUCY2C(4), GUCY2D(1), GUCY2F(8), GUK1(1), HPRT1(1), IMPDH1(2), NME4(1), NME7(2), NPR1(2), NPR2(5), NT5C1A(2), NT5C1B(2), NT5C2(3), NT5C3(4), NT5E(2), NUDT9(2), PAPSS2(1), PDE10A(5), PDE11A(11), PDE1A(2), PDE1C(12), PDE2A(3), PDE3B(3), PDE4B(3), PDE4C(4), PDE4D(1), PDE5A(3), PDE6H(2), PDE7B(1), PDE8A(6), PDE8B(2), PDE9A(2), PFAS(5), PKLR(3), PKM2(1), PNPT1(2), POLA1(5), POLA2(3), POLD1(2), POLD3(1), POLE2(2), POLE4(1), POLR1A(4), POLR1B(4), POLR1C(1), POLR1D(1), POLR2A(2), POLR2B(2), POLR2D(1), POLR2E(1), POLR2H(1), POLR3A(3), POLR3B(2), POLR3G(1), POLR3H(1), PPAT(1), PRIM1(2), PRIM2(10), PRPS1(1), PRPS1L1(1), PRPS2(1), RFC5(2), RRM1(2), RRM2B(2), XDH(9) 44705590 306 131 303 120 93 114 42 20 37 0 0.0084 0.058 89 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(8), AKT1(1), CAMK2B(2), CAMK2D(1), GNAS(4), HRAS(2), MAPK1(1), MAPK14(1), MAPK3(2), PIK3CA(21), PIK3R1(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), RAC1(2), RPS6KA1(4), RPS6KA5(3), SOS1(6) 7817404 74 58 63 12 27 19 18 5 5 0 0.0085 0.058 90 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(21), PIK3R1(1), PTPN11(3) 3418312 37 32 26 8 15 10 8 2 2 0 0.0085 0.058 91 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(2), CD36(1), CD44(3), CD47(2), COL11A1(31), COL11A2(10), COL1A1(8), COL1A2(15), COL2A1(8), COL3A1(10), COL4A1(11), COL4A2(9), COL4A4(9), COL4A6(9), COL5A1(5), COL5A2(12), COL5A3(11), COL6A3(12), COL6A6(20), DAG1(1), FN1(17), FNDC1(7), FNDC3A(1), GP5(4), GP6(3), GP9(1), HMMR(1), HSPG2(8), IBSP(4), ITGA1(4), ITGA10(6), ITGA11(3), ITGA2(5), ITGA2B(1), ITGA3(2), ITGA4(5), ITGA5(1), ITGA6(6), ITGA7(3), ITGA8(9), ITGA9(1), ITGAV(3), ITGB1(4), ITGB3(3), ITGB4(9), ITGB5(2), ITGB6(2), ITGB7(1), ITGB8(3), LAMA1(14), LAMA2(17), LAMA3(7), LAMA4(15), LAMA5(7), LAMB1(6), LAMB2(4), LAMB3(1), LAMB4(3), LAMC1(8), LAMC2(4), LAMC3(1), RELN(26), SDC2(4), SDC3(1), SV2A(3), SV2B(3), SV2C(3), THBS1(1), THBS2(12), THBS3(4), TNC(16), TNN(15), TNR(18), TNXB(16), VWF(16) 62294660 533 148 531 175 145 210 101 22 55 0 0.0089 0.060 92 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), GSK3B(1), IGF1(2), IGF1R(1), INPPL1(3), PDK2(2), PDPK1(1), PIK3CA(21), PIK3R1(1), PTEN(11), RPS6(1), RPS6KB1(1) 5349790 47 42 36 9 16 9 8 4 10 0 0.0098 0.065 93 SMALL_LIGAND_GPCRS C9orf47, CNR1, CNR2, DNMT1, EDG1, EDG2, EDG5, EDG6, MTNR1A, MTNR1B, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, TBXA2R 14 CNR1(3), CNR2(3), DNMT1(4), MTNR1A(1), MTNR1B(8), PTAFR(3), PTGDR(5), PTGER2(1), PTGER4(2), PTGFR(2), PTGIR(1), TBXA2R(2) 3166976 35 30 35 10 11 16 6 0 2 0 0.010 0.067 94 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(2), AGT(1), AKT1(1), CALR(1), CAMK1G(2), CAMK4(3), CREBBP(12), CSNK1A1(1), EDN1(1), ELSPBP1(1), FGF2(2), GSK3B(1), HAND1(1), HAND2(1), HRAS(2), IGF1(2), MAP2K1(2), MAPK1(1), MAPK14(1), MAPK3(2), MAPK8(2), MEF2C(2), MYH2(22), NFATC2(5), NFATC3(3), NFATC4(2), NKX2-5(2), PIK3CA(21), PIK3R1(1), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), RAF1(1), RPS6KB1(1), SYT1(3) 13631774 124 81 113 36 43 35 19 15 12 0 0.011 0.073 95 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(2), KLK2(1), NTRK1(3), PIK3CA(21), PIK3R1(1), PLCG1(2), PRKCA(5), SHC1(1), SOS1(6) 4212014 43 37 32 8 16 11 11 2 3 0 0.012 0.076 96 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(11), BST1(1), CD38(1), ENPP1(7), ENPP3(4), NADSYN1(10), NMNAT1(3), NMNAT2(2), NNMT(1), NNT(7), NT5C1A(2), NT5C1B(2), NT5C2(3), NT5C3(4), NT5E(2), NUDT12(2) 5841960 62 47 60 14 17 25 10 4 6 0 0.012 0.076 97 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(8), REG1A(11), STAT1(2), STAT2(2), TYK2(8) 3383424 35 32 34 9 7 17 4 4 3 0 0.012 0.077 98 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), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAPK1(1), MAPK14(1), MAPK3(2), NFKB1(2), PIK3CA(21), PIK3R1(1), RB1(7), RELA(3), SP1(1) 5286778 52 44 41 9 20 17 7 2 6 0 0.012 0.077 99 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(4), CDKL1(1), CDKL2(2), CDS1(2), CLK1(3), CLK2(2), CLK4(2), COL4A3BP(3), CSNK2A1(2), DGKA(6), DGKB(4), DGKD(5), DGKE(2), DGKG(2), DGKZ(3), IMPA1(1), INPP1(1), INPP4A(5), INPP4B(4), INPP5A(3), INPPL1(3), ITPKA(1), ITPKB(3), MOS(4), NEK1(3), NEK3(1), OCRL(5), PAK4(1), PIK3C2A(4), PIK3C2B(7), PIK3C2G(7), PIK3CA(21), PIK3CB(1), PIK3CG(10), PIM2(2), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PLCG1(2), PLCG2(3), PLK3(3), PRKACA(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), PRKCD(2), PRKCE(5), PRKCG(9), PRKCH(1), PRKCQ(4), PRKD1(9), PRKG1(5), RAF1(1), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KA4(3), RPS6KB1(1), STK11(3), VRK1(1) 31164596 235 116 223 61 77 77 41 15 25 0 0.013 0.083 100 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(4), ARG1(2), ASL(2), CKB(1), CKM(2), CKMT2(1), CPS1(20), GATM(1), GLUD1(3), NAGS(1), ODC1(1), OTC(2), SMS(4) 4693148 44 38 43 8 13 14 9 1 7 0 0.015 0.095 101 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(2), CRKL(1), DOCK1(3), FOS(1), GAB1(2), HGF(6), HRAS(2), ITGA1(4), ITGB1(4), JUN(2), MAP2K1(2), MAP2K2(2), MAP4K1(2), MAPK1(1), MAPK3(2), MAPK8(2), MET(3), PAK1(3), PIK3CA(21), PIK3R1(1), PTEN(11), PTK2(3), PTPN11(3), PXN(3), RAF1(1), RASA1(6), SOS1(6), STAT3(1) 12099016 100 71 89 27 33 26 17 8 16 0 0.019 0.12 102 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(8), ADCY2(16), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), AKAP1(3), AKAP11(7), AKAP12(4), AKAP3(6), AKAP5(1), AKAP6(12), AKAP7(2), AKAP8(3), AKAP9(6), ARHGEF1(2), CHMP1B(1), GNA12(1), GNA13(1), GNA14(1), GNA15(1), GNAI3(1), GNAL(2), GNAZ(2), GNB1(1), GNB2(3), GNB3(2), GNB5(1), GNG12(1), GNG3(1), GNG4(2), GNG5(1), HRAS(2), ITPR1(5), KCNJ3(8), KRAS(1), PDE1A(2), PDE1B(1), PDE1C(12), PDE4B(3), PDE4C(4), PDE4D(1), PDE7B(1), PDE8A(6), PDE8B(2), PLCB3(4), PPP3CA(2), PPP3CC(2), PRKACA(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), PRKCD(2), PRKCE(5), PRKCG(9), PRKCH(1), PRKCI(4), PRKCQ(4), PRKD1(9), PRKD3(2), SLC9A1(3), USP5(3) 31769796 239 114 238 61 78 77 37 21 26 0 0.019 0.12 103 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(8), AKT1(1), GNAI1(2), GNB1(1), ITGAV(3), ITGB3(3), MAPK1(1), MAPK3(2), PDGFRA(8), PIK3CA(21), PIK3R1(1), PLCB1(7), PRKCA(5), PTK2(3), RAC1(2), SMPD1(3), SMPD2(2) 7352290 73 56 62 21 29 23 14 6 1 0 0.020 0.12 104 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(2), INSR(7), IRS1(4), JUN(2), MAP2K1(2), MAPK3(2), MAPK8(2), PIK3CA(21), PIK3R1(1), PTPN11(3), RAF1(1), RASA1(6), SHC1(1), SLC2A4(2), SOS1(6), SRF(2) 6881836 67 52 56 10 25 19 12 5 6 0 0.021 0.13 105 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 0.023 0.13 106 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(4), KHK(1), LCT(15), MPI(1), PGM1(1), PYGM(6), TPI1(4), TREH(1) 3613934 33 31 32 11 11 7 8 3 4 0 0.026 0.15 107 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(3), GNAS(4), GNB1(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5) 2534364 23 23 23 8 5 11 3 1 3 0 0.026 0.15 108 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(4), EDN1(1), EDNRA(2), EDNRB(5), EGF(6), EGFR(9), FOS(1), HRAS(2), JUN(2), MYC(1), NFKB1(2), PLCG1(2), PRKCA(5), RELA(3) 5560898 51 41 50 15 10 20 7 4 10 0 0.026 0.15 109 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(4), C2(1), C3(4), C5(1), C6(14), C7(7), C8A(3), C9(2), MASP1(10), MASP2(1), MBL2(3) 5864922 56 43 56 17 13 21 11 4 7 0 0.027 0.16 110 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(3), CCKBR(1), CCR3(1), CELSR1(10), CELSR2(7), CELSR3(9), CHRM2(6), CHRM3(5), CXCR3(1), DRD4(1), EDNRA(2), EMR2(5), EMR3(3), F2R(2), FSHR(12), GHRHR(3), GPR116(4), GPR132(1), GPR133(2), GPR143(2), GPR17(5), GPR18(1), GPR55(1), GPR56(1), GPR61(2), GPR77(4), GPR84(1), GRM1(13), 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 153 91 152 64 45 55 30 8 15 0 0.028 0.16 111 HSA00471_D_GLUTAMINE_AND_D_GLUTAMATE_METABOLISM Genes involved in D-glutamine and D-glutamate metabolism GLS, GLS2, GLUD1, GLUD2 4 GLS(2), GLUD1(3), GLUD2(7) 1147388 12 12 12 3 3 3 1 2 3 0 0.028 0.16 112 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(6), GNAI1(2), GNB1(1), HRAS(2), MAP2K1(2), MAPK1(1), MAPK3(2), NFKB1(2), PIK3C2G(7), PIK3CA(21), PIK3R1(1), PLCG1(2), PRKCA(5), PTK2(3), PXN(3), RAF1(1), RELA(3) 7686040 69 56 58 20 26 23 12 5 3 0 0.029 0.16 113 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(2), CXCR3(1), IFNG(1), IL12A(1), IL12B(3), IL12RB1(3), IL12RB2(3), JAK2(3), STAT4(4), TYK2(8) 3830026 31 30 31 9 7 9 6 2 7 0 0.032 0.17 114 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(3), IFNG(1), IL12A(1), IL12B(3), IL12RB1(3), IL12RB2(3), IL18R1(2), JAK2(3), JUN(2), MAP2K6(3), MAPK14(1), MAPK8(2), STAT4(4), TYK2(8) 4886634 41 38 41 10 9 16 7 3 6 0 0.033 0.18 115 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(5), ENPP1(7), ENPP3(4), G6PC(2), GANAB(5), GBA3(6), GBE1(1), GCK(1), GPI(5), GUSB(3), GYS1(1), GYS2(3), HK1(4), HK2(6), HK3(7), MGAM(5), PGM1(1), PYGB(2), PYGM(6), SI(33), UGDH(3), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2B15(1), UGT2B4(4), UXS1(3) 15203514 134 81 133 33 38 54 24 8 10 0 0.034 0.18 116 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(2), GNS(1), GUSB(3), HEXA(6), HGSNAT(2), HPSE(3), HPSE2(4), HYAL1(4), IDS(1), IDUA(2), LCT(15), SPAM1(3) 5629962 46 39 45 11 9 15 10 4 8 0 0.034 0.18 117 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(9), SNCAIP(3), UBE2E2(1), UBE2G2(1), UBE2L6(1) 1721794 17 17 17 4 3 2 8 1 3 0 0.035 0.18 118 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(1), CA6(2), CA7(1), CA9(1), CPS1(20), GLS(2), GLUD1(3), GLUD2(7), GLUL(1) 5640108 49 40 48 8 16 14 10 3 6 0 0.036 0.18 119 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(5) 2187264 20 20 19 4 6 6 4 3 1 0 0.036 0.18 120 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(5), PSEN1(1) 2417774 22 22 22 8 3 9 3 2 5 0 0.036 0.18 121 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(6), FIGF(1), HIF1A(1), IGF1(2), MAPK1(1), MAPK3(2), PDPK1(1), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PRKAA2(2), RHEB(1), RICTOR(4), RPS6(1), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KA6(3), RPS6KB1(1), STK11(3), TSC1(6), TSC2(6), ULK1(1), ULK2(3), VEGFC(4) 14641212 113 80 100 30 33 32 27 7 14 0 0.037 0.19 122 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(11), COL4A2(9), COL4A3(5), COL4A4(9), COL4A5(3), COL4A6(9), F10(3), F11(4), F12(1), F2R(2), F5(15), F8(10), F9(4), FGA(5), FGB(3), FGG(1), KLKB1(4), SERPINC1(5) 12073384 103 69 103 31 22 47 20 3 11 0 0.039 0.20 123 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(3), OCRL(5), PIK3C2A(4), PIK3C2B(7), PIK3C2G(7), PIK3CA(21), PIK3CB(1), PIK3CG(10), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PLCG1(2), PLCG2(3) 12318668 101 72 90 29 39 24 22 6 10 0 0.042 0.21 124 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(6) 2761848 27 24 27 4 6 7 6 3 5 0 0.044 0.22 125 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(4), C5(1), C6(14), C7(7), C8A(3), C9(2) 3440384 31 27 31 9 7 9 7 3 5 0 0.044 0.22 126 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(2), DRD1(1), DRD2(2), GRM1(13), PLCB1(7), PPP1CA(1), PPP1R1B(1), PPP3CA(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 4232840 39 34 38 10 12 17 3 3 4 0 0.045 0.22 127 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(6), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH4A1(3), ALDH9A1(2), AMD1(1), AOC2(2), AOC3(3), ARG1(2), ASL(2), CKB(1), CKM(2), CKMT2(1), CPS1(20), DAO(1), GATM(1), GLUD1(3), GOT1(2), GOT2(3), NOS1(10), NOS3(1), ODC1(1), OTC(2), P4HA1(2), P4HA2(3), P4HA3(3), RARS(4), SMS(4) 11910336 94 70 91 28 25 36 15 5 13 0 0.045 0.22 128 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), CCND1(1), CDK2(1), E2F1(3), HRAS(2), MAPK1(1), MAPK3(2), NFKB1(2), PAK1(3), PIK3CA(21), PIK3R1(1), RAC1(2), RAF1(1), RB1(7), RELA(3) 5529036 51 42 40 6 19 15 6 4 7 0 0.048 0.23 129 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(4), C2(1), C3(4), C5(1), C6(14), C7(7), C8A(3), C8B(2), C9(2), MASP1(10) 5718962 54 41 54 18 14 19 11 4 6 0 0.048 0.23 130 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 CDS1(2), DGKA(6), DGKB(4), DGKD(5), DGKE(2), DGKG(2), DGKI(7), DGKZ(3), IMPA1(1), INPP1(1), INPP4A(5), INPP4B(4), INPP5A(3), INPP5B(5), INPP5D(6), INPP5E(2), INPPL1(3), ITPKA(1), ITPKB(3), ITPR1(5), ITPR2(11), ITPR3(3), OCRL(5), PI4KA(4), PI4KB(2), PIK3C2A(4), PIK3C2B(7), PIK3C2G(7), PIK3C3(3), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PIP4K2A(2), PIP4K2B(3), PIP4K2C(3), PIP5K1A(4), PIP5K1B(1), PIP5K1C(2), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PLCD3(2), PLCE1(10), PLCG1(2), PLCG2(3), PLCZ1(3), PRKCA(5), PRKCG(9), PTEN(11), SYNJ1(2), SYNJ2(5) 34411672 247 119 235 76 85 72 43 16 31 0 0.050 0.24 131 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(2), MAP2K1(2), MAP2K2(2), NGFR(1), NTRK1(3), PIK3CA(21), PIK3CD(3), SHC1(1), SOS1(6) 4474208 44 37 33 11 17 14 9 2 2 0 0.052 0.25 132 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(8), ADCY2(16), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), ATF4(1), CACNA1C(16), CACNA1D(3), CACNA1F(8), CACNA1S(8), CAMK2B(2), CAMK2D(1), CDC42(1), EGFR(9), FSHB(1), GNAS(4), HBEGF(1), HRAS(2), ITPR1(5), ITPR2(11), ITPR3(3), JUN(2), KRAS(1), LHB(1), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAP3K4(4), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPK7(1), MAPK8(2), MAPK9(1), MMP14(3), MMP2(4), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PLD1(10), PLD2(4), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCD(2), PRKX(1), RAF1(1), SOS1(6), SOS2(4) 35211604 248 121 245 77 79 87 39 21 22 0 0.053 0.25 133 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(6), GREB1(15), HSPB2(1), MTA1(2), MTA3(3), TUBA8(1) 3050208 30 27 30 10 9 13 6 1 1 0 0.053 0.25 134 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(14), MEF2A(2), MEF2C(2), MEF2D(2) 2222864 22 21 22 8 11 3 4 2 2 0 0.055 0.26 135 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(5), BCAR1(5), CDC42(1), CDH5(2), CLDN1(2), CLDN10(4), CLDN16(4), CLDN17(1), CLDN19(1), CLDN2(1), CLDN22(1), CLDN3(1), CLDN6(1), CLDN8(2), CLDN9(3), CTNNA2(17), CTNNA3(11), CTNNB1(3), CTNND1(4), CXCR4(6), CYBB(6), ESAM(4), EZR(1), F11R(1), GNAI1(2), GNAI3(1), GRLF1(11), ICAM1(2), ITGA4(5), ITGAL(1), ITGAM(3), ITGB1(4), ITGB2(3), ITK(2), MAPK13(2), MAPK14(1), MLLT4(3), MMP2(4), MMP9(6), MSN(3), MYL2(1), MYLPF(1), NCF2(5), NCF4(1), NOX1(2), NOX3(5), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLCG1(2), PLCG2(3), PRKCA(5), PRKCG(9), PTK2(3), PTPN11(3), PXN(3), RAC1(2), RAPGEF4(5), RASSF5(2), RHOH(3), ROCK1(5), ROCK2(3), THY1(2), TXK(3), VASP(2), VAV1(7), VAV2(4), VAV3(1), VCAM1(4), VCL(2) 34291522 282 121 270 98 81 101 52 25 23 0 0.057 0.26 136 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 ALDH6A1(2), TPI1(4) 435032 6 6 5 1 4 1 1 0 0 0 0.060 0.27 137 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), INPP5D(6), JAK1(1), JAK2(3), JAK3(7), NR0B2(1), PI3(1), PIK3CA(21), PPP1R13B(4), RPS6KB1(1), SERPINA4(4), SHC1(1), SOS1(6), SOS2(4), STAT6(1), TYK2(8) 10061984 80 63 69 18 21 26 20 4 9 0 0.061 0.28 138 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(8), ADRB2(3), GNAS(4), PLCE1(10), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 3962102 35 32 34 11 15 9 5 3 3 0 0.062 0.28 139 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(4), CSF1R(3), EGF(6), EGFR(9), MET(3), PDGFRA(8), PRKCA(5), SH3GLB1(1), SH3KBP1(7) 5214866 46 39 45 10 11 20 6 3 6 0 0.064 0.29 140 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(2), CAPN1(2), CAPN2(2), CAPNS2(1), CXCR3(1), EGF(6), EGFR(9), HRAS(2), ITGA1(4), ITGB1(4), MAPK1(1), MAPK3(2), MYL2(1), MYLK(7), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PTK2(3), PXN(3), TLN1(8) 8846956 68 55 66 19 17 27 8 7 9 0 0.065 0.29 141 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(2), CFL1(3), CHN1(2), LIMK1(1), MAP3K1(3), MYL2(1), MYLK(7), NCF2(5), PAK1(3), PDGFRA(8), PIK3CA(21), PIK3R1(1), PLD1(10), PPP1R12B(3), RAC1(2), RALBP1(1), RPS6KB1(1), TRIO(7), VAV1(7) 9449664 88 63 75 27 30 30 18 7 3 0 0.067 0.29 142 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(2), IGF1(2), IGF1R(1), IRS1(4), JUN(2), MAP2K1(2), MAPK3(2), MAPK8(2), PIK3CA(21), PIK3R1(1), PTPN11(3), RAF1(1), RASA1(6), SHC1(1), SOS1(6), SRF(2) 6671084 61 49 50 8 25 16 11 4 5 0 0.068 0.29 143 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(6), CD14(1), CDC42(1), CDH1(4), CLDN1(2), CTNNB1(3), CTTN(4), EZR(1), FYN(4), HCLS1(3), ITGB1(4), KRT18(2), NCK1(3), NCL(1), PRKCA(5), ROCK1(5), ROCK2(3), TLR4(10), TLR5(3), TUBA1B(1), TUBA3C(5), TUBA3D(4), TUBA3E(3), TUBA8(1), TUBAL3(2), TUBB(1), TUBB1(1), TUBB2A(1), TUBB4(4), TUBB4Q(2), TUBB8(2), WAS(5), WASL(2), YWHAQ(1) 14327042 103 73 103 38 21 38 18 12 14 0 0.070 0.30 144 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(6), CD14(1), CDC42(1), CDH1(4), CLDN1(2), CTNNB1(3), CTTN(4), EZR(1), FYN(4), HCLS1(3), ITGB1(4), KRT18(2), NCK1(3), NCL(1), PRKCA(5), ROCK1(5), ROCK2(3), TLR4(10), TLR5(3), TUBA1B(1), TUBA3C(5), TUBA3D(4), TUBA3E(3), TUBA8(1), TUBAL3(2), TUBB(1), TUBB1(1), TUBB2A(1), TUBB4(4), TUBB4Q(2), TUBB8(2), WAS(5), WASL(2), YWHAQ(1) 14327042 103 73 103 38 21 38 18 12 14 0 0.070 0.30 145 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(8), REG1A(11), STAT1(2) 3103786 30 26 29 6 4 15 7 1 3 0 0.072 0.31 146 