rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q 1 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(1), CAD(4), CDA(1), CTPS(1), DCK(1), DCTD(2), DHODH(1), DPYD(9), DPYS(1), DTYMK(1), ENTPD1(1), ENTPD5(2), ENTPD6(2), NME6(3), NME7(2), NT5C1A(1), NT5C1B(5), NT5C2(2), NT5E(1), PNPT1(6), POLA1(3), POLA2(2), POLD1(2), POLD2(1), POLD3(1), POLE(10), POLE2(1), POLR1A(3), POLR1B(5), POLR1C(2), POLR1D(2), POLR2A(1), POLR2B(3), POLR2D(1), POLR2K(1), POLR3A(6), POLR3B(9), POLR3GL(1), POLR3K(1), PRIM2(3), RFC5(1), RRM1(2), TK2(1), TXNRD1(1), TXNRD2(1), UCK2(1), UMPS(1), UPB1(2), UPP2(1), UPRT(2) 14952294 118 49 116 26 39 38 22 0 19 0 2.92e-11 1.80e-08 2 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 ADA(1), ADCY1(5), ADCY2(8), ADCY3(2), ADCY4(2), ADCY5(6), ADCY7(2), ADCY8(3), ADCY9(2), ADSL(2), ADSS(1), AK2(1), AK5(2), AK7(1), ALLC(2), AMPD1(6), AMPD2(3), AMPD3(1), ATIC(1), DCK(1), ENPP3(2), ENTPD1(1), ENTPD5(2), ENTPD6(2), GART(1), GMPR(1), GUCY1A2(6), GUCY1A3(5), GUCY1B3(2), GUCY2C(3), GUCY2D(6), GUCY2F(6), IMPDH1(2), IMPDH2(3), NME6(3), NME7(2), NPR1(2), NPR2(2), NT5C1A(1), NT5C1B(5), NT5C2(2), NT5E(1), NUDT9(1), PAICS(1), PAPSS1(1), PAPSS2(2), PDE10A(7), PDE11A(2), PDE1A(2), PDE1C(5), PDE3B(1), PDE4A(1), PDE4B(3), PDE4D(1), PDE5A(3), PDE7B(1), PDE8B(2), PDE9A(2), PNPT1(6), POLA1(3), POLA2(2), POLD1(2), POLD2(1), POLD3(1), POLE(10), POLE2(1), POLR1A(3), POLR1B(5), POLR1C(2), POLR1D(2), POLR2A(1), POLR2B(3), POLR2D(1), POLR2K(1), POLR3A(6), POLR3B(9), POLR3GL(1), POLR3K(1), PPAT(5), PRIM2(3), PRPS1(1), PRPS2(1), PRUNE(1), RFC5(1), RRM1(2), XDH(1) 30197542 223 64 221 75 79 69 42 1 32 0 2.23e-09 6.87e-07 3 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 126 CADM3(4), CD22(4), CD226(2), CD274(2), CD28(1), CD40(1), CD40LG(4), CD58(1), CD6(1), CD80(1), CDH1(2), CDH15(1), CDH2(8), CDH3(3), CDH4(5), CDH5(1), CLDN10(3), CLDN16(2), CLDN17(3), CLDN2(1), CLDN8(2), CNTN1(7), CNTN2(4), CNTNAP1(3), CNTNAP2(5), CTLA4(1), ESAM(1), GLG1(1), HLA-A(2), HLA-B(1), HLA-DMB(1), HLA-DOA(1), HLA-DPB1(2), HLA-DQA2(2), HLA-DQB1(1), HLA-DRA(3), HLA-DRB1(1), HLA-DRB5(1), HLA-F(1), HLA-G(1), ITGA4(5), ITGA6(2), ITGA8(3), ITGA9(3), ITGAL(4), ITGAM(3), ITGAV(4), ITGB2(2), ITGB7(2), ITGB8(1), L1CAM(2), MAG(2), NCAM1(4), NCAM2(7), NEGR1(3), NEO1(3), NFASC(6), NLGN1(4), NLGN2(2), NLGN3(1), NRCAM(1), NRXN1(4), NRXN2(2), PDCD1LG2(1), PECAM1(1), PTPRC(9), PTPRF(5), PTPRM(14), PVRL1(4), PVRL2(1), PVRL3(1), SDC1(1), SDC2(3), SDC3(1), SDC4(1), SELE(2), SELL(3), SELP(2), SELPLG(1), SIGLEC1(2), SPN(1), VCAM1(2) 24479520 216 59 216 70 67 86 33 4 26 0 7.76e-09 1.59e-06 4 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 125 ABL1(2), ABLIM1(4), ABLIM3(2), ARHGEF12(2), CDC42(1), CXCR4(1), DCC(5), DPYSL2(4), DPYSL5(1), EFNA5(3), EFNB2(1), EFNB3(1), EPHA1(4), EPHA2(2), EPHA3(7), EPHA4(3), EPHA5(9), EPHA7(4), EPHA8(3), EPHB1(3), EPHB2(3), EPHB3(1), EPHB4(4), FYN(1), GNAI1(1), GSK3B(2), L1CAM(2), LIMK1(2), LIMK2(1), LRRC4C(3), MAPK3(1), MET(1), NCK1(1), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), NRP1(1), NTN1(2), NTN4(2), NTNG1(3), PAK1(1), PAK2(3), PAK3(3), PAK7(3), PLXNA2(5), PLXNA3(1), PLXNB1(2), PLXNB3(1), PLXNC1(3), PPP3CA(2), PPP3CB(2), PPP3CC(3), PTK2(1), RASA1(5), RGS3(3), RHOA(1), ROBO1(9), ROBO2(3), ROBO3(3), ROCK1(8), ROCK2(4), SEMA3A(4), SEMA3C(1), SEMA3D(5), SEMA3E(6), SEMA3G(1), SEMA4A(2), SEMA4B(1), SEMA4D(4), SEMA4F(5), SEMA4G(4), SEMA5A(5), SEMA5B(5), SEMA6B(2), SEMA6C(2), SEMA6D(5), SEMA7A(2), SLIT1(3), SLIT2(4), SLIT3(4), SRGAP1(2), SRGAP3(1), UNC5A(1), UNC5B(1), UNC5C(4) 35142832 240 67 240 73 100 65 43 3 29 0 3.48e-07 0.000054 5 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 86 ACVR1(3), ACVR1B(3), ACVR1C(1), ACVR2A(2), ACVR2B(2), ACVRL1(2), BMP2(1), BMP4(2), BMP5(3), BMP6(1), BMP7(2), BMPR1A(1), BMPR1B(1), BMPR2(8), CREBBP(8), CUL1(5), DCN(2), EP300(8), FST(2), GDF5(2), GDF6(1), INHBA(3), INHBC(1), INHBE(1), LTBP1(3), MAPK3(1), NODAL(1), PPP2CA(1), PPP2CB(2), PPP2R1A(1), PPP2R1B(1), PPP2R2B(2), PPP2R2C(2), RBL1(4), RBL2(3), RBX1(1), RHOA(1), ROCK1(8), ROCK2(4), RPS6KB2(1), SMAD1(1), SMAD3(3), SMAD5(1), SMAD9(1), SMURF1(2), SMURF2(2), SP1(1), TFDP1(1), TGFB1(1), TGFB2(4), TGFBR1(5), TGFBR2(2), THBS1(3), THBS2(8), THBS3(2), THBS4(1), ZFYVE16(4), ZFYVE9(4) 17535458 147 47 145 36 48 50 24 1 23 1 3.84e-06 0.00047 6 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 ADCY1(5), CREM(2), FHL5(3), FSHB(2), FSHR(2), GNAS(2), XPO1(1) 1676768 17 16 17 7 7 2 4 1 3 0 0.000031 0.0028 7 ERBB4PATHWAY ErbB4 (aka HER4) is a receptor tyrosine kinase that binds neuregulins as well as members of the EGF family, which also target EGF receptors. ADAM17, ERBB4, NRG2, NRG3, PRKCA, PRKCB1, PSEN1 6 ADAM17(3), ERBB4(7), NRG2(3), NRG3(5), PRKCA(3) 1646150 21 16 21 4 5 8 2 1 5 0 0.000034 0.0028 8 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 107 A4GNT(3), ALG1(1), ALG10B(3), ALG11(1), ALG12(1), ALG14(1), ALG2(1), ALG6(1), ALG8(3), ALG9(1), B3GNT2(1), B3GNT7(2), B4GALT1(2), B4GALT3(3), CHPF(1), CHST1(1), CHST11(1), CHST12(1), CHST13(1), CHST4(3), CHSY1(1), DAD1(2), DDOST(1), DPAGT1(1), EXT1(5), EXTL1(1), EXTL2(5), EXTL3(5), FUT11(1), FUT8(2), GALNT11(1), GALNT12(1), GALNT13(1), GALNT14(4), GALNT2(2), GALNT5(5), GALNT6(1), GALNT7(1), GALNT8(1), GALNTL1(2), GALNTL2(3), GALNTL4(1), GALNTL5(3), GANAB(1), GCNT1(2), GCNT3(2), GCNT4(3), HS2ST1(1), HS3ST1(1), HS3ST2(3), HS6ST3(1), MAN1A1(2), MAN1A2(1), MAN1B1(1), MAN1C1(3), MAN2A1(7), MGAT1(1), MGAT4A(1), MGAT5(2), NDST1(2), NDST2(1), NDST3(6), NDST4(1), OGT(2), RPN2(1), ST3GAL2(1), ST3GAL3(3), ST3GAL4(1), ST6GALNAC1(2), STT3B(4), XYLT1(2), XYLT2(1) 19542070 141 49 141 45 41 43 38 2 17 0 0.000037 0.0028 9 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 80 ACVR1(3), ACVR1B(3), ACVRL1(2), AKT1(1), BMPR1A(1), BMPR2(8), BUB1(2), CDKL1(2), CDS1(2), CDS2(2), CLK1(2), CLK4(2), CSNK2A2(1), DGKA(1), DGKB(2), DGKD(8), DGKE(2), DGKG(2), DGKH(7), DGKZ(1), IMPA1(1), INPP4A(1), INPP4B(2), INPPL1(3), MAP3K10(1), MOS(1), NEK1(2), OCRL(6), PIK3C2A(3), PIK3C2B(6), PIK3C2G(2), PIK3CB(1), PIK3CG(5), PLCB1(1), PLCB3(3), PLCB4(2), PLCD1(4), PLCG1(1), PLCG2(4), PRKACA(1), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PRKCA(3), PRKCE(2), PRKCG(5), PRKCH(1), PRKCQ(2), PRKD1(5), PRKG1(8), RAF1(4), RPS6KA2(4), RPS6KA3(2), TGFBR1(5), VRK1(2) 20222030 154 54 153 47 49 54 31 2 18 0 0.000047 0.0032 10 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 77 ABL1(2), ABL2(3), AKT1(1), AKT2(2), AKT3(1), ARAF(1), CAMK2D(2), CBL(4), CBLB(3), CDKN1A(1), CDKN1B(2), EGFR(5), ERBB3(6), ERBB4(7), EREG(1), GAB1(1), GRB2(2), GSK3B(2), MAP2K1(2), MAP2K2(1), MAP2K4(2), MAPK3(1), MAPK8(6), MAPK9(2), NCK1(1), NRG2(3), NRG3(5), PAK1(1), PAK2(3), PAK3(3), PAK7(3), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PLCG1(1), PLCG2(4), PRKCA(3), PRKCG(5), PTK2(1), RAF1(4), RPS6KB2(1), SHC1(1), SHC2(1), SHC3(1), SHC4(1), SOS1(3), SOS2(6), SRC(3), STAT5B(1) 16575142 127 44 125 38 39 43 23 3 19 0 0.000054 0.0033 11 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 92 ADCY1(5), ADCY2(8), ADCY3(2), ADCY4(2), ADCY5(6), ADCY7(2), ADCY8(3), ADCY9(2), ATF4(1), CACNA1C(2), CACNA1D(3), CACNA1F(5), CACNA1S(7), CAMK2D(2), CDC42(1), CGA(1), EGFR(5), FSHB(2), GNA11(1), GNAQ(1), GNAS(2), GRB2(2), ITPR1(8), ITPR2(6), ITPR3(7), MAP2K1(2), MAP2K2(1), MAP2K3(4), MAP2K4(2), MAP2K6(1), MAP3K1(2), MAP3K2(1), MAP3K3(2), MAP3K4(8), MAPK13(1), MAPK3(1), MAPK8(6), MAPK9(2), MMP14(1), MMP2(3), PLA2G4A(4), PLA2G6(2), PLCB1(1), PLCB3(3), PLCB4(2), PLD1(6), PLD2(1), PRKACA(1), PRKACG(1), PRKCA(3), PTK2B(1), RAF1(4), SOS1(3), SOS2(6), SRC(3) 23424198 164 53 164 59 61 52 27 3 20 1 0.000084 0.0047 12 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 159 ADORA1(4), ADORA2A(2), ADORA2B(1), ADRA1A(1), ADRA1B(2), ADRA2A(1), ADRB1(1), AGTR1(3), AGTR2(1), AVPR1A(1), BDKRB2(1), BRS3(2), C3AR1(3), CCKAR(1), CCKBR(4), CCR1(1), CCR3(2), CCR4(1), CCR5(1), CCR7(2), CCR8(2), CCR9(3), CCRL1(3), CHML(2), CHRM1(1), CHRM2(3), CHRM4(1), CHRM5(2), CNR1(3), CX3CR1(1), CXCR4(1), DRD2(4), DRD3(2), DRD5(4), EDNRA(1), EDNRB(5), F2RL1(1), F2RL2(1), FSHR(2), GALR1(1), GALT(1), GHSR(2), GPR17(1), GPR174(2), GPR37(3), GPR6(2), GPR63(2), GPR77(1), GPR87(2), GRPR(1), HRH2(1), HTR1A(2), HTR1B(2), HTR1D(1), HTR1E(4), HTR2A(1), HTR2B(1), HTR2C(2), HTR4(1), HTR5A(4), HTR7(1), LTB4R(1), MAS1(1), MC4R(2), MC5R(2), MLNR(1), NMUR1(1), NMUR2(5), NPY1R(2), NPY2R(1), NPY5R(1), NTSR2(2), OPN1SW(2), OPRK1(1), OPRM1(2), OR12D3(3), OR1C1(2), OR2H1(1), OR5V1(1), OR7A5(2), OR7C1(2), OR8B8(3), OXTR(1), P2RY1(4), P2RY12(2), P2RY14(3), P2RY2(1), P2RY6(1), PPYR1(3), PTGDR(1), PTGFR(3), RGR(1), RHO(2), RRH(2), SSTR1(2), SSTR2(1), SSTR4(2), SUCNR1(2), TRHR(3) 20800760 187 57 187 64 67 67 36 2 15 0 0.000095 0.0048 13 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(4), CALR(1), CANX(1), CIITA(1), CTSB(3), CTSL1(2), HLA-A(2), HLA-B(1), HLA-DMB(1), HLA-DOA(1), HLA-DPB1(2), HLA-DQA2(2), HLA-DQB1(1), HLA-DRA(3), HLA-DRB1(1), HLA-DRB5(1), HLA-F(1), HLA-G(1), HSP90AA1(1), HSP90AB1(2), HSPA5(1), IFNA10(3), IFNA2(2), IFNA5(1), KIR2DL1(2), KIR2DL4(1), KIR3DL1(1), KIR3DL2(1), KIR3DL3(3), KLRC3(1), LGMN(3), NFYA(3), NFYC(1), PDIA3(1), RFX5(1), RFXAP(1), TAP1(3), TAP2(2), TAPBP(3) 7700344 66 27 66 18 11 26 12 1 14 2 0.00010 0.0048 14 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 90 ADCY1(5), ADCY2(8), ADCY3(2), ADCY4(2), ADCY5(6), ADCY7(2), ADCY8(3), ADCY9(2), AKAP10(2), AKAP11(5), AKAP12(4), AKAP3(5), AKAP4(2), AKAP6(8), AKAP7(1), AKAP9(10), ARHGEF1(2), GNA11(1), GNA14(3), GNA15(1), GNAL(2), GNAO1(2), GNAQ(1), GNB3(2), GNG3(1), GNG4(1), GNGT1(1), IL18BP(2), ITPR1(8), PDE1A(2), PDE1B(2), PDE1C(5), PDE4A(1), PDE4B(3), PDE4D(1), PDE7B(1), PDE8B(2), PLCB3(3), PPP3CA(2), PPP3CC(3), PRKACA(1), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PRKCA(3), PRKCE(2), PRKCG(5), PRKCH(1), PRKCI(1), PRKCQ(2), PRKD1(5), PRKD3(5), RHOA(1), SLC9A1(2), USP5(2) 21406322 156 53 155 63 55 56 21 0 23 1 0.00012 0.0054 15 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(15), CDC25A(1), CDC25B(2), CDC25C(1), MYT1(9), YWHAH(1) 2551134 29 17 29 3 7 14 4 1 2 1 0.00015 0.0062 16 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 136 AXIN1(1), AXIN2(5), BTRC(3), CACYBP(1), CAMK2D(2), CCND2(1), CCND3(1), CHD8(2), CREBBP(8), CSNK2A2(1), CUL1(5), DAAM1(1), DAAM2(4), DKK1(2), DKK2(3), DKK4(3), DVL2(2), DVL3(2), EP300(8), FBXW11(4), FZD1(1), FZD10(2), FZD2(1), FZD4(1), FZD6(4), FZD7(1), GSK3B(2), LEF1(1), LRP5(3), LRP6(8), MAP3K7(2), MAPK8(6), MAPK9(2), MMP7(2), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), NKD1(1), PLCB1(1), PLCB3(3), PLCB4(2), PPARD(1), PPP2CA(1), PPP2CB(2), PPP2R1A(1), PPP2R1B(1), PPP2R2B(2), PPP2R2C(2), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRICKLE1(5), PRICKLE2(3), PRKACA(1), PRKACG(1), PRKCA(3), PRKCG(5), RBX1(1), RHOA(1), ROCK1(8), ROCK2(4), RUVBL1(4), SENP2(2), SFRP1(2), SFRP2(2), SFRP4(1), SIAH1(1), SMAD3(3), TBL1X(1), TBL1Y(1), TCF7(5), TCF7L1(1), VANGL1(1), VANGL2(1), WIF1(1), WNT10B(1), WNT11(1), WNT16(1), WNT2(1), WNT2B(2), WNT3(1), WNT4(1), WNT6(1), WNT8A(1), WNT9B(2) 26259270 196 60 194 55 68 64 36 3 25 0 0.00018 0.0062 17 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 66 A2M(3), BDKRB2(1), C1QB(1), C1QC(1), C1R(1), C1S(4), C2(4), C3(2), C3AR1(3), C4BPA(6), C5(5), C5AR1(2), C6(6), C7(3), C8A(4), C8B(3), C9(2), CD46(1), CD55(2), CFB(2), CFH(6), CPB2(1), CR1(3), CR2(3), F11(1), F13A1(5), F13B(2), F2(2), F3(1), F5(10), F7(1), F8(5), FGA(6), FGB(1), FGG(2), KLKB1(5), KNG1(1), MASP1(5), MASP2(2), PLAT(3), PLAU(1), PLAUR(2), PLG(4), PROS1(3), SERPINA1(3), SERPINA5(2), SERPINC1(1), SERPIND1(1), SERPINE1(3), SERPING1(2), TFPI(3), VWF(7) 16342862 153 48 153 41 42 63 29 0 19 0 0.00018 0.0062 18 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 245 ACVR1(3), ACVR1B(3), ACVR2A(2), ACVR2B(2), BMP2(1), BMP7(2), BMPR1A(1), BMPR1B(1), BMPR2(8), CCL18(1), CCL22(1), CCL27(2), CCL8(1), CCR1(1), CCR3(2), CCR4(1), CCR5(1), CCR7(2), CCR8(2), CCR9(3), CD40(1), CD40LG(4), CD70(1), CSF1(1), CSF2RB(1), CSF3R(5), CX3CL1(1), CX3CR1(1), CXCL10(1), CXCL11(2), CXCL14(2), CXCL16(1), CXCL5(1), CXCL9(2), CXCR4(1), EDA(1), EDA2R(1), EDAR(2), EGFR(5), FAS(2), FLT1(4), FLT3(2), FLT4(1), GDF5(2), GH1(1), GH2(2), GHR(1), HGF(3), IFNA10(3), IFNA2(2), IFNA5(1), IFNAR2(1), IFNGR1(1), IFNGR2(1), IFNK(1), IL10(1), IL10RA(1), IL10RB(3), IL12A(1), IL12B(1), IL12RB2(2), IL13RA1(2), IL15(1), IL17A(2), IL17RA(2), IL18R1(4), IL18RAP(2), IL19(1), IL1B(1), IL1R1(1), IL1R2(5), IL1RAP(1), IL2(2), IL20(1), IL20RA(3), IL21R(4), IL22RA1(1), IL23R(1), IL28RA(1), IL2RB(1), IL3(1), IL4(1), IL5RA(2), IL6(2), IL6R(1), IL6ST(1), IL7(1), IL7R(2), IL8(1), IL9(2), INHBA(3), INHBC(1), INHBE(1), KDR(3), KIT(2), KITLG(1), LEPR(5), LTBR(1), MET(1), MPL(1), NGFR(1), OSMR(2), PDGFC(1), PDGFRA(4), PDGFRB(2), PRL(1), PRLR(2), RELT(1), TGFB1(1), TGFB2(4), TGFBR1(5), TGFBR2(2), TNFRSF10B(4), TNFRSF10D(1), TNFRSF11A(1), TNFRSF17(2), TNFRSF21(2), TNFRSF8(1), TNFRSF9(2), TNFSF13B(1), TPO(4), VEGFC(3), XCL2(1), XCR1(1) 31058602 229 52 227 90 59 92 44 0 33 1 0.00018 0.0062 19 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 120 ARAF(1), BID(1), CASP3(1), FAS(2), FCGR3A(1), FYN(1), GRB2(2), GZMB(2), HLA-A(2), HLA-B(1), HLA-G(1), IFNA10(3), IFNA2(2), IFNA5(1), IFNAR2(1), IFNGR1(1), IFNGR2(1), ITGAL(4), ITGB2(2), KIR2DL1(2), KIR2DL4(1), KIR3DL1(1), KIR3DL2(1), KLRC3(1), LAT(1), LCK(2), LCP2(1), MAP2K1(2), MAP2K2(1), MAPK3(1), MICB(2), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), PAK1(1), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PLCG1(1), PLCG2(4), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKCA(3), PRKCG(5), PTK2B(1), PTPN11(4), RAF1(4), SH2D1A(1), SH3BP2(1), SHC1(1), SHC2(1), SHC3(1), SHC4(1), SOS1(3), SOS2(6), SYK(3), TNFRSF10B(4), TNFRSF10D(1), TYROBP(1), VAV1(7), VAV2(3), VAV3(3), ZAP70(1) 19233256 133 41 133 45 44 45 22 0 22 0 0.00022 0.0070 20 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 11 ATM(15), CDC25A(1), CDC25B(2), CDC25C(1), CDK4(1), MYT1(9), RB1(3), YWHAH(1) 3114652 33 19 33 4 9 14 5 1 3 1 0.00034 0.011 21 ALKPATHWAY Activin receptor-like kinase 3 (ALK3) is required during gestation for cardiac muscle development. ACVR1, APC, ATF2, AXIN1, BMP10, BMP2, BMP4, BMP5, BMP7, BMPR1A, BMPR2, CHRD, CTNNB1, DVL1, FZD1, GATA4, GSK3B, MADH1, MADH4, MADH5, MADH6, MAP3K7, MEF2C, MYL2, NKX2-5, NOG, NPPA, NPPB, RFC1, TCF1, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, WNT1 30 ACVR1(3), ATF2(1), AXIN1(1), BMP10(1), BMP2(1), BMP4(2), BMP5(3), BMP7(2), BMPR1A(1), BMPR2(8), FZD1(1), GSK3B(2), MAP3K7(2), MEF2C(2), NPPB(1), RFC1(4), TGFB1(1), TGFB2(4), TGFBR1(5), TGFBR2(2), TGFBR3(3) 5132282 50 22 49 8 17 18 5 0 10 0 0.00036 0.011 22 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 142 AKT1(1), AKT2(2), AKT3(1), CBL(4), CBLB(3), CCND2(1), CCND3(1), CREBBP(8), CSF2RB(1), CSF3R(5), EP300(8), GH1(1), GH2(2), GHR(1), GRB2(2), IFNA10(3), IFNA2(2), IFNA5(1), IFNAR2(1), IFNGR1(1), IFNGR2(1), IFNK(1), IL10(1), IL10RA(1), IL10RB(3), IL12A(1), IL12B(1), IL12RB2(2), IL13RA1(2), IL13RA2(2), IL15(1), IL19(1), IL2(2), IL20(1), IL20RA(3), IL21R(4), IL22RA1(1), IL23R(1), IL28RA(1), IL2RB(1), IL3(1), IL4(1), IL5RA(2), IL6(2), IL6R(1), IL6ST(1), IL7(1), IL7R(2), IL9(2), IRF9(1), JAK1(1), JAK2(4), JAK3(4), LEPR(5), MPL(1), OSMR(2), PIAS1(1), PIAS2(2), PIAS3(2), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PRL(1), PRLR(2), PTPN11(4), SOCS2(1), SOCS4(1), SOCS5(2), SOS1(3), SOS2(6), SPRED1(2), SPRED2(2), SPRY1(3), SPRY4(1), STAM(1), STAM2(1), STAT1(1), STAT2(4), STAT3(1), STAT4(3), STAT5B(1), STAT6(1), TPO(4) 24726682 173 48 172 54 45 75 34 1 17 1 0.00071 0.020 23 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(1), F13A1(5), F2(2), FGA(6), FGB(1), FGG(2), PLAT(3), PLAU(1), PLG(4), SERPINB2(1), SERPINE1(3) 2470992 29 18 29 2 11 9 5 0 4 0 0.00079 0.021 24 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 DAB1(4), FYN(1), LRP8(4), RELN(13), VLDLR(4) 2538344 26 14 25 9 8 10 4 1 3 0 0.0013 0.032 25 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 24 ATM(15), BMPR1B(1), CCND2(1), CDK4(1), CDKN1B(2), DAZL(1), DMC1(2), EGR1(1), FSHR(2), GJA4(1), INHA(1), MLH1(3), MSH5(2), NCOR1(7), NRIP1(2), PRLR(2), VDR(1), ZP2(1) 6214344 46 23 46 13 11 15 10 1 8 1 0.0013 0.032 26 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(2), C5(5), C6(6), C7(3), C8A(4), C9(2) 2359956 22 14 22 4 6 9 3 0 4 0 0.0018 0.042 27 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 CCNE1(1), CDKN1B(2), CUL1(5), NEDD8(1), RB1(3), RBX1(1), TFDP1(1) 1587438 14 12 14 6 6 0 3 0 5 0 0.0020 0.046 28 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 17 ADCY1(5), ARHGEF1(2), F2(2), GNAI1(1), GNAQ(1), GNGT1(1), MAP3K7(2), PLCB1(1), PPP1R12B(4), PRKCA(3), PTK2B(1), ROCK1(8) 4011552 31 18 31 12 7 10 6 1 7 0 0.0021 0.047 29 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(5), EXTL1(1), EXTL2(5), EXTL3(5), GLCE(4), HS2ST1(1), HS3ST1(1), HS3ST2(3), HS6ST3(1), NDST1(2), NDST2(1), NDST3(6), NDST4(1) 3771612 36 25 36 11 12 12 8 1 3 0 0.0029 0.062 30 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 64 ADCY1(5), ADCY8(3), ARAF(1), ATF4(1), CACNA1C(2), CAMK2D(2), CAMK4(1), CREBBP(8), EP300(8), GNAQ(1), GRIA1(6), GRIA2(6), GRIN1(1), GRIN2A(9), GRIN2B(3), GRIN2C(2), GRIN2D(2), GRM1(5), GRM5(4), ITPR1(8), ITPR2(6), ITPR3(7), MAP2K1(2), MAP2K2(1), MAPK3(1), PLCB1(1), PLCB3(3), PLCB4(2), PPP1CB(1), PPP1CC(1), PPP1R12A(1), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKACA(1), PRKACG(1), PRKCA(3), PRKCG(5), RAF1(4), RAP1A(1), RAP1B(1), RAPGEF3(3), RPS6KA2(4), RPS6KA3(2), RPS6KA6(3) 18310888 139 46 139 49 54 40 27 2 14 2 0.0031 0.064 31 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), AGPAT1(1), AGPAT4(4), AGPAT6(1), CDS1(2), CDS2(2), CHAT(1), CHKA(2), CHPT1(1), DGKA(1), DGKB(2), DGKD(8), DGKE(2), DGKG(2), DGKH(7), DGKI(7), DGKZ(1), ESCO1(6), ESCO2(1), ETNK1(1), ETNK2(2), GNPAT(1), GPAM(1), GPD1L(1), GPD2(1), LCAT(1), MYST3(10), MYST4(7), PCYT1A(2), PCYT1B(1), PEMT(1), PISD(2), PLA2G4A(4), PLA2G6(2), PLD1(6), PLD2(1), PTDSS1(4), SH3GLB1(1) 11931604 102 39 102 30 39 27 24 1 11 0 0.0035 0.068 32 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 66 AGTR1(3), AGTR2(1), ATP8A1(7), AVPR1A(1), BDKRB2(1), BRS3(2), C3AR1(3), CCKAR(1), CCKBR(4), CCR1(1), CCR3(2), CCR4(1), CCR5(1), CCR7(2), CCR8(2), CX3CR1(1), CXCR4(1), EDNRA(1), EDNRB(5), FSHR(2), GALR1(1), GALT(1), GHSR(2), GPR77(1), GRPR(1), MC2R(3), MC4R(2), MC5R(2), NPY1R(2), NPY2R(1), NPY5R(1), NTSR2(2), OPRK1(1), OPRM1(2), OXTR(1), PPYR1(3), SSTR1(2), SSTR2(1), SSTR4(2), TACR1(1), TACR3(3), TRHR(3), TSHR(4) 9151936 84 36 84 32 27 27 23 1 6 0 0.0035 0.068 33 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(5), GNAS(2), GNGT1(1), PRKACA(1), PRKAR1A(4) 1133258 13 11 13 3 4 5 2 0 2 0 0.0044 0.079 34 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 40 FOS(1), FYN(1), GRB2(2), LAT(1), LCK(2), MAP2K1(2), MAP2K4(2), MAP3K1(2), MAPK3(1), MAPK8(6), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), NFKB1(4), PLCG1(1), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKCA(3), PTPN7(2), RAF1(4), RASA1(5), SHC1(1), SOS1(3), VAV1(7), ZAP70(1) 7919278 65 28 65 11 24 20 11 1 9 0 0.0045 0.079 35 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 91 CABIN1(5), CAMK4(1), CD69(1), CDKN1A(1), CNR1(3), CREBBP(8), CTLA4(1), EGR2(3), EP300(8), FCER1A(3), FCGR3A(1), FOS(1), GATA3(1), GRLF1(5), GSK3B(2), IL10(1), IL1B(1), IL2(2), IL3(1), IL4(1), IL6(2), IL8(1), ITK(4), KPNA5(1), MAPK8(6), MAPK9(2), MEF2A(1), MYF5(2), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), NFKB2(2), NPPB(1), NUP214(3), P2RX7(1), PAK1(1), PIN1(1), PPP3CB(2), PPP3CC(3), PTPRC(9), SLA(1), SP1(1), SP3(2), TGFB1(1), TRPV6(4), VAV1(7), VAV2(3), VAV3(3), XPO5(1) 16324112 122 39 122 34 43 40 19 2 18 0 0.0045 0.079 36 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 105 ACTN1(2), ACTN2(5), ACTN3(1), ACTN4(3), ARHGAP5(4), CDC42(1), CDH5(1), CLDN10(3), CLDN16(2), CLDN17(3), CLDN2(1), CLDN8(2), CTNNA1(5), CTNNA2(2), CTNNA3(1), CTNND1(1), CXCR4(1), CYBB(1), ESAM(1), GNAI1(1), GRLF1(5), ITGA4(5), ITGAL(4), ITGAM(3), ITGB2(2), ITK(4), MAPK13(1), MLLT4(3), MMP2(3), MMP9(6), MSN(3), MYL9(2), NCF2(1), NCF4(1), NOX3(4), PECAM1(1), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PLCG1(1), PLCG2(4), PRKCA(3), PRKCG(5), PTK2(1), PTK2B(1), PTPN11(4), RAP1A(1), RAP1B(1), RAPGEF3(3), RASSF5(1), RHOA(1), RHOH(1), ROCK1(8), ROCK2(4), TXK(2), VAV1(7), VAV2(3), VAV3(3), VCAM1(2), VCL(2) 21717220 159 52 159 49 65 59 22 0 13 0 0.0047 0.080 37 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 35 BTK(2), FCER1A(3), FOS(1), GRB2(2), MAP2K1(2), MAP2K4(2), MAP3K1(2), MAPK3(1), MAPK8(6), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), PAK2(3), PLA2G4A(4), PLCG1(1), PPP3CA(2), PPP3CB(2), PPP3CC(3), RAF1(4), SHC1(1), SOS1(3), SYK(3), VAV1(7) 6966356 61 26 61 11 18 18 11 1 13 0 0.0048 0.080 38 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 80 ABL1(2), ATM(15), BUB1(2), BUB1B(3), BUB3(1), CCNA1(3), CCNA2(1), CCNB2(1), CCNB3(6), CCND2(1), CCND3(1), CCNE1(1), CCNE2(1), CCNH(1), CDAN1(3), CDC14A(3), CDC14B(2), CDC20(1), CDC25A(1), CDC25B(2), CDC25C(1), CDC6(1), CDC7(2), CDH1(2), CDK4(1), CDKN1A(1), CHEK2(1), E2F3(2), EP300(8), ESPL1(4), GSK3B(2), HDAC1(2), HDAC3(1), HDAC4(3), HDAC5(1), HDAC6(2), MAD1L1(1), MCM3(2), MCM4(1), MCM5(5), MCM6(1), MCM7(2), MPEG1(2), MPL(1), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(1), PLK1(4), PRKDC(5), PTPRA(1), RB1(3), RBL1(4), TFDP1(1), TGFB1(1) 20190840 124 40 123 35 33 42 29 4 15 1 0.0055 0.088 39 SA_BONE_MORPHOGENETIC Bone morphogenetic protein binds to its receptor to induce ectopic bone formation and promote development of the viscera. BMP1, BMPR1A, BMPR1B, BMPR2, MADH1, MADH4, MADH6 4 BMP1(2), BMPR1A(1), BMPR1B(1), BMPR2(8) 1130000 12 9 12 2 2 4 3 0 3 0 0.0056 0.088 40 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 12 CDH1(2), CREBBP(8), EP300(8), MAP2K1(2), MAP3K7(2), MAPK3(1), SKIL(1), TGFB1(1), TGFB2(4), TGFBR1(5), TGFBR2(2) 3685428 36 18 36 8 8 11 6 1 10 0 0.0062 0.095 41 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 233 ADCYAP1R1(1), ADORA1(4), ADORA2A(2), ADORA2B(1), ADRA1A(1), ADRA1B(2), ADRA2A(1), ADRA2B(1), ADRB1(1), AGTR1(3), AGTR2(1), AVPR1A(1), BDKRB2(1), BRS3(2), C3AR1(3), C5AR1(2), CALCR(4), CALCRL(4), CCKAR(1), CCKBR(4), CGA(1), CHRM1(1), CHRM2(3), CHRM4(1), CHRM5(2), CNR1(3), CRHR1(1), CRHR2(2), CTSG(2), CYSLTR1(2), CYSLTR2(3), DRD2(4), DRD3(2), DRD5(4), EDNRA(1), EDNRB(5), F2(2), F2RL1(1), F2RL2(1), FSHB(2), FSHR(2), GABBR1(4), GABBR2(4), GABRA1(2), GABRA2(3), GABRA3(3), GABRA4(2), GABRA5(1), GABRA6(1), GABRB1(2), GABRB2(3), GABRB3(5), GABRG1(2), GABRG2(4), GABRP(2), GABRQ(2), GABRR2(1), GALR1(1), GH1(1), GH2(2), GHR(1), GHRHR(1), GHSR(2), GLP1R(5), GLP2R(4), GLRA1(1), GLRA2(1), GLRA3(3), GLRB(2), GPR156(3), GPR63(2), GRIA1(6), GRIA2(6), GRIA3(4), GRIA4(9), GRID1(7), GRID2(5), GRIK1(1), GRIK2(4), GRIK3(7), GRIK4(2), GRIK5(1), GRIN1(1), GRIN2A(9), GRIN2B(3), GRIN2C(2), GRIN2D(2), GRIN3A(4), GRM1(5), GRM2(3), GRM3(3), GRM4(2), GRM5(4), GRM6(2), GRM7(5), GRM8(2), GRPR(1), GZMA(2), HRH2(1), HRH4(1), HTR1A(2), HTR1B(2), HTR1D(1), HTR1E(4), HTR2A(1), HTR2B(1), HTR2C(2), HTR4(1), HTR5A(4), HTR7(1), LEPR(5), LTB4R(1), MAS1(1), MC2R(3), MC4R(2), MC5R(2), MCHR2(2), MLNR(1), NMUR1(1), NMUR2(5), NPFFR2(2), NPY1R(2), NPY2R(1), NPY5R(1), NR3C1(1), NTSR2(2), OPRK1(1), OPRM1(2), OXTR(1), P2RX1(1), P2RX2(1), P2RX3(1), P2RX4(1), P2RX7(1), P2RY1(4), P2RY14(3), P2RY2(1), P2RY6(1), PARD3(4), PPYR1(3), PRL(1), PRLR(2), PRSS3(2), PTGDR(1), PTGER3(1), PTGFR(3), PTH2R(4), RXFP1(1), RXFP2(4), SSTR1(2), SSTR2(1), SSTR4(2), TAAR1(1), TAAR5(2), TAAR6(3), TAAR8(1), TAAR9(2), TACR1(1), TACR3(3), THRB(1), TRHR(3), TRPV1(1), TSHB(1), TSHR(4), VIPR1(3), VIPR2(1) 39270818 386 78 385 149 139 134 76 3 33 1 0.0075 0.11 42 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(2), CYP2E1(3), NR1I3(2), PTGS1(4), PTGS2(1) 964354 12 10 12 5 4 4 3 0 1 0 0.0078 0.11 43 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(8), ABCA10(4), ABCA12(20), ABCA13(17), ABCA3(1), ABCA4(5), ABCA5(3), ABCA6(7), ABCA7(1), ABCA8(7), ABCA9(7), ABCB1(6), ABCB10(1), ABCB11(3), ABCB4(6), ABCB5(5), ABCB6(2), ABCB7(1), ABCB8(1), ABCC1(3), ABCC10(1), ABCC11(3), ABCC12(5), ABCC2(5), ABCC3(2), ABCC4(3), ABCC5(2), ABCC6(2), ABCC8(3), ABCC9(6), ABCD1(1), ABCD2(3), ABCD4(1), ABCG1(2), ABCG2(5), ABCG5(1), ABCG8(2), CFTR(5), TAP1(3), TAP2(2) 21243252 165 40 165 50 43 66 33 2 20 1 0.0080 0.12 44 