rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q 1 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 222 ADORA1(4), ADORA2A(6), ADORA2B(1), ADRA1A(2), ADRA1B(4), ADRA2B(4), ADRA2C(2), ADRB2(3), AGTR1(3), AGTR2(4), AVPR1A(3), AVPR1B(2), AVPR2(1), BDKRB1(3), BDKRB2(1), C3AR1(1), C5AR1(1), CALCR(6), CALCRL(4), CCKAR(2), CCKBR(1), CHRM2(6), CHRM3(5), CHRM4(1), CHRM5(2), CNR1(3), CNR2(3), CRHR1(4), CRHR2(3), CTSG(4), CYSLTR1(3), CYSLTR2(1), DRD1(1), DRD2(2), DRD3(5), DRD4(1), DRD5(3), EDNRA(2), EDNRB(5), F2R(2), F2RL1(3), F2RL2(1), F2RL3(2), FPR1(1), FSHB(1), GABBR1(3), GABBR2(3), GABRA1(6), GABRA3(5), GABRA4(3), GABRA5(4), GABRB1(3), GABRB2(6), GABRD(2), GABRE(4), GABRG2(5), GABRP(2), GABRQ(6), GABRR1(2), GABRR2(2), GALR1(3), GH1(1), GH2(2), GHR(2), GHRHR(3), GHSR(3), GLP1R(1), GLP2R(4), GLRA1(2), GLRA2(5), GLRA3(3), GLRB(3), GPR156(2), GPR35(1), GPR50(4), GPR63(2), GPR83(2), GRIA1(6), GRIA2(3), GRIA3(9), GRIA4(7), GRID2(12), GRIK1(4), GRIK2(8), GRIK3(7), GRIK4(4), GRIK5(1), GRIN1(1), GRIN2A(13), GRIN2C(2), GRIN2D(3), GRIN3A(8), GRIN3B(4), GRM2(3), GRM4(1), GRM6(4), GRM7(8), GRM8(9), GRPR(2), GZMA(4), HCRTR2(3), HRH1(3), HRH2(2), HRH3(1), HRH4(3), HTR1B(3), HTR1D(1), HTR1E(5), HTR1F(2), HTR2A(1), HTR2B(2), HTR2C(3), HTR4(3), HTR5A(3), HTR6(1), HTR7(3), LEPR(10), LHB(1), LHCGR(8), LTB4R2(1), MAS1(3), MC2R(2), MC3R(3), MC4R(1), MC5R(3), MCHR1(2), MCHR2(3), MTNR1A(1), NMBR(2), NMUR2(2), NPBWR1(1), NPY1R(3), NPY2R(2), NPY5R(2), NTSR1(3), NTSR2(3), OPRD1(2), OPRK1(1), OPRM1(2), OXTR(1), P2RX2(1), P2RX3(5), P2RX4(2), P2RX7(1), P2RY1(1), P2RY10(2), P2RY13(1), P2RY14(3), P2RY2(2), P2RY4(1), P2RY6(2), PARD3(5), PPYR1(3), PRL(1), PRLHR(1), PRLR(5), PRSS1(3), PRSS3(1), PTAFR(3), PTGDR(5), PTGER2(1), PTGER3(5), PTGER4(2), PTGFR(2), PTGIR(1), PTH2R(5), RXFP1(7), RXFP2(1), SSTR1(1), SSTR2(2), SSTR3(1), SSTR4(2), SSTR5(1), TAAR1(4), TAAR2(2), TAAR5(5), TAAR6(4), TAAR8(2), TAAR9(2), TACR1(2), TACR3(3), TBXA2R(2), THRA(2), THRB(1), TRHR(1), TRPV1(2), TSHR(1) 55037422 557 157 554 207 157 205 106 28 61 0 2.71e-07 0.00017 2 GPCRDB_CLASS_A_RHODOPSIN_LIKE ADORA1, ADORA2A, ADORA2B, ADORA3, ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2C, ADRB1, ADRB2, ADRB3, AGTR1, AGTR2, AGTRL1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BLR1, BRS3, C3AR1, C5R1, CCBP2, CCKAR, CCKBR, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CCRL1, CCRL2, CHML, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CMKLR1, CMKOR1, CNR1, CNR2, CX3CR1, CXCR3, CXCR4, DRD1, DRD2, DRD3, DRD4, DRD5, EDNRA, EDNRB, ELA3A, F2R, F2RL1, F2RL2, F2RL3, FPR1, FPRL1, FPRL2, FSHR, GALR1, GALR2, GALR3, GALT, GHSR, GNB2L1, GPR10, GPR147, GPR17, GPR173, GPR174, GPR23, GPR24, GPR27, GPR3, GPR30, GPR35, GPR37, GPR37L1, GPR4, GPR44, GPR50, GPR6, GPR63, GPR74, GPR77, GPR83, GPR85, GPR87, GPR92, GRPR, HCRTR1, HCRTR2, HRH1, HRH2, HRH3, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, HTR7, LOC93164, IL8RA, IL8RB, LHCGR, LTB4R, MAS1, MC1R, MC3R, MC4R, MC5R, MLNR, MTNR1A, MTNR1B, NMBR, NMUR1, NMUR2, NPY1R, NPY2R, NPY5R, NPY6R, NTSR1, NTSR2, OPN1SW, OPN3, OPRD1, OPRK1, OPRL1, OPRM1, OR10A5, OR11A1, OR12D3, OR1C1, OR1F1, OR1Q1, OR2H1, OR5V1, OR5V1, OR12D3, OR7A5, OR7C1, OR8B8, OXTR, P2RY1, P2RY10, P2RY11, P2RY12, P2RY13, P2RY14, P2RY2, P2RY5, P2RY6, PPYR1, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, Rgr, RGR, RHO, RRH, SSTR1, SSTR2, SSTR3, SSTR4, SUCNR1, TBXA2R, TRHR 159 ADORA1(4), ADORA2A(6), ADORA2B(1), ADRA1A(2), ADRA1B(4), ADRA1D(2), ADRA2C(2), ADRB2(3), AGTR1(3), AGTR2(4), AVPR1A(3), AVPR1B(2), AVPR2(1), BDKRB1(3), BDKRB2(1), C3AR1(1), CCBP2(4), CCKAR(2), CCKBR(1), CCR1(2), CCR10(1), CCR3(1), CCR4(3), CCR6(2), CCR8(3), CCRL1(3), CCRL2(1), CHML(1), CHRM2(6), CHRM3(5), CHRM4(1), CHRM5(2), CMKLR1(1), CNR1(3), CNR2(3), CX3CR1(3), CXCR3(1), DRD1(1), DRD2(2), DRD3(5), DRD4(1), DRD5(3), EDNRA(2), EDNRB(5), F2R(2), F2RL1(3), F2RL2(1), F2RL3(2), FPR1(1), GALR1(3), GALT(1), GHSR(3), GPR17(5), GPR174(4), GPR27(1), GPR35(1), GPR37(2), GPR37L1(2), GPR50(4), GPR6(2), GPR63(2), GPR77(4), GPR83(2), GPR85(2), GPR87(6), GRPR(2), HCRTR2(3), HRH1(3), HRH2(2), HRH3(1), HTR1B(3), HTR1D(1), HTR1E(5), HTR1F(2), HTR2A(1), HTR2B(2), HTR2C(3), HTR4(3), HTR5A(3), HTR6(1), HTR7(3), LHCGR(8), MAS1(3), MC3R(3), MC4R(1), MC5R(3), MTNR1A(1), NMBR(2), NMUR2(2), NPY1R(3), NPY2R(2), NPY5R(2), NTSR1(3), NTSR2(3), OPN1SW(1), OPN3(1), OPRD1(2), OPRK1(1), OPRM1(2), OR10A5(2), OR11A1(4), OR12D3(4), OR1F1(1), OR1Q1(3), OR2H1(1), OR5V1(1), OR7A5(1), OR8B8(5), OXTR(1), P2RY1(1), P2RY10(2), P2RY13(1), P2RY14(3), P2RY2(2), P2RY6(2), PPYR1(3), PTAFR(3), PTGDR(5), PTGER2(1), PTGER4(2), PTGFR(2), PTGIR(1), RGR(2), SSTR1(1), SSTR2(2), SSTR3(1), SSTR4(2), SUCNR1(2), TBXA2R(2), TRHR(1) 31942456 308 137 307 112 86 113 58 14 37 0 0.000019 0.0059 3 C21_STEROID_HORMONE_METABOLISM AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 10 AKR1C4(1), AKR1D1(4), CYP11A1(2), CYP11B2(6), CYP17A1(1), CYP21A2(1), HSD11B1(3), HSD11B2(1), HSD3B1(4), HSD3B2(5) 2150774 28 26 27 3 5 12 4 5 2 0 0.00060 0.091 4 HSA00140_C21_STEROID_HORMONE_METABOLISM Genes involved in C21-steroid hormone metabolism AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 10 AKR1C4(1), AKR1D1(4), CYP11A1(2), CYP11B2(6), CYP17A1(1), CYP21A2(1), HSD11B1(3), HSD11B2(1), HSD3B1(4), HSD3B2(5) 2150774 28 26 27 3 5 12 4 5 2 0 0.00060 0.091 5 BLOOD_CLOTTING_CASCADE F10, F11, F12, F13B, F2, F5, F7, F8, F8A1, F9, FGA, FGB, FGG, LPA, PLG, PLAT, PLAU, PLG, SERPINB2, SERPINE1, SERPINF2, VWF 20 F10(3), F11(4), F12(1), F13B(7), F5(15), F8(10), F9(4), FGA(5), FGB(3), FGG(1), LPA(11), PLAT(1), PLAU(2), PLG(2), SERPINB2(3), SERPINE1(2), SERPINF2(3), VWF(16) 9480458 93 69 92 24 19 37 23 6 8 0 0.00074 0.091 6 FLUMAZENILPATHWAY Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 7 GABRA1(6), GABRA3(5), GABRA4(3), GABRA5(4), PRKCE(5) 1635108 23 23 23 5 9 10 3 0 1 0 0.0012 0.12 7 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 130 ACTB(1), COL11A2(10), COL17A1(4), COL1A1(8), COL1A2(15), COL2A1(8), COL3A1(10), COL4A1(11), COL4A2(9), COL4A4(9), COL4A6(9), COL5A1(5), COL5A2(12), COL5A3(11), COL6A3(12), COMP(2), DES(2), DSC1(4), DSC2(1), DSC3(7), DSG1(8), DSG2(2), DSG3(2), DSG4(5), FN1(17), GJA1(4), GJA10(5), GJA8(2), GJB2(1), GJB4(1), GJB5(1), GJC1(2), GJC2(1), GJC3(1), GJD2(2), GJD4(2), IBSP(4), INA(2), ITGA6(6), ITGB4(9), KRT1(1), KRT10(1), KRT12(3), KRT13(2), KRT14(1), KRT16(3), KRT17(2), KRT18(2), KRT2(4), KRT20(3), KRT23(2), KRT24(4), KRT27(3), KRT28(2), KRT3(2), KRT31(1), KRT32(2), KRT33A(1), KRT35(1), KRT36(3), KRT37(2), KRT4(1), KRT5(1), KRT6A(2), KRT6B(4), KRT6C(2), KRT71(2), KRT72(2), KRT73(7), KRT74(1), KRT75(2), KRT76(2), KRT77(3), KRT78(1), KRT79(4), KRT81(3), KRT82(1), KRT83(1), KRT84(1), KRT85(1), KRT86(1), KRT9(1), LAMA1(14), LAMA2(17), LAMA3(7), LAMA4(15), LAMA5(7), LAMB1(6), LAMB2(4), LAMB3(1), LAMB4(3), LAMC1(8), LAMC2(4), LAMC3(1), NES(11), PRPH(2), RELN(26), THBS1(1), THBS3(4), TNC(16), TNXB(16), VIM(5), VWF(16) 63492600 499 148 498 162 140 188 92 32 47 0 0.0028 0.24 8 HSA04614_RENIN_ANGIOTENSIN_SYSTEM Genes involved in renin-angiotensin system ACE, ACE2, AGT, AGTR1, AGTR2, ANPEP, CMA1, CPA3, CTSA, CTSG, ENPEP, LNPEP, MAS1, MME, NLN, REN, THOP1 17 ACE(4), ACE2(3), AGT(1), AGTR1(3), AGTR2(4), ANPEP(5), CMA1(4), CPA3(4), CTSA(2), CTSG(4), ENPEP(7), LNPEP(2), MAS1(3), MME(6), NLN(2), THOP1(1) 5741924 55 46 55 22 11 23 8 4 9 0 0.0037 0.28 9 GLUCOCORTICOID_MINERALOCORTICOID_METABOLISM CPN2, CYP11A1, CYP11B2, CYP17A1, HSD11B1, HSD11B2, HSD3B1, HSD3B2 8 CPN2(1), CYP11A1(2), CYP11B2(6), CYP17A1(1), HSD11B1(3), HSD11B2(1), HSD3B1(4), HSD3B2(5) 1860812 23 21 22 5 3 11 4 4 1 0 0.0060 0.39 10 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 202 ACTN1(2), ACTN2(6), ACTN3(2), ACTN4(5), APC(9), APC2(2), ARAF(3), ARHGEF1(2), ARHGEF12(3), ARHGEF4(3), ARHGEF6(2), ARHGEF7(3), ARPC1A(2), ARPC1B(1), BCAR1(5), BDKRB1(3), BDKRB2(1), BRAF(7), CD14(1), CDC42(1), CFL1(3), CFL2(1), CHRM2(6), CHRM3(5), CHRM4(1), CHRM5(2), CRKL(1), CYFIP1(6), CYFIP2(7), DIAPH1(1), DIAPH3(5), DOCK1(3), EGF(6), EGFR(9), EZR(1), F2R(2), FGD1(3), FGD3(3), FGF10(2), FGF12(2), FGF14(1), FGF2(2), FGF23(1), FGF3(1), FGF5(3), FGF6(2), FGF8(1), FGFR1(3), FGFR2(6), FGFR3(2), FGFR4(1), FN1(17), GIT1(1), GNA12(1), GNA13(1), GNG12(1), GRLF1(11), GSN(2), HRAS(2), IQGAP1(6), IQGAP2(6), IQGAP3(11), ITGA1(4), ITGA10(6), ITGA11(3), ITGA2(5), ITGA2B(1), ITGA3(2), ITGA4(5), ITGA5(1), ITGA6(6), ITGA7(3), ITGA8(9), ITGA9(1), ITGAD(6), ITGAE(3), ITGAL(1), ITGAM(3), ITGAV(3), ITGAX(9), ITGB1(4), ITGB2(3), ITGB3(3), ITGB4(9), ITGB5(2), ITGB6(2), ITGB7(1), ITGB8(3), KRAS(1), LIMK1(1), LIMK2(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), MOS(4), MRAS(3), MSN(3), MYH10(3), MYH14(4), MYH9(14), MYL2(1), MYLK(7), MYLK2(2), MYLPF(1), NCKAP1(5), NCKAP1L(9), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PDGFB(1), PDGFRA(8), PDGFRB(5), PFN3(1), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PIP4K2A(2), PIP4K2B(3), PIP4K2C(3), PIP5K1A(4), PIP5K1B(1), PIP5K1C(2), PPP1CA(1), PPP1CB(1), PPP1CC(1), PPP1R12B(3), PTK2(3), PXN(3), RAC1(2), RAF1(1), RDX(1), ROCK1(5), ROCK2(3), RRAS2(2), SCIN(1), SLC9A1(3), SOS1(6), SOS2(4), SSH1(1), SSH2(7), TIAM1(9), TIAM2(4), VAV1(7), VAV2(4), VAV3(1), VCL(2), WAS(5), WASL(2) 75493894 527 153 523 165 122 198 93 47 67 0 0.0064 0.39 11 ACE2PATHWAY Angiotensin-converting enzyme 2 (ACE2) digests the blood-pressure regulator angiotensin II (AGT) ultimately to the vasodilator AGT1-7. ACE2, AGT, AGTR1, AGTR2, CMA1, COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6, REN 12 