rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q 1 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 123 ALCAM(2), CADM1(8), CADM3(8), CD2(3), CD22(11), CD226(4), CD274(4), CD28(2), CD34(1), CD4(2), CD40(1), CD40LG(6), CD58(2), CD6(3), CD80(1), CD8B(2), CDH1(5), CDH15(1), CDH3(4), CDH4(11), CDH5(2), CLDN10(4), CLDN11(1), CLDN15(1), CLDN16(5), CLDN17(5), CLDN18(1), CLDN19(1), CLDN2(1), CLDN6(2), CLDN7(2), CLDN8(5), CLDN9(1), CNTN2(7), CNTNAP1(7), CNTNAP2(12), CTLA4(2), ESAM(3), F11R(2), GLG1(4), HLA-A(3), HLA-B(3), HLA-C(2), HLA-DMA(2), HLA-DMB(2), HLA-DOA(1), HLA-DOB(1), HLA-DPA1(1), HLA-DPB1(2), HLA-DQA1(1), HLA-DQA2(3), HLA-DQB1(1), HLA-DRA(5), HLA-DRB1(3), HLA-DRB5(1), HLA-E(1), HLA-F(2), HLA-G(2), ICAM1(2), ICAM2(1), ICOS(1), ITGA4(8), ITGA6(4), ITGA8(8), ITGA9(6), ITGAL(8), ITGAM(8), ITGAV(5), ITGB1(6), ITGB2(5), ITGB7(4), ITGB8(5), JAM3(3), L1CAM(4), MAG(7), MPZL1(1), NCAM1(6), NEGR1(4), NEO1(6), NFASC(17), NLGN1(7), NLGN2(2), NLGN3(4), NRCAM(7), NRXN2(6), OCLN(1), PDCD1LG2(1), PECAM1(2), PTPRC(17), PTPRF(9), PVR(1), PVRL1(6), PVRL2(4), PVRL3(2), SDC1(1), SDC2(3), SDC3(3), SDC4(1), SELE(4), SELL(3), SELP(6), SELPLG(2), SIGLEC1(4), SPN(2), VCAM1(9), VCAN(37) 44797856 448 107 438 174 155 151 79 3 56 4 6.24e-09 3.85e-06 2 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 240 ACVR1(4), ACVR2B(5), AMHR2(2), BMP2(1), BMP7(6), BMPR1A(4), BMPR1B(10), BMPR2(11), CCL13(1), CCL15(1), CCL18(2), CCL22(1), CCL23(2), CCL27(3), CCL7(1), CCL8(1), CCR1(5), CCR3(4), CCR4(1), CCR5(1), CCR6(2), CCR7(3), CCR8(4), CCR9(6), CD27(3), CD40(1), CD40LG(6), CD70(5), CNTF(2), CNTFR(2), CSF1(2), CSF1R(3), CSF2RB(7), CSF3R(10), CX3CL1(1), CX3CR1(3), CXCL10(1), CXCL11(3), CXCL12(1), CXCL14(2), CXCL16(1), CXCL5(2), CXCL6(1), CXCL9(3), CXCR4(4), EDA(2), EDA2R(2), EDAR(3), EGF(3), EGFR(12), FAS(2), FASLG(1), FLT1(13), FLT3(5), FLT3LG(1), FLT4(5), GDF5(2), GH1(2), GH2(3), GHR(6), HGF(8), IFNA1(1), IFNA10(3), IFNA13(2), IFNA16(4), IFNA2(4), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), IFNAR1(3), IFNAR2(2), IFNB1(1), IFNG(1), IFNGR1(3), IFNGR2(2), IFNK(1), IL10(2), IL10RA(2), IL10RB(5), IL11(1), IL11RA(1), IL12A(1), IL12B(2), IL12RB1(2), IL12RB2(6), IL13(1), IL13RA1(2), IL15(2), IL15RA(1), IL17A(2), IL17RA(7), IL17RB(1), IL18RAP(4), IL19(1), IL1A(1), IL1B(1), IL1R1(4), IL1R2(7), IL1RAP(1), IL2(4), IL20(3), IL20RA(5), IL21(2), IL21R(5), IL22(2), IL22RA1(1), IL23R(3), IL24(2), IL25(1), IL26(3), IL28RA(3), IL2RA(2), IL2RB(2), IL3(3), IL4(3), IL4R(1), IL5RA(6), IL6(2), IL6R(3), IL6ST(3), IL7(2), IL7R(3), IL8(1), IL9(2), INHBB(1), INHBC(3), INHBE(1), KDR(10), KIT(8), KITLG(2), LEP(1), LEPR(9), LTB(1), LTBR(3), MET(5), MPL(2), NGFR(3), OSM(1), OSMR(6), PDGFC(3), PDGFRA(17), PDGFRB(6), PLEKHO2(5), PRL(3), PRLR(4), RELT(2), TGFB1(1), TGFB2(9), TGFBR1(9), TNFRSF10A(3), TNFRSF10B(6), TNFRSF10D(1), TNFRSF11A(3), TNFRSF11B(4), TNFRSF13B(4), TNFRSF17(2), TNFRSF19(3), TNFRSF1A(1), TNFRSF21(5), TNFRSF4(1), TNFRSF8(2), TNFRSF9(3), TNFSF10(1), TNFSF11(1), TNFSF12(2), TNFSF13(2), TNFSF13B(1), TNFSF14(3), TNFSF15(3), TNFSF18(1), TNFSF4(1), TNFSF8(1), TPO(11), TSLP(3), VEGFA(2), VEGFB(2), VEGFC(6), XCL2(1), XCR1(1) 55901212 569 118 556 195 182 208 104 0 74 1 1.47e-08 4.53e-06 3 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 143 AKT1(2), AKT2(6), AKT3(1), BCL2L1(1), CBL(5), CBLB(8), CCND2(1), CCND3(1), CNTF(2), CNTFR(2), CREBBP(25), CSF2RB(7), CSF3R(10), EP300(15), GH1(2), GH2(3), GHR(6), GRB2(3), IFNA1(1), IFNA10(3), IFNA13(2), IFNA16(4), IFNA2(4), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), IFNAR1(3), IFNAR2(2), IFNB1(1), IFNG(1), IFNGR1(3), IFNGR2(2), IFNK(1), IL10(2), IL10RA(2), IL10RB(5), IL11(1), IL11RA(1), IL12A(1), IL12B(2), IL12RB1(2), IL12RB2(6), IL13(1), IL13RA1(2), IL13RA2(3), IL15(2), IL15RA(1), IL19(1), IL2(4), IL20(3), IL20RA(5), IL21(2), IL21R(5), IL22(2), IL22RA1(1), IL23R(3), IL24(2), IL26(3), IL28RA(3), IL2RA(2), IL2RB(2), IL3(3), IL4(3), IL4R(1), IL5RA(6), IL6(2), IL6R(3), IL6ST(3), IL7(2), IL7R(3), IL9(2), IRF9(3), JAK1(4), JAK2(9), JAK3(9), LEP(1), LEPR(9), MPL(2), OSM(1), OSMR(6), PIAS1(4), PIAS2(3), PIAS3(4), PIAS4(1), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PIM1(1), PRL(3), PRLR(4), PTPN11(5), PTPN6(4), SOCS2(3), SOCS4(1), SOCS5(5), SOS1(7), SOS2(11), SPRED1(7), SPRED2(6), SPRY1(3), SPRY4(2), STAM(2), STAM2(2), STAT1(6), STAT2(7), STAT3(2), STAT4(3), STAT5B(3), STAT6(2), TPO(11), TSLP(3), TYK2(1) 45825148 418 100 410 130 143 150 76 1 46 2 2.07e-07 0.000042 4 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 82 ACVR1(4), ACVR1C(3), ACVR2B(5), ACVRL1(4), AMHR2(2), BMP2(1), BMP4(2), BMP5(5), BMP6(3), BMP7(6), BMP8A(1), BMPR1A(4), BMPR1B(10), BMPR2(11), CHRD(5), COMP(2), CREBBP(25), CUL1(9), DCN(4), E2F4(1), E2F5(2), EP300(15), FST(3), GDF5(2), GDF6(3), IFNG(1), INHBB(1), INHBC(3), INHBE(1), LTBP1(9), MAPK1(2), MAPK3(3), NODAL(1), PITX2(2), PPP2CA(1), PPP2CB(2), PPP2R1A(5), PPP2R1B(2), PPP2R2A(1), PPP2R2C(4), RBL1(5), RBL2(8), RBX1(1), RHOA(5), ROCK1(15), ROCK2(6), RPS6KB1(3), RPS6KB2(2), SKP1(1), SMAD1(2), SMAD3(9), SMAD5(1), SMAD9(3), SMURF1(3), SMURF2(2), SP1(2), TFDP1(4), TGFB1(1), TGFB2(9), TGFBR1(9), THBS1(10), THBS2(15), THBS3(3), THBS4(2), ZFYVE16(12), ZFYVE9(10) 31056032 313 89 308 105 108 100 59 1 45 0 3.05e-07 0.000047 5 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 108 A4GNT(4), ALG1(1), ALG10(3), ALG10B(8), ALG11(1), ALG12(2), ALG13(1), ALG14(1), ALG2(3), ALG3(1), ALG6(3), ALG8(6), ALG9(2), B3GNT1(2), B3GNT2(2), B3GNT7(6), B4GALT1(6), B4GALT2(3), B4GALT3(7), B4GALT5(2), C1GALT1C1(2), CHPF(3), CHST1(7), CHST11(3), CHST12(3), CHST13(2), CHST14(1), CHST2(1), CHST4(7), CHSY1(5), DAD1(2), DDOST(2), DPAGT1(2), EXT1(11), EXTL1(3), EXTL2(6), EXTL3(9), FUT11(1), FUT8(2), GALNT1(3), GALNT10(5), GALNT11(5), GALNT12(2), GALNT13(5), GALNT14(10), GALNT2(4), GALNT3(4), GALNT5(10), GALNT6(3), GALNT7(3), GALNT8(2), GALNT9(2), GALNTL1(5), GALNTL2(8), GALNTL4(2), GALNTL5(8), GANAB(4), GCNT1(5), GCNT3(4), GCNT4(7), HS2ST1(4), HS3ST1(2), HS3ST2(3), HS3ST3B1(2), HS3ST5(4), HS6ST2(2), HS6ST3(2), MAN1A1(5), MAN1A2(2), MAN1B1(2), MAN1C1(7), MAN2A1(12), MGAT1(2), MGAT3(2), MGAT4A(2), MGAT4B(1), MGAT5(3), MGAT5B(2), NDST1(4), NDST2(5), NDST3(10), NDST4(4), OGT(5), RPN2(1), ST3GAL1(1), ST3GAL2(1), ST3GAL3(4), ST3GAL4(2), ST6GAL1(1), ST6GALNAC1(3), STT3B(6), UST(1), XYLT1(7), XYLT2(2) 36725808 353 97 349 109 130 108 77 3 35 0 7.94e-07 0.000090 6 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 157 ADORA1(8), ADORA2A(5), ADORA2B(1), ADORA3(3), ADRA1A(5), ADRA1B(5), ADRA1D(2), ADRA2A(3), ADRB1(3), ADRB3(1), AGTR1(6), AGTR2(5), AVPR1A(4), AVPR1B(3), AVPR2(6), BDKRB2(3), BRS3(3), C3AR1(4), CCKAR(3), CCKBR(5), CCR1(5), CCR3(4), CCR4(1), CCR5(1), CCR6(2), CCR7(3), CCR8(4), CCR9(6), CCRL1(5), CHML(5), CHRM1(3), CHRM3(4), CHRM4(1), CHRM5(2), CMKLR1(3), CNR1(5), CX3CR1(3), CXCR4(4), DRD1(1), DRD2(5), DRD3(3), DRD5(6), EDNRA(4), F2R(1), F2RL1(1), F2RL2(3), FPR1(2), FSHR(7), GALR1(2), GALT(2), GHSR(5), GPR17(1), GPR173(2), GPR174(3), GPR37(7), GPR37L1(3), GPR4(1), GPR50(5), GPR6(6), GPR63(4), GPR77(2), GPR83(1), GPR85(1), GPR87(5), GRPR(3), HCRTR1(1), HCRTR2(1), HRH1(1), HRH2(4), HTR1A(5), HTR1B(6), HTR1D(2), HTR1F(2), HTR2A(3), HTR2B(1), HTR2C(8), HTR4(3), HTR5A(5), HTR7(7), LHCGR(4), LTB4R(1), MAS1(2), MC3R(1), MC4R(4), MC5R(7), MLNR(3), MTNR1B(3), NMUR1(4), NMUR2(9), NPY1R(4), NPY2R(5), NPY5R(2), NTSR1(1), NTSR2(5), OPN1SW(3), OPN3(1), OPRD1(1), OPRK1(5), OPRM1(3), OR12D3(4), OR1C1(3), OR1F1(2), OR2H1(4), OR5V1(3), OR7A5(3), OR8B8(3), OXTR(3), P2RY1(6), P2RY12(4), P2RY13(2), P2RY14(6), P2RY2(3), P2RY6(1), PPYR1(4), PTAFR(1), PTGDR(1), PTGER2(1), PTGFR(6), PTGIR(1), RGR(3), RHO(3), RRH(4), SSTR1(5), SSTR2(3), SSTR4(4), SUCNR1(2), TRHR(8) 38373828 435 116 433 151 172 151 78 3 31 0 8.77e-07 0.000090 7 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 84 AICDA(4), AK3(1), CAD(12), CDA(1), CTPS(4), CTPS2(4), DCK(2), DCTD(3), DHODH(4), DPYS(7), DTYMK(1), ENTPD1(2), ENTPD3(5), ENTPD4(5), ENTPD5(2), ENTPD6(3), ITPA(2), NME6(4), NME7(5), NT5C1A(1), NT5C1B(10), NT5C2(4), NT5C3(2), NT5E(3), NT5M(1), PNPT1(10), POLA1(8), POLA2(2), POLD1(5), POLD2(1), POLD3(2), POLE(21), POLE2(1), POLE3(1), POLR1A(11), POLR1B(9), POLR1C(2), POLR1D(2), POLR2A(6), POLR2B(8), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLR2K(1), POLR3A(11), POLR3B(11), POLR3GL(1), POLR3H(1), POLR3K(1), RFC5(3), RRM1(2), RRM2(3), TK1(1), TK2(1), TXNRD1(3), TXNRD2(3), TYMS(3), UCK2(1), UMPS(1), UPB1(5), UPP2(2), UPRT(4) 26661776 243 78 239 58 71 91 51 1 29 0 1.41e-06 0.00012 8 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 75 ABL1(4), ABL2(7), AKT1(2), AKT2(6), AKT3(1), ARAF(3), BAD(1), BTC(2), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CBL(5), CBLB(8), CDKN1A(1), CDKN1B(3), CRKL(2), EGF(3), EGFR(12), ERBB2(10), ERBB3(14), EREG(1), GAB1(6), GRB2(3), HBEGF(1), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK3(3), MAPK8(7), MAPK9(5), NCK1(1), NRG2(6), NRG3(7), NRG4(1), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PLCG1(4), PLCG2(13), PRKCA(4), PRKCG(10), PTK2(6), RAF1(6), RPS6KB1(3), RPS6KB2(2), SHC1(3), SHC2(1), SHC3(1), SHC4(5), SOS1(7), SOS2(11), SRC(3), STAT5B(3) 30323256 268 93 256 86 98 84 49 4 33 0 2.90e-06 0.00022 9 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 140 ADA(3), ADCY1(8), ADCY2(15), ADCY3(2), ADCY4(9), ADCY5(11), ADCY6(1), ADCY7(4), ADCY8(12), ADCY9(6), ADK(1), ADSL(7), ADSS(2), AK2(1), AK5(5), AK7(6), ALLC(5), AMPD1(9), AMPD2(5), AMPD3(3), ATIC(4), DCK(2), ENPP1(4), ENPP3(4), ENTPD1(2), ENTPD3(5), ENTPD4(5), ENTPD5(2), ENTPD6(3), FHIT(1), GART(3), GMPR(2), GMPR2(2), GMPS(5), GUCY1A2(12), GUCY1B3(9), GUCY2C(8), GUCY2D(8), GUCY2F(12), HPRT1(2), IMPDH1(2), IMPDH2(4), ITPA(2), NME6(4), NME7(5), NPR1(6), NPR2(10), NT5C1A(1), NT5C1B(10), NT5C2(4), NT5C3(2), NT5E(3), NT5M(1), NUDT9(2), PAICS(1), PAPSS1(2), PAPSS2(4), PDE10A(11), PDE11A(8), PDE1A(4), PDE1C(9), PDE3B(3), PDE4A(4), PDE4B(5), PDE4C(2), PDE4D(5), PDE5A(6), PDE6D(1), PDE7A(3), PDE7B(4), PDE8A(1), PDE8B(7), PDE9A(6), PFAS(1), PKM2(2), PNPT1(10), POLA1(8), POLA2(2), POLD1(5), POLD2(1), POLD3(2), POLE(21), POLE2(1), POLE3(1), POLR1A(11), POLR1B(9), POLR1C(2), POLR1D(2), POLR2A(6), POLR2B(8), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLR2K(1), POLR3A(11), POLR3B(11), POLR3GL(1), POLR3H(1), POLR3K(1), PPAT(6), PRPS1(1), PRPS1L1(1), PRPS2(2), PRUNE(1), RFC5(3), RRM1(2), RRM2(3), XDH(7) 54995680 500 113 493 162 166 172 91 3 68 0 4.11e-06 0.00028 10 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 121 ABL1(4), ABLIM1(6), ABLIM2(4), ABLIM3(5), ARHGEF12(9), CDC42(1), CFL1(1), CXCL12(1), CXCR4(4), DCC(16), DPYSL2(5), DPYSL5(1), EFNA3(1), EFNA4(1), EFNA5(5), EFNB1(3), EFNB2(1), EFNB3(3), EPHA1(6), EPHA2(5), EPHA4(6), EPHA6(5), EPHA7(10), EPHA8(6), EPHB1(9), EPHB2(8), EPHB3(2), EPHB4(5), EPHB6(4), FYN(5), GNAI1(4), ITGB1(6), L1CAM(4), LIMK1(5), LIMK2(5), LRRC4C(8), MAPK1(2), MAPK3(3), MET(5), NCK1(1), NFAT5(5), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), NGEF(1), NRP1(1), NTN1(5), NTN4(6), NTNG1(4), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PLXNA1(2), PLXNA2(8), PLXNA3(4), PLXNB1(5), PLXNB2(2), PLXNB3(3), PLXNC1(9), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PTK2(6), RASA1(9), RGS3(10), RHOA(5), RND1(1), ROBO2(18), ROBO3(5), ROCK1(15), ROCK2(6), SEMA3A(9), SEMA3B(1), SEMA3C(3), SEMA3D(13), SEMA3E(9), SEMA3F(1), SEMA3G(4), SEMA4A(3), SEMA4B(2), SEMA4D(13), SEMA4F(9), SEMA4G(6), SEMA5A(8), SEMA5B(11), SEMA6A(2), SEMA6B(2), SEMA6C(4), SEMA6D(9), SEMA7A(2), SLIT1(11), SLIT2(15), SLIT3(9), SRGAP1(9), SRGAP2(3), SRGAP3(4), UNC5A(2), UNC5B(6), UNC5C(12), UNC5D(9) 63260236 559 125 548 177 229 158 90 6 76 0 9.44e-06 0.00058 11 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(2), ACTR3(3), ARHGAP4(1), ARHGAP5(9), ARHGAP6(3), ARHGEF1(5), ARHGEF11(11), ARHGEF5(7), ARPC1A(5), ARPC1B(2), ARPC2(2), BAIAP2(2), CFL1(1), DIAPH1(1), LIMK1(5), MYL2(1), MYLK(14), OPHN1(7), PIP5K1A(3), PIP5K1B(2), PPP1R12B(9), ROCK1(15), SRC(3), TLN1(7), VCL(2) 15703444 122 63 120 36 40 32 24 2 24 0 0.000024 0.0014 12 HSA04612_ANTIGEN_PROCESSING_AND_PRESENTATION Genes involved in antigen processing and presentation B2M, CALR, CANX, CD4, CD74, CD8A, CD8B, CIITA, CREB1, CTSB, CTSL1, CTSS, HLA-A, HLA-A29.1, HLA-B, HLA-C, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-E, HLA-F, HLA-G, HSP90AA1, HSP90AB1, HSPA5, IFI30, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LGMN, LTA, NFYA, NFYB, NFYC, PDIA3, PSME1, PSME2, RFX5, RFXANK, RFXAP, TAP1, TAP2, TAPBP 72 CALR(1), CANX(2), CD4(2), CD74(1), CD8B(2), CIITA(7), CREB1(1), CTSB(5), CTSL1(4), CTSS(2), HLA-A(3), HLA-B(3), HLA-C(2), HLA-DMA(2), HLA-DMB(2), HLA-DOA(1), HLA-DOB(1), HLA-DPA1(1), HLA-DPB1(2), HLA-DQA1(1), HLA-DQA2(3), HLA-DQB1(1), HLA-DRA(5), HLA-DRB1(3), HLA-DRB5(1), HLA-E(1), HLA-F(2), HLA-G(2), HSP90AA1(3), HSP90AB1(3), HSPA5(2), IFI30(1), IFNA1(1), IFNA10(3), IFNA13(2), IFNA16(4), IFNA2(4), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), KIR2DL1(2), KIR2DL3(1), KIR2DL4(2), KIR3DL1(4), KIR3DL2(4), KIR3DL3(4), KLRC3(3), KLRC4(1), KLRD1(1), LGMN(3), NFYA(3), NFYB(1), NFYC(3), PDIA3(2), RFX5(1), RFXAP(1), TAP1(5), TAP2(5), TAPBP(5) 14893288 146 52 143 43 29 60 28 2 21 6 0.000082 0.0042 13 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 106 ACTN1(5), ACTN2(8), ACTN3(3), ACTN4(3), ARHGAP5(9), CDC42(1), CDH5(2), CLDN10(4), CLDN11(1), CLDN15(1), CLDN16(5), CLDN17(5), CLDN18(1), CLDN19(1), CLDN2(1), CLDN6(2), CLDN7(2), CLDN8(5), CLDN9(1), CTNNA1(12), CTNNA2(12), CTNNA3(9), CTNND1(6), CXCL12(1), CXCR4(4), CYBB(2), ESAM(3), EZR(2), F11R(2), GNAI1(4), GRLF1(12), ICAM1(2), ITGA4(8), ITGAL(8), ITGAM(8), ITGB1(6), ITGB2(5), ITK(11), JAM3(3), MAPK12(2), MAPK13(1), MAPK14(3), MLLT4(6), MMP2(5), MMP9(11), MSN(6), MYL2(1), MYL7(1), MYL9(2), NCF1(1), NCF2(2), NCF4(3), NOX1(1), NOX3(8), OCLN(1), PECAM1(2), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PLCG1(4), PLCG2(13), PRKCA(4), PRKCG(10), PTK2(6), PTK2B(1), PTPN11(5), RAP1A(2), RAP1B(2), RAPGEF3(4), RAPGEF4(7), RASSF5(3), RHOA(5), RHOH(2), ROCK1(15), ROCK2(6), SIPA1(1), TXK(5), VASP(3), VAV1(13), VAV2(4), VAV3(12), VCAM1(9), VCL(2) 40565556 399 104 392 120 165 118 69 1 46 0 0.00012 0.0055 14 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(3), AKR1D1(1), ARSD(3), ARSE(2), CARM1(2), CYP11B1(9), CYP11B2(5), CYP19A1(8), HSD11B1(1), HSD17B12(2), HSD17B2(2), HSD17B3(2), HSD17B8(1), HSD3B1(3), HSD3B2(1), LCMT1(3), LCMT2(2), METTL2B(2), METTL6(8), PRMT2(1), PRMT3(3), PRMT5(1), PRMT6(1), PRMT7(3), PRMT8(5), SRD5A1(1), SRD5A2(2), STS(7), SULT1E1(2), SULT2A1(2), SULT2B1(1), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(2), UGT1A5(3), UGT1A6(1), UGT1A7(2), UGT1A8(1), UGT1A9(6), UGT2A1(8), UGT2A3(7), UGT2B10(1), UGT2B11(6), UGT2B15(2), UGT2B17(7), UGT2B28(3), UGT2B4(3), UGT2B7(6), WBSCR22(1) 16184364 152 62 149 33 44 53 30 2 23 0 0.00019 0.0083 15 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 132 APC2(1), AXIN1(2), AXIN2(9), BTRC(5), CACYBP(2), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CCND2(1), CCND3(1), CER1(3), CHD8(6), CREBBP(25), CSNK1A1(2), CSNK1A1L(5), CSNK2A1(4), CSNK2A2(2), CSNK2B(2), CTBP1(1), CTBP2(2), CTNNBIP1(1), CUL1(9), CXXC4(1), DAAM1(2), DAAM2(9), DKK1(5), DVL2(9), DVL3(4), EP300(15), FBXW11(8), FZD1(1), FZD10(6), FZD2(2), FZD4(2), FZD6(6), FZD7(3), FZD8(1), LEF1(4), LRP5(5), LRP6(17), MAP3K7(4), MAPK8(7), MAPK9(5), MMP7(5), NFAT5(5), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), NKD1(3), NKD2(1), NLK(2), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), PORCN(2), PPARD(2), PPP2CA(1), PPP2CB(2), PPP2R1A(5), PPP2R1B(2), PPP2R2A(1), PPP2R2C(4), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PRICKLE1(11), PRICKLE2(6), PRKACA(1), PRKACB(1), PRKACG(3), PRKCA(4), PRKCG(10), PRKX(2), PSEN1(3), RBX1(1), RHOA(5), ROCK1(15), ROCK2(6), RUVBL1(8), SENP2(3), SFRP1(3), SFRP2(3), SFRP4(4), SFRP5(1), SIAH1(1), SKP1(1), SMAD3(9), SOX17(2), TBL1X(6), TBL1XR1(6), TBL1Y(1), TCF7(6), TCF7L1(3), VANGL1(2), VANGL2(5), WIF1(2), WNT1(1), WNT10B(4), WNT11(3), WNT16(2), WNT2(1), WNT2B(3), WNT3(4), WNT3A(1), WNT4(1), WNT5A(3), WNT6(1), WNT7A(2), WNT7B(2), WNT8A(2), WNT9A(2), WNT9B(2) 48697452 467 116 460 141 182 139 83 5 58 0 0.00020 0.0083 16 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 89 ADCY1(8), ADCY2(15), ADCY3(2), ADCY4(9), ADCY5(11), ADCY6(1), ADCY7(4), ADCY8(12), ADCY9(6), AKAP10(3), AKAP11(7), AKAP12(14), AKAP3(10), AKAP4(4), AKAP5(3), AKAP6(16), AKAP7(3), AKAP8(3), AKAP9(26), ARHGEF1(5), GNA11(1), GNA12(2), GNA13(2), GNA14(6), GNA15(3), GNAL(4), GNAO1(5), GNAQ(4), GNAZ(1), GNB1(1), GNB3(3), GNB5(1), GNG3(2), GNG4(1), GNG7(1), GNGT1(1), IL18BP(2), ITPR1(19), KCNJ3(6), PDE1A(4), PDE1B(3), PDE1C(9), PDE4A(4), PDE4B(5), PDE4C(2), PDE4D(5), PDE7A(3), PDE7B(4), PDE8A(1), PDE8B(7), PLCB3(4), PPP3CA(3), PPP3CC(4), PRKACA(1), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PRKCA(4), PRKCD(3), PRKCE(6), PRKCG(10), PRKCH(3), PRKCI(4), PRKCQ(5), PRKD3(8), RHOA(5), SLC9A1(4), USP5(4) 38909968 355 97 349 133 131 113 60 2 47 2 0.00025 0.0094 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 64 A2M(11), BDKRB2(3), C1QB(1), C1QC(3), C1R(3), C1S(6), C2(4), C3(12), C3AR1(4), C4BPA(7), C5(13), C5AR1(3), C6(13), C7(5), C8A(6), C9(5), CD46(3), CD55(4), CFB(4), CFH(16), CFI(2), CPB2(2), CR1(10), CR2(11), F10(1), F11(4), F12(2), F13B(5), F2(4), F2R(1), F3(2), F5(21), F7(3), F8(18), F9(6), FGB(2), FGG(4), KLKB1(6), KNG1(4), MASP1(12), MASP2(4), PLAT(5), PLAU(3), PLAUR(4), PLG(9), PROC(1), PROS1(6), SERPINA1(3), SERPINA5(4), SERPINC1(3), SERPIND1(2), SERPINE1(3), SERPING1(5), TFPI(3), THBD(2), VWF(15) 28959280 318 85 313 110 87 132 62 0 36 1 0.00026 0.0094 18 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 43 ABCA1(22), ABCA10(10), ABCA13(40), ABCA3(6), ABCA4(14), ABCA5(17), ABCA6(17), ABCA7(5), ABCA8(17), ABCA9(18), ABCB1(11), ABCB10(3), ABCB11(11), ABCB4(11), ABCB5(14), ABCB6(4), ABCB7(4), ABCB8(5), ABCB9(2), ABCC1(11), ABCC10(7), ABCC11(11), ABCC12(11), ABCC2(14), ABCC3(5), ABCC4(9), ABCC5(7), ABCC6(7), ABCC8(8), ABCC9(11), ABCD1(3), ABCD2(10), ABCD3(3), ABCD4(5), ABCG1(6), ABCG2(9), ABCG4(3), ABCG5(1), ABCG8(4), CFTR(12), TAP1(5), TAP2(5) 38041152 398 82 394 115 122 125 94 2 52 3 0.00033 0.011 19 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(12), C5(13), C6(13), C7(5), C8A(6), C9(5) 4331412 54 30 54 14 16 20 10 0 7 1 0.00038 0.012 20 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 226 ADCYAP1R1(2), ADORA1(8), ADORA2A(5), ADORA2B(1), ADORA3(3), ADRA1A(5), ADRA1B(5), ADRA2A(3), ADRA2B(1), ADRB1(3), ADRB3(1), AGTR1(6), AGTR2(5), AVPR1A(4), AVPR1B(3), AVPR2(6), BDKRB2(3), BRS3(3), C3AR1(4), C5AR1(3), CALCR(5), CALCRL(6), CCKAR(3), CCKBR(5), CGA(2), CHRM1(3), CHRM3(4), CHRM4(1), CHRM5(2), CNR1(5), CRHR1(2), CRHR2(6), CTSG(3), CYSLTR1(3), CYSLTR2(4), DRD1(1), DRD2(5), DRD3(3), DRD5(6), EDNRA(4), F2(4), F2R(1), F2RL1(1), F2RL2(3), FPR1(2), FSHB(2), FSHR(7), GABBR1(6), GABBR2(7), GABRA1(4), GABRA2(9), GABRA3(5), GABRA4(8), GABRA6(5), GABRB1(7), GABRB2(7), GABRB3(9), GABRE(5), GABRG2(11), GABRG3(5), GABRP(4), GABRQ(8), GABRR1(2), GABRR2(4), GALR1(2), GH1(2), GH2(3), GHR(6), GHRHR(2), GHSR(5), GLP1R(7), GLP2R(5), GLRA1(2), GLRA2(2), GLRA3(8), GLRB(7), GNRHR(4), GPR156(8), GPR50(5), GPR63(4), GPR83(1), GRIA2(12), GRIA3(8), GRID1(16), GRID2(12), GRIK1(5), GRIK2(14), GRIK4(12), GRIK5(6), GRIN1(1), GRIN2B(10), GRIN2C(5), GRIN2D(5), GRIN3A(6), GRM1(12), GRM2(4), GRM3(7), GRM4(7), GRM5(11), GRM6(10), GRM7(12), GRM8(9), GRPR(3), GZMA(3), HCRTR1(1), HCRTR2(1), HRH1(1), HRH2(4), HRH4(2), HTR1A(5), HTR1B(6), HTR1D(2), HTR1F(2), HTR2A(3), HTR2B(1), HTR2C(8), HTR4(3), HTR5A(5), HTR7(7), LEP(1), LEPR(9), LHB(1), LHCGR(4), LTB4R(1), MAS1(2), MC2R(5), MC3R(1), MC4R(4), MC5R(7), MCHR1(6), MCHR2(3), MLNR(3), MTNR1B(3), NMUR1(4), NMUR2(9), NPBWR1(3), NPFFR2(4), NPY1R(4), NPY2R(5), NPY5R(2), NR3C1(4), NTSR1(1), NTSR2(5), OPRD1(1), OPRK1(5), OPRM1(3), OXTR(3), P2RX1(1), P2RX2(2), P2RX3(2), P2RX4(3), P2RX5(1), P2RX7(3), P2RY1(6), P2RY13(2), P2RY14(6), P2RY2(3), P2RY4(6), P2RY6(1), PARD3(7), PPYR1(4), PRL(3), PRLR(4), PRSS1(3), PRSS2(1), PRSS3(4), PTAFR(1), PTGDR(1), PTGER2(1), PTGER3(7), PTGFR(6), PTGIR(1), PTH2R(7), RXFP1(3), RXFP2(10), SCTR(3), SSTR1(5), SSTR2(3), SSTR4(4), TAAR1(4), TAAR2(2), TAAR5(6), TAAR6(5), TAAR8(2), TAAR9(3), TACR1(2), TACR2(1), TACR3(8), THRA(2), THRB(4), TRHR(8), TRPV1(4), TSHB(1), TSHR(7), VIPR1(4), VIPR2(3) 69545496 870 152 860 329 332 287 171 9 71 0 0.00040 0.012 21 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 ADCY1(8), CREM(4), FHL5(4), FSHB(2), FSHR(7), GNAS(6), XPO1(2) 3165356 33 29 33 12 13 9 7 1 3 0 0.00043 0.013 22 HSA04110_CELL_CYCLE Genes involved in cell cycle ABL1, ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, ATM, ATR, BUB1, BUB1B, BUB3, CCNA1, CCNA2, CCNB1, CCNB2, CCNB3, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNH, CDC14A, CDC14B, CDC16, CDC2, CDC20, CDC23, CDC25A, CDC25B, CDC25C, CDC26, CDC27, CDC45L, CDC6, CDC7, CDK2, CDK4, CDK6, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CHEK1, CHEK2, CREBBP, CUL1, DBF4, E2F1, E2F2, E2F3, EP300, ESPL1, FZR1, GADD45A, GADD45B, GADD45G, GSK3B, hCG_1982709, HDAC1, HDAC2, LOC440917, LOC728919, MAD1L1, MAD2L1, MAD2L2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, PKMYT1, PLK1, PRKDC, PTTG1, PTTG2, RB1, RBL1, RBL2, RBX1, SFN, SKP1, SKP2, SMAD2, SMAD3, SMAD4, SMC1A, SMC1B, TFDP1, TGFB1, TGFB2, TGFB3, TP53, WEE1, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 104 ABL1(4), ANAPC1(4), ANAPC10(2), ANAPC2(1), ANAPC4(4), ANAPC5(3), ANAPC7(4), ATR(18), BUB1(6), BUB1B(6), BUB3(2), CCNA1(6), CCNA2(3), CCNB1(2), CCNB2(2), CCNB3(7), CCND2(1), CCND3(1), CCNE1(3), CCNE2(2), CCNH(2), CDC14A(4), CDC14B(4), CDC16(4), CDC20(3), CDC23(6), CDC25A(2), CDC25B(5), CDC25C(4), CDC27(13), CDC6(1), CDC7(3), CDK2(2), CDK4(3), CDK6(1), CDK7(1), CDKN1A(1), CDKN1B(3), CDKN2C(1), CHEK1(1), CHEK2(1), CREBBP(25), CUL1(9), DBF4(5), E2F2(1), E2F3(2), EP300(15), ESPL1(8), HDAC1(2), HDAC2(2), MAD1L1(2), MAD2L1(1), MAD2L2(1), MCM3(4), MCM4(4), MCM5(6), MCM6(4), MCM7(3), MDM2(4), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(3), PKMYT1(1), PLK1(9), PRKDC(18), PTTG1(1), RB1(7), RBL1(5), RBL2(8), RBX1(1), SKP1(1), SKP2(1), SMAD3(9), SMC1A(10), SMC1B(6), TFDP1(4), TGFB1(1), TGFB2(9), WEE1(3), YWHAB(2), YWHAE(3), YWHAH(1), YWHAQ(2) 42953024 353 84 346 100 104 109 81 7 51 1 0.00048 0.013 23 PEPTIDE_GPCRS AGTR1, AGTR2, ATP8A1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BLR1, BRS3, C3AR1, C5R1, CCKAR, CCKBR, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CX3CR1, CXCR3, CXCR4, CXCR6, EDNRA, EDNRB, ELA3A, FPR1, FPRL1, FPRL2, FSHR, FY, GALR1, GALR2, GALR3, GALT, GHSR, GNB2L1, GNRHR, GPR77, GRPR, IL8RA, IL8RB, LHCGR, MC1R, MC2R, MC3R, MC4R, MC5R, NMBR, NPY1R, NPY2R, NPY5R, NPY6R, NTSR1, NTSR2, OPRD1, OPRK1, OPRL1, OPRM1, OXTR, PPYR1, SSTR1, SSTR2, SSTR3, SSTR4, TAC4, TACR1, TACR2, TACR3, TRHR, TSHR 65 AGTR1(6), AGTR2(5), ATP8A1(9), AVPR1A(4), AVPR1B(3), AVPR2(6), BDKRB2(3), BRS3(3), C3AR1(4), CCKAR(3), CCKBR(5), CCR1(5), CCR3(4), CCR4(1), CCR5(1), CCR6(2), CCR7(3), CCR8(4), CX3CR1(3), CXCR4(4), EDNRA(4), FPR1(2), FSHR(7), GALR1(2), GALT(2), GHSR(5), GNRHR(4), GPR77(2), GRPR(3), LHCGR(4), MC2R(5), MC3R(1), MC4R(4), MC5R(7), NPY1R(4), NPY2R(5), NPY5R(2), NTSR1(1), NTSR2(5), OPRD1(1), OPRK1(5), OPRM1(3), OXTR(3), PPYR1(4), SSTR1(5), SSTR2(3), SSTR4(4), TAC4(1), TACR1(2), TACR2(1), TACR3(8), TRHR(8), TSHR(7) 16762040 202 75 201 76 76 67 47 1 11 0 0.00052 0.014 24 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(8), CD14(1), CD19(3), CD1A(3), CD1B(1), CD1C(1), CD1D(2), CD1E(6), CD2(3), CD22(11), CD33(2), CD34(1), CD36(1), CD37(2), CD38(2), CD3D(1), CD3G(2), CD4(2), CD44(3), CD5(4), CD55(4), CD7(1), CD8B(2), CD9(1), CR1(10), CR2(11), CSF1(2), CSF1R(3), CSF3R(10), DNTT(7), FCER2(1), FCGR1A(1), FLT3(5), FLT3LG(1), GP1BA(1), GP5(7), GYPA(1), HLA-DRA(5), HLA-DRB1(3), HLA-DRB5(1), IL11(1), IL11RA(1), IL1A(1), IL1B(1), IL1R1(4), IL1R2(7), IL2RA(2), IL3(3), IL4(3), IL4R(1), IL5RA(6), IL6(2), IL6R(3), IL7(2), IL7R(3), ITGA1(3), ITGA2(6), ITGA2B(4), ITGA3(4), ITGA4(8), ITGA5(7), ITGA6(4), ITGAM(8), ITGB3(9), KIT(8), KITLG(2), MME(10), MS4A1(4), TFRC(3), THPO(2), TPO(11) 27335152 269 79 263 88 101 104 37 4 21 2 0.00055 0.014 25 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(4), JAK2(9), JAK3(9), PIAS1(4), PIAS3(4), PTPRU(13), REG1A(5), SOAT1(1) 4742888 49 32 47 13 24 11 4 0 8 2 0.00058 0.014 26 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 6 CDK5R1(1), DAB1(7), FYN(5), LRP8(4), VLDLR(6) 2312944 23 20 22 10 6 9 0 1 7 0 0.00061 0.014 27 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 119 ARAF(3), BID(1), CASP3(2), CD244(3), CD247(2), FAS(2), FASLG(1), FCGR3A(1), FYN(5), GRB2(3), GZMB(2), HLA-A(3), HLA-B(3), HLA-C(2), HLA-E(1), HLA-G(2), ICAM1(2), ICAM2(1), IFNA1(1), IFNA10(3), IFNA13(2), IFNA16(4), IFNA2(4), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), IFNAR1(3), IFNAR2(2), IFNB1(1), IFNG(1), IFNGR1(3), IFNGR2(2), ITGAL(8), ITGB2(5), KIR2DL1(2), KIR2DL3(1), KIR2DL4(2), KIR3DL1(4), KIR3DL2(4), KLRC3(3), KLRD1(1), KLRK1(3), LAT(1), LCK(3), LCP2(3), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK3(3), MICB(3), NCR1(1), NCR3(1), NFAT5(5), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), PAK1(5), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PLCG1(4), PLCG2(13), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PRKCA(4), PRKCG(10), PTK2B(1), PTPN11(5), PTPN6(4), RAF1(6), SH2D1A(2), SH2D1B(1), SH3BP2(1), SHC1(3), SHC2(1), SHC3(1), SHC4(5), SOS1(7), SOS2(11), SYK(3), TNFRSF10A(3), TNFRSF10B(6), TNFRSF10D(1), TNFSF10(1), TYROBP(1), ULBP1(2), ULBP2(2), VAV1(13), VAV2(4), VAV3(12), ZAP70(4) 35773624 327 81 321 99 113 112 59 2 39 2 0.00062 0.014 28 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(9), ARHGEF1(5), GNA12(2), GNA13(2), GNAQ(4), GNB1(1), GNGT1(1), MYL2(1), MYLK(14), PLCB1(8), PPP1R12B(9), PRKCA(4), ROCK1(15) 7003500 75 40 73 20 19 22 15 2 17 0 0.00077 0.017 29 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(4), BMPR1A(4), BMPR1B(10), BMPR2(11) 2094716 29 19 28 5 6 7 8 0 8 0 0.00090 0.019 30 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(4), HLA-DRA(5), HLA-DRB1(3), IL3(3) 943012 15 13 14 4 7 5 0 0 1 2 0.00091 0.019 31 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 68 ARAF(3), C7orf16(4), CACNA1A(17), CRHR1(2), GNA11(1), GNA12(2), GNA13(2), GNAI1(4), GNAO1(5), GNAQ(4), GNAS(6), GNAZ(1), GRIA2(12), GRIA3(8), GRID2(12), GRM1(12), GRM5(11), GUCY1A2(12), GUCY1B3(9), GUCY2C(8), GUCY2D(8), GUCY2F(12), IGF1(2), IGF1R(8), ITPR1(19), ITPR2(18), ITPR3(12), LYN(4), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK3(3), NOS1(11), NOS3(2), NPR1(6), NPR2(10), PLA2G1B(1), PLA2G2F(1), PLA2G4A(8), PLA2G6(4), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), PPP2CA(1), PPP2CB(2), PPP2R1A(5), PPP2R1B(2), PPP2R2A(1), PPP2R2C(4), PRKCA(4), PRKCG(10), PRKG1(9), PRKG2(5), RAF1(6), RYR1(25) 35574356 370 103 364 141 154 119 66 2 28 1 0.0011 0.022 32 SMOOTH_MUSCLE_CONTRACTION ACTA1, ACTA2, ACTC, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADM, ADMR, ARRB1, ARRB2, ATF1, ATF2, ATF3, ATF4, ATF5, ATP2A2, ATP2A3, CACNB3, CALCA, CALM1, CALM2, CALM3, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CMKOR1, CNN1, CNN2, CORIN, CREB3, CREBL1, CREBL1, TNXB, CRH, CRHR1, DGKZ, EDG2, ETS2, FOS, GABPA, GABPB2, GBA2, GJA1, GNAQ, GNB1, GNB2, GNB3, GNB4, GNB5, GNG12, GNG13, GNG2, GNG3, GNG4, GNG5, GNG7, GNGT1, GRK4, GRK5, GRK6, GSTO1, GUCA2A, GUCA2B, GUCY1A3, HEAB, IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP6, IL1B, IL6, ITPR1, ITPR2, ITPR3, JUN, LGR7, LGR8, MAFF, MGC11266, MYL2, MYL4, MYLK2, NFKB1, NOS1, NOS3, OXT, OXTR, PDE4B, PDE4D, PKIA, PKIB, PKIG, PLCB3, PLCD1, PLCG1, PLCG2, PRKACA, PRKACB, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCH, PRKCQ, PRKCZ, PRKD1, RAMP1, RAMP2, RAMP3, RCP9, RGS1, RGS10, RGS11, RGS14, RGS16, RGS17, RGS18, RGS19, RGS2, RGS20, RGS3, RGS4, RGS5, RGS6, RGS7, RGS9, RLN1, RYR1, RYR2, RYR3, SARA1, SFN, SLC8A1, SP1, USP5, YWHAB, YWHAH, YWHAQ, YWHAQ, MIB1 135 ACTA1(4), ACTA2(3), ADCY1(8), ADCY2(15), ADCY3(2), ADCY4(9), ADCY5(11), ADCY6(1), ADCY7(4), ADCY8(12), ADCY9(6), ADM(2), ARRB1(1), ATF1(2), ATF2(1), ATF3(1), ATF4(1), ATP2A2(6), ATP2A3(4), CACNB3(2), CALCA(4), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CNN1(1), CNN2(1), CORIN(13), CREB3(3), CRHR1(2), DGKZ(3), ETS2(3), FOS(1), GABPA(4), GABPB2(3), GBA2(5), GJA1(8), GNAQ(4), GNB1(1), GNB3(3), GNB4(4), GNB5(1), GNG3(2), GNG4(1), GNG7(1), GNGT1(1), GRK4(5), GRK5(4), GRK6(3), GSTO1(1), GUCA2B(2), IGFBP1(2), IGFBP2(1), IGFBP3(4), IGFBP4(2), IL1B(1), IL6(2), ITPR1(19), ITPR2(18), ITPR3(12), MIB1(3), MYL2(1), MYL4(1), MYLK2(3), NFKB1(6), NOS1(11), NOS3(2), OXTR(3), PDE4B(5), PDE4D(5), PKIA(1), PKIB(1), PLCB3(4), PLCD1(7), PLCG1(4), PLCG2(13), PRKACA(1), PRKACB(1), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PRKCA(4), PRKCD(3), PRKCE(6), PRKCH(3), PRKCQ(5), RAMP1(1), RAMP3(4), RGS1(1), RGS10(1), RGS16(2), RGS17(2), RGS18(2), RGS2(3), RGS20(4), RGS3(10), RGS4(3), RGS5(1), RGS6(3), RGS7(6), RGS9(7), RLN1(1), RYR1(25), RYR2(59), RYR3(42), SLC8A1(13), SP1(2), TNXB(17), USP5(4), YWHAB(2), YWHAH(1), YWHAQ(2) 57520660 568 131 561 203 238 182 92 2 53 1 0.0013 0.024 33 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 ACTB(2), BAD(1), BCL2(1), CABIN1(11), CAMK2B(2), CAMK4(3), CD3G(2), CD69(1), CDKN1A(1), CNR1(5), CREBBP(25), CSNK2A1(4), CSNK2B(2), CTLA4(2), EGR2(8), EGR3(2), EP300(15), FCER1A(3), FCGR3A(1), FOS(1), GATA3(4), GATA4(1), GRLF1(12), GSK3A(2), ICOS(1), IFNA1(1), IFNB1(1), IFNG(1), IL10(2), IL13(1), IL1B(1), IL2(4), IL2RA(2), IL3(3), IL4(3), IL6(2), IL8(1), ITK(11), KPNA5(4), MAPK14(3), MAPK8(7), MAPK9(5), MEF2A(4), MEF2D(1), MYF5(4), NFAT5(5), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), NFKB2(4), NFKBIB(1), NFKBIE(2), NPPB(1), NUP214(6), OPRD1(1), P2RX7(3), PAK1(5), PIN1(1), PPP3CB(5), PPP3CC(4), PPP3R1(1), PTPRC(17), RELA(2), SLA(4), SP1(2), SP3(3), TGFB1(1), TRAF2(1), TRPV6(11), VAV1(13), VAV2(4), VAV3(12), XPO5(1) 30275432 301 78 297 103 110 90 60 4 37 0 0.0013 0.024 34 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(4), CFL1(1), GNAQ(4), GNAS(6), GNB1(1), GNGT1(1), LIMK1(5), MAP2K1(4), MAPK1(2), MAPK3(3), MYL2(1), NOX1(1), PIK3C2G(9), PLCB1(8), PPP1R12B(9), PRKCA(4), PTK2(6), RAF1(6), ROCK2(6) 8616952 81 47 79 17 30 22 13 1 15 0 0.0014 0.024 35 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(3), CDK2(2), CDKN1B(3), CKS1B(1), CUL1(9), NEDD8(1), RB1(7), RBX1(1), SKP2(1), TFDP1(4) 2933124 32 25 32 7 7 5 10 1 8 1 0.0014 0.024 36 ST_DIFFERENTIATION_PATHWAY_IN_PC12_CELLS