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(2), EGFR(9), ERBB2(3), ERBB4(9), ETS1(2), ETV6(4), ETV7(1), FMN2(24), KRAS(1), MAP2K1(2), MAPK1(1), MAPK3(2), NOTCH1(11), NOTCH2(7), NOTCH3(5), NOTCH4(3), PIWIL1(5), PIWIL2(4), PIWIL3(4), PIWIL4(1), RAF1(1), SOS1(6), SOS2(4), SPIRE1(1) 14423162 119 76 116 37 26 47 16 9 21 0 0.073 0.31 147 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), HRAS(2), MAPK1(1), MAPK3(2), MAPK7(1), MEF2A(2), MEF2C(2), MEF2D(2), NTRK1(3), PIK3CA(21), PIK3R1(1), PLCG1(2), RPS6KA1(4), SHC1(1) 5185496 45 40 34 12 20 12 8 3 2 0 0.073 0.31 148 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), IPMK(1), ITPKA(1), ITPKB(3), OCRL(5), PI4KA(4), PI4KB(2), PIK3C3(3), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIP4K2A(2), PIP4K2B(3), PIP4K2C(3), PIP5K1A(4), PIP5K1B(1), PIP5K1C(2), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PLCD3(2), PLCE1(10), PLCG1(2), PLCG2(3), PLCZ1(3), PTEN(11), SYNJ1(2), SYNJ2(5) 20365336 151 93 139 44 53 42 26 11 19 0 0.075 0.31 149 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), ALDOC(1), FBP2(1), GOT1(2), GOT2(3), GPT(1), GPT2(2), MDH1(1), MDH2(1), ME3(2), PGK1(1), PGK2(5), PKLR(3), PKM2(1), RPIA(1), TKT(1), TKTL1(4), TKTL2(9), TPI1(4) 5308138 46 40 42 15 13 17 8 4 4 0 0.075 0.31 150 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(6), LCT(15), SLC33A1(3), ST3GAL1(1), ST3GAL2(2), ST3GAL5(2), ST6GALNAC3(3), ST6GALNAC5(2), ST8SIA1(2) 4440388 37 33 36 15 12 10 7 3 5 0 0.075 0.31 151 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(10), ASH2L(1), CARM1(1), CTCFL(2), DOT1L(5), EED(2), EHMT2(2), EZH1(4), EZH2(3), FBXO11(4), HSF4(1), JMJD6(1), KDM6A(3), MEN1(4), MLL(5), MLL2(36), MLL3(22), MLL4(6), MLL5(4), NSD1(11), OGT(2), PPP1CA(1), PPP1CB(1), PPP1CC(1), PRDM2(6), PRDM9(11), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), RBBP5(1), SATB1(3), SETD1A(6), SETD2(5), SETD8(1), SETDB1(5), SMYD3(1), STK38(4), SUV39H1(1), SUV39H2(2), SUV420H1(1), SUZ12(2), WHSC1(2), WHSC1L1(12) 32840110 202 112 201 60 41 63 39 12 45 2 0.075 0.31 152 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(3), HSD11B1(3), HSD11B2(1), HSD17B1(1), HSD17B12(1), HSD17B7(1), HSD3B1(4), HSD3B2(5), LCMT1(2), LCMT2(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), SRD5A1(2), SRD5A2(2), STS(3), SULT1E1(1), SULT2A1(3), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4), WBSCR22(4) 13001654 105 72 104 17 30 34 21 11 9 0 0.079 0.32 153 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(8), GNAS(4), GNB1(1), PRKACA(1), PRKAR1A(3) 1804742 17 17 17 5 7 5 3 1 1 0 0.081 0.32 154 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), CAT(1), GH1(1), GHR(2), HRAS(2), IGF1(2), IGF1R(1), PIK3CA(21), PIK3R1(1), SHC1(1), SOD2(1) 3592396 34 31 23 6 16 10 6 2 0 0 0.081 0.32 155 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 2 0 2 2 1 4 0 0.082 0.33 156 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(2), CASP9(1), CDC42(1), CHUK(2), H2AFX(1), HRAS(2), MAP2K1(2), MAPK3(2), NFKB1(2), PIK3CA(21), PIK3R1(1), RAC1(2), RAF1(1), RALA(2), RALBP1(1), RALGDS(1), RELA(3) 5225724 48 40 37 9 20 12 7 6 3 0 0.086 0.34 157 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(2), JAK2(3), JUN(2), MAP2K1(2), MAPK3(2), MPL(3), PIK3CA(21), PIK3R1(1), PLCG1(2), PRKCA(5), RAF1(1), RASA1(6), SHC1(1), SOS1(6), STAT1(2), STAT3(1), STAT5A(2), THPO(1) 8070520 66 53 55 10 26 15 13 4 8 0 0.086 0.34 158 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(3), BDKRB2(1), C1QA(2), C1QB(2), C1R(2), C1S(4), C2(1), C3(4), C3AR1(1), C4BPA(1), C5(1), C5AR1(1), C6(14), C7(7), C8A(3), C8B(2), C9(2), CD46(2), CFB(3), CFH(5), CFI(2), CPB2(2), CR1(4), CR2(9), F10(3), F11(4), F12(1), F13A1(3), F13B(7), F2R(2), F3(2), F5(15), F8(10), F9(4), FGA(5), FGB(3), FGG(1), KLKB1(4), KNG1(4), MASP1(10), MASP2(1), MBL2(3), PLAT(1), PLAU(2), PLG(2), SERPINA1(1), SERPINA5(2), SERPINC1(5), SERPIND1(1), SERPINE1(2), SERPINF2(3), VWF(16) 24590700 199 104 198 66 52 71 45 14 17 0 0.087 0.34 159 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(2), DAB1(5), FYN(4), LRP8(1), RELN(26), VLDLR(1) 3755444 39 28 39 11 7 13 10 7 2 0 0.087 0.34 160 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(1), CHUK(2), GH1(1), GHR(2), NFKB1(2), PDPK1(1), PIK3CA(21), PIK3R1(1), RELA(3) 3843198 35 31 24 10 14 9 6 4 2 0 0.091 0.35 161 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(1), CA6(2), CA7(1), CA9(1), CPS1(20), GLS(2), GLUD1(3), GLUL(1) 5026186 41 35 40 4 14 12 10 1 4 0 0.092 0.35 162 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(4), NR0B2(1), NR1H3(2), NR1H4(4), RXRA(1) 1464406 13 13 13 3 4 4 2 1 2 0 0.094 0.36 163 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(8), ARHGEF1(2), F2R(2), F2RL3(2), GNA12(1), GNA13(1), GNAI1(2), GNB1(1), MAP3K7(3), PIK3CA(21), PIK3R1(1), PLCB1(7), PPP1R12B(3), PRKCA(5), ROCK1(5) 7032780 64 51 53 12 24 22 12 4 2 0 0.095 0.36 164 LYSINE_BIOSYNTHESIS AADAT, AASDH, AASDHPPT, AASS, KARS 5 AADAT(1), AASDH(6), AASDHPPT(1), AASS(6), KARS(3) 1862592 17 17 17 4 3 6 4 2 2 0 0.095 0.36 165 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(2), CHRNG(4), MUSK(3), PIK3CA(21), PIK3R1(1), PTK2(3), RAPSN(3), TERT(5) 4523692 43 37 32 13 24 10 6 1 2 0 0.10 0.38 166 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(5), LPL(3), NCOA1(6), NCOA2(10), RXRA(1) 4966378 37 34 36 14 6 16 7 3 5 0 0.10 0.38 167 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(2), JUN(2), KLK2(1), MAP2K1(2), MAPK3(2), MAPK8(2), NGFR(1), PIK3CA(21), PIK3R1(1), PLCG1(2), RAF1(1), SHC1(1), SOS1(6) 5181046 47 40 36 9 21 11 11 3 1 0 0.10 0.38 168 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(2), CERK(3), ENPP7(4), GAL3ST1(1), GALC(2), GLA(2), LCT(15), NEU1(4), NEU2(2), NEU3(2), PPAP2B(2), SGMS1(2), SGMS2(1), SGPP1(2), SMPD1(3), SMPD2(2), SMPD3(3), SMPD4(8), SPHK2(1), SPTLC2(3), UGT8(6) 9827558 73 57 73 22 19 24 14 9 7 0 0.10 0.38 169 NUCLEOTIDE_GPCRS ADORA1, ADORA2A, ADORA2B, ADORA3, GPR23, LTB4R, P2RY1, P2RY2, P2RY5, P2RY6 8 ADORA1(4), ADORA2A(6), ADORA2B(1), P2RY1(1), P2RY2(2), P2RY6(2) 1601110 16 15 16 5 7 7 1 0 1 0 0.11 0.38 170 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(9), FOS(1), HRAS(2), JAK1(1), JUN(2), MAP2K1(2), MAP3K1(3), MAPK3(2), MAPK8(2), PIK3CA(21), PIK3R1(1), PLCG1(2), PRKCA(5), RAF1(1), RASA1(6), SHC1(1), SOS1(6), SRF(2), STAT1(2), STAT3(1), STAT5A(2) 10098296 82 61 70 15 31 23 15 4 9 0 0.11 0.38 171 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(2), JAK1(1), JUN(2), MAP2K1(2), MAP3K1(3), MAPK3(2), MAPK8(2), PDGFRA(8), PIK3CA(21), PIK3R1(1), PLCG1(2), PRKCA(5), RAF1(1), RASA1(6), SHC1(1), SOS1(6), SRF(2), STAT1(2), STAT3(1), STAT5A(2) 9354434 75 58 64 20 31 18 15 5 6 0 0.11 0.38 172 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(3), CADM3(3), CD2(1), CD22(5), CD226(3), CD276(1), CD34(3), CD4(2), CD40(1), CD40LG(2), CD58(1), CD6(1), CD80(2), CD86(1), CD8B(1), CDH1(4), CDH2(8), CDH3(1), CDH4(6), CDH5(2), CLDN1(2), CLDN10(4), CLDN16(4), CLDN17(1), CLDN19(1), CLDN2(1), CLDN22(1), CLDN3(1), CLDN6(1), CLDN8(2), CLDN9(3), CNTN1(9), CNTN2(1), CNTNAP1(7), CNTNAP2(22), ESAM(4), F11R(1), GLG1(3), HLA-A(7), HLA-B(1), HLA-C(1), HLA-DMA(1), HLA-DMB(1), HLA-DQA2(2), HLA-DRA(1), HLA-DRB1(1), HLA-DRB5(2), HLA-G(1), ICAM1(2), ICAM3(2), ICOS(2), ITGA4(5), ITGA6(6), ITGA8(9), ITGA9(1), ITGAL(1), ITGAM(3), ITGAV(3), ITGB1(4), ITGB2(3), ITGB7(1), ITGB8(3), L1CAM(2), MADCAM1(1), MAG(4), MPZ(2), NCAM1(5), NCAM2(11), NEGR1(2), NEO1(6), NFASC(6), NLGN1(5), NLGN2(1), NLGN3(4), NRCAM(4), NRXN1(18), NRXN2(8), NRXN3(9), PTPRC(3), PTPRF(7), PTPRM(6), PVRL1(3), PVRL3(2), SDC2(4), SDC3(1), SELE(4), SELL(2), SELP(8), SELPLG(1), SIGLEC1(7), VCAM1(4), VCAN(16) 40778020 341 127 339 131 99 124 64 20 32 2 0.11 0.40 173 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(4), EGF(6), EGFR(9), HRAS(2), MAP2K1(2), MAPK1(1), MAPK3(2), PTPRB(15), RAF1(1), RASA1(6), SHC1(1), SOS1(6) 6589916 55 42 54 11 15 19 8 3 10 0 0.11 0.41 174 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(2), ADH7(1), ADHFE1(2), AGPAT3(1), AGPAT6(2), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), CEL(5), DAK(1), DGAT2(2), DGKA(6), DGKB(4), DGKD(5), DGKE(2), DGKG(2), DGKI(7), DGKZ(3), GK(4), GK2(5), GLA(2), GPAM(2), LCT(15), LIPA(2), LIPC(1), LIPF(1), LIPG(2), LPL(3), MGLL(1), PNLIP(8), PNLIPRP1(3), PNLIPRP2(2), PNPLA3(1), PPAP2B(2) 15884364 111 80 110 47 34 43 14 12 8 0 0.12 0.41 175 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(6), CYP11A1(2), EDN1(1), EDNRA(2), EDNRB(5), HSD11B1(3), HSD11B2(1), PLA2G4A(5), PRL(1), PTGDR(5), PTGER2(1), PTGER4(2), PTGFR(2), PTGIR(1), PTGS1(2), TBXAS1(5) 5652568 47 39 45 15 9 19 8 3 8 0 0.12 0.42 176 O_GLYCAN_BIOSYNTHESIS GALNT1, GALNT10, GALNT2, GALNT3, GALNT4, GALNT6, GALNT7, GALNT8, GALNT9, GCNT1, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, WBSCR17 14 GALNT1(1), GALNT10(2), GALNT2(4), GALNT3(2), GALNT6(2), GALNT7(1), GALNT8(2), GCNT1(3), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2), WBSCR17(9) 3854234 31 27 29 11 4 14 7 2 4 0 0.12 0.42 177 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(1), CDC42(1), CHP(2), HRAS(2), KDR(11), KRAS(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPKAPK2(1), NFAT5(3), NFATC2(5), NFATC3(3), NFATC4(2), NOS3(1), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLCG1(2), PLCG2(3), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKCA(5), PRKCG(9), PTK2(3), PXN(3), RAC1(2), RAF1(1), SHC2(3), SPHK2(1) 19897018 155 92 144 52 53 48 20 19 15 0 0.12 0.42 178 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 6 DBH(2), GAD1(5), HDC(3), PNMT(2), TH(2), TPH1(1) 1656468 15 14 15 3 3 7 2 1 2 0 0.12 0.42 179 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(4), C5(1), C6(14), C7(7), ICAM1(2), ITGA4(5), ITGAL(1), ITGB1(4), ITGB2(3), SELP(8), SELPLG(1), VCAM1(4) 6722882 54 42 54 13 13 15 12 6 8 0 0.13 0.43 180 HSA00680_METHANE_METABOLISM Genes involved in methane metabolism ADH5, CAT, EPX, LPO, MPO, MTHFR, PRDX6, SHMT1, SHMT2, TPO 10 ADH5(2), CAT(1), EPX(5), LPO(2), MPO(3), MTHFR(2), PRDX6(1), TPO(11) 3156652 27 26 27 10 5 12 8 2 0 0 0.13 0.43 181 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(2), EIF2B3(1), EIF2B5(1), ELAVL1(1), FLT1(9), FLT4(3), HIF1A(1), HRAS(2), KDR(11), NOS3(1), PIK3CA(21), PIK3R1(1), PLCG1(2), PRKCA(5), PTK2(3), PXN(3), SHC1(1), VHL(1) 9270240 71 56 60 23 25 20 11 9 6 0 0.13 0.45 182 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(7), ADCY3(5), ADCY9(4), ARF5(3), ATP6V0A1(4), ATP6V0A2(5), ATP6V0A4(2), ATP6V0D1(1), ATP6V0D2(2), ATP6V1A(3), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4), ERO1L(1), GNAS(4), PDIA4(2), PLCG1(2), PLCG2(3), PRKCA(5), SEC61A1(4), SEC61A2(1), TRIM23(2) 10010542 69 57 69 21 18 24 16 5 6 0 0.14 0.46 183 INOSITOL_METABOLISM ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 5 ALDH6A1(2), ALDOA(1), ALDOB(2), ALDOC(1), TPI1(4) 1036850 10 10 9 3 5 3 2 0 0 0 0.14 0.47 184 HSA00520_NUCLEOTIDE_SUGARS_METABOLISM Genes involved in nucleotide sugars metabolism GALE, GALT, TGDS, UGDH, UGP2, UXS1 6 GALE(1), GALT(1), TGDS(1), UGDH(3), UGP2(5), UXS1(3) 1352088 14 12 14 1 0 7 4 1 2 0 0.15 0.49 185 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), ACTR2(1), AKT1(1), AKT3(2), ARHGEF6(2), ARHGEF7(3), BCAR1(5), BRAF(7), CDC42(1), CDKN2A(23), CSE1L(3), DOCK1(3), EPHB2(5), FYN(4), GRLF1(11), ILK(1), ITGA1(4), ITGA10(6), ITGA11(3), ITGA2(5), ITGA3(2), ITGA4(5), ITGA5(1), ITGA6(6), ITGA7(3), ITGA8(9), ITGA9(1), ITGB3BP(1), MAP3K11(2), MAPK1(1), MAPK10(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(6), MAPK9(1), MRAS(3), MYLK(7), MYLK2(2), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PIK3CA(21), PIK3CB(1), PKLR(3), PLCG1(2), PLCG2(3), PTEN(11), PTK2(3), RAF1(1), RALA(2), ROCK1(5), ROCK2(3), SHC1(1), SOS1(6), SOS2(4), TLN1(8), TLN2(11), VASP(2), WAS(5) 33437656 255 116 239 72 63 93 47 10 42 0 0.15 0.49 186 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(8), ADRB2(3), CFTR(4), GNAS(4), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 3468864 29 26 29 9 10 8 6 2 3 0 0.15 0.49 187 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), DFFA(1), DFFB(2), GZMA(4), GZMB(1), PRF1(2) 2860104 23 22 23 8 7 7 3 2 4 0 0.15 0.49 188 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(6), ABCA10(8), ABCA12(7), ABCA13(27), ABCA2(6), ABCA3(3), ABCA4(12), ABCA5(3), ABCA6(6), ABCA7(4), ABCA8(5), ABCA9(8), ABCB1(14), ABCB10(6), ABCB11(6), ABCB4(9), ABCB5(7), ABCB6(4), ABCB7(2), ABCB8(1), ABCB9(4), ABCC1(4), ABCC10(4), ABCC11(5), ABCC12(12), ABCC2(4), ABCC3(2), ABCC4(1), ABCC5(7), ABCC6(3), ABCC8(5), ABCC9(9), ABCD1(3), ABCD2(10), ABCD4(1), ABCG1(1), ABCG2(1), ABCG4(1), ABCG5(1), ABCG8(8), CFTR(4), TAP1(2) 32453316 236 117 234 85 57 90 49 13 25 2 0.15 0.49 189 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(9), GNA15(1), GNAI1(2), ITPKA(1), ITPKB(3), ITPR1(5), ITPR2(11), ITPR3(3), KCNJ3(8), KCNJ5(2), KCNJ9(2), MAPK1(1), MAPK10(1), MAPK14(1), PHKA2(4), PIK3CA(21), PIK3CD(3), PIK3R1(1), PITX2(3), PTX3(2), RAF1(1) 14631244 108 77 96 25 38 33 23 5 9 0 0.15 0.50 190 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(2), GOT1(2), GOT2(3), TAT(1), TYR(3) 1255434 11 11 10 2 3 6 0 1 1 0 0.15 0.50 191 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(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2), CEL(5), DGKA(6), DGKB(4), DGKD(5), DGKE(2), DGKG(2), DGKZ(3), GK(4), GLA(2), LCT(15), LIPC(1), LIPF(1), LIPG(2), LPL(3), PNLIP(8), PNLIPRP1(3), PNLIPRP2(2), PPAP2B(2) 13024438 89 69 87 38 25 36 12 8 8 0 0.15 0.50 192 METHANE_METABOLISM ADH5, ATP6V0C, SHMT1, CAT, EPX, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, SHMT1, SHMT2, TPO 13 ADH5(2), CAT(1), EPX(5), LPO(2), MPO(3), PRDX1(1), PRDX6(1), TPO(11) 3214324 26 25 26 11 5 10 9 2 0 0 0.16 0.50 193 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(3), IL16(8), IL4(2), LTA(3) 2643656 21 21 21 5 4 7 5 3 2 0 0.16 0.50 194 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(2), AARS2(6), ABAT(3), ACY3(2), ADSL(1), ADSS(1), ADSSL1(1), AGXT2(2), ASL(2), ASNS(3), ASPA(1), ASS1(4), CAD(10), DARS(1), DARS2(5), DDO(2), DLAT(1), DLD(2), GAD1(5), GAD2(5), GOT1(2), GOT2(3), GPT(1), GPT2(2), NARS(3), NARS2(2), PC(4), PDHA1(2), PDHA2(5) 10270600 83 61 80 27 22 37 10 6 8 0 0.16 0.50 195 GLYCOSAMINOGLYCAN_DEGRADATION ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, IDS, IDUA, LCT, NAGLU 11 ARSB(2), GNS(1), GUSB(3), HEXA(6), IDS(1), IDUA(2), LCT(15) 3961034 30 26 30 7 7 8 6 4 5 0 0.16 0.51 196 P27PATHWAY p27 blocks the G1/S transition by inhibiting the checkpoint kinase cdk2/cyclin E and is inhibited by cdk2-mediated ubiquitination. CCNE1, CDK2, CDKN1B, CKS1B, CUL1, E2F1, NEDD8, RB1, RBX1, SKP1A, SKP2, TFDP1, UBE2M 12 CDK2(1), CKS1B(1), CUL1(3), E2F1(3), RB1(7), RBX1(1), SKP2(1), UBE2M(1) 2348354 18 17 18 1 3 7 0 1 7 0 0.17 0.52 197 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(2), IGF1R(1), IRS1(4), MAP2K1(2), MAPK1(1), MAPK3(2), PIK3CA(21), PIK3R1(1), RAF1(1), SHC1(1), SOS1(6) 5084392 43 38 32 5 19 11 10 2 1 0 0.17 0.52 198 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(3), EPX(5), GGT1(2), LPO(2), LTA4H(2), MPO(3), PLA2G2A(1), PLA2G2E(2), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PRDX1(1), PRDX6(1), PTGS1(2), TBXAS1(5), TPO(11) 7586538 62 48 60 26 13 23 17 4 5 0 0.17 0.53 199 N_GLYCAN_DEGRADATION AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 13 AGA(2), FUCA1(1), HEXA(6), LCT(15), MAN2C1(5), MANBA(2), NEU1(4), NEU2(2), NEU3(2) 4555198 39 29 39 11 9 13 10 3 4 0 0.18 0.56 200 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(11), COL4A2(9), COL4A3(5), COL4A4(9), COL4A5(3), COL4A6(9), SLC23A1(1), SLC23A2(4), SLC2A3(4) 6862612 55 44 55 18 18 25 4 1 7 0 0.18 0.56 201 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(6), ADH1B(1), ADH1C(1), ADH4(2), ADH7(1), ADHFE1(2), ALDH3B2(2), AOC2(2), AOC3(3), AOX1(11), DBH(2), DCT(1), DDC(2), FAH(1), GOT1(2), GOT2(3), GSTZ1(2), HPD(3), PNMT(2), TAT(1), TH(2), TPO(11), TYR(3) 8331112 66 52 65 20 18 32 6 8 2 0 0.18 0.57 202 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(3), PIAS3(4), PTPRU(8), REG1A(11) 3829492 37 29 35 7 5 20 7 2 3 0 0.19 0.57 203 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(8), CD3D(1), CD4(2), CREBBP(12), GNAS(4), GNB1(1), HLA-DRA(1), HLA-DRB1(1), LCK(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PTPRC(3), ZAP70(3) 6185678 48 40 48 17 15 18 5 4 6 0 0.20 0.59 204 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(8), CD3D(1), CD4(2), CREBBP(12), GNAS(4), GNB1(1), HLA-DRA(1), HLA-DRB1(1), LCK(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PTPRC(3), ZAP70(3) 6185678 48 40 48 17 15 18 5 4 6 0 0.20 0.59 205 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(2), IFNG(1), IL12A(1), IL12B(3) 802958 7 6 7 1 1 1 2 0 3 0 0.20 0.60 206 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(4), C2(1), C3(4), C5(1), C6(14), C7(7), C8A(3), C9(2) 4840888 42 32 42 14 10 15 8 3 6 0 0.20 0.60 207 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(5), FYN(4), IL2RG(1), IL7R(3), JAK1(1), JAK3(7), LCK(2), NMI(1), PIK3CA(21), PIK3R1(1), STAT5A(2) 7626588 60 48 48 15 19 18 14 4 5 0 0.20 0.60 208 