ACE2(3), AGT(1), AGTR1(3), AGTR2(4), CMA1(4), COL4A1(11), COL4A2(9), COL4A3(5), COL4A4(9), COL4A5(3), COL4A6(9) 6924734 61 52 61 22 15 31 7 0 8 0 0.0071 0.40 12 HSA04720_LONG_TERM_POTENTIATION Genes involved in long-term potentiation ADCY1, ADCY8, ARAF, ATF4, BRAF, CACNA1C, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CHP, CREBBP, EP300, GNAQ, GRIA1, GRIA2, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRM1, GRM5, HRAS, ITPR1, ITPR2, ITPR3, KRAS, MAP2K1, MAP2K2, MAPK1, MAPK3, NRAS, PLCB1, PLCB2, PLCB3, PLCB4, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R1A, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, RAF1, RAP1A, RAP1B, RAPGEF3, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6 64 ADCY1(8), ADCY8(13), ARAF(3), ATF4(1), BRAF(7), CACNA1C(16), CAMK2B(2), CAMK2D(1), CAMK4(3), CHP(2), CREBBP(12), EP300(5), GRIA1(6), GRIA2(3), GRIN1(1), GRIN2A(13), GRIN2C(2), GRIN2D(3), HRAS(2), ITPR1(5), ITPR2(11), ITPR3(3), KRAS(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PPP1CA(1), PPP1CB(1), PPP1CC(1), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCG(9), PRKX(1), RAF1(1), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KA6(3) 25589102 196 113 195 65 62 64 31 20 19 0 0.0084 0.43 13 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 245 ACVR1B(3), ACVR1C(3), AKT1(1), AKT3(2), ARRB1(3), ATF2(2), ATF4(1), BDNF(1), BRAF(7), CACNA1A(8), CACNA1B(1), CACNA1C(16), CACNA1D(3), CACNA1E(16), CACNA1F(8), CACNA1G(6), CACNA1H(5), CACNA1I(9), CACNA1S(8), CACNA2D1(8), CACNA2D2(5), CACNA2D3(2), CACNA2D4(5), CACNB1(1), CACNB2(2), CACNB3(2), CACNB4(3), CACNG3(2), CACNG4(2), CACNG6(1), CACNG7(4), CD14(1), CDC25B(3), CDC42(1), CHP(2), CHUK(2), CRKL(1), DAXX(3), DUSP10(3), DUSP16(2), DUSP4(1), DUSP5(4), DUSP6(1), DUSP7(1), DUSP9(4), EGF(6), EGFR(9), FAS(1), FASLG(1), FGF10(2), FGF12(2), FGF14(1), FGF2(2), FGF23(1), FGF3(1), FGF5(3), FGF6(2), FGF8(1), FGFR1(3), FGFR2(6), FGFR3(2), FGFR4(1), FLNA(9), FLNB(4), FLNC(13), FOS(1), GADD45A(1), GADD45G(1), GNA12(1), GNG12(1), HRAS(2), IKBKB(3), IL1B(1), IL1R2(3), JUN(2), KRAS(1), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K5(2), MAP2K6(3), MAP3K1(3), MAP3K12(2), MAP3K13(5), MAP3K14(1), MAP3K4(4), MAP3K5(3), MAP3K6(1), MAP3K7(3), MAP4K1(2), MAP4K2(1), MAP4K3(5), MAP4K4(6), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPK7(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(6), MAPK9(1), MAPKAPK2(1), MAPKAPK5(4), MAPT(5), MEF2C(2), MOS(4), MRAS(3), MYC(1), NFATC2(5), NFATC4(2), NFKB1(2), NFKB2(2), NLK(2), NR4A1(4), NTF3(3), NTRK1(3), NTRK2(1), PAK1(3), PAK2(1), PDGFB(1), PDGFRA(8), PDGFRB(5), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PPM1A(2), PPM1B(1), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PPP5C(1), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCG(9), PRKX(1), PTPN5(1), PTPRR(6), RAC1(2), RAF1(1), RAPGEF2(5), RASA1(6), RASA2(3), RASGRF1(5), RASGRF2(4), RASGRP1(1), RASGRP3(8), RASGRP4(4), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KA4(3), RPS6KA5(3), RPS6KA6(3), RRAS2(2), SOS1(6), SOS2(4), SRF(2), STK3(2), STK4(2), TAOK1(6), TAOK2(6), TAOK3(3), TGFB1(1), TGFB2(1), TGFBR2(3), TNFRSF1A(2), TRAF6(1), ZAK(1) 77878204 544 155 539 186 125 215 89 43 72 0 0.010 0.45 14 HSA04510_FOCAL_ADHESION Genes involved in focal adhesion ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, ARHGAP5, BAD, BCAR1, BCL2, BIRC2, BIRC3, BIRC4, BRAF, CAPN2, CAV1, CAV2, CAV3, CCND1, CCND2, CCND3, CDC42, CHAD, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, COMP, CRK, CRKL, CTNNB1, DIAPH1, DOCK1, EGF, EGFR, ELK1, ERBB2, FARP2, FIGF, FLNA, FLNB, FLNC, FLT1, FN1, FYN, GRB2, GRLF1, GSK3B, HGF, HRAS, IBSP, IGF1, IGF1R, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAV, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, JUN, KDR, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, LOC653852, MAP2K1, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MET, MLCK, MRCL3, MRLC2, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARVA, PARVB, PARVG, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP5K1C, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PRKCA, PRKCB1, PRKCG, PTEN, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RAP1A, RAP1B, RAPGEF1, RELN, RHOA, ROCK1, ROCK2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SPP1, SRC, THBS1, THBS2, THBS3, THBS4, TLN1, TLN2, TNC, TNN, TNR, TNXB, VASP, VAV1, VAV2, VAV3, VCL, VEGFA, VEGFB, VEGFC, VTN, VWF, ZYX 185 ACTB(1), ACTN1(2), ACTN2(6), ACTN3(2), ACTN4(5), AKT1(1), AKT3(2), BCAR1(5), BIRC3(3), BRAF(7), CAPN2(2), CAV2(1), CAV3(1), CCND1(1), CCND2(3), CCND3(1), CDC42(1), COL11A2(10), COL1A1(8), COL1A2(15), COL2A1(8), COL3A1(10), COL4A1(11), COL4A2(9), COL4A4(9), COL4A6(9), COL5A1(5), COL5A2(12), COL5A3(11), COL6A3(12), COMP(2), CRKL(1), CTNNB1(3), DIAPH1(1), DOCK1(3), EGF(6), EGFR(9), ERBB2(3), FARP2(6), FIGF(1), FLNA(9), FLNB(4), FLNC(13), FLT1(9), FN1(17), FYN(4), GRLF1(11), GSK3B(1), HGF(6), HRAS(2), IBSP(4), IGF1(2), IGF1R(1), ILK(1), ITGA1(4), ITGA10(6), ITGA11(3), ITGA2(5), ITGA2B(1), ITGA3(2), ITGA4(5), ITGA5(1), ITGA6(6), ITGA7(3), ITGA8(9), ITGA9(1), ITGAV(3), ITGB1(4), ITGB3(3), ITGB4(9), ITGB5(2), ITGB6(2), ITGB7(1), ITGB8(3), JUN(2), KDR(11), LAMA1(14), LAMA2(17), LAMA3(7), LAMA4(15), LAMA5(7), LAMB1(6), LAMB2(4), LAMB3(1), LAMB4(3), LAMC1(8), LAMC2(4), LAMC3(1), MAP2K1(2), MAPK1(1), MAPK10(1), MAPK3(2), MAPK8(2), MAPK9(1), MET(3), MYL2(1), MYLK(7), MYLK2(2), MYLPF(1), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PARVB(1), PARVG(1), PDGFB(1), PDGFC(1), PDGFD(1), PDGFRA(8), PDGFRB(5), PDPK1(1), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PIP5K1C(2), PPP1CA(1), PPP1CB(1), PPP1CC(1), PRKCA(5), PRKCG(9), PTK2(3), PXN(3), RAC1(2), RAF1(1), RAPGEF1(3), RELN(26), ROCK1(5), ROCK2(3), SHC1(1), SHC2(3), SHC3(3), SHC4(4), SOS1(6), SOS2(4), THBS1(1), THBS3(4), TLN1(8), TLN2(11), TNC(16), TNXB(16), VASP(2), VAV1(7), VAV2(4), VAV3(1), VCL(2), VEGFC(4), VWF(16) 96547022 722 162 718 245 193 273 125 54 77 0 0.010 0.45 15 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 61 AKT1(1), AKT3(2), BLNK(1), BTK(5), CARD11(3), CD19(2), CD22(5), CD79A(1), CD81(1), CHP(2), CHUK(2), CR2(9), FCGR2B(2), FOS(1), GSK3B(1), HRAS(2), IKBKB(3), INPP5D(6), JUN(2), KRAS(1), LILRB3(3), LYN(1), MALT1(2), NFAT5(3), NFATC2(5), NFATC3(3), NFATC4(2), NFKB1(2), NFKB2(2), NFKBIB(1), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLCG2(3), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), RAC1(2), RASGRP3(8), SYK(1), VAV1(7), VAV2(4), VAV3(1) 19679502 138 92 138 46 36 42 18 20 22 0 0.011 0.45 16 MONOAMINE_GPCRS ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2C, ADRB1, ADRB2, ADRB3, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, DRD1, DRD2, DRD3, DRD4, DRD5, HRH1, HRH2, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, HTR7, LOC93164 31 ADRA1A(2), ADRA1B(4), ADRA1D(2), ADRA2C(2), ADRB2(3), CHRM2(6), CHRM3(5), CHRM4(1), CHRM5(2), DRD1(1), DRD2(2), DRD3(5), DRD4(1), DRD5(3), HRH1(3), HRH2(2), HTR1B(3), HTR1D(1), HTR1E(5), HTR1F(2), HTR2A(1), HTR2B(2), HTR2C(3), HTR4(3), HTR5A(3), HTR6(1), HTR7(3) 6776282 71 51 71 28 18 25 20 3 5 0 0.016 0.61 17 GPCRDB_CLASS_C_METABOTROPIC_GLUTAMATE_PHEROMONE CASR, GABBR1, GPCR5A, GPR51, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GRM1, GRM2, GRM3, GRM4, GRM5, GRM7, GRM8 10 CASR(8), GABBR1(3), GPRC5A(1), GPRC5C(4), GPRC5D(1), GRM2(3), GRM4(1), GRM7(8), GRM8(9) 3921696 38 33 38 22 8 12 8 5 5 0 0.020 0.70 18 PEPTIDE_GPCRS AGTR1, AGTR2, ATP8A1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BLR1, BRS3, C3AR1, C5R1, CCKAR, CCKBR, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CX3CR1, CXCR3, CXCR4, CXCR6, EDNRA, EDNRB, ELA3A, FPR1, FPRL1, FPRL2, FSHR, FY, GALR1, GALR2, GALR3, GALT, GHSR, GNB2L1, GNRHR, GPR77, GRPR, IL8RA, IL8RB, LHCGR, MC1R, MC2R, MC3R, MC4R, MC5R, NMBR, NPY1R, NPY2R, NPY5R, NPY6R, NTSR1, NTSR2, OPRD1, OPRK1, OPRL1, OPRM1, OXTR, PPYR1, SSTR1, SSTR2, SSTR3, SSTR4, TAC4, TACR1, TACR2, TACR3, TRHR, TSHR 63 AGTR1(3), AGTR2(4), ATP8A1(6), AVPR1A(3), AVPR1B(2), AVPR2(1), BDKRB1(3), BDKRB2(1), C3AR1(1), CCKAR(2), CCKBR(1), CCR1(2), CCR10(1), CCR3(1), CCR4(3), CCR6(2), CCR8(3), CX3CR1(3), CXCR3(1), EDNRA(2), EDNRB(5), FPR1(1), GALR1(3), GALT(1), GHSR(3), GPR77(4), GRPR(2), LHCGR(8), MC2R(2), MC3R(3), MC4R(1), MC5R(3), NMBR(2), NPY1R(3), NPY2R(2), NPY5R(2), NTSR1(3), NTSR2(3), OPRD1(2), OPRK1(1), OPRM1(2), OXTR(1), PPYR1(3), SSTR1(1), SSTR2(2), SSTR3(1), SSTR4(2), TACR1(2), TACR3(3), TRHR(1), TSHR(1) 13275596 118 74 117 50 32 44 18 4 20 0 0.022 0.70 19 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(6), CYP2C9(2) 537204 8 8 8 3 3 1 3 0 1 0 0.023 0.70 20 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(1), GRIN1(1), GRIN2A(13), GRIN2C(2), GRIN2D(3), NOS1(10), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), SYT1(3) 6076030 57 45 57 20 18 19 5 7 8 0 0.023 0.70 21 HSA04730_LONG_TERM_DEPRESSION Genes involved in long-term depression ARAF, BRAF, C7orf16, CACNA1A, CRH, CRHR1, GNA11, GNA12, GNA13, GNAI1, GNAI2, GNAI3, GNAO1, GNAQ, GNAS, GNAZ, GRIA1, GRIA2, GRIA3, GRID2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, IGF1, IGF1R, ITPR1, ITPR2, ITPR3, KRAS, LYN, MAP2K1, MAP2K2, MAPK1, MAPK3, NOS1, NOS2A, NOS3, NPR1, NPR2, NRAS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCB1, PLCB2, PLCB3, PLCB4, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, RAF1, RYR1 71 