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), ATF1(1), CDC42(1), CREB3(2), CREB5(2), DUSP1(2), DUSP10(3), EEF2K(1), IL1R1(1), MAP2K3(4), MAP2K4(2), MAP2K6(1), MAP3K10(1), MAP3K4(8), MAP3K5(3), MAP3K7(2), MAPK13(1), MKNK1(1), MKNK2(1), MYEF2(2), NFKB1(4), NR2C2(1), TRAF6(1) 6061708 46 26 46 11 16 10 12 2 6 0 0.0082 0.12 45 COMPLEMENT_ACTIVATION_CLASSICAL C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C9, DAF, MASP1 13 C1QB(1), C1R(1), C1S(4), C2(4), C3(2), C5(5), C6(6), C7(3), C8A(4), C8B(3), C9(2), MASP1(5) 3779342 40 19 40 8 14 15 5 0 6 0 0.0086 0.12 46 1_AND_2_METHYLNAPHTHALENE_DEGRADATION ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 7 ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3) 1028826 12 10 12 5 3 4 4 0 1 0 0.0087 0.12 47 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 105 ABL1(2), ANAPC1(1), ANAPC4(3), ANAPC5(1), ANAPC7(2), ATM(15), ATR(7), BUB1(2), BUB1B(3), BUB3(1), CCNA1(3), CCNA2(1), CCNB2(1), CCNB3(6), CCND2(1), CCND3(1), CCNE1(1), CCNE2(1), CCNH(1), CDC14A(3), CDC14B(2), CDC16(1), CDC20(1), CDC25A(1), CDC25B(2), CDC25C(1), CDC6(1), CDC7(2), CDK4(1), CDKN1A(1), CDKN1B(2), CHEK2(1), CREBBP(8), CUL1(5), DBF4(4), E2F3(2), EP300(8), ESPL1(4), GSK3B(2), HDAC1(2), MAD1L1(1), MCM3(2), MCM4(1), MCM5(5), MCM6(1), MCM7(2), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(1), PLK1(4), PRKDC(5), RB1(3), RBL1(4), RBL2(3), RBX1(1), SMAD3(3), SMC1A(4), SMC1B(2), TFDP1(1), TGFB1(1), TGFB2(4), YWHAH(1) 24225162 160 41 159 49 44 57 34 4 20 1 0.0088 0.12 48 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 241 ACVR1B(3), ACVR1C(1), AKT1(1), AKT2(2), AKT3(1), ATF2(1), ATF4(1), CACNA1A(9), CACNA1B(4), CACNA1C(2), CACNA1D(3), CACNA1E(6), CACNA1F(5), CACNA1I(2), CACNA1S(7), CACNA2D1(6), CACNA2D3(3), CACNB2(2), CACNB3(1), CACNB4(2), CACNG1(1), CACNG2(1), CACNG3(3), CACNG6(1), CACNG7(3), CACNG8(1), CASP3(1), CDC25B(2), CDC42(1), CHUK(4), DAXX(1), DUSP1(2), DUSP10(3), DUSP16(4), DUSP3(1), DUSP5(2), DUSP6(3), DUSP7(2), ECSIT(1), EGFR(5), ELK4(1), FAS(2), FGF11(1), FGF12(1), FGF13(1), FGF14(2), FGF19(1), FGF20(1), FGF3(1), FGF5(2), FGFR1(1), FGFR2(5), FLNA(1), FLNB(6), FLNC(2), FOS(1), GRB2(2), IKBKB(2), IL1B(1), IL1R1(1), IL1R2(5), MAP2K1(2), MAP2K2(1), MAP2K3(4), MAP2K4(2), MAP2K5(2), MAP2K6(1), MAP3K1(2), MAP3K10(1), MAP3K12(2), MAP3K13(1), MAP3K14(1), MAP3K2(1), MAP3K3(2), MAP3K4(8), MAP3K5(3), MAP3K6(2), MAP3K7(2), MAP3K8(1), MAP4K1(1), MAP4K2(1), MAP4K3(1), MAP4K4(3), MAPK13(1), MAPK3(1), MAPK8(6), MAPK8IP3(1), MAPK9(2), MAPT(1), MEF2C(2), MKNK1(1), MKNK2(1), MOS(1), MRAS(1), NF1(5), NFATC2(3), NFATC4(2), NFKB1(4), NFKB2(2), NR4A1(2), NTRK1(3), NTRK2(1), PAK1(1), PAK2(3), PDGFRA(4), PDGFRB(2), PLA2G4A(4), PLA2G6(2), PPM1B(2), PPP3CA(2), PPP3CB(2), PPP3CC(3), PPP5C(1), PRKACA(1), PRKACG(1), PRKCA(3), PRKCG(5), PTPN7(2), PTPRR(4), RAF1(4), RAP1A(1), RAP1B(1), RAPGEF2(5), RASA1(5), RASA2(2), RASGRF1(6), RASGRF2(4), RASGRP1(3), RASGRP2(2), RASGRP3(3), RASGRP4(1), RPS6KA2(4), RPS6KA3(2), RPS6KA5(4), RPS6KA6(3), RRAS2(1), SOS1(3), SOS2(6), STMN1(1), TAOK1(2), TAOK2(1), TGFB1(1), TGFB2(4), TGFBR1(5), TGFBR2(2), TRAF6(1), ZAK(2) 52240772 349 67 349 123 129 98 77 4 36 5 0.0099 0.13 49 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(3), DARS(3), EPRS(4), FARS2(3), IARS(3), LARS(1), LARS2(1), MARS(4), MARS2(1), NARS(2), QARS(3), RARS(3), SARS(1), TARS(4), WARS(1), WARS2(2), YARS(1) 5850140 42 24 42 8 9 15 11 2 5 0 0.010 0.13 50 ST_STAT3_PATHWAY The transcription factor STAT3 is involved in cell growth regulation and is commonly upregulated in tumors. CISH, IL6, IL6R, JAK1, JAK2, JAK3, PIAS3, PTPRU, REG1A, SRC, STAT3 11 IL6(2), IL6R(1), JAK1(1), JAK2(4), JAK3(4), PIAS3(2), PTPRU(6), REG1A(2), SRC(3), STAT3(1) 2809828 26 18 26 7 14 8 1 0 2 1 0.011 0.13 51 C21_STEROID_HORMONE_METABOLISM AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 AKR1C4(1), AKR1D1(1), CYP11A1(3), CYP11B1(4), CYP21A2(1), HSD3B1(1), HSD3B2(1) 1612278 12 11 12 4 4 5 1 0 2 0 0.011 0.13 52 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(1), CYP11A1(3), CYP11B1(4), CYP21A2(1), HSD3B1(1), HSD3B2(1) 1612278 12 11 12 4 4 5 1 0 2 0 0.011 0.13 53 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 GNAQ(1), GRB2(2), MAP2K1(2), MAP2K2(1), MAP2K3(4), MAP2K4(2), MAP3K1(2), MAPK3(1), MAPK8(6), PAK1(1), PLCG1(1), PRKCA(3), PTK2B(1), RAF1(4), SHC1(1), SOS1(3), SRC(3) 5147972 38 21 38 12 9 13 9 2 5 0 0.011 0.13 54 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 65 AKT1(1), AKT2(2), AKT3(1), CASP9(1), CDC42(1), KDR(3), MAP2K1(2), MAP2K2(1), MAPK13(1), MAPK3(1), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PLA2G4A(4), PLA2G6(2), PLCG1(1), PLCG2(4), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKCA(3), PRKCG(5), PTGS2(1), PTK2(1), RAF1(4), SH2D2A(1), SHC2(1), SPHK1(1), SRC(3) 12033120 71 34 71 28 33 17 9 0 12 0 0.011 0.13 55 MPRPATHWAY Progesterone binding to its intracellular receptor activates the MAPK pathway and induces oocyte maturation; binding to membrane receptor inhibits adenylyl cyclase. ACTA1, ADCY1, CAP1, CCNB1, CDC2, CDC25C, GNAI1, GNAS, GNB1, GNGT1, HRAS, MAPK1, MAPK3, MYT1, PIN1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RPS6KA1, SRC 22 ACTA1(1), ADCY1(5), CAP1(1), CDC25C(1), GNAI1(1), GNAS(2), GNGT1(1), MAPK3(1), MYT1(9), PIN1(1), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), SRC(3) 3678224 33 22 33 11 11 14 5 0 3 0 0.012 0.13 56 PROTEASOME PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB10, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMB8, PSMB9 17 PSMA1(1), PSMA2(1), PSMA3(1), PSMA4(1), PSMA7(1), PSMB3(1), PSMB5(2), PSMB6(1), PSMB8(3) 1509738 12 10 12 4 3 5 1 1 2 0 0.012 0.13 57 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(2), BCL10(1), BCL2L11(2), BID(1), CASP8AP2(6), CASP9(1), CES1(2) 2093652 15 12 15 5 2 7 2 0 4 0 0.013 0.14 58 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(2), ARHGAP5(4), ARHGDIB(1), CASP10(1), CASP3(1), CASP8(5), CASP9(1), GZMB(2) 2347710 17 13 17 6 1 5 7 0 4 0 0.013 0.14 59 PROSTAGLANDIN_SYNTHESIS_REGULATION ANXA1, ANXA2, ANXA3, ANXA4, ANXA5, ANXA6, ANXA8, CYP11A1, EDN1, EDNRA, EDNRB, HPGD, HSD11B1, HSD11B2, PLA2G4A, PRL, PTGDR, PTGDS, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, PTGIS, PTGS1, PTGS2, S100A6, SCGB1A1, TBXAS1 27 ANXA1(1), ANXA3(1), ANXA4(1), ANXA6(1), CYP11A1(3), EDNRA(1), EDNRB(5), PLA2G4A(4), PRL(1), PTGDR(1), PTGFR(3), PTGIS(2), PTGS1(4), PTGS2(1), TBXAS1(3) 3739524 32 21 32 8 12 9 8 0 3 0 0.013 0.14 60 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), EP300(8), HDAC1(2), NFATC1(1), NFATC2(3), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKCA(3) 4237302 31 22 31 6 12 8 5 1 5 0 0.014 0.14 61 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), ACTR3(1), ARHGAP5(4), ARHGAP6(2), ARHGEF1(2), ARHGEF11(6), ARHGEF5(1), ARPC1B(1), ARPC2(1), BAIAP2(1), LIMK1(2), MYLK(5), OPHN1(6), PIP5K1B(1), PPP1R12B(4), ROCK1(8), SRC(3), TLN1(3), VCL(2) 8496328 54 26 54 14 16 16 11 1 10 0 0.015 0.15 62 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(11), ASH2L(1), CARM1(1), CTCFL(2), EHMT2(3), EZH1(2), EZH2(1), FBXO11(2), HSF4(1), MEN1(2), MLL(10), MLL2(3), MLL3(8), MLL4(3), MLL5(7), NSD1(4), OGT(2), PAXIP1(1), PPP1CB(1), PPP1CC(1), PRDM2(8), PRDM7(1), PRDM9(6), PRMT1(1), PRMT7(2), PRMT8(2), SATB1(1), SETD1A(3), SETD2(11), SETD7(2), SETDB1(4), SETDB2(3), SETMAR(1), SMYD3(2), STK38(1), SUV39H1(1), SUV39H2(1), SUV420H1(5), SUZ12(1), WHSC1(4), WHSC1L1(1) 21920454 127 37 127 26 38 37 23 2 26 1 0.015 0.15 63 MYOSINPATHWAY Myosin light chain kinase phosphorylates myosin and promotes muscle contraction and platelet formation; myosin phosphatase antagonizes these processes. ARHGAP5, ARHGEF1, GNA12, GNA13, GNAQ, GNB1, GNGT1, MYL2, MYLK, PLCB1, PPP1R12B, PRKCA, PRKCB1, PRKCL1, ROCK1 13 ARHGAP5(4), ARHGEF1(2), GNAQ(1), GNGT1(1), MYLK(5), PLCB1(1), PPP1R12B(4), PRKCA(3), ROCK1(8) 3811716 29 17 29 8 8 10 5 1 5 0 0.016 0.16 64 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 C1QB(1), C1R(1), C1S(4), C2(4), C3(2), C5(5), C6(6), C7(3), C8A(4), C9(2), MASP1(5), MASP2(2) 3894290 39 19 39 9 13 14 6 0 6 0 0.016 0.16 65 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 GRB2(2), HBXIP(1), PTK2B(1), SHC1(1), SOS1(3), SRC(3) 1600118 11 9 11 4 1 5 3 0 2 0 0.017 0.16 66 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 CD44(2), CHAD(2), COL11A1(8), COL11A2(3), COL1A1(2), COL1A2(6), COL2A1(2), COL3A1(7), COL4A1(5), COL4A2(1), COL4A4(2), COL4A6(5), COL5A1(7), COL5A2(4), COL5A3(6), COL6A2(1), COL6A3(20), COL6A6(5), DAG1(3), FN1(6), FNDC1(8), FNDC3A(4), GP5(2), GP6(1), HMMR(4), HSPG2(1), IBSP(1), ITGA1(1), ITGA10(4), ITGA11(2), ITGA2(2), ITGA2B(3), ITGA4(5), ITGA5(2), ITGA6(2), ITGA8(3), ITGA9(3), ITGAV(4), ITGB3(2), ITGB4(1), ITGB5(4), ITGB6(2), ITGB7(2), ITGB8(1), LAMA1(7), LAMA2(10), LAMA3(8), LAMA4(6), LAMB1(2), LAMB2(3), LAMB3(1), LAMB4(6), LAMC1(6), LAMC2(4), LAMC3(4), RELN(13), SDC1(1), SDC2(3), SDC3(1), SDC4(1), SV2A(1), SV2B(4), THBS1(3), THBS2(8), THBS3(2), THBS4(1), TNC(7), TNN(4), TNR(4), TNXB(4), VTN(3), VWF(7) 40496776 285 66 285 130 100 99 47 5 33 1 0.017 0.16 67 SRCRPTPPATHWAY Activation of Src by Protein-tyrosine phosphatase alpha CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CSK, GRB2, PRKCA, PRKCB1, PTPRA, SRC 9 CDC25A(1), CDC25B(2), CDC25C(1), CSK(2), GRB2(2), PRKCA(3), PTPRA(1), SRC(3) 1701282 15 13 15 3 5 8 1 1 0 0 0.018 0.16 68 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(2), FMOD(1), KERA(4), LUM(2) 666536 10 8 10 1 4 2 3 0 1 0 0.019 0.17 69 G1_TO_S_CELL_CYCLE_REACTOME ATM, CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNG2, CCNH, CDC25A, CDC45L, CDK2, CDK4, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CREB3, CREB3L1, CREB3L3, CREB3L4, CREBL1, CREBL1, TNXB, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, FLJ14001, GADD45A, GBA2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MNAT1, MYC, MYT1, NACA, NACA, FKSG17, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, POLA2, POLE, POLE2, PRIM1, PRIM2A, RB1, RBL1, RPA1, RPA2, RPA3, TFDP1, TFDP2, TP53, WEE1 63 ATM(15), CCNA1(3), CCND2(1), CCND3(1), CCNE1(1), CCNE2(1), CCNH(1), CDC25A(1), CDK4(1), CDKN1A(1), CDKN1B(2), CREB3(2), CREB3L3(2), E2F3(2), GBA2(1), MCM3(2), MCM4(1), MCM5(5), MCM6(1), MCM7(2), MNAT1(1), MYT1(9), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(1), POLA2(2), POLE(10), POLE2(1), RB1(3), RBL1(4), TFDP1(1), TNXB(4) 13357234 86 31 85 25 23 33 15 1 13 1 0.019 0.17 70 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 55 BMP2(1), BMP4(2), BMP5(3), BMP6(1), BMP7(2), BTRC(3), CSNK1D(2), CSNK1G3(1), FBXW11(4), GLI1(2), GLI2(2), GLI3(6), GSK3B(2), HHIP(2), IHH(1), LRP2(25), PRKACA(1), PRKACG(1), PTCH1(4), PTCH2(3), RAB23(1), SMO(1), STK36(2), SUFU(2), WNT10B(1), WNT11(1), WNT16(1), WNT2(1), WNT2B(2), WNT3(1), WNT4(1), WNT6(1), WNT8A(1), WNT9B(2) 10616388 86 37 85 30 38 27 11 0 10 0 0.020 0.17 71 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 63 APAF1(2), ATM(15), ATR(7), BID(1), CASP3(1), CASP8(5), CASP9(1), CCNB2(1), CCNB3(6), CCND2(1), CCND3(1), CCNE1(1), CCNE2(1), CCNG1(1), CDK4(1), CDKN1A(1), CHEK2(1), DDB2(1), EI24(1), FAS(2), GTSE1(2), IGF1(1), IGFBP3(3), MDM4(1), PTEN(4), RFWD2(2), SERPINB5(2), SERPINE1(3), SESN1(1), SESN2(2), SESN3(2), SIAH1(1), THBS1(3), TNFRSF10B(4), TP53I3(2), TSC2(1), ZMAT3(2) 11392532 87 32 87 23 23 40 15 0 8 1 0.020 0.17 72 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 18 B2M(4), HLA-A(2), KLRC3(1), LAT(1), MAP2K1(2), MAPK3(1), PAK1(1), PTK2B(1), SYK(3), VAV1(7) 2740356 23 12 23 3 4 7 6 0 5 1 0.021 0.18 73 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 3 FAH(2), GSTZ1(1), HGD(2) 368276 5 4 5 1 1 2 1 0 1 0 0.021 0.18 74 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 6 ATM(15), ATR(7), CDC25C(1), CHEK2(1), YWHAH(1) 2763972 25 12 25 5 5 15 3 0 1 1 0.022 0.18 75 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 AGPAT1(1), AGPAT4(4), AGPAT6(1), AGPS(1), CHPT1(1), ENPP2(7), ENPP6(1), PAFAH1B3(2), PAFAH2(1), PLA2G4A(4), PLA2G6(2), PLD1(6), PLD2(1) 4249468 32 19 32 13 15 12 2 0 3 0 0.022 0.18 76 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 F2(2), GNAI1(1), GNGT1(1), ITGA1(1), MAP2K1(2), MAPK3(1), PLA2G4A(4), PLCB1(1), PRKCA(3), PTGS1(4), PTK2(1), RAF1(4), SRC(3), SYK(3), TBXAS1(3) 4439922 34 21 34 11 11 12 4 1 6 0 0.023 0.18 77 NUCLEOTIDE_GPCRS ADORA1, ADORA2A, ADORA2B, ADORA3, GPR23, LTB4R, P2RY1, P2RY2, P2RY5, P2RY6 8 ADORA1(4), ADORA2A(2), ADORA2B(1), LTB4R(1), P2RY1(4), P2RY2(1), P2RY6(1) 976514 14 9 14 0 6 6 1 0 1 0 0.023 0.18 78 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(1), CALCR(4), CALCRL(4), CD97(2), CRHR1(1), CRHR2(2), ELTD1(2), EMR1(4), EMR2(5), GHRHR(1), GLP1R(5), GLP2R(4), GPR64(3), LPHN1(2), LPHN2(5), LPHN3(7), VIPR1(3), VIPR2(1) 5078806 56 25 56 17 24 18 10 0 4 0 0.023 0.18 79 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 70 ACTN1(2), ACTN2(5), ACTN3(1), ACTN4(3), ACVR1B(3), ACVR1C(1), BAIAP2(1), CDC42(1), CDH1(2), CREBBP(8), CSNK2A2(1), CTNNA1(5), CTNNA2(2), CTNNA3(1), CTNND1(1), EGFR(5), EP300(8), FARP2(2), FER(2), FGFR1(1), FYN(1), IGF1R(2), INSR(1), IQGAP1(8), LEF1(1), LMO7(6), MAP3K7(2), MAPK3(1), MET(1), MLLT4(3), PARD3(4), PTPN1(4), PTPRF(5), PTPRJ(2), PTPRM(14), PVRL1(4), PVRL2(1), PVRL3(1), PVRL4(1), RHOA(1), SMAD3(3), SNAI2(1), SORBS1(7), SRC(3), SSX2IP(2), TCF7(5), TCF7L1(1), TGFBR1(5), TGFBR2(2), TJP1(2), VCL(2), WASF1(2), WASF2(1), WASF3(4), WASL(2) 20554428 160 44 160 37 58 59 23 3 16 1 0.024 0.19 80 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 ADAM17(3), ATP6V0A1(3), ATP6V0A2(1), ATP6V0A4(3), ATP6V0B(1), ATP6V0D2(4), ATP6V1B1(1), ATP6V1B2(2), ATP6V1C2(1), ATP6V1E2(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(1), CASP3(1), CDC42(1), CHUK(4), CSK(2), EGFR(5), GIT1(1), IGSF5(6), IKBKB(2), IL8(1), MAP2K4(2), MAP3K14(1), MAPK13(1), MAPK8(6), MAPK9(2), MET(1), NFKB1(4), NFKB2(2), NOD1(2), PAK1(1), PLCG1(1), PLCG2(4), PTPN11(4), PTPRZ1(8), SRC(3), TJP1(2) 12754920 90 36 90 25 30 30 19 1 9 1 0.026 0.20 81 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 15 AKT1(1), AKT2(2), AKT3(1), GRB2(2), MAPK3(1), PDK1(2), PIK3CD(2), PTEN(4), PTK2B(1), RBL2(3), SHC1(1), SOS1(3) 3302278 23 14 23 7 5 7 6 0 5 0 0.026 0.20 82 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(5), FOS(1), GNAI1(1), GNAQ(1), GNAS(2), GNGT1(1), MAP2K1(2), MAPK3(1), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), PLCG1(1), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PRKCA(3), RAF1(4), RPS6KA3(2) 6131546 45 26 45 12 19 13 6 0 7 0 0.026 0.20 83 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 BHMT(3), CBS(2), CTH(1), DNMT1(11), DNMT3A(6), DNMT3B(5), MARS(4), MARS2(1), MAT1A(2), MAT2B(1), MTR(1) 3186640 37 19 36 8 16 12 3 2 4 0 0.026 0.20 84 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 55 ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3), AGK(2), AGPAT1(1), AGPAT4(4), AGPAT6(1), AKR1B1(1), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH7A1(2), DAK(2), DGAT2(3), DGKA(1), DGKB(2), DGKD(8), DGKE(2), DGKG(2), DGKH(7), DGKI(7), DGKZ(1), GK(1), GK2(5), GLA(1), GPAM(1), LCT(11), LIPC(1), LIPF(2), LPL(2), MGLL(1), PNLIP(3), PNLIPRP1(1), PNLIPRP2(1) 10636222 97 37 97 22 38 33 19 0 7 0 0.031 0.23 85 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 C1QB(1), C1R(1), C1S(4), C2(4), C3(2), C5(5), C6(6), C7(3), C8A(4), C9(2) 3177600 32 15 32 6 10 12 5 0 5 0 0.031 0.23 86 TOB1PATHWAY TGF-beta signaling activates SMADs, which interact with intracellular Tob to maintain unstimulated T cells by repressing IL-2 expression. CD28, CD3D, CD3E, CD3G, CD3Z, IFNG, IL2, IL2RA, IL4, MADH3, MADH4, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, TOB1, TOB2, TRA@, TRB@ 16 CD28(1), IL2(2), IL4(1), TGFB1(1), TGFB2(4), TGFBR1(5), TGFBR2(2), TGFBR3(3), TOB1(2) 1961202 21 10 21 4 5 8 3 0 5 0 0.033 0.23 87 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 71 CDS1(2), CDS2(2), DGKA(1), DGKB(2), DGKD(8), DGKE(2), DGKG(2), DGKH(7), DGKI(7), DGKZ(1), IMPA1(1), IMPA2(1), INPP4A(1), INPP4B(2), INPP5D(2), INPPL1(3), ITGB1BP3(1), ITPR1(8), ITPR2(6), ITPR3(7), OCRL(6), PI4KA(9), PI4KB(1), PIK3C2A(3), PIK3C2B(6), PIK3C2G(2), PIK3C3(5), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PIP4K2C(1), PIP5K1B(1), PIP5K1C(3), PLCB1(1), PLCB3(3), PLCB4(2), PLCD1(4), PLCE1(2), PLCG1(1), PLCG2(4), PLCZ1(1), PRKCA(3), PRKCG(5), PTEN(4), SYNJ1(4), SYNJ2(1) 22381288 150 48 150 40 59 50 22 1 17 1 0.033 0.23 88 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(1), ACACA(5), ACADL(2), ACADM(4), ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH6A1(2), ECHS1(1), HADHA(1), LDHA(2), LDHB(2), LDHC(1), MCEE(1), MUT(2), PCCA(7), PCCB(3), SDS(1), SUCLA2(3), SUCLG1(1) 6060462 52 23 52 13 18 17 6 0 11 0 0.033 0.23 89 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(2), CD79A(1), CD79B(1), FOS(1), GRB2(2), MAP2K1(2), MAP3K1(2), MAPK3(1), MAPK8(6), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), PLCG1(1), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKCA(3), RAF1(4), SHC1(1), SOS1(3), SYK(3), VAV1(7) 6854016 55 25 55 10 17 19 9 1 9 0 0.036 0.25 90 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 15 APAF1(2), ATM(15), CCNE1(1), CDK4(1), CDKN1A(1), PCNA(1), RB1(3), TIMP3(1) 3197072 25 13 25 7 4 12 4 0 4 1 0.036 0.25 91 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 32 ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3), ALDH1A3(4), ALDH3B1(1), ALDH3B2(1), AOC2(1), AOC3(1), AOX1(3), DBH(2), DCT(7), FAH(2), GOT1(2), GSTZ1(1), HGD(2), HPD(2), MAOA(3), MAOB(1), TAT(3), TPO(4), TYR(1) 5699128 53 27 53 24 14 25 8 0 6 0 0.036 0.25 92 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(4), CREBBP(8), DUSP1(2), EP300(8), IKBKB(2), IL1B(1), IL8(1), MAP2K3(4), MAP2K6(1), MAP3K14(1), MAP3K7(2), MYD88(1), NFKB1(4), NR3C1(1), TGFBR1(5), TGFBR2(2), TLR2(4) 5396954 51 21 51 16 14 15 13 2 7 0 0.037 0.25 93 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), ECHS1(1), HADH(1), HADHA(1), HADHB(1), HSD17B10(1), HSD17B4(1), MECR(1), PPT2(1) 1526816 9 8 9 5 2 2 2 0 3 0 0.040 0.27 94 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(8), EP300(8), ESR1(3), MAPK3(1), SRC(3) 2797134 23 16 23 5 7 9 2 2 3 0 0.041 0.27 95 TERCPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. NFYA, NFYB, NFYC, RB1, SP1, SP3 6 NFYA(3), NFYC(1), RB1(3), SP1(1), SP3(2) 1223664 10 8 10 2 3 5 1 0 1 0 0.042 0.27 96 G1PATHWAY CDK4/6-cyclin D and CDK2-cyclin E phosphorylate Rb, which allows the transcription of genes needed for the G1/S cell cycle transition. ABL1, ATM, ATR, CCNA1, CCND1, CCNE1, CDC2, CDC25A, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, DHFR, E2F1, GSK3B, HDAC1, MADH3, MADH4, RB1, SKP2, TFDP1, TGFB1, TGFB2, TGFB3, TP53 24 ABL1(2), ATM(15), ATR(7), CCNA1(3), CCNE1(1), CDC25A(1), CDK4(1), CDKN1A(1), CDKN1B(2), DHFR(1), GSK3B(2), HDAC1(2), RB1(3), TFDP1(1), TGFB1(1), TGFB2(4) 5324002 47 20 47 10 11 19 9 0 7 1 0.042 0.27 97 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(4), GABRA1(2), GABRA2(3), GABRA3(3), GABRA4(2), GABRA5(1), GABRA6(1), GPHN(5), SRC(3) 2209072 24 14 24 9 6 14 3 0 1 0 0.043 0.27 98 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(17), B3GALT4(1), CDR1(2), DGKI(7), FAU(1), IL6ST(1), PIGK(3), RPL10(1), RPL11(1), RPL19(1), RPL28(1), RPL5(1), RPL6(2), RPL9(2), RPS16(1), RPS18(1), RPS2(1), RPS3(1), RPS4X(1), RPS6KA2(4), RPS6KA3(2), RPS6KA6(3), RPS6KB2(1), RPS9(1), SLC36A2(1), TSPAN9(1), UBB(1) 9436574 60 29 60 16 22 16 13 2 7 0 0.044 0.27 99 HSA04540_GAP_JUNCTION Genes involved in gap junction ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADRB1, CDC2, CSNK1D, DRD1, DRD2, EDG2, EGF, EGFR, GJA1, GJD2, GNA11, GNAI1, GNAI2, GNAI3, GNAQ, GNAS, GRB2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, HTR2A, HTR2B, HTR2C, ITPR1, ITPR2, ITPR3, KRAS, LOC643224, LOC654264, MAP2K1, MAP2K2, MAP2K5, MAP3K2, MAPK1, MAPK3, MAPK7, NPR1, NPR2, NRAS, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PLCB1, PLCB2, PLCB3, PLCB4, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, PRKX, PRKY, RAF1, SOS1, SOS2, SRC, TJP1, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8 90 ADCY1(5), ADCY2(8), ADCY3(2), ADCY4(2), ADCY5(6), ADCY7(2), ADCY8(3), ADCY9(2), ADRB1(1), CSNK1D(2), DRD2(4), EGFR(5), GJA1(4), GJD2(1), GNA11(1), GNAI1(1), GNAQ(1), GNAS(2), GRB2(2), GRM1(5), GRM5(4), GUCY1A2(6), GUCY1A3(5), GUCY1B3(2), GUCY2C(3), GUCY2D(6), GUCY2F(6), HTR2A(1), HTR2B(1), HTR2C(2), ITPR1(8), ITPR2(6), ITPR3(7), MAP2K1(2), MAP2K2(1), MAP2K5(2), MAP3K2(1), MAPK3(1), NPR1(2), NPR2(2), PDGFC(1), PDGFRA(4), PDGFRB(2), PLCB1(1), PLCB3(3), PLCB4(2), PRKACA(1), PRKACG(1), PRKCA(3), PRKCG(5), PRKG1(8), PRKG2(3), RAF1(4), SOS1(3), SOS2(6), SRC(3), TJP1(2), TUBA1B(2), TUBA1C(2), TUBA3C(3), TUBA3D(1), TUBA3E(1), TUBA4A(2), TUBA8(2), TUBAL3(1), TUBB1(1), TUBB2A(2), TUBB3(1), TUBB4(1), TUBB8(1) 23957866 199 57 199 73 76 73 33 1 14 2 0.044 0.27 100 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 78 AIFM1(2), AKT1(1), AKT2(2), AKT3(1), APAF1(2), ATM(15), BID(1), BIRC2(2), BIRC3(5), CAPN2(2), CASP10(1), CASP3(1), CASP6(2), CASP7(1), CASP8(5), CASP9(1), CFLAR(1), CHUK(4), CSF2RB(1), DFFA(2), DFFB(1), FAS(2), IKBKB(2), IL1B(1), IL1R1(1), IL1RAP(1), IL3(1), IRAK3(2), IRAK4(2), MAP3K14(1), MYD88(1), NFKB1(4), NFKB2(2), NTRK1(3), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKACA(1), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), TNFRSF10B(4), TNFRSF10D(1) 14355280 108 32 108 31 31 41 20 0 15 1 0.045 0.28 101 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 36 ACTA1(1), ACTA2(1), ACTN2(5), ACTN3(1), ACTN4(3), FAM48A(3), MYBPC1(2), MYBPC3(1), MYH3(7), MYH6(5), MYH7(5), MYH8(7), MYL4(1), MYL9(2), MYOM1(4), NEB(16), TMOD1(1), TNNT2(2), TPM2(3), TPM3(1), TPM4(1), TTN(105), VIM(3) 24339920 180 45 179 46 60 68 36 1 13 2 0.046 0.28 102 FBW7PATHWAY Cyclin E interacts with cell cycle checkpoint kinase cdk2 to allow transcription of genes required for S phase, including transcription of additional cyclin E. CCNE1, CDC34, CDK2, CUL1, E2F1, FBXW7, RB1, SKP1A, TFDP1 7 CCNE1(1), CUL1(5), RB1(3), TFDP1(1) 1247460 10 9 10 5 4 0 3 0 3 0 0.048 0.29 103 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 137 ACTA1(1), ACTA2(1), ADCY1(5), ADCY2(8), ADCY3(2), ADCY4(2), ADCY5(6), ADCY7(2), ADCY8(3), ADCY9(2), ATF1(1), ATF2(1), ATF4(1), ATP2A2(3), ATP2A3(1), CACNB3(1), CALCA(1), CAMK2D(2), CNN1(1), CNN2(1), CORIN(4), CREB3(2), CRHR1(1), DGKZ(1), ETS2(1), FOS(1), GABPB2(1), GBA2(1), GJA1(4), GNAQ(1), GNB3(2), GNB4(1), GNG3(1), GNG4(1), GNGT1(1), GRK4(1), GRK5(1), GSTO1(1), GUCY1A3(5), IGFBP3(3), IGFBP4(1), IL1B(1), IL6(2), ITPR1(8), ITPR2(6), ITPR3(7), MIB1(3), MYL4(1), MYLK2(2), NFKB1(4), NOS1(6), OXTR(1), PDE4B(3), PDE4D(1), PLCB3(3), PLCD1(4), PLCG1(1), PLCG2(4), PRKACA(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PRKCA(3), PRKCE(2), PRKCH(1), PRKCQ(2), PRKD1(5), RAMP3(1), RGS1(1), RGS17(2), RGS2(3), RGS20(1), RGS3(3), RGS4(2), RGS5(1), RGS7(4), RGS9(3), RLN1(1), RYR1(11), RYR2(11), RYR3(11), SLC8A1(4), SP1(1), TNXB(4), USP5(2), YWHAH(1) 31604422 224 63 224 88 79 94 26 1 23 1 0.048 0.29 104 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@ 15 CD28(1), CD80(1), CTLA4(1), GRB2(2), HLA-DRA(3), HLA-DRB1(1), IL2(2), ITK(4), LCK(2), PTPN11(4) 1588016 21 10 21 5 6 12 2 0 1 0 0.050 0.29 105 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(4) 132248 4 3 4 0 3 1 0 0 0 0 0.050 0.29 106 HSA04664_FC_EPSILON_RI_SIGNALING_PATHWAY Genes involved in Fc epsilon RI signaling pathway AKT1, AKT2, AKT3, BTK, CSF2, FCER1A, FCER1G, FYN, GAB2, GRB2, HRAS, IL13, IL3, IL4, IL5, INPP5D, KRAS, LAT, LCP2, LYN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK9, MS4A2, NRAS, PDK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCD, PRKCE, RAC1, RAC2, RAC3, RAF1, SOS1, SOS2, SYK, TNF, VAV1, VAV2, VAV3 69 AKT1(1), AKT2(2), AKT3(1), BTK(2), FCER1A(3), FYN(1), GAB2(1), GRB2(2), IL3(1), IL4(1), INPP5D(2), LAT(1), LCP2(1), MAP2K1(2), MAP2K2(1), MAP2K3(4), MAP2K4(2), MAP2K6(1), MAPK13(1), MAPK3(1), MAPK8(6), MAPK9(2), MS4A2(2), PDK1(2), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PLA2G4A(4), PLA2G6(2), PLCG1(1), PLCG2(4), PRKCA(3), PRKCE(2), RAF1(4), SOS1(3), SOS2(6), SYK(3), VAV1(7), VAV2(3), VAV3(3) 12033844 100 33 100 25 33 35 17 2 13 0 0.051 0.29 107 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 11 ASAH1(1), CREB3(2), CREB5(2), RAF1(4), SNX13(3), SRC(3), TERF2IP(2) 1867148 17 10 17 4 7 6 2 1 1 0 0.051 0.29 108 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 