Rat-derived PC12 cells respond to nerve growth factor (NGF) and PACAP to differentiate into neuronal cells. AKT1, ASAH1, ATF1, BRAF, CAMP, CREB1, CREB3, CREB5, CREBBP, CRKL, DAG1, EGR1, EGR2, EGR3, EGR4, ELK1, FRS2, GAS, GNAQ, GRF2, JUN, MAP1B, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, NTRK1, OPN1LW, PACAP, PIK3C2G, PIK3CA, PIK3CD, PIK3R1, PTPN11, RPS6KA3, SH2B, SHC1, SRC, TERF2IP, TH, TUBA3 37 AKT1(2), ASAH1(3), ATF1(2), CREB1(1), CREB3(3), CREB5(4), CREBBP(25), CRKL(2), DAG1(5), EGR1(3), EGR2(8), EGR3(2), FRS2(4), GNAQ(4), MAP1B(31), MAPK1(2), MAPK3(3), MAPK8(7), MAPK8IP1(4), MAPK8IP3(2), MAPK9(5), NTRK1(7), OPN1LW(1), PIK3C2G(9), PIK3CD(3), PTPN11(5), RPS6KA3(5), SHC1(3), SRC(3), TERF2IP(2) 15070528 160 62 155 56 46 50 34 2 27 1 0.0014 0.024 37 AMIPATHWAY Endogenous anti-thrombosis pathways are overwhelmed in plaque-narrowed blood vessels, resulting in potentially lethal myocardial infarction. ADCY1, CD3D, CD3E, CD3G, CD3Z, CD4, CREBBP, CSK, GNAS, GNB1, GNGT1, HLA-DRA, HLA-DRB1, LCK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTPRC, TRA@, TRB@, ZAP70 21 ADCY1(8), CD3D(1), CD3G(2), CD4(2), CREBBP(25), CSK(4), GNAS(6), GNB1(1), GNGT1(1), HLA-DRA(5), HLA-DRB1(3), LCK(3), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PTPRC(17), ZAP70(4) 7622744 95 44 95 27 33 28 18 0 14 2 0.0015 0.024 38 CSKPATHWAY Csk inhibits T-cell activation by phosphorylating Lck; Csk is regulated by cAMP-dependent kinases and is opposed by the T-cell activator CD45. ADCY1, CD3D, CD3E, CD3G, CD3Z, CD4, CREBBP, CSK, GNAS, GNB1, GNGT1, HLA-DRA, HLA-DRB1, LCK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTPRC, TRA@, TRB@, ZAP70 21 ADCY1(8), CD3D(1), CD3G(2), CD4(2), CREBBP(25), CSK(4), GNAS(6), GNB1(1), GNGT1(1), HLA-DRA(5), HLA-DRB1(3), LCK(3), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PTPRC(17), ZAP70(4) 7622744 95 44 95 27 33 28 18 0 14 2 0.0015 0.024 39 PHOSPHATIDYLINOSITOL_SIGNALING_SYSTEM ACVR1, ACVR1B, ACVRL1, AKT1, AURKB, BMPR1A, BMPR2, BUB1, CDC2L5, CDIPT, CDKL1, CDKL2, CDS1, CDS2, CLK1, CLK2, CLK4, COL4A3BP, CSNK2A1, CSNK2A1, CSNK2A1P, CSNK2A2, CSNK2B, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKQ, DGKZ, IMPA1, INPP1, INPP4A, INPP4B, INPP5A, INPPL1, ITPKA, ITPKB, MAP3K10, MOS, NEK1, NEK3, OCRL, PAK4, PCTK1, PCTK2, PIK3C2A, PIK3C2B, PIK3C2G, PIK3CA, PIK3CB, PIK3CG, PIK4CA, PIK4CA, LOC220686, PIM2, PIP5K2B, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCG1, PLCG2, PLK3, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCQ, PRKCZ, PRKD1, PRKG1, RAF1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KB1, STK11, TGFBR1, VRK1 79 ACVR1(4), ACVRL1(4), AKT1(2), AURKB(1), BMPR1A(4), BMPR2(11), BUB1(6), CDKL1(4), CDKL2(4), CDS1(2), CDS2(4), CLK1(6), CLK4(2), COL4A3BP(3), CSNK2A1(4), CSNK2A2(2), CSNK2B(2), DGKA(1), DGKB(9), DGKD(12), DGKE(3), DGKG(3), DGKH(10), DGKZ(3), IMPA1(2), INPP1(2), INPP4A(3), INPP4B(7), INPP5A(2), INPPL1(4), ITPKB(4), MAP3K10(3), MOS(3), NEK1(9), NEK3(4), OCRL(9), PIK3C2A(5), PIK3C2B(8), PIK3C2G(9), PIK3CB(2), PIK3CG(14), PIM2(1), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), PLCD1(7), PLCG1(4), PLCG2(13), PLK3(2), PRKACA(1), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PRKCA(4), PRKCD(3), PRKCE(6), PRKCG(10), PRKCH(3), PRKCQ(5), PRKG1(9), RAF1(6), RPS6KA1(1), RPS6KA2(10), RPS6KA3(5), RPS6KB1(3), TGFBR1(9), VRK1(4) 37020356 340 93 333 98 136 100 69 2 33 0 0.0015 0.024 40 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(2), CD3D(1), CD3G(2), CD80(1), CTLA4(2), GRB2(3), HLA-DRA(5), HLA-DRB1(3), ICOS(1), IL2(4), ITK(11), LCK(3), PTPN11(5) 2970320 43 24 42 10 13 19 5 0 4 2 0.0017 0.026 41 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 90 ADCY1(8), ADCY2(15), ADCY3(2), ADCY4(9), ADCY5(11), ADCY6(1), ADCY7(4), ADCY8(12), ADCY9(6), ATF4(1), CACNA1C(12), CACNA1D(9), CACNA1F(14), CACNA1S(15), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CDC42(1), CGA(2), EGFR(12), FSHB(2), GNA11(1), GNAQ(4), GNAS(6), GNRHR(4), GRB2(3), HBEGF(1), ITPR1(19), ITPR2(18), ITPR3(12), LHB(1), MAP2K1(4), MAP2K2(1), MAP2K3(6), MAP2K6(3), MAP3K1(8), MAP3K2(3), MAP3K3(3), MAPK1(2), MAPK12(2), MAPK13(1), MAPK14(3), MAPK3(3), MAPK7(3), MAPK8(7), MAPK9(5), MMP14(4), MMP2(5), PLA2G1B(1), PLA2G2F(1), PLA2G4A(8), PLA2G6(4), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), PLD1(11), PLD2(2), PRKACA(1), PRKACB(1), PRKACG(3), PRKCA(4), PRKCD(3), PRKX(2), PTK2B(1), RAF1(6), SOS1(7), SOS2(11), SRC(3) 41994656 370 101 367 135 145 114 70 5 35 1 0.0020 0.030 42 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 89 ADCY1(8), ADCY2(15), ADCY3(2), ADCY4(9), ADCY5(11), ADCY6(1), ADCY7(4), ADCY8(12), ADCY9(6), ADRB1(3), CSNK1D(4), DRD1(1), DRD2(5), EGF(3), EGFR(12), GJA1(8), GJD2(1), GNA11(1), GNAI1(4), GNAQ(4), GNAS(6), GRB2(3), GRM1(12), GRM5(11), GUCY1A2(12), GUCY1B3(9), GUCY2C(8), GUCY2D(8), GUCY2F(12), HTR2A(3), HTR2B(1), HTR2C(8), ITPR1(19), ITPR2(18), ITPR3(12), MAP2K1(4), MAP2K2(1), MAP2K5(4), MAP3K2(3), MAPK1(2), MAPK3(3), MAPK7(3), NPR1(6), NPR2(10), PDGFA(1), PDGFC(3), PDGFD(3), PDGFRA(17), PDGFRB(6), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), PRKACA(1), PRKACB(1), PRKACG(3), PRKCA(4), PRKCG(10), PRKG1(9), PRKG2(5), PRKX(2), RAF1(6), SOS1(7), SOS2(11), SRC(3), TJP1(7), TUBA1B(2), TUBA1C(2), TUBA3C(9), TUBA3D(3), TUBA3E(5), TUBA4A(3), TUBA8(2), TUBAL3(4), TUBB(1), TUBB1(2), TUBB2A(3), TUBB2B(3), TUBB3(2), TUBB4(3), TUBB4Q(2), TUBB6(3), TUBB8(3) 44008264 468 119 464 172 192 153 79 4 37 3 0.0025 0.037 43 FLUMAZENILPATHWAY Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 8 GABRA1(4), GABRA2(9), GABRA3(5), GABRA4(8), GABRA6(5), GPX1(1), PRKCE(6) 2378852 38 22 37 6 11 17 6 0 4 0 0.0035 0.049 44 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(3), ADH1C(4), ADH4(2), ADH5(1), ADH6(6), ADH7(2), ADHFE1(6), AKR1C2(4), AKR1C3(2), AKR1C4(3), ALDH1A3(6), ALDH3A1(2), ALDH3B1(3), ALDH3B2(1), CYP1A1(7), CYP1A2(3), CYP1B1(3), CYP2C18(2), CYP2C19(4), CYP2C8(4), CYP2C9(7), CYP2E1(6), CYP2F1(4), CYP2S1(3), CYP3A4(1), CYP3A43(2), CYP3A5(3), CYP3A7(6), DHDH(1), EPHX1(5), GSTA1(1), GSTA3(4), GSTA5(2), GSTM2(2), GSTM3(3), GSTM4(2), GSTM5(1), GSTO2(1), GSTZ1(2), MGST1(2), MGST3(1), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(2), UGT1A5(3), UGT1A6(1), UGT1A7(2), UGT1A8(1), UGT1A9(6), UGT2A1(8), UGT2A3(7), UGT2B10(1), UGT2B11(6), UGT2B15(2), UGT2B17(7), UGT2B28(3), UGT2B4(3), UGT2B7(6) 18602456 190 63 189 45 47 65 52 1 24 1 0.0035 0.049 45 COMPLEMENT_ACTIVATION_CLASSICAL C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C9, DAF, MASP1 12 C1QB(1), C1R(3), C1S(6), C2(4), C3(12), C5(13), C6(13), C7(5), C8A(6), C9(5), MASP1(12) 6647924 80 39 80 26 26 28 14 0 11 1 0.0036 0.050 46 TCRAPATHWAY The kinases Lck and Fyn phosphorylate and activate the T cell receptor, which recognizes antigen-bound MHCII and leads to T cell activation. CD3D, CD3E, CD3G, CD3Z, CD4, FYN, HLA-DRA, HLA-DRB1, LCK, PTPRC, TRA@, TRB@, ZAP70 10 CD3D(1), CD3G(2), CD4(2), FYN(5), HLA-DRA(5), HLA-DRB1(3), LCK(3), PTPRC(17), ZAP70(4) 3009476 42 23 42 9 10 16 6 0 8 2 0.0042 0.056 47 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 BMPR1B(10), CCND2(1), CDK4(3), CDKN1B(3), DAZL(2), DMC1(4), EGR1(3), ESR2(3), FSHR(7), GJA4(2), INHA(2), LHCGR(4), MLH1(8), MSH5(5), NCOR1(12), NRIP1(6), PGR(4), PRLR(4), PTGER2(1), SMPD1(6), VDR(2), ZP2(7) 9571248 99 44 99 31 33 25 23 2 16 0 0.0044 0.058 48 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 AHCY(3), BHMT(5), CBS(3), CTH(2), DNMT1(19), DNMT3A(9), DNMT3B(9), MARS(6), MARS2(1), MAT1A(5), MAT2B(3), MTR(7) 5898820 72 39 67 16 35 18 6 3 10 0 0.0049 0.062 49 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 68 ACP1(2), ACTB(2), ACTN1(5), ACTN2(8), ACTN3(3), ACTN4(3), ACVR1C(3), BAIAP2(2), CDC42(1), CDH1(5), CREBBP(25), CSNK2A1(4), CSNK2A2(2), CSNK2B(2), CTNNA1(12), CTNNA2(12), CTNNA3(9), CTNND1(6), EGFR(12), EP300(15), ERBB2(10), FARP2(5), FER(7), FGFR1(4), FYN(5), IGF1R(8), INSR(6), IQGAP1(13), LEF1(4), LMO7(19), MAP3K7(4), MAPK1(2), MAPK3(3), MET(5), MLLT4(6), NLK(2), PARD3(7), PTPN1(5), PTPN6(4), PTPRB(4), PTPRF(9), PTPRJ(4), PVRL1(6), PVRL2(4), PVRL3(2), PVRL4(4), RHOA(5), SMAD3(9), SNAI1(1), SNAI2(2), SORBS1(11), SRC(3), SSX2IP(4), TCF7(6), TCF7L1(3), TGFBR1(9), TJP1(7), VCL(2), WAS(1), WASF1(3), WASF2(2), WASF3(5), WASL(7), YES1(2) 36981708 367 89 360 114 143 117 63 4 39 1 0.0049 0.062 50 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 83 AGRN(1), CD36(1), CD44(3), CD47(3), CHAD(7), COL11A1(24), COL11A2(11), COL1A1(11), COL1A2(16), COL2A1(9), COL3A1(12), COL4A1(14), COL4A2(4), COL4A4(10), COL4A6(15), COL5A1(16), COL5A2(13), COL5A3(10), COL6A2(1), COL6A6(20), DAG1(5), FN1(22), FNDC1(23), FNDC3A(8), FNDC4(1), GP1BA(1), GP5(7), GP6(2), HMMR(6), HSPG2(9), IBSP(3), ITGA1(3), ITGA10(7), ITGA11(4), ITGA2(6), ITGA2B(4), ITGA3(4), ITGA4(8), ITGA5(7), ITGA6(4), ITGA7(6), ITGA8(8), ITGA9(6), ITGAV(5), ITGB1(6), ITGB3(9), ITGB4(3), ITGB5(6), ITGB6(6), ITGB7(4), ITGB8(5), LAMA1(24), LAMA2(25), LAMA3(18), LAMA4(11), LAMB1(8), LAMB2(5), LAMB3(9), LAMB4(16), LAMC1(11), LAMC2(10), LAMC3(8), SDC1(1), SDC2(3), SDC3(3), SDC4(1), SPP1(1), SV2A(5), SV2B(6), SV2C(4), THBS1(10), THBS2(15), THBS3(3), THBS4(2), TNC(16), TNN(17), TNXB(17), VTN(6), VWF(15) 70717952 669 135 663 275 231 238 113 9 77 1 0.0053 0.065 51 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(3), JAK1(4), JAK2(9), JAK3(9), PIAS3(4), PTPRU(13), REG1A(5), SRC(3), STAT3(2) 5233144 54 35 52 20 28 15 3 0 6 2 0.0055 0.066 52 1_AND_2_METHYLNAPHTHALENE_DEGRADATION ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 7 ADH1A(1), ADH1B(3), ADH1C(4), ADH4(2), ADH6(6), ADH7(2), ADHFE1(6) 1888992 24 19 24 9 3 9 11 0 1 0 0.0056 0.067 53 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 28 ACVR1(4), ATF2(1), AXIN1(2), BMP10(3), BMP2(1), BMP4(2), BMP5(5), BMP7(6), BMPR1A(4), BMPR2(11), CHRD(5), FZD1(1), GATA4(1), MAP3K7(4), MEF2C(9), MYL2(1), NKX2-5(1), NPPA(1), NPPB(1), RFC1(14), TGFB1(1), TGFB2(9), TGFBR1(9), TGFBR3(8), WNT1(1) 8912252 105 40 102 28 36 32 18 0 19 0 0.0061 0.071 54 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(8), BAD(1), BAK1(1), BAX(1), BCL10(3), BCL2(1), BCL2L1(1), BCL2L11(3), BID(1), CASP8AP2(18), CASP9(2), CES1(5) 3871512 45 28 43 10 13 16 8 0 8 0 0.0073 0.084 55 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(3), C1S(6), C2(4), C3(12), C5(13), C6(13), C7(5), C8A(6), C9(5), MASP1(12), MASP2(4) 7255088 84 41 84 28 26 30 16 0 11 1 0.0076 0.085 56 GPCRDB_CLASS_C_METABOTROPIC_GLUTAMATE_PHEROMONE CASR, GABBR1, GPCR5A, GPR51, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GRM1, GRM2, GRM3, GRM4, GRM5, GRM7, GRM8 13 CASR(7), GABBR1(6), GPRC5A(2), GPRC5B(2), GPRC5C(2), GPRC5D(1), GRM1(12), GRM2(4), GRM3(7), GRM4(7), GRM5(11), GRM7(12), GRM8(9) 6796908 82 48 80 48 35 23 14 1 9 0 0.0077 0.085 57 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(4), FMOD(2), KERA(7), LUM(6) 1221008 20 16 20 4 7 4 7 0 2 0 0.0079 0.085 58 GAMMA_HEXACHLOROCYCLOHEXANE_DEGRADATION ACP1, ACP2, ACP5, ACPP, ACPT, ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, CYP19A1, CYP1A1, CYP1A2, CYP2A6, CYP2A6, CYP2A7, CYP2A7P1, CYP2A13, CYP2B6, CYP2C18, CYP2C19, CYP2C19, CYP2C9, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP3A4, CYP3A5, CYP3A7, CYP4B1, CYP4F8, CYP51A1, PON1 31 ACP1(2), ACP2(2), ACP5(1), ACPP(4), ALPI(2), ALPL(1), ALPP(1), ALPPL2(1), CYP19A1(8), CYP1A1(7), CYP1A2(3), CYP2A13(7), CYP2A6(6), CYP2A7(5), CYP2C18(2), CYP2C19(4), CYP2C8(4), CYP2C9(7), CYP2E1(6), CYP2F1(4), CYP2J2(3), CYP3A4(1), CYP3A5(3), CYP3A7(6), CYP4B1(9), CYP4F8(4), CYP51A1(3), PON1(6) 9878588 112 52 110 25 40 31 28 0 11 2 0.0088 0.093 59 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_NEOLACTOSERIES ABO, B3GNT1, FUT1, FUT2, FUT9, GCNT2, ST8SIA1 7 ABO(2), B3GNT1(2), FUT1(4), FUT2(1), FUT9(5), GCNT2(10), ST8SIA1(3) 2048552 27 18 27 7 10 8 5 0 4 0 0.0095 0.100 60 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(8), ARHGEF1(5), F2(4), F2R(1), GNA12(2), GNA13(2), GNAI1(4), GNAQ(4), GNB1(1), GNGT1(1), MAP3K7(4), PLCB1(8), PPP1R12B(9), PRKCA(4), PTK2B(1), ROCK1(15) 7465068 73 36 72 25 23 20 15 2 13 0 0.010 0.10 61 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(11), EXTL1(3), EXTL2(6), EXTL3(9), GLCE(6), HS2ST1(4), HS3ST1(2), HS3ST2(3), HS3ST3B1(2), HS3ST5(4), HS6ST2(2), HS6ST3(2), NDST1(4), NDST2(5), NDST3(10), NDST4(4) 7050708 77 45 76 25 31 21 18 1 6 0 0.011 0.11 62 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 61 ADCY1(8), ADCY8(12), ARAF(3), ATF4(1), CACNA1C(12), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CAMK4(3), CREBBP(25), EP300(15), GNAQ(4), GRIA2(12), GRIN1(1), GRIN2B(10), GRIN2C(5), GRIN2D(5), GRM1(12), GRM5(11), ITPR1(19), ITPR2(18), ITPR3(12), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK3(3), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), PPP1CB(2), PPP1CC(2), PPP1R12A(3), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PRKACA(1), PRKACB(1), PRKACG(3), PRKCA(4), PRKCG(10), PRKX(2), RAF1(6), RAP1A(2), RAP1B(2), RAPGEF3(4), RPS6KA1(1), RPS6KA2(10), RPS6KA3(5) 31657272 303 86 301 115 125 81 63 3 30 1 0.011 0.11 63 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 136 ADCY1(8), ADCY2(15), ADCY3(2), ADCY4(9), ADCY5(11), ADCY6(1), ADCY7(4), ADCY8(12), ADCY9(6), ADRA1A(5), ADRA1B(5), ADRA1D(2), ADRB1(3), ADRB3(1), ANXA6(3), ARRB1(1), ATP1A4(8), ATP1B1(1), ATP1B2(2), ATP2A2(6), ATP2A3(4), ATP2B1(9), ATP2B2(11), ATP2B3(4), CACNA1A(17), CACNA1B(11), CACNA1C(12), CACNA1D(9), CACNA1E(21), CACNA1S(15), CACNB1(1), CACNB3(2), CALR(1), CAMK1(3), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CAMK4(3), CASQ1(2), CASQ2(4), CHRM1(3), CHRM3(4), CHRM4(1), CHRM5(2), GJA1(8), GJA4(2), GJA5(3), GJB1(3), GJB3(4), GJB4(1), GNA11(1), GNAO1(5), GNAQ(4), GNAZ(1), GNB1(1), GNB3(3), GNB4(4), GNB5(1), GNG3(2), GNG4(1), GNG7(1), GNGT1(1), GRK4(5), GRK5(4), GRK6(3), ITPR1(19), ITPR2(18), ITPR3(12), KCNB1(5), KCNJ3(6), KCNJ5(4), MIB1(3), MYCBP(1), NME7(5), PEA15(1), PKIA(1), PKIB(1), PLCB3(4), PLN(1), PRKACA(1), PRKACB(1), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PRKCA(4), PRKCD(3), PRKCE(6), PRKCG(10), PRKCH(3), PRKCQ(5), RGS1(1), RGS10(1), RGS16(2), RGS17(2), RGS18(2), RGS2(3), RGS20(4), RGS3(10), RGS4(3), RGS5(1), RGS6(3), RGS7(6), RGS9(7), RYR1(25), RYR2(59), RYR3(42), SLC8A1(13), SLC8A3(7), USP5(4), YWHAB(2), YWHAH(1), YWHAQ(2) 63856100 633 142 628 265 276 197 103 1 54 2 0.012 0.12 64 ACETYLCHOLINE_SYNTHESIS ACHE, CHAT, CHKA, PCYT1A, PDHA1, PDHA2, PEMT, SLC18A3 8 ACHE(2), CHAT(6), CHKA(4), PCYT1A(5), PDHA1(5), PDHA2(8), PEMT(1), SLC18A3(6) 2386116 37 26 36 17 12 12 10 0 3 0 0.012 0.12 65 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(2), CD4(2), CD80(1), HLA-DRA(5), HLA-DRB1(3), IL10(2), IL2(4), IL4(3) 1281264 22 14 22 8 8 11 0 0 1 2 0.013 0.12 66 TRYPTOPHAN_METABOLISM AANAT, ABP1, ACAT1, ACAT2, ACMSD, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, AOC2, AOC3, AOX1, ASMT, CAT, CYP19A1, CYP1A1, CYP1A2, CYP2A6, CYP2A6, CYP2A7, CYP2A7P1, CYP2A13, CYP2B6, CYP2C18, CYP2C19, CYP2C19, CYP2C9, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP3A4, CYP3A5, CYP3A7, CYP4B1, CYP4F8, CYP51A1, DDC, ECHS1, EHHADH, GCDH, HAAO, HADHA, INDO, KMO, KYNU, MAOA, MAOB, SDS, TDO2, TPH1, WARS, WARS2 53 ABP1(1), ACAT1(1), ACAT2(2), ACMSD(4), ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), AOC2(4), AOC3(4), AOX1(8), CAT(3), CYP19A1(8), CYP1A1(7), CYP1A2(3), CYP2A13(7), CYP2A6(6), CYP2A7(5), CYP2C18(2), CYP2C19(4), CYP2C8(4), CYP2C9(7), CYP2E1(6), CYP2F1(4), CYP2J2(3), CYP3A4(1), CYP3A5(3), CYP3A7(6), CYP4B1(9), CYP4F8(4), CYP51A1(3), DDC(1), ECHS1(2), EHHADH(2), GCDH(5), HAAO(2), HADHA(3), KMO(5), KYNU(6), MAOA(3), MAOB(1), SDS(2), TDO2(4), TPH1(3), WARS(3), WARS2(3) 18384232 197 68 196 56 68 68 43 1 16 1 0.013 0.12 67 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(2), CD4(2), HLA-DRA(5), HLA-DRB1(3) 743664 12 10 12 4 4 5 0 0 1 2 0.014 0.13 68 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 11 CDH1(5), CREBBP(25), EP300(15), MAP2K1(4), MAP3K7(4), MAPK3(3), SKIL(1), TGFB1(1), TGFB2(9), TGFBR1(9) 6357648 76 38 75 20 26 18 18 1 13 0 0.015 0.13 69 HSA00271_METHIONINE_METABOLISM Genes involved in methionine metabolism AHCY, AMD1, BHMT, CBS, CTH, DNMT1, DNMT3A, DNMT3B, KIAA0828, MARS, MARS2, MAT1A, MAT2B, MTAP, MTFMT, MTR, SRM, TAT 17 AHCY(3), AMD1(1), BHMT(5), CBS(3), CTH(2), DNMT1(19), DNMT3A(9), DNMT3B(9), MARS(6), MARS2(1), MAT1A(5), MAT2B(3), MTAP(1), MTFMT(2), MTR(7), TAT(5) 7033116 81 41 76 19 36 25 6 3 11 0 0.017 0.15 70 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(2), CALCR(5), CALCRL(6), CD97(5), CRHR1(2), CRHR2(6), ELTD1(7), EMR1(9), EMR2(7), GHRHR(2), GLP1R(7), GLP2R(5), GPR64(6), LPHN1(4), LPHN2(13), LPHN3(17), SCTR(3), VIPR1(4), VIPR2(3) 9335368 113 48 110 36 42 37 23 0 11 0 0.017 0.15 71 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 EGF(3), EGFR(12), ERBB3(14), UBE2D1(1) 2779952 30 25 26 5 15 8 5 1 1 0 0.019 0.17 72 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(4), CD4(2), HLA-DRA(5), HLA-DRB1(3), IL1B(1), IL4(3), IL5RA(6), IL6(2) 1735984 26 16 25 8 11 12 0 0 1 2 0.020 0.17 73 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 10 CDC25A(2), CDC25B(5), CDC25C(4), CDK2(2), CDK4(3), CHEK1(1), MYT1(13), RB1(7), WEE1(3), YWHAH(1) 3601648 41 27 40 7 12 14 9 2 3 1 0.022 0.18 74 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 11 ACE2(9), AGT(5), AGTR1(6), AGTR2(5), COL4A1(14), COL4A2(4), COL4A3(4), COL4A4(10), COL4A6(15), REN(5) 7587156 77 38 76 15 20 25 17 1 14 0 0.022 0.18 75 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(2), AKT2(6), AKT3(1), BAD(1), CASP9(2), CDC42(1), KDR(10), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK12(2), MAPK13(1), MAPK14(3), MAPK3(3), MAPKAPK2(3), MAPKAPK3(1), NFAT5(5), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), NOS3(2), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PLA2G1B(1), PLA2G2F(1), PLA2G4A(8), PLA2G6(4), PLCG1(4), PLCG2(13), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PRKCA(4), PRKCG(10), PTGS2(3), PTK2(6), RAF1(6), SH2D2A(2), SHC2(1), SPHK1(1), SPHK2(1), SRC(3), VEGFA(2) 22726392 177 66 173 67 84 42 27 0 24 0 0.023 0.19 76 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(4), CYP2C9(7) 676032 11 9 11 2 3 3 4 0 1 0 0.024 0.19 77 HSA04614_RENIN_ANGIOTENSIN_SYSTEM Genes involved in renin-angiotensin system ACE, ACE2, AGT, AGTR1, AGTR2, ANPEP, CMA1, CPA3, CTSA, CTSG, ENPEP, LNPEP, MAS1, MME, NLN, REN, THOP1 17 ACE(2), ACE2(9), AGT(5), AGTR1(6), AGTR2(5), ANPEP(8), CPA3(3), CTSA(3), CTSG(3), ENPEP(9), LNPEP(8), MAS1(2), MME(10), NLN(3), REN(5) 7110260 81 43 81 17 22 29 19 0 11 0 0.025 0.20 78 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(3), GNAQ(4), GNB1(1), GNGT1(1), HTR2C(8), PLCB1(8), TUB(5) 2402460 30 20 30 10 14 5 6 1 4 0 0.026 0.21 79 GSPATHWAY Activated G-protein coupled receptors stimulate cAMP production and thus activate protein kinase A, involved in a number of signal transduction pathways. ADCY1, GNAS, GNB1, GNGT1, PRKACA, PRKAR1A 6 ADCY1(8), GNAS(6), GNB1(1), GNGT1(1), PRKACA(1), PRKAR1A(5) 2167436 22 20 22 10 8 7 5 0 2 0 0.026 0.21 80 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(5), CDC40(4), CLK3(3), CLK4(2), COL2A1(9), CPSF1(5), CPSF2(1), CPSF3(2), CPSF4(4), CSTF1(2), CSTF2T(7), CSTF3(4), DDX1(4), DDX20(4), DHX15(3), DHX16(6), DHX38(11), DHX8(6), DHX9(6), DICER1(8), DNAJC8(2), LSM2(1), METTL3(4), NCBP1(6), NCBP2(1), NONO(2), NUDT21(1), NXF1(7), PABPN1(1), PAPOLA(3), PHF5A(1), POLR2A(6), PPM1G(1), PRPF18(4), PRPF3(1), PRPF4(4), PRPF4B(9), PRPF8(11), PSKH1(1), PTBP1(1), PTBP2(4), RBM17(2), RBM5(3), RNGTT(6), RNMT(4), RNPS1(1), SF3A1(3), SF3A2(1), SF3A3(1), SF3B1(10), SF3B2(2), SF3B4(4), SFRS14(2), SFRS4(2), SNRPA(1), SNRPB(1), SNRPB2(1), SNRPD3(1), SNRPE(2), SNRPN(2), SNURF(1), SPOP(2), SRPK1(9), SRPK2(4), SRRM1(11), SUPT5H(11), TXNL4A(1), U2AF1(2), U2AF2(4), XRN2(8) 35458112 269 77 269 74 85 76 64 3 41 0 0.027 0.21 81 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 88 AKT1(2), AKT2(6), AKT3(1), BCL10(3), CARD11(9), CBL(5), CBLB(8), CD247(2), CD28(2), CD3D(1), CD3G(2), CD4(2), CD40LG(6), CD8B(2), CDC42(1), CDK4(3), CHUK(6), CTLA4(2), FOS(1), FYN(5), GRAP2(5), GRB2(3), ICOS(1), IFNG(1), IKBKB(4), IL10(2), IL2(4), IL4(3), ITK(11), LAT(1), LCK(3), LCP2(3), MALT1(7), MAP3K14(3), MAP3K8(2), NCK1(1), NFAT5(5), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), NFKB1(6), NFKB2(4), NFKBIB(1), NFKBIE(2), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PDK1(2), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PLCG1(4), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PRKCQ(5), PTPN6(4), PTPRC(17), RASGRP1(5), RHOA(5), SOS1(7), SOS2(11), TEC(3), VAV1(13), VAV2(4), VAV3(12), ZAP70(4) 32675016 315 82 311 105 123 106 52 2 32 0 0.028 0.21 82 HSA00602_GLYCOSPHINGOLIPID_BIOSYNTHESIS_NEO_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - neo-lactoseries ABO, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALT1, B4GALT2, B4GALT3, B4GALT4, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GCNT2, ST3GAL6, ST8SIA1 21 ABO(2), B3GNT1(2), B3GNT2(2), B3GNT3(1), B3GNT4(1), B3GNT5(1), B4GALT1(6), B4GALT2(3), B4GALT3(7), FUT1(4), FUT2(1), FUT3(4), FUT6(1), FUT9(5), GCNT2(10), ST3GAL6(7), ST8SIA1(3) 5195836 60 34 60 14 25 16 12 1 6 0 0.028 0.21 83 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(18), CPT1A(6), LEP(1), LEPR(9), PRKAA1(3), PRKAA2(9), PRKAB1(2), PRKAB2(1), PRKAG1(1), PRKAG2(3) 4891292 53 29 51 20 20 17 10 0 6 0 0.029 0.21 84 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(6) 242816 6 5 6 0 4 1 0 0 1 0 0.030 0.22 85 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 51 ADORA3(3), ALG6(3), CCKBR(5), CCR3(4), CCR5(1), CELSR1(8), CELSR2(9), CELSR3(6), CHRM3(4), EDNRA(4), EMR2(7), EMR3(8), F2R(1), FSHR(7), GHRHR(2), GNRHR(4), GPR116(11), GPR132(1), GPR133(8), GPR143(2), GPR17(1), GPR18(2), GPR55(1), GPR56(2), GPR61(4), GPR77(2), GPR84(6), GPR88(1), GRM1(12), GRPR(3), HRH4(2), LPHN2(13), LPHN3(17), NTSR1(1), OR8G2(1), P2RY13(2), PTGFR(6), SMO(1), SSTR2(3), TAAR5(6), TSHR(7), VN1R1(4) 21630120 195 74 189 81 77 56 39 5 18 0 0.031 0.23 86 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(5), ACO2(2), FH(1), IDH1(3), IDH2(7), MDH1(1), MDH2(1), SDHB(2), SUCLA2(5) 3003212 27 23 27 9 9 8 6 0 4 0 0.032 0.23 87 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(8), AKT1(2), ASAH1(3), GNAI1(4), GNB1(1), GNGT1(1), ITGAV(5), ITGB3(9), MAPK1(2), MAPK3(3), PDGFA(1), PDGFRA(17), PLCB1(8), PRKCA(4), PTK2(6), SMPD1(6), SPHK1(1), SRC(3) 7930692 84 41 84 32 27 24 20 2 10 1 0.032 0.23 88 MPRPATHWAY Progesterone binding to its intracellular receptor activates the MAPK pathway and induces oocyte maturation; binding to membrane receptor inhibits adenylyl cyclase. ACTA1, ADCY1, CAP1, CCNB1, CDC2, CDC25C, GNAI1, GNAS, GNB1, GNGT1, HRAS, MAPK1, MAPK3, MYT1, PIN1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RPS6KA1, SRC 22 ACTA1(4), ADCY1(8), CAP1(1), CCNB1(2), CDC25C(4), GNAI1(4), GNAS(6), GNB1(1), GNGT1(1), MAPK1(2), MAPK3(3), MYT1(13), PIN1(1), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), RPS6KA1(1), SRC(3) 6838796 67 46 66 22 26 27 10 0 4 0 0.034 0.23 89 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 5 ADAM17(7), NRG2(6), NRG3(7), PRKCA(4), PSEN1(3) 2126880 27 19 26 2 10 8 3 1 5 0 0.034 0.23 90 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(3), C1S(6), C2(4), C3(12), C5(13), C6(13), C7(5), C8A(6), C9(5) 5951592 68 31 68 20 21 24 12 0 10 1 0.034 0.23 91 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 92 ADCY1(8), ADCY2(15), ADCY3(2), ADCY4(9), ADCY5(11), ADCY6(1), ADCY7(4), ADCY8(12), ADCY9(6), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CREB1(1), CREB3(3), CREB3L1(3), CREB3L2(4), CREB3L3(3), CREB3L4(1), CREBBP(25), DCT(13), DVL2(9), DVL3(4), EDN1(1), EP300(15), FZD1(1), FZD10(6), FZD2(2), FZD4(2), FZD6(6), FZD7(3), FZD8(1), GNAI1(4), GNAO1(5), GNAQ(4), GNAS(6), KIT(8), KITLG(2), LEF1(4), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK3(3), MITF(5), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), POMC(2), PRKACA(1), PRKACB(1), PRKACG(3), PRKCA(4), PRKCG(10), PRKX(2), RAF1(6), TCF7(6), TCF7L1(3), TYR(3), TYRP1(2), WNT1(1), WNT10B(4), WNT11(3), WNT16(2), WNT2(1), WNT2B(3), WNT3(4), WNT3A(1), WNT4(1), WNT5A(3), WNT6(1), WNT7A(2), WNT7B(2), WNT8A(2), WNT9A(2), WNT9B(2) 34306904 329 98 326 136 136 99 55 6 33 0 0.034 0.23 92 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 11 APAF1(8), ARHGAP5(9), ARHGDIB(3), CASP1(2), CASP10(2), CASP3(2), CASP9(2), GZMB(2) 3934756 30 24 29 10 4 11 7 0 8 0 0.034 0.23 93 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(12), C5(13), C6(13), C7(5), ICAM1(2), IL1A(1), IL6(2), IL8(1), ITGA4(8), ITGAL(8), ITGB1(6), ITGB2(5), SELP(6), SELPLG(2), VCAM1(9) 8384284 93 42 91 29 32 31 18 0 11 1 0.035 0.23 94 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 53 ADH1A(1), ADH1B(3), ADH1C(4), ADH4(2), ADH5(1), ADH6(6), ADH7(2), ADHFE1(6), AGK(3), AGPAT1(2), AGPAT3(3), AGPAT6(2), AKR1B1(3), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(3), ALDH9A1(1), CEL(1), DAK(4), DGAT2(4), DGKA(1), DGKB(9), DGKD(12), DGKE(3), DGKG(3), DGKH(10), DGKI(10), DGKZ(3), GK(3), GK2(6), GLA(4), GLB1(3), GPAM(3), LCT(20), LIPA(1), LIPC(4), LIPF(3), LIPG(2), LPL(6), MGLL(1), PNLIP(7), PNLIPRP1(4), PNLIPRP2(2), PNPLA3(4), PPAP2B(1) 19401284 198 62 198 66 64 77 42 0 15 0 0.035 0.23 95 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 B3GNT1(2), B3GNT2(2), B3GNT7(6), B4GALT1(6), B4GALT2(3), B4GALT3(7), CHST1(7), CHST2(1), CHST4(7), FUT8(2), ST3GAL1(1), ST3GAL2(1), ST3GAL3(4), ST3GAL4(2) 4036676 51 32 51 15 29 6 10 1 5 0 0.036 0.23 96 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 10 DNM1(11), GABRA1(4), GABRA2(9), GABRA3(5), GABRA4(8), GABRA6(5), NSF(1), SRC(3), UBQLN1(2) 3231760 48 25 46 19 11 23 9 0 5 0 0.038 0.24 97 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 30 ADRA1A(5), ADRA1B(5), ADRA1D(2), ADRA2A(3), ADRB1(3), ADRB3(1), CHRM1(3), CHRM3(4), CHRM4(1), CHRM5(2), DRD1(1), DRD2(5), DRD3(3), DRD5(6), HRH1(1), HRH2(4), HTR1A(5), HTR1B(6), HTR1D(2), HTR1F(2), HTR2A(3), HTR2B(1), HTR2C(8), HTR4(3), HTR5A(5), HTR7(7) 7968192 91 47 90 40 44 26 11 1 9 0 0.038 0.24 98 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@ 15 CD28(2), CD3D(1), CD3G(2), IFNG(1), IL2(4), IL2RA(2), IL4(3), TGFB1(1), TGFB2(9), TGFBR1(9), TGFBR3(8), TOB1(2), TOB2(2) 3205320 46 21 45 13 17 15 6 0 8 0 0.038 0.24 99 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(5), EGFR(12), ERBB2(10), ETS1(1), ETS2(3), ETV6(5), FMN2(7), GRB2(3), MAP2K1(4), MAPK1(2), MAPK3(3), NOTCH2(13), NOTCH3(15), NOTCH4(7), PIWIL1(8), PIWIL2(10), PIWIL3(10), PIWIL4(8), RAF1(6), SOS1(7), SOS2(11), SPIRE1(3), SPIRE2(1) 15615084 154 65 149 43 54 55 31 2 12 0 0.041 0.25 100 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(6), CCNE1(3), CDK2(2), CUL1(9), RB1(7), SKP2(1), TFDP1(4) 2955912 32 22 32 8 7 6 11 1 6 1 0.042 0.26 101 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 ARFIP2(2), CDK5R1(1), CFL1(1), CHN1(2), LIMK1(5), MAP3K1(8), MYL2(1), MYLK(14), NCF2(2), PAK1(5), PDGFRA(17), PLD1(11), PPP1R12B(9), RALBP1(6), RPS6KB1(3), TRIO(13), VAV1(13), WASF1(3) 10561304 116 49 114 33 39 36 21 2 17 1 0.042 0.26 102 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(12), GNAS(6), GNB1(1), GNGT1(1), GRB2(3), IGF1R(8), ITGB1(6), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK3(3), MKNK1(1), MKNK2(3), NGFR(3), PDGFRA(17), PPP2CA(1), PTPRR(5), RAF1(6), RPS6KA1(1), RPS6KA5(6), SHC1(3), SOS1(7), SRC(3), STAT3(2) 11021748 105 53 102 37 37 34 24 0 8 2 0.044 0.27 103 HSA00380_TRYPTOPHAN_METABOLISM Genes involved in tryptophan metabolism AADAT, AANAT, ABP1, ACAT1, ACAT2, ACMSD, AFMID, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, AOC2, AOC3, AOX1, ASMT, CARM1, CAT, CYP1A1, CYP1A2, CYP1B1, DDC, ECHS1, EHHADH, GCDH, HAAO, HADH, HADHA, HEMK1, HSD17B10, HSD17B4, INDO, INDOL1, INMT, KMO, KYNU, LCMT1, LCMT2, LNX1, MAOA, MAOB, METTL2B, METTL6, NFX1, OGDH, OGDHL, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, TDO2, TPH1, TPH2, WARS, WARS2, WBSCR22 57 AADAT(1), ABP1(1), ACAT1(1), ACAT2(2), ACMSD(4), AFMID(1), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(3), ALDH9A1(1), AOC2(4), AOC3(4), AOX1(8), CARM1(2), CAT(3), CYP1A1(7), CYP1A2(3), CYP1B1(3), DDC(1), ECHS1(2), EHHADH(2), GCDH(5), HAAO(2), HADH(1), HADHA(3), HSD17B10(2), HSD17B4(3), INMT(2), KMO(5), KYNU(6), LCMT1(3), LCMT2(2), LNX1(11), MAOA(3), MAOB(1), METTL2B(2), METTL6(8), NFX1(8), OGDH(4), OGDHL(11), PRMT2(1), PRMT3(3), PRMT5(1), PRMT6(1), PRMT7(3), PRMT8(5), TDO2(4), TPH1(3), TPH2(8), WARS(3), WARS2(3), WBSCR22(1) 20235148 193 68 191 60 66 66 38 3 20 0 0.045 0.27 104 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 54 ASH1L(24), ASH2L(2), C17orf79(1), CARM1(2), CTCFL(8), DOT1L(3), EED(2), EHMT1(2), EHMT2(3), EZH1(5), EZH2(4), FBXO11(5), HSF4(1), JMJD6(2), KDM6A(1), MEN1(2), MLL(21), MLL2(17), MLL3(16), MLL4(11), MLL5(17), NSD1(14), OGT(5), PAXIP1(7), PPP1CB(2), PPP1CC(2), PRDM2(15), PRDM7(2), PRMT1(1), PRMT5(1), PRMT6(1), PRMT7(3), PRMT8(5), RBBP5(2), SATB1(2), SETD1A(8), SETD2(16), SETD7(3), SETD8(2), SETDB1(8), SETDB2(3), SETMAR(1), SMYD3(4), STK38(2), SUV39H1(1), SUV39H2(3), SUV420H1(8), SUZ12(3), WHSC1(7), WHSC1L1(4) 40128544 284 72 281 81 106 75 55 2 44 2 0.046 0.27 105 GPCRPATHWAY G-protein coupled receptors activate adenylyl cyclase, which converts ATP to cAMP, to activate second messenger pathways. ADCY1, CALM1, CALM2, CALM3, CREB1, ELK1, FOS, GNAI1, GNAQ, GNAS, GNB1, GNGT1, HRAS, JUN, MAP2K1, MAPK3, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, RAF1, RPS6KA3, SYT1 34 ADCY1(8), CREB1(1), FOS(1), GNAI1(4), GNAQ(4), GNAS(6), GNB1(1), GNGT1(1), MAP2K1(4), MAPK3(3), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), PLCG1(4), PPP3CA(3), PPP3CB(5), PPP3CC(4), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PRKCA(4), RAF1(6), RPS6KA3(5), SYT1(1) 11537852 96 54 95 33 45 22 16 0 13 0 0.046 0.27 106 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 69 ACACB(15), ACSL1(4), ACSL3(6), ACSL4(4), ACSL5(4), ACSL6(6), ADIPOQ(4), ADIPOR1(1), ADIPOR2(3), AKT1(2), AKT2(6), AKT3(1), CAMKK1(1), CAMKK2(1), CD36(1), CHUK(6), CPT1A(6), CPT1B(5), CPT2(2), G6PC(4), G6PC2(1), IKBKB(4), IRS1(9), IRS4(15), JAK1(4), JAK2(9), JAK3(9), LEP(1), LEPR(9), MAPK8(7), MAPK9(5), NFKB1(6), NFKB2(4), NFKBIB(1), NFKBIE(2), NPY(2), PCK1(3), PCK2(4), POMC(2), PPARA(1), PPARGC1A(5), PRKAA1(3), PRKAA2(9), PRKAB1(2), PRKAB2(1), PRKAG1(1), PRKAG2(3), PRKAG3(6), PRKCQ(5), PTPN11(5), RELA(2), RXRA(1), RXRB(3), RXRG(4), SLC2A1(1), SLC2A4(4), STAT3(2), TNFRSF1A(1), TRADD(1), TRAF2(1), TYK2(1) 27451808 241 71 239 80 74 87 45 5 28 2 0.047 