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(3), CD36(1), CD37(2), CD38(1), CD3D(1), CD4(2), CD44(3), CD5(3), CD8B(1), CD9(2), CR1(4), CR2(9), CSF1(2), CSF1R(3), CSF3R(5), DNTT(3), EPOR(2), FCER2(2), FCGR1A(1), FLT3(4), GP5(4), GP9(1), HLA-DRA(1), HLA-DRB1(1), HLA-DRB5(2), IL11RA(2), IL1B(1), IL1R2(3), IL4(2), IL5RA(2), IL6R(1), IL7R(3), ITGA1(4), ITGA2(5), ITGA2B(1), ITGA3(2), ITGA4(5), ITGA5(1), ITGA6(6), ITGAM(3), ITGB3(3), KIT(6), MME(6), MS4A1(3), TFRC(2), THPO(1), TPO(11) 21879404 173 97 173 68 46 76 30 5 16 0 0.20 0.60 209 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(2), CXCR3(1), CXCR4(6), IFNG(1), IFNGR1(3), IFNGR2(1), IL12A(1), IL12B(3), IL12RB1(3), IL12RB2(3), IL18R1(2), IL4(2), TGFB1(1), TGFB2(1) 5101124 38 32 38 16 9 12 9 0 8 0 0.20 0.60 210 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(6), ALDH3B2(2), AOC2(2), AOC3(3), DDC(2), EPX(5), GOT1(2), GOT2(3), HPD(3), LPO(2), MPO(3), PRDX1(1), PRDX6(1), TAT(1), TPO(11) 5946980 47 41 46 20 13 19 11 4 0 0 0.21 0.60 211 HSA00791_ATRAZINE_DEGRADATION Genes involved in atrazine degradation ADAR, APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3F, APOBEC3G, APOBEC4 9 ADAR(7), APOBEC1(6), APOBEC2(1), APOBEC3F(2), APOBEC4(2) 1962984 18 16 18 4 6 6 2 1 3 0 0.21 0.62 212 HSA00430_TAURINE_AND_HYPOTAURINE_METABOLISM Genes involved in taurine and hypotaurine metabolism BAAT, CDO1, CSAD, GAD1, GAD2, GGT1, GGTL3, GGTL4 6 BAAT(3), CSAD(1), GAD1(5), GAD2(5), GGT1(2) 1577970 16 13 16 10 4 7 2 2 1 0 0.22 0.63 213 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(14), GNA12(1), PRKACB(2), PRKACG(1), PRKAR2B(3) 2728562 21 20 21 9 4 11 3 2 1 0 0.22 0.64 214 SA_DIACYLGLYCEROL_SIGNALING DAG (diacylglycerol) signaling activity ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP 10 ESR1(6), ESR2(1), ITPKA(1), PDE1A(2), PDE1B(1), PLCB1(7), PLCB2(5), PRL(1), VIP(2) 3042376 26 23 26 8 10 10 3 2 1 0 0.22 0.64 215 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(4), HRAS(2), JUN(2), LAT(1), LCK(2), MAP2K1(2), MAP3K1(3), MAPK3(2), MAPK8(2), NFATC2(5), NFATC3(3), NFATC4(2), NFKB1(2), PIK3CA(21), PIK3R1(1), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKCA(5), RAC1(2), RAF1(1), RASA1(6), RELA(3), SHC1(1), SOS1(6), SYT1(3), VAV1(7), ZAP70(3) 12961782 104 70 93 20 37 28 17 13 9 0 0.23 0.65 216 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(2), ADCY1(8), CAP1(1), CCNB1(1), CDC25C(1), GNAI1(2), GNAS(4), GNB1(1), HRAS(2), MAPK1(1), MAPK3(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), RPS6KA1(4) 5515508 39 36 39 14 11 14 7 5 2 0 0.23 0.65 217 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(2), CD80(2), HLA-DRA(1), HLA-DRB1(1), IL10(1), IL4(2) 1077612 9 9 9 2 1 3 2 1 2 0 0.23 0.66 218 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(6), ADC(1), ALDH18A1(4), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), AMD1(1), AOC2(2), AOC3(3), ARG1(2), ASL(2), ASS1(4), CPS1(20), GATM(1), NAGS(1), ODC1(1), OTC(2), SMS(4) 8031894 62 49 59 15 20 24 10 3 5 0 0.23 0.66 219 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(7), ACTR2(1), AKT1(1), CDC42(1), CFL1(3), CFL2(1), FLNA(9), FLNC(13), FSCN3(1), GDI1(2), GDI2(1), LIMK1(1), MYH2(22), MYLK(7), MYLK2(2), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), ROCK1(5), ROCK2(3), VASP(2), WASL(2) 13114684 98 69 98 34 22 45 15 6 10 0 0.23 0.66 220 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(2) 2341056 18 16 18 6 2 4 3 3 4 2 0.24 0.67 221 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(4), GNB1(1), NFKB1(2), NOS3(1), PIK3CA(21), PIK3R1(1), RELA(3), SYT1(3) 4937720 40 34 29 12 18 8 9 4 1 0 0.24 0.68 222 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(2), ABAT(3), ADSL(1), ADSS(1), AGXT2(2), ASL(2), ASNS(3), ASPA(1), CAD(10), DARS(1), DDO(2), GAD1(5), GAD2(5), GOT1(2), GOT2(3), GPT(1), GPT2(2), NARS(3), PC(4) 7056632 53 43 52 20 12 26 7 3 5 0 0.26 0.72 223 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(2), CARS(6), DARS(1), EPRS(11), FARS2(1), GARS(1), HARS(2), IARS(3), KARS(3), LARS2(5), MARS(1), NARS(3), RARS(4), SARS(2), TARS(3), WARS(4), WARS2(1), YARS(1) 8565716 54 50 54 18 9 21 17 2 5 0 0.27 0.74 224 HSA00750_VITAMIN_B6_METABOLISM Genes involved in vitamin B6 metabolism AOX1, PDXK, PDXP, PNPO, PSAT1 5 AOX1(11), PDXP(1) 1306342 12 11 12 2 2 5 2 3 0 0 0.27 0.75 225 HSA00591_LINOLEIC_ACID_METABOLISM Genes involved in linoleic acid metabolism AKR1B10, ALOX15, ALOX5, CYP1A2, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2E1, CYP2J2, CYP3A4, CYP3A43, CYP3A5, CYP3A7, HSD3B7, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, RDH11, RDH12, RDH13, RDH14 31 AKR1B10(1), ALOX15(2), CYP1A2(1), CYP2C19(6), CYP2C8(3), CYP2C9(2), CYP2E1(1), CYP2J2(2), CYP3A4(1), CYP3A43(3), CYP3A7(1), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), RDH11(2), RDH12(2), RDH13(1) 6442710 48 40 48 16 16 13 8 4 7 0 0.27 0.75 226 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), ALDOC(1), DLAT(1), DLD(2), ENO2(2), ENO3(1), FBP2(1), G6PC(2), GAPDH(3), GAPDHS(2), GCK(1), GOT1(2), GOT2(3), GPI(5), HK1(4), HK2(6), HK3(7), LDHAL6B(1), LDHB(2), LDHC(1), MDH1(1), MDH2(1), PC(4), PCK1(3), PDHA1(2), PDHA2(5), PFKL(2), PFKM(5), PFKP(2), PGAM2(1), PGK1(1), PGK2(5), PKLR(3), PKM2(1), TPI1(4) 11286268 90 64 87 27 28 38 10 5 9 0 0.28 0.76 227 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(7), CCND2(3), DAZL(1), DMC1(1), EGR1(4), ESR2(1), FSHR(12), INHA(3), LHCGR(8), MLH1(3), MSH5(5), NCOR1(4), NRIP1(3), PGR(3), PRLR(5), PTGER2(1), SMPD1(3), VDR(3), ZP2(2) 9486510 72 54 70 28 27 21 9 7 8 0 0.28 0.76 228 HSA00300_LYSINE_BIOSYNTHESIS Genes involved in lysine biosynthesis AADAT, AASDHPPT, AASS, KARS 4 AADAT(1), AASDHPPT(1), AASS(6), KARS(3) 1265758 11 11 11 3 3 4 3 0 1 0 0.28 0.76 229 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 0.28 0.76 230 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 8 CARS(6), GOT1(2), GOT2(3), LDHB(2), LDHC(1) 1840164 14 13 13 2 1 6 3 2 2 0 0.28 0.76 231 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(2), GLI2(5), GLI3(6), GSK3B(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), SMO(1), SUFU(3) 4465486 31 29 31 15 5 16 4 3 3 0 0.29 0.77 232 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(14), ABCB11(6), ABCB4(9), ABCC1(4), ABCC3(2) 3890190 35 27 35 9 13 10 7 2 1 2 0.29 0.78 233 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(8), ALG2(2), ALG6(3), B3GALT6(1), B3GNT2(1), B3GNT6(1), B3GNT7(2), B4GALT1(1), B4GALT3(2), B4GALT4(1), B4GALT5(3), C1GALT1C1(1), CHPF(1), CHST1(2), CHST11(1), CHST12(1), CHST14(1), CHST2(4), CHST3(2), CHST4(2), CHST6(3), EXT1(2), EXT2(1), EXTL1(2), EXTL3(1), FUT8(2), GALNT1(1), GALNT10(2), GALNT11(2), GALNT12(3), GALNT13(11), GALNT14(4), GALNT2(4), GALNT3(2), GALNT5(6), GALNT6(2), GALNT7(1), GALNT8(2), GALNTL1(3), GALNTL2(1), GALNTL4(4), GALNTL5(3), GANAB(5), GCNT1(3), GCNT3(3), HS3ST2(1), HS3ST5(4), HS6ST1(2), HS6ST3(2), MAN1A1(3), MAN1A2(4), MAN1C1(3), MAN2A1(4), MGAT1(1), MGAT2(2), MGAT3(4), MGAT4A(2), MGAT4B(1), MGAT5(3), MGAT5B(4), NDST1(3), NDST2(1), NDST3(4), NDST4(11), OGT(2), RPN1(1), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2), ST6GAL1(1), ST6GALNAC1(6), STT3B(1), WBSCR17(9), XYLT1(4) 30285098 207 114 204 86 44 90 34 20 19 0 0.29 0.78 234 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 2 FAH(1), GSTZ1(2) 353152 3 3 3 0 1 0 0 1 1 0 0.30 0.78 235 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(2), MAPK8(2), MAPK8IP1(2), MAPK8IP3(6), MAPK9(1), MAPKAPK5(4), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), PIK3CA(21), PIK3CD(3), PIK3R1(1), SYT1(3), TRAF3(1), TRAF5(2), TRAF6(1) 9355680 66 53 55 13 26 19 8 7 6 0 0.30 0.78 236 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(5), CMAS(2), CTBS(4), CYB5R1(2), GFPT2(1), GNE(4), GNPDA2(3), HEXA(6), HK1(4), HK2(6), HK3(7), MTMR1(1), MTMR2(1), MTMR6(3), NANS(1), UAP1(1) 7756350 57 45 57 17 14 24 7 3 9 0 0.30 0.78 237 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), GALE(1), GALK2(1), GALT(1), GANAB(5), GCK(1), GLA(2), HK1(4), HK2(6), HK3(7), LCT(15), MGAM(5), PFKM(5), PFKP(2), PGM1(1) 8911570 60 52 59 24 21 23 5 7 4 0 0.31 0.79 238 ALKALOID_BIOSYNTHESIS_II ABP1, AOC2, AOC3, CES1, ESD 5 ABP1(6), AOC2(2), AOC3(3), CES1(2) 1611612 13 12 13 8 4 5 2 2 0 0 0.31 0.81 239 SIG_CHEMOTAXIS Genes related to chemotaxis ACTR2, ACTR3, AKT1, AKT2, AKT3, ANGPTL2, ARHGAP1, ARHGAP4, ARHGEF11, BTK, CDC42, CFL1, CFL2, GDI1, GDI2, INPPL1, ITPR1, ITPR2, ITPR3, LIMK1, MYLK, MYLK2, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDK1, PIK3CA, PIK3CD, PIK3CG, PIK3R1, PITX2, PPP1R13B, PTEN, RACGAP1, RHO, ROCK1, ROCK2, RPS4X, SAG, WASF1, WASL 44 ACTR2(1), AKT1(1), AKT3(2), ARHGAP1(1), ARHGAP4(1), ARHGEF11(7), BTK(5), CDC42(1), CFL1(3), CFL2(1), GDI1(2), GDI2(1), INPPL1(3), ITPR1(5), ITPR2(11), ITPR3(3), LIMK1(1), MYLK(7), MYLK2(2), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PDK1(1), PIK3CA(21), PIK3CD(3), PIK3CG(10), PIK3R1(1), PITX2(3), PPP1R13B(4), PTEN(11), RACGAP1(1), ROCK1(5), ROCK2(3), WASL(2) 19220618 137 84 125 45 40 41 24 11 21 0 0.32 0.82 240 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT1(2), GOT2(3), TAT(1) 702744 6 6 5 2 2 3 0 1 0 0 0.32 0.82 241 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(3), ABP1(6), ACADL(2), ACADM(1), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2), AOC2(2), AOC3(3), CNDP1(3), DPYD(7), DPYS(4), EHHADH(1), GAD1(5), GAD2(5), HADHA(2), MLYCD(2), SDS(2), SMS(4) 7843214 63 46 62 25 15 28 9 5 6 0 0.32 0.83 242 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(4), PFKL(2), PGK1(1), PKLR(3), TPI1(4) 2381818 21 17 20 4 8 6 4 0 3 0 0.33 0.83 243 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(5), ACVR1B(3), ACVR1C(3), CDC42(1), CDH1(4), CREBBP(12), CSNK2A1(2), CTNNA2(17), CTNNA3(11), CTNNB1(3), CTNND1(4), EGFR(9), EP300(5), ERBB2(3), FARP2(6), FER(2), FGFR1(3), FYN(4), IGF1R(1), INSR(7), IQGAP1(6), LEF1(3), LMO7(7), MAP3K7(3), MAPK1(1), MAPK3(2), MET(3), MLLT4(3), NLK(2), PARD3(5), PTPN1(1), PTPRB(15), PTPRF(7), PTPRJ(3), PTPRM(6), PVRL1(3), PVRL3(2), PVRL4(5), RAC1(2), SMAD2(2), SMAD4(2), SNAI1(3), SNAI2(2), SORBS1(5), SSX2IP(1), TCF7(1), TGFBR2(3), TJP1(9), VCL(2), WAS(5), WASF3(1), WASL(2), YES1(1) 32265170 235 111 233 77 48 89 51 21 26 0 0.33 0.83 244 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(4), PTPRU(8), REG1A(11), STAT3(1) 4228924 36 29 34 7 6 19 6 2 3 0 0.33 0.84 245 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(3) 1445894 10 10 10 4 1 6 2 0 1 0 0.34 0.84 246 GPCRDB_CLASS_A_RHODOPSIN_LIKE2 CYSLTR1, CYSLTR2, GPR109B, GPR161, GPR171, GPR18, GPR34, GPR39, GPR41, GPR42, GPR45, GPR65, GPR68, GPR75, GPR81, LYPDC1 13 CYSLTR1(3), CYSLTR2(1), GPR109B(3), GPR161(2), GPR171(2), GPR18(1), GPR34(1), GPR39(1), GPR45(4), GPR65(1), GPR68(1), GPR75(2) 2642232 22 19 22 8 8 9 4 0 1 0 0.34 0.84 247 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(2), FUCA1(1), GNS(1), GUSB(3), HEXA(6), HGSNAT(2), HPSE(3), HPSE2(4), HYAL1(4), IDS(1), IDUA(2), LCT(15), MAN2B1(1), MAN2B2(3), MAN2C1(5), MANBA(2), NEU1(4), NEU2(2), NEU3(2), SPAM1(3) 9523534 68 48 67 19 12 26 17 4 9 0 0.34 0.86 248 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(3), CRY2(2), EIF4G2(4), ETV6(4), GSTM3(1), HERPUD1(2), HSPA8(3), IDI1(1), KLF9(1), MYF6(1), NCKAP1(5), PER1(6), PER2(3), PIGF(1), PPP1R3C(2), PSMA4(1), PURA(1), SF3A3(1), UCP3(3), UGP2(5), VAPA(1), ZFR(4) 9949310 64 53 64 15 11 22 17 4 10 0 0.35 0.86 249 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(2), SERPINB2(3), SERPINE1(2) 3573172 26 24 25 9 3 13 8 0 2 0 0.35 0.86 250 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP1(1), ACPT(2), ENPP1(7), ENPP3(4), FLAD1(2), TYR(3) 2593104 19 18 19 5 5 10 2 0 2 0 0.35 0.86 251 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(5), CD19(2), DAG1(1), EPHB2(5), ITPKA(1), ITPKB(3), LYN(1), MAP2K1(2), MAP2K2(2), MAPK1(1), NFAT5(3), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), PI3(1), PIK3CA(21), PIK3CD(3), PIK3R1(1), PLCG2(3), PPP1R13B(4), RAF1(1), SERPINA4(4), SHC1(1), SOS1(6), SOS2(4), SYK(1), VAV1(7) 14332916 99 69 88 32 30 29 20 9 11 0 0.36 0.87 252 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(4), ACACB(8), AKT1(1), AKT3(2), ARAF(3), BRAF(7), CBL(4), CBLB(4), CRKL(1), EXOC7(2), FBP2(1), FLOT1(2), G6PC(2), G6PC2(2), GCK(1), GSK3B(1), GYS1(1), GYS2(3), HRAS(2), IKBKB(3), INPP5D(6), INSR(7), IRS1(4), IRS2(2), IRS4(3), KRAS(1), LIPE(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK10(1), MAPK3(2), MAPK8(2), MAPK9(1), PCK1(3), PCK2(1), PDE3A(5), PDE3B(3), PDPK1(1), PFKL(2), PFKM(5), PFKP(2), PHKA1(4), PHKA2(4), PHKB(6), PHKG1(2), PHKG2(1), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PKLR(3), PKM2(1), PPARGC1A(5), PPP1CA(1), PPP1CB(1), PPP1CC(1), PPP1R3A(12), PPP1R3C(2), PPP1R3D(2), PRKAA2(2), PRKAB2(1), PRKACA(1), PRKACB(2), PRKACG(1), PRKAG2(4), PRKAG3(2), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCI(4), PRKX(1), PTPN1(1), PTPRF(7), PYGB(2), PYGM(6), RAF1(1), RAPGEF1(3), RHEB(1), RPS6(1), RPS6KB1(1), SHC1(1), SHC2(3), SHC3(3), SHC4(4), SLC2A4(2), SOCS2(1), SORBS1(5), SOS1(6), SOS2(4), SREBF1(3), TRIP10(2), TSC1(6), TSC2(6) 44062120 294 125 282 102 81 113 52 16 32 0 0.36 0.87 253 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(5), CD19(2), CD22(5), CD81(1), CR2(9), DAG1(1), FLOT1(2), GSK3A(4), GSK3B(1), INPP5D(6), ITPR1(5), ITPR2(11), ITPR3(3), LYN(1), MAP4K1(2), MAPK1(1), MAPK3(2), NFATC2(5), NR0B2(1), PDK1(1), PIK3CA(21), PIK3CD(3), PIK3R1(1), PLCG2(3), PPP1R13B(4), PPP3CA(2), PPP3CB(5), PPP3CC(2), PTPRC(3), RAF1(1), SHC1(1), SOS1(6), SOS2(4), SYK(1), VAV1(7) 20172206 137 84 126 46 45 39 23 12 18 0 0.36 0.87 254 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(8), GNAS(4), GNB1(1), PRKAA2(2), PRKAB2(1), PRKACB(2), PRKACG(1), PRKAG2(4), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 4084922 30 26 30 8 10 10 5 2 3 0 0.36 0.87 255 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(2), BMP5(5), BMP7(1), BTRC(1), CSNK1A1(1), CSNK1A1L(5), CSNK1G1(2), DHH(1), GLI1(3), GLI2(5), GLI3(6), GSK3B(1), HHIP(1), IHH(1), LRP2(39), PRKACA(1), PRKACB(2), PRKACG(1), PRKX(1), PTCH1(6), PTCH2(6), SMO(1), STK36(3), SUFU(3), WNT10B(2), WNT11(2), WNT2(3), WNT2B(2), WNT3(2), WNT3A(1), WNT5A(1), WNT5B(1), WNT6(2), WNT7A(2), WNT7B(1), WNT9A(1), WNT9B(2) 16809964 120 79 120 46 38 34 21 15 12 0 0.36 0.87 256 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(4), AGT(1), AGTR1(3), AGTR2(4), BDKRB2(1), KNG1(4), NOS3(1) 2766476 18 18 18 11 4 7 4 1 2 0 0.36 0.87 257 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 GH1(1), GHR(2), HRAS(2), INSR(7), IRS1(4), JAK2(3), MAP2K1(2), MAPK1(1), MAPK3(2), PIK3CA(21), PIK3R1(1), PLCG1(2), PRKCA(5), RAF1(1), RPS6KA1(4), SHC1(1), SLC2A4(2), SOS1(6), SRF(2), STAT5A(2) 8934888 71 53 60 16 23 24 16 4 4 0 0.36 0.87 258 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(5), ESR1(6), MAPK1(1), MAPK3(2), PELP1(1) 4039354 27 26 26 6 6 10 6 2 3 0 0.37 0.88 259 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(2), EGR1(4), HRAS(2), KLK2(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), NGFR(1), RAF1(1) 2270034 18 16 17 4 5 9 2 1 1 0 0.37 0.88 260 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 AKR1B10(1), B4GALT1(1), G6PC(2), G6PC2(2), GALE(1), GALK2(1), GALT(1), GANC(3), GCK(1), GLA(2), HK1(4), HK2(6), HK3(7), LCT(15), MGAM(5), PFKL(2), PFKM(5), PFKP(2), PGM1(1), RDH11(2), RDH12(2), RDH13(1), UGP2(5) 10583880 72 59 71 25 26 24 7 9 6 0 0.37 0.88 261 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), BTRC(1), CCND1(1), CREBBP(12), CSNK1A1(1), CSNK2A1(2), CTBP1(1), CTNNB1(3), DVL1(3), FZD1(1), GSK3B(1), HDAC1(2), MAP3K7(3), MYC(1), NLK(2), PPARD(2), TLE1(4), WIF1(4) 7875610 53 46 53 11 10 20 10 5 8 0 0.37 0.88 262 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(2), DDC(2), GAD1(5), GAD2(5), HDC(3), PAH(1), PNMT(2), TH(2), TPH1(1) 3978300 27 25 27 11 9 11 4 1 2 0 0.37 0.88 263 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(6), LCT(15), MAN2B1(1), MAN2B2(3), MAN2C1(5), MANBA(2), NEU1(4), NEU2(2), NEU3(2) 5600236 43 31 43 14 9 16 11 3 4 0 0.37 0.88 264 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(2), CD8B(1), CIITA(4), CTSL1(2), CTSS(2), HLA-A(7), HLA-B(1), HLA-C(1), HLA-DMA(1), HLA-DMB(1), HLA-DQA2(2), HLA-DRA(1), HLA-DRB1(1), HLA-DRB5(2), HLA-G(1), HSP90AB1(2), HSPA5(2), IFNA1(1), IFNA10(1), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), KIR2DL1(3), KIR2DL3(4), KIR2DS4(5), KIR3DL1(6), KIR3DL2(1), KIR3DL3(1), KLRC1(1), KLRC3(1), LGMN(1), LTA(3), NFYB(1), PSME1(1), PSME2(1), RFX5(1), RFXAP(1), TAP1(2), TAPBP(3) 12697808 82 57 81 33 10 25 22 8 15 2 0.38 0.88 265 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(2), MMP14(3), MMP2(4), MMP9(6), RECK(3), TIMP2(1) 2030980 19 14 19 4 3 10 3 2 1 0 0.38 0.88 266 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 DIAPH1(1), FYN(4), GSN(2), HRAS(2), ITGA1(4), ITGB1(4), MAP2K1(2), MAPK1(1), MAPK3(2), MYL2(1), MYLK(7), PIK3CA(21), PIK3R1(1), PTK2(3), PXN(3), RAF1(1), ROCK1(5), SHC1(1), TLN1(8) 10127488 73 57 61 17 23 23 14 9 4 0 0.38 0.89 267 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(5), FCER1A(1), FOS(1), HRAS(2), JUN(2), LYN(1), MAP2K1(2), MAP3K1(3), MAPK1(1), MAPK3(2), MAPK8(2), NFATC2(5), NFATC3(3), NFATC4(2), PAK2(1), PIK3CA(21), PIK3R1(1), PLA2G4A(5), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), RAF1(1), SHC1(1), SOS1(6), SYK(1), SYT1(3), VAV1(7) 11633724 90 64 79 30 33 23 17 11 6 0 0.39 0.89 268 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(3), IL12RB1(3), IL12RB2(3), IL18R1(2), IL4(2) 3417422 22 20 22 11 3 7 6 0 6 0 0.39 0.90 