ACP2(1), ACPP(2), ALPPL2(1), CYP19A1(6), CYP1A1(2), CYP1A2(2), CYP2A13(3), CYP2A6(3), CYP2C18(2), CYP2C8(2), CYP2C9(5), CYP2E1(3), CYP2F1(1), CYP2J2(3), CYP3A7(3), CYP4B1(3), PON1(1) 5330408 43 24 43 8 16 7 15 0 4 1 0.054 0.31 109 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(4), JAK3(4), PIAS1(1), PIAS3(2), PTPRU(6), REG1A(2) 2548460 20 13 20 3 9 6 2 0 2 1 0.055 0.31 110 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 16 ABCB1(6), AKT1(1), ATM(15), CDKN1A(1), CPB2(1), CSNK1D(2), FHL2(1), HIF1A(3), IGFBP3(3), MAPK8(6) 3468382 39 16 39 4 8 17 9 1 3 1 0.055 0.31 111 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(5), CFTR(5), GNAS(2), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), SLC9A3R1(1) 2299392 20 13 20 5 6 8 3 0 3 0 0.055 0.31 112 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 25 CPEB1(3), EGFR(5), ERBB4(7), ETS1(1), ETS2(1), ETV6(2), FMN2(3), GRB2(2), MAP2K1(2), MAPK3(1), NOTCH2(6), NOTCH3(5), NOTCH4(6), PIWIL1(3), PIWIL2(5), PIWIL3(3), PIWIL4(3), RAF1(4), SOS1(3), SOS2(6), SPIRE1(1) 8092204 72 31 72 20 18 31 14 2 7 0 0.057 0.31 113 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(2), BID(1), BIRC2(2), BIRC3(5), CASP3(1), CASP6(2), CASP7(1), CASP8(5), CASP9(1), DFFA(2), DFFB(1) 2480842 23 13 23 4 4 9 4 0 6 0 0.059 0.32 114 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 33 ACTA1(1), DOCK1(2), FOS(1), GAB1(1), GRB2(2), HGF(3), ITGA1(1), MAP2K1(2), MAP2K2(1), MAP4K1(1), MAPK3(1), MAPK8(6), MET(1), PAK1(1), PTEN(4), PTK2(1), PTK2B(1), PTPN11(4), RAF1(4), RAP1A(1), RAP1B(1), RASA1(5), SOS1(3), SRC(3), STAT3(1) 7631016 52 22 52 15 16 17 12 1 6 0 0.059 0.32 115 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 AMD1(1), BHMT(3), CBS(2), CTH(1), DNMT1(11), DNMT3A(6), DNMT3B(5), MARS(4), MARS2(1), MAT1A(2), MAT2B(1), MTAP(1), MTFMT(1), MTR(1), TAT(3) 3800838 43 20 42 8 16 18 3 2 4 0 0.060 0.32 116 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(2), BCL2A1(3), BOK(1), CASP10(1), CASP2(1), CASP3(1), CASP4(2), CASP6(2), CASP7(1), CASP8(5), CASP9(1), CD40(1), CD40LG(4), CRADD(1), DAXX(1), DFFA(2), DFFB(1), FAS(2), IKBKE(1), NFKB1(4), NGFR(1), NR3C1(1), NTRK1(3), PTPN13(9), SFRS2IP(3), TFG(1), TRAF1(1), TRAF3(2), TRAF6(1) 7996996 59 26 59 24 13 22 12 0 12 0 0.060 0.32 117 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 8 CARS(3), CTH(1), GOT1(2), LDHA(2), LDHB(2), LDHC(1) 1206468 11 7 11 2 4 4 1 0 2 0 0.061 0.32 118 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 38 AKT1(1), ASAH1(1), ATF1(1), CREB3(2), CREB5(2), CREBBP(8), DAG1(3), EGR1(1), EGR2(3), FRS2(2), GNAQ(1), MAP1B(16), MAP2K4(2), MAPK3(1), MAPK8(6), MAPK8IP3(1), MAPK9(2), NTRK1(3), OPN1LW(1), PIK3C2G(2), PIK3CD(2), PTPN11(4), RPS6KA3(2), SHC1(1), SRC(3), TERF2IP(2) 8101132 73 28 73 23 23 28 9 2 11 0 0.062 0.32 119 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(5), GNAS(2), GNGT1(1), PPP2CA(1), PRKAA1(1), PRKAA2(4), PRKAB1(1), PRKACG(1), PRKAG2(2), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1) 2738406 24 16 24 6 12 6 4 0 2 0 0.066 0.34 120 G2PATHWAY Activated Cdc2-cyclin B kinase regulates the G2/M transition; DNA damage stimulates the DNA-PK/ATM/ATR kinases, which inactivate Cdc2. ATM, ATR, BRCA1, CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CDC34, CDKN1A, CDKN2D, CHEK1, CHEK2, EP300, GADD45A, MDM2, MYT1, PLK, PRKDC, RPS6KA1, TP53, WEE1, YWHAH, YWHAQ 21 ATM(15), ATR(7), BRCA1(2), CDC25A(1), CDC25B(2), CDC25C(1), CDKN1A(1), CHEK2(1), EP300(8), MYT1(9), PRKDC(5), YWHAH(1) 7780192 53 25 53 10 15 23 9 2 3 1 0.066 0.34 121 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 ACMSD(1), ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), AOC2(1), AOC3(1), AOX1(3), CAT(1), CYP19A1(6), CYP1A1(2), CYP1A2(2), CYP2A13(3), CYP2A6(3), CYP2C18(2), CYP2C8(2), CYP2C9(5), CYP2E1(3), CYP2F1(1), CYP2J2(3), CYP3A7(3), CYP4B1(3), ECHS1(1), GCDH(3), HADHA(1), KMO(2), KYNU(2), MAOA(3), MAOB(1), SDS(1), TDO2(2), TPH1(2), WARS(1), WARS2(2) 9962500 79 34 79 24 27 25 19 0 8 0 0.066 0.34 122 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(5), CPT1A(3), LEPR(5), PRKAA1(1), PRKAA2(4), PRKAB1(1), PRKAG2(2) 2663918 21 12 21 11 9 6 4 0 2 0 0.073 0.37 123 ERBB3PATHWAY Neuregulins bind to the receptor tyrosine kinases ErbB3 and ErbB4, surface-localized receptors whose overexpression induces tumor formation. EGF, EGFR, ERBB3, NRG1, UBE2D1 4 EGFR(5), ERBB3(6) 1510562 11 10 9 3 5 3 2 1 0 0 0.073 0.37 124 ACETYLCHOLINE_SYNTHESIS ACHE, CHAT, CHKA, PCYT1A, PDHA1, PDHA2, PEMT, SLC18A3 8 ACHE(2), CHAT(1), CHKA(2), PCYT1A(2), PDHA1(1), PDHA2(4), PEMT(1), SLC18A3(1) 1282068 14 11 14 8 3 4 6 0 1 0 0.078 0.39 125 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 F2(2), F3(1), F5(10), F7(1), FGA(6), FGB(1), FGG(2), PROS1(3), SERPINC1(1), TFPI(3) 2937700 30 13 30 8 6 13 8 0 3 0 0.080 0.39 126 ST_JNK_MAPK_PATHWAY JNKs are MAP kinases regulated by several levels of kinases (MAPKK, MAPKKK) and phosphorylate transcription factors and regulatory proteins. AKT1, ATF2, CDC42, DLD, DUSP10, DUSP4, DUSP8, GAB1, GADD45A, GCK, IL1R1, JUN, MAP2K4, MAP2K5, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K9, MAPK10, MAPK7, MAPK8, MAPK9, MYEF2, NFATC3, NR2C2, PAPPA, SHC1, TP53, TRAF6, ZAK 36 AKT1(1), ATF2(1), CDC42(1), DLD(1), DUSP10(3), GAB1(1), GCK(1), IL1R1(1), MAP2K4(2), MAP2K5(2), MAP3K1(2), MAP3K10(1), MAP3K11(1), MAP3K12(2), MAP3K13(1), MAP3K2(1), MAP3K3(2), MAP3K4(8), MAP3K5(3), MAP3K7(2), MAP3K9(4), MAPK8(6), MAPK9(2), MYEF2(2), NFATC3(1), NR2C2(1), PAPPA(10), SHC1(1), TRAF6(1), ZAK(2) 8743774 67 28 67 18 24 17 14 1 11 0 0.082 0.39 127 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(1), ACAD9(4), ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3), DHRS1(1), DHRS2(1), DHRS3(1), ESCO1(6), ESCO2(1), MYST3(10), MYST4(7), SH3GLB1(1) 4454936 45 20 45 16 14 13 14 1 3 0 0.082 0.39 128 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(2), DLG4(1), EPHB2(3), F2(2), F2RL1(1), F2RL2(1), MAP2K5(2), MAPK8(6), MYEF2(2), PLD1(6), PLD2(1), PLD3(1), PTK2(1), RAF1(4), RASAL1(2), SRC(3), TEC(2), VAV1(7) 5090624 47 22 47 11 16 19 7 1 4 0 0.082 0.39 129 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 6 DBH(2), GAD1(2), HDC(5), TPH1(2) 1044528 11 8 11 8 3 5 2 0 1 0 0.083 0.39 130 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(5), CREBBP(8), CSK(2), GNAS(2), GNGT1(1), HLA-DRA(3), HLA-DRB1(1), LCK(2), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PTPRC(9), ZAP70(1) 4078142 41 19 41 8 15 15 6 0 5 0 0.083 0.39 131 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(5), CREBBP(8), CSK(2), GNAS(2), GNGT1(1), HLA-DRA(3), HLA-DRB1(1), LCK(2), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PTPRC(9), ZAP70(1) 4078142 41 19 41 8 15 15 6 0 5 0 0.083 0.39 132 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(1), CARS(3), DARS(3), DARS2(1), EPRS(4), FARS2(3), FARSB(2), HARS2(3), IARS(3), IARS2(1), LARS(1), LARS2(1), MARS(4), MARS2(1), MTFMT(1), NARS(2), NARS2(3), QARS(3), RARS(3), RARS2(2), SARS(1), TARS(4), TARS2(2), VARS2(2), WARS(1), WARS2(2), YARS(1), YARS2(2) 9549860 62 28 61 16 17 22 15 2 6 0 0.083 0.39 133 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 71 ARAF(1), C7orf16(2), CACNA1A(9), CRHR1(1), GNA11(1), GNAI1(1), GNAO1(2), GNAQ(1), GNAS(2), GRIA1(6), GRIA2(6), GRIA3(4), GRID2(5), GRM1(5), GRM5(4), GUCY1A2(6), GUCY1A3(5), GUCY1B3(2), GUCY2C(3), GUCY2D(6), GUCY2F(6), IGF1(1), IGF1R(2), ITPR1(8), ITPR2(6), ITPR3(7), MAP2K1(2), MAP2K2(1), MAPK3(1), NOS1(6), NPR1(2), NPR2(2), PLA2G4A(4), PLA2G6(2), PLCB1(1), PLCB3(3), PLCB4(2), PPP2CA(1), PPP2CB(2), PPP2R1A(1), PPP2R1B(1), PPP2R2B(2), PPP2R2C(2), PRKCA(3), PRKCG(5), PRKG1(8), PRKG2(3), RAF1(4), RYR1(11) 20003964 171 48 170 65 65 56 35 1 13 1 0.084 0.39 134 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 5 AKT1(1), PLCB1(1), PLCG1(1), PRKCA(3), VAV1(7) 1688532 13 10 13 5 2 6 3 1 1 0 0.085 0.39 135 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(1), IL4(1), MAF(1), MAP2K3(4), NFATC1(1), NFATC2(3), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1) 2004754 18 13 18 6 10 4 2 1 1 0 0.086 0.39 136 HSA04150_MTOR_SIGNALING_PATHWAY Genes involved in mTOR signaling pathway AKT1, AKT2, AKT3, BRAF, CAB39, DDIT4, EIF4B, EIF4EBP1, FIGF, FRAP1, GBL, HIF1A, IGF1, INS, KIAA1303, LYK5, MAPK1, MAPK3, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PRKAA1, PRKAA2, RHEB, RICTOR, RPS6, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6, RPS6KB1, RPS6KB2, STK11, TSC1, TSC2, ULK1, ULK2, ULK3, VEGFA, VEGFB, VEGFC 41 AKT1(1), AKT2(2), AKT3(1), EIF4B(1), FIGF(2), HIF1A(3), IGF1(1), MAPK3(1), PDPK1(1), PGF(1), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PRKAA1(1), PRKAA2(4), RICTOR(5), RPS6KA2(4), RPS6KA3(2), RPS6KA6(3), RPS6KB2(1), TSC1(2), TSC2(1), ULK1(1), VEGFC(3) 8461886 53 22 53 17 19 18 7 0 9 0 0.086 0.39 137 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(2), ARHGDIB(1), BIRC2(2), BIRC3(5), CASP10(1), CASP2(1), CASP3(1), CASP4(2), CASP6(2), CASP7(1), CASP8(5), CASP9(1), DFFA(2), DFFB(1), GZMB(2), LMNB1(3) 3503922 32 16 31 9 6 12 6 0 8 0 0.087 0.39 138 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 ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3), ALDH1A3(4), ALDH3B1(1), ALDH3B2(1), AOC2(1), AOC3(1), AOX1(3), CARM1(1), DBH(2), DCT(7), ESCO1(6), ESCO2(1), FAH(2), GOT1(2), GSTZ1(1), HGD(2), HPD(2), LCMT1(2), MAOA(3), MAOB(1), METTL2B(1), METTL6(3), MYST3(10), MYST4(7), PRMT3(1), PRMT7(2), PRMT8(2), SH3GLB1(1), TAT(3), TPO(4), TYR(1), TYRP1(1), WBSCR22(1) 10738052 92 35 92 34 28 35 17 3 9 0 0.087 0.39 139 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(1), ADC(1), ALDH4A1(1), ALDH5A1(2), CAD(4), CPS1(7), EPRS(4), GAD1(2), GAD2(2), GFPT1(3), GFPT2(1), GLUD2(3), GLUL(2), GOT1(2), GPT2(1), GSS(1), NADSYN1(1), NAGK(1), PPAT(5), QARS(3) 7196566 47 27 47 15 15 18 8 3 3 0 0.088 0.39 140 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 59 AKT1(1), AKT2(2), AKT3(1), BCL10(1), BLNK(1), BTK(2), CARD11(5), CD19(1), CD22(4), CD72(1), CD79A(1), CD79B(1), CHUK(4), CR2(3), FOS(1), GSK3B(2), IKBKB(2), INPP5D(2), LILRB3(1), MALT1(2), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), NFKB1(4), NFKB2(2), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PLCG2(4), PPP3CA(2), PPP3CB(2), PPP3CC(3), RASGRP3(3), SYK(3), VAV1(7), VAV2(3), VAV3(3) 12676758 93 35 93 24 36 35 11 0 11 0 0.088 0.39 141 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(3), CTH(1), GOT1(2), LDHA(2), LDHAL6A(2), LDHAL6B(1), LDHB(2), LDHC(1), SDS(1), SULT1B1(1), SULT1C2(1), SULT1C4(2) 2269768 19 9 18 4 7 5 3 1 3 0 0.091 0.40 142 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 14 AKT1(1), CDKN1B(2), GRB2(2), MAPK3(1), PDK2(1), PDPK1(1), PTEN(4), PTK2(1), SHC1(1), SOS1(3) 2772972 17 11 17 4 1 5 5 0 6 0 0.092 0.40 143 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(3), CCNE1(1), CUL1(5), RB1(3), TFDP1(1) 1604310 13 9 13 6 4 1 4 0 4 0 0.094 0.41 144 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 12 AXIN1(1), CREBBP(8), EP300(8), FZD1(1), GSK3B(2), HDAC1(2), LDB1(2), LEF1(1), TRRAP(9) 4579668 34 23 34 6 14 10 5 1 4 0 0.096 0.41 145 SMALL_LIGAND_GPCRS C9orf47, CNR1, CNR2, DNMT1, EDG1, EDG2, EDG5, EDG6, MTNR1A, MTNR1B, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, TBXA2R 13 CNR1(3), DNMT1(11), PTGDR(1), PTGFR(3) 1957196 18 14 17 2 8 4 4 2 0 0 0.098 0.42 146 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 20 ADCY1(5), AKT1(1), ASAH1(1), GNAI1(1), GNGT1(1), ITGAV(4), ITGB3(2), MAPK3(1), PDGFRA(4), PLCB1(1), PRKCA(3), PTK2(1), SPHK1(1), SRC(3) 4294086 29 17 29 15 7 12 4 1 5 0 0.099 0.42 147 PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS ENO1, ENO2, ENO3, FARS2, FARSLB, GOT1, GOT2, PAH, TAT, YARS 9 ENO2(2), ENO3(2), FARS2(3), GOT1(2), PAH(1), TAT(3), YARS(1) 1514374 14 9 14 5 4 7 1 0 2 0 0.100 0.42 148 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 186 ACTN1(2), ACTN2(5), ACTN3(1), ACTN4(3), AKT1(1), AKT2(2), AKT3(1), ARHGAP5(4), BIRC2(2), BIRC3(5), CAPN2(2), CAV1(1), CAV3(1), CCND2(1), CCND3(1), CDC42(1), CHAD(2), COL11A1(8), COL11A2(3), COL1A1(2), COL1A2(6), COL2A1(2), COL3A1(7), COL4A1(5), COL4A2(1), COL4A4(2), COL4A6(5), COL5A1(7), COL5A2(4), COL5A3(6), COL6A2(1), COL6A3(20), COL6A6(5), DOCK1(2), EGFR(5), FARP2(2), FIGF(2), FLNA(1), FLNB(6), FLNC(2), FLT1(4), FN1(6), FYN(1), GRB2(2), GRLF1(5), GSK3B(2), HGF(3), IBSP(1), IGF1(1), IGF1R(2), ITGA1(1), ITGA10(4), ITGA11(2), ITGA2(2), ITGA2B(3), ITGA4(5), ITGA5(2), ITGA6(2), ITGA8(3), ITGA9(3), ITGAV(4), ITGB3(2), ITGB4(1), ITGB5(4), ITGB6(2), ITGB7(2), ITGB8(1), KDR(3), LAMA1(7), LAMA2(10), LAMA3(8), LAMA4(6), LAMB1(2), LAMB2(3), LAMB3(1), LAMB4(6), LAMC1(6), LAMC2(4), LAMC3(4), MAP2K1(2), MAPK3(1), MAPK8(6), MAPK9(2), MET(1), MYL9(2), MYLK(5), MYLK2(2), PAK1(1), PAK2(3), PAK3(3), PAK7(3), PARVB(2), PDGFC(1), PDGFRA(4), PDGFRB(2), PDPK1(1), PGF(1), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PIP5K1C(3), PPP1CB(1), PPP1CC(1), PPP1R12A(1), PRKCA(3), PRKCG(5), PTEN(4), PTK2(1), RAF1(4), RAP1A(1), RAP1B(1), RAPGEF1(2), RELN(13), RHOA(1), ROCK1(8), ROCK2(4), SHC1(1), SHC2(1), SHC3(1), SHC4(1), SOS1(3), SOS2(6), SRC(3), THBS1(3), THBS2(8), THBS3(2), THBS4(1), TLN1(3), TLN2(4), TNC(7), TNN(4), TNR(4), TNXB(4), VAV1(7), VAV2(3), VAV3(3), VCL(2), VEGFC(3), VTN(3), VWF(7), ZYX(1) 64985332 461 79 461 192 166 161 76 5 52 1 0.10 0.42 149 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), ALG10B(3), ALG11(1), ALG12(1), ALG14(1), ALG2(1), ALG5(1), ALG6(1), ALG8(3), ALG9(1), B4GALT1(2), B4GALT3(3), DAD1(2), DDOST(1), DHDDS(1), DPAGT1(1), FUT8(2), GANAB(1), MAN1A1(2), MAN1A2(1), MAN1B1(1), MAN1C1(3), MAN2A1(7), MGAT1(1), MGAT4A(1), MGAT5(2), RPN2(1), STT3B(4) 7639432 50 24 50 15 17 15 12 0 6 0 0.10 0.42 150 SA_FAS_SIGNALING The TNF-type receptor Fas induces apoptosis on ligand binding. BCL2, CASP3, CASP8, CFL1, CFLAR, P11, PDE6D, TNFRSF6, TNFSF6 6 CASP3(1), CASP8(5), CFLAR(1) 689576 7 6 7 0 0 4 2 0 1 0 0.11 0.44 151 HSA04910_INSULIN_SIGNALING_PATHWAY Genes involved in insulin signaling pathway ACACA, ACACB, AKT1, AKT2, AKT3, ARAF, BAD, BRAF, CALM1, CALM2, CALM3, CALML3, CALML6, CBL, CBLB, CBLC, CRK, CRKL, EIF4EBP1, ELK1, EXOC7, FASN, FBP1, FBP2, FLOT1, FLOT2, FOXO1, FRAP1, G6PC, G6PC2, GCK, GRB2, GSK3B, GYS1, GYS2, HRAS, IKBKB, INPP5D, INS, INSR, IRS1, IRS2, IRS4, KIAA1303, KRAS, LIPE, MAP2K1, MAP2K2, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MKNK1, MKNK2, NRAS, PCK1, PCK2, PDE3A, PDE3B, PDPK1, PFKL, PFKM, PFKP, PHKA1, PHKA2, PHKB, PHKG1, PHKG2, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PKLR, PKM2, PPARGC1A, PPP1CA, PPP1CB, PPP1CC, PPP1R3A, PPP1R3B, PPP1R3C, PPP1R3D, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKACA, PRKACB, PRKACG, PRKAG1, PRKAG2, PRKAG3, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCI, PRKCZ, PRKX, PRKY, PTPN1, PTPRF, PYGB, PYGL, PYGM, RAF1, RAPGEF1, RHEB, RHOQ, RPS6, RPS6KB1, RPS6KB2, SH2B2, SHC1, SHC2, SHC3, SHC4, SKIP, SLC2A4, SOCS1, SOCS2, SOCS3, SOCS4, SORBS1, SOS1, SOS2, SREBF1, TRIP10, TSC1, TSC2 123 ACACA(5), ACACB(5), AKT1(1), AKT2(2), AKT3(1), ARAF(1), CBL(4), CBLB(3), EXOC7(2), FBP2(1), G6PC(1), G6PC2(1), GCK(1), GRB2(2), GSK3B(2), GYS1(2), GYS2(4), IKBKB(2), INPP5D(2), INSR(1), IRS1(4), IRS4(8), LIPE(1), MAP2K1(2), MAP2K2(1), MAPK3(1), MAPK8(6), MAPK9(2), MKNK1(1), MKNK2(1), PCK1(3), PCK2(2), PDE3A(1), PDE3B(1), PDPK1(1), PFKM(3), PFKP(2), PHKA1(5), PHKA2(3), PHKB(2), PHKG2(2), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PPP1CB(1), PPP1CC(1), PPP1R3A(6), PPP1R3C(2), PRKAA1(1), PRKAA2(4), PRKAB1(1), PRKACA(1), PRKACG(1), PRKAG2(2), PRKAG3(3), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PRKCI(1), PTPN1(4), PTPRF(5), PYGB(1), PYGM(3), RAF1(4), RAPGEF1(2), RPS6KB2(1), SHC1(1), SHC2(1), SHC3(1), SHC4(1), SLC2A4(2), SOCS2(1), SOCS4(1), SORBS1(7), SOS1(3), SOS2(6), TSC1(2), TSC2(1) 27166984 184 48 184 63 66 55 37 2 24 0 0.11 0.44 152 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C9(5) 368196 5 3 5 0 1 1 2 0 1 0 0.11 0.44 153 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 20 FOS(1), GRB2(2), JAK2(4), MAP2K1(2), MAPK3(1), MPL(1), PLCG1(1), PRKCA(3), RAF1(4), RASA1(5), SHC1(1), SOS1(3), STAT1(1), STAT3(1), STAT5B(1), THPO(1) 4801932 32 16 32 6 8 12 7 0 4 1 0.11 0.44 154 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 4 FOSB(1), GRIA2(6), PPP1R1B(1) 646316 8 7 8 3 3 0 4 0 1 0 0.11 0.44 155 HSA00641_3_CHLOROACRYLIC_ACID_DEGRADATION Genes involved in 3-chloroacrylic acid degradation ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1 15 ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH7A1(2) 2452602 23 14 23 7 6 9 6 0 2 0 0.11 0.44 156 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(3), FARSB(2), GOT1(2), PAH(1), TAT(3), YARS(1), YARS2(2) 1587016 14 9 14 5 3 8 1 0 2 0 0.11 0.44 157 NUCLEAR_RECEPTORS ALK, AR, ESR1, ESR2, ESRRA, HNF4A, NPM1, NR0B1, NR1D2, NR1H2, NR1H3, NR1I2, NR1I3, NR2C2, NR2E1, NR2F1, NR2F2, NR2F6, NR3C1, NR4A1, NR4A2, NR5A1, NR5A2, PGR, PPARA, PPARD, PPARG, RARA, RARB, RARG, ROR1, RORA, RORC, RXRA, RXRB, RXRG, THRA, THRA, NR1D1, THRB, VDR 40 ALK(5), AR(3), ESR1(3), ESRRA(1), HNF4A(4), NPM1(1), NR0B1(1), NR1D2(3), NR1H3(2), NR1I2(1), NR1I3(2), NR2C2(1), NR2E1(1), NR2F1(2), NR2F2(1), NR2F6(1), NR3C1(1), NR4A1(2), NR4A2(5), PPARA(1), PPARD(1), PPARG(1), RARB(4), RARG(3), ROR1(4), RORA(1), RXRB(1), RXRG(2), THRB(1), VDR(1) 7445558 60 27 60 20 21 19 14 1 5 0 0.11 0.44 158 BIOGENIC_AMINE_SYNTHESIS AANAT, ACHE, CHAT, COMT, DBH, DDC, DXYS155E, GAD1, GAD2, HDC, MAOA, PAH, PNMT, SLC18A3, TH, TPH1 15 ACHE(2), CHAT(1), DBH(2), GAD1(2), GAD2(2), HDC(5), MAOA(3), PAH(1), SLC18A3(1), TPH1(2) 2574880 21 16 21 17 6 9 4 0 2 0 0.11 0.44 159 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 42 ACTR2(1), ACTR3(1), AKT1(1), AKT2(2), AKT3(1), ANGPTL2(4), ARHGEF11(6), BTK(2), CDC42(1), INPPL1(3), ITPR1(8), ITPR2(6), ITPR3(7), LIMK1(2), MYLK(5), MYLK2(2), PAK1(1), PAK2(3), PAK3(3), PAK7(3), PDK1(2), PIK3CD(2), PIK3CG(5), PPP1R13B(1), PTEN(4), RACGAP1(1), RHO(2), ROCK1(8), ROCK2(4), RPS4X(1), WASF1(2), WASL(2) 12250050 96 33 96 21 38 31 11 0 15 1 0.12 0.44 160 HSA00930_CAPROLACTAM_DEGRADATION Genes involved in caprolactam degradation AKR1A1, ASAHL, ECHS1, EHHADH, HADH, HADHA, HSD17B10, HSD17B4, NTAN1, SIRT1, SIRT2, SIRT5, SIRT7, VNN2, VNN3 13 ECHS1(1), HADH(1), HADHA(1), HSD17B10(1), HSD17B4(1), NTAN1(1), SIRT1(2), SIRT2(2), SIRT5(2), VNN2(2) 2146370 14 11 14 5 3 3 4 0 4 0 0.12 0.44 161 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 19 FOS(1), GRB2(2), INSR(1), IRS1(4), MAP2K1(2), MAPK3(1), MAPK8(6), PTPN11(4), RAF1(4), RASA1(5), SHC1(1), SLC2A4(2), SOS1(3) 3886856 36 16 36 4 9 13 8 1 5 0 0.12 0.44 162 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 IFNGR1(1), JAK1(1), JAK2(4), PTPRU(6), REG1A(2), STAT1(1) 2109774 15 10 15 3 9 2 2 0 1 1 0.12 0.44 163 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 18 FOS(1), GRB2(2), IGF1(1), IGF1R(2), IRS1(4), MAP2K1(2), MAPK3(1), MAPK8(6), PTPN11(4), RAF1(4), RASA1(5), SHC1(1), SOS1(3) 3750104 36 17 36 5 11 13 7 1 4 0 0.12 0.45 164 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 45 ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3), AGPAT1(1), AGPAT4(4), AKR1B1(1), ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), DGKA(1), DGKB(2), DGKD(8), DGKE(2), DGKG(2), DGKH(7), DGKZ(1), GK(1), GLA(1), LCT(11), LIPC(1), LIPF(2), LPL(2), PNLIP(3), PNLIPRP1(1), PNLIPRP2(1) 8698548 77 30 77 19 30 24 16 0 7 0 0.12 0.45 165 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 82 ATF2(1), CHUK(4), DAXX(1), FOS(1), GRB2(2), IKBKB(2), MAP2K1(2), MAP2K2(1), MAP2K3(4), MAP2K4(2), MAP2K5(2), MAP2K6(1), MAP3K1(2), MAP3K10(1), MAP3K11(1), MAP3K12(2), MAP3K13(1), MAP3K14(1), MAP3K2(1), MAP3K3(2), MAP3K4(8), MAP3K5(3), MAP3K6(2), MAP3K7(2), MAP3K8(1), MAP3K9(4), MAP4K1(1), MAP4K2(1), MAP4K3(1), MAP4K4(3), MAPK13(1), MAPK3(1), MAPK6(1), MAPK8(6), MAPK9(2), MEF2A(1), MEF2C(2), MKNK1(1), MKNK2(1), NFKB1(4), PAK1(1), PAK2(3), RAF1(4), RPS6KA2(4), RPS6KA3(2), RPS6KA5(4), RPS6KB2(1), SHC1(1), SP1(1), STAT1(1), TGFB1(1), TGFB2(4), TGFBR1(5) 17150644 112 37 112 31 30 34 28 2 18 0 0.12 0.45 166 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(2), HLA-DRA(3), HLA-DRB1(1), IL3(1) 474628 7 5 7 2 3 4 0 0 0 0 0.12 0.45 167 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(1), ARSD(1), CARM1(1), CYP11B1(4), CYP19A1(6), HSD17B2(1), HSD17B3(1), HSD3B1(1), HSD3B2(1), LCMT1(2), METTL2B(1), METTL6(3), PRMT3(1), PRMT7(2), PRMT8(2), SRD5A1(1), SRD5A2(1), STS(1), SULT1E1(1), SULT2A1(1), UGT1A4(1), UGT1A6(1), UGT1A8(1), UGT1A9(1), UGT2A3(2), UGT2B11(2), UGT2B17(4), UGT2B28(1), UGT2B4(2), UGT2B7(2), WBSCR22(1) 8733978 52 27 52 14 12 20 10 2 8 0 0.12 0.45 168 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 97 AKT1(1), AKT2(2), AKT3(1), CASP8(5), CD40(1), CD80(1), CHUK(4), CXCL10(1), CXCL11(2), CXCL9(2), FOS(1), IFNA10(3), IFNA2(2), IFNA5(1), IFNAR2(1), IKBKB(2), IKBKE(1), IL12A(1), IL12B(1), IL1B(1), IL6(2), IL8(1), IRAK4(2), IRF3(2), MAP2K1(2), MAP2K2(1), MAP2K3(4), MAP2K4(2), MAP2K6(1), MAP3K7(2), MAP3K8(1), MAPK13(1), MAPK3(1), MAPK8(6), MAPK9(2), MYD88(1), NFKB1(4), NFKB2(2), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), STAT1(1), TBK1(2), TICAM1(1), TLR1(3), TLR2(4), TLR3(2), TLR4(4), TLR5(2), TLR6(1), TLR7(5), TLR8(3), TLR9(4), TOLLIP(1), TRAF3(2), TRAF6(1) 15337648 119 34 119 30 35 43 26 2 12 1 0.12 0.45 169 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(2), AGTR1(3), ATF2(1), EGFR(5), GNAQ(1), GRB2(2), MAP2K1(2), MAP2K2(1), MAP2K4(2), MAP3K1(2), MAPK3(1), MAPK8(6), MEF2A(1), MEF2C(2), PAK1(1), PRKCA(3), PTK2(1), PTK2B(1), RAF1(4), SHC1(1), SOS1(3), SRC(3) 6244214 48 21 48 9 13 17 9 1 8 0 0.13 0.46 170 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(2), GNAQ(1), GNAS(2), GNGT1(1), LIMK1(2), MAP2K1(2), MAPK3(1), PIK3C2G(2), PLCB1(1), PPP1R12B(4), PRKCA(3), PTK2(1), RAF1(4), ROCK2(4) 4649560 30 17 30 7 9 10 3 1 7 0 0.13 0.46 171 VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION ACAA1, ACAA2, ACADL, ACADM, ACADS, ACADSB, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH9A1, AOX1, BCAT1, BCKDHA, BCKDHB, ECHS1, EHHADH, HADHA, HADHB, HIBADH, HMGCL, IVD, MCCC1, MCCC2, MCEE, MUT, OXCT1, PCCA, PCCB, SDS 36 ACAA1(1), ACAA2(1), ACADL(2), ACADM(4), ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH6A1(2), AOX1(3), ECHS1(1), HADHA(1), HADHB(1), HMGCL(1), MCCC1(4), MCCC2(2), MCEE(1), MUT(2), PCCA(7), PCCB(3), SDS(1) 6617364 50 24 50 15 20 16 5 0 9 0 0.13 0.46 172 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(1), ACADL(2), ACADM(4), ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), AOC2(1), AOC3(1), CNDP1(1), DPYD(9), DPYS(1), ECHS1(1), GAD1(2), GAD2(2), HADHA(1), SDS(1), UPB1(2) 5272030 42 23 42 18 17 14 4 0 7 0 0.13 0.46 173 PORPHYRIN_AND_CHLOROPHYLL_METABOLISM ALAD, BLVRA, BLVRB, CP, CPOX, EPRS, FECH, GUSB, HCCS, HMBS, HMOX1, HMOX2, PPOX, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4, UROD, UROS 26 ALAD(1), BLVRA(1), BLVRB(2), CP(3), CPOX(1), EPRS(4), FECH(1), GUSB(1), HCCS(3), HMOX2(2), PPOX(1), UGT1A4(1), UGT1A6(1), UGT1A8(1), UGT1A9(1), UGT2B4(2), UROD(1) 4743490 27 18 27 7 6 14 4 0 3 0 0.13 0.46 174 IONPATHWAY Activated phospholipase C hydrolyzes the lipid PIP3 into second messengers DAG, which activates protein kinase C, and IP3, which induces calcium influx into the cytoplasm. P2RY2, PLCG1, PRKCA, PRKCB1, PTK2B 4 P2RY2(1), PLCG1(1), PRKCA(3), PTK2B(1) 1227184 6 6 6 3 2 2 1 0 1 0 0.13 0.46 175 IL6PATHWAY IL-6 binding to its receptor activates JAK kinases and a variety of transcription factors, with effects in neuronal differentiation, bone loss, and inflammation. CEBPB, CSNK2A1, ELK1, FOS, GRB2, HRAS, IL6, IL6R, IL6ST, JAK1, JAK2, JAK3, JUN, MAP2K1, MAPK3, PTPN11, RAF1, SHC1, SOS1, SRF, STAT3 20 FOS(1), GRB2(2), IL6(2), IL6R(1), IL6ST(1), JAK1(1), JAK2(4), JAK3(4), MAP2K1(2), MAPK3(1), PTPN11(4), RAF1(4), SHC1(1), SOS1(3), STAT3(1) 4310410 32 17 32 4 10 12 5 0 4 1 0.13 0.46 176 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 37 ANAPC1(1), ANAPC4(3), ANAPC5(1), ANAPC7(2), BTRC(3), CDC16(1), CDC20(1), CUL1(5), CUL2(3), FBXW11(4), ITCH(1), RBX1(1), SMURF1(2), SMURF2(2), UBA1(2), UBE2C(1), UBE2D3(1), UBE2E2(1), VHL(1), WWP1(3) 6768058 39 21 39 21 13 11 9 0 6 0 0.13 0.46 177 