ARAF(3), BRAF(7), C7orf16(1), CACNA1A(8), CRHR1(4), GNA12(1), GNA13(1), GNAI1(2), GNAI3(1), GNAS(4), GNAZ(2), GRIA1(6), GRIA2(3), GRIA3(9), GRID2(12), GUCY1A3(6), GUCY1B3(3), GUCY2C(4), GUCY2D(1), GUCY2F(8), HRAS(2), IGF1(2), IGF1R(1), ITPR1(5), ITPR2(11), ITPR3(3), KRAS(1), LYN(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), NOS1(10), NOS3(1), NPR1(2), NPR2(5), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PPP2R1A(6), PPP2R1B(2), PPP2R2A(1), PPP2R2B(2), PPP2R2C(2), PRKCA(5), PRKCG(9), PRKG1(5), PRKG2(5), RAF1(1), RYR1(29) 28702856 244 113 242 77 63 94 40 17 30 0 0.026 0.70 22 AGPCRPATHWAY G-protein coupled receptors (GPCRs) transduce extracellular signals across the plasma membrane; attenuation occurs by signal molecule degradation or receptor-mediated endocytosis. ARRB1, GNAS, GNB1, GNGT1, GPRK2L, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1 11 ARRB1(3), GNAS(4), GNB1(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5) 2534364 23 23 23 8 5 11 3 1 3 0 0.026 0.70 23 CARDIACEGFPATHWAY Cardiac hypertrophy, a response to high blood pressure, is stimulated by GPCR ligands such as angiotensin II that activate the EGF pathway. ADAM12, AGT, AGTR2, ARHA, EDN1, EDNRA, EDNRB, EGF, EGFR, FOS, HRAS, JUN, MYC, NFKB1, PLCG1, PRKCA, PRKCB1, RELA 16 ADAM12(5), AGT(1), AGTR2(4), EDN1(1), EDNRA(2), EDNRB(5), EGF(6), EGFR(9), FOS(1), HRAS(2), JUN(2), MYC(1), NFKB1(2), PLCG1(2), PRKCA(5), RELA(3) 5560898 51 41 50 15 10 20 7 4 10 0 0.026 0.70 24 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 161 ADCY1(8), ADCY3(5), ADCY4(4), ADCY7(4), ADCY8(13), ADCY9(4), ADORA2A(6), ADORA2B(1), ADRA1A(2), ADRA1B(4), ADRA1D(2), ADRB2(3), AGTR1(3), ATP2A1(2), ATP2A2(6), ATP2A3(2), ATP2B1(4), ATP2B2(6), ATP2B3(3), ATP2B4(5), AVPR1A(3), AVPR1B(2), BDKRB1(3), BDKRB2(1), BST1(1), CACNA1A(8), CACNA1B(1), CACNA1C(16), CACNA1D(3), CACNA1E(16), CACNA1F(8), CACNA1G(6), CACNA1H(5), CACNA1I(9), CACNA1S(8), CAMK2B(2), CAMK2D(1), CAMK4(3), CCKAR(2), CCKBR(1), CD38(1), CHP(2), CHRM2(6), CHRM3(5), CHRM5(2), CYSLTR1(3), CYSLTR2(1), DRD1(1), EDNRA(2), EDNRB(5), EGFR(9), ERBB2(3), ERBB3(3), ERBB4(9), F2R(2), GNA14(1), GNA15(1), GNAL(2), GNAS(4), GRIN1(1), GRIN2A(13), GRIN2C(2), GRIN2D(3), GRPR(2), HRH1(3), HRH2(2), HTR2A(1), HTR2B(2), HTR2C(3), HTR4(3), HTR5A(3), HTR6(1), HTR7(3), ITPKA(1), ITPKB(3), ITPR1(5), ITPR2(11), ITPR3(3), LHCGR(8), LTB4R2(1), MYLK(7), MYLK2(2), NOS1(10), NOS3(1), NTSR1(3), OXTR(1), P2RX2(1), P2RX3(5), P2RX4(2), P2RX7(1), PDE1A(2), PDE1B(1), PDGFRA(8), PDGFRB(5), PHKA1(4), PHKA2(4), PHKB(6), PHKG1(2), PHKG2(1), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PLCD3(2), PLCE1(10), PLCG1(2), PLCG2(3), PLCZ1(3), PLN(1), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCG(9), PRKX(1), PTAFR(3), PTGER3(5), PTGFR(2), RYR1(29), SLC8A3(3), SPHK2(1), TACR1(2), TACR3(3), TBXA2R(2), TNNC1(1), TNNC2(1), TRHR(1), TRPC1(5), VDAC1(1), VDAC2(1) 66805002 521 152 519 180 162 185 78 44 52 0 0.027 0.70 25 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 27 ACTA1(2), AKT1(1), BDKRB2(1), CHRNA1(2), FLT1(9), FLT4(3), KDR(11), NOS3(1), PDE2A(3), PDE3A(5), PDE3B(3), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKG1(5), PRKG2(5), SLC7A1(5), SYT1(3), TNNI1(1) 8525844 70 56 70 35 22 20 9 8 11 0 0.029 0.71 26 NICOTINATE_AND_NICOTINAMIDE_METABOLISM AOX1, CD38, ENPP1, ENPP3, NADSYN1, NMNAT1, NMNAT2, NNMT, NNT, NP, NT5C, NT5E, NT5M, QPRT 12 AOX1(11), CD38(1), ENPP1(7), ENPP3(4), NMNAT1(3), NMNAT2(2), NNMT(1), NNT(7), NT5E(2) 3568188 38 32 37 6 13 14 4 4 3 0 0.030 0.71 27 NO2IL12PATHWAY Macrophages activate NK cells by releasing IL-12, which induces NK cytotoxic activity in coordination with NO produced by inducible nitric oxide synthase II. CCR5, CD2, CD3D, CD3E, CD3G, CD3Z, CD4, CXCR3, IFNG, IL12A, IL12B, IL12RB1, IL12RB2, JAK2, NOS2A, STAT4, TYK2 14 CD2(1), CD3D(1), CD4(2), CXCR3(1), IFNG(1), IL12A(1), IL12B(3), IL12RB1(3), IL12RB2(3), JAK2(3), STAT4(4), TYK2(8) 3830026 31 30 31 9 7 9 6 2 7 0 0.032 0.71 28 HSA04650_NATURAL_KILLER_CELL_MEDIATED_CYTOTOXICITY Genes involved in natural killer cell mediated cytotoxicity ARAF, BID, BRAF, CASP3, CD244, CD247, CD48, CHP, CSF2, FAS, FASLG, FCER1G, FCGR3A, FCGR3B, FYN, GRB2, GZMB, HCST, HLA-A, HLA-B, HLA-C, HLA-E, HLA-G, HRAS, ICAM1, ICAM2, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNG, IFNGR1, IFNGR2, ITGAL, ITGB2, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DS1, KIR2DS2, KIR3DL1, KIR3DL2, KLRC1, KLRC2, KLRC3, KLRD1, KLRK1, KRAS, LAT, LCK, LCP2, LOC652578, MAP2K1, MAP2K2, MAPK1, MAPK3, MICA, MICB, NCR1, NCR2, NCR3, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NRAS, PAK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRF1, PRKCA, PRKCB1, PRKCG, PTK2B, PTPN11, PTPN6, RAC1, RAC2, RAC3, RAF1, SH2D1A, SH2D1B, SH3BP2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SYK, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFSF10, TYROBP, ULBP1, ULBP2, ULBP3, VAV1, VAV2, VAV3, ZAP70 122 ARAF(3), BID(1), BRAF(7), CD244(1), CHP(2), FAS(1), FASLG(1), FCGR3A(3), FCGR3B(2), FYN(4), GZMB(1), HLA-B(1), HLA-C(1), HLA-G(1), HRAS(2), ICAM1(2), IFNA1(1), IFNA10(1), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNAR1(2), IFNB1(1), IFNG(1), IFNGR1(3), IFNGR2(1), ITGAL(1), ITGB2(3), KIR2DL1(3), KIR2DL3(4), KIR3DL1(6), KIR3DL2(1), KLRC1(1), KLRC3(1), KRAS(1), LAT(1), LCK(2), LCP2(2), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), NCR1(5), NCR2(1), NFAT5(3), NFATC2(5), NFATC3(3), NFATC4(2), PAK1(3), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLCG1(2), PLCG2(3), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRF1(2), PRKCA(5), PRKCG(9), PTPN11(3), RAC1(2), RAF1(1), SH2D1A(1), SH3BP2(2), SHC1(1), SHC2(3), SHC3(3), SHC4(4), SOS1(6), SOS2(4), SYK(1), TNFRSF10A(1), TNFRSF10B(1), TNFRSF10D(1), ULBP1(1), ULBP3(1), VAV1(7), VAV2(4), VAV3(1), ZAP70(3) 29957578 214 112 214 68 56 77 41 20 20 0 0.033 0.71 29 IL12PATHWAY IL12 and Stat4 Dependent Signaling Pathway in Th1 Development CCR5, CD3D, CD3E, CD3G, CD3Z, CXCR3, ETV5, IFNG, IL12A, IL12B, IL12RB1, IL12RB2, IL18, IL18R1, JAK2, JUN, MAP2K6, MAPK14, MAPK8, STAT4, TRA@, TRB@, TYK2 19 CD3D(1), CXCR3(1), ETV5(3), IFNG(1), IL12A(1), IL12B(3), IL12RB1(3), IL12RB2(3), IL18R1(2), JAK2(3), JUN(2), MAP2K6(3), MAPK14(1), MAPK8(2), STAT4(4), TYK2(8) 4886634 41 38 41 10 9 16 7 3 6 0 0.033 0.71 30 STEROID_BIOSYNTHESIS CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 9 CYP17A1(1), F13B(7), HSD17B1(1), HSD17B4(1), HSD17B7(1), HSD3B1(4), HSD3B2(5) 2187264 20 20 19 4 6 6 4 3 1 0 0.036 0.71 31 ERBB4PATHWAY ErbB4 (aka HER4) is a receptor tyrosine kinase that binds neuregulins as well as members of the EGF family, which also target EGF receptors. ADAM17, ERBB4, NRG2, NRG3, PRKCA, PRKCB1, PSEN1 6 ERBB4(9), NRG2(2), NRG3(5), PRKCA(5), PSEN1(1) 2417774 22 22 22 8 3 9 3 2 5 0 0.036 0.71 32 INTRINSICPATHWAY The intrinsic prothrombin activation pathway is activated by traumatized blood vessels and induces clot formation. COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6, F10, F11, F12, F2, F2R, F5, F8, F9, FGA, FGB, FGG, KLKB1, KNG, PROC, PROS1, SERPINC1, SERPING1 22 COL4A1(11), COL4A2(9), COL4A3(5), COL4A4(9), COL4A5(3), COL4A6(9), F10(3), F11(4), F12(1), F2R(2), F5(15), F8(10), F9(4), FGA(5), FGB(3), FGG(1), KLKB1(4), SERPINC1(5) 12073384 103 69 103 31 22 47 20 3 11 0 0.039 0.76 33 HSA00592_ALPHA_LINOLENIC_ACID_METABOLISM Genes involved in alpha-Linolenic acid metabolism ACOX1, ACOX3, FADS2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6 15 ACOX1(2), ACOX3(4), FADS2(1), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6) 2761848 27 24 27 4 6 7 6 3 5 0 0.044 0.81 34 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 21 AOX1(11), BST1(1), CD38(1), ENPP1(7), ENPP3(4), NMNAT1(3), NMNAT2(2), NNMT(1), NNT(7), NT5C1A(2), NT5C1B(2), NT5C2(3), NT5C3(4), NT5E(2), NUDT12(2) 5471720 52 42 51 10 17 19 7 4 5 0 0.045 0.81 35 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 81 ACVR1B(3), ACVRL1(3), AKT1(1), BMPR1A(3), BUB1(4), CDKL1(1), CDKL2(2), CDS1(2), CLK1(3), CLK2(2), CLK4(2), COL4A3BP(3), CSNK2A1(2), DGKA(6), DGKB(4), DGKD(5), DGKE(2), DGKG(2), DGKZ(3), IMPA1(1), INPP1(1), INPP4A(5), INPP4B(4), INPP5A(3), INPPL1(3), ITPKA(1), ITPKB(3), MOS(4), NEK1(3), NEK3(1), OCRL(5), PAK4(1), PIK3C2A(4), PIK3C2B(7), PIK3C2G(7), PIK3CB(1), PIK3CG(10), PIM2(2), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PLCG1(2), PLCG2(3), PLK3(3), PRKACA(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), PRKCD(2), PRKCE(5), PRKCG(9), PRKCH(1), PRKCQ(4), PRKD1(9), PRKG1(5), RAF1(1), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KA4(3), RPS6KB1(1), STK11(3), VRK1(1) 30579510 214 111 213 60 64 74 36 15 25 0 0.048 0.85 36 MTA3PATHWAY The estrogen receptor regulates proliferation in mammary epithelia via MTA3 activation; loss of either protein is implicated in breast cancer. ALDOA, CTSD, ESR1, GAPD, GREB1, HSPB1, HSPB2, MTA1, MTA3, PDZK1, TUBA1, TUBA2, TUBA3, TUBA4, TUBA6, TUBA8 10 ALDOA(1), CTSD(1), ESR1(6), GREB1(15), HSPB2(1), MTA1(2), MTA3(3), TUBA8(1) 3050208 30 27 30 10 9 13 6 1 1 0 0.053 0.91 37 STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR 9 EPX(5), GBA3(6), LPO(2), MPO(3), PRDX1(1), PRDX6(1), TYR(3) 2183170 21 19 21 7 3 6 10 0 2 0 0.055 0.92 38 TIDPATHWAY On ligand binding, interferon gamma receptors stimulate JAK2 kinase to phosphorylate STAT transcription factors, which promote expression of interferon responsive genes. DNAJA3, HSPA1A, IFNG, IFNGR1, IFNGR2, IKBKB, JAK2, LIN7A, NFKB1, NFKBIA, RB1, RELA, TIP-1, TNF, TNFRSF1A, TNFRSF1B, TP53, USH1C, WT1 17 IFNG(1), IFNGR1(3), IFNGR2(1), IKBKB(3), JAK2(3), LIN7A(2), NFKB1(2), RB1(7), RELA(3), TNFRSF1A(2), TNFRSF1B(1), USH1C(5), WT1(4) 