269 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(2), JUN(2), LYN(1), MAP2K1(2), MAP3K1(3), MAPK1(1), MAPK3(2), MAPK8IP3(6), PAPPA(8), RAC1(2), RPS6KA1(4), RPS6KA3(1), SHC1(1), SOS1(6), SYK(1), VAV1(7), VAV2(4), VAV3(1) 8747988 59 49 59 14 14 19 15 6 5 0 0.39 0.90 270 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 CCNA1(1), CDK2(1), CUL1(3), E2F1(3), RB1(7), SKP2(1) 2358678 16 15 16 1 3 7 0 0 6 0 0.40 0.90 271 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(3), PXN(3), VCL(2) 5688346 43 34 43 29 11 19 6 6 1 0 0.40 0.90 272 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(2), B4GALT1(1), B4GALT3(2), B4GALT4(1), CHST1(2), CHST2(4), CHST4(2), CHST6(3), FUT8(2), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2) 3427212 25 23 24 16 9 10 4 2 0 0 0.40 0.90 273 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(9), ERBB3(3), NRG1(4), UBE2D1(1) 2762204 23 18 22 5 6 8 3 2 4 0 0.40 0.90 274 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 0.40 0.90 275 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 1 1 1 1 1 0 0 0.41 0.92 276 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 0.42 0.95 277 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(3), ABP1(6), ACADM(1), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), AOC2(2), AOC3(3), CNDP1(3), DPYD(7), DPYS(4), EHHADH(1), GAD1(5), GAD2(5), HADHA(2), HIBCH(1), MLYCD(2), SMS(4) 7313308 57 42 57 24 16 24 7 5 5 0 0.43 0.95 278 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(3), DNM1(1), EPN1(3), EPS15(4), PICALM(3), PPP3CA(2), PPP3CB(5), PPP3CC(2), SYNJ1(2), SYNJ2(5), SYT1(3) 6051110 40 36 40 11 10 12 6 5 7 0 0.43 0.95 279 AMINOSUGARS_METABOLISM CMAS, CYB5R3, GCK, GFPT1, GNE, GNPDA1, GNPDA2, HEXA, HEXB, HK1, HK2, HK3, PGM3, RENBP, UAP1 15 CMAS(2), GCK(1), GNE(4), GNPDA2(3), HEXA(6), HK1(4), HK2(6), HK3(7), UAP1(1) 4584390 34 30 34 9 8 16 3 3 4 0 0.43 0.95 280 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 5 CDK5(2), GRIA2(3), PPP1R1B(1) 1061414 6 6 6 6 0 2 1 0 3 0 0.43 0.95 281 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(5), GNAI1(2), ITPR1(5), ITPR2(11), ITPR3(3), KCNJ3(8), KCNJ5(2), KCNJ9(2), MAPK1(1), PITX2(3), PTX3(2), RAC1(2), RYR1(29) 12603824 88 64 88 22 23 34 16 6 9 0 0.44 0.95 282 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), ACVR2B(1), ACVRL1(3), AMHR2(4), BMP4(2), BMP5(5), BMP7(1), BMPR1A(3), CHRD(2), COMP(2), CREBBP(12), CUL1(3), DCN(1), EP300(5), GDF5(4), GDF6(2), ID4(1), IFNG(1), INHBA(4), INHBC(1), LEFTY2(2), LTBP1(10), MAPK1(1), MAPK3(2), MYC(1), NODAL(3), PITX2(3), PPP2R1A(6), PPP2R1B(2), PPP2R2A(1), PPP2R2B(2), PPP2R2C(2), RBL1(6), RBL2(5), RBX1(1), ROCK1(5), ROCK2(3), RPS6KB1(1), SKP1(1), SMAD1(3), SMAD2(2), SMAD4(2), SMAD7(1), SMURF1(4), SMURF2(1), SP1(1), TGFB1(1), TGFB2(1), TGFBR2(3), THBS1(1), THBS2(12), THBS3(4), ZFYVE16(3), ZFYVE9(5) 27101212 167 98 165 53 28 62 35 19 23 0 0.44 0.96 283 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(5), CAMK2B(2), CAMK2D(1), CLCA1(6), CLCA2(3), CLCA4(2), CNGA3(3), CNGA4(5), CNGB1(5), GNAL(2), GUCA1A(2), PDE1C(12), PRKACA(1), PRKACB(2), PRKACG(1), PRKG1(5), PRKG2(5), PRKX(1) 8251724 63 47 63 14 23 22 5 5 8 0 0.44 0.96 284 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 ALAS1(2), BLVRA(2), COX10(1), CP(3), CPOX(3), EARS2(2), EPRS(11), FECH(2), FTH1(4), FTMT(4), GUSB(3), HMBS(2), HMOX1(1), MMAB(1), PPOX(1), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4), UROD(1) 10816526 76 58 76 15 17 31 17 5 6 0 0.44 0.96 285 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(3), CDK7(1), CHEK1(4), NEK1(3), WEE1(2) 1979716 13 13 13 1 3 7 2 0 1 0 0.45 0.97 286 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(3), CRY2(2), PER1(6) 2337496 18 16 18 3 2 7 7 1 1 0 0.45 0.97 287 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(3), GNAS(4), GNB1(1), HRAS(2), LIMK1(1), MAP2K1(2), MAPK1(1), MAPK3(2), MYL2(1), NOX1(2), PIK3C2G(7), PLCB1(7), PPP1R12B(3), PRKCA(5), PTK2(3), RAF1(1), ROCK2(3) 6923488 49 41 49 18 15 20 7 3 4 0 0.45 0.97 288 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 8 9 4 5 2 0 0.46 0.98 289 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(5), ASCC3(9), ATP13A2(1), DDX18(2), DDX19A(2), DDX23(6), DDX4(1), DDX41(2), DDX50(1), DDX52(1), DDX54(3), DDX55(1), DDX56(1), ENPP1(7), ENPP3(4), ENTPD7(1), ERCC2(3), ERCC3(2), G6PC(2), G6PC2(2), GANC(3), GBA3(6), GBE1(1), GCK(1), GPI(5), GUSB(3), GYS1(1), GYS2(3), HK1(4), HK2(6), HK3(7), IFIH1(3), MGAM(5), NUDT8(1), PGM1(1), PYGB(2), PYGM(6), RAD54L(1), SETX(11), SI(33), SKIV2L2(2), SMARCA2(3), TREH(1), UGDH(3), UGP2(5), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4), UXS1(3) 33165672 214 107 213 58 61 82 43 12 16 0 0.46 0.98 290 HSA00232_CAFFEINE_METABOLISM Genes involved in caffeine metabolism CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH 7 CYP1A2(1), CYP2A13(2), CYP2A6(3), NAT2(1), XDH(9) 2131550 16 14 16 7 4 8 1 1 2 0 0.47 0.99 291 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 0.47 0.99 292 RANPATHWAY RanGEF (aka RCC1) and RanGFP regulate the GTP- or GDP-bound state of Ran, creating a Ran gradient across the nuclear membrane that is used in nuclear import. CHC1, RAN, RANBP1, RANBP2, RANGAP1 4 RAN(2), RANBP2(12), RANGAP1(4) 2248318 18 16 17 7 3 8 3 2 2 0 0.47 1.00 293 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(3), XDH(9) 2705600 20 16 20 4 5 6 2 4 3 0 0.47 1.00 294 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(2), HLA-DRA(1), HLA-DRB1(1) 650412 4 4 4 1 1 1 0 0 2 0 0.48 1.00 295 GANGLIOSIDE_BIOSYNTHESIS B3GALT4, GALGT, SIAT4A, SIAT4B, SIAT7B, SIAT7D, SIAT9, ST3GAL1, ST3GAL2, ST3GAL4, ST3GAL5, ST6GALNAC2, ST6GALNAC4, ST8SIA1 8 B3GALT4(1), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2), ST3GAL5(2), ST8SIA1(2) 1506770 10 10 9 7 2 4 3 0 1 0 0.48 1.00 296 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALE(1), GALT(1), TGDS(1), UGDH(3), UXS1(3) 1073162 9 7 9 1 0 5 2 1 1 0 0.48 1.00 297 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 7 FUT3(3), FUT5(4), FUT6(2) 1397656 9 8 9 3 2 3 3 1 0 0 0.49 1.00 298 CYANOAMINO_ACID_METABOLISM ATP6V0C, SHMT1, GBA3, GGT1, SHMT1, SHMT2 5 GBA3(6), GGT1(2) 1181208 8 7 8 7 1 2 3 1 1 0 0.49 1.00 299 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(6), AKT1(1), AKT3(2), ARAF(3), AREG(2), BRAF(7), CAMK2B(2), CAMK2D(1), CBL(4), CBLB(4), CRKL(1), EGF(6), EGFR(9), ERBB2(3), ERBB3(3), ERBB4(9), EREG(1), GAB1(2), GSK3B(1), HBEGF(1), HRAS(2), JUN(2), KRAS(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK10(1), MAPK3(2), MAPK8(2), MAPK9(1), MYC(1), NCK1(3), NRG1(4), NRG2(2), NRG3(5), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLCG1(2), PLCG2(3), PRKCA(5), PRKCG(9), PTK2(3), RAF1(1), RPS6KB1(1), SHC1(1), SHC2(3), SHC3(3), SHC4(4), SOS1(6), SOS2(4), STAT5A(2), TGFA(1) 28169390 207 103 195 70 63 72 36 13 23 0 0.49 1.00 300 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(4), CREBBP(12), EP300(5), MAP2K1(2), MAP3K7(3), MAPK3(2), TGFB1(1), TGFB2(1), TGFBR2(3) 6897500 42 38 41 11 8 15 10 3 6 0 0.49 1.00 301 GLOBOSIDE_METABOLISM A4GALT, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, ST8SIA1 13 FUT9(1), GBGT1(3), GLA(2), HEXA(6), NAGA(1), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2), ST8SIA1(2) 2748498 20 17 19 7 2 11 4 2 1 0 0.49 1.00 302 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), GABARAP(1), IFNA1(1), IFNA10(1), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNG(1), PIK3C3(3), PIK3R4(6), PRKAA2(2), ULK1(1), ULK2(3) 5718962 34 31 34 10 10 9 11 1 3 0 0.49 1.00 303 ACETYLCHOLINE_SYNTHESIS ACHE, CHAT, CHKA, PCYT1A, PDHA1, PDHA2, PEMT, SLC18A3 8 ACHE(2), CHAT(2), CHKA(2), PCYT1A(2), PDHA1(2), PDHA2(5) 1926672 15 14 15 4 4 7 3 1 0 0 0.50 1.00 304 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 NRF1(1), UBE2A(2), UBE2C(1), UBE2D1(1), UBE2D2(1), UBE2E3(1), UBE2G2(1), UBE2J1(3), UBE2J2(2), UBE2L6(1), UBE2M(1), UBE3A(4) 2847644 19 18 19 4 6 7 2 1 3 0 0.50 1.00 305 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(6), ACAT1(1), ACMSD(1), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2), AOC2(2), AOC3(3), AOX1(11), CAT(1), CYP19A1(3), CYP1A1(7), CYP1A2(1), CYP2A13(2), CYP2A6(3), CYP2B6(3), CYP2C19(6), CYP2C8(3), CYP2C9(2), CYP2D6(3), CYP2E1(1), CYP2F1(4), CYP2J2(2), CYP3A4(1), CYP3A7(1), CYP4B1(3), CYP4F8(1), DDC(2), EHHADH(1), GCDH(1), HAAO(2), HADHA(2), KMO(3), KYNU(3), SDS(2), TDO2(1), TPH1(1), WARS(4), WARS2(1) 14696748 105 73 104 48 27 42 20 8 8 0 0.50 1.00 306 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(8), ADCY2(16), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), CAMK2B(2), CAMK2D(1), CREB3(2), CREB3L2(2), CREB3L3(1), CREB3L4(2), CREBBP(12), CTNNB1(3), DCT(1), DVL1(3), DVL3(3), EDN1(1), EDNRB(5), EP300(5), FZD1(1), FZD10(2), FZD3(4), FZD4(1), FZD6(1), FZD9(3), GNAI1(2), GNAI3(1), GNAS(4), GSK3B(1), HRAS(2), KIT(6), KRAS(1), LEF1(3), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), POMC(2), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCG(9), PRKX(1), RAF1(1), TCF7(1), TYR(3), TYRP1(2), WNT10B(2), WNT11(2), WNT2(3), WNT2B(2), WNT3(2), WNT3A(1), WNT5A(1), WNT5B(1), WNT6(2), WNT7A(2), WNT7B(1), WNT9A(1), WNT9B(2) 29895100 209 103 208 72 65 75 32 21 16 0 0.51 1.00 307 BETAOXIDATIONPATHWAY Beta-Oxidation of Fatty Acids ACADL, ACADM, ACADS, ACAT1, ECHS1, HADHA 6 ACADL(2), ACADM(1), ACADS(3), ACAT1(1), HADHA(2) 1468678 9 9 9 2 2 3 1 1 2 0 0.51 1.00 308 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(2), HLA-DRA(1), HLA-DRB1(1), IL1B(1), IL4(2), IL5RA(2) 1438952 10 9 10 2 2 4 1 0 3 0 0.51 1.00 309 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(4), GSK3B(1), IRS1(4), IRS2(2), JAK1(1), JAK3(7), MAP4K1(2), MAPK1(1), MAPK3(2), PDK1(1), PIK3CA(21), PIK3CD(3), PIK3R1(1), PPP1R13B(4), RAF1(1), SHC1(1), SOS1(6), SOS2(4), STAT6(1) 10077114 70 54 59 22 22 23 15 4 6 0 0.51 1.00 310 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(3), UGDH(3), UGP2(5), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4) 6739792 44 39 44 10 11 14 13 3 3 0 0.51 1.00 311 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(1), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNAR1(2), IFNB1(1), IKBKB(3), IKBKE(3), IL12A(1), IL12B(3), IL1B(1), IRAK1(4), IRF3(1), JUN(2), LBP(5), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K6(3), MAP3K7(3), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPK8(2), MAPK9(1), NFKB1(2), NFKB2(2), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), RAC1(2), RELA(3), STAT1(2), TBK1(3), TICAM1(1), TLR1(3), TLR2(3), TLR3(2), TLR4(10), TLR5(3), TLR7(3), TLR8(2), TLR9(1), TOLLIP(1), TRAF3(1), TRAF6(1) 24430500 162 91 150 46 48 49 30 17 18 0 0.51 1.00 312 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(3), ACPT(2), ENPP1(7), ENPP3(4), FLAD1(2), MTMR1(1), MTMR2(1), MTMR6(3), TYR(3) 4031522 27 24 27 8 7 11 4 0 5 0 0.52 1.00 313 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(4), LPL(3) 1424534 10 10 10 2 5 4 1 0 0 0 0.52 1.00 314 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(4), PRKCA(5), TGM2(1) 1368286 10 9 10 3 3 3 3 0 1 0 0.52 1.00 315 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(6), GOT1(2), GOT2(3), LDHAL6B(1), LDHB(2), LDHC(1), SDS(2), SULT1B1(3), SULT1C2(3), SULT1C4(2) 3393748 25 21 24 4 2 13 6 2 2 0 0.52 1.00 316 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), EHHADH(1), EP300(5), HSD17B4(1), JUN(2), LPL(3), MAPK1(1), MAPK3(2), MYC(1), NCOA1(6), NCOR1(4), NCOR2(6), NR0B2(1), NR1H3(2), NRIP1(3), PIK3CA(21), PIK3R1(1), PPARA(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), RB1(7), RELA(3), RXRA(1), SP1(1), STAT5A(2) 16962866 107 73 95 41 31 34 18 9 15 0 0.52 1.00 317 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), CREB3(2), CREB5(3), CREBBP(12), CRKL(1), DAG1(1), EGR1(4), EGR2(6), EGR3(1), FRS2(3), JUN(2), MAP1B(4), MAPK1(1), MAPK10(1), MAPK3(2), MAPK8(2), MAPK8IP1(2), MAPK8IP3(6), MAPK9(1), NTRK1(3), OPN1LW(2), PIK3C2G(7), PIK3CA(21), PIK3CD(3), PIK3R1(1), PTPN11(3), RPS6KA3(1), SHC1(1), TH(2) 14262962 106 70 94 35 42 33 19 6 6 0 0.53 1.00 318 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), CREBBP(12), EP300(5), NCOA3(4), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), RARA(1), RXRA(1) 5467804 34 30 33 9 7 14 4 5 4 0 0.53 1.00 319 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), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4), FDXR(3) 4317924 25 22 25 11 9 3 7 1 5 0 0.53 1.00 320 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(3), EGF(6), EGFR(9), ETS1(2), FOS(1), HOXA7(3), HRAS(2), IKBKB(3), JUN(2), MAP2K1(2), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAP3K14(1), MAP3K5(3), MAPK1(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPK8(2), NFKB1(2), PRKCA(5), PRKCD(2), PRKCE(5), PRKCG(9), PRKCH(1), PRKCQ(4), RAF1(1), RELA(3), SP1(1), TNFRSF1A(2), TNFRSF1B(1) 13433838 92 65 91 24 26 35 14 6 11 0 0.53 1.00 321 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(9), GNAS(4), GNB1(1), HRAS(2), IGF1R(1), ITGB1(4), KLK2(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), MYC(1), NGFR(1), PDGFRA(8), PTPRR(6), RAF1(1), RPS6KA1(4), RPS6KA5(3), SHC1(1), SOS1(6), STAT3(1) 9071948 61 50 60 18 18 18 18 3 4 0 0.53 1.00 322 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(8), ADCY2(16), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADSL(1), ADSS(1), AK5(2), AMPD1(4), AMPD2(1), AMPD3(6), ATP5A1(2), ATP5B(1), ATP5C1(3), ATP5G2(3), ATP5G3(1), CANT1(3), DCK(1), ENPP1(7), ENPP3(4), ENTPD1(1), ENTPD2(1), GART(2), GDA(6), GUCY1A2(10), GUCY1A3(6), GUCY1B3(3), GUCY2C(4), GUCY2D(1), GUCY2F(8), GUK1(1), HPRT1(1), IMPDH1(2), NPR1(2), NPR2(5), NT5E(2), PAPSS2(1), PDE1A(2), PDE4B(3), PDE4C(4), PDE4D(1), PDE5A(3), PDE6B(3), PDE7B(1), PDE8A(6), PDE9A(2), PFAS(5), PKLR(3), PKM2(1), POLB(1), POLD1(2), POLG(2), POLL(1), POLQ(18), POLR1B(4), POLR2A(2), POLR2B(2), POLR2D(1), POLR2E(1), POLR2H(1), PPAT(1), PRPS1(1), PRPS1L1(1), PRPS2(1), RRM1(2) 35177072 224 113 220 77 67 86 30 19 22 0 0.54 1.00 323 STREPTOMYCIN_BIOSYNTHESIS GCK, HK1, HK2, HK3, IMPA1, PGM1, PGM3, TGDS 8 GCK(1), HK1(4), HK2(6), HK3(7), IMPA1(1), PGM1(1), TGDS(1) 2756330 21 19 21 5 8 9 1 2 1 0 0.54 1.00 324 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(6), AR(4), ESR1(6), ESR2(1), HNF4A(2), NR0B1(4), NR1H3(2), NR1I2(1), NR1I3(1), NR2C2(1), NR2E1(4), NR2F6(1), NR4A1(4), NR4A2(4), NR5A2(4), PGR(3), PPARA(2), PPARD(2), RARA(1), RARB(2), RARG(3), ROR1(4), RORA(3), RORC(3), RXRA(1), RXRG(5), THRA(2), THRB(1), VDR(3) 11522474 80 57 80 26 23 29 14 4 10 0 0.54 1.00 325 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(3), CPOX(3), EPRS(11), FECH(2), GUSB(3), HMBS(2), HMOX1(1), PPOX(1), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2B15(1), UGT2B4(4), UROD(1) 7022990 45 39 45 10 9 20 11 2 3 0 0.54 1.00 326 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(6), FOS(1), JUN(2), MAPK14(1), MAPK8(2), PLCG1(2), PRKCA(5), SYT1(3) 3539708 22 22 22 10 7 7 4 3 1 0 0.54 1.00 327 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(1), TGFBR2(3), TGFBR3(6), TOB2(2) 2875946 17 17 17 8 0 8 6 0 3 0 0.55 1.00 328 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(5), FZD1(1), GSK3B(1), HDAC1(2), LDB1(1), LEF1(3), PITX2(3), TRRAP(12) 8810288 55 46 54 19 10 18 17 3 7 0 0.55 1.00 329 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(2), ENPP2(9), ENPP6(1), PAFAH1B1(1), PAFAH1B2(1), PAFAH2(1), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLD1(10), PLD2(4), PPAP2B(2) 6299776 52 37 50 21 16 22 7 1 6 0 0.55 1.00 330 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(2), JUN(2), MAP2K1(2), MAPK1(1), MAPK3(2), MYC(1), NFKB1(2), PLCB1(7), PRKCA(5), RAF1(1), RELA(3) 4191188 31 25 31 10 10 10 3 6 2 0 0.55 1.00 331 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(2), F5(15), FGA(5), FGB(3), FGG(1), SERPINC1(5) 4394464 36 26 36 8 5 15 13 2 1 0 0.56 1.00 332 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(2), CBL(4), CBLB(4), CCND1(1), CCND2(3), CCND3(1), CNTFR(1), CREBBP(12), CSF2RB(5), CSF3R(5), EP300(5), EPOR(2), GH1(1), GH2(2), GHR(2), IFNA1(1), IFNA10(1), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNAR1(2), IFNB1(1), IFNG(1), IFNGR1(3), IFNGR2(1), IL10(1), IL10RA(1), IL11RA(2), IL12A(1), IL12B(3), IL12RB1(3), IL12RB2(3), IL13RA1(2), IL13RA2(1), IL20(1), IL20RA(1), IL21(1), IL21R(2), IL22(1), IL22RA1(1), IL22RA2(1), IL23R(1), IL26(1), IL28B(1), IL2RB(2), IL2RG(1), IL4(2), IL5RA(2), IL6R(1), IL7R(3), JAK1(1), JAK2(3), JAK3(7), LEPR(10), LIFR(4), MPL(3), MYC(1), OSMR(4), PIAS1(3), PIAS2(2), PIAS3(4), PIAS4(3), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PIM1(2), PRL(1), PRLR(5), PTPN11(3), SOCS2(1), SOCS5(3), SOS1(6), SOS2(4), SPRED1(1), SPRED2(2), STAM(1), STAM2(2), STAT1(2), STAT2(2), STAT3(1), STAT4(4), STAT5A(2), STAT6(1), TPO(11), TYK2(8) 38399228 261 119 248 99 71 95 52 21 22 0 0.57 1.00 333 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), ALDOC(1), FBP2(1), GOT1(2), GOT2(3), GPT(1), GPT2(2), MDH1(1), MDH2(1), ME2(2), ME3(2), PGK1(1), PKLR(3), PKM2(1), RPIA(1), TKT(1), TPI1(4) 4743700 30 28 28 12 8 12 4 2 4 0 0.57 1.00 334 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(2), GNAI1(2), GNB1(1), HRAS(2), ITGA1(4), ITGB1(4), MAP2K1(2), MAPK1(1), MAPK3(2), PLA2G4A(5), PLCB1(7), PRKCA(5), PTGS1(2), PTK2(3), RAF1(1), SYK(1), TBXAS1(5) 6603266 51 37 49 15 13 22 8 3 5 0 0.57 1.00 335 