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(5), ADCY2(8), ADCY3(2), ADCY4(2), ADCY5(6), ADCY7(2), ADCY8(3), ADCY9(2), ADRA1A(1), ADRA1B(2), ADRB1(1), ANXA6(1), ATP1A4(3), ATP1B1(1), ATP1B2(2), ATP2A2(3), ATP2A3(1), ATP2B1(2), ATP2B2(7), ATP2B3(2), CACNA1A(9), CACNA1B(4), CACNA1C(2), CACNA1D(3), CACNA1E(6), CACNA1S(7), CACNB3(1), CALR(1), CAMK1(2), CAMK2D(2), CAMK4(1), CASQ1(1), CASQ2(3), CHRM1(1), CHRM2(3), CHRM4(1), CHRM5(2), GJA1(4), GJA4(1), GJA5(2), GJB3(2), GNA11(1), GNAO1(2), GNAQ(1), GNB3(2), GNB4(1), GNG3(1), GNG4(1), GNGT1(1), GRK4(1), GRK5(1), ITPR1(8), ITPR2(6), ITPR3(7), KCNB1(4), KCNJ5(1), MIB1(3), MYCBP(1), NME7(2), PLCB3(3), PLN(1), PRKACA(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PRKCA(3), PRKCE(2), PRKCG(5), PRKCH(1), PRKCQ(2), PRKD1(5), RGS1(1), RGS17(2), RGS2(3), RGS20(1), RGS3(3), RGS4(2), RGS5(1), RGS7(4), RGS9(3), RYR1(11), RYR2(11), RYR3(11), SLC8A1(4), SLC8A3(6), USP5(2), YWHAH(1) 35372852 253 66 253 110 100 101 31 0 20 1 0.13 0.46 178 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(1), DYRK1B(3), GLI2(2), GLI3(6), GSK3B(2), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), SMO(1), SUFU(2) 2866026 24 15 24 8 6 11 4 0 3 0 0.13 0.46 179 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(4), AMY2A(2), AMY2B(1), ASCC3(8), DDX18(1), DDX19A(1), DDX23(1), DDX4(1), DDX50(1), DDX52(1), DDX55(2), DDX56(2), DHX58(1), ENPP3(2), EP400(7), ERCC2(2), ERCC3(3), G6PC(1), G6PC2(1), GANC(1), GBE1(1), GCK(1), GPI(1), GUSB(1), GYS1(2), GYS2(4), HK1(2), HK3(1), IFIH1(2), MGAM(4), MOV10L1(7), PGM1(3), PGM3(2), PYGB(1), PYGM(3), RAD54B(3), RAD54L(1), SETX(10), SI(4), SKIV2L2(2), SMARCA2(2), SMARCA5(4), UGDH(1), UGP2(3), UGT1A4(1), UGT1A6(1), UGT1A8(1), UGT1A9(1), UGT2A3(2), UGT2B11(2), UGT2B17(4), UGT2B28(1), UGT2B4(2), UGT2B7(2), UXS1(1) 22440112 126 38 126 36 31 41 33 0 21 0 0.13 0.46 180 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 42 CHUK(4), DAXX(1), EGFR(5), ETS1(1), ETS2(1), FOS(1), IKBKB(2), MAP2K1(2), MAP2K3(4), MAP2K4(2), MAP2K6(1), MAP3K1(2), MAP3K14(1), MAP3K5(3), MAPK13(1), MAPK3(1), MAPK8(6), NFKB1(4), PPP2CA(1), PRKCA(3), PRKCE(2), PRKCG(5), PRKCH(1), PRKCQ(2), RAF1(4), SP1(1) 8899820 61 29 61 19 23 19 14 2 3 0 0.14 0.46 181 RECKPATHWAY RECK is a membrane-anchored inhibitor of matrix metalloproteinases, which are expressed by tumor cells and promote metastasis. HRAS, MMP14, MMP2, MMP9, RECK, TIMP1, TIMP2, TIMP3, TIMP4 9 MMP14(1), MMP2(3), MMP9(6), RECK(3), TIMP1(1), TIMP2(1), TIMP3(1) 1382340 16 10 16 4 9 3 3 0 1 0 0.14 0.46 182 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 35 AKT1(1), AKT2(2), AKT3(1), ARHGEF11(6), CDC42(1), DLG4(1), LPA(1), MAP2K4(2), MAP3K1(2), MAP3K5(3), MAPK8(6), NFKB1(4), NFKB2(2), PDK1(2), PHKA2(3), PI3(1), PIK3CB(1), PLD1(6), PLD2(1), PLD3(1), PTK2(1), RDX(1), ROCK1(8), ROCK2(4), SERPINA4(5) 8819000 66 24 66 19 22 21 11 2 10 0 0.14 0.47 183 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(1), ACACA(5), ACACB(5), ACADM(4), ACSS1(1), ACSS2(1), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH6A1(2), ALDH7A1(2), ECHS1(1), HADHA(1), HIBCH(1), LDHA(2), LDHAL6A(2), LDHAL6B(1), LDHB(2), LDHC(1), MCEE(1), MUT(2), PCCA(7), PCCB(3), SUCLA2(3), SUCLG1(1) 7258738 58 24 58 16 15 23 7 0 13 0 0.14 0.47 184 PANTOTHENATE_AND_COA_BIOSYNTHESIS BCAT1, COASY, DPYD, DPYS, ENPP1, ENPP3, PANK1, PANK2, PANK3, PANK4, PPCS, UPB1 12 COASY(1), DPYD(9), DPYS(1), ENPP3(2), PANK3(2), PPCS(1), UPB1(2) 2455336 18 11 18 7 4 9 3 0 2 0 0.14 0.47 185 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 75 ABL1(2), ACTN1(2), ACTR2(1), ACTR3(1), AKT1(1), AKT2(2), AKT3(1), ANGPTL2(4), ARHGEF6(3), ARHGEF7(3), CAV1(1), CDC42(1), DOCK1(2), EPHB2(3), FYN(1), GRB2(2), GRLF1(5), ITGA1(1), ITGA10(4), ITGA11(2), ITGA2(2), ITGA4(5), ITGA5(2), ITGA6(2), ITGA8(3), ITGA9(3), ITGB3BP(3), MAP2K4(2), MAP3K11(1), MAPK8(6), MAPK8IP3(1), MAPK9(2), MRAS(1), MYLK(5), MYLK2(2), PAK1(1), PAK2(3), PAK3(3), PAK7(3), PIK3CB(1), PLCG1(1), PLCG2(4), PTEN(4), PTK2(1), RAF1(4), RALA(1), RHO(2), ROCK1(8), ROCK2(4), SHC1(1), SOS1(3), SOS2(6), SRC(3), TERF2IP(2), TLN1(3), TLN2(4), ZYX(1) 21430800 145 40 145 62 47 46 28 3 21 0 0.14 0.47 186 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(3), FOS(1), MAP2K1(2), MAPK3(1), NFKB1(4), PLCB1(1), PRKCA(3), RAF1(4) 2762048 19 10 19 7 10 4 2 1 2 0 0.14 0.47 187 INOSITOL_PHOSPHATE_METABOLISM IMPA1, INPP1, INPP4A, INPP4B, INPP5A, INPPL1, ITPKA, ITPKB, MIOX, OCRL, PIK3C2A, PIK3C2B, PIK3C2G, PIK3CA, PIK3CB, PIK3CG, PIK4CA, PIK4CA, LOC220686, PIP5K2B, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCG1, PLCG2 22 IMPA1(1), INPP4A(1), INPP4B(2), INPPL1(3), OCRL(6), PIK3C2A(3), PIK3C2B(6), PIK3C2G(2), PIK3CB(1), PIK3CG(5), PLCB1(1), PLCB3(3), PLCB4(2), PLCD1(4), PLCG1(1), PLCG2(4) 7838086 45 26 45 18 14 18 8 1 4 0 0.14 0.47 188 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 24 FOS(1), GRB2(2), JAK1(1), MAP2K1(2), MAP2K4(2), MAP3K1(2), MAPK3(1), MAPK8(6), PDGFRA(4), PLCG1(1), PRKCA(3), RAF1(4), RASA1(5), SHC1(1), SOS1(3), STAT1(1), STAT3(1) 5680042 40 18 40 8 11 15 9 1 4 0 0.14 0.47 189 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 ADA(1), ADCY1(5), ADCY2(8), ADCY3(2), ADCY4(2), ADCY5(6), ADCY7(2), ADCY8(3), ADSL(2), ADSS(1), AK2(1), AK5(2), ALLC(2), AMPD1(6), AMPD2(3), AMPD3(1), ATIC(1), ATP1B1(1), ATP5A1(3), ATP5B(3), ATP5C1(2), DCK(1), ENPP3(2), ENTPD1(1), GART(1), GUCY1A2(6), GUCY1A3(5), GUCY1B3(2), GUCY2C(3), GUCY2D(6), GUCY2F(6), IMPDH1(2), IMPDH2(3), NPR1(2), NPR2(2), NT5E(1), PAICS(1), PAPSS1(1), PAPSS2(2), PDE1A(2), PDE4A(1), PDE4B(3), PDE4D(1), PDE5A(3), PDE6B(4), PDE6C(3), PDE7B(1), PDE9A(2), POLB(3), POLD1(2), POLD2(1), POLE(10), POLG(2), POLL(1), POLQ(5), POLR1B(5), POLR2A(1), POLR2B(3), POLR2D(1), POLR2K(1), PPAT(5), PRPS1(1), PRPS2(1), PRUNE(1), RRM1(2) 23530700 169 49 168 60 61 53 35 1 19 0 0.14 0.47 190 NOTCHPATHWAY Proteolysis and Signaling Pathway of Notch ADAM17, DLL1, FURIN, NOTCH1, PSEN1, RBPSUH 5 ADAM17(3), DLL1(3), FURIN(1) 1353676 7 5 7 1 2 1 0 0 4 0 0.14 0.47 191 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 37 CCNH(1), ERCC3(3), GTF2E1(2), GTF2F2(1), GTF2H1(3), MNAT1(1), POLR1A(3), POLR1B(5), POLR2A(1), POLR2B(3), POLR2K(1), POLR3B(9), POLR3E(4), POLR3K(1), TAF5(3), TAF6(2), TAF7(1), TAF9(1) 6401828 45 22 45 10 16 15 8 0 6 0 0.14 0.47 192 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 20 B3GNT2(1), B3GNT3(1), B3GNT4(1), B4GALT1(2), B4GALT3(3), FUT1(3), FUT3(2), FUT9(2), GCNT2(4), ST3GAL6(4) 2616528 23 15 23 5 12 4 4 1 2 0 0.15 0.47 193 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 33 GTF2A1(1), GTF2E1(2), GTF2F1(3), GTF2F2(1), GTF2H1(3), GTF2IRD1(2), TAF1(6), TAF1L(9), TAF2(5), TAF4(1), TAF4B(2), TAF5(3), TAF5L(2), TAF6(2), TAF7(1), TAF7L(1), TAF9(1), TAF9B(1) 6539876 46 22 46 11 11 18 9 0 8 0 0.15 0.47 194 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 94 ADCY1(5), ADCY2(8), ADCY3(2), ADCY4(2), ADCY5(6), ADCY7(2), ADCY8(3), ADCY9(2), CAMK2D(2), CREB3(2), CREB3L2(1), CREB3L3(2), CREBBP(8), DCT(7), DVL2(2), DVL3(2), EDNRB(5), EP300(8), FZD1(1), FZD10(2), FZD2(1), FZD4(1), FZD6(4), FZD7(1), GNAI1(1), GNAO1(2), GNAQ(1), GNAS(2), GSK3B(2), KIT(2), KITLG(1), LEF1(1), MAP2K1(2), MAP2K2(1), MAPK3(1), MITF(3), PLCB1(1), PLCB3(3), PLCB4(2), PRKACA(1), PRKACG(1), PRKCA(3), PRKCG(5), RAF1(4), TCF7(5), TCF7L1(1), TYR(1), TYRP1(1), WNT10B(1), WNT11(1), WNT16(1), WNT2(1), WNT2B(2), WNT3(1), WNT4(1), WNT6(1), WNT8A(1), WNT9B(2) 18592870 138 46 138 61 54 49 19 3 13 0 0.15 0.47 195 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 166 ADCY1(5), ADCY2(8), ADCY3(2), ADCY4(2), ADCY7(2), ADCY8(3), ADCY9(2), ADORA2A(2), ADORA2B(1), ADRA1A(1), ADRA1B(2), ADRB1(1), AGTR1(3), ATP2A2(3), ATP2A3(1), ATP2B1(2), ATP2B2(7), ATP2B3(2), ATP2B4(3), AVPR1A(1), BDKRB2(1), CACNA1A(9), CACNA1B(4), CACNA1C(2), CACNA1D(3), CACNA1E(6), CACNA1F(5), CACNA1I(2), CACNA1S(7), CAMK2D(2), CAMK4(1), CCKAR(1), CCKBR(4), CD38(2), CHRM1(1), CHRM2(3), CHRM5(2), CHRNA7(1), CYSLTR1(2), CYSLTR2(3), EDNRA(1), EDNRB(5), EGFR(5), ERBB3(6), ERBB4(7), GNA11(1), GNA14(3), GNA15(1), GNAL(2), GNAQ(1), GNAS(2), GRIN1(1), GRIN2A(9), GRIN2C(2), GRIN2D(2), GRM1(5), GRM5(4), GRPR(1), HRH2(1), HTR2A(1), HTR2B(1), HTR2C(2), HTR4(1), HTR5A(4), HTR7(1), ITPR1(8), ITPR2(6), ITPR3(7), MYLK(5), MYLK2(2), NOS1(6), OXTR(1), P2RX1(1), P2RX2(1), P2RX3(1), P2RX4(1), P2RX7(1), PDE1A(2), PDE1B(2), PDE1C(5), PDGFRA(4), PDGFRB(2), PHKA1(5), PHKA2(3), PHKB(2), PHKG2(2), PLCB1(1), PLCB3(3), PLCB4(2), PLCD1(4), PLCE1(2), PLCG1(1), PLCG2(4), PLCZ1(1), PLN(1), PPID(1), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKACA(1), PRKACG(1), PRKCA(3), PRKCG(5), PTGER3(1), PTGFR(3), PTK2B(1), RYR1(11), RYR2(11), RYR3(11), SLC8A1(4), SLC8A2(2), SLC8A3(6), SPHK1(1), TACR1(1), TACR3(3), TRHR(3), TRPC1(2) 49545614 347 84 345 138 135 122 60 3 25 2 0.15 0.47 196 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(2), B4GALT3(3), CHST1(1), CHST4(3), FUT8(2), ST3GAL2(1), ST3GAL3(3), ST3GAL4(1) 2072768 19 12 19 4 7 2 7 1 2 0 0.15 0.47 197 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 14 CREBBP(8), EP300(8), FYN(1), IL7(1), IL7R(2), JAK1(1), JAK3(4), LCK(2), NMI(1), PTK2B(1), STAT5B(1) 4457076 30 16 30 8 6 16 3 1 4 0 0.15 0.48 198 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(2), BIRC2(2), BIRC3(5), CASP10(1), CASP3(1), CASP7(1), CASP8(5), CASP9(1), DFFA(2), DFFB(1), GZMB(2), SCAP(1) 3234720 24 13 24 7 4 10 4 0 6 0 0.15 0.48 199 CALCINEURINPATHWAY Increased intracellular calcium activates the phosphatase calcineurin in differentiating keratinocytes. CALM1, CALM2, CALM3, CDKN1A, GNAQ, MARCKS, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, SP1, SP3, SYT1 17 CDKN1A(1), GNAQ(1), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), PLCG1(1), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKCA(3), SP1(1), SP3(2) 3616518 23 16 23 6 10 6 2 0 5 0 0.16 0.49 200 CELL2CELLPATHWAY Epithelial cell adhesion proteins such as cadherins transduce signals into the cell via catenins, which alter cell shape and motility. ACTN1, ACTN2, ACTN3, BCAR1, CSK, CTNNA1, CTNNA2, CTNNB1, PECAM1, PTK2, PXN, SRC, VCL 12 ACTN1(2), ACTN2(5), ACTN3(1), CSK(2), CTNNA1(5), CTNNA2(2), PECAM1(1), PTK2(1), SRC(3), VCL(2) 3297402 24 18 24 8 14 8 1 0 1 0 0.16 0.49 201 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(1), ACAA1(1), ACAA2(1), ACADM(4), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH6A1(2), ALDH7A1(2), AOX1(3), DLD(1), ECHS1(1), HADH(1), HADHA(1), HADHB(1), HIBCH(1), HMGCL(1), HMGCS2(1), HSD17B10(1), HSD17B4(1), MCCC1(4), MCCC2(2), MCEE(1), MUT(2), PCCA(7), PCCB(3) 7934256 52 25 52 16 19 17 6 0 10 0 0.16 0.49 202 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(4), GZMB(2), HLA-A(2), ITGAL(4), ITGB2(2) 1511848 14 8 14 6 3 4 4 0 2 1 0.16 0.49 203 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(3), IDH1(1), IDH2(1), SUCLA2(3) 1640084 8 7 8 6 1 5 0 0 2 0 0.16 0.50 204 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 APEX1(3), CREBBP(8), DFFA(2), DFFB(1), GZMA(2), GZMB(2) 1965004 18 10 18 5 7 5 2 0 4 0 0.17 0.50 205 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 89 AKT1(1), AKT2(2), AKT3(1), BCL10(1), CARD11(5), CBL(4), CBLB(3), CD28(1), CD40LG(4), CDC42(1), CDK4(1), CHUK(4), CTLA4(1), FOS(1), FYN(1), GRAP2(4), GRB2(2), IKBKB(2), IL10(1), IL2(2), IL4(1), ITK(4), LAT(1), LCK(2), LCP2(1), MALT1(2), MAP3K14(1), MAP3K8(1), NCK1(1), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), NFKB1(4), NFKB2(2), PAK1(1), PAK2(3), PAK3(3), PAK7(3), PDK1(2), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PLCG1(1), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKCQ(2), PTPRC(9), RASGRP1(3), RHOA(1), SOS1(3), SOS2(6), TEC(2), VAV1(7), VAV2(3), VAV3(3), ZAP70(1) 17579110 141 39 140 36 50 54 23 0 14 0 0.17 0.50 206 ST_ERK1_ERK2_MAPK_PATHWAY The Erk1 and Erk2 MAP kinase pathways are regulated by Raf, Mos, and Tpl-2. ARAF1, ATF1, BAD, BRAF, COPEB, CREB1, CREB3, CREB5, DUSP4, DUSP6, DUSP9, EEF2K, EIF4E, GRB2, HTATIP, MAP2K1, MAP2K2, MAP3K8, MAPK1, MAPK3, MKNK1, MKNK2, MOS, NFKB1, RAP1A, RPS6KA1, RPS6KA2, RPS6KA3, SHC1, SOS1, SOS2, TRAF3 28 ATF1(1), CREB3(2), CREB5(2), DUSP6(3), EEF2K(1), GRB2(2), MAP2K1(2), MAP2K2(1), MAP3K8(1), MAPK3(1), MKNK1(1), MKNK2(1), MOS(1), NFKB1(4), RAP1A(1), RPS6KA2(4), RPS6KA3(2), SHC1(1), SOS1(3), SOS2(6), TRAF3(2) 5160384 42 18 42 6 12 16 7 1 6 0 0.17 0.50 207 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 24 EGFR(5), FOS(1), GRB2(2), JAK1(1), MAP2K1(2), MAP2K4(2), MAP3K1(2), MAPK3(1), MAPK8(6), PLCG1(1), PRKCA(3), RAF1(4), RASA1(5), SHC1(1), SOS1(3), STAT1(1), STAT3(1) 6150904 41 20 41 7 13 14 9 1 4 0 0.17 0.50 208 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 47 CPT1B(1), CREBBP(8), DUSP1(2), EP300(8), FABP1(1), HSD17B4(1), LPL(2), MAPK3(1), ME1(3), NCOA1(3), NCOR1(7), NR1H3(2), NR2F1(2), NRIP1(2), PPARA(1), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PRKCA(3), PTGS2(1), RB1(3), SP1(1), STAT5B(1) 10590890 60 27 60 22 21 17 12 1 9 0 0.17 0.51 209 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 ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH3B1(1), ALDH3B2(1), ALDH7A1(2), AOC2(1), AOC3(1), ASPA(2), CARM1(1), CNDP1(1), HAL(1), HARS2(3), HDC(5), LCMT1(2), MAOA(3), MAOB(1), METTL2B(1), METTL6(3), PRMT3(1), PRMT7(2), PRMT8(2), PRPS1(1), PRPS2(1), UROC1(3), WBSCR22(1) 7197958 49 27 48 23 18 18 7 2 4 0 0.17 0.51 210 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 GNAS(2), GNGT1(1), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PRKCA(3) 1716020 13 10 13 1 4 6 2 0 1 0 0.17 0.51 211 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(8), EP300(8), LPL(2), NCOA1(3), NCOA2(3), PPARG(1) 3374258 25 15 25 6 8 7 6 1 3 0 0.18 0.51 212 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 49 ACTA1(1), AGT(2), AKT1(1), CALR(1), CAMK1(2), CAMK1G(3), CAMK4(1), CREBBP(8), ELSPBP1(1), F2(2), GSK3B(2), HAND1(1), HAND2(2), IGF1(1), MAP2K1(2), MAPK3(1), MAPK8(6), MEF2C(2), MYH2(5), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), RAF1(4) 8404398 69 27 69 17 28 20 10 1 10 0 0.18 0.51 213 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(2), PLCD1(4), PRKCA(3), TGM2(2) 916306 11 8 11 2 4 7 0 0 0 0 0.18 0.51 214 BETAOXIDATIONPATHWAY Beta-Oxidation of Fatty Acids ACADL, ACADM, ACADS, ACAT1, ECHS1, HADHA 6 ACADL(2), ACADM(4), ECHS1(1), HADHA(1) 982518 8 5 8 4 2 2 0 0 4 0 0.18 0.51 215 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), AGPAT1(1), AGPAT4(4), AGPS(1), CDS1(2), CDS2(2), CHAT(1), CHKA(2), CLC(1), CPT1B(1), DGKA(1), DGKB(2), DGKD(8), DGKE(2), DGKG(2), DGKH(7), DGKZ(1), ETNK1(1), GNPAT(1), GPD2(1), LCAT(1), PAFAH2(1), PCYT1A(2), PCYT1B(1), PEMT(1), PISD(2), PLA2G4A(4), PLA2G6(2), PLCG1(1), PLCG2(4) 9012318 62 28 62 25 27 11 15 0 9 0 0.18 0.52 216 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(4), JAK3(4), MAPK3(1), STAT3(1) 2151290 11 9 11 2 1 5 1 0 3 1 0.18 0.52 217 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(1), ACADM(4), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH7A1(2), AOC2(1), AOC3(1), CNDP1(1), DPYD(9), DPYS(1), ECHS1(1), GAD1(2), GAD2(2), HADHA(1), HIBCH(1), UPB1(2) 4890732 38 21 38 17 12 15 4 0 7 0 0.19 0.53 218 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), ACMSD(1), AFMID(1), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH7A1(2), AOC2(1), AOC3(1), AOX1(3), CARM1(1), CAT(1), CYP1A1(2), CYP1A2(2), CYP1B1(1), ECHS1(1), GCDH(3), HADH(1), HADHA(1), HSD17B10(1), HSD17B4(1), INMT(2), KMO(2), KYNU(2), LCMT1(2), LNX1(5), MAOA(3), MAOB(1), METTL2B(1), METTL6(3), NFX1(6), OGDH(2), OGDHL(5), PRMT3(1), PRMT7(2), PRMT8(2), TDO2(2), TPH1(2), TPH2(4), WARS(1), WARS2(2), WBSCR22(1) 10946110 85 33 85 25 26 31 16 2 10 0 0.19 0.53 219 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 31 ADRA1A(1), ADRA1B(2), ADRA2A(1), ADRB1(1), CHRM1(1), CHRM2(3), CHRM4(1), CHRM5(2), DRD2(4), DRD3(2), DRD5(4), HRH2(1), HTR1A(2), HTR1B(2), HTR1D(1), HTR1E(4), HTR2A(1), HTR2B(1), HTR2C(2), HTR4(1), HTR5A(4), HTR7(1) 4496280 42 21 42 20 19 14 4 1 4 0 0.19 0.53 220 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 COASY(1), DPYD(9), DPYS(1), ENPP3(2), PANK3(2), PPCS(1), UPB1(2), VNN1(3) 3091356 21 13 21 10 6 10 3 0 2 0 0.19 0.53 221 AKAPCENTROSOMEPATHWAY Protein Kinase A at the Centrosome AKAP9, ARHA, CDC2, MAP2, PCNT1, PCNT2, PPP1CA, PPP2CA, PRKACB, PRKACG, PRKAG1, PRKAR2A, PRKAR2B, PRKCE, PRKCL1 10 AKAP9(10), MAP2(10), PPP2CA(1), PRKACG(1), PRKAR2B(1), PRKCE(2) 3344110 25 15 24 10 5 12 6 0 2 0 0.19 0.53 222 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(4), CD19(1), CD1A(2), CD1B(1), CD1C(1), CD1D(1), CD1E(1), CD22(4), CD33(1), CD38(2), CD44(2), CD5(3), CD55(2), CR1(3), CR2(3), CSF1(1), CSF3R(5), DNTT(3), FCER2(1), FLT3(2), GP5(2), HLA-DRA(3), HLA-DRB1(1), HLA-DRB5(1), IL1B(1), IL1R1(1), IL1R2(5), IL3(1), IL4(1), IL5RA(2), IL6(2), IL6R(1), IL7(1), IL7R(2), ITGA1(1), ITGA2(2), ITGA2B(3), ITGA4(5), ITGA5(2), ITGA6(2), ITGAM(3), ITGB3(2), KIT(2), KITLG(1), MME(7), MS4A1(1), TFRC(1), THPO(1), TPO(4) 14797516 104 35 104 46 31 49 15 3 6 0 0.19 0.53 223 HSA00780_BIOTIN_METABOLISM Genes involved in biotin metabolism BTD, HLCS, SPCS1, SPCS3 4 BTD(1), HLCS(2), SPCS1(1), SPCS3(1) 569752 5 4 5 1 2 1 1 0 1 0 0.19 0.53 224 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 JAK1(1), PTPRU(6), REG1A(2), STAT1(1), STAT2(4) 2294188 14 11 14 4 11 1 1 0 1 0 0.19 0.53 225 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 20 ATM(15), ATR(7), BRCA1(2), BRCA2(13), CHEK2(1), FANCA(5), FANCC(1), FANCD2(5), FANCF(1), FANCG(3), MRE11A(5), RAD17(2), RAD50(7), TREX1(1) 7944010 68 22 68 7 15 33 15 0 4 1 0.20 0.54 226 HSA00642_ETHYLBENZENE_DEGRADATION Genes involved in ethylbenzene degradation ARD1A, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ESCO1, ESCO2, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1 11 DHRS1(1), DHRS2(1), DHRS3(1), ESCO1(6), ESCO2(1), MYST3(10), MYST4(7), SH3GLB1(1) 2905312 28 13 28 8 10 7 8 1 2 0 0.20 0.54 227 INTEGRINPATHWAY Integrins are cell surface receptors commonly present at focal adhensions that interact with the extracellular matrix and transduce extracellular signaling. ACTA1, ACTN1, ACTN2, ACTN3, ARHA, BCAR1, BCR, CAPN1, CAPNS1, CAPNS2, CAV1, CRKL, CSK, FYN, GRB2, GRF2, HRAS, ITGA1, ITGB1, JUN, MAP2K1, MAP2K2, MAPK1, MAPK3, MAPK8, PPP1R12B, PTK2, PXN, RAF1, RAP1A, ROCK1, SHC1, SOS1, SRC, TLN1, TNS, VCL, ZYX 35 ACTA1(1), ACTN1(2), ACTN2(5), ACTN3(1), BCR(2), CAV1(1), CSK(2), FYN(1), GRB2(2), ITGA1(1), MAP2K1(2), MAP2K2(1), MAPK3(1), MAPK8(6), PPP1R12B(4), PTK2(1), RAF1(4), RAP1A(1), ROCK1(8), SHC1(1), SOS1(3), SRC(3), TLN1(3), VCL(2), ZYX(1) 8550694 59 27 59 14 20 21 11 1 6 0 0.20 0.54 228 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(2), ADRBK2(2), CAMK2D(2), CLCA1(4), CLCA2(5), CLCA4(1), CNGA3(2), CNGA4(2), GNAL(2), GUCA1A(1), GUCA1B(1), GUCA1C(1), PDC(1), PDE1C(5), PRKACA(1), PRKACG(1), PRKG1(8), PRKG2(3) 5665708 44 21 44 17 10 21 9 0 4 0 0.20 0.54 229 GPCRDB_CLASS_A_RHODOPSIN_LIKE2 CYSLTR1, CYSLTR2, GPR109B, GPR161, GPR171, GPR18, GPR34, GPR39, GPR41, GPR42, GPR45, GPR65, GPR68, GPR75, GPR81, LYPDC1 13 CYSLTR1(2), CYSLTR2(3), GPR161(2), GPR171(1), GPR18(2), GPR34(2), GPR39(1), GPR45(4), GPR65(1), GPR75(1) 1808444 19 11 19 6 8 4 4 0 3 0 0.20 0.54 230 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(2), ALOX12B(1), ALOX15B(1), ALOX5(1), CYP2C18(2), CYP2C8(2), CYP2C9(5), CYP2E1(3), CYP2J2(3), CYP4A11(2), CYP4A22(1), CYP4F2(2), CYP4F3(1), GPX3(2), GPX5(2), GPX6(1), PLA2G4A(4), PLA2G6(2), PTGIS(2), PTGS1(4), PTGS2(1), TBXAS1(3) 7150870 47 25 47 13 19 13 11 0 4 0 0.20 0.54 231 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(1), BCR(2), BLNK(1), FOS(1), GRB2(2), MAP2K1(2), MAP3K1(2), MAPK3(1), MAPK8IP3(1), PAPPA(10), RPS6KA3(2), SHC1(1), SOS1(3), SYK(3), VAV1(7), VAV2(3), VAV3(3) 5691888 45 21 45 6 12 21 6 0 6 0 0.20 0.54 232 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), EGFR(5), GRB2(2), MAP2K1(2), MAPK3(1), RAF1(4), RASA1(5), SHC1(1), SOS1(3), SPRY1(3), SPRY4(1), SRC(3) 4490396 34 15 34 11 12 12 7 0 3 0 0.21 0.54 233 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(3), CCND2(1), CCND3(1), CCNE1(1), CCNH(1), CDC25A(1), CDK4(1), CDKN1A(1), CDKN1B(2), RB1(3), RBL1(4), TFDP1(1) 2908222 20 13 20 5 6 4 4 0 6 0 0.21 0.54 234 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(3), POLA2(2), POLB(3), POLD1(2), POLD2(1), POLD3(1), POLE(10), POLE2(1), POLG(2), POLH(3), POLI(3), POLK(1), POLL(1), POLM(1), POLQ(5), PRIM2(3), REV1(3), REV3L(9), RFC5(1) 7685812 55 21 53 13 15 19 8 0 12 1 0.21 0.54 235 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 19 AKT1(1), APAF1(2), ATM(15), BID(1), CASP3(1), CASP6(2), CASP7(1), CASP9(1), PRKCA(3), PTK2(1), STAT1(1), TLN1(3) 4913192 32 17 32 7 2 17 7 0 5 1 0.21 0.54 236 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 89 AKT1(1), AKT3(1), CAPN10(1), CAPN11(1), CAPN2(2), CAPN3(4), CAPN5(1), CAPN6(3), CAPN7(2), CAPN9(1), CAV1(1), CAV3(1), CDC42(1), CSK(2), DOCK1(2), FYN(1), GIT2(1), GRB2(2), ITGA10(4), ITGA11(2), ITGA2(2), ITGA2B(3), ITGA4(5), ITGA5(2), ITGA6(2), ITGA8(3), ITGA9(3), ITGAD(2), ITGAE(3), ITGAL(4), ITGAM(3), ITGAV(4), ITGAX(2), ITGB2(2), ITGB3(2), ITGB4(1), ITGB5(4), ITGB6(2), ITGB7(2), ITGB8(1), MAP2K1(2), MAP2K2(1), MAP2K3(4), MAP2K6(1), MAPK6(1), MYLK2(2), PAK1(1), PAK2(3), PAK3(3), PDPK1(1), PTK2(1), RAP1B(1), RAPGEF1(2), RHO(2), ROCK1(8), ROCK2(4), SEPP1(1), SHC1(1), SHC3(1), SORBS1(7), SOS1(3), SRC(3), TLN1(3), TNS1(4), VAV2(3), VAV3(3), VCL(2), ZYX(1) 24627380 155 44 155 58 46 60 27 5 17 0 0.21 0.54 237 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 14 AKT1(1), MAP2K1(2), MAP2K2(1), MAP2K3(4), MAP2K6(1), MAP3K1(2), MAPK3(1), NFKB1(4), RB1(3), SP1(1) 2922658 20 11 20 5 7 5 5 1 2 0 0.21 0.55 238 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 ACE2(3), AGT(2), AGTR1(3), AGTR2(1), ANPEP(4), CPA3(2), CTSG(2), ENPEP(5), LNPEP(4), MAS1(1), MME(7), NLN(2), REN(2) 3819944 38 18 38 9 10 16 9 0 3 0 0.22 0.56 239 HSA00860_PORPHYRIN_AND_CHLOROPHYLL_METABOLISM Genes involved in porphyrin and chlorophyll metabolism ALAD, ALAS1, ALAS2, BLVRA, BLVRB, COX10, COX15, CP, CPOX, EARS2, EPRS, FECH, FTH1, FTMT, GUSB, HCCS, HMBS, HMOX1, HMOX2, MMAB, PPOX, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, UROD, UROS 41 ALAD(1), ALAS1(1), ALAS2(3), BLVRA(1), BLVRB(2), COX15(2), CP(3), CPOX(1), EPRS(4), FECH(1), FTMT(2), GUSB(1), HCCS(3), HMOX2(2), MMAB(1), PPOX(1), UGT1A4(1), UGT1A6(1), UGT1A8(1), UGT1A9(1), UGT2A3(2), UGT2B11(2), UGT2B17(4), UGT2B28(1), UGT2B4(2), UGT2B7(2), UROD(1) 7312754 47 21 47 11 12 24 7 0 4 0 0.22 0.56 240 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 39 ARNTL(3), AZIN1(1), BTG1(1), CBX3(2), CLOCK(3), CRY1(3), DNAJA1(1), ETV6(2), GFRA1(6), GSTM3(1), HSPA8(3), MYF6(1), NCKAP1(3), NCOA4(1), NR1D2(3), PER2(1), PPP1R3C(2), PPP2CB(2), PSMA4(1), TOB1(2), TUBB3(1), UGP2(3), ZFR(5) 6630052 51 19 50 10 7 18 15 1 9 1 0.22 0.57 241 HSA00660_C5_BRANCHED_DIBASIC_ACID_METABOLISM Genes involved in C5-branched dibasic acid metabolism ILVBL, SUCLA2 2 SUCLA2(3) 392246 3 3 3 1 0 2 0 0 1 0 0.23 0.58 242 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 IL10(1), IL12A(1), IL12B(1), IL15(1), IL16(5), IL2(2), IL3(1), IL4(1), IL6(2), IL8(1), IL9(2) 1749872 18 8 18 6 5 10 2 0 1 0 0.23 0.59 243 HSA03050_PROTEASOME Genes involved in proteasome PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMC2, PSMC3, PSMD1, PSMD11, PSMD12, PSMD13, PSMD2, PSMD6 22 PSMA1(1), PSMA2(1), PSMA3(1), PSMA4(1), PSMA7(1), PSMB3(1), PSMB5(2), PSMB6(1), PSMD1(5), PSMD12(2), PSMD13(1), PSMD2(1), PSMD6(2) 2944258 20 10 20 11 8 6 2 1 3 0 0.23 0.59 244 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 6 HDAC1(2), SP1(1), SP3(2), WT1(4) 1100290 9 8 9 1 6 2 1 0 0 0 0.23 0.59 245 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 CAMK1(2), CAMK1G(3), GNA15(1), GNGT1(1), MAP2K1(2), MAP2K2(1), MAP2K3(4), MAP2K6(1), MAP3K1(2), MAPK3(1), NCF2(1), NFATC1(1), NFATC2(3), NFATC3(1), NFATC4(2), NFKB1(4), PAK1(1), PIK3C2G(2), PLCB1(1), PPP3CA(2), PPP3CB(2), PPP3CC(3), RAF1(4) 6974960 45 20 45 18 16 14 7 2 6 0 0.24 0.60 246 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(2), C5(5), C6(6), C7(3), IL6(2), IL8(1), ITGA4(5), ITGAL(4), ITGB2(2), SELP(2), SELPLG(1), VCAM1(2) 4531846 35 16 35 14 13 12 4 0 6 0 0.24 0.60 247 PROTEASOMEPATHWAY Ubiquitinated proteins are targeted for proteolytic degradation by the proteasome, where they are unfolded and degraded to small peptides in an ATP-dependent process. PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMC3, PSMD14, RPN1, RPN2, UBE1, UBE2A, UBE3A 20 PSMA1(1), PSMA2(1), PSMA3(1), PSMA4(1), PSMA7(1), PSMB3(1), PSMB5(2), PSMB6(1), PSMD14(1), RPN2(1), UBE3A(5) 2404936 16 9 16 6 5 6 3 0 2 0 0.24 0.60 248 VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS BCAT1, IARS, LARS, LARS2, PDHA1, PDHA2, PDHB 7 IARS(3), LARS(1), LARS2(1), PDHA1(1), PDHA2(4) 1835808 10 8 10 4 3 2 4 0 1 0 0.24 0.60 249 