0.27 107 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 39 CD3D(1), CD3G(2), FOS(1), FYN(5), GRB2(3), LAT(1), LCK(3), MAP2K1(4), MAP3K1(8), MAPK3(3), MAPK8(7), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), NFKB1(6), PLCG1(4), PPP3CA(3), PPP3CB(5), PPP3CC(4), PRKCA(4), PTPN7(2), RAF1(6), RASA1(9), RELA(2), SHC1(3), SOS1(7), SYT1(1), VAV1(13), ZAP70(4) 14518312 129 52 127 37 53 35 20 1 20 0 0.050 0.28 108 IL6PATHWAY IL-6 binding to its receptor activates JAK kinases and a variety of transcription factors, with effects in neuronal differentiation, bone loss, and inflammation. CEBPB, CSNK2A1, ELK1, FOS, GRB2, HRAS, IL6, IL6R, IL6ST, JAK1, JAK2, JAK3, JUN, MAP2K1, MAPK3, PTPN11, RAF1, SHC1, SOS1, SRF, STAT3 21 CSNK2A1(4), FOS(1), GRB2(3), IL6(2), IL6R(3), IL6ST(3), JAK1(4), JAK2(9), JAK3(9), MAP2K1(4), MAPK3(3), PTPN11(5), RAF1(6), SHC1(3), SOS1(7), SRF(3), STAT3(2) 8097604 71 38 68 16 22 26 12 0 9 2 0.050 0.28 109 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 62 ADAM10(1), ADAM17(7), ATP6AP1(2), ATP6V0A1(3), ATP6V0A2(2), ATP6V0A4(7), ATP6V0B(1), ATP6V0C(1), ATP6V0D1(2), ATP6V1A(2), ATP6V1B1(5), ATP6V1B2(2), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1E2(3), ATP6V1G2(2), ATP6V1G3(2), ATP6V1H(3), CASP3(2), CDC42(1), CHUK(6), CSK(4), EGFR(12), F11R(2), GIT1(3), HBEGF(1), IGSF5(8), IKBKB(4), IL8(1), JAM3(3), LYN(4), MAP3K14(3), MAPK12(2), MAPK13(1), MAPK14(3), MAPK8(7), MAPK9(5), MET(5), NFKB1(6), NFKB2(4), NOD1(4), PAK1(5), PLCG1(4), PLCG2(13), PTPN11(5), PTPRZ1(17), RELA(2), SRC(3), TCIRG1(2), TJP1(7) 23005996 199 64 196 51 73 61 42 2 20 1 0.050 0.28 110 C21_STEROID_HORMONE_METABOLISM AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 AKR1C4(3), AKR1D1(1), CYP11A1(4), CYP11B1(9), CYP11B2(5), CYP17A1(2), CYP21A2(1), HSD11B1(1), HSD3B1(3), HSD3B2(1) 3002640 30 24 30 8 14 10 4 0 2 0 0.051 0.28 111 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(3), AKR1D1(1), CYP11A1(4), CYP11B1(9), CYP11B2(5), CYP17A1(2), CYP21A2(1), HSD11B1(1), HSD3B1(3), HSD3B2(1) 3002640 30 24 30 8 14 10 4 0 2 0 0.051 0.28 112 HSA00520_NUCLEOTIDE_SUGARS_METABOLISM Genes involved in nucleotide sugars metabolism GALE, GALT, TGDS, UGDH, UGP2, UXS1 6 GALE(1), GALT(2), TGDS(1), UGDH(4), UGP2(7), UXS1(7) 1709536 22 16 22 5 7 8 4 0 3 0 0.053 0.29 113 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(2), BAD(1), CREB1(1), CREB3(3), CREB5(4), DUSP4(1), DUSP6(5), DUSP9(1), EEF2K(1), GRB2(3), MAP2K1(4), MAP2K2(1), MAP3K8(2), MAPK1(2), MAPK3(3), MKNK1(1), MKNK2(3), MOS(3), NFKB1(6), RAP1A(2), RPS6KA1(1), RPS6KA2(10), RPS6KA3(5), SHC1(3), SOS1(7), SOS2(11), TRAF3(6) 9579636 92 43 91 23 28 32 16 2 14 0 0.053 0.29 114 CHREBPPATHWAY Carbohydrate responsive element binding protein (chREBP) is a transcription factor inhibited by cAMP and activated by high carbohydrate levels. ADCY1, BG1, BUCS1, GNAS, GNB1, GNGT1, PPP2CA, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKACB, PRKACG, PRKAG1, PRKAG2, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, WBSCR14 17 ADCY1(8), GNAS(6), GNB1(1), GNGT1(1), PPP2CA(1), PRKAA1(3), PRKAA2(9), PRKAB1(2), PRKAB2(1), PRKACB(1), PRKACG(3), PRKAG1(1), PRKAG2(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3) 5079204 49 35 48 20 22 15 8 0 4 0 0.055 0.30 115 HSA00300_LYSINE_BIOSYNTHESIS Genes involved in lysine biosynthesis AADAT, AASDHPPT, AASS, KARS 4 AADAT(1), AASDHPPT(3), AASS(9), KARS(3) 1596912 16 13 16 4 4 4 5 0 3 0 0.057 0.30 116 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 34 BTK(7), FCER1A(3), FOS(1), GRB2(3), LYN(4), MAP2K1(4), MAP3K1(8), MAPK1(2), MAPK3(3), MAPK8(7), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), PAK2(3), PLA2G4A(8), PLCG1(4), PPP3CA(3), PPP3CB(5), PPP3CC(4), RAF1(6), SHC1(3), SOS1(7), SYK(3), SYT1(1), VAV1(13) 12804368 120 50 117 31 46 32 23 1 18 0 0.057 0.30 117 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 17 HLA-A(3), ITGB1(6), KLRC3(3), KLRC4(1), KLRD1(1), LAT(1), MAP2K1(4), MAPK3(3), PAK1(5), PTK2B(1), PTPN6(4), SYK(3), VAV1(13) 4959168 48 30 48 12 17 13 10 1 7 0 0.058 0.30 118 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(2), ACAA2(1), ACAD8(1), ACAD9(5), ADH1A(1), ADH1B(3), ADH1C(4), ADH4(2), ADH5(1), ADH6(6), ADH7(2), ADHFE1(6), AKR1C4(3), AKR1D1(1), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(3), ALDH9A1(1), BAAT(2), CEL(1), CYP27A1(3), CYP7A1(4), HADHB(2), HSD3B7(2), LIPA(1), RDH11(1), RDH12(3), RDH13(1), SLC27A5(4), SOAT1(1), SOAT2(1), SRD5A1(1), SRD5A2(2) 10829152 93 45 93 33 24 39 23 0 7 0 0.060 0.31 119 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 109 ADA(3), ADCY1(8), ADCY2(15), ADCY3(2), ADCY4(9), ADCY5(11), ADCY6(1), ADCY7(4), ADCY8(12), ADK(1), ADSL(7), ADSS(2), AK2(1), AK5(5), ALLC(5), AMPD1(9), AMPD2(5), AMPD3(3), ATIC(4), ATP1B1(1), ATP5A1(5), ATP5B(4), ATP5C1(4), ATP5D(1), ATP5F1(1), ATP5G3(1), ATP5J2(1), DCK(2), ENPP1(4), ENPP3(4), ENTPD1(2), FHIT(1), GART(3), GMPS(5), GUCY1A2(12), GUCY1B3(9), GUCY2C(8), GUCY2D(8), GUCY2F(12), HPRT1(2), IMPDH1(2), IMPDH2(4), ITPA(2), NPR1(6), NPR2(10), NT5E(3), NT5M(1), PAICS(1), PAPSS1(2), PAPSS2(4), PDE1A(4), PDE4A(4), PDE4B(5), PDE4C(2), PDE4D(5), PDE5A(6), PDE6B(5), PDE6C(10), PDE7B(4), PDE8A(1), PDE9A(6), PFAS(1), PKM2(2), POLB(3), POLD1(5), POLD2(1), POLE(21), POLG(5), POLL(1), POLQ(12), POLR1B(9), POLR2A(6), POLR2B(8), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLR2K(1), POLRMT(1), PPAT(6), PRPS1(1), PRPS1L1(1), PRPS2(2), PRUNE(1), RRM1(2), RRM2(3) 43212572 380 94 374 113 130 127 71 3 49 0 0.061 0.31 120 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 ABP1(1), ADH1A(1), ADH1B(3), ADH1C(4), ADH4(2), ADH6(6), ADH7(2), ADHFE1(6), ALDH1A3(6), ALDH3A1(2), ALDH3B1(3), ALDH3B2(1), AOC2(4), AOC3(4), AOX1(8), DBH(5), DCT(13), DDC(1), FAH(2), GOT1(6), GOT2(1), GSTZ1(2), HGD(2), HPD(4), MAOA(3), MAOB(1), TAT(5), TPO(11), TYR(3) 10479052 112 52 110 47 39 39 25 1 8 0 0.062 0.31 121 STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR 10 EPX(7), GBA3(3), LPO(3), MPO(5), PRDX1(1), PRDX6(2), TPO(11), TYR(3) 3284228 35 27 34 16 19 7 4 0 5 0 0.062 0.31 122 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 CSNK2A1(4), FOS(1), GRB2(3), IGF1(2), IGF1R(8), IRS1(9), MAP2K1(4), MAPK3(3), MAPK8(7), PTPN11(5), RAF1(6), RASA1(9), SHC1(3), SOS1(7), SRF(3) 6996356 74 40 72 14 22 26 17 1 8 0 0.063 0.31 123 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(3), BFAR(1), CREB1(1), CREB3(3), CREB5(4), MAPK1(2), RAF1(6), SNX13(9), SRC(3), TERF2IP(2) 3434684 34 20 33 12 12 9 7 1 5 0 0.064 0.31 124 NUCLEOTIDE_GPCRS ADORA1, ADORA2A, ADORA2B, ADORA3, GPR23, LTB4R, P2RY1, P2RY2, P2RY5, P2RY6 8 ADORA1(8), ADORA2A(5), ADORA2B(1), ADORA3(3), LTB4R(1), P2RY1(6), P2RY2(3), P2RY6(1) 1894004 28 20 28 4 12 11 3 1 1 0 0.065 0.31 125 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(4), ACTN1(5), ACTN2(8), ACTN3(3), BCR(7), CAPN1(2), CAPNS1(1), CAPNS2(1), CAV1(1), CRKL(2), CSK(4), FYN(5), GRB2(3), ITGA1(3), ITGB1(6), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK3(3), MAPK8(7), PPP1R12B(9), PTK2(6), RAF1(6), RAP1A(2), ROCK1(15), SHC1(3), SOS1(7), SRC(3), TLN1(7), VCL(2), ZYX(1) 15965992 133 61 130 36 51 44 25 1 12 0 0.065 0.31 126 INFLAMPATHWAY Interleukins and TNF serve as signals to coordinate the inflammatory response, in which macrophages recruit and activate neutrophils, fibroblasts, and T cells. CD4, CSF1, CSF2, CSF3, HLA-DRA, HLA-DRB1, IFNA1, IFNB1, IFNG, IL10, IL11, IL12A, IL12B, IL13, IL15, IL1A, IL2, IL3, IL4, IL5, IL6, IL7, IL8, LTA, PDGFA, TGFB1, TGFB2, TGFB3, TNF 29 CD4(2), CSF1(2), HLA-DRA(5), HLA-DRB1(3), IFNA1(1), IFNB1(1), IFNG(1), IL10(2), IL11(1), IL12A(1), IL12B(2), IL13(1), IL15(2), IL1A(1), IL2(4), IL3(3), IL4(3), IL6(2), IL7(2), IL8(1), PDGFA(1), TGFB1(1), TGFB2(9) 4404944 51 25 50 22 18 23 3 0 5 2 0.066 0.31 127 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(3), CDK2(2), CUL1(9), RB1(7), TFDP1(4) 2300712 25 19 25 6 5 4 9 1 5 1 0.066 0.31 128 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(3), AKT1(2), ASAH1(3), CAV3(3), DAG1(5), DLG4(3), EPHB2(8), GNAI1(4), GNAQ(4), ITPR1(19), ITPR2(18), ITPR3(12), KCNJ3(6), KCNJ5(4), KCNJ9(3), MAPK1(2), PITX2(2), PTX3(2), RHO(3), RYR1(25) 13839816 131 60 130 55 63 38 17 0 12 1 0.066 0.31 129 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(2), AKT3(1), CAPN1(2), CAPN10(3), CAPN11(2), CAPN2(7), CAPN3(6), CAPN5(5), CAPN6(4), CAPN7(4), CAPN9(1), CAPNS1(1), CAV1(1), CAV2(1), CAV3(3), CDC42(1), CSK(4), DOCK1(7), FYN(5), GIT2(7), GRB2(3), ITGA10(7), ITGA11(4), ITGA2(6), ITGA2B(4), ITGA3(4), ITGA4(8), ITGA5(7), ITGA6(4), ITGA7(6), ITGA8(8), ITGA9(6), ITGAD(8), ITGAE(7), ITGAL(8), ITGAM(8), ITGAV(5), ITGAX(6), ITGB1(6), ITGB2(5), ITGB3(9), ITGB4(3), ITGB5(6), ITGB6(6), ITGB7(4), ITGB8(5), MAP2K1(4), MAP2K2(1), MAP2K3(6), MAP2K6(3), MAPK12(2), MAPK4(1), MAPK6(3), MAPK7(3), MYLK2(3), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PDPK1(1), PIK3R2(1), PTK2(6), RAP1B(2), RAPGEF1(6), RHO(3), ROCK1(15), ROCK2(6), SEPP1(1), SHC1(3), SHC3(1), SORBS1(11), SOS1(7), SRC(3), TLN1(7), TNS1(14), VASP(3), VAV2(4), VAV3(12), VCL(2), ZYX(1) 45612860 369 96 361 136 127 127 63 9 43 0 0.066 0.31 130 HSA04070_PHOSPHATIDYLINOSITOL_SIGNALING_SYSTEM Genes involved in phosphatidylinositol signaling system CALM1, CALM2, CALM3, CALML3, CALML6, CARKL, CDIPT, CDS1, CDS2, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKI, DGKQ, DGKZ, FN3K, IMPA1, IMPA2, INPP1, INPP4A, INPP4B, INPP5A, INPP5B, INPP5D, INPP5E, INPPL1, ITGB1BP3, ITPK1, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, OCRL, PI4KA, PI4KB, PIB5PA, PIK3C2A, PIK3C2B, PIK3C2G, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCZ1, PRKCA, PRKCB1, PRKCG, PTEN, PTPMT1, SKIP, SYNJ1, SYNJ2 70 CDS1(2), CDS2(4), DGKA(1), DGKB(9), DGKD(12), DGKE(3), DGKG(3), DGKH(10), DGKI(10), DGKZ(3), IMPA1(2), IMPA2(2), INPP1(2), INPP4A(3), INPP4B(7), INPP5A(2), INPP5B(1), INPP5D(4), INPPL1(4), ITGB1BP3(1), ITPK1(2), ITPKB(4), ITPR1(19), ITPR2(18), ITPR3(12), OCRL(9), PI4KA(15), PI4KB(2), PIK3C2A(5), PIK3C2B(8), PIK3C2G(9), PIK3C3(7), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PIP4K2A(2), PIP4K2B(2), PIP4K2C(3), PIP5K1A(3), PIP5K1B(2), PIP5K1C(4), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), PLCD1(7), PLCD3(2), PLCD4(2), PLCE1(9), PLCG1(4), PLCG2(13), PLCZ1(4), PRKCA(4), PRKCG(10), PTPMT1(2), SYNJ1(11), SYNJ2(6) 41244280 335 91 330 101 141 95 60 2 36 1 0.067 0.31 131 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(3), CAMK1G(5), FPR1(2), GNA15(3), GNB1(1), GNGT1(1), MAP2K1(4), MAP2K2(1), MAP2K3(6), MAP2K6(3), MAP3K1(8), MAPK1(2), MAPK14(3), MAPK3(3), NCF1(1), NCF2(2), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), NFKB1(6), PAK1(5), PIK3C2G(9), PLCB1(8), PPP3CA(3), PPP3CB(5), PPP3CC(4), RAF1(6), RELA(2), SYT1(1) 13013564 115 49 114 40 43 30 19 4 19 0 0.067 0.31 132 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(5), ACACA(18), ACADL(2), ACADM(6), ACADSB(5), ACAT1(1), ACAT2(2), ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH6A1(4), ALDH9A1(1), ECHS1(2), EHHADH(2), HADHA(3), LDHA(2), LDHB(3), LDHC(2), MCEE(2), MLYCD(1), MUT(4), PCCA(9), PCCB(4), SDS(2), SUCLA2(5), SUCLG1(2) 11147916 119 45 117 24 42 38 20 1 18 0 0.067 0.31 133 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 11 AXIN1(2), CREBBP(25), EP300(15), FZD1(1), HDAC1(2), LDB1(5), LEF1(4), PITX2(2), TRRAP(21), WNT1(1) 8204472 78 42 77 27 34 16 16 1 11 0 0.067 0.31 134 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 56 ABP1(1), ADH1A(1), ADH1B(3), ADH1C(4), ADH4(2), ADH5(1), ADH6(6), ADH7(2), ADHFE1(6), ALDH1A3(6), ALDH3A1(2), ALDH3B1(3), ALDH3B2(1), AOC2(4), AOC3(4), AOX1(8), CARM1(2), DBH(5), DCT(13), DDC(1), ECH1(1), ESCO1(11), ESCO2(4), FAH(2), GOT1(6), GOT2(1), GSTZ1(2), HGD(2), HPD(4), LCMT1(3), LCMT2(2), MAOA(3), MAOB(1), METTL2B(2), METTL6(8), MYST3(18), MYST4(10), PNPLA3(4), PRMT2(1), PRMT3(3), PRMT5(1), PRMT6(1), PRMT7(3), PRMT8(5), SH3GLB1(4), TAT(5), TPO(11), TYR(3), TYRP1(2), WBSCR22(1) 19823904 199 67 195 74 69 66 45 4 15 0 0.068 0.31 135 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(2), BAD(1), GRB2(3), IGF1R(8), IRS1(9), MAP2K1(4), MAPK1(2), MAPK3(3), RAF1(6), SHC1(3), SOS1(7), YWHAH(1) 5031620 49 34 47 11 16 17 10 0 6 0 0.069 0.32 136 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(5), AARS2(6), CARS(6), CARS2(1), DARS(4), DARS2(3), EPRS(12), FARS2(5), FARSA(1), FARSB(8), GARS(3), HARS(2), HARS2(4), IARS(6), IARS2(6), KARS(3), LARS(5), LARS2(3), MARS(6), MARS2(1), MTFMT(2), NARS(3), NARS2(6), QARS(8), RARS(4), RARS2(5), SARS(2), SARS2(2), TARS(6), TARS2(5), VARS(1), VARS2(6), WARS(3), WARS2(3), YARS(2), YARS2(4) 17925080 152 55 151 29 52 44 35 2 19 0 0.074 0.33 137 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(5), ADC(1), ALDH4A1(3), ALDH5A1(4), CAD(12), CPS1(14), EPRS(12), GAD1(9), GAD2(4), GCLC(4), GCLM(1), GFPT1(4), GFPT2(4), GLS2(2), GLUD1(2), GLUD2(6), GLUL(4), GMPS(5), GOT1(6), GOT2(1), GPT2(2), GSR(1), GSS(4), NADSYN1(2), NAGK(2), PPAT(6), QARS(8) 13279336 128 55 127 33 44 43 28 3 10 0 0.075 0.33 138 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(3), CYP2E1(6), NR1I3(3), PTGS1(6), PTGS2(3) 1776376 21 17 21 6 9 7 4 0 1 0 0.075 0.33 139 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(9), DIAPH1(1), FYN(5), ITGA1(3), ITGB1(6), MAP2K1(4), MAPK1(2), MAPK3(3), MYL2(1), MYLK(14), PTK2(6), RAF1(6), ROCK1(15), SHC1(3), SRC(3), TLN1(7) 11497936 88 48 85 24 27 30 18 0 13 0 0.076 0.33 140 AKAPCENTROSOMEPATHWAY Protein Kinase A at the Centrosome AKAP9, ARHA, CDC2, MAP2, PCNT1, PCNT2, PPP1CA, PPP2CA, PRKACB, PRKACG, PRKAG1, PRKAR2A, PRKAR2B, PRKCE, PRKCL1 9 AKAP9(26), PPP2CA(1), PRKACB(1), PRKACG(3), PRKAG1(1), PRKAR2B(3), PRKCE(6) 4851972 41 25 40 11 16 11 5 0 9 0 0.076 0.33 141 CFTRPATHWAY The cAMP-regulated chloride channel CFTR (deficient in cystic fibrosis) is regulated by the surface-localized beta-adrenergic receptor. ADCY1, ADRB2, CFTR, GNAS, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, SLC9A3R1, VIL2 11 ADCY1(8), CFTR(12), GNAS(6), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), SLC9A3R1(3) 4287168 42 30 42 13 15 13 9 0 5 0 0.077 0.34 142 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 6 CREBBP(25), EP300(15), MAPK1(2), MAPK3(3), PELP1(2), SRC(3) 4737824 50 32 50 16 17 13 13 1 6 0 0.078 0.34 143 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 73 ABL1(4), ACTN1(5), ACTR2(2), ACTR3(3), AKT1(2), AKT2(6), AKT3(1), ANGPTL2(8), ARHGEF6(10), ARHGEF7(8), CAV1(1), CDC42(1), CSE1L(4), DOCK1(7), EPHB2(8), FYN(5), GRB2(3), GRB7(1), GRLF1(12), ITGA1(3), ITGA10(7), ITGA11(4), ITGA2(6), ITGA3(4), ITGA4(8), ITGA5(7), ITGA6(4), ITGA7(6), ITGA8(8), ITGA9(6), ITGB3BP(3), MAP3K11(4), MAPK1(2), MAPK8(7), MAPK8IP1(4), MAPK8IP3(2), MAPK9(5), MRAS(1), MYLK(14), MYLK2(3), P4HB(2), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PIK3CB(2), PLCG1(4), PLCG2(13), PTK2(6), RAF1(6), RALA(1), RHO(3), ROCK1(15), ROCK2(6), SHC1(3), SOS1(7), SOS2(11), SRC(3), TERF2IP(2), TLN1(7), TLN2(9), VASP(3), WAS(1), ZYX(1) 39349620 325 87 315 126 118 101 54 5 47 0 0.079 0.34 144 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(10), CR2(11), HLA-DRA(5), HLA-DRB1(3), ICAM1(2), ITGAL(8), ITGB2(5), PTPRC(17) 5071208 62 28 62 16 15 26 10 0 9 2 0.080 0.34 145 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 7 CDC25A(2), CDC25B(5), CDC25C(4), CHEK1(1), MYT1(13), WEE1(3), YWHAH(1) 2566992 29 21 28 4 9 12 5 1 2 0 0.080 0.34 146 HSA00940_PHENYLPROPANOID_BIOSYNTHESIS Genes involved in phenylpropanoid biosynthesis EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO 7 EPX(7), GBA3(3), LPO(3), MPO(5), PRDX6(2), TPO(11) 2867192 31 25 30 14 18 7 2 0 4 0 0.083 0.35 147 KREBPATHWAY The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain. ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2 8 ACO2(2), FH(1), IDH2(7), MDH1(1), OGDH(4), SDHA(6), SUCLA2(5) 3178052 26 23 26 11 11 6 5 0 4 0 0.083 0.35 148 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), NFYB(1), NFYC(3), RB1(7), SP1(2), SP3(3) 2252028 19 15 19 4 4 8 5 0 1 1 0.088 0.37 149 SRCRPTPPATHWAY Activation of Src by Protein-tyrosine phosphatase alpha CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CSK, GRB2, PRKCA, PRKCB1, PTPRA, SRC 9 CCNB1(2), CDC25A(2), CDC25B(5), CDC25C(4), CSK(4), GRB2(3), PRKCA(4), PTPRA(2), SRC(3) 3135504 29 24 29 9 7 14 6 1 1 0 0.090 0.37 150 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 134 ACTB(2), CHAD(7), COL11A1(24), COL11A2(11), COL17A1(8), COL1A1(11), COL1A2(16), COL2A1(9), COL3A1(12), COL4A1(14), COL4A2(4), COL4A4(10), COL4A6(15), COL5A1(16), COL5A2(13), COL5A3(10), COL6A2(1), COL6A6(20), COMP(2), DES(1), DSC1(8), DSC2(2), DSC3(4), DSG1(8), DSG2(5), DSG3(8), DSG4(9), FN1(22), GJA1(8), GJA10(10), GJA4(2), GJA5(3), GJA8(5), GJA9(4), GJB1(3), GJB3(4), GJB4(1), GJB7(2), GJC1(4), GJC2(1), GJC3(2), GJD2(1), GJD4(2), IBSP(3), INA(2), ITGA6(4), ITGB4(3), KRT1(4), KRT10(2), KRT12(2), KRT13(4), KRT14(2), KRT15(2), KRT16(2), KRT17(2), KRT18(2), KRT19(2), KRT2(1), KRT20(1), KRT23(2), KRT24(3), KRT25(3), KRT27(2), KRT28(1), KRT3(6), KRT31(4), KRT32(2), KRT33A(2), KRT33B(5), KRT34(4), KRT35(3), KRT36(2), KRT37(6), KRT38(2), KRT4(2), KRT5(4), KRT6A(4), KRT6B(2), KRT6C(2), KRT7(3), KRT71(3), KRT72(5), KRT73(4), KRT74(5), KRT75(6), KRT76(2), KRT77(1), KRT78(4), KRT79(3), KRT8(1), KRT81(1), KRT82(6), KRT83(1), KRT84(9), KRT85(6), KRT9(5), LAMA1(24), LAMA2(25), LAMA3(18), LAMA4(11), LAMB1(8), LAMB2(5), LAMB3(9), LAMB4(16), LAMC1(11), LAMC2(10), LAMC3(8), LMNB1(4), LMNB2(1), NES(7), PRPH(2), SPP1(1), THBS1(10), THBS2(15), THBS3(3), THBS4(2), TNC(16), TNN(17), TNXB(17), VIM(3), VTN(6), VWF(15) 77713980 752 143 746 302 289 268 110 10 74 1 0.091 0.37 151 KERATAN_SULFATE_BIOSYNTHESIS B3GNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT5, FUT8, SIAT4A, SIAT4B, SIAT6, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 10 B3GNT1(2), B4GALT1(6), B4GALT2(3), B4GALT3(7), B4GALT5(2), FUT8(2), ST3GAL1(1), ST3GAL2(1), ST3GAL3(4), ST3GAL4(2) 2644184 30 22 30 6 15 5 7 0 3 0 0.091 0.37 152 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(3), GUSB(2), RPE(2), UGDH(4), UGP2(7), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(2), UGT1A5(3), UGT1A6(1), UGT1A7(2), UGT1A8(1), UGT1A9(6), UGT2A1(8), UGT2A3(7), UGT2B10(1), UGT2B11(6), UGT2B15(2), UGT2B17(7), UGT2B28(3), UGT2B4(3), UGT2B7(6), XYLB(2) 8418552 82 33 81 17 18 33 17 0 14 0 0.092 0.37 153 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(7), CD79A(3), CD79B(1), FOS(1), GRB2(3), LYN(4), MAP2K1(4), MAP3K1(8), MAPK14(3), MAPK3(3), MAPK8(7), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), PLCG1(4), PPP3CA(3), PPP3CB(5), PPP3CC(4), PRKCA(4), RAF1(6), SHC1(3), SOS1(7), SYK(3), SYT1(1), VAV1(13) 12787560 116 50 114 32 46 34 19 1 16 0 0.094 0.38 154 ST_INTERFERON_GAMMA_PATHWAY The interferon gamma pathway resembles the JAK-STAT pathway and activates STAT transcription factors. CISH, IFNG, IFNGR1, JAK1, JAK2, PLA2G2A, PTPRU, REG1A, STAT1, STATIP1 9 IFNG(1), IFNGR1(3), JAK1(4), JAK2(9), PTPRU(13), REG1A(5), STAT1(6) 3888348 41 24 39 11 21 8 7 0 3 2 0.094 0.38 155 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 BCL2(1), CREBBP(25), EP300(15), FYN(5), IL7(2), IL7R(3), JAK1(4), JAK3(9), LCK(3), NMI(2), PTK2B(1), STAT5B(3) 8250864 73 36 72 26 24 24 13 1 11 0 0.095 0.38 156 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 41 ACTR2(2), ACTR3(3), AKT1(2), AKT2(6), AKT3(1), ANGPTL2(8), ARHGAP4(1), ARHGEF11(11), BTK(7), CDC42(1), CFL1(1), GDI1(1), GDI2(1), INPPL1(4), ITPR1(19), ITPR2(18), ITPR3(12), LIMK1(5), MYLK(14), MYLK2(3), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PDK1(2), PIK3CD(3), PIK3CG(14), PITX2(2), PPP1R13B(6), RACGAP1(2), RHO(3), ROCK1(15), ROCK2(6), RPS4X(2), SAG(1), WASF1(3), WASL(7) 22408056 207 66 207 61 77 68 33 1 27 1 0.095 0.38 157 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(5), FARSA(1), FARSB(8), GOT1(6), GOT2(1), PAH(4), TAT(5), YARS(2), YARS2(4) 2933008 36 20 35 7 10 13 7 0 6 0 0.098 0.38 158 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(5), AGTR2(5), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), F2(4), FYN(5), GNA11(1), GNAI1(4), GNB1(1), GNGT1(1), GRB2(3), JAK2(9), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK14(3), MAPK3(3), MAPK8(7), MAPT(5), MYLK(14), PLCG1(4), PRKCA(4), PTK2B(1), RAF1(6), SHC1(3), SOS1(7), STAT1(6), STAT3(2), SYT1(1) 14153160 119 50 117 38 33 43 29 1 11 2 0.098 0.38 159 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 46 APAF1(8), BAD(1), BAX(1), BCL2(1), BCL2A1(3), BCL2L1(1), BOK(1), CASP1(2), CASP10(2), CASP2(4), CASP3(2), CASP4(3), CASP6(2), CASP7(1), CASP9(2), CD40(1), CD40LG(6), CRADD(2), DAXX(1), DFFA(3), DFFB(2), FAS(2), FASLG(1), IKBKE(4), NFKB1(6), NGFR(3), NR3C1(4), NTRK1(7), PTPN13(17), RIPK1(2), SFRS2IP(3), TFG(6), TNFRSF1A(1), TRADD(1), TRAF1(2), TRAF2(1), TRAF3(6), TRAF6(4) 14526248 119 52 116 53 34 43 23 1 17 1 0.10 0.40 160 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(3), ADH1C(4), ADH4(2), ADH5(1), ADH6(6), ADH7(2), ADHFE1(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(3), ALDH9A1(1) 4511676 51 30 51 15 13 20 16 0 2 0 0.11 0.41 161 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 68 AKT1(2), AKT2(6), AKT3(1), BTK(7), FCER1A(3), FYN(5), GAB2(1), GRB2(3), IL13(1), IL3(3), IL4(3), INPP5D(4), LAT(1), LCP2(3), LYN(4), MAP2K1(4), MAP2K2(1), MAP2K3(6), MAP2K6(3), MAPK1(2), MAPK12(2), MAPK13(1), MAPK14(3), MAPK3(3), MAPK8(7), MAPK9(5), MS4A2(3), PDK1(2), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PLA2G1B(1), PLA2G2F(1), PLA2G4A(8), PLA2G6(4), PLCG1(4), PLCG2(13), PRKCA(4), PRKCD(3), PRKCE(6), RAF1(6), SOS1(7), SOS2(11), SYK(3), VAV1(13), VAV2(4), VAV3(12) 22174012 214 66 207 60 84 63 43 3 21 0 0.11 0.41 162 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 28 ANPEP(8), G6PD(3), GCLC(4), GCLM(1), GPX1(1), GPX2(2), GPX3(3), GPX5(4), GSS(4), GSTA1(1), GSTA3(4), GSTM2(2), GSTM3(3), GSTM4(2), GSTM5(1), GSTO2(1), GSTZ1(2), IDH1(3), IDH2(7), MGST1(2), MGST3(1), PGD(1) 5714284 60 33 60 8 13 25 16 0 6 0 0.11 0.41 163 HSA00500_STARCH_AND_SUCROSE_METABOLISM Genes involved in starch and sucrose metabolism AGL, AMY1A, AMY1B, AMY1C, AMY2A, AMY2B, ASCC3, ASCC3L1, ATP13A2, DDX18, DDX19A, DDX23, DDX4, DDX41, DDX47, DDX50, DDX51, DDX52, DDX54, DDX55, DDX56, DHX58, ENPP1, ENPP3, ENTPD7, EP400, ERCC2, ERCC3, G6PC, G6PC2, GAA, GANC, GBA, GBA3, GBE1, GCK, GPI, GUSB, GYS1, GYS2, HK1, HK2, HK3, IFIH1, LYZL1, MGAM, MOV10L1, NUDT5, NUDT8, PGM1, PGM3, PYGB, PYGL, PYGM, RAD54B, RAD54L, RUVBL2, SETX, SI, SKIV2L2, SMARCA2, SMARCA5, TREH, UGDH, UGP2, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, UXS1 79 AGL(10), AMY2B(1), ASCC3(21), ATP13A2(3), DDX18(3), DDX19A(3), DDX23(4), DDX4(3), DDX41(2), DDX47(3), DDX50(3), DDX52(2), DDX54(5), DDX55(3), DDX56(5), DHX58(3), ENPP1(4), ENPP3(4), ENTPD7(4), EP400(20), ERCC2(4), ERCC3(7), G6PC(4), G6PC2(1), GANC(3), GBA3(3), GBE1(5), GCK(2), GPI(2), GUSB(2), GYS1(2), GYS2(11), HK1(6), HK2(3), HK3(5), IFIH1(5), MGAM(13), MOV10L1(13), PGM1(4), PGM3(5), PYGB(4), PYGL(2), PYGM(4), RAD54B(8), RAD54L(3), RUVBL2(1), SETX(20), SI(15), SKIV2L2(4), SMARCA2(11), SMARCA5(7), TREH(2), UGDH(4), UGP2(7), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(2), UGT1A5(3), UGT1A6(1), UGT1A7(2), UGT1A8(1), UGT1A9(6), UGT2A1(8), UGT2A3(7), UGT2B10(1), UGT2B11(6), UGT2B15(2), UGT2B17(7), UGT2B28(3), UGT2B4(3), UGT2B7(6), UXS1(7) 41311176 367 82 362 102 120 117 79 0 50 1 0.11 0.42 164 HSA04742_TASTE_TRANSDUCTION Genes involved in taste transduction ACCN1, ADCY4, ADCY6, ADCY8, CACNA1A, CACNA1B, GNAS, GNAT3, GNB1, GNB3, GNG13, GNG3, GRM4, ITPR3, KCNB1, PDE1A, PLCB2, PRKACA, PRKACB, PRKACG, PRKX, PRKY, SCNN1A, SCNN1B, SCNN1G, TAS1R1, TAS1R2, TAS1R3, TAS2R1, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R3, TAS2R38, TAS2R39, TAS2R4, TAS2R40, TAS2R41, TAS2R42, TAS2R43, TAS2R44, TAS2R45, TAS2R46, TAS2R48, TAS2R49, TAS2R5, TAS2R50, TAS2R60, TAS2R7, TAS2R8, TAS2R9, TRPM5 47 ACCN1(7), ADCY4(9), ADCY6(1), ADCY8(12), CACNA1A(17), CACNA1B(11), GNAS(6), GNAT3(2), GNB1(1), GNB3(3), GNG3(2), GRM4(7), ITPR3(12), KCNB1(5), PDE1A(4), PLCB2(3), PRKACA(1), PRKACB(1), PRKACG(3), PRKX(2), SCNN1A(3), SCNN1B(4), SCNN1G(5), TAS1R1(7), TAS1R2(8), TAS2R1(2), TAS2R10(6), TAS2R13(3), TAS2R14(1), TAS2R16(3), TAS2R3(1), TAS2R38(3), TAS2R39(3), TAS2R4(2), TAS2R41(2), TAS2R46(2), TAS2R5(2), TAS2R50(5), TAS2R60(2), TAS2R7(1), TAS2R8(2), TAS2R9(3) 19170972 179 68 176 71 77 61 29 0 12 0 0.11 0.43 165 SETPATHWAY Cytotoxic T cells release perforin, which to allow entry into target cells of granzyme B, which activates caspases, and granzyme A, which induces caspase-independent apoptosis. ANP32A, APEX1, CREBBP, DFFA, DFFB, GZMA, GZMB, HMGB2, NME1, PRF1, SET 11 ANP32A(1), APEX1(4), CREBBP(25), DFFA(3), DFFB(2), GZMA(3), GZMB(2), HMGB2(1) 3603940 41 25 41 12 12 13 9 0 7 0 0.11 0.43 166 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 48 ACTA1(4), AGT(5), AKT1(2), CALR(1), CAMK1(3), CAMK1G(5), CAMK4(3), CREBBP(25), CSNK1A1(2), EDN1(1), ELSPBP1(1), F2(4), GATA4(1), HAND1(2), HAND2(3), IGF1(2), MAP2K1(4), MAPK1(2), MAPK14(3), MAPK3(3), MAPK8(7), MEF2C(9), MYH2(12), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), NKX2-5(1), NPPA(1), PPP3CA(3), PPP3CB(5), PPP3CC(4), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), RAF1(6), RPS6KB1(3), SYT1(1) 15336960 159 56 158 48 61 44 32 1 21 0 0.12 0.43 167 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 94 AKT1(2), AKT2(6), AKT3(1), CD14(1), CD40(1), CD80(1), CHUK(6), CXCL10(1), CXCL11(3), CXCL9(3), FOS(1), IFNA1(1), IFNA10(3), IFNA13(2), IFNA16(4), IFNA2(4), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), IFNAR1(3), IFNAR2(2), IFNB1(1), IKBKB(4), IKBKE(4), IL12A(1), IL12B(2), IL1B(1), IL6(2), IL8(1), IRAK1(1), IRAK4(4), IRF3(2), IRF5(3), LBP(1), LY96(2), MAP2K1(4), MAP2K2(1), MAP2K3(6), MAP2K6(3), MAP3K7(4), MAP3K8(2), MAPK1(2), MAPK12(2), MAPK13(1), MAPK14(3), MAPK3(3), MAPK8(7), MAPK9(5), MYD88(2), NFKB1(6), NFKB2(4), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), RELA(2), RIPK1(2), SPP1(1), STAT1(6), TBK1(6), TICAM1(2), TIRAP(1), TLR1(5), TLR2(6), TLR3(5), TLR4(10), TLR5(4), TLR6(2), TLR7(7), TLR8(6), TLR9(7), TOLLIP(1), TRAF3(6), TRAF6(4) 27922384 246 66 246 73 69 89 57 4 26 1 0.12 0.43 168 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(3), AKR1D1(1), ARSB(5), ARSD(3), ARSE(2), CYP11B1(9), CYP11B2(5), HSD11B1(1), HSD17B2(2), HSD17B3(2), HSD17B8(1), HSD3B1(3), HSD3B2(1), SRD5A1(1), SRD5A2(2), STS(7), SULT1E1(2), SULT2A1(2), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(2), UGT1A5(3), UGT1A6(1), UGT1A7(2), UGT1A8(1), UGT1A9(6), UGT2B15(2), UGT2B4(3) 8780836 76 40 75 13 33 23 9 0 11 0 0.12 0.43 169 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 ALDH1A1(4), ALDH1A2(6), BCMO1(4), RDH5(1) 1303708 15 13 15 2 6 4 4 0 1 0 0.12 0.43 170 LYSINE_BIOSYNTHESIS AADAT, AASDH, AASDHPPT, AASS, KARS 5 AADAT(1), AASDH(4), AASDHPPT(3), AASS(9), KARS(3) 2347060 20 15 20 8 5 6 6 0 3 0 0.12 0.43 171 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 63 ACHE(2), AGPAT1(2), AGPAT3(3), AGPAT6(2), CDS1(2), CDS2(4), CHAT(6), CHKA(4), CHPT1(1), DGKA(1), DGKB(9), DGKD(12), DGKE(3), DGKG(3), DGKH(10), DGKI(10), DGKZ(3), ESCO1(11), ESCO2(4), ETNK1(2), ETNK2(2), GNPAT(2), GPAM(3), GPD1(1), GPD1L(3), GPD2(4), LCAT(1), MYST3(18), MYST4(10), PCYT1A(5), PCYT1B(5), PEMT(1), PISD(2), PLA2G1B(1), PLA2G2F(1), PLA2G4A(8), PLA2G6(4), PLD1(11), PLD2(2), PNPLA3(4), PPAP2B(1), PTDSS1(7), SH3GLB1(4) 22038864 194 64 192 72 68 66 43 1 16 0 0.12 0.43 172 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 43 AKT1(2), AKT2(6), AKT3(1), BAD(1), BCL2(1), BCR(7), BLNK(1), BTK(7), CD19(3), CD22(11), CR2(11), CSK(4), DAG1(5), FLOT1(3), GRB2(3), GSK3A(2), INPP5D(4), ITPR1(19), ITPR2(18), ITPR3(12), LYN(4), MAP4K1(3), MAPK1(2), MAPK3(3), NFATC1(2), NFATC2(6), PDK1(2), PIK3CD(3), PLCG2(13), PPP1R13B(6), PPP3CA(3), PPP3CB(5), PPP3CC(4), PTPRC(17), RAF1(6), SHC1(3), SOS1(7), SOS2(11), SYK(3), VAV1(13) 23352160 237 66 232 58 91 76 36 2 31 1 0.12 0.44 173 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 CXCL12(1), CXCR4(4), GNAI1(4), GNAQ(4), GNB1(1), GNGT1(1), MAP2K1(4), MAPK1(2), MAPK3(3), NFKB1(6), PIK3C2G(9), PLCG1(4), PRKCA(4), PTK2(6), PTK2B(1), RAF1(6), RELA(2) 8234468 62 35 61 20 26 16 10 0 10 0 0.12 0.44 174 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(2), ACAA2(1), ADH1A(1), ADH1B(3), ADH1C(4), ADH4(2), ADH6(6), ADH7(2), ADHFE1(6), AKR1C4(3), AKR1D1(1), ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), BAAT(2), CEL(1), CYP27A1(3), CYP7A1(4), HADHB(2), SOAT2(1), SRD5A1(1), SRD5A2(2) 7894272 80 40 80 23 22 30 23 0 5 0 0.12 0.44 175 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 CSNK2A1(4), FOS(1), GRB2(3), INSR(6), IRS1(9), MAP2K1(4), MAPK3(3), MAPK8(7), PTPN11(5), RAF1(6), RASA1(9), SHC1(3), SLC2A4(4), SOS1(7), SRF(3) 7253876 74 39 72 18 19 27 18 1 9 0 0.12 0.44 176 HSA00430_TAURINE_AND_HYPOTAURINE_METABOLISM Genes involved in taurine and hypotaurine metabolism BAAT, CDO1, CSAD, GAD1, GAD2, GGT1, GGTL3, GGTL4 5 BAAT(2), CDO1(1), CSAD(2), GAD1(9), GAD2(4) 1593012 18 15 18 6 8 8 2 0 0 0 0.13 0.45 177 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(5), ACACA(18), ACACB(15), ACADM(6), ACAT1(1), ACAT2(2), ACSS1(3), ACSS2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH6A1(4), ALDH7A1(3), ALDH9A1(1), ECHS1(2), EHHADH(2), HADHA(3), HIBCH(1), LDHA(2), LDHAL6A(3), LDHAL6B(2), LDHB(3), LDHC(2), MCEE(2), MLYCD(1), MUT(4), PCCA(9), PCCB(4), SUCLA2(5), SUCLG1(2) 13361500 133 50 131 30 45 46 21 2 19 0 0.13 0.46 178 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(4), F2R(1), GNAI1(4), GNB1(1), GNGT1(1), ITGA1(3), ITGB1(6), MAP2K1(4), MAPK1(2), MAPK3(3), PLA2G4A(8), PLCB1(8), PRKCA(4), PTGS1(6), PTK2(6), RAF1(6), SRC(3), SYK(3), TBXAS1(5) 8223816 78 40 76 23 30 23 17 1 7 0 0.13 0.46 179 HSA01031_GLYCAN_STRUCTURES_BIOSYNTHESIS_2 Genes involved in glycan structures - biosynthesis 2 A4GALT, ABO, B3GALNT1, B3GALT1, B3GALT2, B3GALT4, B3GALT5, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT4, B4GALT6, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GBGT1, GCNT2, PIGA, PIGB, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGU, PIGV, PIGX, PIGZ, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST3GAL5, ST3GAL6, ST6GALNAC3, ST6GALNAC4, ST6GALNAC5, ST6GALNAC6, ST8SIA1, ST8SIA5, UGCG, UGCGL1, UGCGL2 60 A4GALT(3), ABO(2), B3GALNT1(4), B3GALT1(1), B3GALT2(3), B3GALT4(1), B3GALT5(4), B3GNT1(2), B3GNT2(2), B3GNT3(1), B3GNT4(1), B3GNT5(1), B4GALNT1(4), B4GALT1(6), B4GALT2(3), B4GALT3(7), B4GALT6(5), FUT1(4), FUT2(1), FUT3(4), FUT6(1), FUT9(5), GCNT2(10), PIGA(1), PIGB(3), PIGG(3), PIGK(4), PIGM(3), PIGN(2), PIGO(3), PIGQ(1), PIGS(2), PIGT(3), PIGU(1), PIGV(2), PIGX(4), ST3GAL1(1), ST3GAL2(1), ST3GAL3(4), ST3GAL4(2), ST3GAL6(7), ST6GALNAC3(4), ST6GALNAC4(2), ST6GALNAC5(6), ST6GALNAC6(3), ST8SIA1(3), ST8SIA5(6), UGCG(2) 