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(5), DLG4(1), EPHB2(5), F2RL1(3), F2RL2(1), F2RL3(2), JUN(2), MAP2K5(2), MAPK1(1), MAPK7(1), MAPK8(2), MYEF2(3), PLD1(10), PLD2(4), PLD3(1), PTK2(3), RAF1(1), RASAL1(4), TEC(2), VAV1(7) 7510888 60 41 58 18 18 21 10 4 7 0 0.57 1.00 336 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(2), CSF1(2), HLA-DRA(1), HLA-DRB1(1), IFNA1(1), IFNB1(1), IFNG(1), IL10(1), IL12A(1), IL12B(3), IL4(2), LTA(3), TGFB1(1), TGFB2(1) 3596846 21 20 21 7 3 6 5 3 4 0 0.58 1.00 337 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(4), CD3D(1), DAG1(1), EPHB2(5), FBXW7(10), GRAP2(1), ITK(2), ITPKA(1), ITPKB(3), LAT(1), LCK(2), LCP2(2), MAPK1(1), NCK1(3), NFAT5(3), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PLCG1(2), PTPRC(3), RAF1(1), RASGRP1(1), RASGRP3(8), RASGRP4(4), SOS1(6), SOS2(4), VAV1(7), ZAP70(3) 15279876 104 70 102 34 29 35 20 6 14 0 0.58 1.00 338 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), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4) 4058222 22 20 22 11 7 2 7 1 5 0 0.58 1.00 339 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), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4) 4058222 22 20 22 11 7 2 7 1 5 0 0.58 1.00 340 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), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4) 4058222 22 20 22 11 7 2 7 1 5 0 0.58 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 ACTR2(1), AKT1(1), DAG1(1), DGKA(6), ETFA(2), GCA(1), ITGA9(1), ITPKA(1), ITPKB(3), ITPR1(5), ITPR2(11), ITPR3(3), MAP2K1(2), MAPK1(1), MAPK3(2), NR1I3(1), PAK1(3), PDE3A(5), PDE3B(3), PI3(1), PIK3C2G(7), PIK3CA(21), PIK3CD(3), PIK3R1(1), PSME1(1), RIPK3(1), SGCB(1), VASP(2) 13431346 91 67 80 28 40 24 16 3 8 0 0.58 1.00 342 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(6), ALDH3B2(2), AOC2(2), AOC3(3), DDC(2), EPX(5), ESCO1(1), GOT1(2), GOT2(3), HPD(3), LPO(2), MPO(3), MYST3(11), MYST4(3), PNPLA3(1), PRDX6(1), SH3GLB1(1), TAT(1), TPO(11) 9222714 63 51 62 26 17 25 13 5 3 0 0.59 1.00 343 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), CREB3(2), CREB5(3), DUSP4(1), DUSP6(1), DUSP9(4), EEF2K(3), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), MOS(4), NFKB1(2), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), SHC1(1), SOS1(6), SOS2(4), TRAF3(1) 8109146 53 44 52 15 10 15 17 2 9 0 0.60 1.00 344 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), ACVR2B(1), AMHR2(4), BMP7(1), BMPR1A(3), CCL14(2), CCL16(1), CCL20(1), CCL26(2), CCL3(2), CCR1(2), CCR3(1), CCR4(3), CCR6(2), CCR8(3), CD27(2), CD40(1), CD40LG(2), CNTFR(1), CSF1(2), CSF1R(3), CSF2RB(5), CSF3R(5), CX3CR1(3), CXCL5(2), CXCR3(1), CXCR4(6), EDA2R(1), EGF(6), EGFR(9), EPOR(2), FAS(1), FASLG(1), FLT1(9), FLT3(4), FLT4(3), GDF5(4), GH1(1), GH2(2), GHR(2), HGF(6), IFNA1(1), IFNA10(1), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNAR1(2), IFNB1(1), IFNG(1), IFNGR1(3), IFNGR2(1), IL10(1), IL10RA(1), IL11RA(2), IL12A(1), IL12B(3), IL12RB1(3), IL12RB2(3), IL13RA1(2), IL17A(1), IL17RA(3), IL17RB(2), IL18R1(2), IL18RAP(2), IL1B(1), IL1R2(3), IL1RAP(2), IL20(1), IL20RA(1), IL21(1), IL21R(2), IL22(1), IL22RA1(1), IL22RA2(1), IL23R(1), IL26(1), IL28B(1), IL2RB(2), IL2RG(1), IL4(2), IL5RA(2), IL6R(1), IL7R(3), INHBA(4), INHBC(1), KDR(11), KIT(6), LEPR(10), LIFR(4), LTA(3), LTB(1), LTBR(1), MET(3), MPL(3), NGFR(1), OSMR(4), PDGFB(1), PDGFC(1), PDGFRA(8), PDGFRB(5), PF4(1), PLEKHO2(5), PRL(1), PRLR(5), TGFB1(1), TGFB2(1), TGFBR2(3), TNFRSF10A(1), TNFRSF10B(1), TNFRSF10D(1), TNFRSF11A(1), TNFRSF11B(1), TNFRSF13B(2), TNFRSF14(1), TNFRSF18(1), TNFRSF19(1), TNFRSF1A(2), TNFRSF1B(1), TNFRSF21(3), TNFRSF6B(1), TNFRSF9(1), TNFSF11(1), TNFSF13(1), TNFSF14(2), TNFSF18(1), TPO(11), VEGFC(4), XCL1(1), XCR1(1) 47276444 314 125 312 137 84 119 56 19 36 0 0.61 1.00 345 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(7), PRKCA(5), RELA(3) 2235858 17 13 17 6 5 7 1 2 2 0 0.61 1.00 346 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(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2), BAAT(3), CEL(5), CYP27A1(2), CYP7A1(3), HADHB(2), SOAT2(1), SRD5A1(2), SRD5A2(2) 6312592 44 36 42 13 9 21 6 4 4 0 0.61 1.00 347 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), ALDOC(1), DERA(1), FBP2(1), GPI(5), H6PD(4), PFKL(2), PFKM(5), PFKP(2), PGLS(1), PGM1(1), PRPS1(1), PRPS1L1(1), PRPS2(1), RBKS(1), RPIA(1), TALDO1(2), TKT(1), TKTL1(4), TKTL2(9) 6647588 47 37 44 15 16 14 7 4 6 0 0.62 1.00 348 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(7), ATP4A(5), ATP5A1(2), ATP5B(1), ATP5C1(3), ATP5G2(3), ATP5G3(1), ATP5L(1), ATP6V0A1(4), ATP6V0A2(5), ATP6V0A4(2), ATP6V0D1(1), ATP6V0D2(2), ATP6V1A(3), ATP6V1B1(2), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4), COX10(1), COX4I1(1), COX4I2(1), COX6B1(2), COX7A2(1), COX7B2(3), CYC1(4), NDUFA13(2), NDUFA6(2), NDUFA7(1), NDUFAB1(1), NDUFB5(3), NDUFB8(1), NDUFS1(4), NDUFS6(1), NDUFS8(1), NDUFV1(3), NDUFV2(2), SDHA(1), SDHC(1), UQCRB(1), UQCRC2(1) 15113624 90 66 89 31 22 30 22 7 9 0 0.62 1.00 349 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(5), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 3260782 26 20 26 6 12 8 3 1 2 0 0.62 1.00 350 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), ALDOC(1), FBP2(1), FPGT(2), GCK(1), GMPPA(1), HK1(4), HK2(6), HK3(7), KHK(1), MPI(1), PFKFB1(3), PFKM(5), PFKP(2), PMM1(1), TPI1(4) 6506434 43 36 41 15 17 11 8 4 3 0 0.63 1.00 351 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(4), ALDH1B1(3), ALDH2(2), ALDH3B2(2), ALDH9A1(2), ALDOA(1), ALDOB(2), ALDOC(1), BPGM(2), DLAT(1), DLD(2), ENO2(2), ENO3(1), FBP2(1), G6PC(2), GAPDH(3), GCK(1), GPI(5), HK1(4), HK2(6), HK3(7), LDHB(2), LDHC(1), PDHA1(2), PDHA2(5), PFKM(5), PFKP(2), PGK1(1), PGM1(1), PKLR(3), PKM2(1), TPI1(4) 12973530 88 66 85 22 28 38 11 6 5 0 0.63 1.00 352 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(4), ALDH1B1(3), ALDH2(2), ALDH3B2(2), ALDH9A1(2), ALDOA(1), ALDOB(2), ALDOC(1), BPGM(2), DLAT(1), DLD(2), ENO2(2), ENO3(1), FBP2(1), G6PC(2), GAPDH(3), GCK(1), GPI(5), HK1(4), HK2(6), HK3(7), LDHB(2), LDHC(1), PDHA1(2), PDHA2(5), PFKM(5), PFKP(2), PGK1(1), PGM1(1), PKLR(3), PKM2(1), TPI1(4) 12973530 88 66 85 22 28 38 11 6 5 0 0.63 1.00 353 HSA00730_THIAMINE_METABOLISM Genes involved in thiamine metabolism LHPP, MTMR1, MTMR2, MTMR6, NFS1, PHPT1, THTPA, TPK1 8 MTMR1(1), MTMR2(1), MTMR6(3), NFS1(3), TPK1(3) 1721082 11 11 11 3 2 4 4 0 1 0 0.64 1.00 354 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(2), GTF2A1(1), GTF2B(1), GTF2E1(1), HDAC3(1), NCOA1(6), NCOA2(10), NCOA3(4), NCOR2(6), POLR2A(2), RARA(1), RXRA(1), TBP(1) 6895008 37 34 37 18 8 15 5 2 7 0 0.64 1.00 355 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(3), ETS1(2), ETV3(2), FOS(1), HDAC5(1), HRAS(2), JUN(2), NCOR2(6), RBL1(6), RBL2(5), SIN3A(5), SIN3B(3) 7269342 43 37 43 11 6 18 7 7 5 0 0.64 1.00 356 HSA00625_TETRACHLOROETHENE_DEGRADATION Genes involved in tetrachloroethene degradation AKR1B10, EPHX2, HSD3B7, RDH11, RDH12, RDH13, RDH14 7 AKR1B10(1), EPHX2(2), RDH11(2), RDH12(2), RDH13(1) 1309724 8 8 8 2 3 2 0 2 1 0 0.66 1.00 357 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(2), ARSD(1), ARSE(2), GAL3ST1(1), GALC(2), GLA(2), LCT(15), NEU1(4), NEU2(2), NEU3(2), PPAP2B(2), SMPD1(3), SMPD2(2), SPTLC2(3) 6640468 43 36 43 15 13 15 7 5 3 0 0.66 1.00 358 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(2), GPX5(1), GPX6(2), GSR(2), GSS(2), GSTA2(1), GSTA4(2), GSTA5(2), GSTM3(1), GSTM4(3), GSTM5(2), GSTZ1(2), IDH1(2), MGST1(2), OPLAH(3) 6086710 37 34 37 15 8 17 7 4 1 0 0.66 1.00 359 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), CREB3(2), CREB5(3), MAPK1(1), RAF1(1), SNX13(4) 3132622 18 18 18 7 4 4 8 0 2 0 0.67 1.00 360 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 CREM(2), FOS(1), JUN(2), MAPK3(2), OPRK1(1), POLR2A(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 3384492 20 19 20 6 6 8 1 2 3 0 0.67 1.00 361 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(3), IRAK1(4), MAP3K1(3), MAP3K14(1), MAP3K7(3), NFKB1(2), RELA(3), TLR4(10), TNFAIP3(4), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TRAF6(1) 6703836 41 32 41 16 8 14 7 5 7 0 0.68 1.00 362 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(2), AARS2(6), CARS(6), DARS(1), DARS2(5), EARS2(2), EPRS(11), FARS2(1), FARSA(2), GARS(1), HARS(2), HARS2(2), IARS(3), IARS2(4), KARS(3), LARS2(5), MARS(1), NARS(3), NARS2(2), PARS2(1), RARS(4), RARS2(2), SARS(2), SARS2(2), TARS(3), TARS2(2), VARS(4), VARS2(4), WARS(4), WARS2(1), YARS(1), YARS2(1) 14615580 93 66 93 32 15 40 24 5 9 0 0.68 1.00 363 HSA00603_GLYCOSPHINGOLIPID_BIOSYNTHESIS_GLOBOSERIES Genes involved in glycosphingolipid biosynthesis - globoseries A4GALT, B3GALNT1, B3GALT5, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, ST3GAL1, ST3GAL2, ST8SIA1 14 B3GALNT1(1), FUT9(1), GBGT1(3), GLA(2), HEXA(6), NAGA(1), ST3GAL1(1), ST3GAL2(2), ST8SIA1(2) 2913504 19 17 18 7 2 12 2 2 1 0 0.68 1.00 364 UBIQUINONE_BIOSYNTHESIS NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 14 NDUFB5(3), NDUFS1(4), NDUFV1(3), NDUFV2(2) 1823966 12 11 12 3 4 4 3 1 0 0 0.68 1.00 365 PANTOTHENATE_AND_COA_BIOSYNTHESIS BCAT1, COASY, DPYD, DPYS, ENPP1, ENPP3, PANK1, PANK2, PANK3, PANK4, PPCS, UPB1 12 BCAT1(1), COASY(2), DPYD(7), DPYS(4), ENPP1(7), ENPP3(4), PANK3(2), PANK4(1), PPCS(1) 3808488 29 22 29 10 8 12 4 2 3 0 0.68 1.00 366 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 EGF(6), EGFR(9), TF(7), TFRC(2) 3479188 24 20 23 4 8 11 2 0 3 0 0.69 1.00 367 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(5), CAMK1G(2), HDAC5(1), IGF1(2), IGF1R(1), INSR(7), MAP2K6(3), MAPK14(1), MAPK7(1), MEF2A(2), MEF2C(2), MEF2D(2), NFATC2(5), PIK3CA(21), PIK3R1(1), PPP3CA(2), PPP3CB(5), PPP3CC(2), SYT1(3) 9507870 69 50 58 18 26 19 12 8 4 0 0.69 1.00 368 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(4), CBLB(4), CD3D(1), CD4(2), CD40LG(2), CD8B(1), CDC42(1), CHP(2), CHUK(2), FOS(1), FYN(4), GRAP2(1), HRAS(2), ICOS(2), IFNG(1), IKBKB(3), IL10(1), IL4(2), ITK(2), JUN(2), KRAS(1), LAT(1), LCK(2), LCP2(2), MALT1(2), MAP3K14(1), NCK1(3), NFAT5(3), NFATC2(5), NFATC3(3), NFATC4(2), NFKB1(2), NFKB2(2), NFKBIB(1), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PDK1(1), PIK3CA(21), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKCQ(4), PTPRC(3), RASGRP1(1), SOS1(6), SOS2(4), TEC(2), VAV1(7), VAV2(4), VAV3(1), ZAP70(3) 27660132 185 96 174 54 56 55 33 20 21 0 0.69 1.00 369 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(3), ATF2(2), EGFR(9), HRAS(2), JUN(2), MAP2K1(2), MAP2K2(2), MAP3K1(3), MAPK1(1), MAPK3(2), MAPK8(2), MEF2A(2), MEF2C(2), MEF2D(2), PAK1(3), PRKCA(5), PTK2(3), RAC1(2), RAF1(1), SHC1(1), SOS1(6), SYT1(3) 9123746 61 48 60 23 19 19 12 6 5 0 0.69 1.00 370 HSA00770_PANTOTHENATE_AND_COA_BIOSYNTHESIS Genes involved in pantothenate and CoA biosynthesis BCAT1, BCAT2, COASY, DPYD, DPYS, ENPP1, ENPP3, ILVBL, PANK1, PANK2, PANK3, PANK4, PPCDC, PPCS, UPB1, VNN1 16 BCAT1(1), BCAT2(3), COASY(2), DPYD(7), DPYS(4), ENPP1(7), ENPP3(4), ILVBL(2), PANK3(2), PANK4(1), PPCS(1), VNN1(2) 4731952 36 27 36 12 11 13 7 2 3 0 0.69 1.00 371 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(2), EXTL3(1), HS3ST2(1), HS3ST5(4), HS6ST1(2), HS6ST3(2), NDST1(3), NDST2(1), NDST3(4), NDST4(11) 5722344 34 30 34 16 2 17 7 6 2 0 0.69 1.00 372 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), GTF2H2(1), GTF2H4(1), GTF2I(1), GTF2IRD1(4), TAF1(11), TAF1L(17), TAF2(5), TAF4(1), TAF4B(6), TAF5(2), TAF5L(3), TAF6L(2), TAF7L(1), TAF9(2), TBPL2(1) 9710434 61 48 61 21 20 17 10 6 8 0 0.70 1.00 373 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(8), FOS(1), GNAI1(2), GNAS(4), GNB1(1), HRAS(2), JUN(2), MAP2K1(2), MAPK3(2), NFATC2(5), NFATC3(3), NFATC4(2), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), RAF1(1), RPS6KA3(1), SYT1(3) 9434534 65 49 65 21 22 22 7 9 5 0 0.70 1.00 374 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(2), ALPI(1), ALPL(3), ALPP(1), ALPPL2(1), CYP19A1(3), CYP1A1(7), CYP1A2(1), CYP2A13(2), CYP2A6(3), CYP2B6(3), CYP2C19(6), CYP2C8(3), CYP2C9(2), CYP2D6(3), CYP2E1(1), CYP2F1(4), CYP2J2(2), CYP3A4(1), CYP3A7(1), CYP4B1(3), CYP4F8(1), PON1(4) 7937020 59 42 59 28 20 16 14 4 5 0 0.70 1.00 375 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(5), FADD(1), HDAC3(1), IKBKB(3), NFKB1(2), RELA(3), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TRAF6(1) 6117860 34 29 33 10 7 10 6 4 7 0 0.71 1.00 376 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), ACSS2(2), ADH1B(1), ADH1C(1), ADH4(2), ADH5(2), ADH7(1), ADHFE1(2), ALDH1B1(3), ALDH2(2), ALDH3B2(2), ALDH7A1(1), ALDH9A1(2), ALDOA(1), ALDOB(2), ALDOC(1), BPGM(2), DLAT(1), DLD(2), ENO2(2), ENO3(1), FBP2(1), G6PC(2), G6PC2(2), GAPDH(3), GAPDHS(2), GCK(1), GPI(5), HK1(4), HK2(6), HK3(7), LDHAL6B(1), LDHB(2), LDHC(1), PDHA1(2), PDHA2(5), PFKL(2), PFKM(5), PFKP(2), PGAM2(1), PGK1(1), PGK2(5), PGM1(1), PKLR(3), PKM2(1), TPI1(4) 15403764 105 72 103 33 36 42 12 8 7 0 0.71 1.00 377 HSA00900_TERPENOID_BIOSYNTHESIS Genes involved in terpenoid biosynthesis FDFT1, FDPS, GGPS1, IDI1, IDI2, SQLE 6 FDFT1(1), FDPS(1), GGPS1(1), IDI1(1), IDI2(1), SQLE(2) 1174622 7 7 7 0 2 3 1 1 0 0 0.71 1.00 378 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 GLUL(1), PGLYRP2(1) 506410 2 2 2 0 0 1 1 0 0 0 0.71 1.00 379 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(2), ABP1(6), AOC2(2), AOC3(3), CES1(2), CES7(1), DDHD1(4), ESCO1(1), LIPA(2), MYST3(11), MYST4(3), PLA1A(5), PNPLA3(1), PRDX6(1), SH3GLB1(1) 6849084 45 37 45 21 12 18 7 4 4 0 0.72 1.00 380 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 0.72 1.00 381 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(4), CPT1A(3), LEPR(10), PRKAA2(2), PRKAB2(1), PRKAG2(4) 3886986 24 23 24 7 8 8 6 1 1 0 0.72 1.00 382 KERATAN_SULFATE_BIOSYNTHESIS B3GNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT5, FUT8, SIAT4A, SIAT4B, SIAT6, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 10 B4GALT1(1), B4GALT3(2), B4GALT5(3), FUT8(2), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2) 2168218 13 13 12 10 3 6 2 1 1 0 0.72 1.00 383 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(2) 675510 3 3 3 1 1 1 0 0 1 0 0.72 1.00 384 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(9), EPHB2(5), ITPKA(1), ITPKB(3), ITPR1(5), ITPR2(11), ITPR3(3), KCNJ3(8), KCNJ5(2), KCNJ9(2), MAPK1(1), PI3(1), PIK3CB(1), PITX2(3), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), RAF1(1), RGS20(1), SHC1(1), SOS1(6), SOS2(4), STAT3(1) 16020534 102 72 101 28 29 36 20 5 12 0 0.73 1.00 385 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), CRKL(1), FOS(1), HRAS(2), JAK2(3), JUN(2), MAP2K1(2), MAP3K1(3), MAPK3(2), MAPK8(2), MYC(1), PIK3CA(21), PIK3R1(1), RAF1(1), SOS1(6), STAT1(2), STAT5A(2) 7564110 54 42 43 8 22 13 13 4 2 0 0.73 1.00 386 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(2), TYK2(8) 2905494 17 17 17 5 6 6 1 3 1 0 0.73 1.00 387 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), ALDOC(1), FBP2(1), GPI(5), H6PD(4), PFKM(5), PFKP(2), PGLS(1), PGM1(1), PRPS1(1), PRPS1L1(1), PRPS2(1), RBKS(1), RPIA(1), TAL1(2), TALDO1(2), TKT(1) 5552176 33 29 32 14 11 10 3 3 6 0 0.73 1.00 388 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(3), CFLAR(1) 1038452 5 5 5 2 0 4 0 0 1 0 0.73 1.00 389 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(6), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH3B2(2), ALDH9A1(2), AOC2(2), AOC3(3), ASPA(1), CNDP1(3), DDC(2), HARS(2), HDC(3), HNMT(1), PRPS1(1), PRPS2(1) 6575498 38 35 37 17 11 16 6 3 2 0 0.73 1.00 390 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(2), FYN(4), HLA-DRA(1), HLA-DRB1(1), LCK(2), PTPRC(3), ZAP70(3) 2464054 17 14 17 6 4 8 2 1 2 0 0.73 1.00 391 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 AKR1B10(1), ALDOA(1), ALDOB(2), ALDOC(1), FBP2(1), FPGT(2), FUK(1), GMPPA(1), HK1(4), HK2(6), HK3(7), KHK(1), MPI(1), MTMR1(1), MTMR2(1), MTMR6(3), PFKFB1(3), PFKFB2(1), PFKL(2), PFKM(5), PFKP(2), PGM2(5), PMM1(1), RDH11(2), RDH12(2), RDH13(1), TPI1(4) 10174124 62 51 60 18 22 16 10 7 7 0 0.74 1.00 392 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(9), MAP2K1(2), MAP3K1(3), MAPK14(1), NCOR2(6), RARA(1), RXRA(1), THRA(2), THRB(1) 4792828 32 25 31 10 11 12 4 0 5 0 0.74 1.00 393 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(5), CD79A(1), FOS(1), HRAS(2), JUN(2), LYN(1), MAP2K1(2), MAP3K1(3), MAPK14(1), MAPK3(2), MAPK8(2), NFATC2(5), NFATC3(3), NFATC4(2), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKCA(5), RAC1(2), RAF1(1), SHC1(1), SOS1(6), SYK(1), SYT1(3), VAV1(7) 10354616 70 52 70 22 21 20 12 10 7 0 0.74 1.00 394 NOTCHPATHWAY Proteolysis and Signaling Pathway of Notch ADAM17, DLL1, FURIN, NOTCH1, PSEN1, RBPSUH 5 DLL1(1), FURIN(1), NOTCH1(11), PSEN1(1) 2659320 14 12 14 6 2 5 0 1 6 0 0.75 1.00 395 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(4), MBTPS1(3), MBTPS2(2), SCAP(4), SREBF1(3), SREBF2(2) 3331092 19 18 19 3 5 7 3 4 0 0 0.75 1.00 396 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(2), CSNK1A1(1), GSK3B(1), MAPT(5) 2580466 13 13 13 5 2 5 0 1 5 0 0.75 1.00 397 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(2), STAT3(1), TYK2(8) 3262918 23 18 23 4 5 12 4 1 1 0 0.75 1.00 398 TERPENOID_BIOSYNTHESIS FDFT1, FDPS, FDPS, LOC402397, IDI1, SQLE 4 FDFT1(1), FDPS(1), IDI1(1), SQLE(2) 887152 5 5 5 0 2 2 0 1 0 0 0.75 1.00 399 