KERATAN_SULFATE_BIOSYNTHESIS B3GNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT5, FUT8, SIAT4A, SIAT4B, SIAT6, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 10 B4GALT1(2), B4GALT3(3), FUT8(2), ST3GAL2(1), ST3GAL3(3), ST3GAL4(1) 1401722 12 9 12 3 4 2 5 0 1 0 0.24 0.60 250 HSA04742_TASTE_TRANSDUCTION Genes involved in taste transduction ACCN1, ADCY4, ADCY6, ADCY8, CACNA1A, CACNA1B, GNAS, GNAT3, GNB1, GNB3, GNG13, GNG3, GRM4, ITPR3, KCNB1, PDE1A, PLCB2, PRKACA, PRKACB, PRKACG, PRKX, PRKY, SCNN1A, SCNN1B, SCNN1G, TAS1R1, TAS1R2, TAS1R3, TAS2R1, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R3, TAS2R38, TAS2R39, TAS2R4, TAS2R40, TAS2R41, TAS2R42, TAS2R43, TAS2R44, TAS2R45, TAS2R46, TAS2R48, TAS2R49, TAS2R5, TAS2R50, TAS2R60, TAS2R7, TAS2R8, TAS2R9, TRPM5 46 ACCN1(1), ADCY4(2), ADCY8(3), CACNA1A(9), CACNA1B(4), GNAS(2), GNAT3(1), GNB3(2), GNG3(1), GRM4(2), ITPR3(7), KCNB1(4), PDE1A(2), PRKACA(1), PRKACG(1), SCNN1A(2), SCNN1B(2), SCNN1G(3), TAS1R1(2), TAS1R2(4), TAS2R1(1), TAS2R10(3), TAS2R13(1), TAS2R14(1), TAS2R16(2), TAS2R38(1), TAS2R39(1), TAS2R4(1), TAS2R46(1), TAS2R5(2), TAS2R60(1), TAS2R7(1), TAS2R8(1), TAS2R9(2) 10201474 74 33 73 31 33 24 15 0 2 0 0.25 0.61 251 ASBCELLPATHWAY B cells require interaction with helper T cells to produce antigen-specific immunoglobulins as a key element of the human immune response. CD28, CD4, CD80, HLA-DRA, HLA-DRB1, IL10, IL2, IL4, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 8 CD28(1), CD80(1), HLA-DRA(3), HLA-DRB1(1), IL10(1), IL2(2), IL4(1) 663756 10 5 10 1 3 7 0 0 0 0 0.25 0.61 252 BOTULINPATHWAY Blockade of Neurotransmitter Relase by Botulinum Toxin CHRM1, CHRNA1, SNAP25, STX1A, VAMP2 5 CHRM1(1), CHRNA1(4) 595886 5 5 5 2 2 2 1 0 0 0 0.25 0.61 253 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(4), CDA(1), CTPS(1), DCK(1), DCTD(2), DHODH(1), DPYD(9), DPYS(1), DTYMK(1), ENTPD1(1), NT5E(1), POLB(3), POLD1(2), POLD2(1), POLE(10), POLG(2), POLL(1), POLQ(5), POLR1B(5), POLR2A(1), POLR2B(3), POLR2D(1), POLR2K(1), RRM1(2), TK2(1), TXNRD1(1), UCK2(1), UMPS(1), UPB1(2) 10391242 66 32 65 18 23 23 13 0 7 0 0.25 0.62 254 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 CSNK1D(2), DRD2(4), GRM1(5), PLCB1(1), PPP1R1B(1), PPP2CA(1), PPP3CA(2), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1) 2894496 23 14 23 10 11 4 4 1 3 0 0.25 0.62 255 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(4), AGT(2), AGTR2(1), EDNRA(1), EDNRB(5), EGFR(5), FOS(1), NFKB1(4), PLCG1(1), PRKCA(3) 3732178 27 17 27 9 10 9 7 0 1 0 0.26 0.63 256 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 7 FUT1(3), FUT3(2), ST3GAL3(3) 826864 8 6 8 1 5 1 2 0 0 0 0.26 0.63 257 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(5), CASP8(5) 1441642 11 8 11 3 2 6 1 0 2 0 0.26 0.63 258 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), CHPT1(1), LCMT1(2), METTL2B(1), METTL6(3), PCYT1A(2), PCYT1B(1), PRMT3(1), PRMT7(2), PRMT8(2), WBSCR22(1) 2564604 17 12 17 6 6 4 3 2 2 0 0.26 0.63 259 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 11 AKT1(1), CHRNG(2), MUSK(2), PTK2(1), PTK2B(1), SRC(3), YWHAH(1) 2355524 11 10 11 5 3 4 1 0 3 0 0.26 0.63 260 BENZOATE_DEGRADATION_VIA_COA_LIGATION ACAT1, ACAT2, ACYP1, ACYP2, ECHS1, EHHADH, GCDH, HADHA, SDHB, SDS 10 ACYP1(2), ECHS1(1), GCDH(3), HADHA(1), SDS(1) 1434008 8 6 8 2 3 1 1 0 3 0 0.27 0.64 261 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(5), COL4A2(1), COL4A3(1), COL4A4(2), COL4A5(5), COL4A6(5), SLC23A1(2), SLC23A2(4), SLC2A1(1) 4773232 26 17 26 9 9 7 5 1 4 0 0.27 0.65 262 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 CASP8(5), MAP2K1(2), MAP2K4(2), MAP3K1(2), MAPK3(1), MAPK8(6), NFKB1(4), NSMAF(2), RAF1(4) 3736804 28 16 28 9 10 10 4 1 3 0 0.28 0.65 263 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 21 CXCR4(1), GNAI1(1), GNAQ(1), GNGT1(1), MAP2K1(2), MAPK3(1), NFKB1(4), PIK3C2G(2), PLCG1(1), PRKCA(3), PTK2(1), PTK2B(1), RAF1(4) 4406612 23 13 23 8 9 7 3 0 4 0 0.28 0.65 264 HSA00512_O_GLYCAN_BIOSYNTHESIS Genes involved in O-glycan biosynthesis B3GNT6, B4GALT5, C1GALT1, C1GALT1C1, GALNT1, GALNT10, GALNT11, GALNT12, GALNT13, GALNT14, GALNT17, GALNT2, GALNT3, GALNT4, GALNT5, GALNT6, GALNT7, GALNT8, GALNT9, GALNTL1, GALNTL2, GALNTL4, GALNTL5, GCNT1, GCNT3, GCNT4, OGT, ST3GAL1, ST3GAL2, ST6GALNAC1, WBSCR17 29 GALNT11(1), GALNT12(1), GALNT13(1), GALNT14(4), GALNT2(2), GALNT5(5), GALNT6(1), GALNT7(1), GALNT8(1), GALNTL1(2), GALNTL2(3), GALNTL4(1), GALNTL5(3), GCNT1(2), GCNT3(2), GCNT4(3), OGT(2), ST3GAL2(1), ST6GALNAC1(2) 5686048 38 19 38 12 6 16 11 0 5 0 0.28 0.65 265 METHIONINEPATHWAY Catabolic Pathways for Methionine, Isoleucine, Threonine and Valine BCKDHB, BCKDK, CBS, CTH, MUT 5 BCKDK(1), CBS(2), CTH(1), MUT(2) 875660 6 5 6 0 1 3 0 0 2 0 0.28 0.65 266 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(3), PARK2(3), SNCAIP(2), UBE2E2(1) 1150370 9 7 9 3 4 4 1 0 0 0 0.28 0.65 267 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(9), GRIN2B(3), GRIN2C(2), GRIN2D(2), NOS1(6), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PRKCA(3) 4631792 41 18 41 11 18 12 6 0 4 1 0.28 0.65 268 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 136 CHAD(2), COL11A1(8), COL11A2(3), COL17A1(4), COL1A1(2), COL1A2(6), COL2A1(2), COL3A1(7), COL4A1(5), COL4A2(1), COL4A4(2), COL4A6(5), COL5A1(7), COL5A2(4), COL5A3(6), COL6A2(1), COL6A3(20), COL6A6(5), DSC1(2), DSC2(1), DSC3(3), DSG1(3), DSG4(6), FN1(6), GJA1(4), GJA10(5), GJA4(1), GJA5(2), GJA8(1), GJA9(3), GJB3(2), GJB7(1), GJC3(1), GJD2(1), IBSP(1), INA(1), ITGA6(2), ITGB4(1), KRT1(1), KRT12(1), KRT13(2), KRT14(2), KRT15(1), KRT20(1), KRT23(1), KRT24(2), KRT25(1), KRT27(1), KRT28(1), KRT3(1), KRT32(1), KRT33B(2), KRT35(2), KRT36(1), KRT37(5), KRT38(2), KRT5(1), KRT6A(2), KRT6B(1), KRT7(3), KRT72(2), KRT73(2), KRT74(2), KRT75(3), KRT76(1), KRT78(2), KRT79(2), KRT81(1), KRT82(2), KRT84(6), KRT85(3), KRT9(2), LAMA1(7), LAMA2(10), LAMA3(8), LAMA4(6), LAMB1(2), LAMB2(3), LAMB3(1), LAMB4(6), LAMC1(6), LAMC2(4), LAMC3(4), LMNB1(3), NES(3), PRPH(1), RELN(13), THBS1(3), THBS2(8), THBS3(2), THBS4(1), TNC(7), TNN(4), TNR(4), TNXB(4), VIM(3), VTN(3), VWF(7) 44308510 323 73 322 136 126 111 49 4 32 1 0.28 0.65 269 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(1), IL8(1) 308914 2 2 2 0 0 1 0 0 1 0 0.29 0.65 270 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 20 CHN1(1), LIMK1(2), MAP3K1(2), MYLK(5), NCF2(1), PAK1(1), PDGFRA(4), PLD1(6), PPP1R12B(4), RALBP1(2), TRIO(3), VAV1(7), WASF1(2) 5722832 40 21 40 10 11 17 8 0 4 0 0.29 0.65 271 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 54 AXIN1(1), CCND2(1), CCND3(1), DVL2(2), DVL3(2), FBXW2(1), FZD1(1), FZD10(2), FZD2(1), FZD6(4), FZD7(1), GSK3B(2), LDLR(1), MAPK9(2), PLAU(1), PPP2R5C(1), PPP2R5E(2), PRKCA(3), PRKCE(2), PRKCG(5), PRKCH(1), PRKCI(1), PRKCQ(2), PRKD1(5), RHOA(1), SFRP4(1), TCF7(5), WNT10B(1), WNT11(1), WNT16(1), WNT2(1), WNT2B(2), WNT3(1), WNT4(1), WNT6(1) 8707490 61 30 61 20 20 25 7 0 9 0 0.29 0.65 272 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 ALOX5(1), CYP1A2(2), CYP2C18(2), CYP2C8(2), CYP2C9(5), CYP2E1(3), CYP2J2(3), CYP3A43(2), CYP3A7(3), PLA2G4A(4), PLA2G6(2), RDH11(1), RDH12(2) 4384546 32 15 32 9 13 8 7 0 4 0 0.29 0.65 273 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 68 ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3), AKR1C2(2), AKR1C3(2), AKR1C4(1), ALDH1A3(4), ALDH3B1(1), ALDH3B2(1), CYP1A1(2), CYP1A2(2), CYP1B1(1), CYP2C18(2), CYP2C8(2), CYP2C9(5), CYP2E1(3), CYP2F1(1), CYP2S1(1), CYP3A43(2), CYP3A7(3), EPHX1(2), GSTA3(1), GSTA5(1), GSTM3(1), GSTM4(1), GSTO2(1), GSTZ1(1), UGT1A4(1), UGT1A6(1), UGT1A8(1), UGT1A9(1), UGT2A3(2), UGT2B11(2), UGT2B17(4), UGT2B28(1), UGT2B4(2), UGT2B7(2) 10098512 72 27 72 18 18 25 20 0 9 0 0.29 0.65 274 EEA1PATHWAY The FYVE-finger proteins EEA1 and HRS are localized to endosome membranes and regulate sorting and ubiquitination in the vesicle transport system. EEA1, EGF, EGFR, HGS, RAB5A, TF, TFRC 7 EEA1(4), EGFR(5), TF(6), TFRC(1) 2328032 16 10 16 4 6 6 3 0 1 0 0.29 0.65 275 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 22 ADRB1(1), AKT1(1), ASAH1(1), CAV3(1), DAG1(3), DLG4(1), EPHB2(3), GNAI1(1), GNAQ(1), ITPR1(8), ITPR2(6), ITPR3(7), KCNJ5(1), KCNJ9(2), PTX3(2), RHO(2), RYR1(11) 7493784 52 27 52 18 23 19 5 0 4 1 0.29 0.65 276 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(3), POLR1B(5), POLR1C(2), POLR1D(2), POLR2A(1), POLR2B(3), POLR2D(1), POLR2K(1), POLR3A(6), POLR3B(9), POLR3GL(1), POLR3K(1) 4245294 35 17 35 3 13 11 8 0 3 0 0.29 0.66 277 GPCRDB_CLASS_C_METABOTROPIC_GLUTAMATE_PHEROMONE CASR, GABBR1, GPCR5A, GPR51, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GRM1, GRM2, GRM3, GRM4, GRM5, GRM7, GRM8 13 CASR(2), GABBR1(4), GPRC5B(1), GPRC5C(1), GRM1(5), GRM2(3), GRM3(3), GRM4(2), GRM5(4), GRM7(5), GRM8(2) 3572280 32 16 32 20 12 12 5 0 3 0 0.30 0.67 278 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 24 ADCY1(5), AKT1(1), CAMK2D(2), GNAS(2), GRB2(2), MAPK3(1), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PRKCA(3), RPS6KA5(4), SOS1(3) 4577736 30 18 30 9 10 10 8 0 2 0 0.30 0.67 279 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(8), EP300(8), NCOA3(5), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1) 3743808 29 16 29 5 8 11 4 2 4 0 0.30 0.67 280 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(1), BLVRB(2), IL10(1), IL10RA(1), IL10RB(3), IL6(2), JAK1(1), STAT1(1), STAT3(1) 2188676 13 7 12 4 5 3 2 0 3 0 0.30 0.67 281 HSA00053_ASCORBATE_AND_ALDARATE_METABOLISM Genes involved in ascorbate and aldarate metabolism ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, MIOX, UGDH 9 ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH7A1(2), UGDH(1) 1543620 12 8 12 2 3 5 2 0 2 0 0.30 0.67 282 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 44 AKT1(1), AKT2(2), AKT3(1), BCR(2), BLNK(1), BTK(2), CD19(1), CD22(4), CR2(3), CSK(2), DAG1(3), GRB2(2), GSK3B(2), INPP5D(2), ITPR1(8), ITPR2(6), ITPR3(7), MAP4K1(1), MAPK3(1), NFATC1(1), NFATC2(3), PDK1(2), PIK3CD(2), PLCG2(4), PPP1R13B(1), PPP3CA(2), PPP3CB(2), PPP3CC(3), PTPRC(9), RAF1(4), SHC1(1), SOS1(3), SOS2(6), SYK(3), VAV1(7) 12671710 104 31 104 16 36 38 14 0 15 1 0.30 0.67 283 BILE_ACID_BIOSYNTHESIS ACAA1, ACAA2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1C4, AKR1D1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, BAAT, CEL, CYP27A1, CYP7A1, HADHB, SOAT2, SRD5A1, SRD5A2 27 ACAA1(1), ACAA2(1), ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3), AKR1C4(1), AKR1D1(1), ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), CYP27A1(1), CYP7A1(1), HADHB(1), SRD5A1(1), SRD5A2(1) 4276944 34 20 34 14 11 13 8 0 2 0 0.31 0.67 284 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(1), ALDH4A1(1), ALDH5A1(2), CAD(4), CPS1(7), EPRS(4), GAD1(2), GAD2(2), GFPT1(3), GLUL(2), GOT1(2), GPT2(1), GSS(1), NADSYN1(1), PPAT(5), QARS(3) 6038578 41 21 41 12 13 16 7 2 3 0 0.31 0.67 285 PS1PATHWAY Presenilin is required for gamma-secretase activity to activate Notch signaling; presenilin also inhibits beta-catenin in the Wnt/Frizzled pathway. ADAM17, APC, AXIN1, BTRC, CTNNB1, DLL1, DVL1, FZD1, GSK3B, NOTCH1, PSEN1, RBPSUH, TCF1, WNT1 10 ADAM17(3), AXIN1(1), BTRC(3), DLL1(3), FZD1(1), GSK3B(2) 2099038 13 8 13 2 5 3 1 0 4 0 0.31 0.68 286 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 113 ATP12A(7), ATP4A(6), ATP4B(1), ATP5A1(3), ATP5B(3), ATP5C1(2), ATP5L(2), ATP6V0A1(3), ATP6V0A2(1), ATP6V0A4(3), ATP6V0B(1), ATP6V0D2(4), ATP6V1B1(1), ATP6V1B2(2), ATP6V1C2(1), ATP6V1E2(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(1), COX15(2), COX4I1(1), COX4I2(1), LHPP(1), NDUFA12(1), NDUFA4(1), NDUFA9(2), NDUFB6(1), NDUFB9(1), NDUFC2(1), NDUFS1(2), NDUFS2(3), NDUFS4(1), NDUFS5(2), NDUFS6(1), NDUFV3(1), PPA2(2), SDHA(1), UQCRC2(1) 10280784 70 30 70 26 25 21 17 0 7 0 0.31 0.68 287 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(3), ASPH(1), COPS5(1), EP300(8), HIF1A(3), LDHA(2), VHL(1) 2983604 19 13 19 3 5 6 5 1 2 0 0.32 0.68 288 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 29 AKT1(1), AR(3), ASAH1(1), DAG1(3), EGFR(5), GNA11(1), GNA15(1), GNAI1(1), GNAQ(1), ITPR1(8), ITPR2(6), ITPR3(7), KCNJ5(1), KCNJ9(2), PHKA2(3), PIK3CD(2), PTX3(2), RAF1(4), SRC(3) 7655338 55 27 55 19 27 17 6 0 4 1 0.32 0.68 289 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 9 AKT1(1), GRB2(2), NTRK1(3), PLCG1(1), PRKCA(3), SHC1(1), SOS1(3) 2063396 14 9 14 3 1 7 5 0 1 0 0.32 0.68 290 INOSITOL_METABOLISM ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 5 ALDH6A1(2), ALDOB(2), ALDOC(2) 684946 6 5 6 0 3 2 1 0 0 0 0.32 0.68 291 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(3), DLD(1), DLST(1), IDH1(1), IDH2(1), IDH3A(3), PC(4), PCK1(3), SDHA(1), SUCLA2(3), SUCLG1(1) 3802792 22 14 22 12 5 11 2 0 4 0 0.32 0.68 292 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(5), COL4A2(1), COL4A3(1), COL4A4(2), COL4A5(5), COL4A6(5), F11(1), F2(2), F5(10), F8(5), FGA(6), FGB(1), FGG(2), KLKB1(5), PROS1(3), SERPINC1(1), SERPING1(2) 8221012 57 23 57 16 15 23 12 1 6 0 0.33 0.69 293 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(2), B4GALT3(3), DDOST(1), DPAGT1(1), FUT8(2), MAN1A1(2), MAN1B1(1), MGAT1(1), MGAT4A(1), MGAT5(2), RPN2(1) 3469172 18 14 18 9 7 4 3 0 4 0 0.33 0.70 294 PYRUVATE_METABOLISM ACACA, ACAS2, ACAS2L, ACAT1, ACAT2, ACYP1, ACYP2, ADH5, AKR1B1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, CACH_1, DLAT, DLD, GLO1, GRHPR, HAGH, HAGHL, LDHA, LDHB, LDHC, LDHD, MDH1, MDH2, ME1, ME2, ME3, PC, PCK1, PDHA1, PDHA2, PDHB, PKLR, PKM2 36 ACACA(5), ACYP1(2), AKR1B1(1), ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), DLAT(1), DLD(1), GRHPR(1), LDHA(2), LDHB(2), LDHC(1), LDHD(1), ME1(3), ME3(3), PC(4), PCK1(3), PDHA1(1), PDHA2(4) 6696796 48 23 48 22 18 16 8 1 5 0 0.34 0.71 295 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 30 DUSP1(2), GORASP1(3), MAP2K4(2), MAPK13(1), MAPK3(1), MAPK8(6), MAPK8IP3(1), MAPK9(2), NFKB1(4), NFKB2(2), PIK3CD(2), TRAF3(2), TRAF5(3), TRAF6(1) 4903348 32 17 32 10 12 5 7 1 7 0 0.34 0.71 296 FATTY_ACID_BIOSYNTHESIS_PATH_2 ACAA1, ACAA2, ACAT1, ACAT2, ECHS1, EHHADH, HADHA, HADHB, SDS 9 ACAA1(1), ACAA2(1), ECHS1(1), HADHA(1), HADHB(1), SDS(1) 1538662 6 6 6 5 1 2 1 0 2 0 0.34 0.71 297 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 ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH3B1(1), ALDH3B2(1), AOC2(1), AOC3(1), ASPA(2), CNDP1(1), HAL(1), HDC(5), MAOA(3), MAOB(1), PRPS1(1), PRPS2(1) 4480094 32 21 32 20 11 13 6 0 2 0 0.34 0.71 298 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(1), FOS(1), GRB2(2), IL3(1), JAK2(4), MAP2K1(2), MAPK3(1), RAF1(4), SHC1(1), SOS1(3), STAT5B(1) 3102182 21 11 21 4 6 7 4 0 3 1 0.35 0.71 299 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 19 AKT1(1), CASP9(1), CDC42(1), CHUK(4), MAP2K1(2), MAPK3(1), NFKB1(4), RAF1(4), RALA(1), RALBP1(2), RALGDS(1), RHOA(1) 2814164 23 12 23 4 11 2 8 0 2 0 0.35 0.71 300 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 25 ATF1(1), CASP2(1), CHUK(4), CRADD(1), IKBKB(2), MAP2K3(4), MAP2K4(2), MAP2K6(1), MAP3K1(2), MAP3K14(1), MAP4K2(1), MAPK8(6), NFKB1(4), TANK(3) 4429734 33 16 33 14 12 10 8 2 1 0 0.35 0.72 301 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 CSF1(1), IL2(2), IL3(1), IL4(1), IL6(2), IL7(1), IL8(1), IL9(2) 1138680 11 6 11 4 5 5 1 0 0 0 0.35 0.72 302 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_NEOLACTOSERIES ABO, B3GNT1, FUT1, FUT2, FUT9, GCNT2, ST8SIA1 7 FUT1(3), FUT9(2), GCNT2(4) 1074248 9 6 9 3 6 2 0 0 1 0 0.35 0.72 303 NO1PATHWAY Shear stress in endothelial cells increases cytoplasmic calcium, which activates nitric oxide synthase III to release NO, which in turn regulates cardiac contractions. ACTA1, AKT1, BDK, BDKRB2, CALM1, CALM2, CALM3, CAV1, CHRM1, CHRNA1, FLT1, FLT4, HSPCA, KDR, NOS3, PDE2A, PDE3A, PDE3B, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKG1, PRKG2, RYR2, SLC7A1, SYT1, TNNI1, VEGF 28 ACTA1(1), AKT1(1), BDKRB2(1), CAV1(1), CHRM1(1), CHRNA1(4), FLT1(4), FLT4(1), KDR(3), PDE3A(1), PDE3B(1), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PRKG1(8), PRKG2(3), RYR2(11) 7409102 48 24 48 19 11 22 12 0 3 0 0.35 0.72 304 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), MAPK3(1), OPRK1(1), POLR2A(1), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1) 2327288 13 10 13 3 7 3 1 0 2 0 0.36 0.72 305 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 13 AKT1(1), GRB2(2), IGF1R(2), IRS1(4), MAP2K1(2), MAPK3(1), RAF1(4), SHC1(1), SOS1(3), YWHAH(1) 2694596 21 12 21 4 6 7 5 0 3 0 0.36 0.72 306 GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM ACO1, ACO2, CS, GRHPR, HAO1, HAO2, HYI, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 12 ACO1(3), GRHPR(1), HAO2(1), MTHFD1(4), MTHFD1L(3) 2357424 12 10 12 6 3 7 0 1 1 0 0.36 0.72 307 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 20 AKT1(1), CCNE1(1), CDK4(1), CDKN1A(1), CDKN1B(2), MAPK3(1), NFKB1(4), PAK1(1), RAF1(4), RB1(3), TFDP1(1) 3033888 20 11 20 6 10 2 4 0 4 0 0.36 0.72 308 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 17 CCR5(1), CXCR4(1), FOS(1), GNAQ(1), MAPK8(6), PLCG1(1), PRKCA(3), PTK2B(1) 2467340 15 9 15 5 3 6 3 1 2 0 0.36 0.72 309 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), DHRS1(1), DHRS2(1), DHRS3(1), LCMT1(2), METTL2B(1), METTL6(3), PRMT3(1), PRMT7(2), PRMT8(2), WBSCR22(1) 2604928 16 10 16 5 7 3 1 2 3 0 0.36 0.72 310 ST_WNT_BETA_CATENIN_PATHWAY Beta-catenin is degraded in the absence of Wnt signaling; when extracellular Wnt binds Frizzled receptors, beta-catenin accumulates in the nucleus and may promote cell survival. AKT1, AKT2, AKT3, ANKRD6, APC, AXIN1, AXIN2, C22orf2, CER1, CSNK1A1, CTNNB1, DACT1, DKK1, DKK2, DKK3, DKK4, DVL1, FRAT1, FSTL1, GSK3A, GSK3B, IDAX, LAMR1, LRP1, MVP, NKD1, NKD2, PIN1, PSEN1, PTPRA, SENP2, SFRP1, TSHB, WIF1 28 AKT1(1), AKT2(2), AKT3(1), AXIN1(1), AXIN2(5), DACT1(1), DKK1(2), DKK2(3), DKK3(1), DKK4(3), FSTL1(2), GSK3B(2), LRP1(7), MVP(3), NKD1(1), PIN1(1), PTPRA(1), SENP2(2), SFRP1(2), TSHB(1), WIF1(1) 5996116 43 24 43 8 15 13 14 0 1 0 0.36 0.72 311 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(4), CKM(1), LDHA(2), LDHB(2), LDHC(1), NCL(1) 1609008 11 8 11 7 3 7 1 0 0 0 0.37 0.73 312 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(2), HLA-DRA(3), HLA-DRB1(1), IL1B(1), IL4(1), IL5RA(2), IL6(2) 911416 12 6 12 3 6 6 0 0 0 0 0.37 0.73 313 GLUCOCORTICOID_MINERALOCORTICOID_METABOLISM CPN2, CYP11A1, CYP11B2, CYP17A1, HSD11B1, HSD11B2, HSD3B1, HSD3B2 8 CYP11A1(3), HSD3B1(1), HSD3B2(1) 1255480 5 5 5 3 2 2 0 0 1 0 0.37 0.73 314 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 CTSD(1), ESR1(3), GREB1(5), HSPB2(1), MTA1(1), MTA3(1), TUBA8(2) 1868688 14 8 14 2 5 3 2 1 3 0 0.37 0.73 315 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(2), AGTR2(1), CAMK2D(2), F2(2), FYN(1), GNA11(1), GNAI1(1), GNGT1(1), GRB2(2), JAK2(4), MAP2K1(2), MAP2K2(1), MAPK3(1), MAPK8(6), MAPT(1), MYLK(5), PLCG1(1), PRKCA(3), PTK2B(1), RAF1(4), SHC1(1), SOS1(3), STAT1(1), STAT3(1) 7668714 48 19 48 15 12 18 12 1 4 1 0.37 0.73 316 HSA00471_D_GLUTAMINE_AND_D_GLUTAMATE_METABOLISM Genes involved in D-glutamine and D-glutamate metabolism GLS, GLS2, GLUD1, GLUD2 4 GLUD2(3) 792136 3 3 3 1 0 2 1 0 0 0 0.38 0.73 317 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 FLT3(2), IGF1(1), IL3(1), IL6(2), IL9(2), KITLG(1), TGFB1(1), TGFB2(4) 1545104 14 7 14 7 4 6 2 0 2 0 0.38 0.73 318 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 DHRS1(1), DHRS2(1), DHRS3(1), PON1(1), PON2(1), RDH11(1), RDH12(2) 1536472 8 7 8 5 4 3 0 0 1 0 0.38 0.73 319 HSA00020_CITRATE_CYCLE Genes involved in citrate cycle (TCA cycle) ACLY, ACO1, ACO2, CLYBL, CS, DLD, DLST, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, LOC283398, LOC441996, MDH1, MDH2, OGDH, OGDHL, PC, PCK1, PCK2, SDHA, SDHB, SDHC, SDHD, SUCLA2, SUCLG1, SUCLG2 27 ACLY(1), ACO1(3), CLYBL(1), DLD(1), DLST(1), IDH1(1), IDH2(1), IDH3A(3), OGDH(2), OGDHL(5), PC(4), PCK1(3), PCK2(2), SDHA(1), SUCLA2(3), SUCLG1(1) 5495846 33 19 33 14 9 11 8 0 5 0 0.38 0.73 320 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 ACOT11(2), ACYP1(2), DHRS1(1), DHRS2(1), DHRS3(1), ECHS1(1), ESCO1(6), ESCO2(1), GCDH(3), HADHA(1), ITGB1BP3(1), MYST3(10), MYST4(7), SH3GLB1(1) 4623200 38 17 38 12 13 10 9 1 5 0 0.38 0.73 321 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(3), AFMID(1), GRHPR(1), HAO2(1), MTHFD1(4), MTHFD1L(3) 2474084 13 11 13 6 4 7 0 1 1 0 0.38 0.73 322 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 20 AKT1(1), EIF4A2(1), EIF4G1(3), EIF4G3(7), GHR(1), IRS1(4), MAPK3(1), MKNK1(1), PDK2(1), PDPK1(1), PRKCA(3), PTEN(4) 4395398 28 16 28 7 6 9 7 1 5 0 0.38 0.73 323 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT1(2), TAT(3) 480180 5 3 5 1 1 3 0 0 1 0 0.38 0.73 324 1_2_DICHLOROETHANE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1) 1463172 13 9 13 3 6 4 2 0 1 0 0.38 0.73 325 ASCORBATE_AND_ALDARATE_METABOLISM ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1) 1463172 13 9 13 3 6 4 2 0 1 0 0.38 0.73 326 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 ASL(2), CPS1(7), GOT1(2) 1404110 11 6 11 3 3 4 1 0 3 0 0.39 0.73 327 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 ALDH1A1(1), ALDH1A2(3), BCMO1(1) 709252 5 5 5 1 3 1 1 0 0 0 0.39 0.73 328 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 IDH2(1), OGDH(2), SDHA(1), SUCLA2(3) 1735670 7 7 7 5 0 4 2 0 1 0 0.39 0.73 329 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 61 AKT1(1), AKT2(2), AKT3(1), CDC42(1), CDKN1B(2), CREB3(2), CREB5(2), EBP(1), ERBB4(7), F2RL2(1), GAB1(1), GRB2(2), GSK3B(2), IGF1(1), INPPL1(3), IRS1(4), IRS4(8), MET(1), NOLC1(2), PAK1(1), PAK2(3), PAK3(3), PAK7(3), PARD3(4), PARD6A(2), PDK1(2), PIK3CD(2), PPP1R13B(1), PREX1(4), PTEN(4), PTK2(1), PTPN1(4), RPS6KA2(4), RPS6KA3(2), SHC1(1), SLC2A4(2), SOS1(3), SOS2(6), TSC1(2), TSC2(1), YWHAH(1) 13169192 100 30 100 39 30 35 18 1 16 0 0.39 0.73 330 HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - lactoseries ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 10 B3GALT5(2), FUT1(3), FUT3(2), ST3GAL3(3), ST3GAL4(1) 1293926 11 7 11 2 6 1 4 0 0 0 0.39 0.73 331 PLCEPATHWAY Gs-coupled receptors activate adenylyl cyclase, which activates Epac1, leading to the stimulation of PLC and subsequent DAG and IP3 production. ADCY1, ADRB2, GNAS, PLCE1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTGER1, RAP2B 11 ADCY1(5), GNAS(2), PLCE1(2), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), RAP2B(1) 2600718 17 11 17 4 6 7 3 0 1 0 0.39 0.73 332 ACTINYPATHWAY The Arp 2/3 complex localizes to the Y-junction of polymerizing actin fibers that enable lamellipod extension and consequent cell motility. ABI-2, ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, NCK1, NCKAP1, NTRK1, PIR, PSMA7, RAC1, WASF1, WASF2, WASF3, WASL 18 ACTA1(1), ACTR2(1), ACTR3(1), ARPC1B(1), ARPC2(1), NCK1(1), NCKAP1(3), NTRK1(3), PIR(1), PSMA7(1), WASF1(2), WASF2(1), WASF3(4), WASL(2) 2842158 23 11 23 3 7 9 3 0 4 0 0.39 0.73 333 LIMONENE_AND_PINENE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ECHS1, EHHADH, HADHA, SDS 12 ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ECHS1(1), HADHA(1), SDS(1) 2231758 16 11 16 5 7 4 2 0 3 0 0.40 0.73 334 SA_G2_AND_M_PHASES Cdc25 activates the cdc2/cyclin B complex to induce the G2/M transition. CDC2, CDC25A, CDC25B, CDK7, CDKN1A, CHEK1, NEK1, WEE1 7 CDC25A(1), CDC25B(2), CDKN1A(1), NEK1(2) 1394752 6 6 6 0 2 2 0 2 0 0 0.40 0.74 335 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 25 AKT1(1), AKT2(2), AKT3(1), GRB2(2), IARS(3), IL13RA1(2), IL4(1), INPP5D(2), JAK1(1), JAK2(4), JAK3(4), PI3(1), PPP1R13B(1), SERPINA4(5), SHC1(1), SOS1(3), SOS2(6), SRC(3), STAT6(1) 6347774 44 20 44 11 9 19 9 1 5 1 0.40 0.74 336 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 IL12A(1), IL12B(1), IL2(2) 562486 4 3 4 1 0 4 0 0 0 0 0.40 0.74 337 GLUTATHIONE_METABOLISM ANPEP, G6PD, GCLC, GCLM, GGT1, GPX1, GPX2, GPX3, GPX4, GPX5, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, PGD 29 ANPEP(4), G6PD(3), GPX3(2), GPX5(2), GSS(1), GSTA3(1), GSTM3(1), GSTM4(1), GSTO2(1), GSTZ1(1), IDH1(1), IDH2(1) 3275946 19 13 19 3 3 11 4 0 1 0 0.40 0.74 338 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 GNAQ(1), NFKB1(4), PLCB1(1), PRKCA(3) 1504870 9 5 9 6 5 2 0 1 1 0 0.41 0.74 339 BBCELLPATHWAY Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 4 CD28(1), HLA-DRA(3), HLA-DRB1(1) 370956 5 3 5 0 2 3 0 0 0 0 0.41 0.75 340 HSA00300_LYSINE_BIOSYNTHESIS Genes involved in lysine biosynthesis AADAT, AASDHPPT, AASS, KARS 