4848186 37 33 37 7 6 11 9 3 8 0 0.058 0.94 39 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 ALDH6A1(2), TPI1(4) 435032 6 6 5 1 4 1 1 0 0 0 0.060 0.94 40 PLCEPATHWAY Gs-coupled receptors activate adenylyl cyclase, which activates Epac1, leading to the stimulation of PLC and subsequent DAG and IP3 production. ADCY1, ADRB2, GNAS, PLCE1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTGER1, RAP2B 12 ADCY1(8), ADRB2(3), GNAS(4), PLCE1(10), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 3962102 35 32 34 11 15 9 5 3 3 0 0.062 0.95 41 CBLPATHWAY Activated EGF receptors undergo endocytosis into clathrin-coated vesicles, where they are recycled to the membrane or ubiquitinated by Cbl. CBL, CSF1R, EGF, EGFR, GRB2, MET, PDGFRA, PRKCA, PRKCB1, SH3GLB1, SH3GLB2, SH3KBP1, SRC 12 CBL(4), CSF1R(3), EGF(6), EGFR(9), MET(3), PDGFRA(8), PRKCA(5), SH3GLB1(1), SH3KBP1(7) 5214866 46 39 45 10 11 20 6 3 6 0 0.064 0.96 42 MCALPAINPATHWAY In integrin-mediated cell migration, calpains digest links between the actin cytoskeleton and focal adhesion proteins. ACTA1, CAPN1, CAPN2, CAPNS1, CAPNS2, CXCR3, EGF, EGFR, HRAS, ITGA1, ITGB1, MAPK1, MAPK3, MYL2, MYLK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTK2, PXN, TLN1, VIL2 24 ACTA1(2), CAPN1(2), CAPN2(2), CAPNS2(1), CXCR3(1), EGF(6), EGFR(9), HRAS(2), ITGA1(4), ITGB1(4), MAPK1(1), MAPK3(2), MYL2(1), MYLK(7), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PTK2(3), PXN(3), TLN1(8) 8846956 68 55 66 19 17 27 8 7 9 0 0.065 0.96 43 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 73 AKT1(1), AKT3(2), BTK(5), FCER1A(1), FYN(4), HRAS(2), IL4(2), INPP5D(6), KRAS(1), LAT(1), LCP2(2), LYN(1), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K6(3), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPK8(2), MAPK9(1), MS4A2(2), PDK1(1), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLCG1(2), PLCG2(3), PRKCA(5), PRKCD(2), PRKCE(5), RAC1(2), RAF1(1), SOS1(6), SOS2(4), SYK(1), VAV1(7), VAV2(4), VAV3(1) 19044220 136 88 136 41 34 48 23 13 18 0 0.069 0.99 44 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(1), GABARAP(1), GABRA1(6), GABRA3(5), GABRA4(3), GABRA5(4), GPHN(1), NSF(2), UBQLN1(2) 2732656 25 24 25 6 7 13 4 0 1 0 0.075 1.00 45 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 29 AKR1C4(1), AKR1D1(4), ARSB(2), ARSD(1), ARSE(2), CYP11B2(6), HSD11B1(3), HSD11B2(1), HSD3B1(4), HSD3B2(5), SRD5A1(2), SRD5A2(2), STS(3), SULT1E1(1), SULT2A1(3), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2B15(1), UGT2B4(4) 6786072 56 45 55 10 14 18 11 7 6 0 0.076 1.00 46 GSPATHWAY Activated G-protein coupled receptors stimulate cAMP production and thus activate protein kinase A, involved in a number of signal transduction pathways. ADCY1, GNAS, GNB1, GNGT1, PRKACA, PRKAR1A 6 ADCY1(8), GNAS(4), GNB1(1), PRKACA(1), PRKAR1A(3) 1804742 17 17 17 5 7 5 3 1 1 0 0.081 1.00 47 HSA00780_BIOTIN_METABOLISM Genes involved in biotin metabolism BTD, HLCS, SPCS1, SPCS3 4 BTD(1), HLCS(5), SPCS1(1), SPCS3(2) 845144 9 8 9 2 0 2 2 1 4 0 0.082 1.00 48 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(1), ACTN1(2), ACTN2(6), ACTN3(2), ACTN4(5), AKT1(1), AKT3(2), AMOTL1(2), ASH1L(10), CASK(1), CDC42(1), CGN(5), CLDN1(2), CLDN10(4), CLDN16(4), CLDN17(1), CLDN19(1), CLDN2(1), CLDN22(1), CLDN3(1), CLDN6(1), CLDN8(2), CLDN9(3), CSDA(2), CSNK2A1(2), CTNNB1(3), CTTN(4), EPB41(2), EPB41L1(4), EPB41L2(1), EXOC3(2), EXOC4(2), F11R(1), GNAI1(2), GNAI3(1), HCLS1(3), HRAS(2), IGSF5(1), INADL(9), KRAS(1), LLGL1(1), LLGL2(2), MAGI1(5), MAGI2(7), MAGI3(2), MLLT4(3), MPDZ(4), MPP5(2), MRAS(3), MYH1(13), MYH10(3), MYH11(8), MYH13(10), MYH14(4), MYH15(11), MYH3(5), MYH4(14), MYH6(12), MYH7(9), MYH7B(4), MYH9(14), MYL2(1), MYLPF(1), PARD3(5), PARD6A(2), PPM1J(1), PPP2R1A(6), PPP2R1B(2), PPP2R2A(1), PPP2R2B(2), PPP2R2C(2), PPP2R3A(2), PPP2R4(1), PRKCA(5), PRKCD(2), PRKCE(5), PRKCG(9), PRKCH(1), PRKCI(4), PRKCQ(4), RAB13(1), RAB3B(1), RRAS2(2), SPTAN1(2), SYMPK(6), TJAP1(3), TJP1(9), TJP2(5), TJP3(2), VAPA(1), YES1(1), ZAK(1) 48885030 327 136 327 119 81 114 60 31 41 0 0.083 1.00 49 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(2), ACTN2(6), ACTN3(2), ACTN4(5), DES(2), DMD(20), FAM48A(1), MYBPC1(11), MYBPC3(3), MYH3(5), MYH6(12), MYH7(9), MYL1(4), MYL2(1), MYL3(2), MYOM1(8), NEB(23), TNNC2(1), TNNI1(1), TNNI2(1), TNNI3(2), TNNT1(1), TNNT2(2), TNNT3(3), TPM3(2), VIM(5) 16816728 134 82 133 56 42 40 25 10 17 0 0.086 1.00 50 REELINPATHWAY Reelin is secreted by neurons and recognized by receptors including cadherin related neuronal receptors, which promote phosphorylation of Dab1. CDK5, CDK5R1, DAB1, FYN, LRP8, RELN, VLDLR 7 CDK5(2), DAB1(5), FYN(4), LRP8(1), RELN(26), VLDLR(1) 3755444 39 28 39 11 7 13 10 7 2 0 0.087 1.00 51 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 20 ANPEP(5), CD2(1), CD33(2), CD5(3), IFNA1(1), IFNB1(1), IFNG(1), IL10(1), IL12A(1), IL12B(3), IL4(2), ITGAX(9), TLR2(3), TLR7(3), TLR9(1) 4550748 37 34 35 13 10 15 5 2 5 0 0.089 1.00 52 FXRPATHWAY The nuclear receptor transcription factors FXR and LXR are activated by cholesterol metabolites and regulate cholesterol homeostasis. FABP6, LDLR, NR0B2, NR1H3, NR1H4, RXRA 6 FABP6(1), LDLR(4), NR0B2(1), NR1H3(2), NR1H4(4), RXRA(1) 1464406 13 13 13 3 4 4 2 1 2 0 0.094 1.00 53 LYSINE_BIOSYNTHESIS AADAT, AASDH, AASDHPPT, AASS, KARS 5 AADAT(1), AASDH(6), AASDHPPT(1), AASS(6), KARS(3) 1862592 17 17 17 4 3 6 4 2 2 0 0.095 1.00 54 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 28 B3GNT6(1), B4GALT5(3), C1GALT1C1(1), GALNT1(1), GALNT10(2), GALNT11(2), GALNT12(3), GALNT14(4), GALNT2(4), GALNT3(2), GALNT5(6), GALNT6(2), GALNT7(1), GALNT8(2), GALNTL1(3), GALNTL2(1), GALNTL4(4), GALNTL5(3), GCNT1(3), GCNT3(3), OGT(2), ST3GAL1(1), ST3GAL2(2), ST6GALNAC1(6) 8069986 62 53 60 20 9 31 14 3 5 0 0.096 1.00 55 PPARGPATHWAY PPAR-gamma is a nuclear hormone receptor that is activated by fatty acids and regulates transcription through co-activations like Src-1 and Tif2. CREBBP, EP300, LPL, NCOA1, NCOA2, PPARBP, PPARG, PPARGC1, RXRA 7 CREBBP(12), EP300(5), LPL(3), NCOA1(6), NCOA2(10), RXRA(1) 4966378 37 34 36 14 6 16 7 3 5 0 0.10 1.00 56 NUCLEOTIDE_GPCRS ADORA1, ADORA2A, ADORA2B, ADORA3, GPR23, LTB4R, P2RY1, P2RY2, P2RY5, P2RY6 8 ADORA1(4), ADORA2A(6), ADORA2B(1), P2RY1(1), P2RY2(2), P2RY6(2) 1601110 16 15 16 5 7 7 1 0 1 0 0.11 1.00 57 SMALL_LIGAND_GPCRS C9orf47, CNR1, CNR2, DNMT1, EDG1, EDG2, EDG5, EDG6, MTNR1A, MTNR1B, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, TBXA2R 13 CNR1(3), CNR2(3), DNMT1(4), MTNR1A(1), PTAFR(3), PTGDR(5), PTGER2(1), PTGER4(2), PTGFR(2), PTGIR(1), TBXA2R(2) 2971888 27 24 27 10 10 9 6 0 2 0 0.11 1.00 58 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 5 ARG1(2), ASL(2), GLS(2), GLUD1(3), GOT1(2) 1178716 11 11 10 3 1 7 1 0 2 0 0.11 1.00 59 SPRYPATHWAY Four members of the Sprouty protein family block proliferative EGF signals by binding Grb-2, preventing Ras and MAP kinase activation. CBL, EGF, EGFR, GRB2, HRAS, MAP2K1, MAPK1, MAPK3, PTPRB, RAF1, RASA1, SHC1, SOS1, SPRY1, SPRY2, SPRY3, SPRY4, SRC 17 CBL(4), EGF(6), EGFR(9), HRAS(2), MAP2K1(2), MAPK1(1), MAPK3(2), PTPRB(15), RAF1(1), RASA1(6), SHC1(1), SOS1(6) 6589916 55 42 54 11 15 19 8 3 10 0 0.11 1.00 60 PROSTAGLANDIN_SYNTHESIS_REGULATION ANXA1, ANXA2, ANXA3, ANXA4, ANXA5, ANXA6, ANXA8, CYP11A1, EDN1, EDNRA, EDNRB, HPGD, HSD11B1, HSD11B2, PLA2G4A, PRL, PTGDR, PTGDS, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, PTGIS, PTGS1, PTGS2, S100A6, SCGB1A1, TBXAS1 28 ANXA4(1), ANXA5(2), ANXA6(6), CYP11A1(2), EDN1(1), EDNRA(2), EDNRB(5), HSD11B1(3), HSD11B2(1), PLA2G4A(5), PRL(1), PTGDR(5), PTGER2(1), PTGER4(2), PTGFR(2), PTGIR(1), PTGS1(2), TBXAS1(5) 5652568 47 39 45 15 9 19 8 3 8 0 0.12 1.00 61 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(2), ABLIM1(2), ABLIM2(2), ABLIM3(2), ARHGEF12(3), CDC42(1), CDK5(2), CFL1(3), CFL2(1), CHP(2), DCC(12), DPYSL2(2), DPYSL5(5), EFNA1(1), EFNA3(1), EFNB1(2), EFNB2(1), EPHA1(4), EPHA2(1), EPHA3(6), EPHA4(1), EPHA7(7), EPHA8(3), EPHB2(5), EPHB3(9), EPHB4(2), EPHB6(4), FES(1), FYN(4), GNAI1(2), GNAI3(1), GSK3B(1), HRAS(2), ITGB1(4), KRAS(1), L1CAM(2), LIMK1(1), LIMK2(1), MAPK1(1), MAPK3(2), MET(3), NCK1(3), NFAT5(3), NFATC2(5), NFATC3(3), NFATC4(2), NGEF(1), NRP1(4), NTN1(2), NTN4(1), NTNG1(1), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PLXNA1(10), PLXNA2(6), PLXNA3(3), PLXNB1(4), PLXNB3(3), PLXNC1(9), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PTK2(3), RAC1(2), RASA1(6), RGS3(4), ROBO1(7), ROBO2(6), ROBO3(5), ROCK1(5), ROCK2(3), SEMA3A(3), SEMA3B(1), SEMA3C(5), SEMA3D(2), SEMA3E(3), SEMA3F(3), SEMA3G(1), SEMA4A(2), SEMA4B(1), SEMA4C(2), SEMA4D(1), SEMA4F(5), SEMA4G(1), SEMA5A(7), SEMA5B(4), SEMA6C(4), SEMA6D(6), SEMA7A(1), SLIT1(4), SLIT2(9), SLIT3(11), SRGAP1(2), SRGAP2(5), SRGAP3(3), UNC5B(2), UNC5C(6) 51489348 334 133 334 137 80 124 53 29 48 0 0.12 1.00 62 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 6 DBH(2), GAD1(5), HDC(3), PNMT(2), TH(2), TPH1(1) 1656468 15 14 15 3 3 7 2 1 2 0 0.12 1.00 63 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 88 ADCY1(8), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), DRD1(1), DRD2(2), EGF(6), EGFR(9), GJA1(4), GJD2(2), GNAI1(2), GNAI3(1), GNAS(4), GUCY1A3(6), GUCY1B3(3), GUCY2C(4), GUCY2D(1), GUCY2F(8), HRAS(2), HTR2A(1), HTR2B(2), HTR2C(3), ITPR1(5), ITPR2(11), ITPR3(3), KRAS(1), MAP2K1(2), MAP2K2(2), MAP2K5(2), MAPK1(1), MAPK3(2), MAPK7(1), NPR1(2), NPR2(5), PDGFB(1), PDGFC(1), PDGFD(1), PDGFRA(8), PDGFRB(5), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCG(9), PRKG1(5), PRKG2(5), PRKX(1), RAF1(1), SOS1(6), SOS2(4), TJP1(9), TUBA1B(1), TUBA3C(5), TUBA3D(4), TUBA3E(3), TUBA8(1), TUBAL3(2), TUBB(1), TUBB1(1), TUBB2A(1), TUBB4(4), TUBB4Q(2), TUBB8(2) 