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(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2) 6087244 33 31 33 12 9 15 6 2 1 0 0.75 1.00 400 VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS BCAT1, IARS, LARS, LARS2, PDHA1, PDHA2, PDHB 7 BCAT1(1), IARS(3), LARS2(5), PDHA1(2), PDHA2(5) 2688156 16 15 16 3 2 8 4 1 1 0 0.75 1.00 401 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 ALDH1A2(4), BCMO1(1) 1037384 5 5 4 3 0 2 1 0 2 0 0.76 1.00 402 PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS ENO1, ENO2, ENO3, FARS2, FARSLB, GOT1, GOT2, PAH, TAT, YARS 9 ENO2(2), ENO3(1), FARS2(1), GOT1(2), GOT2(3), PAH(1), TAT(1), YARS(1) 2211650 12 12 11 5 5 4 1 1 1 0 0.76 1.00 403 HSA00521_STREPTOMYCIN_BIOSYNTHESIS Genes involved in streptomycin biosynthesis GCK, HK1, HK2, HK3, IMPA1, IMPA2, ISYNA1, PGM1, PGM3, TGDS 10 GCK(1), HK1(4), HK2(6), HK3(7), IMPA1(1), PGM1(1), TGDS(1) 3175520 21 19 21 5 8 9 1 2 1 0 0.76 1.00 404 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(2), ABAT(3), ACADS(3), ACAT1(1), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH5A1(1), ALDH9A1(2), EHHADH(1), GAD1(5), GAD2(5), HADHA(2), HMGCL(1), L2HGDH(1), OXCT1(2), PDHA1(2), PDHA2(5), SDS(2) 6966742 47 36 46 20 9 23 4 4 7 0 0.76 1.00 405 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(6), ADH1B(1), ADH1C(1), ADH4(2), ADH5(2), ADH7(1), ADHFE1(2), ALDH3B2(2), AOC2(2), AOC3(3), AOX1(11), CARM1(1), DBH(2), DCT(1), DDC(2), ECH1(1), ESCO1(1), FAH(1), GOT1(2), GOT2(3), GSTZ1(2), HPD(3), LCMT1(2), LCMT2(1), MYST3(11), MYST4(3), PNMT(2), PNPLA3(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), SH3GLB1(1), TAT(1), TH(2), TPO(11), TYR(3), TYRP1(2), WBSCR22(4) 15827048 105 70 104 31 30 45 11 11 8 0 0.76 1.00 406 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(2), ADH7(1), ADHFE1(2), AKR1B10(1), AKR1C4(1), AKR1D1(4), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), BAAT(3), CEL(5), CYP27A1(2), CYP7A1(3), HADHB(2), LIPA(2), RDH11(2), RDH12(2), RDH13(1), SLC27A5(4), SOAT2(1), SRD5A1(2), SRD5A2(2) 8668778 60 45 59 16 16 26 6 7 5 0 0.76 1.00 407 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), CCND1(1), CCND2(3), CCND3(1), CTNNB1(3), DVL1(3), DVL3(3), FZD1(1), FZD10(2), FZD3(4), FZD6(1), FZD9(3), GSK3B(1), JUN(2), LDLR(4), MAPK10(1), MAPK9(1), MYC(1), PAFAH1B1(1), PLAU(2), PPP2R5C(7), PRKCA(5), PRKCD(2), PRKCE(5), PRKCG(9), PRKCH(1), PRKCI(4), PRKCQ(4), PRKD1(9), RAC1(2), SFRP4(3), TCF7(1), WNT10B(2), WNT11(2), WNT2(3), WNT2B(2), WNT3(2), WNT5A(1), WNT5B(1), WNT6(2), WNT7A(2), WNT7B(1) 16330076 117 72 117 34 36 44 21 10 6 0 0.77 1.00 408 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(5), ITGAL(1), ITGAM(3), ITGB1(4), ITGB2(3), SELE(4), SELL(2), SELP(8) 4718780 35 24 35 7 9 10 9 2 5 0 0.77 1.00 409 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 AKR1B10(1), DHRS2(1), PON1(4), PON2(1), PON3(1), RDH11(2), RDH12(2), RDH13(1) 2268076 13 12 13 3 3 5 1 2 2 0 0.77 1.00 410 HSA00460_CYANOAMINO_ACID_METABOLISM Genes involved in cyanoamino acid metabolism ASRGL1, GBA, GBA3, GGT1, GGTL3, GGTL4, SHMT1, SHMT2 6 GBA3(6), GGT1(2) 1569604 8 7 8 9 1 2 3 1 1 0 0.78 1.00 411 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), JAK1(1), JAK2(3), TYK2(8) 2816850 15 15 15 6 3 6 4 1 1 0 0.79 1.00 412 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), JAK1(1), JAK2(3), TYK2(8) 2816850 15 15 15 6 3 6 4 1 1 0 0.79 1.00 413 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(2), PLCG1(2), PRKCA(5) 1819516 9 9 9 5 2 5 1 0 1 0 0.79 1.00 414 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(5), IKBKB(3), IL1B(1), MAP2K3(2), MAP2K6(3), MAP3K14(1), MAP3K7(3), MAPK14(1), NFKB1(2), RELA(3), TGFBR2(3), TLR2(3) 8069630 44 39 42 14 11 15 7 3 8 0 0.79 1.00 415 GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM ACO1, ACO2, CS, GRHPR, HAO1, HAO2, HYI, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 12 ACO1(1), ACO2(2), GRHPR(1), HAO1(6), MDH1(1), MDH2(1), MTHFD1(3), MTHFD1L(2), MTHFD2(3) 3428992 20 18 20 2 5 8 5 1 1 0 0.79 1.00 416 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 2 0 1 0 0 2 0 0.79 1.00 417 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(3), CD3D(1), CD4(2), CD58(1) 1701146 8 8 8 7 3 3 0 0 2 0 0.80 1.00 418 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(1), CTNNB1(3), DACT1(4), DKK1(3), DKK2(1), DKK4(1), DVL1(3), FSTL1(2), GSK3A(4), GSK3B(1), LRP1(14), MVP(3), NKD1(1), NKD2(2), PSEN1(1), SENP2(3), SFRP1(1), WIF1(4) 10938100 64 51 63 21 18 21 13 2 10 0 0.80 1.00 419 BOTULINPATHWAY Blockade of Neurotransmitter Relase by Botulinum Toxin CHRM1, CHRNA1, SNAP25, STX1A, VAMP2 5 CHRNA1(2), SNAP25(2) 869530 4 4 4 6 1 2 1 0 0 0 0.80 1.00 420 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(6), HMGCL(1), HMGCS1(1), HMGCS2(1), OXCT1(2) 1973842 12 11 12 6 4 6 1 1 0 0 0.80 1.00 421 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(2), GPX5(1), GSS(2), GSTA2(1), GSTA4(2), GSTM3(1), GSTM4(3), GSTM5(2), GSTZ1(2), IDH1(2), MGST1(2) 4947866 28 27 28 13 8 13 4 3 0 0 0.81 1.00 422 1_2_DICHLOROETHANE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2) 2153800 11 11 10 0 1 7 1 1 1 0 0.81 1.00 423 ASCORBATE_AND_ALDARATE_METABOLISM ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2) 2153800 11 11 10 0 1 7 1 1 1 0 0.81 1.00 424 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(3), CYP2C9(2), CYP2E1(1), CYP2J2(2), CYP4A22(1), CYP4F2(3), CYP4F3(3), EPHX2(2), GGT1(2), GPX5(1), GPX6(2), LTA4H(2), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PTGES(1), PTGS1(2), TBXAS1(5) 10638882 66 50 64 32 18 18 19 3 8 0 0.81 1.00 425 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(2), ACTR2(1), ARPC1A(2), ARPC1B(1), NCK1(3), NCKAP1(5), NTRK1(3), RAC1(2), WASF3(1), WASL(2) 4129422 22 21 22 15 3 11 2 2 4 0 0.82 1.00 426 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 5 2 7 2 1 2 0 0.82 1.00 427 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 1 0 5 0 0 2 0 0.82 1.00 428 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(3), LTA(3), MAP3K1(3), MAP3K14(1), NFKB1(2), RELA(3), TANK(4), TNFAIP3(4), TNFRSF1B(1), TRAF1(4), TRAF3(1) 6090804 33 26 33 14 5 9 6 5 8 0 0.82 1.00 429 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 4 3 4 0 0 0 0 0.83 1.00 430 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 0.83 1.00 431 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 ALAS1(2), CPO(1), FECH(2), GATA1(3), HBB(2), HMBS(2), UROD(1) 2209870 13 12 13 3 4 6 0 1 2 0 0.83 1.00 432 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), GOT1(2), GOT2(3), PAH(1), TAT(1), YARS(1), YARS2(1) 2348888 12 12 11 8 6 4 0 1 1 0 0.83 1.00 433 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 5 3 0 5 1 0 0 0.83 1.00 434 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(2), RAB4A(3) 1158068 5 5 5 10 3 2 0 0 0 0 0.83 1.00 435 AKAPCENTROSOMEPATHWAY Protein Kinase A at the Centrosome AKAP9, ARHA, CDC2, MAP2, PCNT1, PCNT2, PPP1CA, PPP2CA, PRKACB, PRKACG, PRKAG1, PRKAR2A, PRKAR2B, PRKCE, PRKCL1 10 AKAP9(6), MAP2(9), PPP1CA(1), PRKACB(2), PRKACG(1), PRKAR2B(3), PRKCE(5) 4900162 27 24 27 11 8 5 9 3 2 0 0.83 1.00 436 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(4), CAMK2B(2), CAMK2D(1), CDK5(2), FYN(4), GNAI1(2), GNB1(1), HRAS(2), JAK2(3), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK14(1), MAPK3(2), MAPK8(2), MAPT(5), MYLK(7), PLCG1(2), PRKCA(5), RAF1(1), SHC1(1), SOS1(6), STAT1(2), STAT3(1), STAT5A(2), SYT1(3) 11315994 67 54 67 20 14 28 13 5 7 0 0.84 1.00 437 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(3), IRAK1(4), JUN(2), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAP3K14(1), MAP3K7(3), MAPK14(1), MAPK8(2), NFKB1(2), PPARA(2), RELA(3), TLR2(3), TLR3(2), TLR4(10), TLR7(3), TLR9(1), TOLLIP(1), TRAF6(1) 9909082 56 45 55 17 17 17 8 6 8 0 0.84 1.00 438 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(2), BMP5(5), BMP7(1), BMPR1A(3), CHRD(2), CTNNB1(3), DVL1(3), FZD1(1), GSK3B(1), MAP3K7(3), MEF2C(2), MYL2(1), NKX2-5(2), RFC1(1), TGFB1(1), TGFB2(1), TGFBR2(3), TGFBR3(6) 9785906 53 43 53 18 10 16 14 7 6 0 0.84 1.00 439 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(1), ACO2(2), FH(2), IDH1(2), MDH1(1), MDH2(1), SUCLA2(2) 2378792 11 11 11 4 1 7 1 1 1 0 0.84 1.00 440 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(2), GRHPR(1), HAO1(6), MDH1(1), MDH2(1), MTHFD1(3), MTHFD1L(2), MTHFD2(3) 3592396 20 18 20 2 5 8 5 1 1 0 0.85 1.00 441 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(2), JAK2(3), MAP2K1(2), MAPK3(2), RAF1(1), SHC1(1), SOS1(6), STAT5A(2) 4575846 25 24 25 5 7 9 5 1 3 0 0.85 1.00 442 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(6), DGKB(4), DGKD(5), DGKE(2), DGKG(2), DGKZ(3), ETNK1(3), GPD1(2), GPD2(2), LYPLA1(5), PAFAH1B1(1), PAFAH2(1), PCYT1A(2), PCYT1B(1), PISD(1), PLA2G2A(1), PLA2G2E(2), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLCB2(5), PLCG1(2), PLCG2(3), PPAP2B(2) 13840390 80 60 80 34 22 32 13 5 8 0 0.85 1.00 443 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 3 2 2 0 1 0 0.85 1.00 444 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), BTRC(1), CTNNB1(3), DLL1(1), DVL1(3), FZD1(1), GSK3B(1), NOTCH1(11), PSEN1(1) 5808318 31 27 31 8 6 11 5 1 8 0 0.85 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), AKR1B10(1), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), BBOX1(2), DLST(1), DOT1L(5), EHHADH(1), EHMT2(2), GCDH(1), HADH(1), HADHA(2), HSD17B4(1), NSD1(11), OGDH(3), OGDHL(4), PIPOX(1), PLOD1(2), PLOD2(4), PLOD3(4), RDH11(2), RDH12(2), RDH13(1), SETD1A(6), SETDB1(5), SPCS1(1), SPCS3(2), SUV39H1(1), SUV39H2(2) 15838974 85 64 85 46 12 30 21 8 14 0 0.85 1.00 446 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), ACSL5(1), ACSL6(2), ADIPOQ(1), ANGPTL4(1), APOA2(1), APOA5(3), AQP7(2), CD36(1), CPT1A(3), CPT1C(5), CPT2(2), CYP27A1(2), CYP4A22(1), CYP7A1(3), DBI(1), EHHADH(1), FABP5(1), FABP6(1), FABP7(1), FADS2(1), GK(4), GK2(5), HMGCS2(1), ILK(1), LPL(3), MMP1(3), NR1H3(2), PCK1(3), PCK2(1), PDPK1(1), PLTP(2), PPARA(2), PPARD(2), RXRA(1), RXRG(5), SCD(1), SCP2(1), SLC27A1(1), SLC27A2(2), SLC27A4(1), SLC27A5(4), SLC27A6(3), SORBS1(5), UBC(1), UCP1(2) 17498112 103 71 103 54 26 36 26 6 9 0 0.86 1.00 447 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 4 4 0 1 0 0.86 1.00 448 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), CREB3(2), CREB5(3), DAG1(1), EPHB2(5), FOS(1), ITPKA(1), ITPKB(3), JUN(2), MAPK1(1), MAPK10(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(6), MAPK9(1) 7865998 43 37 43 11 11 15 10 2 5 0 0.87 1.00 449 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(2), ADH7(1), ADHFE1(2), AKR1C2(1), AKR1C3(1), AKR1C4(1), ALDH3B2(2), CYP1A1(7), CYP1A2(1), CYP2B6(3), CYP2C19(6), CYP2C8(3), CYP2C9(2), CYP2E1(1), CYP2F1(4), CYP2S1(1), CYP3A4(1), CYP3A43(3), CYP3A7(1), GSTA2(1), GSTA4(2), GSTA5(2), GSTM3(1), GSTM4(3), GSTM5(2), GSTZ1(2), MGST1(2), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4) 14907500 95 65 95 37 29 28 24 8 6 0 0.87 1.00 450 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(2), AADAC(2), ABAT(3), ACADS(3), ACAT1(1), ACSM1(6), AKR1B10(1), ALDH1B1(3), ALDH2(2), ALDH5A1(1), ALDH7A1(1), ALDH9A1(2), BDH1(6), DDHD1(4), EHHADH(1), GAD1(5), GAD2(5), HADH(1), HADHA(2), HMGCL(1), HMGCS1(1), HMGCS2(1), HSD17B4(1), ILVBL(2), L2HGDH(1), OXCT1(2), PDHA1(2), PDHA2(5), PLA1A(5), PRDX6(1), RDH11(2), RDH12(2), RDH13(1) 11071778 78 49 78 30 18 33 8 10 9 0 0.87 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(2), PSMB6(1), PSMC3(1), PSMD14(3), RPN1(1), UBE2A(2), UBE3A(4) 3479544 17 17 17 6 4 8 3 0 2 0 0.87 1.00 452 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(3), PLCB1(7) 1924358 11 10 11 5 4 5 0 2 0 0 0.87 1.00 453 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), MECR(1), PPT1(1), PPT2(1) 2306524 10 10 10 2 2 1 2 3 2 0 0.88 1.00 454 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(6), ACY3(2), ALDH1B1(3), ALDH2(2), ALDH3B2(2), ALDH7A1(1), ALDH9A1(2), AMDHD1(2), AOC2(2), AOC3(3), ASPA(1), CARM1(1), CNDP1(3), DDC(2), HARS(2), HARS2(2), HDC(3), HNMT(1), LCMT1(2), LCMT2(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), PRPS1(1), PRPS2(1), UROC1(3), WBSCR22(4) 10716134 61 50 61 24 23 22 8 4 4 0 0.88 1.00 455 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(5), ITGAL(1), ITGB1(4), ITGB2(3), SELE(4), SELL(2) 3655764 24 17 24 3 6 7 7 2 2 0 0.88 1.00 456 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(2), CASP1(2), CASP10(4), CASP2(1), CASP4(3), CASP6(1), CASP7(2), CASP8(1), CASP9(1), CD40(1), CD40LG(2), CRADD(1), DAXX(3), DFFA(1), DFFB(2), FADD(1), FAS(1), FASLG(1), IKBKE(3), LTA(3), 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 63 49 63 27 14 24 6 7 12 0 0.88 1.00 457 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(2), ACTR2(1), ARPC1A(2), ARPC1B(1), CDC42(1), RAC1(2), WASL(2) 2180856 11 11 11 7 1 7 2 1 0 0 0.88 1.00 458 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(2), B4GALT4(1), FUT3(3), FUT5(4), FUT6(2), FUT9(1), GCNT2(1), ST3GAL6(1), ST8SIA1(2) 4446796 24 20 24 19 8 7 6 2 1 0 0.88 1.00 459 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(3), ACAT1(1), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH6A1(2), ALDH9A1(2), AOX1(11), BCAT1(1), BCKDHB(2), EHHADH(1), HADHA(2), HADHB(2), HMGCL(1), MCCC1(7), MUT(1), OXCT1(2), PCCA(2), PCCB(6), SDS(2) 9687116 61 43 60 19 9 25 12 8 7 0 0.88 1.00 460 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(4), ACAT1(1), ADH5(2), ALDH1A2(4), ALDH1B1(3), 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(2), PC(4), PCK1(3), PDHA1(2), PDHA2(5), PKLR(3), PKM2(1) 9947530 56 46 55 21 12 28 6 4 6 0 0.88 1.00 461 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(5), CAMK2B(2), CAMK4(3), CNR1(3), CREBBP(12), CSNK2A1(2), EGR2(6), EGR3(1), EP300(5), FCER1A(1), FCGR3A(3), FKBP1B(1), FOS(1), GATA3(5), GRLF1(11), GSK3A(4), GSK3B(1), HRAS(2), 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(3), NFATC2(5), NFATC3(3), NFATC4(2), NFKB2(2), NFKBIB(1), NUP214(5), OPRD1(2), P2RX7(1), PAK1(3), PPP3CB(5), PPP3CC(2), PPP3R1(1), PTPRC(3), RELA(3), SFN(2), SLA(2), SP1(1), SP3(1), TGFB1(1), TRPV6(5), VAV1(7), VAV2(4), VAV3(1), XPO5(3) 24820854 161 87 160 55 50 46 28 17 20 0 0.88 1.00 462 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(1), TNFRSF1A(2), TNFRSF1B(1) 3779118 21 17 21 9 6 5 5 2 3 0 0.88 1.00 463 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(4), CASP7(2), CASP8(1), CASP9(1), DFFA(1), DFFB(2), GZMB(1), PRF1(2), SCAP(4), SREBF1(3), SREBF2(2) 5027432 27 24 27 11 7 11 4 3 2 0 0.88 1.00 464 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(2), ICAM1(2), ITGAL(1), ITGB2(3), PTPRC(3), THY1(2) 3034544 15 15 15 8 3 8 1 2 1 0 0.89 1.00 465 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(2), DLAT(1), DLD(2), DLST(1), FH(2), IDH3A(2), IDH3B(3), MDH1(1), MDH2(1), OGDH(3), PC(4), PDHA1(2), PDHA2(5), PDK1(1), PDK2(2), PDK3(2), PDK4(2), PDP2(4), SDHA(1), SDHC(1), SUCLA2(2), SUCLG2(1) 7678564 45 36 45 16 5 21 7 6 6 0 0.89 1.00 466 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(24), B3GALT4(1), CDR1(2), DGKI(7), MRPL19(1), PIGK(1), RPL14(1), RPL19(1), RPL28(1), RPL30(1), RPL32(1), RPL37(1), RPL3L(1), RPL4(1), RPL5(2), RPL7(1), RPL8(4), RPLP0(2), RPS11(1), RPS18(2), RPS2(1), RPS21(1), RPS26(1), RPS6(1), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KA6(3), RPS6KB1(1), RPS8(1), SLC36A2(1), TBC1D10C(1), TSPAN9(1), UBB(1), UBC(1) 14395750 77 62 77 43 22 21 22 10 2 0 0.89 1.00 467 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 4 2 4 0 1 0 0 0.89 1.00 468 HEME_BIOSYNTHESIS ALAD, ALAS1, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, UROS 9 ALAS1(2), CPOX(3), FECH(2), HMBS(2), PPOX(1), UROD(1) 2065156 11 10 11 1 2 7 0 1 1 0 0.89 1.00 469 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(3), BTRC(1), CDC27(3), CUL1(3), CUL3(8), FBXW7(10), ITCH(2), RBX1(1), SKP1(1), SKP2(1), SMURF1(4), SMURF2(1), UBA1(5), UBE2C(1), UBE2D1(1), UBE2D2(1), UBE2E2(1), UBE2E3(1), VHL(1), WWP1(1), WWP2(1) 10982956 58 47 56 14 15 14 9 8 12 0 0.89 1.00 470 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(3), MYC(1), NFATC2(5), NFKB1(2), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), RELA(3), SYT1(3), VIP(2) 7466566 49 34 49 15 16 14 5 8 6 0 0.89 1.00 471 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 0.89 1.00 472 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ5(2), COQ7(2), NDUFA13(2) 1115170 6 6 6 2 2 3 1 0 0 0 0.90 1.00 473 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), CCND1(1), CREBBP(12), EP300(5), ERCC3(2), ESR1(6), GRIP1(5), GTF2A1(1), GTF2E1(1), HDAC1(2), HDAC3(1), HDAC4(5), HDAC5(1), MEF2C(2), NCOR2(6), NR0B1(4), NRIP1(3), PELP1(1), POLR2A(2), TBP(1) 12822586 68 54 67 24 20 19 13 7 9 0 0.90 1.00 474 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(2), FH(2), MDH1(1), OGDH(3), SDHA(1), SUCLA2(2) 2517098 11 11 11 8 0 5 2 3 1 0 0.90 1.00 475 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(3), UGDH(3), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2B15(1), UGT2B4(4) 4394820 22 20 22 5 6 8 6 1 1 0 0.90 1.00 476 CAPROLACTAM_DEGRADATION AKR1A1, ECHS1, EHHADH, HADHA, SDS 5 EHHADH(1), HADHA(2), SDS(2) 1318802 5 5 5 7 0 2 1 0 2 0 0.90 1.00 477 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), LUM(1) 967608 4 4 4 2 0 3 1 0 0 0 0.90 1.00 478 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 AHCY(1), CBS(4), DNMT1(4), DNMT3A(6), DNMT3B(3), MARS(1), MAT1A(1), MTR(5) 