16392716 148 51 147 44 57 41 29 1 20 0 0.14 0.48 180 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 78 ABL1(4), BUB1(6), BUB1B(6), BUB3(2), CCNA1(6), CCNA2(3), CCNB1(2), CCNB2(2), CCNB3(7), CCND2(1), CCND3(1), CCNE1(3), CCNE2(2), CCNH(2), CDAN1(3), CDC14A(4), CDC14B(4), CDC20(3), CDC25A(2), CDC25B(5), CDC25C(4), CDC6(1), CDC7(3), CDH1(5), CDK2(2), CDK4(3), CDKN1A(1), CHEK1(1), CHEK2(1), DTX4(3), E2F2(1), E2F3(2), E2F4(1), E2F5(2), EP300(15), ESPL1(8), HDAC1(2), HDAC2(2), HDAC3(2), HDAC4(5), HDAC5(2), HDAC6(7), MAD1L1(2), MAD2L1(1), MAD2L2(1), MCM3(4), MCM4(4), MCM5(6), MCM6(4), MCM7(3), MDM2(4), MPEG1(4), MPL(2), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(3), PLK1(9), PRKDC(18), PTPRA(2), PTTG1(1), RB1(7), RBL1(5), SKP2(1), TBC1D8(5), TFDP1(4), TGFB1(1), WEE1(3) 34750908 239 73 235 70 66 75 61 6 30 1 0.14 0.48 181 HSA00680_METHANE_METABOLISM Genes involved in methane metabolism ADH5, CAT, EPX, LPO, MPO, MTHFR, PRDX6, SHMT1, SHMT2, TPO 10 ADH5(1), CAT(3), EPX(7), LPO(3), MPO(5), MTHFR(7), PRDX6(2), SHMT1(2), SHMT2(2), TPO(11) 3940752 43 30 42 16 24 11 5 0 3 0 0.14 0.49 182 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(2), ACTR3(3), AKT1(2), ANGPTL2(8), DAG1(5), DGKA(1), ETFA(3), ITGA9(6), ITPKB(4), ITPR1(19), ITPR2(18), ITPR3(12), MAP2K1(4), MAPK1(2), MAPK3(3), NR1I3(3), PAK1(5), PDE3A(5), PDE3B(3), PI3(1), PIK3C2G(9), PIK3CD(3), PLDN(1), RIPK3(4), RPS4X(2), SGCB(4), VASP(3) 15493376 135 53 135 40 49 37 24 3 20 2 0.15 0.50 183 INOSITOL_METABOLISM ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 5 ALDH6A1(4), ALDOA(1), ALDOB(5), ALDOC(3), TPI1(1) 1279096 14 13 14 1 4 7 3 0 0 0 0.15 0.50 184 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(5), CARS(6), DARS(4), EPRS(12), FARS2(5), GARS(3), HARS(2), IARS(6), KARS(3), LARS(5), LARS2(3), MARS(6), MARS2(1), NARS(3), QARS(8), RARS(4), SARS(2), TARS(6), WARS(3), WARS2(3), YARS(2) 10758584 92 43 92 16 30 26 24 2 10 0 0.15 0.50 185 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 3 FAH(2), GSTZ1(2), HGD(2) 576560 6 5 6 4 1 2 2 0 1 0 0.15 0.50 186 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(5), ADH1A(1), ADH1B(3), ADH1C(4), ADH4(2), ADH5(1), ADH6(6), ADH7(2), ADHFE1(6), DHRS1(1), DHRS2(3), DHRS3(2), ESCO1(11), ESCO2(4), MYST3(18), MYST4(10), PNPLA3(4), SH3GLB1(4) 8215268 88 40 87 31 28 27 26 1 6 0 0.15 0.50 187 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 28 DUSP1(2), GORASP1(4), MAPK1(2), MAPK12(2), MAPK13(1), MAPK14(3), MAPK3(3), MAPK8(7), MAPK8IP1(4), MAPK8IP3(2), MAPK9(5), MAPKAPK5(1), NFKB1(6), NFKB2(4), NFKBIB(1), NFKBIE(2), PIK3CD(3), SYT1(1), TRAF2(1), TRAF3(6), TRAF5(6), TRAF6(4) 9242376 70 40 69 26 22 14 14 4 16 0 0.15 0.50 188 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(2), AR(6), ASAH1(3), CCL13(1), CCL15(1), DAG1(5), EGFR(12), GNA11(1), GNA15(3), GNAI1(4), GNAQ(4), ITPKB(4), ITPR1(19), ITPR2(18), ITPR3(12), KCNJ3(6), KCNJ5(4), KCNJ9(3), MAPK1(2), MAPK14(3), PHKA2(7), PIK3CD(3), PITX2(2), PTX3(2), RAF1(6), SRC(3) 14211388 136 58 135 55 64 37 23 0 11 1 0.15 0.50 189 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(7), PARK2(6), SNCA(1), SNCAIP(3), UBE2E2(1), UBE2F(1), UBE2G1(2), UBE2L3(2) 2137016 23 17 23 8 6 11 5 0 1 0 0.15 0.50 190 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(6), CCNA2(3), CCNE1(3), CCNE2(2), CDK2(2), CDK4(3), CDKN1B(3), E2F2(1), E2F4(1), PRB1(1) 2935608 25 20 25 7 7 6 6 1 5 0 0.16 0.51 191 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 5 ATR(18), CDC25C(4), CHEK1(1), CHEK2(1), YWHAH(1) 2983932 25 16 25 4 9 10 2 0 4 0 0.16 0.52 192 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(5), CD28(2), CD3D(1), CSK(4), CTLA4(2), DAG1(5), DTYMK(1), EPHB2(8), GRAP2(5), GRB2(3), ITK(11), ITPKB(4), LAT(1), LCK(3), LCP2(3), MAPK1(2), NCK1(1), NFAT5(5), NFKB1(6), NFKB2(4), NFKBIB(1), NFKBIE(2), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PLCG1(4), PTPRC(17), RAF1(6), RASGRP1(5), RASGRP2(7), RASGRP3(7), RASGRP4(2), SOS1(7), SOS2(11), VAV1(13), ZAP70(4) 18270412 183 62 179 57 70 64 31 2 16 0 0.16 0.52 193 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), ALG10(3), ALG10B(8), ALG11(1), ALG12(2), ALG13(1), ALG14(1), ALG2(3), ALG3(1), ALG5(3), ALG6(3), ALG8(6), ALG9(2), B4GALT1(6), B4GALT2(3), B4GALT3(7), DAD1(2), DDOST(2), DHDDS(1), DPAGT1(2), DPM1(1), FUT8(2), GANAB(4), MAN1A1(5), MAN1A2(2), MAN1B1(2), MAN1C1(7), MAN2A1(12), MGAT1(2), MGAT3(2), MGAT4A(2), MGAT4B(1), MGAT5(3), MGAT5B(2), RPN2(1), ST6GAL1(1), STT3B(6) 14281672 113 52 111 28 37 37 30 0 9 0 0.16 0.52 194 NO1PATHWAY Shear stress in endothelial cells increases cytoplasmic calcium, which activates nitric oxide synthase III to release NO, which in turn regulates cardiac contractions. ACTA1, AKT1, BDK, BDKRB2, CALM1, CALM2, CALM3, CAV1, CHRM1, CHRNA1, FLT1, FLT4, HSPCA, KDR, NOS3, PDE2A, PDE3A, PDE3B, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKG1, PRKG2, RYR2, SLC7A1, SYT1, TNNI1, VEGF 28 ACTA1(4), AKT1(2), BDKRB2(3), CAV1(1), CHRM1(3), CHRNA1(4), FLT1(13), FLT4(5), KDR(10), NOS3(2), PDE3A(5), PDE3B(3), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PRKG1(9), PRKG2(5), RYR2(59), SLC7A1(2), SYT1(1), TNNI1(2) 13801952 146 54 146 57 46 54 32 1 13 0 0.17 0.53 195 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 A4GALT(3), B3GALNT1(4), B3GALT5(4), FUT1(4), FUT2(1), FUT9(5), GLA(4), HEXB(3), NAGA(1), ST3GAL1(1), ST3GAL2(1), ST8SIA1(3) 3554180 34 20 33 12 14 8 7 0 5 0 0.17 0.54 196 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(2), AKT2(6), AKT3(1), BAD(1), BCR(7), BLNK(1), BTK(7), CD19(3), CSK(4), DAG1(5), EPHB2(8), GRB2(3), ITPKB(4), LYN(4), MAP2K1(4), MAP2K2(1), MAPK1(2), NFAT5(5), NFKB1(6), NFKB2(4), NFKBIB(1), NFKBIE(2), PI3(1), PIK3CD(3), PLCG2(13), PPP1R13B(6), RAF1(6), SERPINA4(5), SHC1(3), SOS1(7), SOS2(11), SYK(3), VAV1(13) 16282968 152 59 147 39 63 43 29 2 15 0 0.17 0.54 197 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(6), MAP3K14(3), MAPK14(3), MAPK8(7), NFKB1(6), RELA(2), TNFRSF13B(4), TNFRSF17(2), TNFSF13(2), TNFSF13B(1), TRAF2(1), TRAF3(6), TRAF5(6), TRAF6(4) 4968172 53 29 52 15 21 12 9 3 8 0 0.17 0.54 198 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(2), PLCB1(8), PLCG1(4), PRKCA(4), VAV1(13) 3087972 31 24 31 12 14 9 5 1 2 0 0.18 0.54 199 HSA04020_CALCIUM_SIGNALING_PATHWAY Genes involved in calcium signaling pathway ADCY1, ADCY2, ADCY3, ADCY4, ADCY7, ADCY8, ADCY9, ADORA2A, ADORA2B, ADRA1A, ADRA1B, ADRA1D, ADRB1, ADRB2, ADRB3, AGTR1, ATP2A1, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, ATP2B4, AVPR1A, AVPR1B, BDKRB1, BDKRB2, BST1, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, CACNA1I, CACNA1S, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CCKAR, CCKBR, CD38, CHP, CHRM1, CHRM2, CHRM3, CHRM5, CHRNA7, CYSLTR1, CYSLTR2, DRD1, EDNRA, EDNRB, EGFR, ERBB2, ERBB3, ERBB4, F2R, GNA11, GNA14, GNA15, GNAL, GNAQ, GNAS, GRIN1, GRIN2A, GRIN2C, GRIN2D, GRM1, GRM5, GRPR, HRH1, HRH2, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, LHCGR, LTB4R2, MLCK, MYLK, MYLK2, NOS1, NOS2A, NOS3, NTSR1, OXTR, P2RX1, P2RX2, P2RX3, P2RX4, P2RX5, P2RX7, P2RXL1, PDE1A, PDE1B, PDE1C, PDGFRA, PDGFRB, PHKA1, PHKA2, PHKB, PHKG1, PHKG2, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCZ1, PLN, PPID, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PTAFR, PTGER1, PTGER3, PTGFR, PTK2B, RYR1, RYR2, RYR3, SLC25A4, SLC25A5, SLC25A6, SLC8A1, SLC8A2, SLC8A3, SPHK1, SPHK2, TACR1, TACR2, TACR3, TBXA2R, TNNC1, TNNC2, TRHR, TRPC1, VDAC1, VDAC2, VDAC3 163 ADCY1(8), ADCY2(15), ADCY3(2), ADCY4(9), ADCY7(4), ADCY8(12), ADCY9(6), ADORA2A(5), ADORA2B(1), ADRA1A(5), ADRA1B(5), ADRA1D(2), ADRB1(3), ADRB3(1), AGTR1(6), ATP2A1(6), ATP2A2(6), ATP2A3(4), ATP2B1(9), ATP2B2(11), ATP2B3(4), ATP2B4(8), AVPR1A(4), AVPR1B(3), BDKRB2(3), CACNA1A(17), CACNA1B(11), CACNA1C(12), CACNA1D(9), CACNA1E(21), CACNA1F(14), CACNA1G(11), CACNA1H(2), CACNA1I(5), CACNA1S(15), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CAMK4(3), CCKAR(3), CCKBR(5), CD38(2), CHRM1(3), CHRM3(4), CHRM5(2), CHRNA7(1), CYSLTR1(3), CYSLTR2(4), DRD1(1), EDNRA(4), EGFR(12), ERBB2(10), ERBB3(14), F2R(1), GNA11(1), GNA14(6), GNA15(3), GNAL(4), GNAQ(4), GNAS(6), GRIN1(1), GRIN2C(5), GRIN2D(5), GRM1(12), GRM5(11), GRPR(3), HRH1(1), HRH2(4), HTR2A(3), HTR2B(1), HTR2C(8), HTR4(3), HTR5A(5), HTR7(7), ITPKB(4), ITPR1(19), ITPR2(18), ITPR3(12), LHCGR(4), MYLK(14), MYLK2(3), NOS1(11), NOS3(2), NTSR1(1), OXTR(3), P2RX1(1), P2RX2(2), P2RX3(2), P2RX4(3), P2RX5(1), P2RX7(3), PDE1A(4), PDE1B(3), PDE1C(9), PDGFRA(17), PDGFRB(6), PHKA1(8), PHKA2(7), PHKB(5), PHKG2(3), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), PLCD1(7), PLCD3(2), PLCD4(2), PLCE1(9), PLCG1(4), PLCG2(13), PLCZ1(4), PLN(1), PPID(3), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PRKACA(1), PRKACB(1), PRKACG(3), PRKCA(4), PRKCG(10), PRKX(2), PTAFR(1), PTGER3(7), PTGFR(6), PTK2B(1), RYR1(25), RYR2(59), RYR3(42), SLC25A4(1), SLC25A5(1), SLC8A1(13), SLC8A2(4), SLC8A3(7), SPHK1(1), SPHK2(1), TACR1(2), TACR2(1), TACR3(8), TNNC2(1), TRHR(8), TRPC1(6), VDAC1(1), VDAC3(1) 90276576 899 165 883 349 375 276 160 7 78 3 0.18 0.55 200 PROTEASOME PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB10, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMB8, PSMB9 17 PSMA1(1), PSMA2(1), PSMA3(3), PSMA4(2), PSMA5(1), PSMA7(1), PSMB2(2), PSMB3(1), PSMB5(2), PSMB6(2), PSMB8(3), PSMB9(4) 2851344 23 18 23 7 6 7 5 2 3 0 0.18 0.55 201 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(2), HADH(1), HADHA(3), HADHB(2), HSD17B10(2), HSD17B4(3), MECR(1), PPT2(2) 2848532 17 14 17 9 3 5 2 0 7 0 0.18 0.56 202 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(2), INPP1(2), INPP4A(3), INPP4B(7), INPP5A(2), INPPL1(4), ITPKB(4), MIOX(1), OCRL(9), PIK3C2A(5), PIK3C2B(8), PIK3C2G(9), PIK3CB(2), PIK3CG(14), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), PLCD1(7), PLCG1(4), PLCG2(13) 14561824 121 53 119 33 50 38 21 1 11 0 0.19 0.57 203 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(4), JAK2(9), JAK3(9), MAPK1(2), MAPK3(3), STAT3(2), TYK2(1) 4021052 30 21 29 10 9 9 4 0 6 2 0.19 0.57 204 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 8 CARS(6), CTH(2), GOT1(6), GOT2(1), LDHA(2), LDHB(3), LDHC(2) 2260944 22 15 21 4 9 7 3 0 3 0 0.19 0.57 205 BIOGENIC_AMINE_SYNTHESIS AANAT, ACHE, CHAT, COMT, DBH, DDC, DXYS155E, GAD1, GAD2, HDC, MAOA, PAH, PNMT, SLC18A3, TH, TPH1 15 ACHE(2), CHAT(6), DBH(5), DDC(1), GAD1(9), GAD2(4), HDC(8), MAOA(3), PAH(4), SLC18A3(6), TPH1(3) 4854580 51 35 51 24 19 20 9 0 3 0 0.19 0.57 206 NTHIPATHWAY Hemophilus influenzae infections activate NF-kB via several pathways, inducing the inflammatory response. CHUK, CREBBP, DUSP1, EP300, IKBKB, IL1B, IL8, MADH3, MADH4, MAP2K3, MAP2K6, MAP3K14, MAP3K7, MAPK11, MAPK14, MYD88, NFKB1, NFKBIA, NR3C1, RELA, TGFBR1, TGFBR2, TLR2, TNF 21 CHUK(6), CREBBP(25), DUSP1(2), EP300(15), IKBKB(4), IL1B(1), IL8(1), MAP2K3(6), MAP2K6(3), MAP3K14(3), MAP3K7(4), MAPK14(3), MYD88(2), NFKB1(6), NR3C1(4), RELA(2), TGFBR1(9), TLR2(6) 9617228 102 40 101 33 33 28 27 3 11 0 0.20 0.58 207 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(4), ACO1(5), ACO2(2), ACSS1(3), ACSS2(6), FH(1), IDH1(3), IDH2(7), MDH1(1), MDH2(1), SUCLA2(5) 4470360 38 26 38 12 15 11 7 1 4 0 0.20 0.58 208 PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS ENO1, ENO2, ENO3, FARS2, FARSLB, GOT1, GOT2, PAH, TAT, YARS 9 ENO2(3), ENO3(4), FARS2(5), GOT1(6), GOT2(1), PAH(4), TAT(5), YARS(2) 2781724 30 19 29 7 8 11 6 0 5 0 0.20 0.58 209 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(5), ACTN2(8), ACTN3(3), CSK(4), CTNNA1(12), CTNNA2(12), PECAM1(2), PTK2(6), SRC(3), VCL(2) 6312012 57 36 57 24 31 15 4 1 6 0 0.20 0.58 210 HSA00480_GLUTATHIONE_METABOLISM Genes involved in glutathione metabolism ANPEP, G6PD, GCLC, GCLM, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GSR, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, OPLAH, TXNDC12 34 ANPEP(8), G6PD(3), GCLC(4), GCLM(1), GPX1(1), GPX2(2), GPX3(3), GPX5(4), GPX6(3), GSR(1), GSS(4), GSTA1(1), GSTA3(4), GSTA5(2), GSTM2(2), GSTM3(3), GSTM4(2), GSTM5(1), GSTO2(1), GSTZ1(2), IDH1(3), IDH2(7), MGST1(2), MGST3(1), TXNDC12(2) 6949940 67 36 67 10 14 27 19 0 7 0 0.20 0.58 211 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 37 AR(6), ESR2(3), ESRRA(3), HNF4A(6), NPM1(1), NR0B1(3), NR1D1(4), NR1D2(6), NR1H3(4), NR1I2(2), NR1I3(3), NR2C2(4), NR2E1(2), NR2F1(3), NR2F2(5), NR2F6(1), NR3C1(4), NR4A1(2), NR4A2(7), NR5A2(4), PGR(4), PPARA(1), PPARD(2), PPARG(1), RARG(5), ROR1(9), RORA(2), RORC(1), RXRA(1), RXRB(3), RXRG(4), THRA(2), THRB(4), VDR(2) 12308568 114 55 113 44 50 32 24 2 6 0 0.20 0.58 212 METHANE_METABOLISM ADH5, ATP6V0C, SHMT1, CAT, EPX, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, SHMT1, SHMT2, TPO 13 ADH5(1), ATP6V0C(1), CAT(3), EPX(7), LPO(3), MPO(5), PRDX1(1), PRDX6(2), SHMT1(2), SHMT2(2), TPO(11) 4010432 38 29 37 16 22 9 3 0 4 0 0.20 0.58 213 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(2), CREB1(1), MAP2K1(4), MAP2K2(1), MAP2K3(6), MAP2K6(3), MAP3K1(8), MAPK1(2), MAPK14(3), MAPK3(3), NFKB1(6), RB1(7), RELA(2), SP1(2) 5375656 50 27 50 13 17 13 12 2 5 1 0.20 0.58 214 HSA00232_CAFFEINE_METABOLISM Genes involved in caffeine metabolism CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH 7 CYP1A2(3), CYP2A13(7), CYP2A6(6), CYP2A7(5), XDH(7) 2686328 28 18 28 12 7 11 6 0 4 0 0.20 0.58 215 VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS BCAT1, IARS, LARS, LARS2, PDHA1, PDHA2, PDHB 7 BCAT1(1), IARS(6), LARS(5), LARS2(3), PDHA1(5), PDHA2(8), PDHB(2) 3376212 30 19 29 7 11 9 6 0 4 0 0.20 0.58 216 HSA00512_O_GLYCAN_BIOSYNTHESIS Genes involved in O-glycan biosynthesis B3GNT6, B4GALT5, C1GALT1, C1GALT1C1, GALNT1, GALNT10, GALNT11, GALNT12, GALNT13, GALNT14, GALNT17, GALNT2, GALNT3, GALNT4, GALNT5, GALNT6, GALNT7, GALNT8, GALNT9, GALNTL1, GALNTL2, GALNTL4, GALNTL5, GCNT1, GCNT3, GCNT4, OGT, ST3GAL1, ST3GAL2, ST6GALNAC1, WBSCR17 29 B4GALT5(2), C1GALT1C1(2), GALNT1(3), GALNT10(5), GALNT11(5), GALNT12(2), GALNT13(5), GALNT14(10), GALNT2(4), GALNT3(4), GALNT5(10), GALNT6(3), GALNT7(3), GALNT8(2), GALNT9(2), GALNTL1(5), GALNTL2(8), GALNTL4(2), GALNTL5(8), GCNT1(5), GCNT3(4), GCNT4(7), OGT(5), ST3GAL1(1), ST3GAL2(1), ST6GALNAC1(3) 10485352 111 45 110 28 37 41 19 0 14 0 0.20 0.58 217 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 57 AKT1(2), AKT2(6), AKT3(1), BCL10(3), BLNK(1), BTK(7), CARD11(9), CD19(3), CD22(11), CD72(4), CD79A(3), CD79B(1), CHUK(6), CR2(11), FOS(1), IFITM1(1), IKBKB(4), INPP5D(4), LILRB3(2), LYN(4), MALT1(7), NFAT5(5), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), NFKB1(6), NFKB2(4), NFKBIB(1), NFKBIE(2), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PLCG2(13), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PTPN6(4), RASGRP3(7), SYK(3), VAV1(13), VAV2(4), VAV3(12) 23232368 222 67 217 64 98 71 31 1 21 0 0.21 0.58 218 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 10 COL4A1(14), COL4A2(4), COL4A3(4), COL4A4(10), COL4A6(15), P4HB(2), SLC23A1(2), SLC23A2(7), SLC2A1(1), SLC2A3(1) 7547300 60 32 59 16 18 17 11 1 13 0 0.21 0.58 219 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(2), ACAA2(1), ACADL(2), ACADM(6), ACADSB(5), ACAT1(1), ACAT2(2), ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH6A1(4), ALDH9A1(1), AOX1(8), BCAT1(1), BCKDHA(3), BCKDHB(1), ECHS1(2), EHHADH(2), HADHA(3), HADHB(2), HMGCL(1), MCCC1(8), MCCC2(2), MCEE(2), MUT(4), OXCT1(3), PCCA(9), PCCB(4), SDS(2) 12168408 113 48 112 27 41 41 15 0 16 0 0.21 0.58 220 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 6 DBH(5), GAD1(9), HDC(8), TPH1(3) 1993740 25 19 25 8 9 12 3 0 1 0 0.21 0.58 221 ST_TYPE_I_INTERFERON_PATHWAY Type I interferon is an antiviral cytokine that induces a JAK-STAT type pathway leading to ISGF3 activation and a cellular antiviral response. IFNAR1, IFNB1, ISGF3G, JAK1, PTPRU, REG1A, STAT1, STAT2, TYK2 8 IFNAR1(3), IFNB1(1), JAK1(4), PTPRU(13), REG1A(5), STAT1(6), STAT2(7), TYK2(1) 4233004 40 27 38 9 23 7 6 0 4 0 0.21 0.58 222 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 24 AKT1(2), AKT2(6), AKT3(1), BAD(1), BCL2(1), GRB2(3), GSK3A(2), IL4R(1), IRS1(9), JAK1(4), JAK3(9), MAP4K1(3), MAPK1(2), MAPK3(3), PDK1(2), PIK3CD(3), PPP1R13B(6), RAF1(6), SHC1(3), SOS1(7), SOS2(11), STAT6(2) 10694424 87 41 84 24 27 29 16 0 15 0 0.22 0.60 223 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 33 AKT1(2), ATF1(2), CDC42(1), CREB1(1), CREB3(3), CREB5(4), DUSP1(2), DUSP10(5), EEF2K(1), IL1R1(4), MAP2K3(6), MAP2K6(3), MAP3K10(3), MAP3K5(7), MAP3K7(4), MAPK1(2), MAPK12(2), MAPK13(1), MAPK14(3), MAPKAPK2(3), MAPKAPK5(1), MKNK1(1), MKNK2(3), MYEF2(7), NFKB1(6), NR2C2(4), SRF(3), TRAF6(4) 10002000 88 42 88 20 27 28 19 3 11 0 0.22 0.60 224 HSA00785_LIPOIC_ACID_METABOLISM Genes involved in lipoic acid metabolism LIAS, LIPT1, LOC387787 2 LIAS(4), LIPT1(4) 512736 8 6 8 1 0 6 1 0 1 0 0.22 0.61 225 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(6), CCNB1(2), CCND2(1), CCND3(1), CCNE1(3), CCNH(2), CDC25A(2), CDK2(2), CDK4(3), CDK6(1), CDK7(1), CDKN1A(1), CDKN1B(3), CDKN2C(1), RB1(7), RBL1(5), TFDP1(4) 5369992 45 31 45 12 14 10 12 1 7 1 0.23 0.63 226 GLOBOSIDE_METABOLISM A4GALT, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, ST8SIA1 13 A4GALT(3), FUT1(4), FUT2(1), FUT9(5), GLA(4), HEXB(3), NAGA(1), ST3GAL1(1), ST3GAL2(1), ST3GAL4(2), ST8SIA1(3) 3348292 28 19 28 11 9 7 7 0 5 0 0.23 0.63 227 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALE(1), GALT(2), TGDS(1), UGDH(4), UXS1(7) 1358528 15 12 15 4 5 6 2 0 2 0 0.24 0.64 228 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 62 CCNA1(6), CCNB1(2), CCND2(1), CCND3(1), CCNE1(3), CCNE2(2), CCNH(2), CDC25A(2), CDK2(2), CDK4(3), CDK7(1), CDKN1A(1), CDKN1B(3), CDKN2C(1), CREB3(3), CREB3L1(3), CREB3L3(3), CREB3L4(1), E2F2(1), E2F3(2), E2F4(1), E2F5(2), GBA2(5), MCM3(4), MCM4(4), MCM5(6), MCM6(4), MCM7(3), MDM2(4), MNAT1(1), MYT1(13), NACA(5), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(3), POLA2(2), POLE(21), POLE2(1), RB1(7), RBL1(5), RPA1(2), RPA2(1), TFDP1(4), TFDP2(1), TNXB(17), WEE1(3) 23077576 166 60 163 42 50 59 33 2 21 1 0.24 0.64 229 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(8), AKT1(2), BAD(1), BAX(1), BCL2(1), BCL2L1(1), CSF2RB(7), IGF1(2), IGF1R(8), IL3(3), KIT(8), KITLG(2), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), YWHAH(1) 5784420 58 37 57 24 27 18 8 0 5 0 0.24 0.64 230 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 124 ACACA(18), ACACB(15), AKT1(2), AKT2(6), AKT3(1), ARAF(3), BAD(1), CBL(5), CBLB(8), CRKL(2), EXOC7(2), FASN(1), FBP2(3), FLOT1(3), FOXO1(1), G6PC(4), G6PC2(1), GCK(2), GRB2(3), GYS1(2), GYS2(11), IKBKB(4), INPP5D(4), INSR(6), IRS1(9), IRS4(15), LIPE(4), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK3(3), MAPK8(7), MAPK9(5), MKNK1(1), MKNK2(3), PCK1(3), PCK2(4), PDE3A(5), PDE3B(3), PDPK1(1), PFKL(1), PFKM(4), PFKP(2), PHKA1(8), PHKA2(7), PHKB(5), PHKG2(3), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PKM2(2), PPARGC1A(5), PPP1CB(2), PPP1CC(2), PPP1R3A(13), PPP1R3B(1), PPP1R3C(4), PPP1R3D(1), PRKAA1(3), PRKAA2(9), PRKAB1(2), PRKAB2(1), PRKACA(1), PRKACB(1), PRKACG(3), PRKAG1(1), PRKAG2(3), PRKAG3(6), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PRKCI(4), PRKX(2), PTPN1(5), PTPRF(9), PYGB(4), PYGL(2), PYGM(4), RAF1(6), RAPGEF1(6), RPS6KB1(3), RPS6KB2(2), SHC1(3), SHC2(1), SHC3(1), SHC4(5), SLC2A4(4), SOCS2(3), SOCS4(1), SORBS1(11), SOS1(7), SOS2(11), SREBF1(1), TSC1(4), TSC2(2) 51106708 403 97 394 155 147 130 76 5 45 0 0.24 0.64 231 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(2), AGT(5), AGTR1(6), AGTR2(5), BDKRB2(3), KNG1(4), NOS3(2), REN(5) 3308712 32 22 31 9 9 10 6 0 7 0 0.24 0.64 232 HSA00780_BIOTIN_METABOLISM Genes involved in biotin metabolism BTD, HLCS, SPCS1, SPCS3 4 BTD(2), HLCS(6), SPCS1(1), SPCS3(1) 1054048 10 9 8 3 6 1 1 0 2 0 0.24 0.64 233 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(7), DLG4(3), EPHB2(8), F2(4), F2RL1(1), F2RL2(3), MAP2K5(4), MAPK1(2), MAPK7(3), MAPK8(7), MYEF2(7), PLD1(11), PLD2(2), PLD3(5), PTK2(6), RAF1(6), RASAL1(2), SRC(3), TEC(3), VAV1(13) 9394616 100 44 98 30 47 31 15 1 6 0 0.24 0.64 234 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(6), ALAS2(6), BLVRA(2), BLVRB(2), COX10(2), COX15(3), CP(6), CPOX(1), EPRS(12), FECH(3), FTMT(4), GUSB(2), HCCS(3), HMBS(2), HMOX1(2), HMOX2(3), MMAB(3), PPOX(3), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(2), UGT1A5(3), UGT1A6(1), UGT1A7(2), UGT1A8(1), UGT1A9(6), UGT2A1(8), UGT2A3(7), UGT2B10(1), UGT2B11(6), UGT2B15(2), UGT2B17(7), UGT2B28(3), UGT2B4(3), UGT2B7(6), UROD(1), UROS(1) 13510988 130 46 127 28 35 59 23 0 13 0 0.25 0.65 235 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(5), FOS(1), MAP2K1(4), MAPK1(2), MAPK3(3), NFKB1(6), PLCB1(8), PRKCA(4), RAF1(6), RELA(2) 5163740 41 24 40 14 18 9 8 1 5 0 0.25 0.66 236 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 22 ABL1(4), ATR(18), CCNA1(6), CCNE1(3), CDC25A(2), CDK2(2), CDK4(3), CDK6(1), CDKN1A(1), CDKN1B(3), DHFR(1), HDAC1(2), RB1(7), SKP2(1), TFDP1(4), TGFB1(1), TGFB2(9) 7411204 68 33 68 19 22 16 16 1 12 1 0.25 0.66 237 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(2), ACTR3(3), ARPC1A(5), ARPC1B(2), ARPC2(2), CDC42(1), PAK1(5), PDGFRA(17), WASL(7) 3258184 44 17 44 14 12 13 10 1 7 1 0.26 0.66 238 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(2), GRB2(3), IL4(3), IL4R(1), IRS1(9), JAK1(4), JAK3(9), RPS6KB1(3), SHC1(3), STAT6(2) 4961496 39 26 37 12 11 14 5 0 9 0 0.26 0.66 239 HSA04120_UBIQUITIN_MEDIATED_PROTEOLYSIS Genes involved in ubiquitin mediated proteolysis ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, BTRC, CDC16, CDC20, CDC23, CDC26, CDC27, CUL1, CUL2, CUL3, FBXW11, FBXW7, FZR1, ITCH, LOC728919, RBX1, SKP1, SKP2, SMURF1, SMURF2, TCEB1, TCEB2, UBA1, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2D4, UBE2E1, UBE2E2, UBE2E3, VHL, WWP1, WWP2 38 ANAPC1(4), ANAPC10(2), ANAPC2(1), ANAPC4(4), ANAPC5(3), ANAPC7(4), BTRC(5), CDC16(4), CDC20(3), CDC23(6), CDC27(13), CUL1(9), CUL2(5), CUL3(1), FBXW11(8), ITCH(3), RBX1(1), SKP1(1), SKP2(1), SMURF1(3), SMURF2(2), UBA1(2), UBE2C(2), UBE2D1(1), UBE2D3(1), UBE2D4(1), UBE2E1(3), UBE2E2(1), VHL(1), WWP1(8), WWP2(4) 13111512 107 45 102 40 31 36 23 0 17 0 0.26 0.67 240 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 32 GTF2A1(2), GTF2B(1), GTF2E1(5), GTF2F1(5), GTF2F2(1), GTF2H1(4), GTF2H3(4), GTF2H4(1), GTF2IRD1(9), TAF1(12), TAF2(8), TAF4(5), TAF4B(6), TAF5(4), TAF5L(2), TAF6(3), TAF6L(2), TAF7(2), TAF7L(4), TAF9(1), TAF9B(1), TBPL1(1), TBPL2(1) 10882476 84 43 84 18 30 22 21 0 11 0 0.26 0.67 241 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 25 AKT1(2), AKT2(6), AKT3(1), ANKRD6(5), AXIN1(2), AXIN2(9), CER1(3), CSNK1A1(2), DACT1(6), DKK1(5), DKK3(2), FSTL1(6), GSK3A(2), LRP1(18), MVP(4), NKD1(3), NKD2(1), PIN1(1), PSEN1(3), PTPRA(2), SENP2(3), SFRP1(3), TSHB(1), WIF1(2) 10507140 92 47 91 32 39 21 21 0 11 0 0.26 0.67 242 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 23 CSNK2A1(4), FOS(1), GRB2(3), JAK1(4), MAP2K1(4), MAP3K1(8), MAPK3(3), MAPK8(7), PDGFA(1), PDGFRA(17), PLCG1(4), PRKCA(4), RAF1(6), RASA1(9), SHC1(3), SOS1(7), SRF(3), STAT1(6), STAT3(2) 10211944 96 39 93 26 29 32 23 1 10 1 0.26 0.67 243 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 43 ADH1A(1), ADH1B(3), ADH1C(4), ADH4(2), ADH6(6), ADH7(2), ADHFE1(6), AGPAT1(2), AGPAT3(3), AKR1B1(3), ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), CEL(1), DGKA(1), DGKB(9), DGKD(12), DGKE(3), DGKG(3), DGKH(10), DGKZ(3), GK(3), GLA(4), GLB1(3), LCT(20), LIPC(4), LIPF(3), LIPG(2), LPL(6), PNLIP(7), PNLIPRP1(4), PNLIPRP2(2), PPAP2B(1) 15824776 166 51 166 49 53 60 39 0 14 0 0.27 0.67 244 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 27 CRKL(2), GNAQ(4), GRB2(3), MAP2K1(4), MAP2K2(1), MAP2K3(6), MAP3K1(8), MAPK1(2), MAPK14(3), MAPK3(3), MAPK8(7), PAK1(5), PLCG1(4), PRKCA(4), PTK2B(1), RAF1(6), SHC1(3), SOS1(7), SRC(3), SYT1(1) 9362552 77 38 75 24 20 27 17 4 9 0 0.27 0.68 245 HBXPATHWAY Hbx is a hepatitis B protein that activates a number of transcription factors, possibly by inducing calcium release from the mitochondrion to the cytoplasm. CREB1, GRB2, HBXIP, HRAS, PTK2B, SHC1, SOS1, SRC 8 CREB1(1), GRB2(3), HBXIP(2), PTK2B(1), SHC1(3), SOS1(7), SRC(3) 2968856 20 17 19 7 2 10 5 0 3 0 0.27 0.68 246 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 20 COL4A1(14), COL4A2(4), COL4A3(4), COL4A4(10), COL4A6(15), F10(1), F11(4), F12(2), F2(4), F2R(1), F5(21), F8(18), F9(6), FGB(2), FGG(4), KLKB1(6), PROC(1), PROS1(6), SERPINC1(3), SERPING1(5) 13400776 131 45 127 35 28 55 26 1 21 0 0.27 0.68 247 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 16 CD28(2), HLA-DRA(5), HLA-DRB1(3), IFNG(1), IFNGR1(3), IFNGR2(2), IL12A(1), IL12B(2), IL12RB1(2), IL12RB2(6), IL2(4), IL2RA(2), IL4(3), IL4R(1) 3858816 37 20 37 13 13 16 3 0 3 2 0.27 0.68 248 METHIONINEPATHWAY Catabolic Pathways for Methionine, Isoleucine, Threonine and Valine BCKDHB, BCKDK, CBS, CTH, MUT 5 BCKDHB(1), BCKDK(3), CBS(3), CTH(2), MUT(4) 1640048 13 11 13 1 5 4 0 0 4 0 0.28 0.68 249 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(5), EGF(3), EGFR(12), GRB2(3), MAP2K1(4), MAPK1(2), MAPK3(3), PTPRB(4), RAF1(6), RASA1(9), SHC1(3), SOS1(7), SPRY1(3), SPRY4(2), SRC(3) 8266640 69 35 67 25 24 22 17 0 6 0 0.28 0.68 250 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(4), NFKB1(6), PLCB1(8), PRKCA(4), RELA(2) 2786092 24 16 24 9 10 6 3 1 4 0 0.28 0.68 251 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(9), EGF(3), EGFR(12), TF(11), TFRC(3) 4321724 38 23 38 7 17 10 7 0 3 1 0.28 0.69 252 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 13 AKT1(2), CDKN1B(3), GRB2(3), ITGB1(6), MAPK1(2), MAPK3(3), PDK2(2), PDPK1(1), PTK2(6), SHC1(3), SOS1(7) 4953864 38 26 37 11 6 14 11 0 7 0 0.28 0.69 253 HSA00730_THIAMINE_METABOLISM Genes involved in thiamine metabolism LHPP, MTMR1, MTMR2, MTMR6, NFS1, PHPT1, THTPA, TPK1 8 LHPP(2), MTMR1(5), MTMR2(2), MTMR6(4), NFS1(2), PHPT1(1), THTPA(1), TPK1(3) 2155772 20 15 20 5 8 6 4 0 2 0 0.28 0.69 254 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 182 ACTB(2), ACTN1(5), ACTN2(8), ACTN3(3), ACTN4(3), AKT1(2), AKT2(6), AKT3(1), ARHGAP5(9), BAD(1), BCL2(1), BIRC2(4), BIRC3(7), CAPN2(7), CAV1(1), CAV2(1), CAV3(3), CCND2(1), CCND3(1), CDC42(1), CHAD(7), COL11A1(24), COL11A2(11), COL1A1(11), COL1A2(16), COL2A1(9), COL3A1(12), COL4A1(14), COL4A2(4), COL4A4(10), COL4A6(15), COL5A1(16), COL5A2(13), COL5A3(10), COL6A2(1), COL6A6(20), COMP(2), CRKL(2), DIAPH1(1), DOCK1(7), EGF(3), EGFR(12), ERBB2(10), FARP2(5), FIGF(2), FLNA(3), FLNB(16), FLNC(13), FLT1(13), FN1(22), FYN(5), GRB2(3), GRLF1(12), HGF(8), IBSP(3), IGF1(2), IGF1R(8), ITGA1(3), ITGA10(7), ITGA11(4), ITGA2(6), ITGA2B(4), ITGA3(4), ITGA4(8), ITGA5(7), ITGA6(4), ITGA7(6), ITGA8(8), ITGA9(6), ITGAV(5), ITGB1(6), ITGB3(9), ITGB4(3), ITGB5(6), ITGB6(6), ITGB7(4), ITGB8(5), KDR(10), LAMA1(24), LAMA2(25), LAMA3(18), LAMA4(11), LAMB1(8), LAMB2(5), LAMB3(9), LAMB4(16), LAMC1(11), LAMC2(10), LAMC3(8), MAP2K1(4), MAPK1(2), MAPK3(3), MAPK8(7), MAPK9(5), MET(5), MYL2(1), MYL7(1), MYL9(2), MYLK(14), MYLK2(3), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PARVA(1), PARVB(5), PARVG(3), PDGFA(1), PDGFC(3), PDGFD(3), PDGFRA(17), PDGFRB(6), PDPK1(1), PGF(2), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PIP5K1C(4), PPP1CB(2), PPP1CC(2), PPP1R12A(3), PRKCA(4), PRKCG(10), PTK2(6), RAF1(6), RAP1A(2), RAP1B(2), RAPGEF1(6), RHOA(5), ROCK1(15), ROCK2(6), SHC1(3), SHC2(1), SHC3(1), SHC4(5), SOS1(7), SOS2(11), SPP1(1), SRC(3), THBS1(10), THBS2(15), THBS3(3), THBS4(2), TLN1(7), TLN2(9), TNC(16), TNN(17), TNXB(17), VASP(3), VAV1(13), VAV2(4), VAV3(12), VCL(2), VEGFA(2), VEGFB(2), VEGFC(6), VTN(6), VWF(15), ZYX(1) 116451300 1080 162 1064 412 385 365 192 11 125 2 0.29 0.69 255 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(1), GOT1(6), GOT2(1), TAT(5), TYR(3) 1578396 16 12 15 7 6 5 3 0 2 0 0.29 0.69 256 HSA05050_DENTATORUBROPALLIDOLUYSIAN_ATROPHY Genes involved in dentatorubropallidoluysian atrophy (DRPLA) ATN1, BAIAP2, CASP1, CASP3, CASP7, CASP8, GAPDH, INS, INSR, ITCH, MAGI1, MAGI2, RERE, WWP1, WWP2 14 ATN1(4), BAIAP2(2), CASP1(2), CASP3(2), CASP7(1), INSR(6), ITCH(3), MAGI1(13), MAGI2(11), RERE(3), WWP1(8), WWP2(4) 7534216 59 38 58 23 20 19 10 0 10 0 0.29 0.69 257 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 55 ALG2(3), BAK1(1), BAX(1), BFAR(1), BTK(7), CAD(12), CASP10(2), CASP3(2), CASP8AP2(18), CD7(1), CSNK1A1(2), DAXX(1), DEDD(1), DFFA(3), DIABLO(1), EGFR(12), EPHB2(8), FAF1(4), FAIM2(3), IL1A(1), IL8(1), MAP3K1(8), MAP3K5(7), MAPK1(2), MAPK8(7), MAPK8IP1(4), MAPK8IP3(2), MAPK9(5), MET(5), NFAT5(5), NFKB1(6), NFKB2(4), NFKBIB(1), NFKBIE(2), PFN2(1), PTPN13(17), RALBP1(6), RIPK1(2), ROCK1(15), SMPD1(6), TPX2(8), TRAF2(1), TUFM(1) 23567284 200 58 195 57 65 68 42 3 21 1 0.29 0.69 258 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(2), CHPT1(1), LCMT1(3), LCMT2(2), METTL2B(2), METTL6(8), PCYT1A(5), PCYT1B(5), PRMT2(1), PRMT3(3), PRMT5(1), PRMT6(1), PRMT7(3), PRMT8(5), WBSCR22(1) 4760052 43 28 42 16 12 14 11 2 4 0 0.29 0.69 259 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 CDK5R1(1), CSNK1D(4), DRD1(1), DRD2(5), GRM1(12), PLCB1(8), PPP1R1B(1), PPP2CA(1), PPP3CA(3), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3) 5320056 49 32 49 19 22 10 8 2 7 0 0.29 0.69 260 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(11), CAPN2(7), CAPNS1(1), CAPNS2(1), EP300(15), HDAC1(2), HDAC2(2), MEF2D(1), NFATC1(2), NFATC2(6), PPP3CA(3), PPP3CB(5), PPP3CC(4), PRKCA(4), SYT1(1) 8018748 65 36 65 18 28 14 11 1 11 0 0.29 0.69 261 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(4), ACO1(5), ACO2(2), CLYBL(6), DLD(1), DLST(1), FH(1), IDH1(3), IDH2(7), IDH3A(4), IDH3G(2), MDH1(1), MDH2(1), OGDH(4), OGDHL(11), PC(6), PCK1(3), PCK2(4), SDHA(6), SDHB(2), SDHD(1), SUCLA2(5), SUCLG1(2) 10087580 82 46 81 30 31 24 18 1 8 0 0.29 0.69 262 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(2), CDK7(1), ERCC3(7), GTF2B(1), GTF2E1(5), GTF2F2(1), GTF2H1(4), GTF2H4(1), MNAT1(1), POLR1A(11), POLR1B(9), POLR2A(6), POLR2B(8), POLR2E(1), POLR2H(1), POLR2I(1), POLR2K(1), POLR3B(11), POLR3D(3), POLR3E(6), POLR3H(1), POLR3K(1), TAF5(4), TAF6(3), TAF7(2), TAF9(1), TBP(1) 11874536 94 45 94 26 33 31 18 1 11 0 0.29 0.69 263 HSA00340_HISTIDINE_METABOLISM Genes involved in histidine metabolism