33858982 251 118 249 86 81 85 40 20 25 0 0.14 1.00 64 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 80 AGRN(2), CD36(1), CD44(3), CD47(2), COL11A2(10), COL1A1(8), COL1A2(15), COL2A1(8), COL3A1(10), COL4A1(11), COL4A2(9), COL4A4(9), COL4A6(9), COL5A1(5), COL5A2(12), COL5A3(11), COL6A3(12), DAG1(1), FN1(17), FNDC1(7), FNDC3A(1), GP5(4), GP6(3), GP9(1), HMMR(1), HSPG2(8), IBSP(4), ITGA1(4), ITGA10(6), ITGA11(3), ITGA2(5), ITGA2B(1), ITGA3(2), ITGA4(5), ITGA5(1), ITGA6(6), ITGA7(3), ITGA8(9), ITGA9(1), ITGAV(3), ITGB1(4), ITGB3(3), ITGB4(9), ITGB5(2), ITGB6(2), ITGB7(1), ITGB8(3), LAMA1(14), LAMA2(17), LAMA3(7), LAMA4(15), LAMA5(7), LAMB1(6), LAMB2(4), LAMB3(1), LAMB4(3), LAMC1(8), LAMC2(4), LAMC3(1), RELN(26), SDC3(1), SV2A(3), SV2B(3), SV2C(3), THBS1(1), THBS3(4), TNC(16), TNXB(16), VWF(16) 57882752 433 140 432 146 120 167 80 21 45 0 0.14 1.00 65 INOSITOL_METABOLISM ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 5 ALDH6A1(2), ALDOA(1), ALDOB(2), ALDOC(1), TPI1(4) 1036850 10 10 9 3 5 3 2 0 0 0 0.14 1.00 66 HSA00520_NUCLEOTIDE_SUGARS_METABOLISM Genes involved in nucleotide sugars metabolism GALE, GALT, TGDS, UGDH, UGP2, UXS1 6 GALE(1), GALT(1), TGDS(1), UGDH(3), UGP2(5), UXS1(3) 1352088 14 12 14 1 0 7 4 1 2 0 0.15 1.00 67 CFTRPATHWAY The cAMP-regulated chloride channel CFTR (deficient in cystic fibrosis) is regulated by the surface-localized beta-adrenergic receptor. ADCY1, ADRB2, CFTR, GNAS, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, SLC9A3R1, VIL2 11 ADCY1(8), ADRB2(3), CFTR(4), GNAS(4), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 3468864 29 26 29 9 10 8 6 2 3 0 0.15 1.00 68 SETPATHWAY Cytotoxic T cells release perforin, which to allow entry into target cells of granzyme B, which activates caspases, and granzyme A, which induces caspase-independent apoptosis. ANP32A, APEX1, CREBBP, DFFA, DFFB, GZMA, GZMB, HMGB2, NME1, PRF1, SET 11 ANP32A(1), CREBBP(12), DFFA(1), DFFB(2), GZMA(4), GZMB(1), PRF1(2) 2860104 23 22 23 8 7 7 3 2 4 0 0.15 1.00 69 FBW7PATHWAY Cyclin E interacts with cell cycle checkpoint kinase cdk2 to allow transcription of genes required for S phase, including transcription of additional cyclin E. CCNE1, CDC34, CDK2, CUL1, E2F1, FBXW7, RB1, SKP1A, TFDP1 7 CDK2(1), CUL1(3), E2F1(3), RB1(7) 1838028 14 14 14 1 1 7 0 0 6 0 0.15 1.00 70 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(2), GOT1(2), GOT2(3), TAT(1), TYR(3) 1255434 11 11 10 2 3 6 0 1 1 0 0.15 1.00 71 CYTOKINEPATHWAY Intercellular signaling in the immune system occurs via secretion of cytokines, which promote antigen-dependent B and T cell response. IFNA1, IFNB1, IFNG, IL10, IL12A, IL12B, IL13, IL14, IL15, IL16, IL17, IL18, IL1A, IL2, IL3, IL4, IL5, IL6, IL8, IL9, LTA, TNF 20 IFNA1(1), IFNB1(1), IFNG(1), IL10(1), IL12A(1), IL12B(3), IL16(8), IL4(2), LTA(3) 2643656 21 21 21 5 4 7 5 3 2 0 0.16 1.00 72 HSA00252_ALANINE_AND_ASPARTATE_METABOLISM Genes involved in alanine and aspartate metabolism AARS, AARS2, ABAT, ACY3, ADSL, ADSS, ADSSL1, AGXT, AGXT2, ASL, ASNS, ASPA, ASRGL1, ASS1, CAD, CRAT, DARS, DARS2, DDO, DLAT, DLD, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, NARS2, PC, PDHA1, PDHA2, PDHB 33 AARS(2), AARS2(6), ABAT(3), ACY3(2), ADSL(1), ADSS(1), ADSSL1(1), AGXT2(2), ASL(2), ASNS(3), ASPA(1), ASS1(4), CAD(10), DARS(1), DARS2(5), DDO(2), DLAT(1), DLD(2), GAD1(5), GAD2(5), GOT1(2), GOT2(3), GPT(1), GPT2(2), NARS(3), NARS2(2), PC(4), PDHA1(2), PDHA2(5) 10270600 83 61 80 27 22 37 10 6 8 0 0.16 1.00 73 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 25 ADCY1(8), AKT1(1), CAMK2B(2), CAMK2D(1), GNAS(4), HRAS(2), MAPK1(1), MAPK14(1), MAPK3(2), PIK3R1(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), RAC1(2), RPS6KA1(4), RPS6KA5(3), SOS1(6) 7232318 53 45 53 11 14 16 13 5 5 0 0.16 1.00 74 P27PATHWAY p27 blocks the G1/S transition by inhibiting the checkpoint kinase cdk2/cyclin E and is inhibited by cdk2-mediated ubiquitination. CCNE1, CDK2, CDKN1B, CKS1B, CUL1, E2F1, NEDD8, RB1, RBX1, SKP1A, SKP2, TFDP1, UBE2M 12 CDK2(1), CKS1B(1), CUL1(3), E2F1(3), RB1(7), RBX1(1), SKP2(1), UBE2M(1) 2348354 18 17 18 1 3 7 0 1 7 0 0.17 1.00 75 HSA00940_PHENYLPROPANOID_BIOSYNTHESIS Genes involved in phenylpropanoid biosynthesis EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO 6 EPX(5), GBA3(6), LPO(2), MPO(3), PRDX6(1) 1850310 17 15 17 6 3 4 9 0 1 0 0.18 1.00 76 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 133 ADCY1(8), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), ADRA1A(2), ADRA1B(4), ADRA1D(2), ADRB2(3), ANXA6(6), ARRB1(3), ATP1A4(4), ATP1B2(1), ATP2A2(6), ATP2A3(2), ATP2B1(4), ATP2B2(6), ATP2B3(3), CACNA1A(8), CACNA1B(1), CACNA1C(16), CACNA1D(3), CACNA1E(16), CACNA1S(8), CACNB1(1), CACNB3(2), CALR(1), CAMK2B(2), CAMK2D(1), CAMK4(3), CASQ1(1), CASQ2(1), CHRM2(6), CHRM3(5), CHRM4(1), CHRM5(2), GJA1(4), GJB2(1), GJB4(1), GJB5(1), GNAI3(1), GNAZ(2), GNB1(1), GNB2(3), GNB3(2), GNB4(2), GNB5(1), GNG12(1), GNG3(1), GNG4(2), GNG5(1), GRK4(1), GRK5(2), GRK6(1), ITPR1(5), ITPR2(11), ITPR3(3), KCNB1(1), KCNJ5(2), MIB1(2), NME7(2), PEA15(1), PLCB3(4), PLN(1), PRKACA(1), PRKACB(2), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), PRKCD(2), PRKCE(5), PRKCG(9), PRKCH(1), PRKCQ(4), PRKD1(9), RGS1(2), RGS10(1), RGS11(1), RGS16(1), RGS17(2), RGS18(1), RGS20(1), RGS3(4), RGS5(2), RGS6(4), RGS9(2), RYR1(29), SFN(2), SLC8A3(3), USP5(3), YWHAB(2), YWHAQ(1) 44979888 331 123 330 113 98 133 43 23 34 0 0.18 1.00 77 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 17 CALCR(6), CALCRL(4), CRHR1(4), CRHR2(3), EMR1(9), EMR2(5), GHRHR(3), GLP1R(1), GLP2R(4), GPR64(3), LPHN1(4), LPHN2(6) 6101662 52 40 52 21 13 18 10 4 7 0 0.18 1.00 78 VITCBPATHWAY Vitamin C (ascorbic acid), in addition to its role in collagen modification, serves as an antioxidant and is imported into cells by Svct2 in the brain and Svct1 in intestinal epithelium. COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6, P4HB, SLC23A1, SLC23A2, SLC2A1, SLC2A3 11 COL4A1(11), COL4A2(9), COL4A3(5), COL4A4(9), COL4A5(3), COL4A6(9), SLC23A1(1), SLC23A2(4), SLC2A3(4) 6862612 55 44 55 18 18 25 4 1 7 0 0.18 1.00 79 AMIPATHWAY Endogenous anti-thrombosis pathways are overwhelmed in plaque-narrowed blood vessels, resulting in potentially lethal myocardial infarction. ADCY1, CD3D, CD3E, CD3G, CD3Z, CD4, CREBBP, CSK, GNAS, GNB1, GNGT1, HLA-DRA, HLA-DRB1, LCK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTPRC, TRA@, TRB@, ZAP70 21 ADCY1(8), CD3D(1), CD4(2), CREBBP(12), GNAS(4), GNB1(1), HLA-DRA(1), HLA-DRB1(1), LCK(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PTPRC(3), ZAP70(3) 6185678 48 40 48 17 15 18 5 4 6 0 0.20 1.00 80 CSKPATHWAY Csk inhibits T-cell activation by phosphorylating Lck; Csk is regulated by cAMP-dependent kinases and is opposed by the T-cell activator CD45. ADCY1, CD3D, CD3E, CD3G, CD3Z, CD4, CREBBP, CSK, GNAS, GNB1, GNGT1, HLA-DRA, HLA-DRB1, LCK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTPRC, TRA@, TRB@, ZAP70 21 ADCY1(8), CD3D(1), CD4(2), CREBBP(12), GNAS(4), GNB1(1), HLA-DRA(1), HLA-DRB1(1), LCK(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PTPRC(3), ZAP70(3) 6185678 48 40 48 17 15 18 5 4 6 0 0.20 1.00 81 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 ADCY3(5), ADCY9(4), ARF5(3), ATP6V0A1(4), ATP6V0A2(5), ATP6V0A4(2), ATP6V0D1(1), ATP6V0D2(2), ATP6V1A(3), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4), ERO1L(1), GNAS(4), PDIA4(2), PLCG1(2), PLCG2(3), PRKCA(5), SEC61A1(4), SEC61A2(1), TRIM23(2) 9803528 62 54 62 21 18 18 16 4 6 0 0.20 1.00 82 IL18PATHWAY Pro-inflammatory IL-18 is activated in macrophages by caspase-1 cleavage and, in conjunction with IL-12, stimulates Th1 cell differentiation. CASP1, IFNG, IL12A, IL12B, IL18, IL2 6 CASP1(2), IFNG(1), IL12A(1), IL12B(3) 802958 7 6 7 1 1 1 2 0 3 0 0.20 1.00 83 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 32 ALDH4A1(3), ARG1(2), ASL(2), ASS1(4), CKB(1), CKM(2), CKMT2(1), DAO(1), EPRS(11), GATM(1), GLUD1(3), GOT1(2), GOT2(3), LAP3(1), NOS1(10), NOS3(1), OTC(2), P4HA1(2), P4HA2(3), P4HA3(3), PARS2(1), RARS(4), RARS2(2) 8582448 65 51 62 18 14 27 12 2 10 0 0.21 1.00 84 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 133 ACTA1(2), ADCY1(8), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), ARRB1(3), ATF2(2), ATF4(1), ATP2A2(6), ATP2A3(2), CACNB3(2), CALCA(1), CAMK2B(2), CAMK2D(1), CNN1(1), CNN2(1), CORIN(6), CREB3(2), CRHR1(4), DGKZ(3), FOS(1), GABPA(2), GABPB2(1), GBA2(2), GJA1(4), GNB1(1), GNB2(3), GNB3(2), GNB4(2), GNB5(1), GNG12(1), GNG3(1), GNG4(2), GNG5(1), GRK4(1), GRK5(2), GRK6(1), GSTO1(1), GUCA2B(1), GUCY1A3(6), IGFBP3(1), IGFBP6(1), IL1B(1), ITPR1(5), ITPR2(11), ITPR3(3), JUN(2), MIB1(2), MYL2(1), MYLK2(2), NFKB1(2), NOS1(10), NOS3(1), OXTR(1), PDE4B(3), PDE4D(1), PLCB3(4), PLCG1(2), PLCG2(3), PRKACA(1), PRKACB(2), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), PRKCD(2), PRKCE(5), PRKCH(1), PRKCQ(4), PRKD1(9), RAMP2(1), RGS1(2), RGS10(1), RGS11(1), RGS16(1), RGS17(2), RGS18(1), RGS20(1), RGS3(4), RGS5(2), RGS6(4), RGS9(2), RYR1(29), SFN(2), SP1(1), TNXB(16), USP5(3), YWHAB(2), YWHAQ(1) 41029356 284 121 283 103 90 115 38 14 27 0 0.22 1.00 85 HSA00430_TAURINE_AND_HYPOTAURINE_METABOLISM Genes involved in taurine and hypotaurine metabolism BAAT, CDO1, CSAD, GAD1, GAD2, GGT1, GGTL3, GGTL4 6 BAAT(3), CSAD(1), GAD1(5), GAD2(5), GGT1(2) 