4 AADAT(1), AASDHPPT(1), AASS(2) 871590 4 4 4 2 0 1 2 0 1 0 0.41 0.75 341 MALATEXPATHWAY The tricarboxylate transfer pathway shuttles acetyl groups of acetyl-CoA between mitochondria and the cytoplasm. ACLY, CS, MDH1, ME1, PC, PDHA1, SLC25A1, SLC25A11 8 ACLY(1), ME1(3), PC(4), PDHA1(1), SLC25A11(1) 1682666 10 8 10 4 8 2 0 0 0 0 0.41 0.75 342 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(4), ACADVL(1), ACSL3(1), ACSL4(1), CPT1A(3), CPT2(2), HADHA(1), SCP2(1), SLC25A20(1) 3066288 17 11 17 8 5 5 4 0 3 0 0.42 0.75 343 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 CSF1(1), HLA-DRA(3), HLA-DRB1(1), IL10(1), IL12A(1), IL12B(1), IL15(1), IL2(2), IL3(1), IL4(1), IL6(2), IL7(1), IL8(1), TGFB1(1), TGFB2(4) 2343830 22 9 22 6 6 12 2 0 2 0 0.42 0.75 344 HSP27PATHWAY Hsp27 oligomers have molecular chaperone activity and protect heat-stressed cells against apoptosis. ACTA1, APAF1, BCL2, CASP3, CASP9, CYCS, DAXX, FAS, FASLG, HSPB1, HSPB2, IL1A, MAPKAPK2, MAPKAPK3, TNF, TNFRSF6 15 ACTA1(1), APAF1(2), CASP3(1), CASP9(1), DAXX(1), FAS(2), HSPB2(1) 2005770 9 7 9 3 1 1 5 0 2 0 0.42 0.75 345 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 FOS(1), GRB2(2), IL2(2), IL2RB(1), JAK1(1), JAK3(4), LCK(2), MAP2K1(2), MAPK3(1), MAPK8(6), RAF1(4), SHC1(1), SOS1(3), STAT5B(1), SYK(3) 4273464 34 15 34 5 7 14 6 1 6 0 0.42 0.75 346 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), CASP3(1), CASP8(5), CRADD(1), DFFA(2), DFFB(1), LMNB1(3), MADD(6), MAP2K4(2), MAP3K1(2), MAP3K7(2), MAPK8(6), PAK1(1), PAK2(3), PRKDC(5), RB1(3), SPTAN1(7) 7246438 53 24 52 19 17 13 12 1 10 0 0.43 0.76 347 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 GLUL(2), PGLYRP2(2) 325350 4 3 4 0 1 2 1 0 0 0 0.43 0.76 348 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(2), AGTR1(3), AGTR2(1), COL4A1(5), COL4A2(1), COL4A3(1), COL4A4(2), COL4A5(5), COL4A6(5), REN(2) 4777490 30 15 30 8 10 9 6 1 4 0 0.43 0.76 349 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 16 CHUK(4), CREBBP(8), EP300(8), HDAC3(1), IKBKB(2), NFKB1(4), TRAF6(1) 4067752 28 15 28 8 12 9 4 1 2 0 0.43 0.76 350 NUCLEOTIDE_METABOLISM ADSL, ADSS, DHFR, HPRT1, IMPDH1, MTHFD2, NME2, OAZ1, POLA, POLB, POLD1, POLG, PRPS2, RRM1, SAT, SRM 14 ADSL(2), ADSS(1), DHFR(1), IMPDH1(2), POLB(3), POLD1(2), POLG(2), PRPS2(1), RRM1(2) 2336086 16 12 16 4 8 6 1 0 1 0 0.43 0.76 351 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 28 BAG4(1), BIRC2(2), BIRC3(5), CASP3(1), CASP8(5), CFLAR(1), MAP2K4(2), MAP3K3(2), MAP3K7(2), NFKB1(4), NFKB2(2), NR2C2(1), RALBP1(2), TNFAIP3(1) 4744694 31 16 31 8 10 9 7 0 5 0 0.44 0.76 352 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 195 ABI2(1), ACTN1(2), ACTN2(5), ACTN3(1), ACTN4(3), ARAF(1), ARHGEF1(2), ARHGEF12(2), ARHGEF4(2), ARHGEF6(3), ARHGEF7(3), ARPC1B(1), ARPC2(1), ARPC5L(2), BAIAP2(1), BDKRB2(1), CDC42(1), CHRM1(1), CHRM2(3), CHRM4(1), CHRM5(2), CSK(2), CYFIP1(3), CYFIP2(1), DIAPH2(6), DIAPH3(2), DOCK1(2), EGFR(5), F2(2), FGD1(3), FGD3(1), FGF11(1), FGF12(1), FGF13(1), FGF14(2), FGF19(1), FGF20(1), FGF3(1), FGF5(2), FGFR1(1), FGFR2(5), FN1(6), GIT1(1), GRLF1(5), IQGAP1(8), IQGAP2(8), IQGAP3(4), ITGA1(1), ITGA10(4), ITGA11(2), ITGA2(2), ITGA2B(3), ITGA4(5), ITGA5(2), ITGA6(2), ITGA8(3), ITGA9(3), ITGAD(2), ITGAE(3), ITGAL(4), ITGAM(3), ITGAV(4), ITGAX(2), ITGB2(2), ITGB3(2), ITGB4(1), ITGB5(4), ITGB6(2), ITGB7(2), ITGB8(1), LIMK1(2), LIMK2(1), MAP2K1(2), MAP2K2(1), MAPK3(1), MOS(1), MRAS(1), MSN(3), MYH10(6), MYH14(3), MYH9(6), MYL9(2), MYLK(5), MYLK2(2), NCKAP1(3), NCKAP1L(6), PAK1(1), PAK2(3), PAK3(3), PAK7(3), PDGFRA(4), PDGFRB(2), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIK3R3(4), PIP4K2C(1), PIP5K1B(1), PIP5K1C(3), PPP1CB(1), PPP1CC(1), PPP1R12A(1), PPP1R12B(4), PTK2(1), RAF1(4), RDX(1), RHOA(1), ROCK1(8), ROCK2(4), RRAS2(1), SCIN(1), SLC9A1(2), SOS1(3), SOS2(6), SSH1(2), SSH2(1), SSH3(1), TIAM1(6), TIAM2(5), VAV1(7), VAV2(3), VAV3(3), VCL(2), WASF1(2), WASF2(1), WASL(2) 48945410 325 66 325 110 113 118 52 4 38 0 0.44 0.76 353 MITRPATHWAY The MyoD/MEF2 transcription factors induce muscle cell differentiation and are repressed by the transcriptional repressor MITR. CAMK1, CAMK1G, HDAC9, MEF2A, MEF2B, MEF2C, MEF2D, MYOD1, YWHAH 9 CAMK1(2), CAMK1G(3), HDAC9(2), MEF2A(1), MEF2C(2), YWHAH(1) 1543128 11 6 11 7 1 6 1 0 3 0 0.44 0.76 354 HSA00061_FATTY_ACID_BIOSYNTHESIS Genes involved in fatty acid biosynthesis ACACA, ACACB, FASN, MCAT, OLAH, OXSM 6 ACACA(5), ACACB(5), OLAH(1), OXSM(2) 2573408 13 10 13 7 4 5 1 0 3 0 0.44 0.76 355 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 17 AKT1(1), EIF2B5(3), GSK3B(2), IGF1(1), IGF1R(2), INPPL1(3), PDK2(1), PDPK1(1), PPP2CA(1), PTEN(4) 2916166 19 13 19 5 7 5 5 0 2 0 0.44 0.77 356 HSA00232_CAFFEINE_METABOLISM Genes involved in caffeine metabolism CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH 7 CYP1A2(2), CYP2A13(3), CYP2A6(3), XDH(1) 1464878 9 7 9 6 3 3 2 0 1 0 0.44 0.77 357 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(2), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH7A1(2), CYP2C9(5), DHRS1(1), DHRS2(1), DHRS3(1), ECHS1(1), ESCO1(6), ESCO2(1), HADHA(1), MYST3(10), MYST4(7), SH3GLB1(1) 5545920 48 18 48 12 14 15 12 1 6 0 0.45 0.77 358 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 10 AKT1(1), CAT(1), GH1(1), GHR(1), IGF1(1), IGF1R(2), SHC1(1) 1695240 8 8 8 8 4 1 2 0 1 0 0.45 0.77 359 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 CCNH(1), CDC25A(1), CDC25B(2), CDC25C(1), MNAT1(1), XPO1(1) 1572344 7 6 7 4 3 2 0 1 1 0 0.45 0.77 360 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 16 DNAJA3(2), IFNGR1(1), IFNGR2(1), IKBKB(2), JAK2(4), LIN7A(2), NFKB1(4), RB1(3), USH1C(5), WT1(4) 3119846 28 10 28 7 10 10 3 0 4 1 0.45 0.77 361 HSA00120_BILE_ACID_BIOSYNTHESIS Genes involved in bile acid biosynthesis ACAA1, ACAA2, ACAD8, ACAD9, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AKR1B10, AKR1C4, AKR1D1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, BAAT, CEL, CYP27A1, CYP7A1, HADHB, HSD3B7, LIPA, RDH11, RDH12, RDH13, RDH14, SLC27A5, SOAT1, SOAT2, SRD5A1, SRD5A2 38 ACAA1(1), ACAA2(1), ACAD8(1), ACAD9(4), ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3), AKR1C4(1), AKR1D1(1), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH7A1(2), CYP27A1(1), CYP7A1(1), HADHB(1), RDH11(1), RDH12(2), SLC27A5(1), SRD5A1(1), SRD5A2(1) 5861650 41 22 41 18 10 19 10 0 2 0 0.45 0.77 362 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(3), CDKN1A(1), GRIN1(1), HIF1A(3), JAK2(4), NFKB1(4) 2340732 16 9 16 6 5 5 2 0 3 1 0.46 0.77 363 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(3), CCNA2(1), CCNE1(1), CCNE2(1), CDK4(1), CDKN1B(2), PRB1(1) 1587780 10 6 10 4 2 2 2 0 4 0 0.46 0.77 364 HSA00730_THIAMINE_METABOLISM Genes involved in thiamine metabolism LHPP, MTMR1, MTMR2, MTMR6, NFS1, PHPT1, THTPA, TPK1 8 LHPP(1), MTMR1(2), MTMR2(1), NFS1(1), PHPT1(1), TPK1(3) 1169534 9 6 9 3 5 1 2 0 1 0 0.46 0.77 365 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 ALDH6A1(2) 283888 2 2 2 0 0 1 1 0 0 0 0.46 0.77 366 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(3), ATP6V0A4(3), ATP6V0B(1), ATP6V1B1(1), ATP6V1B2(2), ATP6V1C2(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(1), SHMT1(1) 2799818 15 10 15 6 4 6 4 0 1 0 0.46 0.77 367 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(3), ATP6V0A4(3), ATP6V0B(1), ATP6V1B1(1), ATP6V1B2(2), ATP6V1C2(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(1), SHMT1(1) 2799818 15 10 15 6 4 6 4 0 1 0 0.46 0.77 368 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(3), ATP6V0A4(3), ATP6V0B(1), ATP6V1B1(1), ATP6V1B2(2), ATP6V1C2(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(1), SHMT1(1) 2799818 15 10 15 6 4 6 4 0 1 0 0.46 0.77 369 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 35 ANPEP(4), G6PD(3), GPX3(2), GPX5(2), GPX6(1), GSS(1), GSTA3(1), GSTA5(1), GSTM3(1), GSTM4(1), GSTO2(1), GSTZ1(1), IDH1(1), IDH2(1), TXNDC12(2) 3859006 23 15 23 3 4 13 5 0 1 0 0.46 0.78 370 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 CSF1(1), IL6(2), LDLR(1), LPL(2) 968554 6 5 6 2 4 1 0 0 1 0 0.47 0.78 371 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(2), ALOX5(1), CYP4F2(2), CYP4F3(1), EPX(1), LPO(1), MPO(2), PLA2G4A(4), PLA2G6(2), PRDX1(1), PTGIS(2), PTGS1(4), PTGS2(1), TBXAS1(3), TPO(4) 5067506 31 19 31 13 16 9 3 0 3 0 0.47 0.78 372 HSA00360_PHENYLALANINE_METABOLISM Genes involved in phenylalanine metabolism ABP1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, ARD1A, DDC, EPX, ESCO1, ESCO2, GOT1, GOT2, HPD, LPO, LYCAT, MAOA, MAOB, MIF, MPO, MYST3, MYST4, NAT5, NAT6, PNPLA3, PRDX6, SH3GLB1, TAT, TPO 26 ALDH1A3(4), ALDH3B1(1), ALDH3B2(1), AOC2(1), AOC3(1), EPX(1), ESCO1(6), ESCO2(1), GOT1(2), HPD(2), LPO(1), MAOA(3), MAOB(1), MPO(2), MYST3(10), MYST4(7), SH3GLB1(1), TAT(3), TPO(4) 6226298 52 23 52 20 18 20 10 1 3 0 0.47 0.78 373 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 CARM1(1), CBS(2), CTH(1), LCMT1(2), MARS(4), MARS2(1), MAT1A(2), MAT2B(1), METTL2B(1), METTL6(3), PAPSS1(1), PAPSS2(2), PRMT3(1), PRMT7(2), PRMT8(2), SEPHS1(2), WBSCR22(1) 4504020 29 16 29 7 9 10 4 2 4 0 0.47 0.78 374 HSA00720_REDUCTIVE_CARBOXYLATE_CYCLE Genes involved in reductive carboxylate cycle (CO2 fixation) ACLY, ACO1, ACO2, ACSS1, ACSS2, FH, IDH1, IDH2, LOC441996, MDH1, MDH2, SUCLA2 11 ACLY(1), ACO1(3), ACSS1(1), ACSS2(1), IDH1(1), IDH2(1), SUCLA2(3) 2434746 11 8 11 8 3 6 0 0 2 0 0.47 0.78 375 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(1), CASP3(1), CASP6(2), CASP7(1), CASP8(5), CFLAR(1), DAXX(1), DFFA(2), DFFB(1), FAF1(3), LMNB1(3), MAP2K4(2), MAP3K1(2), MAP3K7(2), MAPK8(6), PAK1(1), PAK2(3), PRKDC(5), PTPN13(9), RB1(3), RIPK2(1), SPTAN1(7) 7870544 63 23 62 14 13 24 14 1 11 0 0.47 0.78 376 HSA00520_NUCLEOTIDE_SUGARS_METABOLISM Genes involved in nucleotide sugars metabolism GALE, GALT, TGDS, UGDH, UGP2, UXS1 6 GALT(1), TGDS(1), UGDH(1), UGP2(3), UXS1(1) 934744 7 4 7 0 1 3 1 0 2 0 0.48 0.78 377 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), CD28(1), CSK(2), CTLA4(1), DAG1(3), DTYMK(1), EPHB2(3), GRAP2(4), GRB2(2), ITK(4), LAT(1), LCK(2), LCP2(1), NCK1(1), NFKB1(4), NFKB2(2), PAK1(1), PAK2(3), PAK3(3), PAK7(3), PLCG1(1), PTPRC(9), RAF1(4), RASGRP1(3), RASGRP2(2), RASGRP3(3), RASGRP4(1), SOS1(3), SOS2(6), VAV1(7), ZAP70(1) 9768406 86 28 85 21 31 33 14 0 8 0 0.48 0.78 378 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 ACOX3(3), FADS2(1), PLA2G4A(4), PLA2G6(2) 1899676 10 7 10 3 7 1 0 0 2 0 0.48 0.78 379 HSA00785_LIPOIC_ACID_METABOLISM Genes involved in lipoic acid metabolism LIAS, LIPT1, LOC387787 2 LIAS(1), LIPT1(2) 279258 3 2 3 1 0 2 1 0 0 0 0.48 0.78 380 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(2), B3GALT5(2), FUT1(3), FUT9(2), GLA(1), HEXB(2), ST3GAL2(1) 1884644 13 8 13 5 7 3 3 0 0 0 0.48 0.78 381 LYSINE_BIOSYNTHESIS AADAT, AASDH, AASDHPPT, AASS, KARS 5 AADAT(1), AASDH(2), AASDHPPT(1), AASS(2) 1279732 6 5 6 3 0 3 2 0 1 0 0.49 0.78 382 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 12 CREBBP(8), DAXX(1), PAX3(3), PML(1), RB1(3), SIRT1(2), SP100(1) 3252958 19 12 19 6 9 2 4 0 4 0 0.49 0.78 383 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(1), CDC42(1), DAXX(1), GRB2(2), HSPB2(1), MAP2K4(2), MAP2K6(1), MAP3K1(2), MAP3K5(3), MAP3K7(2), MAP3K9(4), MEF2A(1), MEF2C(2), MKNK1(1), PLA2G4A(4), RPS6KA5(4), SHC1(1), STAT1(1), TGFB1(1), TGFB2(4), TGFBR1(5) 6751124 44 18 44 11 13 12 9 0 10 0 0.49 0.78 384 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 20 ARHGAP5(4), FYN(1), ITGA1(1), MAP2K1(2), MAPK3(1), MYLK(5), PTK2(1), RAF1(4), ROCK1(8), SHC1(1), SRC(3), TLN1(3) 6271048 34 19 34 10 11 13 6 0 4 0 0.49 0.78 385 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(1), CDC7(2), DIAPH2(6), MCM10(4), MCM3(2), MCM4(1), MCM5(5), MCM6(1), MCM7(2), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(1), POLA2(2), POLD1(2), POLD2(1), POLD3(1), POLE(10), POLE2(1), RFC1(4), RFC5(1), RPA4(1), UBB(1) 9237568 53 23 52 17 18 24 4 0 7 0 0.49 0.78 386 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 49 ABL1(2), ARHGEF2(2), ARPC5L(2), CDC42(1), CDH1(2), CTTN(1), FYN(1), NCK1(1), NCL(1), PRKCA(3), RHOA(1), ROCK1(8), ROCK2(4), TLR4(4), TLR5(2), TUBA1B(2), TUBA1C(2), TUBA3C(3), TUBA3D(1), TUBA3E(1), TUBA4A(2), TUBA8(2), TUBAL3(1), TUBB1(1), TUBB2A(2), TUBB3(1), TUBB4(1), TUBB8(1), WASL(2) 8776756 57 23 57 18 19 20 11 0 7 0 0.49 0.78 387 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 49 ABL1(2), ARHGEF2(2), ARPC5L(2), CDC42(1), CDH1(2), CTTN(1), FYN(1), NCK1(1), NCL(1), PRKCA(3), RHOA(1), ROCK1(8), ROCK2(4), TLR4(4), TLR5(2), TUBA1B(2), TUBA1C(2), TUBA3C(3), TUBA3D(1), TUBA3E(1), TUBA4A(2), TUBA8(2), TUBAL3(1), TUBB1(1), TUBB2A(2), TUBB3(1), TUBB4(1), TUBB8(1), WASL(2) 8776756 57 23 57 18 19 20 11 0 7 0 0.49 0.78 388 UBIQUINONE_BIOSYNTHESIS NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 15 NDUFA4(1), NDUFB6(1), NDUFS1(2), NDUFS2(3) 1293062 7 5 7 4 3 2 1 0 1 0 0.50 0.78 389 ALKALOID_BIOSYNTHESIS_II ABP1, AOC2, AOC3, CES1, ESD 5 AOC2(1), AOC3(1), CES1(2), ESD(1) 1056596 5 5 5 6 1 4 0 0 0 0 0.50 0.78 390 STREPTOMYCIN_BIOSYNTHESIS GCK, HK1, HK2, HK3, IMPA1, PGM1, PGM3, TGDS 8 GCK(1), HK1(2), HK3(1), IMPA1(1), PGM1(3), PGM3(2), TGDS(1) 1846130 11 8 11 3 4 5 2 0 0 0 0.50 0.78 391 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(2), KHK(1), LCT(11), PGM1(3), PYGM(3) 2492302 20 13 20 2 11 4 5 0 0 0 0.50 0.78 392 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(2), JAK1(1), JAK2(4) 1910018 9 6 9 5 1 3 3 0 1 1 0.50 0.78 393 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(2), JAK1(1), JAK2(4) 1910018 9 6 9 5 1 3 3 0 1 1 0.50 0.78 394 GLUCONEOGENESIS ACYP1, ACYP2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GCK, GPI, HK1, HK2, HK3, LDHA, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKM, PFKP, PGAM1, PGK1, PGM1, PGM3, PKLR, PKM2, TPI1 53 ACYP1(2), ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3), ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH3B1(1), ALDH3B2(1), ALDOB(2), ALDOC(2), DLAT(1), DLD(1), ENO2(2), ENO3(2), FBP2(1), G6PC(1), GCK(1), GPI(1), HK1(2), HK3(1), LDHA(2), LDHB(2), LDHC(1), PDHA1(1), PDHA2(4), PFKM(3), PFKP(2), PGK1(1), PGM1(3), PGM3(2) 8864350 67 27 67 24 25 21 16 0 5 0 0.50 0.78 395 GLYCOLYSIS ACYP1, ACYP2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GCK, GPI, HK1, HK2, HK3, LDHA, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKM, PFKP, PGAM1, PGK1, PGM1, PGM3, PKLR, PKM2, TPI1 53 ACYP1(2), ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3), ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH3B1(1), ALDH3B2(1), ALDOB(2), ALDOC(2), DLAT(1), DLD(1), ENO2(2), ENO3(2), FBP2(1), G6PC(1), GCK(1), GPI(1), HK1(2), HK3(1), LDHA(2), LDHB(2), LDHC(1), PDHA1(1), PDHA2(4), PFKM(3), PFKP(2), PGK1(1), PGM1(3), PGM3(2) 8864350 67 27 67 24 25 21 16 0 5 0 0.50 0.78 396 SELENOAMINO_ACID_METABOLISM AHCY, CBS, CTH, GGT1, MARS, MARS2, MAT1A, MAT2B, PAPSS1, PAPSS2, SCLY, SEPHS1 12 CBS(2), CTH(1), MARS(4), MARS2(1), MAT1A(2), MAT2B(1), PAPSS1(1), PAPSS2(2), SEPHS1(2) 2241632 16 9 16 4 4 7 3 0 2 0 0.50 0.78 397 HSA00620_PYRUVATE_METABOLISM Genes involved in pyruvate metabolism ACACA, ACACB, ACAT1, ACAT2, ACOT12, ACSS1, ACSS2, ACYP1, ACYP2, AKR1B1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, DLAT, DLD, GLO1, GRHPR, HAGH, HAGHL, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, LDHD, MDH1, MDH2, ME1, ME2, ME3, PC, PCK1, PCK2, PDHA1, PDHA2, PDHB, PKLR, PKM2 41 ACACA(5), ACACB(5), ACOT12(5), ACSS1(1), ACSS2(1), ACYP1(2), AKR1B1(1), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH7A1(2), DLAT(1), DLD(1), GRHPR(1), LDHA(2), LDHAL6A(2), LDHAL6B(1), LDHB(2), LDHC(1), LDHD(1), ME1(3), ME3(3), PC(4), PCK1(3), PCK2(2), PDHA1(1), PDHA2(4) 8485218 63 24 63 26 19 25 9 1 9 0 0.50 0.78 398 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(1), ARSB(1), ARSD(1), CYP11B1(4), HSD17B2(1), HSD17B3(1), HSD3B1(1), HSD3B2(1), SRD5A1(1), SRD5A2(1), STS(1), SULT1E1(1), SULT2A1(1), UGT1A4(1), UGT1A6(1), UGT1A8(1), UGT1A9(1), UGT2B4(2) 4734292 23 15 23 7 6 11 2 0 4 0 0.50 0.78 399 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 ATG3(1), ATG5(1), BECN1(1), IFNA10(3), IFNA2(2), IFNA5(1), PIK3C3(5), PIK3R4(4), PRKAA1(1), PRKAA2(4), ULK1(1) 3756230 24 12 24 3 5 8 6 0 5 0 0.51 0.78 400 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 GOT1(2), TAT(3), TYR(1) 858990 6 4 6 2 2 3 0 0 1 0 0.51 0.78 401 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(4), AMY2A(2), AMY2B(1), ENPP3(2), G6PC(1), GANAB(1), GBE1(1), GCK(1), GPI(1), GUSB(1), GYS1(2), GYS2(4), HK1(2), HK3(1), MGAM(4), PGM1(3), PGM3(2), PYGB(1), PYGM(3), SI(4), UCHL1(2), UCHL3(1), UGDH(1), UGT1A4(1), UGT1A6(1), UGT1A8(1), UGT1A9(1), UGT2B4(2), UXS1(1) 10241350 52 21 52 14 14 17 13 0 8 0 0.51 0.78 402 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 ALDOB(2), ALDOC(2), DERA(1), FBP2(1), G6PD(3), GPI(1), H6PD(2), PFKM(3), PFKP(2), PGM1(3), PGM3(2), PRPS1(1), PRPS2(1), TALDO1(2), TKT(1), TKTL1(3), TKTL2(3) 4375808 33 19 33 10 14 15 2 0 2 0 0.51 0.78 403 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(10) 1509262 12 6 12 3 2 4 6 0 0 0 0.51 0.78 404 STEROID_BIOSYNTHESIS CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 9 F13B(2), HSD17B2(1), HSD17B3(1), HSD17B4(1), HSD3B1(1), HSD3B2(1) 1462344 7 5 7 3 1 3 2 0 1 0 0.51 0.78 405 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 65 APAF1(2), BCL2L11(2), BID(1), BIRC2(2), BIRC3(5), BNIP3L(2), CASP10(1), CASP2(1), CASP3(1), CASP4(2), CASP6(2), CASP7(1), CASP8(5), CASP9(1), CHUK(4), DFFA(2), DFFB(1), FAS(2), GZMB(2), HELLS(2), IKBKB(2), IRF3(2), IRF4(2), MAP2K4(2), MAP3K1(2), NFKB1(4), TNFRSF10B(4), TNFRSF21(2), TRAF1(1), TRAF3(2) 9936874 64 27 64 25 20 20 12 0 12 0 0.51 0.78 406 N_GLYCAN_DEGRADATION AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 13 AGA(2), FUCA1(2), HEXB(2), LCT(11), MANBA(5), NEU1(1) 2917678 23 12 23 4 7 7 6 0 3 0 0.51 0.78 407 GLYCOSAMINOGLYCAN_DEGRADATION ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, IDS, IDUA, LCT, NAGLU 11 ARSB(1), GALNS(1), GNS(3), GUSB(1), HEXB(2), LCT(11), NAGLU(2) 2631970 21 12 21 5 8 6 5 0 2 0 0.52 0.78 408 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 F11(1), F13B(2), F2(2), F5(10), F7(1), F8(5), FGA(6), FGB(1), FGG(2), LPA(1), PLAT(3), PLAU(1), PLG(4), SERPINB2(1), SERPINE1(3), VWF(7) 6324806 50 21 50 20 14 25 7 0 4 0 0.52 0.78 409 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(3), CD38(2), ENPP3(2), NADK(2), NADSYN1(1), NMNAT1(1), NMNAT2(1), NMNAT3(1), NNMT(3), NNT(3), NT5C1A(1), NT5C1B(5), NT5C2(2), NT5E(1) 3967292 28 16 28 11 10 9 5 0 4 0 0.52 0.78 410 ATMPATHWAY The tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair. ABL1, ATM, BRCA1, CDKN1A, CHEK1, CHEK2, GADD45A, JUN, MAPK8, MDM2, MRE11A, NBS1, NFKB1, NFKBIA, RAD50, RAD51, RBBP8, RELA, TP53, TP73 18 ABL1(2), ATM(15), BRCA1(2), CDKN1A(1), CHEK2(1), MAPK8(6), MRE11A(5), NFKB1(4), RAD50(7) 5204634 43 15 43 7 11 20 9 1 1 1 0.52 0.78 411 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 20 CCR5(1), ETV5(3), IL12A(1), IL12B(1), IL12RB2(2), IL18R1(4), JAK2(4), MAP2K6(1), MAPK8(6), STAT4(3) 3424790 26 12 26 5 1 11 9 1 3 1 0.52 0.78 412 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 LPL(2), NR3C1(1), PPARG(1) 994466 4 4 4 4 0 1 1 0 2 0 0.52 0.78 413 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(4), CD33(1), CD5(3), IL10(1), IL12A(1), IL12B(1), IL3(1), IL4(1), ITGAX(2), TLR2(4), TLR4(4), TLR7(5), TLR9(4) 3391860 32 14 32 5 9 13 9 0 1 0 0.53 0.79 414 HSA00521_STREPTOMYCIN_BIOSYNTHESIS Genes involved in streptomycin biosynthesis GCK, HK1, HK2, HK3, IMPA1, IMPA2, ISYNA1, PGM1, PGM3, TGDS 10 GCK(1), HK1(2), HK3(1), IMPA1(1), IMPA2(1), PGM1(3), PGM3(2), TGDS(1) 2072792 12 9 12 3 5 5 2 0 0 0 0.53 0.79 415 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 30 ACTR2(1), ACTR3(1), AKT1(1), ANGPTL2(4), DAG1(3), DGKA(1), ETFA(1), ITGA9(3), ITPR1(8), ITPR2(6), ITPR3(7), MAP2K1(2), MAPK3(1), NR1I3(2), PAK1(1), PDE3A(1), PDE3B(1), PI3(1), PIK3C2G(2), PIK3CD(2), RIPK3(1), RPS4X(1), SGCB(4) 8373266 55 23 55 13 19 17 10 0 7 2 0.53 0.79 416 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 125 ACTN1(2), ACTN2(5), ACTN3(1), ACTN4(3), AKT1(1), AKT2(2), AKT3(1), AMOTL1(3), ASH1L(11), CASK(2), CDC42(1), CDK4(1), CGN(2), CLDN10(3), CLDN16(2), CLDN17(3), CLDN2(1), CLDN8(2), CSDA(1), CSNK2A2(1), CTNNA1(5), CTNNA2(2), CTNNA3(1), CTTN(1), EPB41L1(5), EPB41L2(3), EPB41L3(6), EXOC4(4), GNAI1(1), IGSF5(6), INADL(2), LLGL2(2), MAGI1(6), MAGI2(7), MAGI3(3), MLLT4(3), MPDZ(4), MRAS(1), MYH1(8), MYH10(6), MYH11(12), MYH13(5), MYH14(3), MYH15(4), MYH2(5), MYH3(7), MYH4(4), MYH6(5), MYH7(5), MYH7B(2), MYH8(7), MYH9(6), MYL9(2), PARD3(4), PARD6A(2), PARD6G(1), PPP2CA(1), PPP2CB(2), PPP2R1A(1), PPP2R1B(1), PPP2R2B(2), PPP2R2C(2), PPP2R3A(4), PRKCA(3), PRKCE(2), PRKCG(5), PRKCH(1), PRKCI(1), PRKCQ(2), PTEN(4), RHOA(1), RRAS2(1), SPTAN1(7), SRC(3), TJAP1(1), TJP1(2), TJP2(2), ZAK(2) 34800560 248 55 246 78 103 80 33 0 31 1 0.53 0.79 417 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(2), ITGAL(4), ITGAM(3), ITGB2(2), PECAM1(1), SELE(2), SELL(3) 2051062 17 9 17 7 4 9 2 0 2 0 0.53 0.79 418 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 ACP2(1), ACPP(2), ENPP3(2), FLAD1(1), LHPP(1), MTMR1(2), MTMR2(1), PHPT1(1), TYR(1) 2759858 12 10 12 10 6 1 3 0 1 1 0.54 0.79 419 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(3), ATP6V0A4(3), ATP6V0B(1), ATP6V1B1(1), ATP6V1B2(2), ATP6V1C2(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(1), SHMT1(1) 2957068 15 10 15 6 4 6 4 0 1 0 0.54 0.79 420 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 19 ADCY1(5), AKT1(1), CSF2RB(1), IGF1(1), IGF1R(2), IL3(1), KIT(2), KITLG(1), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), YWHAH(1) 3139662 22 14 22 15 10 8 3 0 1 0 0.54 0.79 421 APOPTOSIS_GENMAPP APAF1, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, FADD, FAS, FASLG, GZMB, IKBKG, JUN, MAP2K4, MAP3K1, MAP3K14, MAPK10, MCL1, MDM2, MYC, NFKB1, NFKBIA, PARP1, PRF1, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TNFSF10, TP53, TRADD, TRAF1, TRAF2 40 APAF1(2), BID(1), BIRC2(2), BIRC3(5), CASP2(1), CASP3(1), CASP6(2), CASP7(1), CASP8(5), CASP9(1), FAS(2), GZMB(2), MAP2K4(2), MAP3K1(2), MAP3K14(1), NFKB1(4), TRAF1(1) 6448680 35 18 35 16 10 10 8 0 7 0 0.54 0.79 422 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 15 FOS(1), GRB2(2), MAP2K1(2), MAPK3(1), MAPK8(6), NGFR(1), PLCG1(1), RAF1(4), SHC1(1), SOS1(3) 2646404 22 10 22 4 6 7 6 1 2 0 0.54 0.79 423 HEME_BIOSYNTHESIS ALAD, ALAS1, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, UROS 9 ALAD(1), ALAS1(1), ALAS2(3), CPOX(1), FECH(1), PPOX(1), UROD(1) 1417428 9 6 9 3 5 2 2 0 0 0 0.54 0.79 424 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), GRB2(2), IL4(1), IRS1(4), JAK1(1), JAK3(4), SHC1(1), STAT6(1) 2628144 15 9 15 3 2 8 2 0 3 0 0.54 0.79 425 EICOSANOID_SYNTHESIS ALOX12, ALOX15, ALOX15B, ALOX5, ALOX5AP, DPEP1, GGT1, IPLA2(GAMMA), LTA4H, LTC4S, PLA2G2A, PLA2G6, PTGDS, PTGES, PTGIS, PTGS1, PTGS2, TBXAS1 17 ALOX15B(1), ALOX5(1), PLA2G6(2), PTGIS(2), PTGS1(4), PTGS2(1), TBXAS1(3) 2723648 14 12 14 5 6 5 3 0 0 0 0.54 0.79 426 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(6), ABCB11(3), ABCB4(6), ABCC1(3), ABCC3(2) 2668386 20 9 20 8 4 8 5 1 2 0 0.55 0.79 427 HSA00680_METHANE_METABOLISM Genes involved in methane metabolism ADH5, CAT, EPX, LPO, MPO, MTHFR, PRDX6, SHMT1, SHMT2, TPO 10 CAT(1), EPX(1), LPO(1), MPO(2), MTHFR(3), SHMT1(1), SHMT2(1), TPO(4) 2131884 14 10 14 8 7 4 3 0 0 0 0.55 0.79 428 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(4), MAP3K14(1), MAPK8(6), NFKB1(4), TNFRSF17(2), TNFSF13B(1), TRAF3(2), TRAF5(3), TRAF6(1) 2690512 24 11 24 6 9 5 7 1 2 0 0.55 0.79 429 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 14 CDK4(1), CDKN1A(1), CDKN1B(2), PRB1(1) 1296856 5 5 5 2 1 1 0 0 3 0 0.55 0.80 430 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 12 AKT1(1), CASP9(1), CHUK(4), GH1(1), GHR(1), NFKB1(4), PDPK1(1), PPP2CA(1), YWHAH(1) 1898262 15 8 15 4 7 2 6 0 0 0 0.56 0.80 431 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(5), AP2A1(1), BIN1(1), DNM1(4), EPN1(1), EPS15(3), PPP3CA(2), PPP3CB(2), PPP3CC(3), SYNJ1(4), SYNJ2(1) 4154042 27 12 27 8 9 8 2 0 8 0 0.56 0.80 432 CAPROLACTAM_DEGRADATION AKR1A1, ECHS1, EHHADH, HADHA, SDS 5 ECHS1(1), HADHA(1), SDS(1) 891806 3 3 3 2 1 0 0 0 2 0 0.57 0.81 433 