ABP1, ACY3, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH7A1, ALDH9A1, AMDHD1, AOC2, AOC3, ASPA, CARM1, CNDP1, DDC, FTCD, HAL, HARS, HARS2, HDC, HEMK1, HNMT, LCMT1, LCMT2, MAOA, MAOB, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, PRPS1, PRPS2, UROC1, WBSCR22 41 ABP1(1), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH3B1(3), ALDH3B2(1), ALDH7A1(3), ALDH9A1(1), AMDHD1(4), AOC2(4), AOC3(4), ASPA(5), CARM1(2), CNDP1(3), DDC(1), FTCD(2), HAL(4), HARS(2), HARS2(4), HDC(8), HNMT(4), LCMT1(3), LCMT2(2), MAOA(3), MAOB(1), METTL2B(2), METTL6(8), PRMT2(1), PRMT3(3), PRMT5(1), PRMT6(1), PRMT7(3), PRMT8(5), PRPS1(1), PRPS2(2), UROC1(3), WBSCR22(1) 13338664 118 52 116 43 43 41 23 2 9 0 0.29 0.69 264 HSA00190_OXIDATIVE_PHOSPHORYLATION Genes involved in oxidative phosphorylation ATP12A, ATP4A, ATP4B, ATP5A1, ATP5B, ATP5C1, ATP5D, ATP5E, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP5I, ATP5J, ATP5J2, ATP5L, ATP5O, ATP6, ATP6AP1, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E1, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ATP8, COX1, COX10, COX15, COX17, COX2, COX3, COX4I1, COX4I2, COX5A, COX5B, COX6A1, COX6A2, COX6B1, COX6B2, COX6C, COX7A1, COX7A2, COX7B, COX7B2, COX7C, COX8A, COX8C, CYC1, CYTB, LHPP, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA1, NDUFA10, NDUFA11, NDUFA12, NDUFA13, NDUFA2, NDUFA3, NDUFA4, NDUFA4L2, NDUFA5, NDUFA6, NDUFA7, NDUFA8, NDUFA9, NDUFAB1, NDUFB1, NDUFB10, NDUFB11, NDUFB2, NDUFB3, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFB8, NDUFB9, NDUFC1, NDUFC2, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS5, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NDUFV3, PPA1, PPA2, SDHA, SDHB, SDHC, SDHD, TCIRG1, UCRC, UQCR, UQCRB, UQCRC1, UQCRC2, UQCRFS1, UQCRH, UQCRQ 112 ATP12A(18), ATP4A(10), ATP4B(1), ATP5A1(5), ATP5B(4), ATP5C1(4), ATP5D(1), ATP5F1(1), ATP5G3(1), ATP5J2(1), ATP5L(2), ATP5O(2), ATP6AP1(2), ATP6V0A1(3), ATP6V0A2(2), ATP6V0A4(7), ATP6V0B(1), ATP6V0C(1), ATP6V0D1(2), ATP6V1A(2), ATP6V1B1(5), ATP6V1B2(2), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1E2(3), ATP6V1G2(2), ATP6V1G3(2), ATP6V1H(3), COX10(2), COX15(3), COX17(1), COX4I1(2), COX4I2(3), COX6A2(1), COX6C(1), COX7A1(1), COX7B2(1), COX8C(1), CYC1(1), LHPP(2), NDUFA1(1), NDUFA10(2), NDUFA12(2), NDUFA13(1), NDUFA4(2), NDUFA9(3), NDUFB1(1), NDUFB11(1), NDUFB2(1), NDUFB3(1), NDUFB6(1), NDUFB9(2), NDUFC2(1), NDUFS1(6), NDUFS2(3), NDUFS3(2), NDUFS4(1), NDUFS5(2), NDUFS6(2), NDUFV1(2), NDUFV3(1), PPA1(2), PPA2(3), SDHA(6), SDHB(2), SDHD(1), TCIRG1(2), UQCRB(2), UQCRC1(2), UQCRC2(3), UQCRFS1(2), UQCRH(1) 18698360 175 59 173 47 71 56 33 0 15 0 0.30 0.70 265 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 11 AKT1(2), CAT(3), GH1(2), GHR(6), IGF1(2), IGF1R(8), SHC1(3), SOD2(4) 3192880 30 24 29 13 14 9 5 0 2 0 0.30 0.70 266 AT1RPATHWAY Binding of angiotensin II to AT1-R activates Ca2+ signaling and the JNK pathway. AGT, AGTR1, ATF2, CALM1, CALM2, CALM3, EGFR, ELK1, GNAQ, GRB2, HRAS, JUN, MAP2K1, MAP2K2, MAP2K4, MAP3K1, MAPK1, MAPK3, MAPK8, MEF2A, MEF2B, MEF2C, MEF2D, PAK1, PRKCA, PRKCB1, PTK2, PTK2B, RAC1, RAF1, SHC1, SOS1, SRC, SYT1 32 AGT(5), AGTR1(6), ATF2(1), EGFR(12), GNAQ(4), GRB2(3), MAP2K1(4), MAP2K2(1), MAP3K1(8), MAPK1(2), MAPK3(3), MAPK8(7), MEF2A(4), MEF2C(9), MEF2D(1), PAK1(5), PRKCA(4), PTK2(6), PTK2B(1), RAF1(6), SHC1(3), SOS1(7), SRC(3), SYT1(1) 11220428 106 42 104 29 31 37 22 2 14 0 0.30 0.70 267 HSA00660_C5_BRANCHED_DIBASIC_ACID_METABOLISM Genes involved in C5-branched dibasic acid metabolism ILVBL, SUCLA2 2 ILVBL(2), SUCLA2(5) 724256 7 7 7 3 3 3 0 0 1 0 0.30 0.70 268 HSA00272_CYSTEINE_METABOLISM Genes involved in cysteine metabolism CARS, CARS2, CDO1, CTH, GOT1, GOT2, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, MPST, SDS, SULT1B1, SULT1C2, SULT1C4, SULT4A1 16 CARS(6), CARS2(1), CDO1(1), CTH(2), GOT1(6), GOT2(1), LDHA(2), LDHAL6A(3), LDHAL6B(2), LDHB(3), LDHC(2), SDS(2), SULT1B1(4), SULT1C2(2), SULT4A1(1) 4004612 38 21 37 7 14 14 6 0 4 0 0.31 0.70 269 CYTOKINEPATHWAY Intercellular signaling in the immune system occurs via secretion of cytokines, which promote antigen-dependent B and T cell response. IFNA1, IFNB1, IFNG, IL10, IL12A, IL12B, IL13, IL14, IL15, IL16, IL17, IL18, IL1A, IL2, IL3, IL4, IL5, IL6, IL8, IL9, LTA, TNF 20 IFNA1(1), IFNB1(1), IFNG(1), IL10(2), IL12A(1), IL12B(2), IL13(1), IL15(2), IL16(10), IL1A(1), IL2(4), IL3(3), IL4(3), IL6(2), IL8(1), IL9(2) 3264776 37 21 36 20 14 18 3 0 2 0 0.31 0.72 270 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 CDK5R1(1), EGR1(3), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK3(3), NGFR(3), RAF1(6) 2576256 23 17 22 6 9 4 6 0 4 0 0.31 0.72 271 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 45 ACOX1(3), APOA2(1), CD36(1), CITED2(1), CPT1B(5), CREBBP(25), DUSP1(2), EHHADH(2), EP300(15), FABP1(1), HSD17B4(3), LPL(6), MAPK1(2), MAPK3(3), NCOA1(8), NCOR1(12), NCOR2(2), NR1H3(4), NR2F1(3), NRIP1(6), PDGFA(1), PPARA(1), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PRKCA(4), PTGS2(3), RB1(7), RELA(2), RXRA(1), SP1(2), STAT5B(3) 19236808 142 51 142 53 45 43 32 2 19 1 0.31 0.72 272 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(5), ACAA1(2), ACAA2(1), ACADM(6), ACAT1(1), ACAT2(2), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH6A1(4), ALDH7A1(3), ALDH9A1(1), AOX1(8), AUH(1), BCAT1(1), BCAT2(1), BCKDHA(3), BCKDHB(1), DLD(1), ECHS1(2), EHHADH(2), HADH(1), HADHA(3), HADHB(2), HIBCH(1), HMGCL(1), HMGCS1(1), HMGCS2(1), HSD17B10(2), HSD17B4(3), MCCC1(8), MCCC2(2), MCEE(2), MUT(4), OXCT1(3), OXCT2(1), PCCA(9), PCCB(4) 14612196 115 50 114 32 44 39 15 0 17 0 0.32 0.72 273 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(2), BLVRB(2), CP(6), CPOX(1), EPRS(12), FECH(3), GUSB(2), HCCS(3), HMBS(2), HMOX1(2), HMOX2(3), PPOX(3), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(2), UGT1A5(3), UGT1A6(1), UGT1A7(2), UGT1A8(1), UGT1A9(6), UGT2B15(2), UGT2B4(3), UROD(1), UROS(1) 8767900 68 36 67 19 22 27 12 0 7 0 0.32 0.72 274 HSA00053_ASCORBATE_AND_ALDARATE_METABOLISM Genes involved in ascorbate and aldarate metabolism ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, MIOX, UGDH 9 ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(3), ALDH9A1(1), MIOX(1), UGDH(4) 2871660 31 20 31 6 10 12 5 0 4 0 0.32 0.72 275 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(2), BAD(1), BCL2L1(1), CASP9(2), CDC42(1), CHUK(6), MAP2K1(4), MAPK3(3), NFKB1(6), RAF1(6), RALA(1), RALBP1(6), RALGDS(1), RELA(2), RHOA(5) 5232176 47 28 46 11 23 5 13 0 6 0 0.32 0.72 276 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(2), CCNE1(3), CDK2(2), CDK4(3), CDK6(1), CDKN1A(1), CDKN1B(3), MAPK1(2), MAPK3(3), NFKB1(6), PAK1(5), RAF1(6), RB1(7), RELA(2), TFDP1(4) 5625708 50 28 49 12 18 9 13 2 7 1 0.32 0.72 277 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(5), ABAT(5), ADSL(7), ADSS(2), AGXT2(5), ASL(2), ASNS(1), ASPA(5), CAD(12), CRAT(3), DARS(4), DDO(2), GAD1(9), GAD2(4), GOT1(6), GOT2(1), GPT2(2), NARS(3), PC(6) 8800792 84 44 83 29 38 31 10 0 5 0 0.32 0.72 278 ACTINYPATHWAY The Arp 2/3 complex localizes to the Y-junction of polymerizing actin fibers that enable lamellipod extension and consequent cell motility. ABI-2, ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, NCK1, NCKAP1, NTRK1, PIR, PSMA7, RAC1, WASF1, WASF2, WASF3, WASL 18 ACTA1(4), ACTR2(2), ACTR3(3), ARPC1A(5), ARPC1B(2), ARPC2(2), NCK1(1), NCKAP1(9), NTRK1(7), PIR(1), PSMA7(1), WASF1(3), WASF2(2), WASF3(5), WASL(7) 5208456 54 29 53 12 17 18 13 0 6 0 0.33 0.72 279 GPCRDB_CLASS_A_RHODOPSIN_LIKE2 CYSLTR1, CYSLTR2, GPR109B, GPR161, GPR171, GPR18, GPR34, GPR39, GPR41, GPR42, GPR45, GPR65, GPR68, GPR75, GPR81, LYPDC1 13 CYSLTR1(3), CYSLTR2(4), GPR161(7), GPR171(4), GPR18(2), GPR34(6), GPR39(3), GPR45(7), GPR65(1), GPR75(2) 3322532 39 23 39 12 17 9 8 0 5 0 0.33 0.72 280 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 CSNK2A1(4), FOS(1), GRB2(3), JAK2(9), MAP2K1(4), MAPK3(3), MPL(2), PLCG1(4), PRKCA(4), RAF1(6), RASA1(9), SHC1(3), SOS1(7), STAT1(6), STAT3(2), STAT5B(3), THPO(2) 8850108 72 33 70 19 21 26 15 0 8 2 0.33 0.72 281 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(7), FOS(1), GRB2(3), IL3(3), JAK2(9), MAP2K1(4), MAPK3(3), PTPN6(4), RAF1(6), SHC1(3), SOS1(7), STAT5B(3) 5724296 53 28 50 11 20 16 9 0 6 2 0.34 0.74 282 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(11), ABCB11(11), ABCB4(11), ABCC1(11), ABCC3(5) 4897596 49 26 49 13 9 18 14 1 7 0 0.34 0.74 283 HSA00471_D_GLUTAMINE_AND_D_GLUTAMATE_METABOLISM Genes involved in D-glutamine and D-glutamate metabolism GLS, GLS2, GLUD1, GLUD2 4 GLS2(2), GLUD1(2), GLUD2(6) 1449628 10 10 10 6 6 3 1 0 0 0 0.34 0.74 284 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(5), PLCD1(7), PRKCA(4), TGM2(7) 1700380 23 15 23 6 10 11 1 0 1 0 0.34 0.74 285 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(2), GRB2(3), NTRK1(7), PLCG1(4), PRKCA(4), SHC1(3), SOS1(7) 3814532 30 23 28 9 6 13 8 0 3 0 0.34 0.74 286 BETAOXIDATIONPATHWAY Beta-Oxidation of Fatty Acids ACADL, ACADM, ACADS, ACAT1, ECHS1, HADHA 6 ACADL(2), ACADM(6), ACAT1(1), ECHS1(2), HADHA(3) 1824120 14 9 13 5 2 4 1 0 7 0 0.34 0.74 287 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 14 AKT1(2), AKT2(6), AKT3(1), BPNT1(1), GRB2(3), MAPK1(2), MAPK3(3), PDK1(2), PIK3CD(3), PTK2B(1), RBL2(8), SHC1(3), SOS1(7) 5844760 42 26 41 14 11 13 10 0 8 0 0.34 0.74 288 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(3), DHRS3(2), HSD3B7(2), PON1(6), PON2(2), PON3(2), RDH11(1), RDH12(3), RDH13(1) 2836156 23 18 23 10 10 7 2 0 4 0 0.35 0.74 289 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(2), AKT2(6), AKT3(1), ASAH1(3), DAG1(5), DRD2(5), EGFR(12), EPHB2(8), GRB2(3), ITPKB(4), ITPR1(19), ITPR2(18), ITPR3(12), KCNJ3(6), KCNJ5(4), KCNJ9(3), MAPK1(2), PI3(1), PIK3CB(2), PITX2(2), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), RAF1(6), RGS20(4), SHC1(3), SOS1(7), SOS2(11), SRC(3), STAT3(2), TERF2IP(2) 19468504 181 61 178 55 76 57 31 1 15 1 0.35 0.75 290 UREACYCLEPATHWAY Ammonia released from amino acid deamination is used to produce carbamoyl phosphate, which is used to convert ornithine to citrulline, from which urea is eventually formed. ARG1, ASL, ASS, CPS1, GLS, GLUD1, GOT1 6 ARG1(1), ASL(2), CPS1(14), GLUD1(2), GOT1(6) 2556608 25 14 24 6 6 9 4 0 6 0 0.36 0.76 291 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(4), MMP2(5), MMP9(11), RECK(5), TIMP1(2), TIMP2(2), TIMP3(3), TIMP4(2) 2546160 34 22 34 8 19 7 7 0 1 0 0.36 0.76 292 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(2), AKT2(6), AKT3(1), GRB2(3), IARS(6), IL13RA1(2), IL4(3), IL4R(1), INPP5D(4), JAK1(4), JAK2(9), JAK3(9), PI3(1), PPP1R13B(6), RPS6KB1(3), SERPINA4(5), SHC1(3), SOS1(7), SOS2(11), SRC(3), STAT6(2), TYK2(1) 11778356 92 41 89 30 26 33 16 1 14 2 0.36 0.76 293 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 ALDH6A1(4), TPI1(1) 533176 5 5 5 0 0 2 3 0 0 0 0.37 0.77 294 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(5), IGF1(2), IL11(1), IL1A(1), IL3(3), IL6(2), IL9(2), KITLG(2), TGFB1(1), TGFB2(9) 2857640 28 18 27 13 9 11 4 0 4 0 0.37 0.78 295 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(9), AP2A1(3), AP2M1(4), BIN1(2), DNM1(11), EPN1(2), EPS15(7), PICALM(2), PPP3CA(3), PPP3CB(5), PPP3CC(4), SYNJ1(11), SYNJ2(6), SYT1(1) 7621532 70 30 67 25 22 22 10 0 16 0 0.37 0.78 296 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), RANBP1(1), RANBP2(17), RANGAP1(1) 2797624 21 12 20 4 5 5 7 0 4 0 0.38 0.78 297 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT1(6), GOT2(1), TAT(5) 882876 12 8 11 2 4 5 1 0 2 0 0.38 0.78 298 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 23 POLA1(8), POLA2(2), POLB(3), POLD1(5), POLD2(1), POLD3(2), POLE(21), POLE2(1), POLE3(1), POLG(5), POLG2(1), POLH(5), POLI(10), POLK(3), POLL(1), POLM(2), POLQ(12), REV1(7), REV3L(22), RFC5(3) 13771996 115 42 110 34 30 46 23 0 14 2 0.38 0.78 299 EPHA4PATHWAY Eph Kinases and ephrins support platelet aggregation ACTA1, EPHA4, EPHB1, FYN, ITGA1, ITGB1, L1CAM, LYN, RAP1B, SELP 10 ACTA1(4), EPHA4(6), EPHB1(9), FYN(5), ITGA1(3), ITGB1(6), L1CAM(4), LYN(4), RAP1B(2), SELP(6) 5303624 49 28 48 14 19 18 8 0 4 0 0.38 0.78 300 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(2), CREB1(1), CREBBP(25), EP300(15), NCOA3(11), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), RXRA(1) 6877044 68 35 68 17 21 22 15 2 8 0 0.38 0.78 301 KERATINOCYTEPATHWAY Keratinocyte differentiation, which models the differentiation of epidermal cells, requires the four main MAP kinase pathways. BCL2, CEBPA, CHUK, DAXX, EGF, EGFR, ETS1, ETS2, FOS, HOXA7, HRAS, IKBKB, JUN, MAP2K1, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K1, MAP3K14, MAP3K5, MAPK1, MAPK13, MAPK14, MAPK3, MAPK8, NFKB1, NFKBIA, PPP2CA, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCQ, RAF1, RELA, RIPK1, SP1, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TRAF2 41 BCL2(1), CHUK(6), DAXX(1), EGF(3), EGFR(12), ETS1(1), ETS2(3), FOS(1), HOXA7(1), IKBKB(4), MAP2K1(4), MAP2K3(6), MAP2K6(3), MAP3K1(8), MAP3K14(3), MAP3K5(7), MAPK1(2), MAPK13(1), MAPK14(3), MAPK3(3), MAPK8(7), NFKB1(6), PPP2CA(1), PRKCA(4), PRKCD(3), PRKCE(6), PRKCG(10), PRKCH(3), PRKCQ(5), RAF1(6), RELA(2), RIPK1(2), SP1(2), TNFRSF1A(1), TRAF2(1) 16316384 132 58 131 41 58 36 30 3 5 0 0.39 0.80 302 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(3), PSMA4(2), PSMA5(1), PSMA7(1), PSMB2(2), PSMB3(1), PSMB5(2), PSMB6(2), PSMC2(1), PSMC3(3), PSMD1(8), PSMD11(3), PSMD12(4), PSMD13(2), PSMD2(4), PSMD6(3) 5395420 44 25 43 16 15 14 9 2 4 0 0.39 0.80 303 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(25), EP300(15), LPL(6), NCOA1(8), NCOA2(7), PPARG(1), RXRA(1) 6220160 63 30 63 21 19 19 17 1 7 0 0.39 0.80 304 ST_GA13_PATHWAY G-alpha-13 influences the actin cytoskeleton and activates protein kinase D, PI3K, and Pyk2. AKT1, AKT2, AKT3, ARHGEF11, BCL2, BF, CDC42, DLG4, GNA13, IKBKG, LPA, MAP2K4, MAP3K1, MAP3K5, MAPK8, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PDK1, PHKA2, PI3, PIK3CB, PLD1, PLD2, PLD3, PRKCM, PTK2, RDX, ROCK1, ROCK2, SERPINA4, SRF, TBXA2R 33 AKT1(2), AKT2(6), AKT3(1), ARHGEF11(11), BCL2(1), CDC42(1), DLG4(3), GNA13(2), LPA(10), MAP3K1(8), MAP3K5(7), MAPK8(7), NFKB1(6), NFKB2(4), NFKBIB(1), NFKBIE(2), PDK1(2), PHKA2(7), PI3(1), PIK3CB(2), PLD1(11), PLD2(2), PLD3(5), PTK2(6), RDX(3), ROCK1(15), ROCK2(6), SERPINA4(5), SRF(3) 16188040 140 48 140 44 57 42 21 3 17 0 0.40 0.80 305 STEMPATHWAY In the absence of infection, bone marrow stromal cells release hematopoietic cytokines; activated macrophages and Th cells induce hematopoiesis during infection. CD4, CD8A, CSF1, CSF2, CSF3, EPO, IL11, IL2, IL3, IL4, IL5, IL6, IL7, IL8, IL9 15 CD4(2), CSF1(2), IL11(1), IL2(4), IL3(3), IL4(3), IL6(2), IL7(2), IL8(1), IL9(2) 2111556 22 14 21 8 9 10 2 0 1 0 0.40 0.80 306 CALCINEURINPATHWAY Increased intracellular calcium activates the phosphatase calcineurin in differentiating keratinocytes. CALM1, CALM2, CALM3, CDKN1A, GNAQ, MARCKS, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, SP1, SP3, SYT1 18 CDKN1A(1), GNAQ(4), MARCKS(1), NFATC1(2), NFATC2(6), NFATC3(5), NFATC4(5), PLCG1(4), PPP3CA(3), PPP3CB(5), PPP3CC(4), PRKCA(4), SP1(2), SP3(3), SYT1(1) 6903604 50 33 50 18 22 12 5 0 11 0 0.40 0.80 307 CYANOAMINO_ACID_METABOLISM ATP6V0C, SHMT1, GBA3, GGT1, SHMT1, SHMT2 4 ATP6V0C(1), GBA3(3), SHMT1(2), SHMT2(2) 1097828 8 7 8 4 2 3 0 0 3 0 0.40 0.80 308 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(8), GNAS(6), PLCE1(9), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), RAP2B(1) 4839720 37 27 37 11 15 12 6 0 4 0 0.40 0.80 309 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(5), ALDH4A1(3), ALDH5A1(4), CAD(12), CPS1(14), EPRS(12), GAD1(9), GAD2(4), GCLC(4), GCLM(1), GFPT1(4), GLS2(2), GLUD1(2), GLUL(4), GMPS(5), GOT1(6), GOT2(1), GPT2(2), GSS(4), NADSYN1(2), PPAT(6), QARS(8) 11133376 114 44 113 23 36 40 26 2 10 0 0.41 0.80 310 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(5), AARS2(6), ABAT(5), ADSL(7), ADSS(2), AGXT2(5), ASL(2), ASNS(1), ASPA(5), ASS1(2), CAD(12), CRAT(3), DARS(4), DARS2(3), DDO(2), DLAT(3), DLD(1), GAD1(9), GAD2(4), GOT1(6), GOT2(1), GPT2(2), NARS(3), NARS2(6), PC(6), PDHA1(5), PDHA2(8), PDHB(2) 12804920 120 50 118 38 53 39 17 0 11 0 0.41 0.80 311 AGPCRPATHWAY G-protein coupled receptors (GPCRs) transduce extracellular signals across the plasma membrane; attenuation occurs by signal molecule degradation or receptor-mediated endocytosis. ARRB1, GNAS, GNB1, GNGT1, GPRK2L, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1 11 ARRB1(1), GNAS(6), GNB1(1), GNGT1(1), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PRKCA(4) 3168296 26 22 26 8 11 9 4 0 2 0 0.41 0.80 312 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 26 ANXA1(1), ANXA2(2), ANXA3(1), ANXA4(4), ANXA5(1), ANXA6(3), CYP11A1(4), EDN1(1), EDNRA(4), HSD11B1(1), PLA2G4A(8), PRL(3), PTGDR(1), PTGER2(1), PTGFR(6), PTGIR(1), PTGIS(5), PTGS1(6), PTGS2(3), TBXAS1(5) 6621316 61 31 60 13 26 19 10 0 6 0 0.41 0.80 313 HSA00290_VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS Genes involved in valine, leucine and isoleucine biosynthesis BCAT1, BCAT2, IARS, IARS2, ILVBL, LARS, LARS2, PDHA1, PDHA2, PDHB, VARS, VARS2 12 BCAT1(1), BCAT2(1), IARS(6), IARS2(6), ILVBL(2), LARS(5), LARS2(3), PDHA1(5), PDHA2(8), PDHB(2), VARS(1), VARS2(6) 5917736 46 29 45 14 20 12 8 0 6 0 0.41 0.80 314 THELPERPATHWAY Helper T cells coordinate the actions of B cells, macrophages, and other immune cells via surface molecules such as T cell receptor/CD3 and their characteristic marker CD4. CD2, CD28, CD3D, CD3E, CD3G, CD3Z, CD4, ICAM1, ITGAL, ITGB2, PTPRC, THY1, TRA@, TRB@ 11 CD2(3), CD28(2), CD3D(1), CD3G(2), CD4(2), ICAM1(2), ITGAL(8), ITGB2(5), PTPRC(17) 3788088 42 22 42 16 9 18 7 0 8 0 0.41 0.80 315 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 59 AKT1(2), AKT2(6), AKT3(1), BAD(1), BCL2L1(1), CDC42(1), CDK2(2), CDKN1B(3), CREB1(1), CREB3(3), CREB5(4), EBP(2), F2RL2(3), GAB1(6), GRB2(3), GSK3A(2), IGF1(2), IGFBP1(2), INPPL1(4), IRS1(9), IRS4(15), MET(5), NOLC1(8), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PARD3(7), PARD6A(2), PDK1(2), PIK3CD(3), PPP1R13B(6), PREX1(16), PTK2(6), PTPN1(5), RPS6KA1(1), RPS6KA2(10), RPS6KA3(5), RPS6KB1(3), SHC1(3), SLC2A4(4), SOS1(7), SOS2(11), TSC1(4), TSC2(2), YWHAB(2), YWHAE(3), YWHAH(1), YWHAQ(2) 23432616 212 59 209 77 72 73 34 3 30 0 0.41 0.80 316 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(2), EHHADH(2), HADH(1), HADHA(3), HSD17B10(2), HSD17B4(3), NTAN1(3), SIRT1(5), SIRT2(2), SIRT5(4), SIRT7(1), VNN2(2) 3953912 30 21 30 12 9 7 6 0 8 0 0.41 0.80 317 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 50 AKR1C3(2), ALOX12(2), ALOX12B(2), ALOX15B(5), ALOX5(4), CYP2C18(2), CYP2C19(4), CYP2C8(4), CYP2C9(7), CYP2E1(6), CYP2J2(3), CYP2U1(1), CYP4A11(3), CYP4A22(2), CYP4F2(8), CYP4F3(3), EPHX2(1), GPX1(1), GPX2(2), GPX3(3), GPX5(4), GPX6(3), PLA2G1B(1), PLA2G2F(1), PLA2G4A(8), PLA2G6(4), PTGIS(5), PTGS1(6), PTGS2(3), TBXAS1(5) 12888908 105 50 104 37 41 36 19 2 7 0 0.41 0.80 318 IL2PATHWAY IL-2 promotes proliferation via JAK and MAP kinase and has surface receptors on activated B cells, LPS-treated monocytes, and many T cells. CSNK2A1, ELK1, FOS, GRB2, HRAS, IL2, IL2RA, IL2RB, IL2RG, JAK1, JAK3, JUN, LCK, MAP2K1, MAPK3, MAPK8, RAF1, SHC1, SOS1, STAT5A, STAT5B, SYK 22 CSNK2A1(4), FOS(1), GRB2(3), IL2(4), IL2RA(2), IL2RB(2), JAK1(4), JAK3(9), LCK(3), MAP2K1(4), MAPK3(3), MAPK8(7), RAF1(6), SHC1(3), SOS1(7), STAT5B(3), SYK(3) 7957296 68 34 65 19 19 27 12 1 9 0 0.41 0.80 319 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(5), GPD2(4), NDUFA1(1), SDHA(6), SDHB(2), SDHD(1), UQCRC1(2) 2201480 21 15 21 4 6 11 3 0 1 0 0.42 0.80 320 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 14 APAF1(8), BAX(1), BCL2(1), CCNE1(3), CDK2(2), CDK4(3), CDKN1A(1), MDM2(4), PCNA(3), RB1(7), TIMP3(3) 3794024 36 21 36 9 9 12 10 1 3 1 0.42 0.80 321 TCYTOTOXICPATHWAY Cytotoxic T cells release perforin and granzyme to lyse foreign cell targets and express Fas ligand to promote Fas-induced apoptosis. CD2, CD28, CD3D, CD3E, CD3G, CD3Z, CD8A, ICAM1, ITGAL, ITGB2, PTPRC, THY1, TRA@, TRB@ 11 CD2(3), CD28(2), CD3D(1), CD3G(2), ICAM1(2), ITGAL(8), ITGB2(5), PTPRC(17) 3589836 40 21 40 14 9 16 7 0 8 0 0.42 0.80 322 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 BET1(1), BNIP1(1), GOSR1(3), GOSR2(3), SEC22B(3), SNAP23(1), SNAP25(1), SNAP29(3), STX11(2), STX12(3), STX16(3), STX17(1), STX18(1), STX19(2), STX2(3), STX3(3), STX4(2), STX5(3), STX6(1), STX7(3), STX8(4), TSNARE1(1), VAMP1(1), VAMP3(2), VAMP4(3), VAMP5(2), VAMP8(1), VTI1A(1), VTI1B(1), YKT6(1) 5513852 60 26 58 17 23 14 9 0 14 0 0.42 0.80 323 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 16 ABCA1(22), APOC1(1), APOC2(1), APOE(1), CETP(7), CYP7A1(4), HMGCR(3), LCAT(1), LDLR(5), LIPC(4), LPL(6), LRP1(18), SCARB1(1), SOAT1(1) 8566096 75 37 75 23 31 23 13 1 7 0 0.43 0.81 324 SMALL_LIGAND_GPCRS C9orf47, CNR1, CNR2, DNMT1, EDG1, EDG2, EDG5, EDG6, MTNR1A, MTNR1B, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, TBXA2R 13 C9orf47(1), CNR1(5), DNMT1(19), MTNR1B(3), PTAFR(1), PTGDR(1), PTGER2(1), PTGFR(6), PTGIR(1) 3740564 38 26 34 9 18 9 7 3 1 0 0.43 0.81 325 RELAPATHWAY Acetylated NF-kB proteins are immune to IkB regulation and promote transcription until the histone deacetylase HDAC3 deacetylates the RelA subunit of NF-kB. CHUK, CREBBP, EP300, FADD, HDAC3, IKBKB, IKBKG, NFKB1, NFKBIA, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF6 15 CHUK(6), CREBBP(25), EP300(15), HDAC3(2), IKBKB(4), NFKB1(6), RELA(2), RIPK1(2), TNFRSF1A(1), TRADD(1), TRAF6(4) 7527600 68 34 68 22 26 18 16 1 7 0 0.43 0.81 326 IFNGPATHWAY IFN gamma signaling pathway IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 6 IFNG(1), IFNGR1(3), IFNGR2(2), JAK1(4), JAK2(9), STAT1(6) 2773344 25 15 24 7 8 6 6 0 3 2 0.43 0.81 327 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 5 FOSB(2), GRIA2(12), PPP1R1B(1) 1277456 15 12 14 5 6 3 5 0 1 0 0.43 0.81 328 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 15 ADAM12(9), AGT(5), AGTR2(5), EDN1(1), EDNRA(4), EGF(3), EGFR(12), FOS(1), NFKB1(6), PLCG1(4), PRKCA(4), RELA(2) 6592856 56 33 56 16 25 16 10 0 5 0 0.44 0.82 329 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(4), GLB1(3), HEXB(3), LCT(20), SLC33A1(2), ST3GAL1(1), ST3GAL2(1), ST6GALNAC3(4), ST6GALNAC4(2), ST6GALNAC5(6), ST6GALNAC6(3), ST8SIA1(3), ST8SIA5(6) 5547116 59 31 58 20 27 16 11 0 5 0 0.44 0.82 330 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 CDK2(2), CDK4(3), CDKN1A(1), CDKN1B(3), CFL1(1), E2F2(1), MDM2(4), NXT1(1), PRB1(1) 2416612 17 14 17 5 3 4 5 1 4 0 0.44 0.83 331 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 40 AGL(10), AMY2B(1), ENPP1(4), ENPP3(4), G6PC(4), GANAB(4), GBA3(3), GBE1(5), GCK(2), GPI(2), GUSB(2), GYS1(2), GYS2(11), HK1(6), HK2(3), HK3(5), MGAM(13), PGM1(4), PGM3(5), PYGB(4), PYGL(2), PYGM(4), SI(15), UCHL1(2), UCHL3(2), UGDH(4), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(2), UGT1A5(3), UGT1A6(1), UGT1A7(2), UGT1A8(1), UGT1A9(6), UGT2B15(2), UGT2B4(3), UXS1(7) 18819492 154 54 154 54 52 52 31 0 19 0 0.45 0.83 332 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(4), ATG7(1), BECN1(3), IFNA1(1), IFNA10(3), IFNA13(2), IFNA16(4), IFNA2(4), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), IFNG(1), PIK3C3(7), PIK3R4(12), PRKAA1(3), PRKAA2(9), ULK1(1), ULK2(4), ULK3(3) 7033388 72 32 71 17 14 32 20 0 6 0 0.45 0.83 333 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(8), CKM(5), FBL(3), LDHA(2), LDHB(3), LDHC(2), MAPK14(3), NCL(3) 2992944 29 21 29 14 12 12 4 0 1 0 0.45 0.83 334 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(4), ACTB(2), ARHGEF2(5), ARPC5(1), ARPC5L(2), CD14(1), CDC42(1), CDH1(5), CTTN(1), EZR(2), FYN(5), ITGB1(6), KRT18(2), LY96(2), NCK1(1), NCL(3), OCLN(1), PRKCA(4), RHOA(5), ROCK1(15), ROCK2(6), TLR4(10), TLR5(4), TUBA1B(2), TUBA1C(2), TUBA3C(9), TUBA3D(3), TUBA3E(5), TUBA4A(3), TUBA8(2), TUBAL3(4), TUBB(1), TUBB1(2), TUBB2A(3), TUBB2B(3), TUBB3(2), TUBB4(3), TUBB4Q(2), TUBB6(3), TUBB8(3), WAS(1), WASL(7), YWHAQ(2) 16587304 150 52 149 52 54 54 26 1 15 0 0.45 0.83 335 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(4), ACTB(2), ARHGEF2(5), ARPC5(1), ARPC5L(2), CD14(1), CDC42(1), CDH1(5), CTTN(1), EZR(2), FYN(5), ITGB1(6), KRT18(2), LY96(2), NCK1(1), NCL(3), OCLN(1), PRKCA(4), RHOA(5), ROCK1(15), ROCK2(6), TLR4(10), TLR5(4), TUBA1B(2), TUBA1C(2), TUBA3C(9), TUBA3D(3), TUBA3E(5), TUBA4A(3), TUBA8(2), TUBAL3(4), TUBB(1), TUBB1(2), TUBB2A(3), TUBB2B(3), TUBB3(2), TUBB4(3), TUBB4Q(2), TUBB6(3), TUBB8(3), WAS(1), WASL(7), YWHAQ(2) 16587304 150 52 149 52 54 54 26 1 15 0 0.45 0.83 336 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 30 AKR1C3(2), ALOX12(2), ALOX5(4), CYP4F2(8), CYP4F3(3), EPX(7), LPO(3), MPO(5), PLA2G1B(1), PLA2G4A(8), PLA2G6(4), PRDX1(1), PRDX6(2), PTGIS(5), PTGS1(6), PTGS2(3), TBXAS1(5), TPO(11) 9056448 80 42 78 29 42 22 8 2 6 0 0.45 0.83 337 MITOCHONDRIAPATHWAY Pro-apoptotic signaling induces mitochondria to release cytochrome c, which stimulates Apaf-1 to activate caspase 9. APAF1, BAK1, BAX, BCL2, BCL2L1, BID, BIK, BIRC2, BIRC3, BIRC4, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, DFFA, DFFB, DIABLO, ENDOG, PDCD8 18 APAF1(8), BAK1(1), BAX(1), BCL2(1), BCL2L1(1), BID(1), BIK(1), BIRC2(4), BIRC3(7), CASP3(2), CASP6(2), CASP7(1), CASP9(2), DFFA(3), DFFB(2), DIABLO(1) 4202528 38 24 38 9 11 15 7 0 5 0 0.45 0.83 338 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(3), CAMK1G(5), HDAC9(13), MEF2A(4), MEF2C(9), MEF2D(1), YWHAH(1) 2816904 36 18 36 15 9 14 10 0 3 0 0.46 0.84 339 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(5), ACO2(2), DLD(1), DLST(1), FH(1), IDH1(3), IDH2(7), IDH3A(4), IDH3G(2), MDH1(1), MDH2(1), PC(6), PCK1(3), SDHA(6), SDHB(2), SUCLA2(5), SUCLG1(2) 6978460 52 34 52 23 20 17 8 0 7 0 0.46 0.84 340 HSA00330_ARGININE_AND_PROLINE_METABOLISM Genes involved in arginine and proline metabolism ALDH4A1, ARG1, ARG2, ASL, ASS1, CKB, CKM, CKMT1A, CKMT1B, CKMT2, CPS1, DAO, EPRS, GAMT, GATM, GLUD1, GLUD2, GOT1, GOT2, LAP3, NOS1, NOS2A, NOS3, OAT, OTC, P4HA1, P4HA2, P4HA3, PARS2, PRODH, PYCR1, PYCR2, PYCRL, RARS, RARS2 34 ALDH4A1(3), ARG1(1), ARG2(5), ASL(2), ASS1(2), CKM(5), CKMT1B(1), CKMT2(5), CPS1(14), DAO(6), EPRS(12), GAMT(1), GATM(1), GLUD1(2), GLUD2(6), GOT1(6), GOT2(1), LAP3(2), NOS1(11), NOS3(2), OAT(1), OTC(5), P4HA1(1), P4HA2(2), P4HA3(2), RARS(4), RARS2(5) 11973188 108 41 107 37 35 35 20 1 17 0 0.46 0.84 341 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(3), DHRS3(2), ESCO1(11), ESCO2(4), MYST3(18), MYST4(10), PNPLA3(4), SH3GLB1(4) 5363104 57 27 56 17 24 14 13 1 5 0 0.46 0.84 342 BOTULINPATHWAY Blockade of Neurotransmitter Relase by Botulinum Toxin CHRM1, CHRNA1, SNAP25, STX1A, VAMP2 5 CHRM1(3), CHRNA1(4), SNAP25(1), STX1A(2) 1094156 10 10 10 4 6 2 2 0 0 0 0.47 0.85 343 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 32 ACTA1(4), CRKL(2), DOCK1(7), FOS(1), GAB1(6), GRB2(3), HGF(8), ITGA1(3), ITGB1(6), MAP2K1(4), MAP2K2(1), MAP4K1(3), MAPK1(2), MAPK3(3), MAPK8(7), MET(5), PAK1(5), PTK2(6), PTK2B(1), PTPN11(5), RAF1(6), RAP1A(2), RAP1B(2), RASA1(9), SOS1(7), SRC(3), STAT3(2) 13708104 113 44 110 30 30 44 27 2 10 0 0.47 0.85 344 LDLPATHWAY Low density lipoproteins (LDL) are present in blood plasma, contain cholesterol and triglycerides, and contribute to atherogenic plaque formation. ACAT1, CCL2, CSF1, IL6, LDLR, LPL 6 ACAT1(1), CSF1(2), IL6(2), LDLR(5), LPL(6) 1784860 16 12 16 4 6 4 4 0 2 0 0.48 0.85 345 HSA00910_NITROGEN_METABOLISM Genes involved in nitrogen metabolism AMT, ASNS, ASRGL1, CA1, CA12, CA13, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA8, CA9, CPS1, CTH, GLS, GLS2, GLUD1, GLUD2, GLUL, HAL 24 ASNS(1), CA1(1), CA13(1), CA14(2), CA2(1), CA3(2), CA4(1), CA5A(2), CA6(2), CA8(3), CA9(2), CPS1(14), CTH(2), GLS2(2), GLUD1(2), GLUD2(6), GLUL(4), HAL(4) 7083264 52 30 52 26 20 17 6 0 9 0 0.48 0.85 346 PTDINSPATHWAY Phosphoinositide 3 kinase (PI3K) phosphorylate inositol rings of phosphoinositide lipids, influencing vesicle trafficking, cell proliferation, and migration. AKT1, AP2A1, AP2M1, ARF1, BAD, BTK, EEA1, GRASP, GSK3A, GSK3B, LYN, PDPK1, PFKL, PFKM, PFKP, PFKX, PLCG1, PRKCE, PRKCZ, RAB5A, RAC1, RPS6KB1, VAV2 21 AKT1(2), AP2A1(3), AP2M1(4), BAD(1), BTK(7), EEA1(9), GRASP(1), GSK3A(2), LYN(4), PDPK1(1), PFKL(1), PFKM(4), PFKP(2), PLCG1(4), PRKCE(6), RPS6KB1(3), VAV2(4) 8299376 58 32 58 19 20 19 10 0 8 1 0.48 0.85 347 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), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CLCA1(6), CLCA2(7), CLCA4(6), CNGA3(6), CNGA4(6), CNGB1(7), GNAL(4), GUCA1A(3), GUCA1B(3), GUCA1C(1), PDC(2), PDE1C(9), PRKACA(1), PRKACB(1), PRKACG(3), PRKG1(9), PRKG2(5), PRKX(2) 10394224 93 39 91 41 28 38 16 1 10 0 0.48 0.85 348 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(3), ACSS2(6), ACYP1(2), ADH1A(1), ADH1B(3), ADH1C(4), ADH4(2), ADH5(1), ADH6(6), ADH7(2), ADHFE1(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH3B1(3), ALDH3B2(1), ALDH7A1(3), ALDH9A1(1), ALDOA(1), ALDOB(5), ALDOC(3), DLAT(3), DLD(1), ENO2(3), ENO3(4), FBP2(3), G6PC(4), G6PC2(1), GALM(2), GCK(2), GPI(2), HK1(6), HK2(3), HK3(5), LDHA(2), LDHAL6A(3), LDHAL6B(2), LDHB(3), LDHC(2), PDHA1(5), PDHA2(8), PDHB(2), PFKL(1), PFKM(4), PFKP(2), PGAM1(3), PGAM2(1), PGK1(3), PGK2(7), PGM1(4), PGM3(5), PKM2(2), TPI1(1) 19321516 174 59 172 59 57 68 36 1 12 0 0.48 0.85 349 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 CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), DAG1(5), ITPKB(4), ITPR1(19), ITPR2(18), ITPR3(12), NFAT5(5), PDE6A(7), PDE6B(5), PDE6C(10), PDE6D(1), SLC6A13(6), TF(11) 12253428 111 44 111 27 44 34 21 0 11 1 0.48 0.85 350 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(11), POLR1B(9), POLR1C(2), POLR1D(2), POLR2A(6), POLR2B(8), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLR2K(1), POLR3A(11), POLR3B(11), POLR3GL(1), POLR3H(1), POLR3K(1) 7851096 68 37 68 12 25 24 13 1 5 0 0.48 0.85 351 HSA00360_PHENYLALANINE_METABOLISM Genes involved in phenylalanine metabolism ABP1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, ARD1A, DDC, EPX, ESCO1, ESCO2, GOT1, GOT2, HPD, LPO, LYCAT, MAOA, MAOB, MIF, MPO, MYST3, MYST4, NAT5, NAT6, PNPLA3, PRDX6, SH3GLB1, TAT, TPO 27 ABP1(1), ALDH1A3(6), ALDH3A1(2), ALDH3B1(3), ALDH3B2(1), AOC2(4), AOC3(4), DDC(1), EPX(7), ESCO1(11), ESCO2(4), GOT1(6), GOT2(1), HPD(4), LPO(3), MAOA(3), MAOB(1), MPO(5), MYST3(18), MYST4(10), PNPLA3(4), PRDX6(2), SH3GLB1(4), TAT(5), TPO(11) 11521728 121 49 118 38 55 36 21 1 8 0 0.49 0.85 352 HSA00791_ATRAZINE_DEGRADATION Genes involved in atrazine degradation ADAR, APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3F, APOBEC3G, APOBEC4 9 