1577970 16 13 16 10 4 7 2 2 1 0 0.22 1.00 86 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 22 ABAT(3), ALDH4A1(3), ALDH5A1(1), CAD(10), EPRS(11), GAD1(5), GAD2(5), GCLC(2), GCLM(1), GLS(2), GLUD1(3), GLUL(1), GOT1(2), GOT2(3), GPT(1), GPT2(2), GSS(2), PPAT(1) 7688176 58 47 57 18 11 29 11 3 4 0 0.22 1.00 87 AKAP13PATHWAY A-kinase anchor protein 13 (AKAP13) localizes protein kinase A holoenzyme and is a nucleotide exchange factor for Rho/Rac. AKAP13, ARHA, EDG2, EDG4, EDG7, GNA12, PRKACB, PRKACG, PRKAG1, PRKAR2A, PRKAR2B 7 AKAP13(14), GNA12(1), PRKACB(2), PRKACG(1), PRKAR2B(3) 2728562 21 20 21 9 4 11 3 2 1 0 0.22 1.00 88 SA_DIACYLGLYCEROL_SIGNALING DAG (diacylglycerol) signaling activity ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP 10 ESR1(6), ESR2(1), ITPKA(1), PDE1A(2), PDE1B(1), PLCB1(7), PLCB2(5), PRL(1), VIP(2) 3042376 26 23 26 8 10 10 3 2 1 0 0.22 1.00 89 MPRPATHWAY Progesterone binding to its intracellular receptor activates the MAPK pathway and induces oocyte maturation; binding to membrane receptor inhibits adenylyl cyclase. ACTA1, ADCY1, CAP1, CCNB1, CDC2, CDC25C, GNAI1, GNAS, GNB1, GNGT1, HRAS, MAPK1, MAPK3, MYT1, PIN1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RPS6KA1, SRC 22 ACTA1(2), ADCY1(8), CAP1(1), CCNB1(1), CDC25C(1), GNAI1(2), GNAS(4), GNB1(1), HRAS(2), MAPK1(1), MAPK3(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), RPS6KA1(4) 5515508 39 36 39 14 11 14 7 5 2 0 0.23 1.00 90 ASBCELLPATHWAY B cells require interaction with helper T cells to produce antigen-specific immunoglobulins as a key element of the human immune response. CD28, CD4, CD80, HLA-DRA, HLA-DRB1, IL10, IL2, IL4, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 8 CD4(2), CD80(2), HLA-DRA(1), HLA-DRB1(1), IL10(1), IL4(2) 1077612 9 9 9 2 1 3 2 1 2 0 0.23 1.00 91 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 43 AKT1(1), AKT3(2), BRAF(7), CAB39(1), DDIT4(2), EIF4B(6), FIGF(1), HIF1A(1), IGF1(2), MAPK1(1), MAPK3(2), PDPK1(1), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PRKAA2(2), RHEB(1), RICTOR(4), RPS6(1), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KA6(3), RPS6KB1(1), STK11(3), TSC1(6), TSC2(6), ULK1(1), ULK2(3), VEGFC(4) 14056126 92 70 90 29 20 29 22 7 14 0 0.23 1.00 92 EPHA4PATHWAY Eph Kinases and ephrins support platelet aggregation ACTA1, EPHA4, EPHB1, FYN, ITGA1, ITGB1, L1CAM, LYN, RAP1B, SELP 9 ACTA1(2), EPHA4(1), FYN(4), ITGA1(4), ITGB1(4), L1CAM(2), LYN(1), SELP(8) 3687448 26 24 26 14 6 4 7 1 8 0 0.24 1.00 93 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 80 ANPEP(5), CD14(1), CD19(2), CD1A(4), CD1B(5), CD1C(5), CD1D(3), CD1E(4), CD2(1), CD22(5), CD33(2), CD34(3), CD36(1), CD37(2), CD38(1), CD3D(1), CD4(2), CD44(3), CD5(3), CD8B(1), CD9(2), CR1(4), CR2(9), CSF1(2), CSF1R(3), CSF3R(5), DNTT(3), EPOR(2), FCER2(2), FCGR1A(1), FLT3(4), GP5(4), GP9(1), HLA-DRA(1), HLA-DRB1(1), HLA-DRB5(2), IL11RA(2), IL1B(1), IL1R2(3), IL4(2), IL5RA(2), IL6R(1), IL7R(3), ITGA1(4), ITGA2(5), ITGA2B(1), ITGA3(2), ITGA4(5), ITGA5(1), ITGA6(6), ITGAM(3), ITGB3(3), KIT(6), MME(6), MS4A1(3), TFRC(2), THPO(1) 21426928 162 95 162 67 44 70 28 4 16 0 0.24 1.00 94 HSA04610_COMPLEMENT_AND_COAGULATION_CASCADES Genes involved in complement and coagulation cascades A2M, BDKRB1, BDKRB2, C1QA, C1QB, C1QC, C1R, C1S, C2, C3, C3AR1, C4A, C4B, C4BPA, C4BPB, C5, C5AR1, C6, C7, C8A, C8B, C8G, C9, CD46, CD55, CD59, CFB, CFD, CFH, CFI, CPB2, CR1, CR2, F10, F11, F12, F13A1, F13B, F2, F2R, F3, F5, F7, F8, F9, FGA, FGB, FGG, KLKB1, KNG1, MASP1, MASP2, MBL2, PLAT, PLAU, PLAUR, PLG, PROC, PROS1, SERPINA1, SERPINA5, SERPINC1, SERPIND1, SERPINE1, SERPINF2, SERPING1, TFPI, THBD, VWF 66 A2M(4), BDKRB1(3), BDKRB2(1), C1QA(2), C1QB(2), C1R(2), C1S(4), C2(1), C3(4), C3AR1(1), C4BPA(1), C5(1), C5AR1(1), C7(7), C8A(3), C8B(2), C9(2), CD46(2), CFB(3), CFH(5), CFI(2), CPB2(2), CR1(4), CR2(9), F10(3), F11(4), F12(1), F13A1(3), F13B(7), F2R(2), F3(2), F5(15), F8(10), F9(4), FGA(5), FGB(3), FGG(1), KLKB1(4), KNG1(4), MASP1(10), MASP2(1), MBL2(3), PLAT(1), PLAU(2), PLG(2), SERPINA1(1), SERPINA5(2), SERPINC1(5), SERPIND1(1), SERPINE1(2), SERPINF2(3), VWF(16) 24079306 185 99 184 64 48 67 43 13 14 0 0.25 1.00 95 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 53 AKR1C4(1), AKR1D1(4), ARSD(1), ARSE(2), CARM1(1), CYP11B2(6), CYP19A1(3), HSD11B1(3), HSD11B2(1), HSD17B1(1), HSD17B12(1), HSD17B7(1), HSD3B1(4), HSD3B2(5), LCMT1(2), LCMT2(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), SRD5A1(2), SRD5A2(2), STS(3), SULT1E1(1), SULT2A1(3), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4), WBSCR22(4) 12726110 94 66 93 17 27 28 19 11 9 0 0.26 1.00 96 ALANINE_AND_ASPARTATE_METABOLISM AARS, ABAT, ADSL, ADSS, AGXT, AGXT2, ASL, ASNS, ASPA, ASS, CAD, CRAT, DARS, DDO, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, PC 21 AARS(2), ABAT(3), ADSL(1), ADSS(1), AGXT2(2), ASL(2), ASNS(3), ASPA(1), CAD(10), DARS(1), DDO(2), GAD1(5), GAD2(5), GOT1(2), GOT2(3), GPT(1), GPT2(2), NARS(3), PC(4) 7056632 53 43 52 20 12 26 7 3 5 0 0.26 1.00 97 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 13 C1QA(2), C1QB(2), C1R(2), C1S(4), C2(1), C3(4), C5(1), C7(7), C8A(3), C9(2), MASP1(10), MASP2(1), MBL2(3) 5353528 42 34 42 15 9 17 9 3 4 0 0.26 1.00 98 AMINOACYL_TRNA_BIOSYNTHESIS AARS, CARS, DARS, EPRS, FARS2, FARSLB, GARS, HARS, HARSL, IARS, KARS, LARS, LARS2, MARS, MARS2, NARS, QARS, RARS, SARS, TARS, WARS, WARS2, YARS 21 AARS(2), CARS(6), DARS(1), EPRS(11), FARS2(1), GARS(1), HARS(2), IARS(3), KARS(3), LARS2(5), MARS(1), NARS(3), RARS(4), SARS(2), TARS(3), WARS(4), WARS2(1), YARS(1) 8565716 54 50 54 18 9 21 17 2 5 0 0.27 1.00 99 HSA00750_VITAMIN_B6_METABOLISM Genes involved in vitamin B6 metabolism AOX1, PDXK, PDXP, PNPO, PSAT1 5 AOX1(11), PDXP(1) 1306342 12 11 12 2 2 5 2 3 0 0 0.27 1.00 100 HSA00591_LINOLEIC_ACID_METABOLISM Genes involved in linoleic acid metabolism AKR1B10, ALOX15, ALOX5, CYP1A2, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2E1, CYP2J2, CYP3A4, CYP3A43, CYP3A5, CYP3A7, HSD3B7, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, RDH11, RDH12, RDH13, RDH14 31 AKR1B10(1), ALOX15(2), CYP1A2(1), CYP2C19(6), CYP2C8(3), CYP2C9(2), CYP2E1(1), CYP2J2(2), CYP3A4(1), CYP3A43(3), CYP3A7(1), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), RDH11(2), RDH12(2), RDH13(1) 6442710 48 40 48 16 16 13 8 4 7 0 0.27 1.00 101 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 16 CDK5(2), DRD1(1), DRD2(2), PLCB1(7), PPP1CA(1), PPP1R1B(1), PPP3CA(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 3577444 26 25 26 6 9 12 0 2 3 0 0.28 1.00 102 GLYCOLYSIS_AND_GLUCONEOGENESIS Genes involved in glycolysis and gluconeogenesis ALDOA, ALDOB, ALDOC, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GAPDHS, GAPDS, GCK, GOT1, GOT2, GPI, HK1, HK2, HK3, LDHA, LDHAL6B, LDHB, LDHC, MDH1, MDH2, PC, PCK1, PDHA1, PDHA2, PDHB, PDHX, PFKL, PFKM, PFKP, PGAM1, PGAM2, PGK1, PGK2, PKLR, PKM2, TNFAIP1, TPI1 43 ALDOA(1), ALDOB(2), ALDOC(1), DLAT(1), DLD(2), ENO2(2), ENO3(1), FBP2(1), G6PC(2), GAPDH(3), GAPDHS(2), GCK(1), GOT1(2), GOT2(3), GPI(5), HK1(4), HK2(6), HK3(7), LDHAL6B(1), LDHB(2), LDHC(1), MDH1(1), MDH2(1), PC(4), PCK1(3), PDHA1(2), PDHA2(5), PFKL(2), PFKM(5), PFKP(2), PGAM2(1), PGK1(1), PGK2(5), PKLR(3), PKM2(1), TPI1(4) 11286268 90 64 87 27 28 38 10 5 9 0 0.28 1.00 103 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 20 ADCY1(8), AKT1(1), BAX(1), BCL2L1(2), CSF2RB(5), IGF1(2), IGF1R(1), KIT(6), PIK3R1(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 5036332 37 34 37 8 12 15 4 3 3 0 0.28 1.00 104 HSA00300_LYSINE_BIOSYNTHESIS Genes involved in lysine biosynthesis AADAT, AASDHPPT, AASS, KARS 4 AADAT(1), AASDHPPT(1), AASS(6), KARS(3) 1265758 11 11 11 3 3 4 3 0 1 0 0.28 1.00 105 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 CMBL(1) 134924 1 1 1 0 0 0 1 0 0 0 0.28 1.00 106 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 7 IFNAR1(2), IFNB1(1), JAK1(1), PTPRU(8), STAT1(2), STAT2(2), TYK2(8) 3290686 24 24 23 6 7 11 1 3 2 0 0.28 1.00 107 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 28 ABAT(3), ADC(1), ALDH4A1(3), ALDH5A1(1), CAD(10), EARS2(2), EPRS(11), GAD1(5), GAD2(5), GCLC(2), GCLM(1), GFPT2(1), GLS(2), GLUD1(3), GLUL(1), GOT1(2), GOT2(3), GPT(1), GPT2(2), GSR(2), GSS(2), PPAT(1) 9113066 64 51 63 22 11 31 12 5 5 0 0.28 1.00 108 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 8 CARS(6), GOT1(2), GOT2(3), LDHB(2), LDHC(1) 1840164 14 13 13 2 1 6 3 2 2 0 0.28 1.00 109 SHHPATHWAY Sonic hedgehog (Shh) signaling in the developing CNS induces neuronal proliferation via interaction with the patched (Ptc-1) and smoothened receptors. DYRK1A, DYRK1B, GLI, GLI2, GLI3, GSK3B, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTCH, SHH, SMO, SUFU 14 DYRK1A(3), DYRK1B(2), GLI2(5), GLI3(6), GSK3B(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), SMO(1), SUFU(3) 4465486 31 29 31 15 5 16 4 3 3 0 0.29 1.00 110 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 6 AKT1(1), PIK3R1(1), PLCB1(7), PLCG1(2), PRKCA(5), VAV1(7) 2863130 23 21 23 7 7 8 3 4 1 0 0.29 1.00 111 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 2 FAH(1), GSTZ1(2) 353152 3 3 3 0 1 0 0 1 1 0 0.30 1.00 112 HSA00530_AMINOSUGARS_METABOLISM Genes involved in aminosugars metabolism AMDHD2, CHIA, CHIT1, CMAS, CTBS, CYB5R1, CYB5R3, GFPT1, GFPT2, GNE, GNPDA1, GNPDA2, GNPNAT1, HEXA, HEXB, HK1, HK2, HK3, LHPP, MTMR1, MTMR2, MTMR6, NAGK, NANS, NPL, PGM3, PHPT1, RENBP, UAP1 29 AMDHD2(1), CHIA(5), CHIT1(5), CMAS(2), CTBS(4), CYB5R1(2), GFPT2(1), GNE(4), GNPDA2(3), HEXA(6), HK1(4), HK2(6), HK3(7), MTMR1(1), MTMR2(1), MTMR6(3), NANS(1), UAP1(1) 