4733020 25 22 25 17 5 11 6 1 2 0 0.90 1.00 479 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(2), IL2RB(2), IL2RG(1), JAK1(1), JAK3(7), JUN(2), LCK(2), MAP2K1(2), MAPK3(2), MAPK8(2), RAF1(1), SHC1(1), SOS1(6), STAT5A(2), SYK(1) 6428648 37 31 37 13 10 14 8 2 3 0 0.91 1.00 480 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), CRKL(1), HRAS(2), JUN(2), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP3K1(3), MAPK1(1), MAPK14(1), MAPK3(2), MAPK8(2), PAK1(3), PLCG1(2), PRKCA(5), RAC1(2), RAF1(1), SHC1(1), SOS1(6), SYT1(3) 7794620 48 39 48 14 18 14 9 5 2 0 0.91 1.00 481 FOLATE_BIOSYNTHESIS ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, DHFR, FPGS, GCH1, GGH, SPR 9 ALPI(1), ALPL(3), ALPP(1), ALPPL2(1), GCH1(2), SPR(1) 1834468 9 9 9 3 4 4 0 1 0 0 0.91 1.00 482 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(6), ACAT1(1), ACMSD(1), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), AOC2(2), AOC3(3), AOX1(11), CARM1(1), CAT(1), CYP1A1(7), CYP1A2(1), DDC(2), EHHADH(1), GCDH(1), HAAO(2), HADH(1), HADHA(2), HSD17B4(1), INMT(3), KMO(3), KYNU(3), LCMT1(2), LCMT2(1), LNX1(2), NFX1(1), OGDH(3), OGDHL(4), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), TDO2(1), TPH1(1), TPH2(8), WARS(4), WARS2(1), WBSCR22(4) 16210282 103 68 102 43 23 46 15 10 9 0 0.91 1.00 483 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(2), ADH7(1), ADHFE1(2), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2) 3593286 17 17 17 5 6 9 0 2 0 0 0.91 1.00 484 HSA00053_ASCORBATE_AND_ALDARATE_METABOLISM Genes involved in ascorbate and aldarate metabolism ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, MIOX, UGDH 9 ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), UGDH(3) 2317560 11 11 11 1 2 8 0 1 0 0 0.91 1.00 485 SRCRPTPPATHWAY Activation of Src by Protein-tyrosine phosphatase alpha CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CSK, GRB2, PRKCA, PRKCB1, PTPRA, SRC 9 CCNB1(1), CDC25B(3), CDC25C(1), PRKCA(5) 2502858 10 10 10 4 1 6 1 1 1 0 0.91 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(3), ACADVL(1), ACSL1(2), ACSL3(1), CPT1A(3), CPT2(2), DCI(1), EHHADH(1), HADHA(2), PECR(1), SCP2(1), SLC25A20(1) 4528320 22 22 22 12 4 9 5 1 3 0 0.91 1.00 487 HSA00290_VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS Genes involved in valine, leucine and isoleucine biosynthesis BCAT1, BCAT2, IARS, IARS2, ILVBL, LARS, LARS2, PDHA1, PDHA2, PDHB, VARS, VARS2 12 BCAT1(1), BCAT2(3), IARS(3), IARS2(4), ILVBL(2), LARS2(5), PDHA1(2), PDHA2(5), VARS(4), VARS2(4) 5037400 33 24 33 10 5 18 6 1 3 0 0.92 1.00 488 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(3), JUN(2), LTA(3), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAP3K14(1), MAP4K2(1), MAPK14(1), MAPK8(2), NFKB1(2), RELA(3), TANK(4), TNFRSF1A(2), TRADD(1) 6698318 37 29 37 12 8 13 6 3 7 0 0.92 1.00 489 FATTY_ACID_BIOSYNTHESIS_PATH_2 ACAA1, ACAA2, ACAT1, ACAT2, ECHS1, EHHADH, HADHA, HADHB, SDS 9 ACAA2(1), ACAT1(1), EHHADH(1), HADHA(2), HADHB(2), SDS(2) 2252946 9 9 9 9 1 2 2 2 2 0 0.92 1.00 490 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(5), CAPN2(2), CAPNS2(1), EP300(5), HDAC1(2), MEF2D(2), NFATC2(5), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKCA(5), SYT1(3) 6598994 39 30 38 12 12 11 6 6 4 0 0.92 1.00 491 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(7), CDC25B(3), CDC25C(1), CHEK1(4), WEE1(2) 3709342 17 16 17 1 4 8 2 1 2 0 0.92 1.00 492 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), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4), CDC42(1), CHUK(2), EGFR(9), F11R(1), GIT1(1), HBEGF(1), IGSF5(1), IKBKB(3), JUN(2), LYN(1), MAP3K14(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK8(2), MAPK9(1), MET(3), NFKB1(2), NFKB2(2), NOD1(5), PAK1(3), PLCG1(2), PLCG2(3), PTPN11(3), PTPRZ1(8), RAC1(2), RELA(3), TJP1(9) 19090856 108 66 107 28 32 29 19 10 18 0 0.93 1.00 493 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(2), CDS1(2), CHAT(2), CHKA(2), CRLS1(1), DGKA(6), DGKB(4), DGKD(5), DGKE(2), DGKG(2), DGKI(7), DGKZ(3), ESCO1(1), ETNK1(3), GPAM(2), GPD1(2), GPD1L(1), GPD2(2), LYPLA1(5), MYST3(11), MYST4(3), PCYT1A(2), PCYT1B(1), PISD(1), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLD1(10), PLD2(4), PNPLA3(1), PPAP2B(2), PTDSS1(1), SH3GLB1(1) 18095124 114 70 112 48 34 44 16 7 13 0 0.93 1.00 494 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), GNA15(1), GNB1(1), HRAS(2), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAPK1(1), MAPK14(1), MAPK3(2), NCF2(5), NFATC2(5), NFATC3(3), NFATC4(2), NFKB1(2), PAK1(3), PIK3C2G(7), PLCB1(7), PPP3CA(2), PPP3CB(5), PPP3CC(2), RAC1(2), RAF1(1), RELA(3), SYT1(3) 10537956 75 50 74 26 26 29 6 10 4 0 0.93 1.00 495 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(3), BTK(5), GSK3A(4), GSK3B(1), LYN(1), PDPK1(1), PFKL(2), PFKM(5), PFKP(2), PLCG1(2), PRKCE(5), RAC1(2), RPS6KB1(1), VAV2(4) 6962292 39 30 38 16 11 9 8 3 8 0 0.93 1.00 496 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(5), NFATC3(3), NFATC4(2), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKCA(5), SP1(1), SP3(1), SYT1(3) 5691372 32 27 32 11 11 11 2 5 3 0 0.93 1.00 497 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), LCMT2(1), PCYT1A(2), PCYT1B(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), WBSCR22(4) 3831272 20 18 20 5 8 7 2 1 2 0 0.93 1.00 498 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(4), JUN(2), MAPK14(1), THBS1(1) 1984344 10 9 10 1 2 2 4 2 0 0 0.93 1.00 499 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), DFFA(1), DFFB(2), FADD(1), JUN(2), MADD(3), MAP3K1(3), MAP3K7(3), MAPK8(2), PAK1(3), PAK2(1), PRKDC(15), RB1(7), SPTAN1(2), TNFRSF1A(2), TRADD(1) 10863874 53 45 52 20 13 21 5 1 13 0 0.93 1.00 500 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), CHST11(1), CHST12(1), PAPSS2(1), SULT1A1(1), SULT1A2(2), SULT1E1(1), SULT2A1(3) 2544332 11 11 11 6 3 3 2 1 2 0 0.93 1.00 501 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(4), DNMT3A(6), DNMT3B(3), MARS(1), MAT1A(1), MTAP(1), MTR(5), TAT(1) 5640642 28 25 28 19 6 12 6 1 3 0 0.94 1.00 502 HSA00930_CAPROLACTAM_DEGRADATION Genes involved in caprolactam degradation AKR1A1, ASAHL, ECHS1, EHHADH, HADH, HADHA, HSD17B10, HSD17B4, NTAN1, SIRT1, SIRT2, SIRT5, SIRT7, VNN2, VNN3 13 EHHADH(1), HADH(1), HADHA(2), HSD17B4(1), SIRT1(1), SIRT2(2), VNN2(5) 3154338 13 12 13 9 1 4 3 1 4 0 0.94 1.00 503 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(2), ACSS1(3), ACSS2(2), FH(2), IDH1(2), MDH1(1), MDH2(1), SUCLA2(2) 3552346 16 15 16 10 3 8 2 2 1 0 0.94 1.00 504 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(2), DLD(2), DLST(1), FH(2), IDH1(2), IDH3A(2), IDH3B(3), MDH1(1), MDH2(1), PC(4), PCK1(3), SDHA(1), SUCLA2(2), SUCLG2(1) 5541852 28 24 28 10 6 11 3 3 5 0 0.94 1.00 505 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), BID(1), BIRC3(3), CASP2(1), CASP6(1), CASP7(2), CASP8(1), CASP9(1), CFLAR(1), CHUK(2), CRADD(1), DAXX(3), DFFA(1), DFFB(2), FADD(1), GSN(2), MAP3K1(3), MAP3K14(1), MAP3K5(3), MAPK8(2), MDM2(1), NFKB1(2), NUMA1(3), PAK2(1), PRKCD(2), PRKDC(15), PSEN1(1), PSEN2(2), PTK2(3), RASA1(6), RB1(7), RELA(3), SPTAN1(2), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TRAF1(4) 19149418 91 66 90 32 18 33 10 7 23 0 0.94 1.00 506 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(3), CAD(10), CANT1(3), CDA(1), CTPS(2), CTPS2(2), DCK(1), DPYD(7), DPYS(4), ENTPD1(1), ENTPD3(1), ENTPD5(1), ENTPD6(3), NME4(1), NME7(2), NT5C1A(2), NT5C1B(2), NT5C2(3), NT5C3(4), NT5E(2), PNPT1(2), POLA1(5), POLA2(3), POLD1(2), POLD3(1), POLE2(2), POLE4(1), POLR1A(4), POLR1B(4), POLR1C(1), POLR1D(1), POLR2A(2), POLR2B(2), POLR2D(1), POLR2E(1), POLR2H(1), POLR3A(3), POLR3B(2), POLR3G(1), POLR3H(1), PRIM1(2), PRIM2(10), RFC5(2), RRM1(2), RRM2B(2), TK2(1), TXNRD1(2), TXNRD2(3), TYMS(1), UMPS(1), UPP1(3), UPP2(1), UPRT(1) 22105464 126 78 124 65 28 51 20 6 21 0 0.94 1.00 507 LIMONENE_AND_PINENE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ECHS1, EHHADH, HADHA, SDS 12 ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2), EHHADH(1), HADHA(2), SDS(2) 3292822 16 14 15 7 1 9 2 1 3 0 0.94 1.00 508 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(3), ACPT(2), ALPI(1), ALPL(3), ALPP(1), ALPPL2(1), CMBL(1), CYP3A4(1), CYP3A43(3), CYP3A7(1), DHRS2(1), PON1(4), PON2(1), PON3(1) 4730528 25 21 25 9 8 8 3 2 4 0 0.94 1.00 509 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(2), CASP10(4), CASP2(1), CASP4(3), CASP6(1), CASP7(2), CASP8(1), CASP9(1), DFFA(1), DFFB(2), GZMB(1), PRF1(2) 5233378 26 23 26 11 6 10 3 2 5 0 0.94 1.00 510 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 7 2 8 1 2 0 0 0.94 1.00 511 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(8), CAPN7(1), CAPN9(1), CAV2(1), CAV3(1), CDC42(1), DOCK1(3), FYN(4), ILK(1), ITGA10(6), ITGA11(3), ITGA2(5), ITGA2B(1), ITGA3(2), ITGA4(5), ITGA5(1), ITGA6(6), ITGA7(3), ITGA8(9), ITGA9(1), ITGAD(6), ITGAE(3), ITGAL(1), ITGAM(3), ITGAV(3), ITGAX(9), ITGB1(4), ITGB2(3), ITGB3(3), ITGB4(9), ITGB5(2), ITGB6(2), ITGB7(1), ITGB8(3), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K6(3), MAPK10(1), MAPK4(1), MAPK6(2), MAPK7(1), MYLK2(2), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PDPK1(1), PIK3R2(4), PTK2(3), PXN(3), RAC1(2), RAPGEF1(3), ROCK1(5), ROCK2(3), SDCCAG8(5), SHC1(1), SHC3(3), SORBS1(5), SOS1(6), TLN1(8), TNS1(8), VASP(2), VAV2(4), VAV3(1), VCL(2) 36879464 235 108 232 81 60 98 41 14 22 0 0.94 1.00 512 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), GNA13(1), LPA(11), MAP3K1(3), MAP3K5(3), MAPK8(2), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), PDK1(1), PHKA2(4), PI3(1), PIK3CB(1), PLD1(10), PLD2(4), PLD3(1), PTK2(3), RDX(1), ROCK1(5), ROCK2(3), SERPINA4(4), SRF(2), TBXA2R(2) 13379548 85 57 82 30 17 37 15 10 6 0 0.94 1.00 513 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(2), TGFB1(1), TGFB2(1) 2290504 10 10 10 10 2 4 4 0 0 0 0.94 1.00 514 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(2), CBL(4), CFLAR(1), CRKL(1), E2F1(3), FOS(1), HRAS(2), IL2RB(2), IL2RG(1), IRS1(4), JAK1(1), JAK3(7), MAPK1(1), MAPK3(2), MYC(1), NMI(1), PIK3CA(21), PIK3R1(1), RAF1(1), RPS6KB1(1), SHC1(1), SOS1(6), STAT5A(2), SYK(1) 9874728 69 46 58 17 23 25 14 3 4 0 0.95 1.00 515 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), ARHGDIB(1), CASP1(2), CASP10(4), CASP8(1), CASP9(1), GZMB(1), JUN(2), PRF1(2) 3454802 15 15 15 10 5 4 2 2 2 0 0.95 1.00 516 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 HRAS(2), SHC1(1), SOS1(6) 2388582 9 9 9 2 1 2 4 1 1 0 0.95 1.00 517 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(7), ATP6V0A1(4), ATP6V0A4(2), ATP6V0D1(1), ATP6V1A(3), ATP6V1B1(2), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4), ATP7B(1), COX10(1), COX4I1(1), COX6B1(2), COX7A2(1), NDUFB5(3), NDUFS1(4), NDUFV1(3), NDUFV2(2), SDHA(1), UQCRB(1) 9402494 49 38 48 20 15 13 12 3 6 0 0.95 1.00 518 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(6), AASDHPPT(1), AASS(6), ACAT1(1), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2), BBOX1(2), DLST(1), DOT1L(5), EHHADH(1), EHMT2(2), GCDH(1), HADHA(2), PLOD1(2), PLOD2(4), PLOD3(4), SDS(2) 10099720 52 42 51 28 5 21 15 4 7 0 0.95 1.00 519 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 5 3 2 0 2 3 0 0.95 1.00 520 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(2), ACTN1(2), ACTN2(6), ACTN3(2), CAPN1(2), CAPNS2(1), ITGA1(4), ITGB1(4), ITGB3(3), PTK2(3), PXN(3), RAC1(2), SPTAN1(2), TLN1(8) 7784474 44 33 43 22 13 15 5 6 5 0 0.95 1.00 521 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(4), ADCY8(13), CACNA1A(8), CACNA1B(1), GNAS(4), GNAT3(1), GNB1(1), GNB3(2), GNG3(1), GRM4(1), ITPR3(3), KCNB1(1), PDE1A(2), PLCB2(5), PRKACA(1), PRKACB(2), PRKACG(1), PRKX(1), SCNN1B(2), SCNN1G(3), TAS1R1(2), TAS2R1(3), TAS2R10(3), TAS2R16(5), TAS2R38(2), TAS2R39(2), TAS2R4(1), TAS2R40(2), TAS2R41(5), TAS2R42(1), TAS2R5(1), TAS2R60(7), TAS2R7(1), TAS2R8(1), TAS2R9(3) 15460190 100 62 100 40 28 35 23 7 7 0 0.95 1.00 522 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(3), IL4(2), JUN(2), MAP3K1(3), MAP3K5(3), MAP4K5(1), MAPK14(1), MAPK8(2), NFKB1(2), RELA(3), TNFRSF9(1) 5344806 28 23 28 12 5 8 9 2 4 0 0.95 1.00 523 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(2), JAK2(3), JUN(2), MAP2K1(2), MAPK3(2), MAPK8(2), PLCG1(2), RAF1(1), SHC1(1), SOS1(6), STAT5A(2) 5861184 30 27 30 8 9 10 6 2 3 0 0.96 1.00 524 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 ARHGEF1(2), GNA12(1), GNA13(1), GNB1(1), MYL2(1), MYLK(7), PLCB1(7), PPP1R12B(3), PRKCA(5), ROCK1(5) 5569976 33 26 33 11 6 16 6 3 2 0 0.96 1.00 525 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(2), ACTN1(2), ACTN2(6), ACTN3(2), BCAR1(5), BCR(1), CAPN1(2), CAPNS2(1), CRKL(1), FYN(4), HRAS(2), ITGA1(4), ITGB1(4), JUN(2), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), MAPK8(2), PPP1R12B(3), PTK2(3), PXN(3), RAF1(1), ROCK1(5), SHC1(1), SOS1(6), TLN1(8), VCL(2) 12940422 79 54 78 27 19 29 15 10 6 0 0.96 1.00 526 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), LCMT2(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), WBSCR22(4) 3890012 18 17 18 4 8 5 2 1 2 0 0.96 1.00 527 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(3), ACAA2(1), ACADM(1), ACADS(3), ACAT1(1), ALDH1B1(3), ALDH2(2), ALDH6A1(2), ALDH7A1(1), ALDH9A1(2), AOX1(11), AUH(1), BCAT1(1), BCAT2(3), BCKDHB(2), DBT(1), DLD(2), EHHADH(1), HADH(1), HADHA(2), HADHB(2), HIBCH(1), HMGCL(1), HMGCS1(1), HMGCS2(1), HSD17B4(1), MCCC1(7), MUT(1), OXCT1(2), PCCA(2), PCCB(6) 11653660 69 48 69 22 15 23 13 10 8 0 0.96 1.00 528 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(2), MST1R(1) 1782314 6 6 6 3 2 3 1 0 0 0 0.96 1.00 529 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(5), POLA2(3), POLB(1), POLD1(2), POLD3(1), POLE2(2), POLE4(1), POLG(2), POLG2(1), POLI(2), POLK(3), POLL(1), POLM(1), POLQ(18), PRIM1(2), PRIM2(10), REV1(5), REV3L(4), RFC5(2) 11221120 66 46 64 17 17 22 13 4 10 0 0.96 1.00 530 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(2), MEF2D(2), PPARA(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), SLC2A4(2), SYT1(3) 5542920 31 23 31 11 11 6 3 7 4 0 0.96 1.00 531 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(3), CDC25C(1), CDK7(1), XPO1(2) 2376300 8 8 8 5 0 4 1 3 0 0 0.96 1.00 532 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(6), APOC2(2), CYP7A1(3), HMGCR(2), LDLR(4), LIPC(1), LPL(3), LRP1(14), SCARB1(3) 6764356 38 32 37 22 16 15 5 0 2 0 0.97 1.00 533 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), SDHC(1) 1766116 6 6 6 2 0 3 1 2 0 0 0.97 1.00 534 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), DFFA(1), DFFB(2), GZMB(1), TOP2A(3), TOP2B(3) 2721976 12 11 12 5 1 5 4 1 1 0 0.97 1.00 535 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(3), ACACA(4), ACADL(2), ACADM(1), ACAT1(1), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH6A1(2), ALDH9A1(2), EHHADH(1), HADHA(2), LDHB(2), LDHC(1), MLYCD(2), MUT(1), PCCA(2), PCCB(6), SDS(2), SUCLA2(2), SUCLG2(1) 8878106 46 37 45 16 8 22 7 3 6 0 0.97 1.00 536 BENZOATE_DEGRADATION_VIA_COA_LIGATION ACAT1, ACAT2, ACYP1, ACYP2, ECHS1, EHHADH, GCDH, HADHA, SDHB, SDS 10 ACAT1(1), EHHADH(1), GCDH(1), HADHA(2), SDS(2) 2113928 7 7 7 10 1 2 2 0 2 0 0.97 1.00 537 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(2), IL6R(1), JAK1(1), JAK2(3), JAK3(7), JUN(2), MAP2K1(2), MAPK3(2), PTPN11(3), RAF1(1), SHC1(1), SOS1(6), SRF(2), STAT3(1) 6555740 37 30 37 9 9 15 8 3 2 0 0.97 1.00 538 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(2), BID(1), CASP8AP2(6), CASP9(1), CES1(2) 3102540 15 12 15 7 4 4 4 2 1 0 0.97 1.00 539 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(3), TNFRSF11A(1), TNFSF11(1), TRAF6(1) 3013540 15 12 15 3 5 5 0 3 2 0 0.97 1.00 540 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), DAXX(3), HRAS(2), HSPB2(1), MAP2K6(3), MAP3K1(3), MAP3K5(3), MAP3K7(3), MAP3K9(4), MAPK14(1), MAPKAPK2(1), MAPKAPK5(4), MEF2A(2), MEF2C(2), MEF2D(2), MYC(1), PLA2G4A(5), RAC1(2), RPS6KA5(3), SHC1(1), STAT1(2), TGFB1(1), TGFB2(1), TRADD(1) 9996480 54 42 54 21 11 20 12 5 6 0 0.97 1.00 541 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(2), PSMB6(1), PSMB8(3), PSMB9(2) 2341234 11 10 10 6 5 4 1 0 1 0 0.97 1.00 542 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(4), CASP6(1), CASP7(2), CASP8(1), CFLAR(1), DAXX(3), DFFA(1), DFFB(2), FADD(1), FAF1(1), JUN(2), MAP3K1(3), MAP3K7(3), MAPK8(2), PAK1(3), PAK2(1), PRKDC(15), PTPN13(3), RB1(7), RIPK2(1), SPTAN1(2) 11532976 60 46 59 14 15 27 6 1 11 0 0.97 1.00 543 IL22BPPATHWAY IL-22 is produced by T cells and induces the acute phase inflammatory response in hepatocytes. IL10RA, IL22, IL22RA1, IL22RA2, JAK1, JAK2, JAK3, SOCS3, STAT1, STAT3, STAT5A, STAT5B, TYK2 13 IL10RA(1), IL22(1), IL22RA1(1), IL22RA2(1), JAK1(1), JAK2(3), JAK3(7), STAT1(2), STAT3(1), STAT5A(2), TYK2(8) 5072466 28 22 28 9 9 12 4 1 2 0 0.97 1.00 544 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(4), ACACB(8), ACAT1(1), ACOT12(1), ACSS1(3), ACSS2(2), ALDH1B1(3), 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(2), PC(4), PCK1(3), PCK2(1), PDHA1(2), PDHA2(5), PKLR(3), PKM2(1) 12575344 67 52 67 32 19 32 6 4 6 0 0.97 1.00 545 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(2), BID(1), BIRC3(3), CASP6(1), CASP7(2), CASP8(1), CASP9(1), DFFA(1), DFFB(2) 3689762 17 15 17 8 3 7 2 2 3 0 