ADAR(8), APOBEC1(2), APOBEC2(1), APOBEC3A(1), APOBEC3C(3), APOBEC3F(2), APOBEC3G(3), APOBEC4(4) 2471012 24 16 24 5 10 8 3 1 2 0 0.49 0.86 353 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(3), AASS(9), ACAT1(1), ACAT2(2), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(3), ALDH9A1(1), BBOX1(3), DLST(1), DOT1L(3), ECHS1(2), EHHADH(2), EHMT1(2), EHMT2(3), GCDH(5), HADH(1), HADHA(3), HSD17B10(2), HSD17B4(3), HSD3B7(2), NSD1(14), OGDH(4), OGDHL(11), PIPOX(4), PLOD1(4), PLOD2(5), PLOD3(4), RDH11(1), RDH12(3), RDH13(1), SETD1A(8), SETD7(3), SETDB1(8), SHMT1(2), SHMT2(2), SPCS1(1), SPCS3(1), SUV39H1(1), SUV39H2(3), TMLHE(3) 19406496 157 55 154 43 63 40 29 2 23 0 0.49 0.86 354 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(2), AKT2(6), AKT3(1), CDKN1A(1), GRB2(3), MAP2K1(4), MAP2K2(1), NGFR(3), NTRK1(7), PIK3CD(3), SHC1(3), SOS1(7) 4772900 41 27 39 13 11 14 12 0 4 0 0.50 0.86 355 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(4), ABAT(5), ACAT1(1), ACAT2(2), ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH5A1(4), ALDH9A1(1), ECHS1(2), EHHADH(2), GAD1(9), GAD2(4), HADHA(3), HMGCL(1), L2HGDH(3), OXCT1(3), PDHA1(5), PDHA2(8), PDHB(2), SDHB(2), SDS(2) 8712916 95 41 94 25 36 36 15 0 8 0 0.50 0.87 356 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 91 B3GALT4(1), CDR1(2), DGKI(10), FAU(1), IL6ST(3), MRPL19(1), PIGK(4), RPL10(1), RPL11(1), RPL18A(1), RPL19(1), RPL21(1), RPL22(2), RPL24(1), RPL28(2), RPL3(2), RPL31(1), RPL32(1), RPL35(1), RPL39(1), RPL3L(1), RPL4(2), RPL5(1), RPL6(3), RPL7(1), RPL9(4), RPLP0(2), RPS11(1), RPS13(1), RPS16(2), RPS18(2), RPS2(1), RPS20(1), RPS23(4), RPS3(2), RPS4X(2), RPS6KA1(1), RPS6KA2(10), RPS6KA3(5), RPS6KB1(3), RPS6KB2(2), RPS9(2), RPSA(1), SLC36A2(2), TBC1D10C(3), TSPAN9(2), UBA52(2), UBB(2) 14474408 103 48 101 31 35 28 24 1 15 0 0.50 0.87 357 CIRCADIAN_EXERCISE ARNTL, AZIN1, BTG1, C10orf110, C1orf1, CBX3, CEBPB, CLDN5, CLOCK, CRY1, CRY2, DAZAP2, DAZAP2, LOC401029, DNAJA1, EIF4G2, ETV6, G0S2, GENX_3414, GFRA1, GSTM3, GSTP1, HERPUD1, HLA_DMA, HSPA8, IDI1, KLF9, MAP3K7IP2, MYF6, NCKAP1, NCOA4, NR1D2, OAZIN, PER1, PER2, PIGF, PPP1R3C, PPP2CB, PSMA4, PURA, SF3A3, SUMO3, TOB1, TUBB3, UCP3, UGP2, VAPA, ZFR 40 ARNTL(10), AZIN1(2), BTG1(1), CBX3(3), CLOCK(8), CRY1(5), CRY2(1), DNAJA1(2), EIF4G2(7), ETV6(5), GFRA1(8), GSTM3(3), HERPUD1(1), HSPA8(4), IDI1(1), MYF6(2), NCKAP1(9), NCOA4(4), NR1D2(6), PER1(1), PER2(2), PPP1R3C(4), PPP2CB(2), PSMA4(2), SF3A3(1), SUMO3(1), TOB1(2), TUBB3(2), UCP3(2), UGP2(7), ZFR(7) 12361876 115 40 111 22 38 34 27 1 14 1 0.50 0.87 358 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 10 CPB2(2), F2(4), F2R(1), FGB(2), FGG(4), PLAT(5), PLAU(3), PLG(9), SERPINB2(5), SERPINE1(3) 3433168 38 20 38 12 12 16 6 0 4 0 0.50 0.87 359 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(2), BAD(1), CHRNB1(3), CHRNG(3), MUSK(4), PTK2(6), PTK2B(1), RAPSN(2), SRC(3), TERT(2), YWHAH(1) 4371248 28 23 28 17 10 8 2 1 7 0 0.51 0.87 360 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 80 ATF2(1), CHUK(6), CREB1(1), DAXX(1), FOS(1), GRB2(3), IKBKB(4), MAP2K1(4), MAP2K2(1), MAP2K3(6), MAP2K5(4), MAP2K6(3), MAP3K1(8), MAP3K10(3), MAP3K11(4), MAP3K12(6), MAP3K13(9), MAP3K14(3), MAP3K2(3), MAP3K3(3), MAP3K5(7), MAP3K6(6), MAP3K7(4), MAP3K8(2), MAP3K9(4), MAP4K1(3), MAP4K2(1), MAP4K3(4), MAP4K4(8), MAP4K5(2), MAPK1(2), MAPK12(2), MAPK13(1), MAPK14(3), MAPK3(3), MAPK4(1), MAPK6(3), MAPK7(3), MAPK8(7), MAPK9(5), MAPKAPK2(3), MAPKAPK3(1), MAPKAPK5(1), MAX(1), MEF2A(4), MEF2C(9), MEF2D(1), MKNK1(1), MKNK2(3), NFKB1(6), PAK1(5), PAK2(3), RAF1(6), RELA(2), RIPK1(2), RPS6KA1(1), RPS6KA2(10), RPS6KA3(5), RPS6KA5(6), RPS6KB1(3), RPS6KB2(2), SHC1(3), SP1(2), STAT1(6), TGFB1(1), TGFB2(9), TGFBR1(9), TRADD(1), TRAF2(1) 30655068 252 67 248 69 86 74 55 4 33 0 0.51 0.87 361 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 23 CSNK2A1(4), EGF(3), EGFR(12), FOS(1), GRB2(3), JAK1(4), MAP2K1(4), MAP3K1(8), MAPK3(3), MAPK8(7), PLCG1(4), PRKCA(4), RAF1(6), RASA1(9), SHC1(3), SOS1(7), SRF(3), STAT1(6), STAT3(2) 11109064 93 41 90 23 34 29 22 1 7 0 0.51 0.87 362 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 74 AIFM1(2), AKT1(2), AKT2(6), AKT3(1), APAF1(8), BAD(1), BAX(1), BCL2(1), BCL2L1(1), BID(1), BIRC2(4), BIRC3(7), CAPN1(2), CAPN2(7), CASP10(2), CASP3(2), CASP6(2), CASP7(1), CASP9(2), CFLAR(3), CHUK(6), CSF2RB(7), DFFA(3), DFFB(2), FAS(2), FASLG(1), IKBKB(4), IL1A(1), IL1B(1), IL1R1(4), IL1RAP(1), IL3(3), IRAK1(1), IRAK2(8), IRAK3(3), IRAK4(4), MAP3K14(3), MYD88(2), NFKB1(6), NFKB2(4), NTRK1(7), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PRKACA(1), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), RELA(2), RIPK1(2), TNFRSF10A(3), TNFRSF10B(6), TNFRSF10D(1), TNFRSF1A(1), TNFSF10(1), TRADD(1), TRAF2(1) 23859160 200 59 197 62 76 62 38 0 24 0 0.51 0.87 363 NKTPATHWAY T cell differentiation into Th1 and Th2 cells occurs by differential chemokine receptor expression, which mediates tissue localization and immune response. CCL3, CCL4, CCR1, CCR2, CCR3, CCR4, CCR5, CCR7, CD28, CD4, CSF2, CXCR3, CXCR4, IFNG, IFNGR1, IFNGR2, IL12A, IL12B, IL12RB1, IL12RB2, IL18R1, IL2, IL4, IL4R, IL5, TGFB1, TGFB2, TGFB3, TNFSF5 27 CCR1(5), CCR3(4), CCR4(1), CCR5(1), CCR7(3), CD28(2), CD4(2), CXCR4(4), IFNG(1), IFNGR1(3), IFNGR2(2), IL12A(1), IL12B(2), IL12RB1(2), IL12RB2(6), IL2(4), IL4(3), IL4R(1), TGFB1(1), TGFB2(9) 6202380 57 28 57 29 15 30 6 0 6 0 0.52 0.88 364 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(3), CDK2(2), DIAPH2(12), GMNN(1), MCM10(8), MCM3(4), MCM4(4), MCM5(6), MCM6(4), MCM7(3), NACA(5), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(3), POLA2(2), POLD1(5), POLD2(1), POLD3(2), POLE(21), POLE2(1), RFC1(14), RFC4(3), RFC5(3), RPA1(2), RPA2(1), RPA4(3), UBA52(2), UBB(2) 17190508 122 48 119 29 29 55 20 1 17 0 0.52 0.88 365 PHENYLALANINE_METABOLISM ABP1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, DDC, EPX, GOT1, GOT2, HPD, LPO, MAOA, MAOB, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TAT, TPO 22 ABP1(1), ALDH1A3(6), ALDH3A1(2), ALDH3B1(3), ALDH3B2(1), AOC2(4), AOC3(4), DDC(1), EPX(7), GOT1(6), GOT2(1), HPD(4), LPO(3), MAOA(3), MAOB(1), MPO(5), PRDX1(1), PRDX6(2), TAT(5), TPO(11) 7429544 71 41 69 26 35 22 8 0 6 0 0.52 0.88 366 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 12 F10(1), F2(4), F2R(1), F3(2), F5(21), F7(3), FGB(2), FGG(4), PROC(1), PROS1(6), SERPINC1(3), TFPI(3) 4875624 51 23 51 16 10 28 9 0 4 0 0.52 0.88 367 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(3), GUSB(2), RPE(2), UCHL1(2), UCHL3(2), UGDH(4), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(2), UGT1A5(3), UGT1A6(1), UGT1A7(2), UGT1A8(1), UGT1A9(6), UGT2B15(2), UGT2B4(3) 5467492 39 22 39 11 15 14 3 0 7 0 0.53 0.88 368 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(25), DAXX(1), PAX3(7), PML(4), RB1(7), SIRT1(5), SP100(4), TNFRSF1A(1) 6122116 54 30 53 23 20 12 14 0 7 1 0.53 0.88 369 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(2), ACOX1(3), ACOX3(7), ELOVL2(3), ELOVL5(1), ELOVL6(1), FADS2(4), FASN(1), HADHA(3), HSD17B12(2), SCD(2) 4616912 29 23 29 10 13 7 4 1 4 0 0.54 0.88 370 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(2), DHRS1(1), DHRS2(3), DHRS3(2), LCMT1(3), LCMT2(2), METTL2B(2), METTL6(8), PRMT2(1), PRMT3(3), PRMT5(1), PRMT6(1), PRMT7(3), PRMT8(5), WBSCR22(1) 4834036 38 24 37 15 13 10 7 2 6 0 0.54 0.88 371 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(4), IL13(1), IL4(3), MAF(1), MAP2K3(6), MAPK14(3), NFATC1(2), NFATC2(6), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3) 3873292 39 26 39 12 21 9 4 2 3 0 0.54 0.88 372 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 GLUL(4), PGLYRP2(3) 615540 7 6 7 2 2 3 1 0 1 0 0.54 0.88 373 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 26 ABAT(5), ABP1(1), ACADL(2), ACADM(6), ACADSB(5), ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), AOC2(4), AOC3(4), CNDP1(3), DPYS(7), ECHS1(2), EHHADH(2), GAD1(9), GAD2(4), HADHA(3), MLYCD(1), SDS(2), SMS(2), UPB1(5) 9046744 100 40 99 24 37 35 16 1 11 0 0.54 0.88 374 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(8), AKT1(2), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CREB1(1), GNAS(6), GRB2(3), MAPK1(2), MAPK14(3), MAPK3(3), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PRKCA(4), RPS6KA1(1), RPS6KA5(6), SOS1(7) 8480868 67 39 66 23 25 23 16 0 3 0 0.54 0.88 375 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 25 AHCY(3), CARM1(2), CBS(3), CTH(2), LCMT1(3), LCMT2(2), MARS(6), MARS2(1), MAT1A(5), MAT2B(3), METTL2B(2), METTL6(8), PAPSS1(2), PAPSS2(4), PRMT2(1), PRMT3(3), PRMT5(1), PRMT6(1), PRMT7(3), PRMT8(5), SCLY(1), SEPHS1(3), SEPHS2(3), WBSCR22(1) 8020396 68 36 66 21 23 24 12 2 7 0 0.54 0.88 376 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 53 BMP2(1), BMP4(2), BMP5(5), BMP6(3), BMP7(6), BMP8A(1), BTRC(5), CSNK1A1(2), CSNK1A1L(5), CSNK1D(4), CSNK1G1(1), CSNK1G3(3), DHH(1), FBXW11(8), GLI1(4), GLI2(4), GLI3(14), HHIP(5), IHH(1), PRKACA(1), PRKACB(1), PRKACG(3), PRKX(2), PTCH1(9), PTCH2(6), RAB23(2), SMO(1), STK36(5), SUFU(4), WNT1(1), WNT10B(4), WNT11(3), WNT16(2), WNT2(1), WNT2B(3), WNT3(4), WNT3A(1), WNT4(1), WNT5A(3), WNT6(1), WNT7A(2), WNT7B(2), WNT8A(2), WNT9A(2), WNT9B(2), ZIC2(1) 16733816 144 58 144 69 64 35 24 1 20 0 0.54 0.88 377 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 40 ACTG2(3), ADCY3(2), ADCY9(6), ARF4(3), ARF6(1), ARL4D(1), ATP6V0A1(3), ATP6V0A2(2), ATP6V0A4(7), ATP6V0B(1), ATP6V0C(1), ATP6V0D1(2), ATP6V1A(2), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1E2(3), ATP6V1G2(2), ATP6V1G3(2), ATP6V1H(3), ERO1L(2), GNAS(6), PDIA4(5), PLCG1(4), PLCG2(13), PRKCA(4), SEC61A1(5), SEC61A2(1), SEC61B(1), TRIM23(9) 12198812 99 48 92 32 47 25 19 1 7 0 0.54 0.88 378 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@ 9 CD3D(1), CD3G(2), GZMB(2), HLA-A(3), ICAM1(2), ITGAL(8), ITGB2(5) 2770024 23 17 23 8 7 6 4 0 6 0 0.54 0.88 379 HSA00710_CARBON_FIXATION Genes involved in carbon fixation ALDOA, ALDOB, ALDOC, FBP1, FBP2, GOT1, GOT2, GPT, GPT2, MDH1, MDH2, ME1, ME3, PGK1, PGK2, PKLR, PKM2, RPE, RPIA, TKT, TKTL1, TKTL2, TPI1 22 ALDOA(1), ALDOB(5), ALDOC(3), FBP2(3), GOT1(6), GOT2(1), GPT2(2), MDH1(1), MDH2(1), ME3(5), PGK1(3), PGK2(7), PKM2(2), RPE(2), RPIA(3), TKT(3), TKTL1(5), TKTL2(7), TPI1(1) 6247096 61 34 60 25 21 26 9 0 5 0 0.55 0.89 380 GHPATHWAY Growth hormone receptors dimerize on ligand binding and activate the JAK2 protein kinase. GH1, GHR, GRB2, HRAS, INS, INSR, IRS1, JAK2, MAP2K1, MAPK1, MAPK3, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTPN6, RAF1, RPS6KA1, SHC1, SLC2A4, SOCS1, SOS1, SRF, STAT5A, STAT5B, TCF1 23 GH1(2), GHR(6), GRB2(3), INSR(6), IRS1(9), JAK2(9), MAP2K1(4), MAPK1(2), MAPK3(3), PLCG1(4), PRKCA(4), PTPN6(4), RAF1(6), RPS6KA1(1), SHC1(3), SLC2A4(4), SOS1(7), SRF(3), STAT5B(3) 9835524 83 38 81 29 29 29 15 0 8 2 0.55 0.89 381 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(4), IFNG(1), IFNGR1(3), IFNGR2(2), IKBKB(4), JAK2(9), LIN7A(2), NFKB1(6), RB1(7), RELA(2), TNFRSF1A(1), USH1C(8), WT1(6) 5834372 55 25 55 18 18 18 9 0 7 3 0.56 0.90 382 HSA00592_ALPHA_LINOLENIC_ACID_METABOLISM Genes involved in alpha-Linolenic acid metabolism ACOX1, ACOX3, FADS2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6 15 ACOX1(3), ACOX3(7), FADS2(4), PLA2G1B(1), PLA2G2F(1), PLA2G4A(8), PLA2G6(4) 3482308 28 18 27 9 14 4 6 1 3 0 0.56 0.91 383 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(2), ACAA2(1), ACADL(2), ACADM(6), ACADSB(5), ACADVL(1), ACAT1(1), ACAT2(2), ACOX1(3), ACOX3(7), ACSL1(4), ACSL3(6), ACSL4(4), ACSL5(4), ACSL6(6), ADH1A(1), ADH1B(3), ADH1C(4), ADH4(2), ADH5(1), ADH6(6), ADH7(2), ADHFE1(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(3), ALDH9A1(1), CPT1A(6), CPT1B(5), CPT2(2), CYP4A11(3), CYP4A22(2), ECHS1(2), EHHADH(2), GCDH(5), HADH(1), HADHA(3), HADHB(2), HSD17B10(2), HSD17B4(3), PECI(1) 16484772 144 49 143 45 39 49 35 4 17 0 0.57 0.91 384 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(2), CD36(1), FOS(1), FYN(5), MAPK14(3), THBS1(10) 2470356 22 16 22 8 7 10 3 0 2 0 0.57 0.91 385 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 40 AKT1(2), AKT2(6), AKT3(1), EIF4B(2), FIGF(2), HIF1A(3), IGF1(2), MAPK1(2), MAPK3(3), PDPK1(1), PGF(2), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PRKAA1(3), PRKAA2(9), RICTOR(13), RPS6KA1(1), RPS6KA2(10), RPS6KA3(5), RPS6KB1(3), RPS6KB2(2), TSC1(4), TSC2(2), ULK1(1), ULK2(4), ULK3(3), VEGFA(2), VEGFB(2), VEGFC(6) 15534456 121 44 119 39 47 38 20 0 16 0 0.57 0.91 386 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 45 IMPA1(2), IMPA2(2), INPP1(2), INPP4A(3), INPP4B(7), INPP5A(2), INPP5B(1), INPPL1(4), IPMK(2), ITGB1BP3(1), ITPK1(2), ITPKB(4), MINPP1(1), MIOX(1), OCRL(9), PI4KA(15), PI4KB(2), PIK3C3(7), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIP4K2A(2), PIP4K2B(2), PIP4K2C(3), PIP5K1A(3), PIP5K1B(2), PIP5K1C(4), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), PLCD1(7), PLCD3(2), PLCD4(2), PLCE1(9), PLCG1(4), PLCG2(13), PLCZ1(4), PTPMT1(2), SYNJ1(11), SYNJ2(6) 24177448 187 61 183 53 75 51 36 2 22 1 0.57 0.91 387 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 31 AKT1(2), AKT2(6), AKT3(1), BCR(7), BTK(7), CD19(3), DAPP1(2), FLOT1(3), GAB1(6), ITPR1(19), ITPR2(18), ITPR3(12), LYN(4), PDK1(2), PHF11(2), PITX2(2), PLCG2(13), PPP1R13B(6), PREX1(16), PTPRC(17), RPS6KA1(1), RPS6KA2(10), RPS6KA3(5), RPS6KB1(3), SAG(1), SYK(3), TEC(3), VAV1(13) 17807280 187 55 184 56 72 58 30 2 24 1 0.57 0.91 388 SIG_REGULATION_OF_THE_ACTIN_CYTOSKELETON_BY_RHO_GTPASES Genes related to regulation of the actin cytoskeleton ACTG1, ACTG2, ACTR2, ACTR3, AKT1, ANGPTL2, CDC42, CFL1, CFL2, FLNA, FLNC, FSCN1, FSCN2, FSCN3, GDI1, GDI2, LIMK1, MYH2, MYLK, MYLK2, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PFN1, PFN2, RHO, ROCK1, ROCK2, RPS4X, VASP, WASF1, WASL 35 ACTG2(3), ACTR2(2), ACTR3(3), AKT1(2), ANGPTL2(8), CDC42(1), CFL1(1), FLNA(3), FLNC(13), FSCN3(2), GDI1(1), GDI2(1), LIMK1(5), MYH2(12), MYLK(14), MYLK2(3), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PFN2(1), RHO(3), ROCK1(15), ROCK2(6), RPS4X(2), VASP(3), WASF1(3), WASL(7) 16002580 135 53 135 37 45 45 23 1 21 0 0.58 0.92 389 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 19 AXIN1(2), BTRC(5), CREBBP(25), CSNK1A1(2), CSNK1D(4), CSNK2A1(4), CTBP1(1), FZD1(1), HDAC1(2), MAP3K7(4), NLK(2), PPARD(2), PPP2CA(1), TLE1(1), WIF1(2), WNT1(1) 7016728 59 34 59 23 22 12 15 1 9 0 0.58 0.92 390 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 59 APAF1(8), ATR(18), BAI1(2), BAX(1), BID(1), CASP3(2), CASP9(2), CCNB1(2), CCNB2(2), CCNB3(7), CCND2(1), CCND3(1), CCNE1(3), CCNE2(2), CCNG1(3), CDK2(2), CDK4(3), CDK6(1), CDKN1A(1), CHEK1(1), CHEK2(1), DDB2(1), EI24(1), FAS(2), GTSE1(2), IGF1(2), IGFBP3(4), MDM2(4), MDM4(3), PPM1D(4), RCHY1(2), RFWD2(5), RPRM(1), RRM2(3), SERPINB5(2), SERPINE1(3), SESN1(2), SESN2(4), SIAH1(1), STEAP3(1), THBS1(10), TNFRSF10B(6), TP53I3(2), TSC2(2), ZMAT3(5) 18345844 136 55 136 39 42 53 28 1 12 0 0.58 0.92 391 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(4), APAF1(8), BCL2(1), CASP3(2), CASP9(2), DAXX(1), FAS(2), FASLG(1), HSPB2(2), IL1A(1), MAPKAPK2(3), MAPKAPK3(1) 3763944 28 20 28 11 7 11 6 0 4 0 0.58 0.92 392 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 CSNK2A1(4), FOS(1), GRB2(3), MAP2K1(4), MAPK3(3), MAPK8(7), NGFR(3), PLCG1(4), RAF1(6), SHC1(3), SOS1(7) 4952828 45 26 43 9 14 15 12 1 3 0 0.58 0.92 393 GLYCINE_SERINE_AND_THREONINE_METABOLISM ABP1, AGXT, AGXT2, ALAS1, ALAS2, AMT, AOC2, AOC3, ATP6V0C, SHMT1, BHMT, CBS, CHDH, CHKA, CHKB, CHKB, CPT1B, CTH, DAO, DLD, DMGDH, GAMT, GARS, GATM, GCAT, GLDC, MAOA, MAOB, PEMT, PISD, PLCB2, PLCG1, PLCG2, PSPH, SARDH, SARS, SHMT1, SHMT2, TARS 37 ABP1(1), AGXT2(5), ALAS1(6), ALAS2(6), AOC2(4), AOC3(4), ATP6V0C(1), BHMT(5), CBS(3), CHDH(2), CHKA(4), CPT1B(5), CTH(2), DAO(6), DLD(1), DMGDH(7), GAMT(1), GARS(3), GATM(1), GCAT(1), GLDC(3), MAOA(3), MAOB(1), PEMT(1), PISD(2), PLCB2(3), PLCG1(4), PLCG2(13), PSPH(1), SARDH(8), SARS(2), SHMT1(2), SHMT2(2), TARS(6) 14310036 119 49 117 43 52 41 12 0 14 0 0.59 0.92 394 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(3), ADH1C(4), ADH4(2), ADH6(6), ADH7(2), ADHFE1(6), ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH3B1(3), ALDH3B2(1), ALDH9A1(1), ALDOA(1), ALDOB(5), ALDOC(3), DLAT(3), DLD(1), ENO2(3), ENO3(4), FBP2(3), G6PC(4), GCK(2), GPI(2), HK1(6), HK2(3), HK3(5), LDHA(2), LDHB(3), LDHC(2), PDHA1(5), PDHA2(8), PDHB(2), PFKM(4), PFKP(2), PGAM1(3), PGK1(3), PGM1(4), PGM3(5), PKM2(2), TPI1(1) 16298620 154 54 152 50 51 58 35 0 10 0 0.59 0.92 395 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(3), ADH1C(4), ADH4(2), ADH6(6), ADH7(2), ADHFE1(6), ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH3B1(3), ALDH3B2(1), ALDH9A1(1), ALDOA(1), ALDOB(5), ALDOC(3), DLAT(3), DLD(1), ENO2(3), ENO3(4), FBP2(3), G6PC(4), GCK(2), GPI(2), HK1(6), HK2(3), HK3(5), LDHA(2), LDHB(3), LDHC(2), PDHA1(5), PDHA2(8), PDHB(2), PFKM(4), PFKP(2), PGAM1(3), PGK1(3), PGM1(4), PGM3(5), PKM2(2), TPI1(1) 16298620 154 54 152 50 51 58 35 0 10 0 0.59 0.92 396 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3D(1), CD3G(2) 387336 3 2 3 1 1 1 0 0 1 0 0.59 0.92 397 IL18PATHWAY Pro-inflammatory IL-18 is activated in macrophages by caspase-1 cleavage and, in conjunction with IL-12, stimulates Th1 cell differentiation. CASP1, IFNG, IL12A, IL12B, IL18, IL2 6 CASP1(2), IFNG(1), IL12A(1), IL12B(2), IL2(4) 1022608 10 7 10 6 0 10 0 0 0 0 0.59 0.92 398 IL12PATHWAY IL12 and Stat4 Dependent Signaling Pathway in Th1 Development CCR5, CD3D, CD3E, CD3G, CD3Z, CXCR3, ETV5, IFNG, IL12A, IL12B, IL12RB1, IL12RB2, IL18, IL18R1, JAK2, JUN, MAP2K6, MAPK14, MAPK8, STAT4, TRA@, TRB@, TYK2 19 CCR5(1), CD3D(1), CD3G(2), ETV5(6), IFNG(1), IL12A(1), IL12B(2), IL12RB1(2), IL12RB2(6), JAK2(9), MAP2K6(3), MAPK14(3), MAPK8(7), STAT4(3), TYK2(1) 5851812 48 24 48 21 8 21 9 1 7 2 0.60 0.92 399 KREBS_TCA_CYCLE ACO2, CGI_48, CS, DLAT, DLD, DLST, DLST, DLSTP, FH, IDH2, IDH3A, IDH3B, IDH3G, KIAA1348, MDH1, MDH2, OGDH, PC, PDHA1, PDHA2, PDHB, PDHX, PDK1, PDK2, PDK3, PDK4, PDP2, PPM2C, SDHA, SDHA, SDHAL2, SDHB, SDHC, SDHD, SUCLA2, SUCLG1, SUCLG2, WDR50 30 ACO2(2), DLAT(3), DLD(1), DLST(1), FH(1), IDH2(7), IDH3A(4), IDH3G(2), MDH1(1), MDH2(1), OGDH(4), PC(6), PDHA1(5), PDHA2(8), PDHB(2), PDHX(2), PDK1(2), PDK2(2), PDK3(1), PDK4(3), PDP2(1), SDHA(6), SDHB(2), SDHD(1), SUCLA2(5), SUCLG1(2) 9641104 75 37 74 29 32 20 11 0 12 0 0.60 0.93 400 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 20 DLG4(3), GRIN1(1), GRIN2B(10), GRIN2C(5), GRIN2D(5), NOS1(11), PPP3CA(3), PPP3CB(5), PPP3CC(4), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PRKCA(4), SYT1(1) 7587044 65 32 65 28 30 17 8 0 10 0 0.60 0.93 401 SA_FAS_SIGNALING The TNF-type receptor Fas induces apoptosis on ligand binding. BCL2, CASP3, CASP8, CFL1, CFLAR, P11, PDE6D, TNFRSF6, TNFSF6 5 BCL2(1), CASP3(2), CFL1(1), CFLAR(3), PDE6D(1) 891972 8 7 8 2 2 4 2 0 0 0 0.61 0.93 402 LYMPHOCYTEPATHWAY B and T cell lymphocytes interact with other cells via transmembrane adhesion proteins such as CD44, which interacts with endothelial cells. CD44, ICAM1, ITGA4, ITGAL, ITGB1, ITGB2, PECAM1, SELE, SELL 9 CD44(3), ICAM1(2), ITGA4(8), ITGAL(8), ITGB1(6), ITGB2(5), PECAM1(2), SELE(4), SELL(3) 4417984 41 22 39 11 9 19 9 0 4 0 0.61 0.93 403 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(11), AKT1(2), BAX(1), CDKN1A(1), CPB2(2), CSNK1A1(2), CSNK1D(4), FHL2(2), HIF1A(3), IGFBP3(4), MAPK8(7), MDM2(4), NFKBIB(1), NQO1(1) 4462340 45 25 45 5 11 14 15 2 3 0 0.61 0.93 404 UBIQUINONE_BIOSYNTHESIS NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 15 NDUFA1(1), NDUFA10(2), NDUFA4(2), NDUFB2(1), NDUFB6(1), NDUFS1(6), NDUFS2(3), NDUFV1(2) 2338256 18 14 18 7 7 6 3 0 2 0 0.61 0.93 405 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(3), PSMA4(2), PSMA5(1), PSMA7(1), PSMB2(2), PSMB3(1), PSMB5(2), PSMB6(2), PSMC3(3), PSMD14(1), RPN2(1), UBE2A(2), UBE3A(11) 4398832 34 18 34 13 10 11 9 1 3 0 0.61 0.93 406 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 20 ATR(18), BRCA1(6), CCNB1(2), CDC25A(2), CDC25B(5), CDC25C(4), CDKN1A(1), CHEK1(1), CHEK2(1), EP300(15), MDM2(4), MYT1(13), PRKDC(18), RPS6KA1(1), WEE1(3), YWHAH(1), YWHAQ(2) 12184192 97 42 96 24 30 34 21 2 10 0 0.61 0.93 407 GLYCOSAMINOGLYCAN_DEGRADATION ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, IDS, IDUA, LCT, NAGLU 11 ARSB(5), GALNS(4), GLB1(3), GNS(4), GUSB(2), HEXB(3), IDS(2), IDUA(1), LCT(20), NAGLU(4) 4901776 48 27 48 13 21 12 10 0 5 0 0.61 0.93 408 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(18), ACACB(15), ACAT1(1), ACAT2(2), ACOT12(9), ACSS1(3), ACSS2(6), ACYP1(2), AKR1B1(3), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(3), ALDH9A1(1), DLAT(3), DLD(1), GRHPR(1), LDHA(2), LDHAL6A(3), LDHAL6B(2), LDHB(3), LDHC(2), LDHD(1), MDH1(1), MDH2(1), ME2(3), ME3(5), PC(6), PCK1(3), PCK2(4), PDHA1(5), PDHA2(8), PDHB(2), PKM2(2) 15314464 143 46 141 43 48 52 23 2 18 0 0.62 0.93 409 ALKALOID_BIOSYNTHESIS_II ABP1, AOC2, AOC3, CES1, ESD 5 ABP1(1), AOC2(4), AOC3(4), CES1(5), ESD(1) 1980104 15 14 15 9 6 7 2 0 0 0 0.62 0.94 410 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 19 F10(1), F11(4), F12(2), F13B(5), F2(4), F5(21), F7(3), F8(18), F9(6), FGB(2), FGG(4), LPA(10), PLAT(5), PLAU(3), PLG(9), SERPINB2(5), SERPINE1(3), VWF(15) 11177176 120 41 117 43 29 56 20 0 15 0 0.62 0.94 411 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(18), ACAT1(1), ACAT2(2), ACYP1(2), ADH5(1), AKR1B1(3), ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), DLAT(3), DLD(1), GRHPR(1), LDHA(2), LDHB(3), LDHC(2), LDHD(1), MDH1(1), MDH2(1), ME2(3), ME3(5), PC(6), PCK1(3), PDHA1(5), PDHA2(8), PDHB(2), PKM2(2) 12020216 109 41 107 36 38 38 20 1 12 0 0.63 0.94 412 CASPASEPATHWAY Caspases are cysteine proteases active in apoptosis; caspase-8 and 9 cleave and activate other caspases, while 3, 6, and 7 cleave cellular targets. ADPRT, APAF1, ARHGDIB, BIRC2, BIRC3, BIRC4, CASP1, CASP10, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CYCS, DFFA, DFFB, GZMB, LMNA, LMNB1, LMNB2, PRF1 20 APAF1(8), ARHGDIB(3), BIRC2(4), BIRC3(7), CASP1(2), CASP10(2), CASP2(4), CASP3(2), CASP4(3), CASP6(2), CASP7(1), CASP9(2), DFFA(3), DFFB(2), GZMB(2), LMNB1(4), LMNB2(1) 6110152 52 28 51 15 12 22 10 0 8 0 0.63 0.94 413 FATTY_ACID_BIOSYNTHESIS_PATH_2 ACAA1, ACAA2, ACAT1, ACAT2, ECHS1, EHHADH, HADHA, HADHB, SDS 9 ACAA1(2), ACAA2(1), ACAT1(1), ACAT2(2), ECHS1(2), EHHADH(2), HADHA(3), HADHB(2), SDS(2) 2829676 17 13 17 7 3 8 2 0 4 0 0.63 0.94 414 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 62 APAF1(8), BAD(1), BAK1(1), BAX(1), BCL2(1), BCL2L1(1), BCL2L11(3), BID(1), BIRC2(4), BIRC3(7), BNIP3L(3), CASP1(2), CASP10(2), CASP2(4), CASP3(2), CASP4(3), CASP6(2), CASP7(1), CASP9(2), CHUK(6), DFFA(3), DFFB(2), FAS(2), FASLG(1), GZMB(2), HELLS(5), IKBKB(4), IRF1(1), IRF2(3), IRF3(2), IRF4(3), IRF5(3), IRF6(2), MAP3K1(8), MDM2(4), NFKB1(6), NFKBIB(1), NFKBIE(2), RELA(2), RIPK1(2), TNFRSF10B(6), TNFRSF1A(1), TNFRSF21(5), TNFSF10(1), TRADD(1), TRAF1(2), TRAF2(1), TRAF3(6) 17957824 136 52 135 46 47 44 25 2 18 0 0.63 0.94 415 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(2), CDC25B(5), CDK7(1), CDKN1A(1), CHEK1(1), NEK1(9), WEE1(3) 2529196 22 14 21 7 7 8 4 2 1 0 0.63 0.94 416 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(5), EIF2B1(2), EIF2B2(1), EIF2B3(2), EIF2B5(5), EIF2S2(1), EIF2S3(1), ELAVL1(3), FLT1(13), FLT4(5), HIF1A(3), KDR(10), NOS3(2), PLCG1(4), PRKCA(4), PTK2(6), SHC1(3), VHL(1) 10076004 71 39 70 28 24 23 14 0 10 0 0.64 0.94 417 GANGLIOSIDE_BIOSYNTHESIS B3GALT4, GALGT, SIAT4A, SIAT4B, SIAT7B, SIAT7D, SIAT9, ST3GAL1, ST3GAL2, ST3GAL4, ST3GAL5, ST6GALNAC2, ST6GALNAC4, ST8SIA1 8 B3GALT4(1), ST3GAL1(1), ST3GAL2(1), ST3GAL4(2), ST6GALNAC2(2), ST6GALNAC4(2), ST8SIA1(3) 1894452 12 11 12 4 2 3 5 0 2 0 0.64 0.94 418 ST_GAQ_PATHWAY G-alpha-q activates phospholipase C, resulting in calcium influx and increasing protein kinase C activity. ADRBK1, AKT1, AKT2, AKT3, BF, DAG1, GNAQ, IKBKG, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PDK1, PHKA2, PIK3CB, PITX2, PLD1, PLD2, PLD3, VN1R1 26 ADRBK1(1), AKT1(2), AKT2(6), AKT3(1), DAG1(5), GNAQ(4), ITPKB(4), ITPR1(19), ITPR2(18), ITPR3(12), NFKB1(6), NFKB2(4), NFKBIB(1), NFKBIE(2), PDK1(2), PHKA2(7), PIK3CB(2), PITX2(2), PLD1(11), PLD2(2), PLD3(5), VN1R1(4) 15142744 120 46 120 41 51 35 18 2 13 1 0.64 0.94 419 SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES ACAT1, ACAT2, BDH, HMGCL, OXCT1 4 ACAT1(1), ACAT2(2), HMGCL(1), OXCT1(3) 1135008 7 7 7 3 2 4 1 0 0 0 0.64 0.94 420 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(5), GALNS(4), GLB1(3), GNS(4), GUSB(2), HEXB(3), HGSNAT(6), HPSE(2), HPSE2(12), IDS(2), IDUA(1), LCT(20), NAGLU(4), SPAM1(4) 6988988 72 32 70 19 28 20 15 1 8 0 0.64 0.94 421 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(5), CDKN1A(1), GRIN1(1), HIF1A(3), JAK2(9), NFKB1(6), RELA(2), SOD2(4) 4318920 31 20 31 9 10 9 5 0 5 2 0.64 0.94 422 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 ATP5O(2), ATP6AP1(2), ATP6V0A1(3), ATP6V0A4(7), ATP6V0B(1), ATP6V0C(1), ATP6V0D1(2), ATP6V1A(2), ATP6V1B1(5), ATP6V1B2(2), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1G2(2), ATP6V1G3(2), ATP6V1H(3), SHMT1(2) 5125316 41 25 40 10 14 15 8 0 4 0 0.64 0.94 423 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 ATP5O(2), ATP6AP1(2), ATP6V0A1(3), ATP6V0A4(7), ATP6V0B(1), ATP6V0C(1), ATP6V0D1(2), ATP6V1A(2), ATP6V1B1(5), ATP6V1B2(2), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1G2(2), ATP6V1G3(2), ATP6V1H(3), SHMT1(2) 5125316 41 25 40 10 14 15 8 0 4 0 0.64 0.94 424 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 ATP5O(2), ATP6AP1(2), ATP6V0A1(3), ATP6V0A4(7), ATP6V0B(1), ATP6V0C(1), ATP6V0D1(2), ATP6V1A(2), ATP6V1B1(5), ATP6V1B2(2), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1G2(2), ATP6V1G3(2), ATP6V1H(3), SHMT1(2) 5125316 41 25 40 10 14 15 8 0 4 0 0.64 0.94 425 IFNAPATHWAY Interferon alpha, active in the immune response, binds to the IFN receptor and activates Jak1 and Tyk2, which phosphorylate Stat1 and Stat2. IFNA1, IFNAR1, IFNAR2, IFNB1, ISGF3G, JAK1, STAT1, STAT2, TYK2 8 IFNA1(1), IFNAR1(3), IFNAR2(2), IFNB1(1), JAK1(4), STAT1(6), STAT2(7), TYK2(1) 3630512 25 18 24 6 11 6 5 0 3 0 0.65 0.94 426 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 14 APAF1(8), BIRC2(4), BIRC3(7), CASP10(2), CASP3(2), CASP7(1), CASP9(2), DFFA(3), DFFB(2), GZMB(2), SCAP(3), SREBF1(1), SREBF2(3) 5722936 40 24 40 16 8 17 7 0 8 0 0.65 0.94 427 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), CXCL12(1), CXCR4(4), FOS(1), GNAQ(4), MAPK14(3), MAPK8(7), PLCG1(4), PRKCA(4), PTK2B(1), SYT1(1) 4495712 31 21 31 12 9 11 5 1 5 0 0.65 0.94 428 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 22 ASAH1(3), CASP3(2), CERK(1), CREB1(1), CREB3(3), CREB5(4), DAG1(5), EPHB2(8), FOS(1), GNAQ(4), ITPKB(4), MAPK1(2), MAPK8(7), MAPK8IP1(4), MAPK8IP3(2), MAPK9(5) 6942480 56 29 54 20 17 14 12 2 11 0 0.65 0.94 429 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 CHIA(5), CHIT1(5), CMAS(8), CTBS(4), CYB5R1(3), CYB5R3(1), GFPT1(4), GFPT2(4), GNE(2), GNPDA2(1), HEXB(3), HK1(6), HK2(3), HK3(5), LHPP(2), MTMR1(5), MTMR2(2), MTMR6(4), NAGK(2), NANS(1), NPL(3), PGM3(5), PHPT1(1), RENBP(1) 9678628 80 41 79 24 32 27 14 1 6 0 0.65 0.94 430 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 19 BAD(1), BAX(1), BCL2(1), MAP2K1(4), MAP3K1(8), MAPK1(2), MAPK3(3), MAPK8(7), NFKB1(6), NSMAF(3), RAF1(6), RELA(2), RIPK1(2), SMPD1(6), TNFRSF1A(1), TRADD(1), TRAF2(1) 6318392 55 29 54 17 25 14 10 2 4 0 0.66 0.95 431 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 GPX1(1), GSR(1), GSS(4), IL8(1), NFKB1(6), NOX1(1), RELA(2), XDH(7) 3343964 23 16 23 8 8 6 6 0 3 0 0.66 0.95 432 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(3), COQ6(2), COQ7(1), NDUFA12(2), NDUFA13(1), NDUFB11(1) 1402476 10 8 10 2 2 4 2 0 2 0 0.66 0.95 433 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(2), IL22(2), IL22RA1(1), JAK1(4), JAK2(9), JAK3(9), STAT1(6), STAT3(2), STAT5B(3), TYK2(1) 6252292 39 25 38 17 12 12 7 0 6 2 0.67 0.95 434 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(3), ABP1(1), AOC2(4), AOC3(4), CES1(5), CES7(1), DDHD1(3), ESCO1(11), ESCO2(4), LIPA(1), MYST3(18), MYST4(10), PLA1A(3), PNPLA3(4), PPME1(2), PRDX6(2), SH3GLB1(4) 8536896 80 35 79 27 31 24 17 1 7 0 0.67 0.95 435 1_2_DICHLOROETHANE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1) 2697372 33 19 33 5 13 12 7 0 1 0 0.67 0.95 436 ASCORBATE_AND_ALDARATE_METABOLISM ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1) 2697372 33 19 33 5 13 12 7 0 1 0 0.67 0.95 437 HISTIDINE_METABOLISM ABP1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, AOC2, AOC3, ASPA, CNDP1, DDC, HAL, HARS, HARSL, HDC, HNMT, MAOA, MAOB, PRPS1, PRPS2 24 ABP1(1), ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH3B1(3), ALDH3B2(1), ALDH9A1(1), AOC2(4), AOC3(4), ASPA(5), CNDP1(3), DDC(1), HAL(4), HARS(2), HDC(8), HNMT(4), MAOA(3), MAOB(1), PRPS1(1), PRPS2(2) 8248076 80 40 80 27 31 30 16 0 3 0 0.68 0.95 438 BENZOATE_DEGRADATION_VIA_COA_LIGATION ACAT1, ACAT2, ACYP1, ACYP2, ECHS1, EHHADH, GCDH, HADHA, SDHB, SDS 10 ACAT1(1), ACAT2(2), ACYP1(2), ECHS1(2), EHHADH(2), GCDH(5), HADHA(3), SDHB(2), SDS(2) 2645360 21 13 21 3 6 7 2 1 5 0 0.68 0.95 439 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 24 ABAT(5), ABP1(1), ACADM(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(3), ALDH9A1(1), AOC2(4), AOC3(4), CNDP1(3), DPYS(7), ECHS1(2), EHHADH(2), GAD1(9), GAD2(4), HADHA(3), HIBCH(1), MLYCD(1), SMS(2), UPB1(5) 8361792 85 36 84 24 30 31 13 1 10 0 0.68 0.95 440 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(5), CSF1R(3), EGF(3), EGFR(12), GRB2(3), MET(5), PDGFRA(17), PRKCA(4), SH3GLB1(4), SH3GLB2(2), SH3KBP1(4), SRC(3) 6577212 65 28 65 29 20 25 15 0 4 1 0.68 0.95 441 SALMONELLAPATHWAY Salmonella induces membrane ruffling in infected cells via bacterial proteins including SipA, SipC, and SopE, which alter actin structure. ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, RAC1, WASF1, WASL 12 ACTA1(4), ACTR2(2), ACTR3(3), ARPC1A(5), ARPC1B(2), ARPC2(2), CDC42(1), WASF1(3), WASL(7) 2755360 29 17 29 6 11 9 6 0 3 0 0.68 0.95 442 SA_DIACYLGLYCEROL_SIGNALING DAG (diacylglycerol) signaling activity ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP 9 ESR2(3), PDE1A(4), PDE1B(3), PLCB1(8), PLCB2(3), PRL(3), TRH(2) 3389904 26 18 26 11 11 8 4 1 2 0 0.69 0.96 443 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 13 DYRK1A(5), DYRK1B(4), GLI2(4), GLI3(14), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), SMO(1), SUFU(4) 5122500 45 28 45 24 19 13 7 0 6 0 0.69 0.96 444 HSA00670_ONE_CARBON_POOL_BY_FOLATE Genes involved in one carbon pool by folate ALDH1L1, AMT, ATIC, DHFR, FTCD, GART, MTFMT, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 16 ALDH1L1(6), ATIC(4), DHFR(1), FTCD(2), GART(3), MTFMT(2), MTHFD1(6), MTHFD1L(8), MTHFR(7), MTHFS(1), MTR(7), SHMT1(2), SHMT2(2), TYMS(3) 6387856 54 30 53 16 22 18 7 1 6 0 0.69 0.96 445 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(6), ACADVL(1), ACSL1(4), ACSL3(6), ACSL4(4), CPT1A(6), CPT2(2), EHHADH(2), HADHA(3), SCP2(3), SLC25A20(2) 5661168 41 23 40 14 11 15 8 0 7 0 0.70 0.96 446 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(2), CD3D(1), CD3G(2), CD4(2) 949080 8 6 8 5 3 4 0 0 1 0 0.70 0.96 447 HEME_BIOSYNTHESIS ALAD, ALAS1, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, UROS 9 ALAD(1), ALAS1(6), ALAS2(6), CPOX(1), FECH(3), HMBS(2), PPOX(3), UROD(1), UROS(1) 2600832 24 15 24 5 13 8 2 0 1 0 0.70 0.96 448 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(2), IL8(1) 570136 3 3 3 3 0 2 0 0 1 0 0.70 0.96 449 DREAMPATHWAY The transcription factor DREAM blocks expression of the prodynorphin gene, which encodes the ligand of an opioid receptor that blocks pain signaling. CREB1, CREM, CSEN, FOS, JUN, MAPK3, OPRK1, POLR2A, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 13 CREB1(1), CREM(4), FOS(1), MAPK3(3), OPRK1(5), POLR2A(6), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3) 4266716 33 23 33 8 16 7 6 1 3 0 0.70 0.96 450 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), MAX(1), SP1(2), SP3(3), WT1(6) 2055316 14 12 14 4 8 3 3 0 0 0 0.70 0.96 451 HSA00565_ETHER_LIPID_METABOLISM Genes involved in ether lipid metabolism AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, AGPS, CHPT1, ENPP2, ENPP6, LYCAT, PAFAH1B1, PAFAH1B2, PAFAH1B3, PAFAH2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLD1, PLD2, PPAP2A, PPAP2B, PPAP2C 29 AGPAT1(2), AGPAT3(3), AGPAT6(2), AGPS(3), CHPT1(1), ENPP2(14), ENPP6(2), PAFAH1B1(3), PAFAH1B3(2), PAFAH2(1), PLA2G1B(1), PLA2G2F(1), PLA2G4A(8), PLA2G6(4), PLD1(11), PLD2(2), PPAP2B(1) 7597596 61 32 60 28 23 24 11 0 3 0 0.70 0.96 452 MONOCYTEPATHWAY Monocytes are a class of immune phagocytes that can develop into macrophages and express LFA-1, CD44, and other surface signaling proteins. CD44, ICAM1, ITGA4, ITGAL, ITGAM, ITGB1, ITGB2, PECAM1, SELE, SELL, SELP 11 CD44(3), ICAM1(2), ITGA4(8), ITGAL(8), ITGAM(8), ITGB1(6), ITGB2(5), PECAM1(2), SELE(4), SELL(3), SELP(6) 5770408 55 26 53 16 15 24 10 0 6 0 0.71 0.96 453 HSA00750_VITAMIN_B6_METABOLISM Genes involved in vitamin B6 metabolism AOX1, PDXK, PDXP, PNPO, PSAT1 5 AOX1(8), PNPO(1), PSAT1(4) 1634620 13 9 13 5 4 5 2 0 2 0 0.71 0.97 454 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(2), IFNAR1(3), IFNAR2(2), IFNB1(1), MAPK8(7), NFKB1(6), RELA(2), TNFRSF11A(3), TNFSF11(1), TRAF6(4) 3708116 32 17 32 11 12 9 5 1 5 0 0.72 0.97 455 NOTCHPATHWAY Proteolysis and Signaling Pathway of Notch ADAM17, DLL1, FURIN, NOTCH1, PSEN1, RBPSUH 5 ADAM17(7), DLL1(4), FURIN(3), PSEN1(3) 2877556 17 13 17 3 7 2 2 0 6 0 0.72 0.97 456 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(4), CYP1A2(3), CYP2C18(2), CYP2C19(4), CYP2C8(4), CYP2C9(7), CYP2E1(6), CYP2J2(3), CYP3A4(1), CYP3A43(2), CYP3A5(3), CYP3A7(6), HSD3B7(2), PLA2G1B(1), PLA2G2F(1), PLA2G4A(8), PLA2G6(4), RDH11(1), RDH12(3), RDH13(1) 8076436 66 31 65 28 26 19 16 0 4 1 0.72 0.97 457 SA_B_CELL_RECEPTOR_COMPLEXES Antigen binding to B cell receptors activates protein tyrosine kinases, such as the Src family, which ultimate activate MAP kinases. ATF2, BCR, BLNK, ELK1, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP3K1, MAPK1, MAPK3, MAPK8IP3, PAPPA, RAC1, RPS6KA1, RPS6KA3, SHC1, SOS1, SYK, VAV1, VAV2, VAV3 23 ATF2(1), BCR(7), BLNK(1), FOS(1), GRB2(3), LYN(4), MAP2K1(4), MAP3K1(8), MAPK1(2), MAPK3(3), MAPK8IP3(2), RPS6KA1(1), RPS6KA3(5), SHC1(3), SOS1(7), SYK(3), VAV1(13), VAV2(4), VAV3(12) 9684908 84 39 82 18 30 31 15 0 8 0 0.72 0.97 458 CARBON_FIXATION ALDOA, ALDOB, ALDOC, FBP1, FBP2, GOT1, GOT2, GPT, GPT2, MDH1, MDH2, ME1, ME2, ME3, PGK1, PKLR, PKM2, RPE, RPE, LOC440001, RPIA, TKT, TPI1 20 ALDOA(1), ALDOB(5), ALDOC(3), FBP2(3), GOT1(6), GOT2(1), GPT2(2), MDH1(1), MDH2(1), ME2(3), ME3(5), PGK1(3), PKM2(2), RPE(2), RPIA(3), TKT(3), TPI1(1) 5538892 45 28 44 18 15 19 7 0 4 0 0.72 0.97 459 HSA00260_GLYCINE_SERINE_AND_THREONINE_METABOLISM Genes involved in glycine, serine and threonine metabolism ABP1, AGXT, AGXT2, AKR1B10, ALAS1, ALAS2, AMT, AOC2, AOC3, BHMT, CBS, CHDH, CHKA, CHKB, CTH, DAO, DLD, DMGDH, GAMT, GARS, GATM, GCAT, GLDC, GNMT, HSD3B7, MAOA, MAOB, PEMT, PHGDH, PIPOX, PISD, PSAT1, PSPH, RDH11, RDH12, RDH13, RDH14, SARDH, SARS, SARS2, SDS, SHMT1, SHMT2, TARS, TARS2 45 ABP1(1), AGXT2(5), ALAS1(6), ALAS2(6), AOC2(4), AOC3(4), BHMT(5), CBS(3), CHDH(2), CHKA(4), CTH(2), DAO(6), DLD(1), DMGDH(7), GAMT(1), GARS(3), GATM(1), GCAT(1), GLDC(3), GNMT(1), HSD3B7(2), MAOA(3), MAOB(1), PEMT(1), PHGDH(2), PIPOX(4), PISD(2), PSAT1(4), PSPH(1), RDH11(1), RDH12(3), RDH13(1), SARDH(8), SARS(2), SARS2(2), SDS(2), SHMT1(2), SHMT2(2), TARS(6), TARS2(5) 14581668 120 47 120 45 48 45 14 0 13 0 0.73 0.97 460 HSA03320_PPAR_SIGNALING_PATHWAY Genes involved in PPAR signaling pathway ACAA1, ACADL, ACADM, ACOX1, ACOX2, ACOX3, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADIPOQ, ANGPTL4, APOA1, APOA2, APOA5, APOC3, AQP7, CD36, CPT1A, CPT1B, CPT1C, CPT2, CYP27A1, CYP4A11, CYP4A22, CYP7A1, CYP8B1, DBI, EHHADH, FABP1, FABP2, FABP3, FABP4, FABP5, FABP5L1, FABP6, FABP7, FADS2, GK, GK2, HMGCS2, ILK, LOC642956, LPL, ME1, MMP1, NR1H3, OLR1, PCK1, PCK2, PDPK1, PLIN, PLTP, PPARA, PPARD, PPARG, RXRA, RXRB, RXRG, SCD, SCP2, SLC27A1, SLC27A2, SLC27A4, SLC27A5, SLC27A6, SORBS1, UBC, UCP1 65 ACAA1(2), ACADL(2), ACADM(6), ACOX1(3), ACOX2(2), ACOX3(7), ACSL1(4), ACSL3(6), ACSL4(4), ACSL5(4), ACSL6(6), ADIPOQ(4), APOA2(1), APOA5(1), AQP7(1), CD36(1), CPT1A(6), CPT1B(5), CPT2(2), CYP27A1(3), CYP4A11(3), CYP4A22(2), CYP7A1(4), CYP8B1(3), EHHADH(2), FABP1(1), FABP2(2), FABP3(1), FABP4(1), FABP5(1), FABP6(1), FABP7(1), FADS2(4), GK(3), GK2(6), HMGCS2(1), LPL(6), MMP1(2), NR1H3(4), OLR1(2), PCK1(3), PCK2(4), PDPK1(1), PLTP(7), PPARA(1), PPARD(2), PPARG(1), RXRA(1), RXRB(3), RXRG(4), SCD(2), SCP2(3), SLC27A1(2), SLC27A2(3), SLC27A4(1), SLC27A5(4), SLC27A6(9), SORBS1(11), UCP1(1) 21344000 183 58 180 57 55 70 34 6 18 0 0.73 0.97 461 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 59 ATP12A(18), ATP4B(1), ATP5O(2), ATP6AP1(2), ATP6V0A1(3), ATP6V0A4(7), ATP6V0B(1), ATP6V0C(1), ATP6V0D1(2), ATP6V1A(2), ATP6V1B1(5), ATP6V1B2(2), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1G2(2), ATP6V1G3(2), ATP6V1H(3), ATP7B(4), COX10(2), COX4I1(2), COX6A2(1), COX6C(1), COX7A1(1), NDUFA1(1), NDUFA10(2), NDUFA4(2), NDUFB2(1), NDUFB6(1), NDUFS1(6), NDUFS2(3), NDUFV1(2), PPA2(3), SDHA(6), SDHB(2), SHMT1(2), UQCRB(2), UQCRC1(2), UQCRFS1(2), UQCRH(1) 11886872 107 41 106 32 41 40 17 0 9 0 0.73 0.97 462 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 30 AKT1(2), AKT2(6), AKT3(1), BAD(1), BTK(7), DAPP1(2), GRB2(3), GSK3A(2), IARS(6), IGFBP1(2), INPP5D(4), PDK1(2), PPP1R13B(6), RPS6KA1(1), RPS6KA2(10), RPS6KA3(5), RPS6KB1(3), SHC1(3), SOS1(7), SOS2(11), TEC(3), YWHAB(2), YWHAE(3), YWHAH(1), YWHAQ(2) 10842672 95 38 93 27 28 34 21 0 12 0 0.73 0.97 463 STRIATED_MUSCLE_CONTRACTION ACTA1, ACTA2, ACTC, ACTN2, ACTN3, ACTN4, C9orf97, DES, DES, FAM48A, DMD, MYBPC1, MYBPC2, MYBPC3, MYH3, MYH6, MYH6, MYH7, MYH8, MYL1, MYL2, MYL3, MYL4, MYL9, MYOM1, NEB, TCAP, TMOD1, TNNC2, TNNI1, TNNI2, TNNI3, TNNT1, TNNT2, TNNT3, TPM1, TPM2, TPM3, TPM4, TPM4, TTN, VIM 35 ACTA1(4), ACTA2(3), ACTN2(8), ACTN3(3), ACTN4(3), DES(1), FAM48A(6), MYBPC1(7), MYBPC2(4), MYBPC3(3), MYH3(14), MYH6(12), MYH7(12), MYH8(20), MYL1(2), MYL2(1), MYL4(1), MYL9(2), MYOM1(12), NEB(54), TMOD1(3), TNNC2(1), TNNI1(2), TNNI3(1), TNNT2(3), TPM1(2), TPM2(6), TPM3(3), TPM4(4), VIM(3) 19817992 200 57 192 70 82 70 26 3 18 1 0.73 0.97 464 GLUCOCORTICOID_MINERALOCORTICOID_METABOLISM CPN2, CYP11A1, CYP11B2, CYP17A1, HSD11B1, HSD11B2, HSD3B1, HSD3B2 8 CPN2(1), CYP11A1(4), CYP11B2(5), CYP17A1(2), HSD11B1(1), HSD3B1(3), HSD3B2(1) 2321788 17 13 17 8 7 7 2 0 1 0 0.73 0.97 465 O_GLYCAN_BIOSYNTHESIS GALNT1, GALNT10, GALNT2, GALNT3, GALNT4, GALNT6, GALNT7, GALNT8, GALNT9, GCNT1, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, WBSCR17 13 GALNT1(3), GALNT10(5), GALNT2(4), GALNT3(4), GALNT6(3), GALNT7(3), GALNT8(2), GALNT9(2), GCNT1(5), ST3GAL1(1), ST3GAL2(1), ST3GAL4(2) 4434692 35 20 35 14 13 9 7 0 6 0 0.73 0.97 466 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 32 AKT1(2), BAD(1), BCL2(1), BCL2L1(1), CBL(5), CFLAR(3), CRKL(2), FOS(1), GRB2(3), IL2RA(2), IL2RB(2), IRS1(9), JAK1(4), JAK3(9), MAPK1(2), MAPK3(3), NMI(2), PTPN6(4), RAF1(6), RPS6KB1(3), SHC1(3), SOS1(7), STAT5B(3), SYK(3) 10852692 81 36 78 29 27 31 10 0 13 0 0.74 0.97 467 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 33 AKT1(2), ATF2(1), CDC42(1), DLD(1), DUSP10(5), DUSP4(1), GAB1(6), GCK(2), IL1R1(4), MAP2K5(4), MAP3K1(8), MAP3K10(3), MAP3K11(4), MAP3K12(6), MAP3K13(9), MAP3K2(3), MAP3K3(3), MAP3K5(7), MAP3K7(4), MAP3K9(4), MAPK7(3), MAPK8(7), MAPK9(5), MYEF2(7), NFATC3(5), NR2C2(4), SHC1(3), TRAF6(4), ZAK(6) 14005808 122 46 121 29 43 35 23 1 20 0 0.74 0.97 468 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(7), CREBBP(25), CTBP1(1), CTBP2(2), DLL1(4), DLL3(3), DLL4(2), DTX1(4), DTX2(5), DTX3(1), DTX3L(3), DTX4(3), DVL2(9), DVL3(4), EP300(15), HDAC1(2), HDAC2(2), HES1(1), JAG1(8), MAML1(4), MAML2(3), MAML3(1), NCOR2(2), NCSTN(5), NOTCH2(13), NOTCH3(15), NOTCH4(7), NUMB(2), NUMBL(3), PSEN1(3), PSEN2(2), PTCRA(2), RBPJ(5), RBPJL(3), SNW1(5) 22901968 176 60 173 67 62 53 32 1 28 0 0.74 0.97 469 NEUTROPHILPATHWAY Neutrophils are phagocytotic leukocytes that destroy foreign cells with reactive oxygen species or enzymatic digestion and express CD11 and CD18. CD44, ICAM1, ITGAL, ITGAM, ITGB2, PECAM1, SELE, SELL 8 CD44(3), ICAM1(2), ITGAL(8), ITGAM(8), ITGB2(5), PECAM1(2), SELE(4), SELL(3) 3904096 35 21 35 10 10 16 5 0 4 0 0.74 0.97 470 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(5), GPI(2), HK1(6), PFKL(1), PGAM1(3), PGK1(3), TPI1(1) 2944848 21 20 20 14 9 7 5 0 0 0 0.75 0.97 471 STREPTOMYCIN_BIOSYNTHESIS GCK, HK1, HK2, HK3, IMPA1, PGM1, PGM3, TGDS 8 GCK(2), HK1(6), HK2(3), HK3(5), IMPA1(2), PGM1(4), PGM3(5), TGDS(1) 3425600 28 20 28 12 9 15 4 0 0 0 0.75 0.97 472 HSA00460_CYANOAMINO_ACID_METABOLISM Genes involved in cyanoamino acid metabolism ASRGL1, GBA, GBA3, GGT1, GGTL3, GGTL4, SHMT1, SHMT2 5 GBA3(3), SHMT1(2), SHMT2(2) 1587648 7 7 7 7 2 2 0 0 3 0 0.75 0.97 473 GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM ACO1, ACO2, CS, GRHPR, HAO1, HAO2, HYI, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 12 ACO1(5), ACO2(2), GRHPR(1), HAO1(5), HAO2(4), HYI(1), MDH1(1), MDH2(1), MTHFD1(6), MTHFD1L(8) 4322352 34 21 33 13 12 11 6 2 3 0 0.75 0.97 474 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 48 ACHE(2), AGPAT1(2), AGPAT3(3), AGPS(3), CDS1(2), CDS2(4), CHAT(6), CHKA(4), CLC(3), CPT1B(5), DGKA(1), DGKB(9), DGKD(12), DGKE(3), DGKG(3), DGKH(10), DGKZ(3), ETNK1(2), GNPAT(2), GPD1(1), GPD2(4), LCAT(1), PAFAH1B1(3), PAFAH2(1), PCYT1A(5), PCYT1B(5), PEMT(1), PISD(2), PLA2G1B(1), PLA2G4A(8), PLA2G6(4), PLCB2(3), PLCG1(4), PLCG2(13), PPAP2B(1) 16681472 136 50 133 53 53 40 28 0 15 0 0.75 0.97 475 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(6), ALAS2(6), CPO(3), FECH(3), GATA1(5), HBB(3), HMBS(2), UROD(1), UROS(1) 2771624 31 17 30 6 16 12 2 0 1 0 0.75 0.97 476 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(8), C9orf95(1), CD38(2), ENPP1(4), ENPP3(4), NADK(2), NADSYN1(2), NMNAT1(2), NMNAT2(2), NMNAT3(2), NNMT(3), NNT(3), NT5C1A(1), NT5C1B(10), NT5C2(4), NT5C3(2), NT5E(3), NT5M(1), NUDT12(2), QPRT(1) 7314932 59 32 59 24 20 20 11 0 8 0 0.75 0.97 477 HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - lactoseries ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 10 ABO(2), B3GALT1(1), B3GALT2(3), B3GALT5(4), B3GNT5(1), FUT1(4), FUT2(1), FUT3(4), ST3GAL3(4), ST3GAL4(2) 2414396 26 16 26 5 13 7 4 0 2 0 0.75 0.97 478 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(5), ACO2(2), AFMID(1), GRHPR(1), HAO1(5), HAO2(4), HYI(1), MDH1(1), MDH2(1), MTHFD1(6), MTHFD1L(8) 4532648 35 22 34 13 13 11 6 2 3 0 0.76 0.97 479 ONE_CARBON_POOL_BY_FOLATE ALDH1L1, AMT, ATIC, ATP6V0C, SHMT1, DHFR, GART, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 15 ALDH1L1(6), ATIC(4), ATP6V0C(1), DHFR(1), GART(3), MTHFD1(6), MTHFD1L(8), MTHFR(7), MTHFS(1), MTR(7), SHMT1(2), SHMT2(2), TYMS(3) 6058280 51 29 50 15 21 18 7 1 4 0 0.76 0.97 480 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(4), AADAC(3), ABAT(5), ACAT1(1), ACAT2(2), ACSM1(5), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH5A1(4), ALDH7A1(3), ALDH9A1(1), BDH1(1), DDHD1(3), ECHS1(2), EHHADH(2), GAD1(9), GAD2(4), HADH(1), HADHA(3), HMGCL(1), HMGCS1(1), HMGCS2(1), HSD17B10(2), HSD17B4(3), HSD3B7(2), ILVBL(2), L2HGDH(3), OXCT1(3), OXCT2(1), PDHA1(5), PDHA2(8), PDHB(2), PLA1A(3), PPME1(2), PRDX6(2), RDH11(1), RDH12(3), RDH13(1) 13826240 121 45 120 42 49 41 18 0 13 0 0.76 0.97 481 PTC1PATHWAY The binding of extracellular signaling protein Sonic hedgehog to the Patched receptor (Ptc1) allows progression through G1 and may inhibit the G2/M transition. CCNB1, CCNH, CDC2, CDC25A, CDC25B, CDC25C, CDK7, MNAT1, PTCH, SHH, XPO1 9 CCNB1(2), CCNH(2), CDC25A(2), CDC25B(5), CDC25C(4), CDK7(1), MNAT1(1), XPO1(2) 2934044 19 14 19 9 6 8 3 1 1 0 0.76 0.97 482 SELENOAMINO_ACID_METABOLISM AHCY, CBS, CTH, GGT1, MARS, MARS2, MAT1A, MAT2B, PAPSS1, PAPSS2, SCLY, SEPHS1 11 AHCY(3), CBS(3), CTH(2), MARS(6), MARS2(1), MAT1A(5), MAT2B(3), PAPSS1(2), PAPSS2(4), SCLY(1), SEPHS1(3) 3814092 33 19 32 10 13 12 5 0 3 0 0.76 0.97 483 HSA00632_BENZOATE_DEGRADATION_VIA_COA_LIGATION Genes involved in benzoate degradation via CoA ligation ACAT1, ACAT2, ACOT11, ACYP1, ACYP2, ARD1A, CARKL, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ECHS1, EHHADH, ESCO1, ESCO2, FN3K, GCDH, HADHA, ITGB1BP3, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1, YOD1 23 ACAT1(1), ACAT2(2), ACOT11(3), ACYP1(2), DHRS1(1), DHRS2(3), DHRS3(2), ECHS1(2), EHHADH(2), ESCO1(11), ESCO2(4), GCDH(5), HADHA(3), ITGB1BP3(1), MYST3(18), MYST4(10), PNPLA3(4), SH3GLB1(4), YOD1(1) 8546528 79 35 78 23 31 21 15 2 10 0 0.76 0.97 484 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 21 AKT1(2), AXIN1(2), CD14(1), FZD1(1), GJA1(8), GNAI1(4), IRAK1(1), LBP(1), LEF1(4), LY96(2), MYD88(2), NFKB1(6), PDPK1(1), PPP2CA(1), RELA(2), TIRAP(1), TLR4(10), TOLLIP(1), WNT1(1) 6084236 51 31 50 22 25 10 11 0 5 0 0.76 0.97 485 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(2), ALDH18A1(5), ARG1(1), ARG2(5), ASL(2), CKM(5), CKMT1B(1), CKMT2(5), CPS1(14), GAMT(1), GATM(1), GLUD1(2), NAGS(1), OAT(1), ODC1(5), OTC(5), SMS(2) 5843016 58 26 58 18 19 20 9 0 10 0 0.77 0.97 486 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(3), PLCG1(4), PRKCA(4), PTK2B(1) 2269828 12 11 12 5 6 3 2 0 1 0 0.77 0.97 487 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 196 ABI2(1), ACTN1(5), ACTN2(8), ACTN3(3), ACTN4(3), APC2(1), ARAF(3), ARHGEF1(5), ARHGEF12(9), ARHGEF4(4), ARHGEF6(10), ARHGEF7(8), ARPC1A(5), ARPC1B(2), ARPC2(2), ARPC5(1), ARPC5L(2), BAIAP2(2), BDKRB2(3), CD14(1), CDC42(1), CFL1(1), CHRM1(3), CHRM3(4), CHRM4(1), CHRM5(2), CRKL(2), CSK(4), CYFIP1(6), CYFIP2(5), DIAPH1(1), DIAPH2(12), DIAPH3(5), DOCK1(7), EGF(3), EGFR(12), EZR(2), F2(4), F2R(1), FGD1(8), FGD3(2), FGF1(2), FGF11(3), FGF12(3), FGF13(3), FGF14(5), FGF17(1), FGF19(1), FGF20(2), FGF21(2), FGF23(1), FGF3(1), FGF5(4), FGF6(3), FGF7(1), FGF8(1), FGF9(1), FGFR1(4), FGFR2(6), FGFR3(2), FGFR4(2), FN1(22), GIT1(3), GNA12(2), GNA13(2), GRLF1(12), IQGAP1(13), IQGAP2(12), IQGAP3(12), ITGA1(3), ITGA10(7), ITGA11(4), ITGA2(6), ITGA2B(4), ITGA3(4), ITGA4(8), ITGA5(7), ITGA6(4), ITGA7(6), ITGA8(8), ITGA9(6), ITGAD(8), ITGAE(7), ITGAL(8), ITGAM(8), ITGAV(5), ITGAX(6), ITGB1(6), ITGB2(5), ITGB3(9), ITGB4(3), ITGB5(6), ITGB6(6), ITGB7(4), ITGB8(5), LIMK1(5), LIMK2(5), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK3(3), MOS(3), MRAS(1), MSN(6), MYH10(10), MYH14(12), MYH9(12), MYL2(1), MYL7(1), MYL9(2), MYLK(14), MYLK2(3), NCKAP1(9), NCKAP1L(11), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PDGFA(1), PDGFRA(17), PDGFRB(6), PFN2(1), PFN4(1), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R2(1), PIK3R3(4), PIK3R5(1), PIP4K2A(2), PIP4K2B(2), PIP4K2C(3), PIP5K1A(3), PIP5K1B(2), PIP5K1C(4), PPP1CB(2), PPP1CC(2), PPP1R12A(3), PPP1R12B(9), PTK2(6), RAF1(6), RDX(3), RHOA(5), ROCK1(15), ROCK2(6), RRAS2(2), SCIN(3), SLC9A1(4), SOS1(7), SOS2(11), SSH1(6), SSH2(4), SSH3(1), TIAM1(18), TIAM2(16), TMSL3(1), VAV1(13), VAV2(4), VAV3(12), VCL(2), WAS(1), WASF1(3), WASF2(2), WASL(7) 90440932 810 140 800 270 318 249 145 8 88 2 0.77 0.97 488 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(2), ANXA1(1), GNAS(6), GNB1(1), GNGT1(1), NFKB1(6), NOS3(2), NPPA(1), NR3C1(4), RELA(2), SYT1(1) 4728068 27 21 27 17 13 6 4 0 4 0 0.77 0.97 489 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(3), B4GALT1(6), B4GALT2(3), FBP2(3), G6PC(4), GALE(1), GALK2(3), GALT(2), GANAB(4), GCK(2), GLA(4), GLB1(3), HK1(6), HK2(3), HK3(5), LALBA(2), LCT(20), MGAM(13), PFKM(4), PFKP(2), PGM1(4), PGM3(5) 11029324 102 45 101 35 46 35 18 0 3 0 0.77 0.97 490 HSA00521_STREPTOMYCIN_BIOSYNTHESIS Genes involved in streptomycin biosynthesis GCK, HK1, HK2, HK3, IMPA1, IMPA2, ISYNA1, PGM1, PGM3, TGDS 10 GCK(2), HK1(6), HK2(3), HK3(5), IMPA1(2), IMPA2(2), PGM1(4), PGM3(5), TGDS(1) 3892472 30 22 30 12 10 15 4 0 1 0 0.77 0.97 491 LIMONENE_AND_PINENE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ECHS1, EHHADH, HADHA, SDS 12 ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), ECHS1(2), EHHADH(2), HADHA(3), SDS(2) 4118656 42 23 42 8 16 14 7 0 5 0 0.78 0.97 492 HSA00790_FOLATE_BIOSYNTHESIS Genes involved in folate biosynthesis ALPI, ALPL, ALPP, ALPPL2, ASCC3, ASCC3L1, ATP13A2, DDX18, DDX19A, DDX23, DDX4, DDX41, DDX47, DDX50, DDX51, DDX52, DDX54, DDX55, DDX56, DHFR, DHX58, ENTPD7, EP400, ERCC2, ERCC3, FPGS, GCH1, GGH, IFIH1, MOV10L1, NUDT5, NUDT8, PTS, QDPR, RAD54B, RAD54L, RUVBL2, SETX, SKIV2L2, SMARCA2, SMARCA5, SPR 41 ALPI(2), ALPL(1), ALPP(1), ALPPL2(1), ASCC3(21), ATP13A2(3), DDX18(3), DDX19A(3), DDX23(4), DDX4(3), DDX41(2), DDX47(3), DDX50(3), DDX52(2), DDX54(5), DDX55(3), DDX56(5), DHFR(1), DHX58(3), ENTPD7(4), EP400(20), ERCC2(4), ERCC3(7), GGH(1), IFIH1(5), MOV10L1(13), RAD54B(8), RAD54L(3), RUVBL2(1), SETX(20), SKIV2L2(4), SMARCA2(11), SMARCA5(7) 21329036 177 52 173 42 68 48 36 0 24 1 0.78 0.97 493 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 ATP5O(2), ATP6AP1(2), ATP6V0A1(3), ATP6V0A4(7), ATP6V0B(1), ATP6V0C(1), ATP6V0D1(2), ATP6V1A(2), ATP6V1B1(5), ATP6V1B2(2), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1G2(2), ATP6V1G3(2), ATP6V1H(3), FDXR(1), SHMT1(2) 5431384 42 25 41 11 14 16 8 0 4 0 0.78 0.97 494 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 IL13(1), IL13RA1(2), IL13RA2(3), IL4R(1), JAK1(4), JAK2(9), TYK2(1) 3524168 21 16 20 9 8 4 5 0 2 2 0.78 0.97 495 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 IL13(1), IL13RA1(2), IL13RA2(3), IL4R(1), JAK1(4), JAK2(9), TYK2(1) 3524168 21 16 20 9 8 4 5 0 2 2 0.78 0.97 496 HSA04710_CIRCADIAN_RHYTHM Genes involved in circadian rhythm ARNTL, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, NPAS2, NR1D1, PER1, PER2, PER3 11 ARNTL(10), CLOCK(8), CRY1(5), CRY2(1), CSNK1D(4), NPAS2(5), NR1D1(4), PER1(1), PER2(2), PER3(9) 5763680 49 27 47 9 20 13 8 2 5 1 0.78 0.97 497 IL10PATHWAY The cytokine IL-10 inhibits the inflammatory response by macrophages via activation of heme oxygenase 1. BLVRA, BLVRB, HMOX1, IL10, IL10RA, IL10RB, IL1A, IL6, JAK1, STAT1, STAT3, STAT5A, TNF 13 BLVRA(2), BLVRB(2), HMOX1(2), IL10(2), IL10RA(2), IL10RB(5), IL1A(1), IL6(2), JAK1(4), STAT1(6), STAT3(2) 4071596 30 19 27 18 12 8 7 0 3 0 0.78 0.97 498 CD40PATHWAY The CD40 receptor is a TNF-type receptor that regulates immunoglobulin expression in B cells and moderates T cell activation via T-cell expression of its ligand. CHUK, DUSP1, IKBKAP, IKBKB, IKBKG, MAP3K1, MAP3K14, NFKB1, NFKBIA, RELA, TNFAIP3, TNFRSF5, TNFSF5, TRAF3, TRAF6 12 CHUK(6), DUSP1(2), IKBKAP(2), IKBKB(4), MAP3K1(8), MAP3K14(3), NFKB1(6), RELA(2), TNFAIP3(3), TRAF3(6), TRAF6(4) 6191184 46 25 46 16 20 13 6 1 6 0 0.79 0.98 499 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 52 AXIN1(2), CCND2(1), CCND3(1), DVL2(9), DVL3(4), FBXW2(3), FZD1(1), FZD10(6), FZD2(2), FZD6(6), FZD7(3), FZD8(1), LDLR(5), MAPK9(5), PAFAH1B1(3), PLAU(3), PPP2R5C(3), PPP2R5E(2), PRKCA(4), PRKCD(3), PRKCE(6), PRKCG(10), PRKCH(3), PRKCI(4), PRKCQ(5), RHOA(5), SFRP4(4), TCF7(6), WNT1(1), WNT10B(4), WNT11(3), WNT16(2), WNT2(1), WNT2B(3), WNT3(4), WNT4(1), WNT5A(3), WNT6(1), WNT7A(2), WNT7B(2) 15717508 137 60 134 51 62 36 21 1 17 0 0.79 0.98 500 NITROGEN_METABOLISM AMT, ASNS, CA1, CA12, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA8, CA9, CPS1, CTH, GLS, GLS2, GLUD1, GLUL, HAL 21 ASNS(1), CA1(1), CA14(2), CA2(1), CA3(2), CA4(1), CA5A(2), CA6(2), CA8(3), CA9(2), CPS1(14), CTH(2), GLS2(2), GLUD1(2), GLUL(4), HAL(4) 6325556 45 23 45 23 17 15 5 0 8 0 0.79 0.98 501 HSA00740_RIBOFLAVIN_METABOLISM Genes involved in riboflavin metabolism ACP1, ACP2, ACP5, ACP6, ACPP, ACPT, ENPP1, ENPP3, FLAD1, LHPP, MTMR1, MTMR2, MTMR6, PHPT1, RFK, TYR 16 ACP1(2), ACP2(2), ACP5(1), ACPP(4), ENPP1(4), ENPP3(4), FLAD1(1), LHPP(2), MTMR1(5), MTMR2(2), MTMR6(4), PHPT1(1), TYR(3) 5070056 35 22 34 19 14 9 8 0 3 1 0.80 0.98 502 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(10), CLOCK(8), CRY1(5), CRY2(1), PER1(1) 2894204 25 14 24 5 8 7 5 0 4 1 0.80 0.98 503 N_GLYCAN_DEGRADATION AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 13 AGA(5), FUCA1(3), GLB1(3), HEXB(3), LCT(20), MAN2C1(6), MANBA(7), NEU1(1), NEU2(1), NEU3(1) 5527960 50 28 50 15 20 12 14 0 4 0 0.80 0.98 504 CAPROLACTAM_DEGRADATION AKR1A1, ECHS1, EHHADH, HADHA, SDS 5 ECHS1(2), EHHADH(2), HADHA(3), SDS(2) 1647524 9 7 9 3 3 2 0 0 4 0 0.80 0.98 505 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(2), CREB1(1), GRB2(3), MAPK1(2), MAPK3(3), MAPK7(3), MEF2A(4), MEF2C(9), MEF2D(1), NTRK1(7), PLCG1(4), RPS6KA1(1), SHC1(3) 5297900 43 25 41 15 15 9 14 0 5 0 0.80 0.98 506 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 AK3(1), CAD(12), CDA(1), CTPS(4), CTPS2(4), DCK(2), DCTD(3), DHODH(4), DPYS(7), DTYMK(1), ENTPD1(2), ITPA(2), NT5E(3), NT5M(1), POLB(3), POLD1(5), POLD2(1), POLE(21), POLG(5), POLL(1), POLQ(12), POLR1B(9), POLR2A(6), POLR2B(8), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLR2K(1), POLRMT(1), RRM1(2), RRM2(3), TK1(1), TK2(1), TXNRD1(3), TYMS(3), UCK2(1), UMPS(1), UNG(1), UPB1(5) 18763032 145 53 142 39 44 54 32 1 14 0 0.81 0.98 507 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(5), ASPH(3), COPS5(1), CREB1(1), EDN1(1), EP300(15), HIF1A(3), LDHA(2), NOS3(2), P4HB(2), VHL(1) 5609492 36 24 36 11 12 7 12 1 4 0 0.81 0.98 508 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(3), DAG1(5), GNAQ(4), ITPKB(4) 2002588 16 11 16 6 5 4 4 0 3 0 0.81 0.98 509 STEROID_BIOSYNTHESIS CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 9 CYP17A1(2), F13B(5), HSD17B2(2), HSD17B3(2), HSD17B4(3), HSD3B1(3), HSD3B2(1) 2715720 18 12 18 4 5 7 4 0 2 0 0.82 0.98 510 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 25 ARHGDIB(3), CASP10(2), CASP3(2), CASP6(2), CASP7(1), CFLAR(3), DAXX(1), DFFA(3), DFFB(2), FAF1(4), LMNB1(4), LMNB2(1), MAP3K1(8), MAP3K7(4), MAPK8(7), PAK1(5), PAK2(3), PRKDC(18), PTPN13(17), RB1(7), RIPK2(3), SPTAN1(13) 13834656 113 41 111 36 24 42 24 2 18 3 0.82 0.98 511 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), CD2(3), CD3D(1), CD3G(2), CD4(2), IFNG(1), IL12A(1), IL12B(2), IL12RB1(2), IL12RB2(6), JAK2(9), STAT4(3), TYK2(1) 4905964 34 18 34 19 5 17 6 0 4 2 0.82 0.98 512 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 7 ABO(2), FUT1(4), FUT2(1), FUT3(4), FUT6(1), ST3GAL3(4) 1627768 16 12 16 5 10 4 2 0 0 0 0.82 0.99 513 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(6), IFNA1(1), IFNB1(1), IKBKB(4), IL1A(1), IL1B(1), IL1R1(4), IL1RAP(1), IL1RN(3), IL6(2), IRAK1(1), IRAK2(8), IRAK3(3), MAP2K3(6), MAP2K6(3), MAP3K1(8), MAP3K14(3), MAP3K7(4), MAPK14(3), MAPK8(7), MYD88(2), NFKB1(6), RELA(2), TGFB1(1), TGFB2(9), TOLLIP(1), TRAF6(4) 9990076 95 34 94 24 36 29 17 3 10 0 0.82 0.99 514 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 24 BRCA1(6), CARM1(2), CREBBP(25), EP300(15), ERCC3(7), GRIP1(8), GTF2A1(2), GTF2E1(5), GTF2F1(5), HDAC1(2), HDAC2(2), HDAC3(2), HDAC4(5), HDAC5(2), HDAC6(7), MEF2C(9), NCOR2(2), NR0B1(3), NRIP1(6), PELP1(2), POLR2A(6), TBP(1) 15606776 124 48 123 33 48 32 28 3 13 0 0.82 0.99 515 SA_MMP_CYTOKINE_CONNECTION Cytokines can induce activation of matrix metalloproteinases, which degrade extracellular matrix. ACE, CD44, CSF1, FCGR3A, IL1B, IL6R, SELL, SPN, TGFB1, TGFB2, TNF, TNFRSF1A, TNFRSF1B, TNFRSF8, TNFSF8 15 ACE(2), CD44(3), CSF1(2), FCGR3A(1), IL1B(1), IL6R(3), SELL(3), SPN(2), TGFB1(1), TGFB2(9), TNFRSF1A(1), TNFRSF8(2), TNFSF8(1) 4625192 31 18 31 14 8 11 5 0 7 0 0.83 0.99 516 MALATEXPATHWAY The tricarboxylate transfer pathway shuttles acetyl groups of acetyl-CoA between mitochondria and the cytoplasm. ACLY, CS, MDH1, ME1, PC, PDHA1, SLC25A1, SLC25A11 7 ACLY(4), MDH1(1), PC(6), PDHA1(5), SLC25A11(1) 2723708 17 16 17 7 8 5 2 0 2 0 0.83 0.99 517 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 ARSA(1), ARSD(3), ARSE(2), ASAH1(3), B4GALT6(5), CERK(1), DEGS1(2), ENPP7(2), GAL3ST1(2), GALC(1), GLA(4), GLB1(3), LCT(20), NEU1(1), NEU2(1), NEU3(1), PPAP2B(1), SGMS1(3), SGMS2(6), SGPP1(2), SGPP2(4), SMPD1(6), SMPD3(3), SMPD4(1), SPHK1(1), SPHK2(1), SPTLC1(4), SPTLC2(2), UGCG(2), UGT8(8) 11820736 96 42 94 34 35 26 25 2 7 1 0.83 0.99 518 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(6), EGR2(8), EGR3(2), GNAQ(4), MAP3K1(8), NFATC1(2), NFATC2(6), NFKB1(6), PLCG1(4), PPP3CA(3), PPP3CB(5), PPP3CC(4), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), RELA(2), SYT1(1), VIPR2(3) 9165212 77 36 76 25 37 16 12 0 12 0 0.83 0.99 519 TERPENOID_BIOSYNTHESIS FDFT1, FDPS, FDPS, LOC402397, IDI1, SQLE 4 FDFT1(3), IDI1(1), SQLE(2) 1124384 6 5 6 3 1 2 2 0 1 0 0.83 0.99 520 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(3), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(3), ALDH9A1(1), CYP2C19(4), CYP2C9(7), DHRS1(1), DHRS2(3), DHRS3(2), ECHS1(2), EHHADH(2), ESCO1(11), ESCO2(4), HADHA(3), MYST3(18), MYST4(10), PNPLA3(4), SH3GLB1(4), YOD1(1) 10243836 105 36 104 28 40 31 22 1 11 0 0.84 0.99 521 EICOSANOID_SYNTHESIS ALOX12, ALOX15, ALOX15B, ALOX5, ALOX5AP, DPEP1, GGT1, IPLA2(GAMMA), LTA4H, LTC4S, PLA2G2A, PLA2G6, PTGDS, PTGES, PTGIS, PTGS1, PTGS2, TBXAS1 16 ALOX12(2), ALOX15B(5), ALOX5(4), ALOX5AP(1), DPEP1(1), PLA2G6(4), PTGIS(5), PTGS1(6), PTGS2(3), TBXAS1(5) 4740216 36 25 36 10 15 13 6 1 1 0 0.84 0.99 522 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(4), AASDHPPT(3), AASS(9), ACAT1(1), ACAT2(2), ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), ATP6V0C(1), BBOX1(3), DLST(1), DOT1L(3), ECHS1(2), EHHADH(2), EHMT1(2), EHMT2(3), GCDH(5), HADHA(3), PLOD1(4), PLOD2(5), PLOD3(4), SDS(2), SHMT1(2), SHMT2(2), TMLHE(3) 12250168 100 40 98 25 36 29 18 2 15 0 0.85 0.99 523 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(8), GNA12(2), PRKACB(1), PRKACG(3), PRKAG1(1), PRKAR2B(3) 3412280 18 14 18 12 6 6 0 0 6 0 0.85 0.99 524 STRESSPATHWAY Tumor necrosis factor receptor TNFR1 promotes apoptosis and activates the pro-inflammatory NF-kB, while TNFR2 activates stress-activated protein kinases (SAPKs). ATF1, CASP2, CHUK, CRADD, IKBKB, IKBKG, JUN, LTA, MAP2K3, MAP2K4, MAP2K6, MAP3K1, MAP3K14, MAP4K2, MAPK14, MAPK8, NFKB1, NFKBIA, RELA, RIPK1, TANK, TNF, TNFRSF1A, TRADD, TRAF2 23 ATF1(2), CASP2(4), CHUK(6), CRADD(2), IKBKB(4), MAP2K3(6), MAP2K6(3), MAP3K1(8), MAP3K14(3), MAP4K2(1), MAPK14(3), MAPK8(7), NFKB1(6), RELA(2), RIPK1(2), TANK(6), TNFRSF1A(1), TRADD(1), TRAF2(1) 7970204 68 31 67 24 26 20 16 3 3 0 0.85 0.99 525 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(2), CASP7(1), DFFA(3), DFFB(2), GZMB(2), HMGB1(1), HMGB2(1), TOP2A(5), TOP2B(9) 3488500 26 14 25 6 4 12 7 0 3 0 0.85 0.99 526 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(2), BAD(1), CASP9(2), CHUK(6), GH1(2), GHR(6), NFKB1(6), PDPK1(1), PPP2CA(1), RELA(2), YWHAH(1) 3524040 30 16 30 10 13 7 8 0 2 0 0.85 0.99 527 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 45 AKT1(2), AKT2(6), AKT3(1), BRD4(4), CAP1(1), CBL(5), CDC42(1), F2RL2(3), FLOT1(3), GRB2(3), GSK3A(2), IGFBP1(2), INPPL1(4), IRS1(9), IRS4(15), LNPEP(8), MAPK1(2), MAPK3(3), PARD3(7), PARD6A(2), PDK1(2), PIK3CD(3), PPYR1(4), PTPN1(5), RAF1(6), RPS6KA1(1), RPS6KA2(10), RPS6KA3(5), RPS6KB1(3), SERPINB6(2), SHC1(3), SLC2A4(4), SORBS1(11), SOS1(7), SOS2(11), YWHAB(2), YWHAE(3), YWHAH(1), YWHAQ(2) 17858512 168 52 164 51 59 59 29 3 18 0 0.85 0.99 528 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(4), MDM2(4), POLR1A(11), POLR1B(9), POLR1C(2), POLR1D(2), RB1(7) 5173112 39 23 39 9 11 12 12 0 3 1 0.85 0.99 529 ARGININE_AND_PROLINE_METABOLISM ABP1, AGMAT, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH4A1, ALDH9A1, AMD1, AOC2, AOC3, ARG1, ARG2, ASL, ASS, CKB, CKM, CKMT1, CKMT1B, CKMT1A, CKMT2, CPS1, DAO, GAMT, GATM, GLUD1, GOT1, GOT2, MAOA, MAOB, NOS1, NOS2A, NOS3, OAT, ODC1, OTC, P4HA1, P4HA2, P4HA3, P4HB, PYCR1, RARS, SAT, SMS 43 ABP1(1), AGMAT(4), ALDH1A1(4), ALDH1A2(6), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH4A1(3), ALDH9A1(1), AMD1(1), AOC2(4), AOC3(4), ARG1(1), ARG2(5), ASL(2), CKM(5), CKMT1B(1), CKMT2(5), CPS1(14), DAO(6), GAMT(1), GATM(1), GLUD1(2), GOT1(6), GOT2(1), MAOA(3), MAOB(1), NOS1(11), NOS3(2), OAT(1), ODC1(5), OTC(5), P4HA1(1), P4HA2(2), P4HA3(2), P4HB(2), RARS(4), SMS(2) 14740640 141 46 139 48 54 47 21 1 18 0 0.85 0.99 530 HSA00900_TERPENOID_BIOSYNTHESIS Genes involved in terpenoid biosynthesis FDFT1, FDPS, GGPS1, IDI1, IDI2, SQLE 6 FDFT1(3), GGPS1(1), IDI1(1), IDI2(1), SQLE(2) 1486144 8 6 8 5 1 3 2 0 2 0 0.85 0.99 531 RABPATHWAY Rab family GTPases regulate vesicle transport, endocytosis and exocytosis, and vesicle docking via interactions with the rabphilins. ACTA1, MEL, RAB11A, RAB1A, RAB2, RAB27A, RAB3A, RAB4A, RAB5A, RAB6A, RAB7, RAB9A 9 ACTA1(4), RAB11A(1), RAB27A(2), RAB3A(2), RAB4A(1), RAB6A(2), RAB9A(1) 1457536 13 9 13 2 4 6 2 0 1 0 0.85 0.99 532 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(2), CABIN1(11), CAMK1(3), CAMK1G(5), HDAC5(2), IGF1(2), IGF1R(8), INSR(6), MAP2K6(3), MAPK14(3), MAPK7(3), MEF2A(4), MEF2C(9), MEF2D(1), NFATC1(2), NFATC2(6), PPP3CA(3), PPP3CB(5), PPP3CC(4), SYT1(1), YWHAH(1) 