7756350 57 45 57 17 14 24 7 3 9 0 0.30 1.00 113 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 6 ADCY1(8), CREM(2), FSHB(1), GNAS(4), XPO1(2) 2218948 17 16 17 8 6 4 3 3 1 0 0.31 1.00 114 ALKALOID_BIOSYNTHESIS_II ABP1, AOC2, AOC3, CES1, ESD 5 ABP1(6), AOC2(2), AOC3(3), CES1(2) 1611612 13 12 13 8 4 5 2 2 0 0 0.31 1.00 115 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT1(2), GOT2(3), TAT(1) 702744 6 6 5 2 2 3 0 1 0 0 0.32 1.00 116 BETA_ALANINE_METABOLISM ABAT, ABP1, ACADL, ACADM, ACADSB, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, AOC2, AOC3, CNDP1, DPYD, DPYS, ECHS1, EHHADH, GAD1, GAD2, HADHA, MLYCD, SDS, SMS, UPB1 27 ABAT(3), ABP1(6), ACADL(2), ACADM(1), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2), AOC2(2), AOC3(3), CNDP1(3), DPYD(7), DPYS(4), EHHADH(1), GAD1(5), GAD2(5), HADHA(2), MLYCD(2), SDS(2), SMS(4) 7843214 63 46 62 25 15 28 9 5 6 0 0.32 1.00 117 GLYCOLYSISPATHWAY Glycolysis is an evolutionarily conserved pathway by which one glucose molecule is converted to two pyruvate molecules for a gain of 2 ATP. ALDOB, ENO1, GAPD, GPI, HK1, PFKL, PGAM1, PGK1, PKLR, TPI1 9 ALDOB(2), GPI(5), HK1(4), PFKL(2), PGK1(1), PKLR(3), TPI1(4) 2381818 21 17 20 4 8 6 4 0 3 0 0.33 1.00 118 ARGININECPATHWAY Related catabolic pathways process arginine, histidine, glutamine, and proline through glutamate to alpha-ketoglutamate, which feeds into the citric acid cycle. ALDH4A1, ARG1, GLS, GLUD1, OAT, PRODH 6 ALDH4A1(3), ARG1(2), GLS(2), GLUD1(3) 1445894 10 10 10 4 1 6 2 0 1 0 0.34 1.00 119 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 143 APC(9), APC2(2), BTRC(1), CAMK2B(2), CAMK2D(1), CCND1(1), CCND2(3), CCND3(1), CHD8(13), CHP(2), CREBBP(12), CSNK1A1(1), CSNK1A1L(5), CSNK2A1(2), CTBP1(1), CTNNB1(3), CUL1(3), DAAM1(1), DAAM2(5), DKK1(3), DKK2(1), DKK4(1), DVL1(3), DVL3(3), EP300(5), FZD1(1), FZD10(2), FZD3(4), FZD4(1), FZD6(1), FZD9(3), GSK3B(1), JUN(2), LEF1(3), LRP5(6), LRP6(6), MAP3K7(3), MAPK10(1), MAPK8(2), MAPK9(1), MYC(1), NFAT5(3), NFATC2(5), NFATC3(3), NFATC4(2), NKD1(1), NKD2(2), NLK(2), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PORCN(2), PPARD(2), PPP2R1A(6), PPP2R1B(2), PPP2R2A(1), PPP2R2B(2), PPP2R2C(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRICKLE1(5), PRICKLE2(1), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCG(9), PRKX(1), PSEN1(1), RAC1(2), RBX1(1), ROCK1(5), ROCK2(3), RUVBL1(1), SENP2(3), SFRP1(1), SFRP4(3), SIAH1(1), SKP1(1), SMAD2(2), SMAD4(2), TBL1XR1(2), TBL1Y(2), TCF7(1), VANGL1(1), VANGL2(2), WIF1(4), WNT10B(2), WNT11(2), WNT2(3), WNT2B(2), WNT3(2), WNT3A(1), WNT5A(1), WNT5B(1), WNT6(2), WNT7A(2), WNT7B(1), WNT9A(1), WNT9B(2) 44342292 275 126 272 98 80 99 39 27 30 0 0.34 1.00 120 GPCRDB_CLASS_A_RHODOPSIN_LIKE2 CYSLTR1, CYSLTR2, GPR109B, GPR161, GPR171, GPR18, GPR34, GPR39, GPR41, GPR42, GPR45, GPR65, GPR68, GPR75, GPR81, LYPDC1 13 CYSLTR1(3), CYSLTR2(1), GPR109B(3), GPR161(2), GPR171(2), GPR18(1), GPR34(1), GPR39(1), GPR45(4), GPR65(1), GPR68(1), GPR75(2) 2642232 22 19 22 8 8 9 4 0 1 0 0.34 1.00 121 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(2), ALDOC(1), FBP2(1), GOT1(2), GOT2(3), GPT(1), GPT2(2), MDH1(1), MDH2(1), ME3(2), PGK1(1), PGK2(5), PKLR(3), PKM2(1), RPIA(1), TKT(1), TKTL1(4), TPI1(4) 4972608 37 33 33 14 11 15 5 2 4 0 0.34 1.00 122 CIRCADIAN_EXERCISE ARNTL, AZIN1, BTG1, C10orf110, C1orf1, CBX3, CEBPB, CLDN5, CLOCK, CRY1, CRY2, DAZAP2, DAZAP2, LOC401029, DNAJA1, EIF4G2, ETV6, G0S2, GENX_3414, GFRA1, GSTM3, GSTP1, HERPUD1, HLA_DMA, HSPA8, IDI1, KLF9, MAP3K7IP2, MYF6, NCKAP1, NCOA4, NR1D2, OAZIN, PER1, PER2, PIGF, PPP1R3C, PPP2CB, PSMA4, PURA, SF3A3, SUMO3, TOB1, TUBB3, UCP3, UGP2, VAPA, ZFR 40 ARNTL(2), AZIN1(1), BTG1(1), CLOCK(5), CRY1(3), CRY2(2), EIF4G2(4), ETV6(4), GSTM3(1), HERPUD1(2), HSPA8(3), IDI1(1), KLF9(1), MYF6(1), NCKAP1(5), PER1(6), PER2(3), PIGF(1), PPP1R3C(2), PSMA4(1), PURA(1), SF3A3(1), UCP3(3), UGP2(5), VAPA(1), ZFR(4) 9949310 64 53 64 15 11 22 17 4 10 0 0.35 1.00 123 FIBRINOLYSISPATHWAY Thrombin cleavage of fibrinogen results in rapid formation of fibrin threads that form a mesh to capture platelets and other blood cells into a clot. CPB2, F13A1, F2, F2R, FGA, FGB, FGG, PLAT, PLAU, PLG, SERPINB2, SERPINE1 12 CPB2(2), F13A1(3), F2R(2), FGA(5), FGB(3), FGG(1), PLAT(1), PLAU(2), PLG(2), SERPINB2(3), SERPINE1(2) 3573172 26 24 25 9 3 13 8 0 2 0 0.35 1.00 124 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP1(1), ACPT(2), ENPP1(7), ENPP3(4), FLAD1(2), TYR(3) 2593104 19 18 19 5 5 10 2 0 2 0 0.35 1.00 125 INOSITOL_PHOSPHATE_METABOLISM IMPA1, INPP1, INPP4A, INPP4B, INPP5A, INPPL1, ITPKA, ITPKB, MIOX, OCRL, PIK3C2A, PIK3C2B, PIK3C2G, PIK3CA, PIK3CB, PIK3CG, PIK4CA, PIK4CA, LOC220686, PIP5K2B, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCG1, PLCG2 22 IMPA1(1), INPP1(1), INPP4A(5), INPP4B(4), INPP5A(3), INPPL1(3), ITPKA(1), ITPKB(3), OCRL(5), PIK3C2A(4), PIK3C2B(7), PIK3C2G(7), PIK3CB(1), PIK3CG(10), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PLCG1(2), PLCG2(3) 11733582 80 60 80 28 26 21 17 6 10 0 0.35 1.00 126 COMPLEMENT_ACTIVATION_CLASSICAL C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C9, DAF, MASP1 12 C1QA(2), C1QB(2), C1R(2), C1S(4), C2(1), C3(4), C5(1), C7(7), C8A(3), C8B(2), C9(2), MASP1(10) 5207568 40 32 40 16 10 15 9 3 3 0 0.36 1.00 127 ARGININE_AND_PROLINE_METABOLISM ABP1, AGMAT, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH4A1, ALDH9A1, AMD1, AOC2, AOC3, ARG1, ARG2, ASL, ASS, CKB, CKM, CKMT1, CKMT1B, CKMT1A, CKMT2, CPS1, DAO, GAMT, GATM, GLUD1, GOT1, GOT2, MAOA, MAOB, NOS1, NOS2A, NOS3, OAT, ODC1, OTC, P4HA1, P4HA2, P4HA3, P4HB, PYCR1, RARS, SAT, SMS 42 ABP1(6), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH4A1(3), ALDH9A1(2), AMD1(1), AOC2(2), AOC3(3), ARG1(2), ASL(2), CKB(1), CKM(2), CKMT2(1), DAO(1), GATM(1), GLUD1(3), GOT1(2), GOT2(3), NOS1(10), NOS3(1), ODC1(1), OTC(2), P4HA1(2), P4HA2(3), P4HA3(3), RARS(4), SMS(4) 11077830 74 59 72 26 16 32 11 4 11 0 0.36 1.00 128 CHREBPPATHWAY Carbohydrate responsive element binding protein (chREBP) is a transcription factor inhibited by cAMP and activated by high carbohydrate levels. ADCY1, BG1, BUCS1, GNAS, GNB1, GNGT1, PPP2CA, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKACB, PRKACG, PRKAG1, PRKAG2, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, WBSCR14 17 ADCY1(8), GNAS(4), GNB1(1), PRKAA2(2), PRKAB2(1), PRKACB(2), PRKACG(1), PRKAG2(4), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 4084922 30 26 30 8 10 10 5 2 3 0 0.36 1.00 129 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(4), AGT(1), AGTR1(3), AGTR2(4), BDKRB2(1), KNG1(4), NOS3(1) 2766476 18 18 18 11 4 7 4 1 2 0 0.36 1.00 130 PELP1PATHWAY Pelp1 acts downstream of activated estrogen receptor to promote cell proliferation and is overexpressed in many breast tumors. CREBBP, EP300, ESR1, MAPK1, MAPK3, PELP1, SRC 7 CREBBP(12), EP300(5), ESR1(6), MAPK1(1), MAPK3(2), PELP1(1) 4039354 27 26 26 6 6 10 6 2 3 0 0.37 1.00 131 INSULINPATHWAY Insulin regulates glucose levels via Ras-mediated transcriptional activation. CSNK2A1, ELK1, FOS, GRB2, HRAS, INS, INSR, IRS1, JUN, MAP2K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PTPN11, RAF1, RASA1, SHC1, SLC2A4, SOS1, SRF 20 CSNK2A1(2), FOS(1), HRAS(2), INSR(7), IRS1(4), JUN(2), MAP2K1(2), MAPK3(2), MAPK8(2), PIK3R1(1), PTPN11(3), RAF1(1), RASA1(6), SHC1(1), SLC2A4(2), SOS1(6), SRF(2) 6296750 46 38 46 9 12 16 7 5 6 0 0.37 1.00 132 CDK5PATHWAY Cdk5, a regulatory kinase implicated in neuronal development, represses Mek1, which downregulates the MAP kinase pathway. CDK5, CDK5R1, DPM2, EGR1, HRAS, KLK2, MAP2K1, MAP2K2, MAPK1, MAPK3, NGFB, NGFR, RAF1 12 CDK5(2), EGR1(4), HRAS(2), KLK2(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), NGFR(1), RAF1(1) 2270034 18 16 17 4 5 9 2 1 1 0 0.37 1.00 133 MTORPATHWAY Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation. AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2 19 AKT1(1), EIF4A1(3), EIF4A2(3), EIF4B(6), EIF4G1(8), EIF4G2(4), EIF4G3(3), PDK2(2), PDPK1(1), PIK3R1(1), RPS6(1), RPS6KB1(1), TSC1(6), TSC2(6) 6686392 46 37 45 14 5 21 9 3 8 0 0.37 1.00 134 WNTPATHWAY The Wnt glycoprotein binds to membrane-bound receptors such as Frizzled to activate a number of signaling pathways, including that of beta-catenin. APC, AXIN1, BTRC, CCND1, CREBBP, CSNK1A1, CSNK1D, CSNK2A1, CTBP1, CTNNB1, DVL1, FRAT1, FZD1, GSK3B, HDAC1, MADH4, MAP3K7, MAP3K7IP1, MYC, NLK, PPARD, PPP2CA, TCF1, TLE1, WIF1, WNT1 22 APC(9), BTRC(1), CCND1(1), CREBBP(12), CSNK1A1(1), CSNK2A1(2), CTBP1(1), CTNNB1(3), DVL1(3), FZD1(1), GSK3B(1), HDAC1(2), MAP3K7(3), MYC(1), NLK(2), PPARD(2), TLE1(4), WIF1(4) 7875610 53 46 53 11 10 20 10 5 8 0 0.37 1.00 135 BIOGENIC_AMINE_SYNTHESIS AANAT, ACHE, CHAT, COMT, DBH, DDC, DXYS155E, GAD1, GAD2, HDC, MAOA, PAH, PNMT, SLC18A3, TH, TPH1 15 ACHE(2), CHAT(2), DBH(2), DDC(2), GAD1(5), GAD2(5), HDC(3), PAH(1), PNMT(2), TH(2), TPH1(1) 3978300 27 25 27 11 9 11 4 1 2 0 0.37 1.00 136 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(12), DAXX(3), HRAS(2), PAX3(3), RARA(1), RB1(7), SIRT1(1), SP100(1), TNFRSF1A(2), TNFRSF1B(1) 5006962 33 28 33 10 7 12 2 4 8 0 0.38 1.00 137 RECKPATHWAY RECK is a membrane-anchored inhibitor of matrix metalloproteinases, which are expressed by tumor cells and promote metastasis. HRAS, MMP14, MMP2, MMP9, RECK, TIMP1, TIMP2, TIMP3, TIMP4 9 HRAS(2), MMP14(3), MMP2(4), MMP9(6), RECK(3), TIMP2(1) 2030980 19 14 19 4 3 10 3 2 1 0 0.38 1.00 138 