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(2), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH7A1(2), BBOX1(2), DLST(1), ECHS1(1), EHMT2(3), GCDH(3), HADH(1), HADHA(1), HSD17B10(1), HSD17B4(1), NSD1(4), OGDH(2), OGDHL(5), PIPOX(1), PLOD1(2), PLOD2(1), PLOD3(1), RDH11(1), RDH12(2), SETD1A(3), SETD7(2), SETDB1(4), SHMT1(1), SHMT2(1), SPCS1(1), SPCS3(1), SUV39H1(1), SUV39H2(1), TMLHE(2) 10330230 65 24 65 20 25 16 11 0 13 0 0.57 0.81 434 ST_G_ALPHA_I_PATHWAY Gi and Go proteins are members of the same family that transduce cellular signals through both their alpha and beta subunits. AKT1, AKT2, AKT3, ASAH1, BF, BRAF, DAG1, DRD2, EGFR, EPHB2, GRB2, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, PI3, PIK3CB, PITX2, PLCB1, PLCB2, PLCB3, PLCB4, RAF1, RAP1GA1, RGS20, SHC1, SOS1, SOS2, SRC, STAT3, TERF2IP 33 AKT1(1), AKT2(2), AKT3(1), ASAH1(1), DAG1(3), DRD2(4), EGFR(5), EPHB2(3), GRB2(2), ITPR1(8), ITPR2(6), ITPR3(7), KCNJ5(1), KCNJ9(2), PI3(1), PIK3CB(1), PLCB1(1), PLCB3(3), PLCB4(2), RAF1(4), RGS20(1), SHC1(1), SOS1(3), SOS2(6), SRC(3), STAT3(1), TERF2IP(2) 10515760 75 28 75 19 33 24 11 1 5 1 0.58 0.81 435 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(1), ADSL(2), ADSS(1), ASL(2), ASPA(2), CAD(4), CRAT(2), DARS(3), GAD1(2), GAD2(2), GOT1(2), GPT2(1), NARS(2), PC(4) 4757104 32 18 32 17 16 10 5 0 1 0 0.58 0.81 436 ERKPATHWAY Cell growth is promoted by Ras activation of the anti-apoptotic p44/42 MAP kinase pathway. DPM2, EGFR, ELK1, GNAS, GNB1, GNGT1, GRB2, HRAS, IGF1R, ITGB1, KLK2, MAP2K1, MAP2K2, MAPK1, MAPK3, MKNK1, MKNK2, MYC, NGFB, NGFR, PDGFRA, PPP2CA, PTPRR, RAF1, RPS6KA1, RPS6KA5, SHC1, SOS1, SRC, STAT3 28 EGFR(5), GNAS(2), GNGT1(1), GRB2(2), IGF1R(2), MAP2K1(2), MAP2K2(1), MAPK3(1), MKNK1(1), MKNK2(1), NGFR(1), PDGFRA(4), PPP2CA(1), PTPRR(4), RAF1(4), RPS6KA5(4), SHC1(1), SOS1(3), SRC(3), STAT3(1) 5909202 44 20 44 14 15 14 12 0 2 1 0.58 0.81 437 ONE_CARBON_POOL_BY_FOLATE ALDH1L1, AMT, ATIC, ATP6V0C, SHMT1, DHFR, GART, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 14 ALDH1L1(3), ATIC(1), DHFR(1), GART(1), MTHFD1(4), MTHFD1L(3), MTHFR(3), MTHFS(1), MTR(1), SHMT1(1), SHMT2(1) 3201222 20 14 20 4 8 8 4 0 0 0 0.58 0.81 438 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 ARFGEF2(4), CLTA(2), COPA(2), GBF1(7), GPLD1(4), KDELR2(1), KDELR3(1) 2964972 21 11 20 6 7 6 4 1 3 0 0.58 0.81 439 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 46 IMPA1(1), IMPA2(1), INPP4A(1), INPP4B(2), INPPL1(3), ITGB1BP3(1), MINPP1(1), OCRL(6), PI4KA(9), PI4KB(1), PIK3C3(5), PIK3CB(1), PIK3CD(2), PIK3CG(5), PIP4K2C(1), PIP5K1B(1), PIP5K1C(3), PLCB1(1), PLCB3(3), PLCB4(2), PLCD1(4), PLCE1(2), PLCG1(1), PLCG2(4), PLCZ1(1), PTEN(4), SYNJ1(4), SYNJ2(1) 13122250 71 28 71 24 20 27 11 1 12 0 0.58 0.82 440 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 IARS(3), IARS2(1), LARS(1), LARS2(1), PDHA1(1), PDHA2(4), VARS2(2) 3031136 13 11 13 7 5 2 5 0 1 0 0.59 0.82 441 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 ACY1(1), ADC(1), AGMAT(4), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH7A1(2), AMD1(1), AOC2(1), AOC3(1), ARG2(2), ASL(2), ASS1(1), CPS1(7), MAOA(3), MAOB(1), NAGS(1), ODC1(4), OTC(2), SAT2(1) 5418414 44 18 43 13 14 17 6 0 7 0 0.59 0.82 442 SIG_REGULATION_OF_THE_ACTIN_CYTOSKELETON_BY_RHO_GTPASES Genes related to regulation of the actin cytoskeleton ACTG1, ACTG2, ACTR2, ACTR3, AKT1, ANGPTL2, CDC42, CFL1, CFL2, FLNA, FLNC, FSCN1, FSCN2, FSCN3, GDI1, GDI2, LIMK1, MYH2, MYLK, MYLK2, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PFN1, PFN2, RHO, ROCK1, ROCK2, RPS4X, VASP, WASF1, WASL 34 ACTG2(1), ACTR2(1), ACTR3(1), AKT1(1), ANGPTL2(4), CDC42(1), FLNA(1), FLNC(2), LIMK1(2), MYH2(5), MYLK(5), MYLK2(2), PAK1(1), PAK2(3), PAK3(3), PAK7(3), RHO(2), ROCK1(8), ROCK2(4), RPS4X(1), WASF1(2), WASL(2) 8451086 55 24 55 13 23 16 6 0 10 0 0.59 0.82 443 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 13 CHUK(4), DUSP1(2), IKBKAP(1), IKBKB(2), MAP3K1(2), MAP3K14(1), NFKB1(4), TNFAIP3(1), TRAF3(2), TRAF6(1) 3411268 20 12 20 5 7 7 5 0 1 0 0.59 0.82 444 METHANE_METABOLISM ADH5, ATP6V0C, SHMT1, CAT, EPX, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, SHMT1, SHMT2, TPO 13 CAT(1), EPX(1), LPO(1), MPO(2), PRDX1(1), SHMT1(1), SHMT2(1), TPO(4) 2168516 12 9 12 9 6 4 1 0 1 0 0.59 0.82 445 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 13 ABL1(2), POLR1A(3), POLR1B(5), POLR1C(2), POLR1D(2), RB1(3) 2764484 17 11 17 3 6 4 6 0 1 0 0.59 0.82 446 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 32 AKT1(1), AKT2(2), AKT3(1), BTK(2), DAPP1(1), GRB2(2), GSK3B(2), IARS(3), INPP5D(2), PDK1(2), PPP1R13B(1), PTEN(4), RPS6KA2(4), RPS6KA3(2), SHC1(1), SOS1(3), SOS2(6), TEC(2), YWHAH(1) 6177642 42 18 42 13 10 17 10 0 5 0 0.59 0.82 447 WNTPATHWAY The Wnt glycoprotein binds to membrane-bound receptors such as Frizzled to activate a number of signaling pathways, including that of beta-catenin. APC, AXIN1, BTRC, CCND1, CREBBP, CSNK1A1, CSNK1D, CSNK2A1, CTBP1, CTNNB1, DVL1, FRAT1, FZD1, GSK3B, HDAC1, MADH4, MAP3K7, MAP3K7IP1, MYC, NLK, PPARD, PPP2CA, TCF1, TLE1, WIF1, WNT1 20 AXIN1(1), BTRC(3), CREBBP(8), CSNK1D(2), FZD1(1), GSK3B(2), HDAC1(2), MAP3K7(2), PPARD(1), PPP2CA(1), WIF1(1) 3927526 24 15 24 6 9 5 6 0 4 0 0.59 0.82 448 HSA05110_CHOLERA_INFECTION Genes involved in cholera - infection ACTG1, ACTG2, ADCY3, ADCY9, AK1, ARF1, ARF3, ARF4, ARF5, ARF6, ARL4D, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E1, ATP6V1A, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ERO1L, GNAS, PDIA4, PLCG1, PLCG2, PRKCA, SEC61A1, SEC61A2, SEC61B, SEC61G, TRIM23 41 ACTG2(1), ADCY3(2), ADCY9(2), ARF4(2), ATP6V0A1(3), ATP6V0A2(1), ATP6V0A4(3), ATP6V0B(1), ATP6V0D2(4), ATP6V1C2(1), ATP6V1E2(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(1), ERO1L(1), GNAS(2), PDIA4(4), PLCG1(1), PLCG2(4), PRKCA(3), SEC61A1(1), TRIM23(4) 6705474 44 21 44 15 18 13 10 0 3 0 0.60 0.82 449 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(2), GABRA2(3), GABRA3(3), GABRA4(2), GABRA5(1), GABRA6(1), PRKCE(2) 1447048 14 5 14 6 2 10 1 0 1 0 0.60 0.82 450 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 ALDH1A3(4), ALDH3B1(1), ALDH3B2(1), AOC2(1), AOC3(1), EPX(1), GOT1(2), HPD(2), LPO(1), MAOA(3), MAOB(1), MPO(2), PRDX1(1), TAT(3), TPO(4) 4021724 28 17 28 15 10 13 2 0 3 0 0.60 0.82 451 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP2(1), ACPP(2), ENPP3(2), FLAD1(1), TYR(1) 1791284 7 6 7 5 2 1 3 0 0 1 0.60 0.82 452 HSA00960_ALKALOID_BIOSYNTHESIS_II Genes involved in alkaloid biosynthesis II AADAC, ABP1, AOC2, AOC3, ARD1A, CES1, CES7, DDHD1, ESCO1, ESCO2, LIPA, LYCAT, MYST3, MYST4, NAT5, NAT6, PLA1A, PNPLA3, PPME1, PRDX6, SH3GLB1 18 AADAC(1), AOC2(1), AOC3(1), CES1(2), CES7(1), DDHD1(2), ESCO1(6), ESCO2(1), MYST3(10), MYST4(7), SH3GLB1(1) 4612140 33 16 33 13 10 11 9 1 2 0 0.60 0.82 453 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(2), BID(1), BIRC2(2), BIRC3(5), CASP10(1), CASP3(1), CASP6(2), CASP7(1), CASP8(5), CASP9(1), CFLAR(1), CHUK(4), DFFA(2), DFFB(1), MAP3K14(1), NFKB1(4), SPTAN1(7), TNFRSF10B(4) 6142536 45 19 45 16 15 14 8 0 8 0 0.60 0.82 454 TH1TH2PATHWAY Helper T subtype Th1 produces pro-inflammatory cytokines that stimulate phagocytosis, while Th2 cells promote antibody production and activate eosinophils. CD28, CD86, HLA-DRA, HLA-DRB1, IFNG, IFNGR1, IFNGR2, IL12A, IL12B, IL12RB1, IL12RB2, IL18, IL18R1, IL2, IL2RA, IL4, IL4R, TNFRSF5, TNFSF5 17 CD28(1), HLA-DRA(3), HLA-DRB1(1), IFNGR1(1), IFNGR2(1), IL12A(1), IL12B(1), IL12RB2(2), IL18R1(4), IL2(2), IL4(1) 2273702 18 8 18 4 4 9 3 0 2 0 0.60 0.82 455 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 20 AKT1(1), BCR(2), FOS(1), GRB2(2), JAK2(4), MAP2K1(2), MAP2K4(2), MAP3K1(2), MAPK3(1), MAPK8(6), RAF1(4), SOS1(3), STAT1(1), STAT5B(1) 4308534 32 14 32 5 8 10 9 1 3 1 0.60 0.82 456 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALT(1), TGDS(1), UGDH(1), UXS1(1) 743570 4 3 4 0 1 2 0 0 1 0 0.61 0.82 457 DNA_POLYMERASE POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLS 7 POLB(3), POLD1(2), POLD2(1), POLE(10), POLG(2), POLL(1), POLQ(5) 3106712 24 12 23 6 9 8 3 0 4 0 0.61 0.82 458 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 23 AKT1(1), AKT2(2), AKT3(1), GRB2(2), GSK3B(2), IRS1(4), JAK1(1), JAK3(4), MAP4K1(1), MAPK3(1), PDK1(2), PIK3CD(2), PPP1R13B(1), RAF1(4), SHC1(1), SOS1(3), SOS2(6), STAT6(1) 5722110 39 17 39 8 10 17 7 0 5 0 0.62 0.82 459 GALACTOSE_METABOLISM AKR1B1, B4GALT1, B4GALT2, FBP2, G6PC, GAA, GALE, GALK1, GALK2, GALT, GANAB, GCK, GLA, GLB1, HK1, HK2, HK3, LALBA, LCT, MGAM, PFKM, PFKP, PGM1, PGM3 24 AKR1B1(1), B4GALT1(2), FBP2(1), G6PC(1), GALK2(2), GALT(1), GANAB(1), GCK(1), GLA(1), HK1(2), HK3(1), LALBA(1), LCT(11), MGAM(4), PFKM(3), PFKP(2), PGM1(3), PGM3(2) 5922694 40 21 40 8 18 14 7 0 1 0 0.62 0.82 460 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(2), ITGA4(5), ITGAL(4), ITGAM(3), ITGB2(2), PECAM1(1), SELE(2), SELL(3), SELP(2) 3066388 24 11 24 10 5 12 4 0 3 0 0.62 0.82 461 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 60 ATP12A(7), ATP4B(1), ATP6V0A1(3), ATP6V0A4(3), ATP6V0B(1), ATP6V1B1(1), ATP6V1B2(2), ATP6V1C2(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(1), ATP7A(3), COX4I1(1), NDUFA4(1), NDUFB6(1), NDUFS1(2), NDUFS2(3), PPA2(2), SDHA(1), SHMT1(1) 6908068 37 20 37 20 10 18 6 0 3 0 0.62 0.82 462 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 CASP3(1), CASP7(1), DFFA(2), DFFB(1), GZMB(2), TOP2A(3), TOP2B(4) 1928716 14 5 14 2 2 5 4 0 3 0 0.62 0.82 463 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 22 GH1(1), GHR(1), GRB2(2), INSR(1), IRS1(4), JAK2(4), MAP2K1(2), MAPK3(1), PLCG1(1), PRKCA(3), RAF1(4), SHC1(1), SLC2A4(2), SOS1(3), STAT5B(1) 5277888 31 15 31 11 8 10 7 0 5 1 0.62 0.82 464 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 ALDOB(2), ALDOC(2), FBP2(1), GOT1(2), GPT2(1), ME1(3), ME3(3), PGK1(1), PGK2(1), TKT(1), TKTL1(3), TKTL2(3) 3602002 23 15 23 15 11 8 3 0 1 0 0.62 0.82 465 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 27 ADRBK1(1), AKT1(1), AKT2(2), AKT3(1), DAG1(3), GNAQ(1), ITPR1(8), ITPR2(6), ITPR3(7), NFKB1(4), NFKB2(2), PDK1(2), PHKA2(3), PIK3CB(1), PLD1(6), PLD2(1), PLD3(1) 8124728 50 19 50 11 21 14 6 1 7 1 0.62 0.82 466 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(1), ARG2(2), ASL(2), ASS1(1), CKM(1), CKMT2(3), CPS1(7), DAO(4), EPRS(4), GLUD2(3), GOT1(2), LAP3(1), NOS1(6), OAT(1), OTC(2), P4HA1(1), P4HA3(1), RARS(3), RARS2(2) 6406640 47 17 47 17 15 18 6 1 7 0 0.63 0.83 467 SA_TRKA_RECEPTOR The TrkA receptor binds nerve growth factor to activate MAP kinase pathways and promote cell growth. AKT1, AKT2, AKT3, ARHA, CDKN1A, ELK1, GRB2, HRAS, MAP2K1, MAP2K2, NGFB, NGFR, NTRK1, PIK3CA, PIK3CD, SHC1, SOS1 14 AKT1(1), AKT2(2), AKT3(1), CDKN1A(1), GRB2(2), MAP2K1(2), MAP2K2(1), NGFR(1), NTRK1(3), PIK3CD(2), SHC1(1), SOS1(3) 2544302 20 10 20 5 4 8 7 0 1 0 0.63 0.83 468 HSA00670_ONE_CARBON_POOL_BY_FOLATE Genes involved in one carbon pool by folate ALDH1L1, AMT, ATIC, DHFR, FTCD, GART, MTFMT, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 15 ALDH1L1(3), ATIC(1), DHFR(1), GART(1), MTFMT(1), MTHFD1(4), MTHFD1L(3), MTHFR(3), MTHFS(1), MTR(1), SHMT1(1), SHMT2(1) 3358214 21 14 21 4 8 9 4 0 0 0 0.63 0.83 469 CDK5PATHWAY Cdk5, a regulatory kinase implicated in neuronal development, represses Mek1, which downregulates the MAP kinase pathway. CDK5, CDK5R1, DPM2, EGR1, HRAS, KLK2, MAP2K1, MAP2K2, MAPK1, MAPK3, NGFB, NGFR, RAF1 11 EGR1(1), MAP2K1(2), MAP2K2(1), MAPK3(1), NGFR(1), RAF1(4) 1361436 10 6 10 2 5 2 2 0 1 0 0.63 0.83 470 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(4), EGR2(3), GNAQ(1), MAP3K1(2), NFATC1(1), NFATC2(3), NFKB1(4), PLCG1(1), PPP3CA(2), PPP3CB(2), PPP3CC(3), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), VIPR2(1) 4886618 34 16 34 11 16 7 6 0 5 0 0.63 0.83 471 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 ALDOB(2), ALDOC(2), FBP2(1), G6PD(3), GPI(1), H6PD(2), PFKM(3), PFKP(2), PGM1(3), PGM3(2), PRPS1(1), PRPS2(1), TALDO1(2), TKT(1) 3681812 26 15 26 8 12 12 1 0 1 0 0.63 0.83 472 GLOBOSIDE_METABOLISM A4GALT, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, ST8SIA1 13 FUT1(3), FUT9(2), GLA(1), HEXB(2), ST3GAL2(1), ST3GAL4(1) 1773310 10 7 10 4 4 3 3 0 0 0 0.64 0.84 473 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(1), HK1(2), PGK1(1) 1579986 6 6 6 5 1 2 3 0 0 0 0.64 0.84 474 HSA00430_TAURINE_AND_HYPOTAURINE_METABOLISM Genes involved in taurine and hypotaurine metabolism BAAT, CDO1, CSAD, GAD1, GAD2, GGT1, GGTL3, GGTL4 6 CSAD(2), GAD1(2), GAD2(2) 1047182 6 5 6 5 4 2 0 0 0 0 0.65 0.84 475 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 ALAS1(1), ALAS2(3), AOC2(1), AOC3(1), BHMT(3), CBS(2), CHDH(2), CHKA(2), CPT1B(1), CTH(1), DAO(4), DLD(1), DMGDH(2), GCAT(1), GLDC(1), MAOA(3), MAOB(1), PEMT(1), PISD(2), PLCG1(1), PLCG2(4), SARDH(2), SARS(1), SHMT1(1), SHMT2(1), TARS(4) 7706250 47 22 47 19 20 16 6 0 5 0 0.65 0.84 476 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 CAMK2D(2), DAG1(3), ITPR1(8), ITPR2(6), ITPR3(7), PDE6A(3), PDE6B(4), PDE6C(3), SLC6A13(2), TF(6) 6629148 44 18 44 6 17 14 7 0 5 1 0.65 0.84 477 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(2), ARHGDIB(1), BAG4(1), BID(1), BIRC2(2), BIRC3(5), CASP2(1), CASP3(1), CASP6(2), CASP7(1), CASP8(5), CASP9(1), CFLAR(1), CHUK(4), CRADD(1), DAXX(1), DFFA(2), DFFB(1), LMNB1(3), MAP3K1(2), MAP3K14(1), MAP3K5(3), MAPK8(6), NFKB1(4), NUMA1(5), PAK2(3), PRKDC(5), PTK2(1), RASA1(5), RB1(3), SPTAN1(7), TRAF1(1) 12683506 82 26 81 19 24 25 19 1 13 0 0.65 0.84 478 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 CD28(1), ITGAL(4), ITGB2(2), PTPRC(9) 1937232 16 7 16 7 4 7 2 0 3 0 0.66 0.84 479 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(1), EIF2AK4(1), EIF2B5(3), EIF5(1), GSK3B(2) 2096620 8 7 8 2 2 4 2 0 0 0 0.66 0.84 480 HSA00040_PENTOSE_AND_GLUCURONATE_INTERCONVERSIONS Genes involved in pentose and glucuronate interconversions AKR1B1, DCXR, GUSB, RPE, UGDH, UGP2, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, XYLB 25 AKR1B1(1), GUSB(1), UGDH(1), UGP2(3), UGT1A4(1), UGT1A6(1), UGT1A8(1), UGT1A9(1), UGT2A3(2), UGT2B11(2), UGT2B17(4), UGT2B28(1), UGT2B4(2), UGT2B7(2), XYLB(1) 4556424 24 10 24 4 2 12 5 0 5 0 0.66 0.84 481 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 ALAS1(1), ALAS2(3), AOC2(1), AOC3(1), BHMT(3), CBS(2), CHDH(2), CHKA(2), CTH(1), DAO(4), DLD(1), DMGDH(2), GCAT(1), GLDC(1), GNMT(1), MAOA(3), MAOB(1), PEMT(1), PIPOX(1), PISD(2), PSAT1(3), RDH11(1), RDH12(2), SARDH(2), SARS(1), SDS(1), SHMT1(1), SHMT2(1), TARS(4), TARS2(2) 7879554 52 22 52 23 22 20 6 0 4 0 0.66 0.84 482 STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR 10 EPX(1), LPO(1), MPO(2), PRDX1(1), TPO(4), TYR(1) 1773914 10 7 10 6 6 3 0 0 1 0 0.66 0.84 483 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), KEAP1(1), MAPK8(6), NFE2L2(3), PRKCA(3) 1551000 14 7 14 0 5 5 2 1 1 0 0.66 0.84 484 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(2), ITGA4(5), ITGAL(4), ITGB2(2), PECAM1(1), SELE(2), SELL(3) 2323108 19 8 19 7 3 10 4 0 2 0 0.66 0.84 485 BUTANOATE_METABOLISM AACS, ABAT, ACADS, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH5A1, ALDH9A1, BDH, BUCS1, ECHS1, EHHADH, GAD1, GAD2, HADHA, HMGCL, L2HGDH, OXCT1, PDHA1, PDHA2, PDHB, SDHB, SDS 27 AACS(1), ABAT(1), ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH5A1(2), ECHS1(1), GAD1(2), GAD2(2), HADHA(1), HMGCL(1), PDHA1(1), PDHA2(4), SDS(1) 4720738 30 18 30 16 16 7 4 0 3 0 0.67 0.85 486 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), IL22RA1(1), JAK1(1), JAK2(4), JAK3(4), STAT1(1), STAT3(1), STAT5B(1) 3345598 14 10 14 7 1 6 3 0 3 1 0.67 0.85 487 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 57 ALG2(1), BTK(2), CAD(4), CASP10(1), CASP3(1), CASP8(5), CASP8AP2(6), DAXX(1), DEDD(1), DFFA(2), EGFR(5), EPHB2(3), FAF1(3), IL8(1), MAP2K4(2), MAP3K1(2), MAP3K5(3), MAPK8(6), MAPK8IP3(1), MAPK9(2), MET(1), NFKB1(4), NFKB2(2), PTPN13(9), RALBP1(2), ROCK1(8), TPX2(3) 12855684 81 26 81 26 21 32 18 1 9 0 0.68 0.85 488 TUBBYPATHWAY Tubby is activated by phospholipase C activity and hydrolysis of PIP2, after which it enters the nucleus and regulates transcription. CHRM1, GNAQ, GNB1, GNGT1, HTR2C, PLCB1, TUB 7 CHRM1(1), GNAQ(1), GNGT1(1), HTR2C(2), PLCB1(1), TUB(2) 1299738 8 4 8 6 3 2 1 1 1 0 0.68 0.85 489 HSA03060_PROTEIN_EXPORT Genes involved in protein export OXA1L, SEC61A2, SRP19, SRP54, SRP68, SRP72, SRP9, SRPR 8 OXA1L(2), SRP54(3), SRP68(3), SRP72(1), SRPR(1) 1375068 10 5 10 3 2 6 1 0 1 0 0.68 0.85 490 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 64 ACSS1(1), ACSS2(1), ACYP1(2), ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH3B1(1), ALDH3B2(1), ALDH7A1(2), ALDOB(2), ALDOC(2), DLAT(1), DLD(1), ENO2(2), ENO3(2), FBP2(1), G6PC(1), G6PC2(1), GCK(1), GPI(1), HK1(2), HK3(1), LDHA(2), LDHAL6A(2), LDHAL6B(1), LDHB(2), LDHC(1), PDHA1(1), PDHA2(4), PFKM(3), PFKP(2), PGK1(1), PGK2(1), PGM1(3), PGM3(2) 10494640 72 27 72 27 23 26 17 0 6 0 0.68 0.85 491 IFNGPATHWAY IFN gamma signaling pathway IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 6 IFNGR1(1), IFNGR2(1), JAK1(1), JAK2(4), STAT1(1) 1510482 8 4 8 1 1 2 2 0 2 1 0.68 0.85 492 ST_B_CELL_ANTIGEN_RECEPTOR B cell receptors bind antigens and promote B cell activation. AKT1, AKT2, AKT3, BAD, BCR, BLNK, BTK, CD19, CSK, DAG1, EPHB2, GRB2, ITPKA, ITPKB, LYN, MAP2K1, MAP2K2, MAPK1, NFAT5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PAG, PI3, PIK3CA, PIK3CD, PIK3R1, PLCG2, PPP1R13B, RAF1, SERPINA4, SHC1, SOS1, SOS2, SYK, VAV1 37 AKT1(1), AKT2(2), AKT3(1), BCR(2), BLNK(1), BTK(2), CD19(1), CSK(2), DAG1(3), EPHB2(3), GRB2(2), MAP2K1(2), MAP2K2(1), NFKB1(4), NFKB2(2), PI3(1), PIK3CD(2), PLCG2(4), PPP1R13B(1), RAF1(4), SERPINA4(5), SHC1(1), SOS1(3), SOS2(6), SYK(3), VAV1(7) 8646228 66 24 66 15 26 21 11 1 7 0 0.68 0.86 493 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 CD28(1), ITGAL(4), ITGB2(2), PTPRC(9) 2049192 16 7 16 7 4 7 2 0 3 0 0.69 0.86 494 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(1), DDX20(1), ETS1(1), ETS2(1), ETV3(1), FOS(1), HDAC5(1), RBL1(4), RBL2(3), SIN3A(8), SIN3B(3) 4780998 25 14 25 11 11 10 2 0 2 0 0.69 0.86 495 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 23 ASAH1(1), CASP3(1), CERK(1), CREB3(2), CREB5(2), DAG1(3), EPHB2(3), FOS(1), GNAQ(1), MAP2K4(2), MAPK8(6), MAPK8IP3(1), MAPK9(2) 3711078 26 12 26 4 9 5 5 2 5 0 0.69 0.86 496 HSA00531_GLYCOSAMINOGLYCAN_DEGRADATION Genes involved in glycosaminoglycan degradation ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, HGSNAT, HPSE, HPSE2, HYAL1, HYAL2, IDS, IDUA, LCT, NAGLU, SPAM1 17 ARSB(1), GALNS(1), GNS(3), GUSB(1), HEXB(2), HPSE2(3), LCT(11), NAGLU(2), SPAM1(4) 3762830 28 14 28 6 11 8 6 1 2 0 0.70 0.86 497 GANGLIOSIDE_BIOSYNTHESIS B3GALT4, GALGT, SIAT4A, SIAT4B, SIAT7B, SIAT7D, SIAT9, ST3GAL1, ST3GAL2, ST3GAL4, ST3GAL5, ST6GALNAC2, ST6GALNAC4, ST8SIA1 8 B3GALT4(1), ST3GAL2(1), ST3GAL4(1), ST6GALNAC2(2), ST6GALNAC4(2) 1031022 7 6 7 2 1 3 3 0 0 0 0.70 0.86 498 PENTOSE_AND_GLUCURONATE_INTERCONVERSIONS AKR1B1, DCXR, GUSB, RPE, RPE, LOC440001, UCHL1, UCHL3, UGDH, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4 18 AKR1B1(1), GUSB(1), UCHL1(2), UCHL3(1), UGDH(1), UGT1A4(1), UGT1A6(1), UGT1A8(1), UGT1A9(1), UGT2B4(2) 2949112 12 7 12 3 2 7 0 0 3 0 0.70 0.86 499 HSA00750_VITAMIN_B6_METABOLISM Genes involved in vitamin B6 metabolism AOX1, PDXK, PDXP, PNPO, PSAT1 5 AOX1(3), PSAT1(3) 886042 6 3 6 1 1 4 0 0 1 0 0.70 0.86 500 HDACPATHWAY Myocyte enhancer factor MEF2 activates transcription of genes required for muscle cell differentiation and is inhibited by histone deacetylases. AKT1, AVP, CABIN1, CALM1, CALM2, CALM3, CAMK1, CAMK1G, HDAC5, IGF1, IGF1R, INS, INSR, MAP2K6, MAPK14, MAPK7, MEF2A, MEF2B, MEF2C, MEF2D, MYOD1, NFATC1, NFATC2, PIK3CA, PIK3R1, PPP3CA, PPP3CB, PPP3CC, SYT1, YWHAH 28 AKT1(1), CABIN1(5), CAMK1(2), CAMK1G(3), HDAC5(1), IGF1(1), IGF1R(2), INSR(1), MAP2K6(1), MEF2A(1), MEF2C(2), NFATC1(1), NFATC2(3), PPP3CA(2), PPP3CB(2), PPP3CC(3), YWHAH(1) 5501146 32 17 32 15 12 9 3 0 8 0 0.71 0.86 501 SA_DIACYLGLYCEROL_SIGNALING DAG (diacylglycerol) signaling activity ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP 10 ESR1(3), PDE1A(2), PDE1B(2), PLCB1(1), PRL(1), TRH(2) 2020516 11 7 11 4 4 4 1 2 0 0 0.71 0.86 502 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 ASAH1(1), DAG1(3), GNAQ(1) 1035730 5 4 5 1 1 2 1 0 1 0 0.71 0.86 503 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 FYN(1), HLA-DRA(3), HLA-DRB1(1), LCK(2), PTPRC(9), ZAP70(1) 1597490 17 6 17 1 4 8 3 0 2 0 0.71 0.86 504 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 CD44(2), CSF1(1), FCGR3A(1), IL1B(1), IL6R(1), SELL(3), SPN(1), TGFB1(1), TGFB2(4), TNFRSF8(1) 2459630 16 7 16 6 4 4 4 0 4 0 0.71 0.86 505 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 32 CHUK(4), FOS(1), IKBKB(2), MAP2K3(4), MAP2K4(2), MAP2K6(1), MAP3K1(2), MAP3K14(1), MAP3K7(2), MAPK8(6), MYD88(1), NFKB1(4), PPARA(1), TLR10(3), TLR2(4), TLR3(2), TLR4(4), TLR6(1), TLR7(5), TLR9(4), TOLLIP(1), TRAF6(1) 6697938 56 19 56 16 18 18 14 2 3 1 0.71 0.87 506 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 GOSR1(1), GOSR2(1), SEC22B(1), SNAP23(1), SNAP29(1), STX11(1), STX16(1), STX17(1), STX18(1), STX19(1), STX2(1), STX3(1), STX7(1), STX8(2), VAMP1(1), VAMP3(2), VAMP4(1), VAMP5(1), VTI1A(1), YKT6(1) 2976602 22 10 22 11 6 7 4 0 5 0 0.72 0.87 507 CHONDROITIN B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 B3GAT3(1), HS3ST1(1), HS3ST2(3), XYLT1(2), XYLT2(1) 1152396 8 4 8 1 4 1 0 1 2 0 0.72 0.88 508 HEPARAN_SULFATE_BIOSYNTHESIS B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 B3GAT3(1), HS3ST1(1), HS3ST2(3), XYLT1(2), XYLT2(1) 1152396 8 4 8 1 4 1 0 1 2 0 0.72 0.88 509 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 68 ACACB(5), ACSL3(1), ACSL4(1), ACSL5(1), ACSL6(2), ADIPOR1(1), ADIPOR2(2), AKT1(1), AKT2(2), AKT3(1), CAMKK1(1), CHUK(4), CPT1A(3), CPT1B(1), CPT2(2), G6PC(1), G6PC2(1), IKBKB(2), IRS1(4), IRS4(8), JAK1(1), JAK2(4), JAK3(4), LEPR(5), MAPK8(6), MAPK9(2), NFKB1(4), NFKB2(2), NPY(2), PCK1(3), PCK2(2), PPARA(1), PRKAA1(1), PRKAA2(4), PRKAB1(1), PRKAG2(2), PRKAG3(3), PRKCQ(2), PTPN11(4), RXRB(1), RXRG(2), SLC2A1(1), SLC2A4(2), STAT3(1) 14465990 104 31 104 35 31 39 19 2 12 1 0.72 0.88 510 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 23 ARNT(3), EIF2B2(1), EIF2B5(3), FLT1(4), FLT4(1), HIF1A(3), KDR(3), PLCG1(1), PRKCA(3), PTK2(1), SHC1(1), VHL(1) 5340348 25 15 25 13 7 8 6 0 4 0 0.73 0.89 511 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 ACP2(1), ACPP(2), ALPPL2(1), CYP3A43(2), CYP3A7(3), DHRS1(1), DHRS2(1), DHRS3(1), PON1(1), PON2(1) 3151444 14 9 14 7 6 4 2 0 1 1 0.74 0.89 512 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 46 AKT1(1), AKT2(2), AKT3(1), CAP1(1), CBL(4), CDC42(1), F2RL2(1), GRB2(2), GSK3B(2), INPPL1(3), IRS1(4), IRS4(8), LNPEP(4), MAPK3(1), PARD3(4), PARD6A(2), PDK1(2), PIK3CD(2), PPYR1(3), PTEN(4), PTPN1(4), RAF1(4), RPS6KA2(4), RPS6KA3(2), SERPINB6(1), SHC1(1), SLC2A4(2), SORBS1(7), SOS1(3), SOS2(6), YWHAH(1) 9717712 87 24 87 19 31 26 18 1 11 0 0.74 0.89 513 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(1), CCKBR(4), CCR3(2), CCR5(1), CELSR1(1), CELSR2(2), CELSR3(1), CHRM2(3), EDNRA(1), EMR2(5), EMR3(2), FSHR(2), GHRHR(1), GPR116(6), GPR133(2), GPR17(1), GPR18(2), GPR56(1), GPR77(1), GPR84(4), GRM1(5), GRPR(1), HRH4(1), LPHN2(5), LPHN3(7), PTGFR(3), SMO(1), SSTR2(1), TAAR5(2), TSHR(4) 11723154 73 28 73 35 25 22 19 1 6 0 0.74 0.89 514 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 IFNAR2(1), JAK1(1), STAT1(1), STAT2(4) 1965566 7 5 7 3 3 2 1 0 1 0 0.74 0.89 515 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 ADAM17(3), CREBBP(8), DLL1(3), DLL3(1), DLL4(1), DTX1(3), DTX2(2), DTX3(1), DVL2(2), DVL3(2), EP300(8), HDAC1(2), JAG1(2), MAML1(3), NCSTN(1), NOTCH2(6), NOTCH3(5), NOTCH4(6), PTCRA(1), RBPJ(5), SNW1(2) 11787028 67 28 67 19 24 23 9 1 10 0 0.74 0.89 516 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(1), BAIAP2(1), CASP3(1), CASP7(1), CASP8(5), INSR(1), ITCH(1), MAGI1(6), MAGI2(7), WWP1(3) 4271616 27 13 27 7 9 6 8 0 4 0 0.75 0.89 517 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 CHIT1(2), CMAS(3), CTBS(1), CYB5R1(2), GFPT1(3), GFPT2(1), HEXB(2), HK1(2), HK3(1), LHPP(1), MTMR1(2), MTMR2(1), NAGK(1), NANS(1), NPL(2), PGM3(2), PHPT1(1) 5233978 28 16 28 10 12 8 5 1 2 0 0.75 0.89 518 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 AKR1B1(1), B4GALT1(2), G6PC(1), G6PC2(1), GALK2(2), GALT(1), GANC(1), GCK(1), GLA(1), HK1(2), HK3(1), LALBA(1), LCT(11), MGAM(4), PFKM(3), PFKP(2), PGM1(3), PGM3(2), RDH11(1), RDH12(2), UGP2(3) 