10372972 84 40 83 39 39 22 11 0 12 0 0.85 0.99 533 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 124 ACTB(2), ACTN1(5), ACTN2(8), ACTN3(3), ACTN4(3), AKT1(2), AKT2(6), AKT3(1), AMOTL1(13), ASH1L(24), CASK(5), CDC42(1), CDK4(3), CGN(7), CLDN10(4), CLDN11(1), CLDN15(1), CLDN16(5), CLDN17(5), CLDN18(1), CLDN19(1), CLDN2(1), CLDN6(2), CLDN7(2), CLDN8(5), CLDN9(1), CSDA(2), CSNK2A1(4), CSNK2A2(2), CSNK2B(2), CTNNA1(12), CTNNA2(12), CTNNA3(9), CTTN(1), EPB41(3), EPB41L1(9), EPB41L2(6), EPB41L3(18), EXOC4(7), F11R(2), GNAI1(4), IGSF5(8), INADL(5), JAM3(3), LLGL1(1), LLGL2(2), MAGI1(13), MAGI2(11), MAGI3(6), MLLT4(6), MPDZ(11), MPP5(3), MRAS(1), MYH1(15), MYH10(10), MYH11(28), MYH13(17), MYH14(12), MYH15(13), MYH2(12), MYH3(14), MYH4(12), MYH6(12), MYH7(12), MYH7B(7), MYH8(20), MYH9(12), MYL2(1), MYL7(1), MYL9(2), OCLN(1), PARD3(7), PARD6A(2), PARD6G(2), PPP2CA(1), PPP2CB(2), PPP2R1A(5), PPP2R1B(2), PPP2R2A(1), PPP2R2C(4), PPP2R3A(5), PRKCA(4), PRKCD(3), PRKCE(6), PRKCG(10), PRKCH(3), PRKCI(4), PRKCQ(5), RAB3B(1), RHOA(5), RRAS2(2), SPTAN1(13), SRC(3), SYMPK(5), TJAP1(1), TJP1(7), TJP2(5), TJP3(1), YES1(2), ZAK(6) 63940364 593 106 583 193 253 180 93 3 61 3 0.86 0.99 534 IL17PATHWAY Activated T cells secrete IL-17, which stimulates fibroblasts and other cells to secrete inflammatory and hematopoietic cytokines. CD2, CD34, CD3D, CD3E, CD3G, CD3Z, CD4, CD58, CD8A, CSF3, IL17, IL3, IL6, IL8, KITLG, TRA@, TRB@ 13 CD2(3), CD34(1), CD3D(1), CD3G(2), CD4(2), CD58(2), IL3(3), IL6(2), IL8(1), KITLG(2) 2136968 19 11 18 8 6 9 3 0 1 0 0.86 0.99 535 VOBESITYPATHWAY The adipose tissue of obese individuals overexpresses a key glucocorticoid-metabolizing enzyme, activating inactive circulating corticosteroids and inducing insulin resistance. APM1, HSD11B1, LPL, NR3C1, PPARG, RETN, RXRA, TNF 7 HSD11B1(1), LPL(6), NR3C1(4), PPARG(1), RXRA(1) 1886864 13 9 13 10 1 6 3 0 3 0 0.86 0.99 536 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(4), UBE2A(2), UBE2B(2), UBE2C(2), UBE2D1(1), UBE2D3(1), UBE2E1(3), UBE2G1(2), UBE2I(2), UBE2J2(1), UBE2L3(2), UBE3A(11) 3526084 33 15 33 10 9 11 8 0 5 0 0.86 0.99 537 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP1(2), ACP2(2), ACP5(1), ACPP(4), ENPP1(4), ENPP3(4), FLAD1(1), TYR(3) 3277220 21 14 20 12 8 5 6 0 1 1 0.87 0.99 538 HSA00361_GAMMA_HEXACHLOROCYCLOHEXANE_DEGRADATION Genes involved in gamma-hexachlorocyclohexane degradation ACP1, ACP2, ACP5, ACP6, ACPP, ACPT, ALPI, ALPL, ALPP, ALPPL2, CMBL, CYP3A4, CYP3A43, CYP3A5, CYP3A7, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, PON1, PON2, PON3 22 ACP1(2), ACP2(2), ACP5(1), ACPP(4), ALPI(2), ALPL(1), ALPP(1), ALPPL2(1), CYP3A4(1), CYP3A43(2), CYP3A5(3), CYP3A7(6), DHRS1(1), DHRS2(3), DHRS3(2), PON1(6), PON2(2), PON3(2) 5862196 42 24 41 17 16 12 8 0 4 2 0.87 0.99 539 N_GLYCAN_BIOSYNTHESIS ALG3, ALG5, B4GALT1, B4GALT2, B4GALT3, B4GALT5, DDOST, DPAGT1, DPM1, FUT8, GCS1, MAN1A1, MAN1B1, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT5, RPN1, RPN2, ST6GAL1 21 ALG3(1), ALG5(3), B4GALT1(6), B4GALT2(3), B4GALT3(7), B4GALT5(2), DDOST(2), DPAGT1(2), DPM1(1), FUT8(2), MAN1A1(5), MAN1B1(2), MGAT1(2), MGAT3(2), MGAT4A(2), MGAT4B(1), MGAT5(3), RPN2(1), ST6GAL1(1) 6566708 48 31 48 17 20 14 10 0 4 0 0.87 0.99 540 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(8), CD2(3), CD33(2), CD5(4), CD7(1), IFNA1(1), IFNB1(1), IFNG(1), IL10(2), IL12A(1), IL12B(2), IL13(1), IL3(3), IL4(3), ITGAX(6), TLR2(6), TLR4(10), TLR7(7), TLR9(7) 6257856 69 28 68 22 25 22 19 0 3 0 0.87 0.99 541 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 51 APAF1(8), ARHGDIB(3), BAG4(2), BCL2(1), BID(1), BIRC2(4), BIRC3(7), CASP2(4), CASP3(2), CASP6(2), CASP7(1), CASP9(2), CFLAR(3), CHUK(6), CRADD(2), DAXX(1), DFFA(3), DFFB(2), LMNB1(4), LMNB2(1), MAP3K1(8), MAP3K14(3), MAP3K5(7), MAPK8(7), MDM2(4), NFKB1(6), NUMA1(10), PAK2(3), PRKCD(3), PRKDC(18), PSEN1(3), PSEN2(2), PTK2(6), RASA1(9), RB1(7), RELA(2), RIPK1(2), SPTAN1(13), TNFRSF1A(1), TRADD(1), TRAF1(2), TRAF2(1) 23264096 177 52 176 55 57 51 45 1 21 2 0.87 0.99 542 NUCLEOTIDE_METABOLISM ADSL, ADSS, DHFR, HPRT1, IMPDH1, MTHFD2, NME2, OAZ1, POLA, POLB, POLD1, POLG, PRPS2, RRM1, SAT, SRM 14 ADSL(7), ADSS(2), DHFR(1), HPRT1(2), IMPDH1(2), POLB(3), POLD1(5), POLG(5), PRPS2(2), RRM1(2) 4338448 31 23 31 12 15 12 2 0 2 0 0.87 0.99 543 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(5), ARSB(5), FUCA1(3), GALNS(4), GLB1(3), GNS(4), GUSB(2), HEXB(3), HGSNAT(6), HPSE(2), HPSE2(12), IDS(2), IDUA(1), LCT(20), MAN2B1(5), MAN2B2(1), MAN2C1(6), MANBA(7), NAGLU(4), NEU1(1), NEU2(1), NEU3(1), SPAM1(4) 11667372 102 38 100 35 37 28 24 1 12 0 0.87 0.99 544 HYPERTROPHY_MODEL ADAM10, ANKRD1, ATF3, CYR61, DUSP14, EIF4E, EIF4EBP1, GDF8, HBEGF, IFNG, IFRD1, IL18, IL1A, IL1R1, JUND, MYOG, NR4A3, TCF8, VEGF, WDR1 17 ADAM10(1), ANKRD1(6), ATF3(1), CYR61(2), HBEGF(1), IFNG(1), IFRD1(5), IL1A(1), IL1R1(4), MYOG(1), NR4A3(4), WDR1(3) 3716372 30 16 30 6 9 11 7 0 3 0 0.87 0.99 545 SULFUR_METABOLISM BPNT1, PAPSS1, PAPSS2, SULT1A2, SULT1A3, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SUOX 7 BPNT1(1), PAPSS1(2), PAPSS2(4), SULT1A2(1), SULT1E1(2), SULT2A1(2), SUOX(2) 2042004 14 8 14 1 5 5 1 0 3 0 0.88 0.99 546 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 19 ATR(18), BRCA1(6), BRCA2(23), CHEK1(1), CHEK2(1), FANCA(7), FANCC(3), FANCD2(11), FANCF(2), FANCG(4), HUS1(1), MRE11A(8), RAD1(2), RAD17(4), RAD50(11), TREX1(2) 12495808 104 34 104 16 29 36 24 0 15 0 0.88 0.99 547 HSA00030_PENTOSE_PHOSPHATE_PATHWAY Genes involved in pentose phosphate pathway ALDOA, ALDOB, ALDOC, DERA, FBP1, FBP2, G6PD, GPI, H6PD, PFKL, PFKM, PFKP, PGD, PGLS, PGM1, PGM3, PRPS1, PRPS1L1, PRPS2, RBKS, RPE, RPIA, TALDO1, TKT, TKTL1, TKTL2 26 ALDOA(1), ALDOB(5), ALDOC(3), DERA(2), FBP2(3), G6PD(3), GPI(2), H6PD(4), PFKL(1), PFKM(4), PFKP(2), PGD(1), PGM1(4), PGM3(5), PRPS1(1), PRPS1L1(1), PRPS2(2), RPE(2), RPIA(3), TALDO1(3), TKT(3), TKTL1(5), TKTL2(7) 8185100 67 38 67 22 27 29 8 0 3 0 0.88 0.99 548 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(2), BCL2(1), EGFR(12), IGF1R(8), POLR2A(6), PPP2CA(1), PRKCA(4), RB1(7), TEP1(7), TERF1(1), TERT(2), TNKS(4), XRCC5(6) 9238124 61 38 61 20 27 17 11 1 4 1 0.88 0.99 549 HSA00061_FATTY_ACID_BIOSYNTHESIS Genes involved in fatty acid biosynthesis ACACA, ACACB, FASN, MCAT, OLAH, OXSM 6 ACACA(18), ACACB(15), FASN(1), MCAT(1), OLAH(1), OXSM(5) 5111576 41 22 40 11 16 13 8 0 4 0 0.89 1.00 550 HSA00220_UREA_CYCLE_AND_METABOLISM_OF_AMINO_GROUPS Genes involved in urea cycle and metabolism of amino groups ABP1, ACY1, ADC, AGMAT, ALDH18A1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, AMD1, AOC2, AOC3, ARG1, ARG2, ASL, ASS1, CPS1, GATM, MAOA, MAOB, NAGS, ODC1, OTC, SAT1, SAT2, SMS, SRM 29 ABP1(1), ACY1(2), ADC(1), AGMAT(4), ALDH18A1(5), ALDH1A3(6), ALDH1B1(7), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(3), ALDH9A1(1), AMD1(1), AOC2(4), AOC3(4), ARG1(1), ARG2(5), ASL(2), ASS1(2), CPS1(14), GATM(1), MAOA(3), MAOB(1), NAGS(1), ODC1(5), OTC(5), SAT2(3), SMS(2) 9900000 93 37 92 30 31 37 15 0 10 0 0.89 1.00 551 S1PPATHWAY At low cholesterol concentrations, sterol-regulatory element binding proteins (SREBPs) act as transcription factors to promote cholesterol uptake and biosynthesis. EPLIN, HMGCS1, LDLR, MBTPS1, MBTPS2, SCAP, SREBF1, SREBF2 7 HMGCS1(1), LDLR(5), MBTPS1(8), SCAP(3), SREBF1(1), SREBF2(3) 3992908 21 15 21 12 7 7 3 0 4 0 0.89 1.00 552 MCALPAINPATHWAY In integrin-mediated cell migration, calpains digest links between the actin cytoskeleton and focal adhesion proteins. ACTA1, CAPN1, CAPN2, CAPNS1, CAPNS2, CXCR3, EGF, EGFR, HRAS, ITGA1, ITGB1, MAPK1, MAPK3, MYL2, MYLK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTK2, PXN, TLN1, VIL2 24 ACTA1(4), CAPN1(2), CAPN2(7), CAPNS1(1), CAPNS2(1), EGF(3), EGFR(12), ITGA1(3), ITGB1(6), MAPK1(2), MAPK3(3), MYL2(1), MYLK(14), PRKACB(1), PRKACG(3), PRKAR1A(5), PRKAR1B(1), PRKAR2B(3), PTK2(6), TLN1(7) 11184912 85 41 85 25 35 26 18 0 6 0 0.89 1.00 553 NICOTINATE_AND_NICOTINAMIDE_METABOLISM AOX1, CD38, ENPP1, ENPP3, NADSYN1, NMNAT1, NMNAT2, NNMT, NNT, NP, NT5C, NT5E, NT5M, QPRT 13 AOX1(8), CD38(2), ENPP1(4), ENPP3(4), NADSYN1(2), NMNAT1(2), NMNAT2(2), NNMT(3), NNT(3), NT5E(3), NT5M(1), QPRT(1) 4937944 35 19 35 17 11 13 6 0 5 0 0.90 1.00 554 DNA_POLYMERASE POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLS 7 POLB(3), POLD1(5), POLD2(1), POLE(21), POLG(5), POLL(1), POLQ(12) 5719952 48 24 45 14 17 19 6 0 6 0 0.90 1.00 555 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 235 ACVR1C(3), AKT1(2), AKT2(6), AKT3(1), ARRB1(1), ATF2(1), ATF4(1), BDNF(1), CACNA1A(17), CACNA1B(11), CACNA1C(12), CACNA1D(9), CACNA1E(21), CACNA1F(14), CACNA1G(11), CACNA1H(2), CACNA1I(5), CACNA1S(15), CACNA2D1(11), CACNA2D2(1), CACNA2D3(6), CACNA2D4(3), CACNB1(1), CACNB2(6), CACNB3(2), CACNB4(2), CACNG1(2), CACNG2(3), CACNG4(2), CACNG5(5), CACNG6(1), CACNG8(1), CASP3(2), CD14(1), CDC25B(5), CDC42(1), CHUK(6), CRKL(2), DAXX(1), DUSP1(2), DUSP10(5), DUSP16(5), DUSP3(1), DUSP4(1), DUSP5(2), DUSP6(5), DUSP7(2), DUSP9(1), ECSIT(3), EGF(3), EGFR(12), ELK4(2), FAS(2), FASLG(1), FGF1(2), FGF11(3), FGF12(3), FGF13(3), FGF14(5), FGF17(1), FGF19(1), FGF20(2), FGF21(2), FGF23(1), FGF3(1), FGF5(4), FGF6(3), FGF7(1), FGF8(1), FGF9(1), FGFR1(4), FGFR2(6), FGFR3(2), FGFR4(2), FLNA(3), FLNB(16), FLNC(13), FOS(1), GNA12(2), GRB2(3), IKBKB(4), IL1A(1), IL1B(1), IL1R1(4), IL1R2(7), MAP2K1(4), MAP2K2(1), MAP2K3(6), MAP2K5(4), MAP2K6(3), MAP3K1(8), MAP3K10(3), MAP3K12(6), MAP3K13(9), MAP3K14(3), MAP3K2(3), MAP3K3(3), MAP3K5(7), MAP3K6(6), MAP3K7(4), MAP3K8(2), MAP4K1(3), MAP4K2(1), MAP4K3(4), MAP4K4(8), MAPK1(2), MAPK12(2), MAPK13(1), MAPK14(3), MAPK3(3), MAPK7(3), MAPK8(7), MAPK8IP1(4), MAPK8IP3(2), MAPK9(5), MAPKAPK2(3), MAPKAPK3(1), MAPKAPK5(1), MAPT(5), MAX(1), MEF2C(9), MKNK1(1), MKNK2(3), MOS(3), MRAS(1), NF1(9), NFATC2(6), NFATC4(5), NFKB1(6), NFKB2(4), NLK(2), NR4A1(2), NTF3(1), NTRK1(7), NTRK2(4), PAK1(5), PAK2(3), PDGFA(1), PDGFRA(17), PDGFRB(6), PLA2G1B(1), PLA2G2F(1), PLA2G4A(8), PLA2G6(4), PPM1A(7), PPM1B(2), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PPP5C(4), PRKACA(1), PRKACB(1), PRKACG(3), PRKCA(4), PRKCG(10), PRKX(2), PTPN5(1), PTPN7(2), PTPRR(5), RAF1(6), RAP1A(2), RAP1B(2), RAPGEF2(13), RASA1(9), RASA2(3), RASGRF1(12), RASGRF2(9), RASGRP1(5), RASGRP2(7), RASGRP3(7), RASGRP4(2), RPS6KA1(1), RPS6KA2(10), RPS6KA3(5), RPS6KA5(6), RRAS2(2), SOS1(7), SOS2(11), SRF(3), STK3(3), STK4(3), STMN1(2), TAOK1(5), TAOK2(3), TAOK3(4), TGFB1(1), TGFB2(9), TGFBR1(9), TNFRSF1A(1), TRAF2(1), TRAF6(4), ZAK(6) 94253556 816 132 803 299 330 227 162 7 84 6 0.90 1.00 556 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 18 AKT1(2), EIF4G1(9), EIF4G2(7), EIF4G3(11), GHR(6), IRS1(9), MAPK1(2), MAPK14(3), MAPK3(3), MKNK1(1), PABPC1(3), PDK2(2), PDPK1(1), PRKCA(4), RPS6KB1(3) 7596940 66 30 66 20 18 24 16 0 8 0 0.90 1.00 557 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(3), CAMK1G(5), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CAMK4(3), ESRRA(3), HDAC5(2), MEF2A(4), MEF2C(9), MEF2D(1), PPARA(1), PPP3CA(3), PPP3CB(5), PPP3CC(4), SLC2A4(4), SYT1(1), YWHAH(1) 7001120 57 27 56 28 23 13 12 1 8 0 0.90 1.00 558 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 15 AKT1(2), EIF2B5(5), EIF2S2(1), EIF2S3(1), IGF1(2), IGF1R(8), INPPL1(4), PDK2(2), PDPK1(1), PPP2CA(1), RPS6KB1(3) 4823320 30 23 30 13 12 8 6 0 4 0 0.91 1.00 559 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 15 BCAT1(1), BCAT2(1), COASY(1), DPYS(7), ENPP1(4), ENPP3(4), ILVBL(2), PANK1(2), PANK3(3), PANK4(1), PPCS(2), UPB1(5), VNN1(6) 5083212 39 22 38 15 10 18 8 0 3 0 0.91 1.00 560 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(6), KHK(1), LCT(20), MPI(1), PGM1(4), PYGL(2), PYGM(4), TPI1(1), TREH(2) 4563208 41 26 41 15 18 12 11 0 0 0 0.92 1.00 561 UCALPAINPATHWAY Calpains promote formation of integrin adhesion clusters which recruit Rac to enable the formation of mature focal adhesions that do not contain calpain. ACTA1, ACTN1, ACTN2, ACTN3, ARHA, CAPN1, CAPNS1, CAPNS2, ITGA1, ITGB1, ITGB3, PTK2, PXN, RAC1, SPTAN1, SRC, TLN1, VIL2 16 ACTA1(4), ACTN1(5), ACTN2(8), ACTN3(3), CAPN1(2), CAPNS1(1), CAPNS2(1), ITGA1(3), ITGB1(6), ITGB3(9), PTK2(6), SPTAN1(13), SRC(3), TLN1(7) 9787700 71 38 71 31 34 23 10 0 3 1 0.92 1.00 562 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(3), ALDOA(1), ALDOB(5), ALDOC(3), FBP2(3), FPGT(5), GCK(2), GMDS(1), GMPPA(7), HK1(6), HK2(3), HK3(5), KHK(1), MPI(1), PFKFB1(7), PFKFB4(2), PFKM(4), PFKP(2), PMM1(3), SORD(2), TPI1(1) 8156180 67 37 67 26 25 32 7 0 3 0 0.92 1.00 563 IRINOTECAN_PATHWAY_PHARMGKB ABCC1, ABCC2, ABCG2, BCHE, CES1, CES2, CES4, CYP3A4, CYP3A5, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6 16 ABCC1(11), ABCC2(14), ABCG2(9), CES1(5), CES2(1), CYP3A4(1), CYP3A5(3), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(2), UGT1A5(3), UGT1A6(1), UGT1A7(2), UGT1A8(1), UGT1A9(6) 7248572 63 25 63 20 23 18 14 1 7 0 0.92 1.00 564 MTA3PATHWAY The estrogen receptor regulates proliferation in mammary epithelia via MTA3 activation; loss of either protein is implicated in breast cancer. ALDOA, CTSD, ESR1, GAPD, GREB1, HSPB1, HSPB2, MTA1, MTA3, PDZK1, TUBA1, TUBA2, TUBA3, TUBA4, TUBA6, TUBA8 9 ALDOA(1), CTSD(3), GREB1(12), HSPB2(2), MTA1(1), MTA3(1), PDZK1(1), TUBA8(2) 3242564 23 16 23 10 8 8 4 0 3 0 0.92 1.00 565 PENTOSE_PHOSPHATE_PATHWAY ALDOA, ALDOB, ALDOC, FBP1, FBP2, G6PD, GPI, H6PD, PFKM, PFKP, PGD, PGLS, PGM1, PGM3, PRPS1, PRPS1L1, PRPS2, RBKS, RPE, RPE, LOC440001, RPIA, TAL1, TALDO1, TALDO1, HSUP1, TKT 23 ALDOA(1), ALDOB(5), ALDOC(3), FBP2(3), G6PD(3), GPI(2), H6PD(4), PFKM(4), PFKP(2), PGD(1), PGM1(4), PGM3(5), PRPS1(1), PRPS1L1(1), PRPS2(2), RPE(2), RPIA(3), TALDO1(3), TKT(3) 6863396 52 34 52 18 21 25 5 0 1 0 0.92 1.00 566 HSA03060_PROTEIN_EXPORT Genes involved in protein export OXA1L, SEC61A2, SRP19, SRP54, SRP68, SRP72, SRP9, SRPR 8 OXA1L(4), SEC61A2(1), SRP19(1), SRP54(3), SRP68(4), SRP72(4), SRPR(1) 2528892 18 12 18 5 6 8 2 1 1 0 0.92 1.00 567 TOLLPATHWAY Toll-like receptors are activated by bacterial lipoproteins, lipopolysaccharides, and other surface molecules, and activate pro-inflammatory factors such as NF-kB. CD14, CHUK, ELK1, FOS, IKBKB, IKBKG, IRAK1, JUN, LY96, MAP2K3, MAP2K4, MAP2K6, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAPK14, MAPK8, MYD88, NFKB1, NFKBIA, PGLYRP, PPARA, PRKR, RELA, SITPEC, TIRAP, TLR10, TLR2, TLR3, TLR4, TLR6, TLR7, TLR9, TOLLIP, TRAF6 30 CD14(1), CHUK(6), FOS(1), IKBKB(4), IRAK1(1), LY96(2), MAP2K3(6), MAP2K6(3), MAP3K1(8), MAP3K14(3), MAP3K7(4), MAPK14(3), MAPK8(7), MYD88(2), NFKB1(6), PPARA(1), RELA(2), TIRAP(1), TLR10(4), TLR2(6), TLR3(5), TLR4(10), TLR6(2), TLR7(7), TLR9(7), TOLLIP(1), TRAF6(4) 12078284 107 38 107 33 35 32 27 3 9 1 0.92 1.00 568 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 8 EIF2AK3(2), EIF2AK4(6), EIF2B5(5), EIF2S2(1), EIF2S3(1), EIF5(3) 3594112 18 13 18 5 3 5 7 0 3 0 0.93 1.00 569 EPOPATHWAY Erythropoietin, which activates the MAPK pathway, stimulates erythrocyte production and is an effective treatment for anemia. CSNK2A1, ELK1, EPO, EPOR, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAPK3, MAPK8, PLCG1, PTPN6, RAF1, SHC1, SOS1, STAT5A, STAT5B 19 CSNK2A1(4), FOS(1), GRB2(3), JAK2(9), MAP2K1(4), MAPK3(3), MAPK8(7), PLCG1(4), PTPN6(4), RAF1(6), SHC1(3), SOS1(7), STAT5B(3) 7317592 58 27 56 13 20 18 12 1 5 2 0.93 1.00 570 DEATHPATHWAY Death receptors such as Fas and DR3, 4, and 5 transduce pro-apoptotic signaling by oligomerizing to activate the caspase cascade. APAF1, BCL2, BID, BIRC2, BIRC3, BIRC4, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHUK, CYCS, DFFA, DFFB, FADD, GAS2, LMNA, MAP3K14, NFKB1, NFKBIA, RELA, RIPK1, SPTAN1, TNFRSF10A, TNFRSF10B, TNFRSF25, TNFSF10, TNFSF12, TRADD, TRAF2 31 APAF1(8), BCL2(1), BID(1), BIRC2(4), BIRC3(7), CASP10(2), CASP3(2), CASP6(2), CASP7(1), CASP9(2), CFLAR(3), CHUK(6), DFFA(3), DFFB(2), GAS2(2), MAP3K14(3), NFKB1(6), RELA(2), RIPK1(2), SPTAN1(13), TNFRSF10A(3), TNFRSF10B(6), TNFSF10(1), TNFSF12(2), TRADD(1), TRAF2(1) 10995520 86 37 86 33 32 31 13 0 9 1 0.93 1.00 571 HSA00920_SULFUR_METABOLISM Genes involved in sulfur metabolism BPNT1, CHST11, CHST12, CHST13, PAPSS1, PAPSS2, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SULT2B1, SUOX 12 BPNT1(1), CHST11(3), CHST12(3), CHST13(2), PAPSS1(2), PAPSS2(4), SULT1A1(2), SULT1A2(1), SULT1E1(2), SULT2A1(2), SULT2B1(1), SUOX(2) 3092160 25 14 25 5 10 8 4 0 3 0 0.93 1.00 572 GLYCOLYSIS_AND_GLUCONEOGENESIS Genes involved in glycolysis and gluconeogenesis ALDOA, ALDOB, ALDOC, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GAPDHS, GAPDS, GCK, GOT1, GOT2, GPI, HK1, HK2, HK3, LDHA, LDHAL6B, LDHB, LDHC, MDH1, MDH2, PC, PCK1, PDHA1, PDHA2, PDHB, PDHX, PFKL, PFKM, PFKP, PGAM1, PGAM2, PGK1, PGK2, PKLR, PKM2, TNFAIP1, TPI1 43 ALDOA(1), ALDOB(5), ALDOC(3), DLAT(3), DLD(1), ENO2(3), ENO3(4), FBP2(3), G6PC(4), GCK(2), GOT1(6), GOT2(1), GPI(2), HK1(6), HK2(3), HK3(5), LDHA(2), LDHAL6B(2), LDHB(3), LDHC(2), MDH1(1), MDH2(1), PC(6), PCK1(3), PDHA1(5), PDHA2(8), PDHB(2), PDHX(2), PFKL(1), PFKM(4), PFKP(2), PGAM1(3), PGAM2(1), PGK1(3), PGK2(7), PKM2(2), TNFAIP1(3), TPI1(1) 14078660 116 44 113 48 47 42 16 0 11 0 0.94 1.00 573 TNFR1PATHWAY Tumor necrosis factor alpha binds to its receptor TNFR1 and induces caspase-dependent apoptosis. ADPRT, ARHGDIB, BAG4, CASP2, CASP3, CASP8, CRADD, DFFA, DFFB, FADD, JUN, LMNA, LMNB1, LMNB2, MADD, MAP2K4, MAP3K1, MAP3K7, MAPK8, PAK1, PAK2, PRKDC, RB1, RIPK1, SPTAN1, TNF, TNFRSF1A, TRADD, TRAF2 26 ARHGDIB(3), BAG4(2), CASP2(4), CASP3(2), CRADD(2), DFFA(3), DFFB(2), LMNB1(4), LMNB2(1), MADD(14), MAP3K1(8), MAP3K7(4), MAPK8(7), PAK1(5), PAK2(3), PRKDC(18), RB1(7), RIPK1(2), SPTAN1(13), TNFRSF1A(1), TRADD(1), TRAF2(1) 12827132 107 39 106 40 32 28 27 2 16 2 0.94 1.00 574 PANTOTHENATE_AND_COA_BIOSYNTHESIS BCAT1, COASY, DPYD, DPYS, ENPP1, ENPP3, PANK1, PANK2, PANK3, PANK4, PPCS, UPB1 11 BCAT1(1), COASY(1), DPYS(7), ENPP1(4), ENPP3(4), PANK1(2), PANK3(3), PANK4(1), PPCS(2), UPB1(5) 3918016 30 16 29 9 6 15 6 0 3 0 0.94 1.00 575 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(3), CAMK1G(5), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CAMK4(3), CAMKK1(1), CAMKK2(1), CREB1(1), SYT1(1) 3947040 23 15 23 14 7 8 6 0 2 0 0.94 1.00 576 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 38 ATF2(1), CDC42(1), CREB1(1), DAXX(1), GRB2(3), HSPB2(2), MAP2K6(3), MAP3K1(8), MAP3K5(7), MAP3K7(4), MAP3K9(4), MAPK14(3), MAPKAPK2(3), MAPKAPK5(1), MAX(1), MEF2A(4), MEF2C(9), MEF2D(1), MKNK1(1), PLA2G4A(8), RIPK1(2), RPS6KA5(6), SHC1(3), STAT1(6), TGFB1(1), TGFB2(9), TGFBR1(9), TRADD(1), TRAF2(1) 12227444 104 33 100 33 38 29 23 0 14 0 0.95 1.00 577 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(3), B4GALT1(6), B4GALT2(3), G6PC(4), G6PC2(1), GALE(1), GALK2(3), GALT(2), GANC(3), GCK(2), GLA(4), GLB1(3), HK1(6), HK2(3), HK3(5), HSD3B7(2), LALBA(2), LCT(20), MGAM(13), PFKL(1), PFKM(4), PFKP(2), PGM1(4), PGM3(5), RDH11(1), RDH12(3), RDH13(1), UGP2(7) 13025704 114 43 113 38 51 39 20 0 4 0 0.95 1.00 578 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 25 BAG4(2), BIRC2(4), BIRC3(7), CASP3(2), CFLAR(3), MAP3K3(3), MAP3K7(4), NFKB1(6), NFKB2(4), NFKBIB(1), NFKBIE(2), NR2C2(4), RALBP1(6), RIPK1(2), TNFAIP3(3), TNFRSF1A(1), TRADD(1), TRAF2(1) 8346188 56 29 56 14 20 17 14 1 4 0 0.96 1.00 579 TNFR2PATHWAY Tumor necrosis factor beta, produced by activated lymphocytes, binds to its receptor TNFR2 to induce activation in immune cells and apoptosis in many other cells. CHUK, DUSP1, IKBKAP, IKBKB, IKBKG, LTA, MAP3K1, MAP3K14, NFKB1, NFKBIA, RELA, RIPK1, TANK, TNFAIP3, TNFRSF1B, TRAF1, TRAF2, TRAF3 17 CHUK(6), DUSP1(2), IKBKAP(2), IKBKB(4), MAP3K1(8), MAP3K14(3), NFKB1(6), RELA(2), RIPK1(2), TANK(6), TNFAIP3(3), TRAF1(2), TRAF2(1), TRAF3(6) 7611944 53 26 52 18 25 13 9 1 5 0 0.96 1.00 580 CHONDROITIN B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 B3GAT3(1), HS3ST1(2), HS3ST2(3), HS3ST3B1(2), XYLT1(7), XYLT2(2) 2235840 17 12 16 13 8 4 2 1 2 0 0.96 1.00 581 HEPARAN_SULFATE_BIOSYNTHESIS B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 B3GAT3(1), HS3ST1(2), HS3ST2(3), HS3ST3B1(2), XYLT1(7), XYLT2(2) 2235840 17 12 16 13 8 4 2 1 2 0 0.96 1.00 582 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 19 AKT1(2), BCL2(1), BCR(7), CRKL(2), FOS(1), GRB2(3), JAK2(9), MAP2K1(4), MAP3K1(8), MAPK3(3), MAPK8(7), RAF1(6), SOS1(7), STAT1(6), STAT5B(3) 7814520 69 30 68 15 25 20 17 1 4 2 0.96 1.00 583 AMINOSUGARS_METABOLISM CMAS, CYB5R3, GCK, GFPT1, GNE, GNPDA1, GNPDA2, HEXA, HEXB, HK1, HK2, HK3, PGM3, RENBP, UAP1 15 CMAS(8), CYB5R3(1), GCK(2), GFPT1(4), GNE(2), GNPDA2(1), HEXB(3), HK1(6), HK2(3), HK3(5), PGM3(5), RENBP(1) 5735140 41 25 40 13 13 19 8 0 1 0 0.96 1.00 584 ETSPATHWAY The Ets transcription factors are activated by Ras and promote macrophage differentiation. CSF1, CSF1R, DDX20, E2F1, E2F4, ETS1, ETS2, ETV3, FOS, HDAC2, HDAC5, HRAS, JUN, NCOR2, RBL1, RBL2, SIN3A, SIN3B 18 CSF1(2), CSF1R(3), DDX20(4), E2F4(1), ETS1(1), ETS2(3), ETV3(1), FOS(1), HDAC2(2), HDAC5(2), NCOR2(2), RBL1(5), RBL2(8), SIN3A(10), SIN3B(4) 8946576 49 25 48 28 17 15 9 0 8 0 0.97 1.00 585 ARAPPATHWAY ADP-ribosylation factors (ARFs), members of the Ras superfamily, regulate eukaryotic vesicular trafficking and activate phospholipase D's. ARF1, ARFGAP1, ARFGAP3, ARFGEF2, BIG1, CENTD1, CENTD2, CLTA, CLTB, COP, COPA, DDEF1, DDEF2, GBF1, GPLD1, KDELR1, KDELR2, KDELR3, PSCD1, PSCD2, PSCD3, PSCD4 12 ARFGAP1(1), ARFGAP3(3), ARFGEF2(8), CLTA(2), COPA(2), GBF1(12), GPLD1(6), KDELR1(2), KDELR2(1), KDELR3(1) 5467848 38 22 37 15 16 9 8 1 4 0 0.97 1.00 586 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 18 AKT1(2), APAF1(8), BAD(1), BAX(1), BCL2(1), BCL2L1(1), BID(1), CASP3(2), CASP6(2), CASP7(1), CASP9(2), PRKCA(4), PTK2(6), STAT1(6), TLN1(7) 6946508 45 28 45 16 15 16 9 0 5 0 0.97 1.00 587 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 9 ADAM17(7), AXIN1(2), BTRC(5), DLL1(4), FZD1(1), PSEN1(3), WNT1(1) 4003612 23 15 23 10 10 3 4 0 6 0 0.97 1.00 588 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 36 EEF1A2(1), EEF1B2(1), EEF1G(1), EEF2(3), EEF2K(1), EIF2AK1(6), EIF2AK2(1), EIF2AK3(2), EIF2B1(2), EIF2B2(1), EIF2B3(2), EIF2B5(5), EIF2S2(1), EIF2S3(1), EIF4EBP2(1), EIF4G1(9), EIF4G3(11), EIF5(3), EIF5A(2), EIF5B(4), ETF1(5), GSPT2(1), KIAA0664(4), PABPC1(3), PABPC3(6), PAIP1(4), SLC35A4(2) 14639220 83 39 82 25 26 20 21 2 14 0 0.97 1.00 589 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(2), RPL10L(2), RPL11(1), RPL18A(1), RPL19(1), RPL21(1), RPL22L1(1), RPL24(1), RPL28(2), RPL3(2), RPL31(1), RPL32(1), RPL35(1), RPL39(1), RPL3L(1), RPL6(3), RPL7(1), RPL9(4), RPS11(1), RPS13(1), RPS15A(1), RPS16(2), RPS18(2), RPS2(1), RPS20(1), RPS23(4), RPS3(2), RPS9(2), RPSA(1) 7558400 47 28 46 15 14 12 16 1 4 0 0.97 1.00 590 BIOSYNTHESIS_OF_STEROIDS DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, IDI1, LSS, MVD, MVK, NQO1, NQO2, PMVK, SC5DL, SQLE, VKORC1 14 DHCR7(2), FDFT1(3), HMGCR(3), IDI1(1), LSS(2), MVK(1), NQO1(1), NQO2(1), PMVK(1), SC5DL(4), SQLE(2) 3786500 21 17 21 8 10 6 4 0 1 0 0.97 1.00 591 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 ARSA(1), ARSB(5), ARSD(3), ARSE(2), ASAH1(3), GAL3ST1(2), GALC(1), GLA(4), GLB1(3), LCT(20), NEU1(1), NEU2(1), NEU3(1), PPAP2B(1), SMPD1(6), SPTLC1(4), SPTLC2(2), UGCG(2) 8022488 62 30 62 23 24 18 14 2 4 0 0.97 1.00 592 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(5), FUCA1(3), GLB1(3), HEXB(3), LCT(20), MAN2B1(5), MAN2B2(1), MAN2C1(6), MANBA(7), NEU1(1), NEU2(1), NEU3(1) 6812068 56 29 56 21 21 16 15 0 4 0 0.97 1.00 593 FXRPATHWAY The nuclear receptor transcription factors FXR and LXR are activated by cholesterol metabolites and regulate cholesterol homeostasis. FABP6, LDLR, NR0B2, NR1H3, NR1H4, RXRA 6 FABP6(1), LDLR(5), NR1H3(4), NR1H4(2), RXRA(1) 1809836 13 10 13 7 6 3 3 1 0 0 0.98 1.00 594 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 13 CREB1(1), FOS(1), KEAP1(3), MAPK1(2), MAPK14(3), MAPK8(7), NFE2L2(4), PRKCA(4) 2938936 25 13 25 3 6 10 7 1 1 0 0.98 1.00 595 CHOLESTEROL_BIOSYNTHESIS C10orf110, CYP51A1, DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, HMGCS1, IDI1, LSS, MVD, MVK, NSDHL, PMVK, SC4MOL, SC5DL, SQLE 15 CYP51A1(3), DHCR7(2), FDFT1(3), HMGCR(3), HMGCS1(1), IDI1(1), LSS(2), MVK(1), NSDHL(2), PMVK(1), SC4MOL(1), SC5DL(4), SQLE(2) 4506660 26 17 26 11 11 8 5 0 2 0 0.98 1.00 596 HSA00072_SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES Genes involved in synthesis and degradation of ketone bodies ACAT1, ACAT2, BDH1, BDH2, HMGCL, HMGCS1, HMGCS2, OXCT1, OXCT2 9 ACAT1(1), ACAT2(2), BDH1(1), HMGCL(1), HMGCS1(1), HMGCS2(1), OXCT1(3), OXCT2(1) 2448320 11 10 11 5 6 4 1 0 0 0 0.98 1.00 597 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(6), DNAJC3(1), EIF2S2(1), MAP3K14(3), NFKB1(6), RELA(2) 3150696 19 9 19 7 11 2 4 0 2 0 0.99 1.00 598 EGFR_SMRTEPATHWAY EGF receptor activation inhibits SMRT, a transcriptional co-repressor that interacts with transcription factor complexes and gene silencers. EGF, EGFR, MAP2K1, MAP3K1, MAPK14, NCOR2, RARA, RXRA, THRA, THRB, ZNF145 10 EGF(3), EGFR(12), MAP2K1(4), MAP3K1(8), MAPK14(3), NCOR2(2), RXRA(1), THRA(2), THRB(4) 5849792 39 22 39 15 18 11 8 0 2 0 0.99 1.00 599 RNA_POLYMERASE POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT 14 POLR1B(9), POLR2A(6), POLR2B(8), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLR2K(1), POLRMT(1) 4496660 29 16 29 4 10 9 8 1 1 0 0.99 1.00 600 SODDPATHWAY Some members of the tumor necrosis factor receptor family have cytoplasmic death domains that promote apoptosis when active and are repressed by silencers called SODDs. BAG4, BIRC3, CASP8, FADD, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF2 9 BAG4(2), BIRC3(7), RIPK1(2), TNFRSF1A(1), TRADD(1), TRAF2(1) 2393432 14 11 14 6 5 5 3 0 1 0 0.99 1.00 601 ARGININECPATHWAY Related catabolic pathways process arginine, histidine, glutamine, and proline through glutamate to alpha-ketoglutamate, which feeds into the citric acid cycle. ALDH4A1, ARG1, GLS, GLUD1, OAT, PRODH 6 ALDH4A1(3), ARG1(1), GLUD1(2), OAT(1) 1833156 7 6 7 3 4 1 2 0 0 0 0.99 1.00 602 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(3), ALDOA(1), ALDOB(5), ALDOC(3), FBP2(3), FPGT(5), FUK(1), GMDS(1), GMPPA(7), HK1(6), HK2(3), HK3(5), HSD3B7(2), KHK(1), LHPP(2), MPI(1), MTMR1(5), MTMR2(2), MTMR6(4), PFKFB1(7), PFKFB4(2), PFKL(1), PFKM(4), PFKP(2), PHPT1(1), PMM1(3), RDH11(1), RDH12(3), RDH13(1), SORD(2), TPI1(1), TSTA3(1) 12661132 89 40 89 40 36 39 9 0 5 0 0.99 1.00 603 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(6), IFNG(1), IKBKB(4), IL2(4), IL4(3), MAP3K1(8), MAP3K5(7), MAP4K5(2), MAPK14(3), MAPK8(7), NFKB1(6), RELA(2), TNFRSF9(3), TRAF2(1) 6686712 58 23 58 15 21 24 10 1 2 0 0.99 1.00 604 NFKBPATHWAY Inactive nuclear factor kB (NF-kB) is inhibited by the IkB family in the cytoplasm; active NF-kB is localized in the nucleus and regulates transcription of a variety of genes. CHUK, FADD, IKBKB, IKBKG, IL1A, IL1R1, IRAK1, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MYD88, NFKB1, NFKBIA, RELA, RIPK1, TLR4, TNF, TNFAIP3, TNFRSF1A, TNFRSF1B, TRADD, TRAF6 21 CHUK(6), IKBKB(4), IL1A(1), IL1R1(4), IRAK1(1), MAP3K1(8), MAP3K14(3), MAP3K7(4), MYD88(2), NFKB1(6), RELA(2), RIPK1(2), TLR4(10), TNFAIP3(3), TNFRSF1A(1), TRADD(1), TRAF6(4) 8211660 62 25 62 18 23 19 14 0 6 0 0.99 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(3), CYP51A1(3), DHCR24(2), DHCR7(2), EBP(2), FDFT1(3), GGCX(5), GGPS1(1), HMGCR(3), IDI1(1), IDI2(1), LSS(2), MVK(1), NQO1(1), NSDHL(2), PMVK(1), SC4MOL(1), SC5DL(4), SQLE(2) 6569804 40 23 40 15 15 15 6 0 4 0 0.99 1.00 606 HSA00563_GLYCOSYLPHOSPHATIDYLINOSITOL_ANCHOR_BIOSYNTHESIS Genes involved in glycosylphosphatidylinositol(GPI)-anchor biosynthesis GPAA1, GPLD1, PGAP1, PIGA, PIGB, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGU, PIGV, PIGW, PIGX, PIGZ 23 GPAA1(3), GPLD1(6), PGAP1(8), PIGA(1), PIGB(3), PIGG(3), PIGK(4), PIGM(3), PIGN(2), PIGO(3), PIGQ(1), PIGS(2), PIGT(3), PIGU(1), PIGV(2), PIGW(1), PIGX(4) 8312940 50 23 49 19 15 16 12 0 7 0 0.99 1.00 607 HSA00625_TETRACHLOROETHENE_DEGRADATION Genes involved in tetrachloroethene degradation AKR1B10, EPHX2, HSD3B7, RDH11, RDH12, RDH13, RDH14 7 EPHX2(1), HSD3B7(2), RDH11(1), RDH12(3), RDH13(1) 1627788 8 6 8 4 4 4 0 0 0 0 0.99 1.00 608 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 10 APP(1), CAPN1(2), CAPNS1(1), CAPNS2(1), CDK5R1(1), CSNK1A1(2), CSNK1D(4), MAPT(5), PPP2CA(1) 2891456 18 12 18 8 9 4 3 1 1 0 1.00 1.00 609 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(7), GTF2A1(2), GTF2B(1), GTF2E1(5), GTF2F1(5), HDAC3(2), NCOA1(8), NCOA2(7), NCOA3(11), NCOR2(2), POLR2A(6), RXRA(1), TBP(1) 8507856 58 30 58 21 19 22 13 1 3 0 1.00 1.00 610 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 37 APAF1(8), BAK1(1), BAX(1), BCL2(1), BCL2L1(1), BID(1), BIRC2(4), BIRC3(7), CASP2(4), CASP3(2), CASP6(2), CASP7(1), CASP9(2), FAS(2), FASLG(1), GZMB(2), MAP3K1(8), MAP3K14(3), MDM2(4), NFKB1(6), PARP1(5), RELA(2), RIPK1(2), TNFRSF1A(1), TNFSF10(1), TRADD(1), TRAF1(2), TRAF2(1) 11353428 76 32 76 30 30 21 18 0 7 0 1.00 1.00 611 MSPPATHWAY Macrophage stimulating protein is synthesized as pro-MSP by the liver and, on proteolysis, binds to monocyte receptor kinase RON to induce macrophage development. CCL2, CSF1, IL1B, MST1, MST1R, TNF 6 CSF1(2), IL1B(1), MST1(1), MST1R(1) 2077248 5 5 5 4 3 2 0 0 0 0 1.00 1.00 612 HSA00532_CHONDROITIN_SULFATE_BIOSYNTHESIS Genes involved in chondroitin sulfate biosynthesis B3GALT6, B3GAT1, B3GAT2, B3GAT3, B4GALT7, ChGn, CHPF, CHST11, CHST12, CHST13, CHST14, CHST3, CHST7, CHSY-2, CHSY1, CSGlcA-T, DSE, GALNAC4S-6ST, GALNACT-2, UST, XYLT1, XYLT2 17 B3GAT1(1), B3GAT3(1), CHPF(3), CHST11(3), CHST12(3), CHST13(2), CHST14(1), CHSY1(5), DSE(3), UST(1), XYLT1(7), XYLT2(2) 4799936 32 18 32 25 12 12 6 0 2 0 1.00 1.00 613 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 17 ABL1(4), BRCA1(6), CDKN1A(1), CHEK1(1), CHEK2(1), MAPK8(7), MDM2(4), MRE11A(8), NFKB1(6), RAD50(11), RBBP8(2), RELA(2) 7606680 53 20 53 11 16 18 14 1 4 0 1.00 1.00 614 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 17 AKT1(2), EIF4B(2), EIF4G1(9), EIF4G2(7), EIF4G3(11), MKNK1(1), PDK2(2), PDPK1(1), PPP2CA(1), RPS6KB1(3), TSC1(4), TSC2(2) 7418424 45 21 45 20 16 12 11 0 6 0 1.00 1.00 615 FOLATE_BIOSYNTHESIS ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, DHFR, FPGS, GCH1, GGH, SPR 9 ALPI(2), ALPL(1), ALPP(1), ALPPL2(1), DHFR(1), GGH(1) 2173660 7 7 7 1 2 4 1 0 0 0 1.00 1.00 616 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 169792 0 0 0 1 0 0 0 0 0 0 1.00 1.00