0.97 1.00 546 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 B3GALNT1(1), B3GALT1(2), B3GALT2(2), B3GALT4(1), B3GNT2(1), B3GNT3(4), B3GNT4(1), B4GALT1(1), B4GALT3(2), B4GALT4(1), B4GALT6(2), FUT3(3), FUT5(4), FUT6(2), FUT9(1), GBGT1(3), GCNT2(1), PIGA(1), PIGB(1), PIGF(1), PIGG(4), PIGH(1), PIGK(1), PIGL(2), PIGM(1), PIGN(2), PIGO(2), PIGQ(1), PIGS(1), PIGX(1), PIGZ(3), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2), ST3GAL5(2), ST3GAL6(1), ST6GALNAC3(3), ST6GALNAC5(2), ST8SIA1(2) 13400908 69 54 68 41 17 22 17 6 7 0 0.97 1.00 547 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(2), LTA4H(2), PLA2G2A(1), PLA2G6(6), PTGES(1), PTGS1(2), TBXAS1(5) 4144552 22 17 20 7 4 12 4 1 1 0 0.98 1.00 548 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), CHST11(1), CHST12(1), CHST14(1), CHST3(2), DSE(1), XYLT1(4) 4030810 16 15 16 13 2 7 3 2 2 0 0.98 1.00 549 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(2), CASP7(2), CASP8(1), GAPDH(3), INSR(7), ITCH(2), MAGI1(5), MAGI2(7), RERE(3), WWP1(1), WWP2(1) 6378808 36 25 36 13 8 12 6 3 7 0 0.98 1.00 550 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(3), IL1B(1), IL1RAP(2), IL1RN(1), IRAK1(4), IRAK2(1), IRAK3(3), JUN(2), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAP3K14(1), MAP3K7(3), MAPK14(1), MAPK8(2), NFKB1(2), RELA(3), TGFB1(1), TGFB2(1), TOLLIP(1), TRAF6(1) 8061264 45 34 45 18 14 16 6 5 4 0 0.98 1.00 551 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(3), TNFRSF13B(2), TNFSF13(1), TRAF3(1), TRAF5(2), TRAF6(1) 3974740 18 15 18 9 6 4 1 1 6 0 0.98 1.00 552 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(2), ADH7(1), ADHFE1(2), DHRS2(1), ESCO1(1), MYST3(11), MYST4(3), PNPLA3(1), SH3GLB1(1) 6562148 32 28 32 12 11 11 4 2 4 0 0.98 1.00 553 DNA_POLYMERASE POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLS 7 POLB(1), POLD1(2), POLG(2), POLL(1), POLQ(18) 4560360 24 20 22 4 6 11 3 3 1 0 0.98 1.00 554 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(3), ACACA(4), ACACB(8), ACADM(1), ACAT1(1), ACSS1(3), ACSS2(2), ALDH1B1(3), ALDH2(2), ALDH6A1(2), ALDH7A1(1), ALDH9A1(2), EHHADH(1), HADHA(2), HIBCH(1), LDHAL6B(1), LDHB(2), LDHC(1), MLYCD(2), MUT(1), PCCA(2), PCCB(6), SUCLA2(2), SUCLG2(1) 10649918 54 43 54 24 15 23 6 4 6 0 0.98 1.00 555 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(2), CSF1(2), IL4(2) 1697764 6 5 6 6 2 2 1 0 1 0 0.98 1.00 556 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(2), MTHFD2(3), POLB(1), POLD1(2), POLG(2), PRPS2(1), RRM1(2) 3494318 16 14 16 5 5 6 3 1 1 0 0.98 1.00 557 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(2) 2985950 10 10 10 8 1 4 1 2 2 0 0.98 1.00 558 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(1), B4GALT1(1), B4GALT3(2), B4GALT5(3), FUT8(2), MAN1A1(3), MGAT1(1), MGAT2(2), MGAT3(4), MGAT4A(2), MGAT4B(1), MGAT5(3), RPN1(1), ST6GAL1(1) 5405504 27 22 27 18 11 8 2 3 3 0 0.99 1.00 559 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), IRS1(4), JAK1(1), JAK3(7), RPS6KB1(1), SHC1(1), STAT6(1) 4071928 19 16 19 9 3 10 5 0 1 0 0.99 1.00 560 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(3), CRY2(2), NPAS2(1), PER1(6), PER2(3), PER3(1) 4651140 23 19 23 11 4 10 7 1 1 0 0.99 1.00 561 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(2), DLD(2), DLST(1), FH(2), IDH1(2), IDH3A(2), IDH3B(3), MDH1(1), MDH2(1), OGDH(3), OGDHL(4), PC(4), PCK1(3), PCK2(1), SDHA(1), SDHC(1), SUCLA2(2), SUCLG2(1) 8013026 37 31 37 25 8 15 4 4 6 0 0.99 1.00 562 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(2), EIF2B5(1), EIF5(1), GSK3B(1), PPP1CA(1) 3140988 13 13 13 6 5 6 1 0 1 0 0.99 1.00 563 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), PIGA(1), PIGB(1), PIGF(1), PIGG(4), PIGH(1), PIGK(1), PIGL(2), PIGM(1), PIGN(2), PIGO(2), PIGQ(1), PIGS(1), PIGX(1), PIGZ(3) 6629788 28 25 28 18 6 7 5 6 4 0 0.99 1.00 564 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(2), LCMT1(2), LCMT2(1), MARS(1), MAT1A(1), PAPSS2(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), SEPHS1(3), WBSCR22(4) 6761864 30 27 30 15 11 11 2 2 4 0 0.99 1.00 565 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_NEOLACTOSERIES ABO, B3GNT1, FUT1, FUT2, FUT9, GCNT2, ST8SIA1 7 FUT9(1), GCNT2(1), ST8SIA1(2) 1700256 4 4 4 4 1 1 1 0 1 0 0.99 1.00 566 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), ACSL5(1), ACSL6(2), ADIPOQ(1), ADIPOR1(1), ADIPOR2(2), AKT1(1), AKT3(2), CD36(1), CHUK(2), CPT1A(3), CPT1C(5), CPT2(2), G6PC(2), G6PC2(2), IKBKB(3), IRS1(4), IRS2(2), IRS4(3), JAK1(1), JAK2(3), JAK3(7), LEPR(10), MAPK10(1), MAPK8(2), MAPK9(1), NFKB1(2), NFKB2(2), NFKBIB(1), PCK1(3), PCK2(1), POMC(2), PPARA(2), PPARGC1A(5), PRKAA2(2), PRKAB2(1), PRKAG2(4), PRKAG3(2), PRKCQ(4), PTPN11(3), RELA(3), RXRA(1), RXRG(5), SLC2A4(2), STAT3(1), STK11(3), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TYK2(8) 22732024 136 79 135 49 42 55 20 7 12 0 0.99 1.00 567 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(3), MAP3K1(3), MAP3K14(1), NFKB1(2), RELA(3), TNFAIP3(4), TRAF3(1), TRAF6(1) 4931312 22 17 22 10 5 6 4 2 5 0 0.99 1.00 568 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(3) 1687262 5 5 5 3 3 1 1 0 0 0 0.99 1.00 569 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(2), AKT1(1), AKT3(2), DAG1(1), ITPKA(1), ITPKB(3), ITPR1(5), ITPR2(11), ITPR3(3), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), PDK1(1), PHKA2(4), PIK3CB(1), PITX2(3), PLD1(10), PLD2(4), PLD3(1), VN1R1(2) 12327212 66 48 64 21 18 29 7 6 6 0 0.99 1.00 570 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(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), CYP2C19(6), CYP2C9(2), DHRS2(1), EHHADH(1), ESCO1(1), HADHA(2), MYST3(11), MYST4(3), PNPLA3(1), SH3GLB1(1) 8198324 38 33 38 17 10 14 6 2 6 0 0.99 1.00 571 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), CYP2E1(1), NR1I3(1), PTGS1(2) 1417058 5 4 5 4 1 3 0 1 0 0 0.99 1.00 572 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(2), GOSR1(1), SEC22B(4), SNAP23(1), SNAP25(2), STX10(1), STX11(1), STX5(2), STX7(1), TSNARE1(2), USE1(1), YKT6(1) 4427750 19 18 19 11 6 6 4 2 1 0 0.99 1.00 573 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 0.99 1.00 574 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(2), MTHFD1(3), MTHFD1L(2), MTHFD2(3), MTHFR(2), MTR(5), TYMS(1) 4817926 21 19 21 13 4 6 8 2 1 0 0.99 1.00 575 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(2), DTX2(2), DTX3(2), DTX3L(1), DTX4(2), DVL1(3), DVL3(3), EP300(5), HDAC1(2), JAG2(1), LFNG(1), MAML1(2), MAML2(6), MAML3(2), MFNG(2), NCOR2(6), NCSTN(3), NOTCH1(11), NOTCH2(7), NOTCH3(5), NOTCH4(3), PSEN1(1), PSEN2(2), PSENEN(2), SNW1(2) 19396660 93 68 92 34 27 26 15 6 19 0 0.99 1.00 576 CHONDROITIN B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 HS3ST2(1), XYLT1(4) 1890716 5 5 5 7 1 3 1 0 0 0 0.99 1.00 577 HEPARAN_SULFATE_BIOSYNTHESIS B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 HS3ST2(1), XYLT1(4) 1890716 5 5 5 7 1 3 1 0 0 0 0.99 1.00 578 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 ARFGAP1(1), ARFGAP3(1), ARFGEF2(1), CLTB(2), COPA(8), GBF1(3), KDELR2(2) 4367764 18 17 17 8 8 4 4 1 1 0 0.99 1.00 579 SELENOAMINO_ACID_METABOLISM AHCY, CBS, CTH, GGT1, MARS, MARS2, MAT1A, MAT2B, PAPSS1, PAPSS2, SCLY, SEPHS1 12 AHCY(1), CBS(4), GGT1(2), MARS(1), MAT1A(1), PAPSS2(1), SEPHS1(3) 3369540 13 11 13 11 4 6 0 1 2 0 0.99 1.00 580 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(8), ALG2(2), ALG5(1), ALG6(3), B4GALT1(1), B4GALT3(2), DHDDS(2), DOLPP1(1), FUT8(2), GANAB(5), MAN1A1(3), MAN1A2(4), MAN1C1(3), MAN2A1(4), MGAT1(1), MGAT2(2), MGAT3(4), MGAT4A(2), MGAT4B(1), MGAT5(3), MGAT5B(4), RPN1(1), ST6GAL1(1), STT3B(1) 11591360 62 45 62 25 23 22 5 6 6 0 0.99 1.00 581 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), SYT1(3) 3177478 11 10 11 6 4 1 1 4 1 0 0.99 1.00 582 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(3), EDN1(1), EP300(5), HIF1A(1), JUN(2), NOS3(1), VHL(1) 4582432 18 16 17 10 3 5 6 3 1 0 0.99 1.00 583 BIOSYNTHESIS_OF_STEROIDS DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, IDI1, LSS, MVD, MVK, NQO1, NQO2, PMVK, SC5DL, SQLE, VKORC1 14 DHCR7(2), FDFT1(1), FDPS(1), HMGCR(2), IDI1(1), MVD(1), PMVK(1), SC5DL(1), SQLE(2) 3072458 12 11 12 5 3 6 2 1 0 0 0.99 1.00 584 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(3), ACADVL(1), ACAT1(1), ACOX1(2), ACOX3(4), ACSL1(2), ACSL3(1), ACSL5(1), ACSL6(2), ADH1B(1), ADH1C(1), ADH4(2), ADH5(2), ADH7(1), ADHFE1(2), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), CPT1A(3), CPT1C(5), CPT2(2), CYP4A22(1), DCI(1), EHHADH(1), GCDH(1), HADH(1), HADHA(2), HADHB(2), HSD17B4(1), PECI(1) 13166660 59 50 59 30 12 25 9 8 5 0 0.99 1.00 585 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(2), APAF1(1), CASP9(1), DAXX(3), FAS(1), FASLG(1), HSPB2(1), MAPKAPK2(1) 3068186 11 10 11 11 4 4 1 1 1 0 0.99 1.00 586 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(4), PDHA1(2) 2508910 7 7 7 7 0 4 0 1 2 0 0.99 1.00 587 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), CREB3(2), CREB5(3), DUSP10(3), EEF2K(3), GADD45A(1), MAP2K3(2), MAP2K6(3), MAP3K4(4), MAP3K5(3), MAP3K7(3), MAPK1(1), MAPK13(2), MAPK14(1), MAPKAPK2(1), MAPKAPK5(4), MYEF2(3), NFKB1(2), NR2C2(1), SRF(2), TRAF6(1) 9192632 47 35 47 18 6 18 13 5 5 0 0.99 1.00 588 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(6), AGXT2(2), AKR1B10(1), ALAS1(2), AOC2(2), AOC3(3), CBS(4), CHKA(2), DAO(1), DLD(2), DMGDH(2), GARS(1), GATM(1), GLDC(3), GNMT(1), PHGDH(2), PIPOX(1), PISD(1), PSPH(1), RDH11(2), RDH12(2), RDH13(1), SARDH(4), SARS(2), SARS2(2), SDS(2), TARS(3), TARS2(2) 11695846 58 44 58 25 13 25 12 4 4 0 1.00 1.00 589 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(3), MAPK1(1), MAPK3(2), MAPK8(2), NFKB1(2), NSMAF(3), RAF1(1), RELA(3), SMPD1(3), TNFRSF1A(2), TRADD(1) 5630140 28 20 28 13 9 9 5 2 3 0 1.00 1.00 590 HSA00061_FATTY_ACID_BIOSYNTHESIS Genes involved in fatty acid biosynthesis ACACA, ACACB, FASN, MCAT, OLAH, OXSM 6 ACACA(4), ACACB(8), MCAT(4), OLAH(1), OXSM(1) 4429352 18 17 17 11 6 10 1 0 1 0 1.00 1.00 591 HSA03060_PROTEIN_EXPORT Genes involved in protein export OXA1L, SEC61A2, SRP19, SRP54, SRP68, SRP72, SRP9, SRPR 8 SEC61A2(1), SRP54(1), SRP68(1), SRP72(1), SRPR(1) 2013536 5 5 5 4 1 2 2 0 0 0 1.00 1.00 592 CHOLESTEROL_BIOSYNTHESIS C10orf110, CYP51A1, DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, HMGCS1, IDI1, LSS, MVD, MVK, NSDHL, PMVK, SC4MOL, SC5DL, SQLE 15 DHCR7(2), FDFT1(1), FDPS(1), HMGCR(2), HMGCS1(1), IDI1(1), MVD(1), NSDHL(1), PMVK(1), SC5DL(1), SQLE(2) 3632980 14 13 14 5 3 7 2 2 0 0 1.00 1.00 593 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 MRPS7(2), RPL10L(4), RPL14(1), RPL19(1), RPL28(1), RPL30(1), RPL32(1), RPL37(1), RPL3L(1), RPL7(1), RPL8(4), RPS11(1), RPS18(2), RPS2(1), RPS21(1), RPS26(1), RPS6(1), RPS8(1) 6262930 26 23 25 12 5 10 6 3 2 0 1.00 1.00 594 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(2), MTHFD1(3), MTHFD1L(2), MTHFD2(3), MTHFR(2), MTR(5), TYMS(1) 5119102 21 19 21 13 4 6 8 2 1 0 1.00 1.00 595 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(2), MAP3K7(3), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), NR2C2(1), RALBP1(1), TNFAIP3(4), TNFRSF1A(2), TNFRSF1B(1), TRADD(1) 7490062 33 26 33 15 7 11 4 7 4 0 1.00 1.00 596 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(3), ITPR1(5), ITPR2(11), ITPR3(3), NFAT5(3), PDE6A(3), PDE6B(3), PDE6H(2), SLC6A13(4), TF(7) 9814920 49 39 49 15 20 14 8 1 6 0 1.00 1.00 597 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(11), MYST4(3), PNPLA3(1), SH3GLB1(1) 4289088 18 15 18 8 5 6 3 1 3 0 1.00 1.00 598 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), DAXX(3), FOS(1), HRAS(2), IKBKB(3), JUN(2), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K5(2), MAP2K6(3), MAP3K1(3), MAP3K11(2), MAP3K12(2), MAP3K13(5), MAP3K14(1), MAP3K4(4), MAP3K5(3), MAP3K6(1), MAP3K7(3), MAP3K9(4), MAP4K1(2), MAP4K2(1), MAP4K3(5), MAP4K4(6), MAP4K5(1), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPK4(1), MAPK6(2), MAPK7(1), MAPK8(2), MAPK9(1), MAPKAPK2(1), MAPKAPK5(4), MEF2A(2), MEF2C(2), MEF2D(2), MYC(1), NFKB1(2), PAK1(3), PAK2(1), RAC1(2), RAF1(1), RELA(3), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KA4(3), RPS6KA5(3), RPS6KB1(1), SHC1(1), SP1(1), STAT1(2), TGFB1(1), TGFB2(1), TRADD(1) 26589284 136 80 135 53 34 46 26 12 18 0 1.00 1.00 599 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 1.00 1.00 600 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(2), PSMB6(1), PSMC2(4), PSMC3(1), PSMD1(2), PSMD11(1), PSMD12(1), PSMD13(1) 4277518 16 15 16 12 5 8 2 0 1 0 1.00 1.00 601 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(3), SOD2(1) 3452132 14 10 14 2 3 5 2 1 3 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), HMOX1(1), IL10(1), IL10RA(1), JAK1(1), STAT1(2), STAT3(1), STAT5A(2) 3285880 11 10 11 8 3 5 2 1 0 0 1.00 1.00 603 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(2), EEF1B2(1), EEF1D(1), EEF1G(2), EEF2(1), EEF2K(3), EIF2AK3(7), EIF2B1(1), EIF2B2(2), EIF2B3(1), EIF2B5(1), EIF4A1(3), EIF4A2(3), EIF4G1(8), EIF4G3(3), EIF5(1), EIF5B(1), ETF1(2), KIAA0664(1), PABPC1(1), PABPC3(7), PAIP1(1) 12059144 53 44 53 29 10 21 15 2 5 0 1.00 1.00 604 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(6), AGXT2(2), ALAS1(2), AOC2(2), AOC3(3), CBS(4), CHKA(2), DAO(1), DLD(2), DMGDH(2), GARS(1), GATM(1), GLDC(3), PISD(1), PLCB2(5), PLCG1(2), PLCG2(3), PSPH(1), SARDH(4), SARS(2), TARS(3) 11524254 52 40 52 23 13 21 11 3 4 0 1.00 1.00 605 RNA_POLYMERASE POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT 14 POLR1B(4), POLR2A(2), POLR2B(2), POLR2D(1), POLR2E(1), POLR2H(1) 3743518 11 10 11 5 3 4 0 1 3 0 1.00 1.00 606 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(2), CLK3(2), CLK4(2), COL2A1(8), CPSF1(3), CPSF2(2), CPSF3(1), CPSF4(4), CSTF2(2), CSTF2T(2), CSTF3(2), DDX1(5), DHX15(2), DHX16(2), DHX8(2), DHX9(7), DICER1(7), FUS(1), METTL3(1), NCBP1(2), NONO(1), NXF1(2), PAPOLA(1), POLR2A(2), PRPF3(1), PRPF4(3), PRPF4B(4), PRPF8(9), PSKH1(1), PTBP2(1), RBM17(1), RBM5(1), RNGTT(1), RNPS1(1), SF3A2(2), SF3A3(1), SF3B1(3), SF3B2(2), SF3B4(1), SF4(3), SFRS12(1), SFRS14(6), SFRS2(2), SFRS4(1), SFRS6(3), SFRS8(3), SNRPA(1), SNRPB(3), SNRPD1(1), SNRPD2(2), SNRPN(1), SPOP(1), SRPK1(2), SRPK2(1), SRRM1(2), SUPT5H(3), U2AF2(1), XRN2(4) 28537138 142 82 136 48 36 53 32 10 11 0 1.00 1.00 607 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), CDK2(1), GMNN(2), MCM10(4), MCM2(1), MCM3(1), MCM4(4), MCM5(6), MCM6(2), MCM7(3), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), POLA2(3), POLD1(2), POLD3(1), POLE2(2), PRIM1(2), RFC1(1), RFC4(4), RFC5(2), RPA4(2), UBB(1), UBC(1) 13878660 54 45 54 24 13 18 13 1 9 0 1.00 1.00 608 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), EBP(1), FDFT1(1), FDPS(1), GGPS1(1), HMGCR(2), HSD17B7(1), IDI1(1), IDI2(1), MVD(1), NSDHL(1), PMVK(1), SC5DL(1), SQLE(2), TM7SF2(2) 5284998 19 17 19 8 4 10 4 1 0 0 1.00 1.00 609 RHOPATHWAY RhoA is a G protein whose active form stabilizes actin structures such as focal adhesions and activates Rock1, which phosphorylates myosin light chains. ACTR2, ACTR3, ARHA, ARHGAP1, ARHGAP4, ARHGAP5, ARHGAP6, ARHGEF1, ARHGEF11, ARHGEF5, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, BAIAP2, CFL1, DIAPH1, GSN, LIMK1, MYL2, MYLK, OPHN1, PFN1, PIP5K1A, PIP5K1B, PPP1R12B, ROCK1, SRC, TLN1, VCL 30 ACTR2(1), ARHGAP1(1), ARHGAP4(1), ARHGAP6(5), ARHGEF1(2), ARHGEF11(7), ARHGEF5(1), ARPC1A(2), ARPC1B(1), CFL1(3), DIAPH1(1), GSN(2), LIMK1(1), MYL2(1), MYLK(7), OPHN1(1), PIP5K1A(4), PIP5K1B(1), PPP1R12B(3), ROCK1(5), TLN1(8), VCL(2) 12577124 60 43 58 20 10 28 13 6 3 0 1.00 1.00 610 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(4), POLR1B(4), POLR1C(1), POLR1D(1), POLR2A(2), POLR2B(2), POLR2D(1), POLR2E(1), POLR2H(1), POLR3A(3), POLR3B(2), POLR3G(1), POLR3H(1) 6292478 24 20 23 20 7 11 1 2 3 0 1.00 1.00 611 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), EHHADH(1), ESCO1(1), GCDH(1), HADHA(2), MYST3(11), MYST4(3), PNPLA3(1), SH3GLB1(1) 6846592 24 21 24 16 6 8 4 1 5 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(10), CANT1(3), CDA(1), CTPS(2), CTPS2(2), DCK(1), DPYD(7), DPYS(4), ENTPD1(1), NT5E(2), POLB(1), POLD1(2), POLG(2), POLL(1), POLQ(18), POLR1B(4), POLR2A(2), POLR2B(2), POLR2D(1), POLR2E(1), POLR2H(1), RRM1(2), TK2(1), TXNRD1(2), TYMS(1), UMPS(1), UPP1(3) 15680732 78 53 76 30 16 36 11 6 9 0 1.00 1.00 613 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), BID(1), BIRC3(3), CASP10(4), CASP6(1), CASP7(2), CASP8(1), CASP9(1), CFLAR(1), CHUK(2), DFFA(1), DFFB(2), FADD(1), GAS2(2), MAP3K14(1), NFKB1(2), RELA(3), SPTAN1(2), TNFRSF10A(1), TNFRSF10B(1), TRADD(1) 9154184 34 27 34 14 9 12 2 4 7 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(2), GTF2B(1), GTF2E1(1), GTF2H2(1), GTF2H4(1), ILK(1), POLR1A(4), POLR1B(4), POLR2A(2), POLR2B(2), POLR2E(1), POLR2H(1), POLR3B(2), POLR3D(1), POLR3E(2), POLR3H(1), TAF5(2), TAF9(2), TBP(1) 9538486 33 26 33 22 11 9 3 3 7 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 ALPI(1), ALPL(3), ALPP(1), ALPPL2(1), ASCC3(9), ATP13A2(1), DDX18(2), DDX19A(2), DDX23(6), DDX4(1), DDX41(2), DDX50(1), DDX52(1), DDX54(3), DDX55(1), DDX56(1), ENTPD7(1), ERCC2(3), ERCC3(2), GCH1(2), IFIH1(3), NUDT8(1), RAD54L(1), SETX(11), SKIV2L2(2), SMARCA2(3), SPR(1) 17193732 66 45 66 24 18 29 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