6960784 46 21 46 10 17 18 9 0 2 0 0.75 0.89 519 NICOTINATE_AND_NICOTINAMIDE_METABOLISM AOX1, CD38, ENPP1, ENPP3, NADSYN1, NMNAT1, NMNAT2, NNMT, NNT, NP, NT5C, NT5E, NT5M, QPRT 13 AOX1(3), CD38(2), ENPP3(2), NADSYN1(1), NMNAT1(1), NMNAT2(1), NNMT(3), NNT(3), NT5E(1) 2681092 17 8 17 8 4 7 3 0 3 0 0.76 0.90 520 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 28 CCR1(1), CCR3(2), CCR4(1), CCR5(1), CCR7(2), CD28(1), CXCR4(1), IFNGR1(1), IFNGR2(1), IL12A(1), IL12B(1), IL12RB2(2), IL18R1(4), IL2(2), IL4(1), TGFB1(1), TGFB2(4) 3652448 27 10 27 9 5 13 5 0 4 0 0.76 0.90 521 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(3), CLOCK(3), CRY1(3) 1554740 9 4 9 2 1 3 2 0 2 1 0.77 0.91 522 HSA04710_CIRCADIAN_RHYTHM Genes involved in circadian rhythm ARNTL, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, NPAS2, NR1D1, PER1, PER2, PER3 11 ARNTL(3), CLOCK(3), CRY1(3), CSNK1D(2), NPAS2(1), PER2(1), PER3(3) 3098420 16 9 16 2 3 5 4 0 3 1 0.77 0.91 523 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 59 B3GALNT1(2), B3GALT4(1), B3GALT5(2), B3GNT2(1), B3GNT3(1), B3GNT4(1), B4GALNT1(2), B4GALT1(2), B4GALT3(3), B4GALT6(2), FUT1(3), FUT3(2), FUT9(2), GCNT2(4), PIGA(1), PIGB(1), PIGG(3), PIGK(3), PIGM(3), PIGN(1), PIGO(1), PIGQ(1), PIGS(1), PIGT(2), PIGU(1), PIGV(2), PIGX(2), ST3GAL2(1), ST3GAL3(3), ST3GAL4(1), ST3GAL6(4), ST6GALNAC3(1), ST6GALNAC4(2), ST6GALNAC5(3), ST8SIA5(2), UGCG(1) 8682400 68 24 68 19 27 22 14 1 4 0 0.77 0.91 524 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(3), GPD2(1), SDHA(1) 1189436 5 4 5 0 1 1 3 0 0 0 0.78 0.91 525 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(4), IKBKB(2), IL1B(1), IL1R1(1), IL1RAP(1), IL1RN(2), IL6(2), IRAK3(2), MAP2K3(4), MAP2K6(1), MAP3K1(2), MAP3K14(1), MAP3K7(2), MAPK8(6), MYD88(1), NFKB1(4), TGFB1(1), TGFB2(4), TOLLIP(1), TRAF6(1) 5370700 43 14 43 10 16 12 9 2 4 0 0.78 0.91 526 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 CA1(1), CA3(1), CA5A(2), CA8(1), CPS1(7), CTH(1), GLUD2(3), GLUL(2), HAL(1) 3851292 19 10 19 11 5 9 2 0 3 0 0.78 0.91 527 SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES ACAT1, ACAT2, BDH, HMGCL, OXCT1 4 HMGCL(1) 618174 1 1 1 2 1 0 0 0 0 0 0.78 0.91 528 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), ASAH1(1), B4GALT6(2), CERK(1), DEGS1(1), ENPP7(1), GAL3ST1(2), GLA(1), LCT(11), NEU1(1), SGMS1(1), SGMS2(2), SGPP1(2), SGPP2(3), SMPD3(1), SPHK1(1), SPTLC1(1), UGCG(1), UGT8(3) 6189214 37 17 36 12 14 10 9 0 3 1 0.78 0.91 529 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 15 CCR5(1), IL12A(1), IL12B(1), IL12RB2(2), JAK2(4), STAT4(3) 2711230 12 7 12 3 0 5 5 0 1 1 0.78 0.91 530 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 AGMAT(4), ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH4A1(1), AMD1(1), AOC2(1), AOC3(1), ARG2(2), ASL(2), CKM(1), CKMT2(3), CPS1(7), DAO(4), GOT1(2), MAOA(3), MAOB(1), NOS1(6), OAT(1), ODC1(4), OTC(2), P4HA1(1), P4HA3(1), RARS(3) 7915616 64 22 63 25 26 20 7 1 10 0 0.78 0.91 531 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(1), CR1(3), CR2(3), HLA-DRA(3), HLA-DRB1(1), ITGAL(4), ITGB2(2), PTPRC(9) 2709092 26 9 26 8 5 14 4 0 3 0 0.79 0.91 532 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 ALDOB(2), ALDOC(2), FBP2(1), GOT1(2), GPT2(1), ME1(3), ME3(3), PGK1(1), TKT(1) 3217240 16 11 16 12 9 4 2 0 1 0 0.79 0.91 533 UCALPAINPATHWAY Calpains promote formation of integrin adhesion clusters which recruit Rac to enable the formation of mature focal adhesions that do not contain calpain. ACTA1, ACTN1, ACTN2, ACTN3, ARHA, CAPN1, CAPNS1, CAPNS2, ITGA1, ITGB1, ITGB3, PTK2, PXN, RAC1, SPTAN1, SRC, TLN1, VIL2 16 ACTA1(1), ACTN1(2), ACTN2(5), ACTN3(1), ITGA1(1), ITGB3(2), PTK2(1), SPTAN1(7), SRC(3), TLN1(3) 5326934 26 17 26 14 12 11 1 0 2 0 0.79 0.91 534 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(1), ABAT(1), ADSL(2), ADSS(1), ASL(2), ASPA(2), ASS1(1), CAD(4), CRAT(2), DARS(3), DARS2(1), DLAT(1), DLD(1), GAD1(2), GAD2(2), GOT1(2), GPT2(1), NARS(2), NARS2(3), PC(4), PDHA1(1), PDHA2(4) 6919520 45 21 45 21 22 12 9 0 2 0 0.79 0.91 535 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 14 AKT1(1), EGFR(5), IGF1R(2), POLR2A(1), PPP2CA(1), PRKCA(3), RB1(3), TEP1(3), TERF1(1), TNKS(1), XRCC5(4) 4967078 25 17 25 6 9 7 7 0 2 0 0.79 0.91 536 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 ACY1(1), ARG2(2), ASL(2), CKM(1), CKMT2(3), CPS1(7), NAGS(1), OAT(1), ODC1(4), OTC(2) 3153684 24 9 24 9 8 7 4 0 5 0 0.80 0.92 537 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 22 AKT1(1), AXIN1(1), FZD1(1), GJA1(4), GNAI1(1), GSK3B(2), LEF1(1), MYD88(1), NFKB1(4), PDPK1(1), PPP2CA(1), TLR4(4), TOLLIP(1) 3372128 23 12 23 8 11 6 6 0 0 0 0.80 0.92 538 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 CAMK1(2), CAMK1G(3), CAMK2D(2), CAMK4(1), ESRRA(1), HDAC5(1), MEF2A(1), MEF2C(2), PPARA(1), PPP3CA(2), PPP3CB(2), PPP3CC(3), SLC2A4(2), YWHAH(1) 3824840 24 10 24 10 8 7 4 0 5 0 0.80 0.92 539 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 19 AKT1(1), EIF4A2(1), EIF4B(1), EIF4G1(3), EIF4G3(7), MKNK1(1), PDK2(1), PDPK1(1), PPP2CA(1), PTEN(4), TSC1(2), TSC2(1) 4264414 24 13 24 7 5 7 7 1 4 0 0.80 0.92 540 HSA00071_FATTY_ACID_METABOLISM Genes involved in fatty acid metabolism ACAA1, ACAA2, ACADL, ACADM, ACADS, ACADSB, ACADVL, ACAT1, ACAT2, ACOX1, ACOX3, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, CPT1A, CPT1B, CPT1C, CPT2, CYP4A11, CYP4A22, DCI, ECHS1, EHHADH, GCDH, HADH, HADHA, HADHB, HSD17B10, HSD17B4, PECI 47 ACAA1(1), ACAA2(1), ACADL(2), ACADM(4), ACADVL(1), ACOX3(3), ACSL3(1), ACSL4(1), ACSL5(1), ACSL6(2), ADH1A(1), ADH1B(2), ADH1C(1), ADH4(2), ADH6(2), ADH7(1), ADHFE1(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH7A1(2), CPT1A(3), CPT1B(1), CPT2(2), CYP4A11(2), CYP4A22(1), ECHS1(1), GCDH(3), HADH(1), HADHA(1), HADHB(1), HSD17B10(1), HSD17B4(1) 8939832 58 21 58 24 17 18 14 1 8 0 0.80 0.92 541 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 CAMK1(2), CAMK1G(3), CAMK2D(2), CAMK4(1), CAMKK1(1) 2126238 9 5 9 5 1 5 2 0 1 0 0.81 0.92 542 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 ALAD(1), ALAS1(1), ALAS2(3), FECH(1), GATA1(1), HBB(2), UROD(1) 1505294 10 6 10 4 5 5 0 0 0 0 0.81 0.92 543 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ2(1), COQ6(1), NDUFA12(1) 763446 3 2 3 2 0 1 1 0 1 0 0.82 0.92 544 SULFUR_METABOLISM BPNT1, PAPSS1, PAPSS2, SULT1A2, SULT1A3, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SUOX 7 PAPSS1(1), PAPSS2(2), SULT1A2(1), SULT1E1(1), SULT2A1(1), SUOX(1) 1110132 7 3 7 0 1 4 1 0 1 0 0.82 0.92 545 CYANOAMINO_ACID_METABOLISM ATP6V0C, SHMT1, GBA3, GGT1, SHMT1, SHMT2 5 SHMT1(1), SHMT2(1) 779356 2 2 2 1 1 1 0 0 0 0 0.82 0.92 546 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 FOS(1), GRB2(2), JAK2(4), MAP2K1(2), MAPK3(1), MAPK8(6), PLCG1(1), RAF1(4), SHC1(1), SOS1(3), STAT5B(1) 3958936 26 11 26 5 6 8 7 1 3 1 0.82 0.92 547 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 15 AKT1(1), ANXA1(1), GNAS(2), GNGT1(1), NFKB1(4), NR3C1(1) 2475092 10 7 10 6 5 2 2 0 1 0 0.82 0.92 548 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 CD58(1), IL3(1), IL6(2), IL8(1), KITLG(1) 1162154 6 4 6 2 3 2 1 0 0 0 0.82 0.92 549 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), B4GALNT1(2), HEXB(2), LCT(11), SLC33A1(1), ST3GAL2(1), ST6GALNAC3(1), ST6GALNAC4(2), ST6GALNAC5(3), ST8SIA5(2) 3002624 26 12 26 7 10 10 6 0 0 0 0.82 0.92 550 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(1), BTK(2), EEA1(4), GSK3B(2), PDPK1(1), PFKM(3), PFKP(2), PLCG1(1), PRKCE(2), VAV2(3) 4612148 22 12 22 11 5 11 4 0 2 0 0.83 0.93 551 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), EGFR(5), GRB2(2), MET(1), PDGFRA(4), PRKCA(3), SH3GLB1(1), SH3GLB2(2), SH3KBP1(1), SRC(3) 3588918 26 11 26 15 10 13 3 0 0 0 0.83 0.93 552 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@ 6 CCR5(1), CD28(1) 561990 2 2 2 0 1 1 0 0 0 0 0.83 0.93 553 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(2), AASDHPPT(1), AASS(2), ALDH1A1(1), ALDH1A2(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), BBOX1(2), DLST(1), ECHS1(1), EHMT2(3), GCDH(3), HADHA(1), PLOD1(2), PLOD2(1), PLOD3(1), SDS(1), SHMT1(1), SHMT2(1), TMLHE(2) 6462688 39 18 39 11 16 11 5 0 7 0 0.83 0.93 554 GLYCOSPHINGOLIPID_METABOLISM ARSA, ARSB, ARSD, ARSE, ASAH1, GAL3ST1, GALC, GBA, GBAP, GLA, GLB1, LCT, NEU1, NEU2, NEU3, NEU4, PPAP2A, PPAP2B, PPAP2C, SMPD1, SMPD2, SPTLC1, SPTLC2, UGCG 23 ARSB(1), ARSD(1), ASAH1(1), GAL3ST1(2), GLA(1), LCT(11), NEU1(1), SPTLC1(1), UGCG(1) 4217276 20 14 20 7 8 6 4 0 2 0 0.83 0.93 555 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 15 AKT1(1), GRB2(2), MAPK3(1), MEF2A(1), MEF2C(2), NTRK1(3), PLCG1(1), SHC1(1) 2902940 12 8 12 5 1 5 3 0 3 0 0.83 0.93 556 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 DLAT(1), DLD(1), DLST(1), IDH2(1), IDH3A(3), OGDH(2), PC(4), PDHA1(1), PDHA2(4), PDK1(2), PDK2(1), PDK3(1), PDK4(2), PDP2(1), SDHA(1), SUCLA2(3), SUCLG1(1) 5241028 30 14 30 15 10 9 7 0 4 0 0.84 0.93 557 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(2), CARM1(1), CREBBP(8), EP300(8), ERCC3(3), ESR1(3), GRIP1(1), GTF2A1(1), GTF2E1(2), GTF2F1(3), HDAC1(2), HDAC3(1), HDAC4(3), HDAC5(1), HDAC6(2), MEF2C(2), NR0B1(1), NRIP1(2), POLR2A(1) 8632998 47 21 47 14 15 18 7 3 4 0 0.85 0.94 558 HSA00940_PHENYLPROPANOID_BIOSYNTHESIS Genes involved in phenylpropanoid biosynthesis EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO 7 EPX(1), LPO(1), MPO(2), TPO(4) 1547618 8 6 8 5 5 3 0 0 0 0 0.85 0.94 559 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 ACAA1(1), ACOX3(3), ELOVL2(1), FADS2(1), HADHA(1), SCD(1) 2303654 8 8 8 7 4 2 1 0 1 0 0.86 0.94 560 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(2), HEXB(2), LCT(11), MAN2B1(1), MANBA(5), NEU1(1) 3602944 24 12 24 8 8 7 6 0 3 0 0.86 0.94 561 HSA00791_ATRAZINE_DEGRADATION Genes involved in atrazine degradation ADAR, APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3F, APOBEC3G, APOBEC4 9 ADAR(2), APOBEC3F(1), APOBEC3G(1), APOBEC4(3) 1346156 7 4 7 2 2 3 2 0 0 0 0.86 0.94 562 RNA_POLYMERASE POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT 14 POLR1B(5), POLR2A(1), POLR2B(3), POLR2D(1), POLR2K(1) 2351498 11 6 11 1 4 3 4 0 0 0 0.87 0.95 563 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 EEF1B2(1), EEF2K(1), EIF2AK1(2), EIF2AK2(1), EIF2AK3(1), EIF2B2(1), EIF2B5(3), EIF4A2(1), EIF4EBP2(1), EIF4G1(3), EIF4G3(7), EIF5(1), EIF5A(1), ETF1(3), PABPC3(2), PAIP1(3), SLC35A4(1) 8012956 33 20 33 8 8 12 7 1 5 0 0.87 0.95 564 IRINOTECAN_PATHWAY_PHARMGKB ABCC1, ABCC2, ABCG2, BCHE, CES1, CES2, CES4, CYP3A4, CYP3A5, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6 16 ABCC1(3), ABCC2(5), ABCG2(5), CES1(2), UGT1A4(1), UGT1A6(1), UGT1A8(1), UGT1A9(1) 3946118 19 10 19 4 5 10 2 1 1 0 0.87 0.95 565 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 31 AKT1(1), CBL(4), CFLAR(1), FOS(1), GRB2(2), IL2RB(1), IRS1(4), JAK1(1), JAK3(4), MAPK3(1), NMI(1), RAF1(4), SHC1(1), SOS1(3), STAT5B(1), SYK(3) 5756496 33 13 33 9 7 15 4 0 7 0 0.87 0.95 566 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 8 CHUK(4), MAP3K14(1), NFKB1(4) 1711578 9 5 9 3 5 1 3 0 0 0 0.87 0.95 567 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 GPLD1(4), PGAP1(4), PIGA(1), PIGB(1), PIGG(3), PIGK(3), PIGM(3), PIGN(1), PIGO(1), PIGQ(1), PIGS(1), PIGT(2), PIGU(1), PIGV(2), PIGX(2) 4513848 30 12 29 8 9 12 6 0 3 0 0.88 0.96 568 HSA00920_SULFUR_METABOLISM Genes involved in sulfur metabolism BPNT1, CHST11, CHST12, CHST13, PAPSS1, PAPSS2, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SULT2B1, SUOX 12 CHST11(1), CHST12(1), CHST13(1), PAPSS1(1), PAPSS2(2), SULT1A2(1), SULT1E1(1), SULT2A1(1), SUOX(1) 1634172 10 5 10 2 2 5 2 0 1 0 0.89 0.96 569 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), CSNK1D(2), GSK3B(2), MAPT(1), PPP2CA(1) 1715162 7 5 7 4 4 1 2 0 0 0 0.89 0.96 570 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 18 CHUK(4), DUSP1(2), IKBKAP(1), IKBKB(2), MAP3K1(2), MAP3K14(1), NFKB1(4), TANK(3), TNFAIP3(1), TRAF1(1), TRAF3(2) 4167600 23 11 23 8 9 7 6 0 1 0 0.89 0.96 571 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 LDLR(1), MBTPS1(5), SCAP(1) 2084080 7 3 7 6 3 3 0 0 1 0 0.89 0.96 572 HSA00650_BUTANOATE_METABOLISM Genes involved in butanoate metabolism AACS, AADAC, ABAT, ACADS, ACAT1, ACAT2, ACSM1, AKR1B10, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH5A1, ALDH7A1, ALDH9A1, BDH1, BDH2, DDHD1, ECHS1, EHHADH, GAD1, GAD2, HADH, HADHA, HMGCL, HMGCS1, HMGCS2, HSD17B10, HSD17B4, HSD3B7, ILVBL, L2HGDH, OXCT1, OXCT2, PDHA1, PDHA2, PDHB, PLA1A, PPME1, PRDX6, RDH11, RDH12, RDH13, RDH14 45 AACS(1), AADAC(1), ABAT(1), ACSM1(3), ALDH1A3(4), ALDH1B1(2), ALDH2(2), ALDH3A2(1), ALDH5A1(2), ALDH7A1(2), BDH1(1), DDHD1(2), ECHS1(1), GAD1(2), GAD2(2), HADH(1), HADHA(1), HMGCL(1), HMGCS2(1), HSD17B10(1), HSD17B4(1), PDHA1(1), PDHA2(4), RDH11(1), RDH12(2) 7481738 41 19 41 22 17 12 7 0 5 0 0.90 0.96 573 RABPATHWAY Rab family GTPases regulate vesicle transport, endocytosis and exocytosis, and vesicle docking via interactions with the rabphilins. ACTA1, MEL, RAB11A, RAB1A, RAB2, RAB27A, RAB3A, RAB4A, RAB5A, RAB6A, RAB7, RAB9A 9 ACTA1(1), RAB11A(1), RAB3A(1), RAB9A(1) 793924 4 2 4 0 2 1 0 0 1 0 0.90 0.96 574 EPHA4PATHWAY Eph Kinases and ephrins support platelet aggregation ACTA1, EPHA4, EPHB1, FYN, ITGA1, ITGB1, L1CAM, LYN, RAP1B, SELP 10 ACTA1(1), EPHA4(3), EPHB1(3), FYN(1), ITGA1(1), L1CAM(2), RAP1B(1), SELP(2) 2882654 14 8 14 9 6 4 3 0 1 0 0.90 0.97 575 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(1), CDC40(2), CLK3(3), CLK4(2), COL2A1(2), CPSF1(1), CPSF2(1), CPSF3(2), CPSF4(1), CSTF1(1), CSTF2T(4), CSTF3(3), DDX1(2), DDX20(1), DHX15(2), DHX16(3), DHX38(4), DHX8(3), DHX9(1), DICER1(1), LSM2(1), METTL3(1), NCBP1(3), NCBP2(1), NONO(1), NXF1(3), PAPOLA(3), PHF5A(1), POLR2A(1), PPM1G(1), PRPF18(2), PRPF3(1), PRPF4B(7), PRPF8(3), PTBP2(1), RBM17(1), RBM5(2), RNGTT(1), RNMT(2), RNPS1(1), SF3A1(1), SF3B1(3), SFRS14(2), SFRS4(2), SNRPA(1), SNRPB(1), SNRPB2(1), SNRPD3(1), SPOP(1), SRPK1(2), SRPK2(3), SRRM1(5), SUPT5H(5), U2AF1(1), U2AF2(1), XRN2(3) 19105370 110 32 110 20 34 39 27 1 9 0 0.91 0.97 576 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 BDH1(1), HMGCL(1), HMGCS2(1) 1317242 3 3 3 4 3 0 0 0 0 0 0.91 0.98 577 MCALPAINPATHWAY In integrin-mediated cell migration, calpains digest links between the actin cytoskeleton and focal adhesion proteins. ACTA1, CAPN1, CAPN2, CAPNS1, CAPNS2, CXCR3, EGF, EGFR, HRAS, ITGA1, ITGB1, MAPK1, MAPK3, MYL2, MYLK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTK2, PXN, TLN1, VIL2 24 ACTA1(1), CAPN2(2), EGFR(5), ITGA1(1), MAPK3(1), MYLK(5), PRKACG(1), PRKAR1A(4), PRKAR1B(1), PRKAR2B(1), PTK2(1), TLN1(3) 6115308 26 16 26 12 10 9 4 0 3 0 0.92 0.98 578 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 LDLR(1), NR1H3(2), NR1H4(1) 970682 4 3 4 2 2 1 1 0 0 0 0.92 0.98 579 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 32 AKT1(1), AKT2(2), AKT3(1), BCR(2), BTK(2), CD19(1), DAPP1(1), GAB1(1), ITPR1(8), ITPR2(6), ITPR3(7), PDK1(2), PLCG2(4), PPP1R13B(1), PREX1(4), PTEN(4), PTPRC(9), RPS6KA2(4), RPS6KA3(2), SYK(3), TEC(2), VAV1(7) 9783828 74 23 74 22 24 27 11 0 11 1 0.92 0.98 580 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), IFNAR2(1), MAPK8(6), NFKB1(4), TNFRSF11A(1), TRAF6(1) 1981256 15 6 15 5 7 5 2 1 0 0 0.92 0.98 581 HSA00460_CYANOAMINO_ACID_METABOLISM Genes involved in cyanoamino acid metabolism ASRGL1, GBA, GBA3, GGT1, GGTL3, GGTL4, SHMT1, SHMT2 6 SHMT1(1), SHMT2(1) 1046612 2 2 2 2 1 1 0 0 0 0 0.92 0.98 582 FRUCTOSE_AND_MANNOSE_METABOLISM AKR1B1, ALDOA, ALDOB, ALDOC, FBP1, FBP2, FPGT, GCK, GMDS, GMPPA, GMPPB, HK1, HK2, HK3, KHK, MPI, PFKFB1, PFKFB3, PFKFB4, PFKM, PFKP, PMM1, PMM2, SORD, TPI1 25 AKR1B1(1), ALDOB(2), ALDOC(2), FBP2(1), FPGT(2), GCK(1), GMPPA(4), HK1(2), HK3(1), KHK(1), PFKFB1(2), PFKM(3), PFKP(2), PMM1(2), SORD(2) 4427774 28 14 28 10 10 13 4 0 1 0 0.92 0.98 583 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 18 ABCA1(8), APOC1(1), APOC2(1), CETP(4), CYP7A1(1), HMGCR(1), LCAT(1), LDLR(1), LIPC(1), LPL(2), LRP1(7), SCARB1(1) 4802826 29 13 29 7 13 9 4 0 3 0 0.93 0.98 584 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(1), CHUK(4), IKBKB(2), IL2(2), IL4(1), MAP3K1(2), MAP3K5(3), MAPK8(6), NFKB1(4), TNFRSF9(2) 3623958 27 10 27 6 7 12 7 1 0 0 0.93 0.98 585 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 66 ACAA1(1), ACADL(2), ACADM(4), ACOX2(1), ACOX3(3), ACSL3(1), ACSL4(1), ACSL5(1), ACSL6(2), CPT1A(3), CPT1B(1), CPT2(2), CYP27A1(1), CYP4A11(2), CYP4A22(1), CYP7A1(1), CYP8B1(1), FABP1(1), FABP2(1), FABP3(1), FABP7(1), FADS2(1), GK(1), GK2(5), HMGCS2(1), LPL(2), ME1(3), MMP1(1), NR1H3(2), OLR1(1), PCK1(3), PCK2(2), PDPK1(1), PLTP(3), PPARA(1), PPARD(1), PPARG(1), RXRB(1), RXRG(2), SCD(1), SCP2(1), SLC27A2(1), SLC27A4(1), SLC27A5(1), SLC27A6(5), SORBS1(7), UCP1(1) 11660570 82 24 82 25 28 27 17 2 8 0 0.93 0.98 586 HSA01032_GLYCAN_STRUCTURES_DEGRADATION Genes involved in degradation of glycan structures AGA, ARSB, FLJ21865, FUCA1, FUCA2, GALNS, GBA, GLB1, GNS, GUSB, HEXA, HEXB, HGSNAT, HPSE, HPSE2, HYAL1, HYAL2, IDS, IDUA, LCT, MAN2B1, MAN2B2, MAN2C1, MANBA, NAGLU, NEU1, NEU2, NEU3, NEU4, SPAM1 29 AGA(2), ARSB(1), FUCA1(2), GALNS(1), GNS(3), GUSB(1), HEXB(2), HPSE2(3), LCT(11), MAN2B1(1), MANBA(5), NAGLU(2), NEU1(1), SPAM1(4) 6210066 39 16 39 12 14 11 8 1 5 0 0.93 0.98 587 TSP1PATHWAY Thrombospondin-1 (TSP-1) inhibits angiogenesis by inducing caspase-dependent apoptosis in microvascular endothelial cells. CASP3, CD36, FOS, FYN, JUN, MAPK14, THBS1 7 CASP3(1), FOS(1), FYN(1), THBS1(3) 1333260 6 3 6 1 3 2 1 0 0 0 0.94 0.98 588 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 ALPPL2(1), ASCC3(8), DDX18(1), DDX19A(1), DDX23(1), DDX4(1), DDX50(1), DDX52(1), DDX55(2), DDX56(2), DHFR(1), DHX58(1), EP400(7), ERCC2(2), ERCC3(3), IFIH1(2), MOV10L1(7), RAD54B(3), RAD54L(1), SETX(10), SKIV2L2(2), SMARCA2(2), SMARCA5(4) 11476448 64 24 64 20 18 20 15 0 11 0 0.94 0.98 589 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 GSS(1), IL8(1), NFKB1(4), XDH(1) 1793564 7 4 7 3 4 1 2 0 0 0 0.94 0.98 590 SALMONELLAPATHWAY Salmonella induces membrane ruffling in infected cells via bacterial proteins including SipA, SipC, and SopE, which alter actin structure. ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, RAC1, WASF1, WASL 12 ACTA1(1), ACTR2(1), ACTR3(1), ARPC1B(1), ARPC2(1), CDC42(1), WASF1(2), WASL(2) 1505656 10 3 10 1 5 1 2 0 2 0 0.94 0.98 591 NITROGEN_METABOLISM AMT, ASNS, CA1, CA12, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA8, CA9, CPS1, CTH, GLS, GLS2, GLUD1, GLUL, HAL 21 CA1(1), CA3(1), CA5A(2), CA8(1), CPS1(7), CTH(1), GLUL(2), HAL(1) 3445382 16 7 16 10 5 7 1 0 3 0 0.95 0.99 592 HYPERTROPHY_MODEL ADAM10, ANKRD1, ATF3, CYR61, DUSP14, EIF4E, EIF4EBP1, GDF8, HBEGF, IFNG, IFRD1, IL18, IL1A, IL1R1, JUND, MYOG, NR4A3, TCF8, VEGF, WDR1 16 ANKRD1(3), IFRD1(3), IL1R1(1), MYOG(1), NR4A3(2) 1982408 10 4 10 1 4 3 2 0 1 0 0.95 0.99 593 HSA00625_TETRACHLOROETHENE_DEGRADATION Genes involved in tetrachloroethene degradation AKR1B10, EPHX2, HSD3B7, RDH11, RDH12, RDH13, RDH14 7 RDH11(1), RDH12(2) 877272 3 2 3 2 1 2 0 0 0 0 0.95 0.99 594 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 16 B3GAT3(1), CHPF(1), CHST11(1), CHST12(1), CHST13(1), CHSY1(1), DSE(1), XYLT1(2), XYLT2(1) 2473008 10 6 10 6 3 3 2 0 2 0 0.96 0.99 595 AMINOSUGARS_METABOLISM CMAS, CYB5R3, GCK, GFPT1, GNE, GNPDA1, GNPDA2, HEXA, HEXB, HK1, HK2, HK3, PGM3, RENBP, UAP1 15 CMAS(3), GCK(1), GFPT1(3), HEXB(2), HK1(2), HK3(1), PGM3(2) 3108130 14 7 14 3 3 8 3 0 0 0 0.96 0.99 596 TERPENOID_BIOSYNTHESIS FDFT1, FDPS, FDPS, LOC402397, IDI1, SQLE 4 FDFT1(1), SQLE(1) 616016 2 1 2 2 0 1 1 0 0 0 0.96 0.99 597 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(3), GTF2A1(1), GTF2E1(2), GTF2F1(3), HDAC3(1), NCOA1(3), NCOA2(3), NCOA3(5), POLR2A(1) 4556784 22 12 22 8 7 8 5 0 2 0 0.96 0.99 598 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(1), IL1B(1) 1055922 2 2 2 3 2 0 0 0 0 0 0.96 0.99 599 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 ALDOB(2), ALDOC(2), DLAT(1), DLD(1), ENO2(2), ENO3(2), FBP2(1), G6PC(1), GCK(1), GOT1(2), GPI(1), HK1(2), HK3(1), LDHA(2), LDHAL6B(1), LDHB(2), LDHC(1), PC(4), PCK1(3), PDHA1(1), PDHA2(4), PFKM(3), PFKP(2), PGK1(1), PGK2(1), TNFAIP1(1) 7611248 45 18 45 23 16 16 9 0 4 0 0.96 0.99 600 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(3), PRKACG(1), PRKAR2B(1) 1848722 5 4 5 4 2 2 0 0 1 0 0.97 1.00 601 BIOSYNTHESIS_OF_STEROIDS DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, IDI1, LSS, MVD, MVK, NQO1, NQO2, PMVK, SC5DL, SQLE, VKORC1 14 DHCR7(1), FDFT1(1), HMGCR(1), LSS(1), NQO2(1), SC5DL(2), SQLE(1) 2025878 8 5 8 4 4 1 3 0 0 0 0.97 1.00 602 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 AGT(2), AGTR1(3), AGTR2(1), BDKRB2(1), KNG1(1), REN(2) 1723428 10 4 10 5 2 5 1 0 2 0 0.97 1.00 603 HSA03010_RIBOSOME Genes involved in ribosome C15orf15, FAU, hCG_1644323, hCG_1984468, hCG_2041321, hCG_21078, hCG_26523, LOC283412, LOC284064, LOC284230, LOC284288, LOC284393, LOC285053, LOC342994, LOC347292, LOC388720, LOC389342, LOC390876, LOC391656, LOC400652, LOC402057, LOC439992, LOC440055, LOC440589, LOC440733, LOC440737, LOC441377, LOC441876, LOC441907, MRPL13, MRPS7, RPL10A, RPL10L, RPL11, RPL12, RPL13, RPL13A, RPL14, RPL18, RPL18A, RPL19, RPL21, RPL22L1, RPL23A, RPL23AP2, RPL24, RPL26, RPL27, RPL27A, RPL28, RPL29, RPL3, RPL30, RPL31, RPL32, RPL34, RPL35, RPL35A, RPL36A, RPL36AL, RPL37, RPL37A, RPL38, RPL39, RPL3L, RPL41, RPL6, RPL7, RPL8, RPL9, RPS10, RPS11, RPS12, RPS13, RPS15A, RPS16, RPS18, RPS2, RPS20, RPS21, RPS23, RPS24, RPS25, RPS26, RPS26P10, RPS27, RPS28, RPS29, RPS3, RPS3A, RPS4Y1, RPS5, RPS6, RPS7, RPS8, RPS9, RPSA, tcag7.23 67 FAU(1), MRPL13(1), RPL10A(1), RPL11(1), RPL19(1), RPL28(1), RPL6(2), RPL9(2), RPS15A(1), RPS16(1), RPS18(1), RPS2(1), RPS3(1), RPS9(1) 3969530 16 9 16 4 1 5 8 1 1 0 0.97 1.00 604 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(2), UBE2C(1), UBE2D3(1), UBE2I(1), UBE3A(5) 1894288 10 3 10 4 2 4 3 0 1 0 0.98 1.00 605 HSA00100_BIOSYNTHESIS_OF_STEROIDS Genes involved in biosynthesis of steroids CYP27B1, CYP51A1, DHCR24, DHCR7, EBP, FDFT1, FDPS, GGCX, GGPS1, HMGCR, HSD17B7, IDI1, IDI2, LSS, MVD, MVK, NQO1, NSDHL, PMVK, SC4MOL, SC5DL, SQLE, TM7SF2, VKORC1 24 CYP27B1(1), DHCR24(1), DHCR7(1), EBP(1), FDFT1(1), GGCX(3), GGPS1(1), HMGCR(1), LSS(1), NSDHL(1), SC4MOL(1), SC5DL(2), SQLE(1) 3541322 16 9 16 9 6 8 2 0 0 0 0.98 1.00 606 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 12 ACTR2(1), ACTR3(1), ARPC1B(1), ARPC2(1), CDC42(1), PAK1(1), PDGFRA(4), WASL(2) 1780510 12 3 12 5 4 2 4 0 2 0 0.98 1.00 607 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 EGFR(5), MAP2K1(2), MAP3K1(2), THRB(1) 3103340 10 7 10 4 4 4 2 0 0 0 0.98 1.00 608 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 AKR1B1(1), ALDOB(2), ALDOC(2), FBP2(1), FPGT(2), GMPPA(4), HK1(2), HK3(1), KHK(1), LHPP(1), MTMR1(2), MTMR2(1), PFKFB1(2), PFKM(3), PFKP(2), PHPT1(1), PMM1(2), RDH11(1), RDH12(2), SORD(2) 6831016 35 15 35 17 14 15 4 0 2 0 0.99 1.00 609 CHOLESTEROL_BIOSYNTHESIS C10orf110, CYP51A1, DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, HMGCS1, IDI1, LSS, MVD, MVK, NSDHL, PMVK, SC4MOL, SC5DL, SQLE 15 DHCR7(1), FDFT1(1), HMGCR(1), LSS(1), NSDHL(1), SC4MOL(1), SC5DL(2), SQLE(1) 2424840 9 5 9 6 4 3 2 0 0 0 0.99 1.00 610 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 22 CHUK(4), IKBKB(2), IL1R1(1), MAP3K1(2), MAP3K14(1), MAP3K7(2), MYD88(1), NFKB1(4), TLR4(4), TNFAIP3(1), TRAF6(1) 4416028 23 9 23 7 8 7 7 0 1 0 0.99 1.00 611 O_GLYCAN_BIOSYNTHESIS GALNT1, GALNT10, GALNT2, GALNT3, GALNT4, GALNT6, GALNT7, GALNT8, GALNT9, GCNT1, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, WBSCR17 13 GALNT2(2), GALNT6(1), GALNT7(1), GALNT8(1), GCNT1(2), ST3GAL2(1), ST3GAL4(1) 2413868 9 4 9 5 3 2 4 0 0 0 0.99 1.00 612 HSA00900_TERPENOID_BIOSYNTHESIS Genes involved in terpenoid biosynthesis FDFT1, FDPS, GGPS1, IDI1, IDI2, SQLE 6 FDFT1(1), GGPS1(1), SQLE(1) 813046 3 1 3 4 0 2 1 0 0 0 0.99 1.00 613 FOLATE_BIOSYNTHESIS ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, DHFR, FPGS, GCH1, GGH, SPR 9 ALPPL2(1), DHFR(1) 1122448 2 2 2 0 0 2 0 0 0 0 1.00 1.00 614 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(1), OAT(1) 1004610 2 1 2 1 1 0 1 0 0 0 1.00 1.00 615 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 92476 0 0 0 0 0 0 0 0 0 0 1.00 1.00 616 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 213324 0 0 0 0 0 0 0 0 0 0 1.00 1.00