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(1), ALOX15(2), CYP4F2(3), CYP4F3(3), EPX(5), GGT1(2), LPO(2), LTA4H(2), MPO(3), PLA2G2A(1), PLA2G2E(2), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PRDX1(1), PRDX6(1), PTGS1(2), TBXAS1(5) 7134062 51 42 49 25 11 17 15 3 5 0 0.38 1.00 139 TH1TH2PATHWAY Helper T subtype Th1 produces pro-inflammatory cytokines that stimulate phagocytosis, while Th2 cells promote antibody production and activate eosinophils. CD28, CD86, HLA-DRA, HLA-DRB1, IFNG, IFNGR1, IFNGR2, IL12A, IL12B, IL12RB1, IL12RB2, IL18, IL18R1, IL2, IL2RA, IL4, IL4R, TNFRSF5, TNFSF5 17 CD86(1), HLA-DRA(1), HLA-DRB1(1), IFNG(1), IFNGR1(3), IFNGR2(1), IL12A(1), IL12B(3), IL12RB1(3), IL12RB2(3), IL18R1(2), IL4(2) 3417422 22 20 22 11 3 7 6 0 6 0 0.39 1.00 140 SA_B_CELL_RECEPTOR_COMPLEXES Antigen binding to B cell receptors activates protein tyrosine kinases, such as the Src family, which ultimate activate MAP kinases. ATF2, BCR, BLNK, ELK1, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP3K1, MAPK1, MAPK3, MAPK8IP3, PAPPA, RAC1, RPS6KA1, RPS6KA3, SHC1, SOS1, SYK, VAV1, VAV2, VAV3 24 ATF2(2), BCR(1), BLNK(1), FOS(1), HRAS(2), JUN(2), LYN(1), MAP2K1(2), MAP3K1(3), MAPK1(1), MAPK3(2), MAPK8IP3(6), PAPPA(8), RAC1(2), RPS6KA1(4), RPS6KA3(1), SHC1(1), SOS1(6), SYK(1), VAV1(7), VAV2(4), VAV3(1) 8747988 59 49 59 14 14 19 15 6 5 0 0.39 1.00 141 SKP2E2FPATHWAY E2F-1, a transcription factor that promotes the G1/S transition, is repressed by Rb and activated by cdk2/cyclin E. CCNA1, CCNE1, CDC34, CDK2, CUL1, E2F1, RB1, SKP1A, SKP2, TFDP1 9 CCNA1(1), CDK2(1), CUL1(3), E2F1(3), RB1(7), SKP2(1) 2358678 16 15 16 1 3 7 0 0 6 0 0.40 1.00 142 HSA00533_KERATAN_SULFATE_BIOSYNTHESIS Genes involved in keratan sulfate biosynthesis B3GNT1, B3GNT2, B3GNT7, B4GALT1, B4GALT2, B4GALT3, B4GALT4, CHST1, CHST2, CHST4, CHST6, FUT8, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 16 B3GNT2(1), B3GNT7(2), B4GALT1(1), B4GALT3(2), B4GALT4(1), CHST1(2), CHST2(4), CHST4(2), CHST6(3), FUT8(2), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2) 3427212 25 23 24 16 9 10 4 2 0 0 0.40 1.00 143 ERBB3PATHWAY Neuregulins bind to the receptor tyrosine kinases ErbB3 and ErbB4, surface-localized receptors whose overexpression induces tumor formation. EGF, EGFR, ERBB3, NRG1, UBE2D1 5 EGF(6), EGFR(9), ERBB3(3), NRG1(4), UBE2D1(1) 2762204 23 18 22 5 6 8 3 2 4 0 0.40 1.00 144 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(1) 192952 1 1 1 0 0 0 0 0 1 0 0.40 1.00 145 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 94 ADCY1(8), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), ATF4(1), CACNA1C(16), CACNA1D(3), CACNA1F(8), CACNA1S(8), CAMK2B(2), CAMK2D(1), CDC42(1), EGFR(9), FSHB(1), GNAS(4), HBEGF(1), HRAS(2), ITPR1(5), ITPR2(11), ITPR3(3), JUN(2), KRAS(1), LHB(1), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAP3K4(4), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPK7(1), MAPK8(2), MAPK9(1), MMP14(3), MMP2(4), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PLD1(10), PLD2(4), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCD(2), PRKX(1), RAF1(1), SOS1(6), SOS2(4) 34618686 232 114 229 74 73 85 37 17 20 0 0.40 1.00 146 HSA00230_PURINE_METABOLISM Genes involved in purine metabolism ADA, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADK, ADSL, ADSS, ADSSL1, AK1, AK2, AK3L1, AK5, AK7, ALLC, AMPD1, AMPD2, AMPD3, APRT, ATIC, CANT1, DCK, DGUOK, ECGF1, ENPP1, ENPP3, ENTPD1, ENTPD2, ENTPD3, ENTPD4, ENTPD5, ENTPD6, ENTPD8, FHIT, GART, GDA, GMPR, GMPR2, GMPS, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, GUK1, HPRT1, IMPDH1, IMPDH2, ITPA, NME1, NME2, NME4, NME6, NME7, NP, NPR1, NPR2, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT2, NUDT5, NUDT9, PAICS, PAPSS1, PAPSS2, PDE10A, PDE11A, PDE1A, PDE1C, PDE2A, PDE3B, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A, PDE6D, PDE6G, PDE6H, PDE7A, PDE7B, PDE8A, PDE8B, PDE9A, PFAS, PKLR, PKM2, PNPT1, POLA1, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, PPAT, PRIM1, PRIM2, PRPS1, PRPS1L1, PRPS2, PRUNE, RFC5, RRM1, RRM2, RRM2B, SAC, XDH, ZNRD1 138 ADCY1(8), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), ADSL(1), ADSS(1), ADSSL1(1), AK5(2), AK7(1), AMPD1(4), AMPD2(1), AMPD3(6), CANT1(3), DCK(1), ENPP1(7), ENPP3(4), ENTPD1(1), ENTPD2(1), ENTPD3(1), ENTPD5(1), ENTPD6(3), GART(2), GDA(6), GUCY1A3(6), GUCY1B3(3), GUCY2C(4), GUCY2D(1), GUCY2F(8), GUK1(1), HPRT1(1), IMPDH1(2), NME4(1), NME7(2), NPR1(2), NPR2(5), NT5C1A(2), NT5C1B(2), NT5C2(3), NT5C3(4), NT5E(2), NUDT9(2), PAPSS2(1), PDE10A(5), PDE11A(11), PDE1A(2), PDE2A(3), PDE3B(3), PDE4B(3), PDE4C(4), PDE4D(1), PDE5A(3), PDE6H(2), PDE7B(1), PDE8A(6), PDE8B(2), PDE9A(2), PFAS(5), PKLR(3), PKM2(1), PNPT1(2), POLA1(5), POLA2(3), POLD1(2), POLD3(1), POLE2(2), POLE4(1), POLR1A(4), POLR1B(4), POLR1C(1), POLR1D(1), POLR2A(2), POLR2B(2), POLR2D(1), POLR2E(1), POLR2H(1), POLR3A(3), POLR3B(2), POLR3G(1), POLR3H(1), PPAT(1), PRIM1(2), PRPS1(1), PRPS1L1(1), PRPS2(1), RFC5(2), RRM1(2), RRM2B(2), XDH(9) 43127264 258 121 255 112 78 102 39 13 26 0 0.40 1.00 147 HSA00660_C5_BRANCHED_DIBASIC_ACID_METABOLISM Genes involved in C5-branched dibasic acid metabolism ILVBL, SUCLA2 2 ILVBL(2), SUCLA2(2) 579390 4 4 4 1 1 1 1 1 0 0 0.41 1.00 148 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(5), AMY2B(5), ENPP1(7), ENPP3(4), G6PC(2), GANAB(5), GBA3(6), GBE1(1), GCK(1), GPI(5), GUSB(3), GYS1(1), GYS2(3), HK1(4), HK2(6), HK3(7), MGAM(5), PGM1(1), PYGB(2), PYGM(6), UGDH(3), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2B15(1), UGT2B4(4), UXS1(3) 14193898 101 68 100 31 29 41 17 6 8 0 0.41 1.00 149 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 50 ABL1(2), ACTB(1), ARHGEF2(6), CD14(1), CDC42(1), CDH1(4), CLDN1(2), CTNNB1(3), CTTN(4), EZR(1), FYN(4), HCLS1(3), ITGB1(4), KRT18(2), NCK1(3), NCL(1), PRKCA(5), ROCK1(5), ROCK2(3), TLR5(3), TUBA1B(1), TUBA3C(5), TUBA3D(4), TUBA3E(3), TUBA8(1), TUBAL3(2), TUBB(1), TUBB1(1), TUBB2A(1), TUBB4(4), TUBB4Q(2), TUBB8(2), WAS(5), WASL(2), YWHAQ(1) 13876346 93 66 93 34 21 35 15 10 12 0 0.42 1.00 150 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 50 ABL1(2), ACTB(1), ARHGEF2(6), CD14(1), CDC42(1), CDH1(4), CLDN1(2), CTNNB1(3), CTTN(4), EZR(1), FYN(4), HCLS1(3), ITGB1(4), KRT18(2), NCK1(3), NCL(1), PRKCA(5), ROCK1(5), ROCK2(3), TLR5(3), TUBA1B(1), TUBA3C(5), TUBA3D(4), TUBA3E(3), TUBA8(1), TUBAL3(2), TUBB(1), TUBB1(1), TUBB2A(1), TUBB4(4), TUBB4Q(2), TUBB8(2), WAS(5), WASL(2), YWHAQ(1) 13876346 93 66 93 34 21 35 15 10 12 0 0.42 1.00 151 HSA00531_GLYCOSAMINOGLYCAN_DEGRADATION Genes involved in glycosaminoglycan degradation ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, HGSNAT, HPSE, HPSE2, HYAL1, HYAL2, IDS, IDUA, LCT, NAGLU, SPAM1 16 ARSB(2), GNS(1), GUSB(3), HEXA(6), HGSNAT(2), HPSE(3), HPSE2(4), HYAL1(4), IDS(1), IDUA(2), SPAM1(3) 4588306 31 27 30 6 4 13 7 1 6 0 0.42 1.00 152 TERCPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. NFYA, NFYB, NFYC, RB1, SP1, SP3 6 NFYB(1), RB1(7), SP1(1), SP3(1) 1794596 10 10 10 1 1 3 0 0 6 0 0.42 1.00 153 HSA00410_BETA_ALANINE_METABOLISM Genes involved in beta-alanine metabolism ABAT, ABP1, ACADM, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, AOC2, AOC3, CNDP1, DPYD, DPYS, ECHS1, EHHADH, GAD1, GAD2, HADHA, HIBCH, MLYCD, SMS, SRM, UPB1 25 ABAT(3), ABP1(6), ACADM(1), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), AOC2(2), AOC3(3), CNDP1(3), DPYD(7), DPYS(4), EHHADH(1), GAD1(5), GAD2(5), HADHA(2), HIBCH(1), MLYCD(2), SMS(4) 7313308 57 42 57 24 16 24 7 5 5 0 0.43 1.00 154 NDKDYNAMINPATHWAY Endocytotic role of NDK, Phosphins and Dynamin AMPH, AP2A1, AP2M1, BIN1, CALM1, CALM2, CALM3, DNM1, EPN1, EPS15, NME1, NME2, PICALM, PPP3CA, PPP3CB, PPP3CC, SYNJ1, SYNJ2, SYT1 19 AMPH(7), AP2A1(3), DNM1(1), EPN1(3), EPS15(4), PICALM(3), PPP3CA(2), PPP3CB(5), PPP3CC(2), SYNJ1(2), SYNJ2(5), SYT1(3) 6051110 40 36 40 11 10 12 6 5 7 0 0.43 1.00 155 AMINOSUGARS_METABOLISM CMAS, CYB5R3, GCK, GFPT1, GNE, GNPDA1, GNPDA2, HEXA, HEXB, HK1, HK2, HK3, PGM3, RENBP, UAP1 15 CMAS(2), GCK(1), GNE(4), GNPDA2(3), HEXA(6), HK1(4), HK2(6), HK3(7), UAP1(1) 4584390 34 30 34 9 8 16 3 3 4 0 0.43 1.00 156 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 5 CDK5(2), GRIA2(3), PPP1R1B(1) 1061414 6 6 6 6 0 2 1 0 3 0 0.43 1.00 157 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 27 BRAF(7), CPEB1(2), EGFR(9), ERBB2(3), ERBB4(9), ETS1(2), ETV6(4), ETV7(1), KRAS(1), MAP2K1(2), MAPK1(1), MAPK3(2), NOTCH1(11), NOTCH2(7), NOTCH3(5), NOTCH4(3), PIWIL1(5), PIWIL2(4), PIWIL3(4), PIWIL4(1), RAF1(1), SOS1(6), SOS2(4), SPIRE1(1) 13594750 95 66 94 29 21 36 12 8 18 0 0.44 1.00 158 HSA00860_PORPHYRIN_AND_CHLOROPHYLL_METABOLISM Genes involved in porphyrin and chlorophyll metabolism ALAD, ALAS1, ALAS2, BLVRA, BLVRB, COX10, COX15, CP, CPOX, EARS2, EPRS, FECH, FTH1, FTMT, GUSB, HCCS, HMBS, HMOX1, HMOX2, MMAB, PPOX, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, UROD, UROS 41 ALAS1(2), BLVRA(2), COX10(1), CP(3), CPOX(3), EARS2(2), EPRS(11), FECH(2), FTH1(4), FTMT(4), GUSB(3), HMBS(2), HMOX1(1), MMAB(1), PPOX(1), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4), UROD(1) 10816526 76 58 76 15 17 31 17 5 6 0 0.44 1.00 159 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 10 FOS(1), JUN(2), MAPK1(1), MAPK14(1), MAPK8(2), PRKCA(5) 1727846 12 12 12 3 4 3 3 1 1 0 0.45 1.00 160 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 129 ACACA(4), ACACB(8), AKT1(1), AKT3(2), ARAF(3), BRAF(7), CBL(4), CBLB(4), CRKL(1), EXOC7(2), FBP2(1), FLOT1(2), G6PC(2), G6PC2(2), GCK(1), GSK3B(1), GYS1(1), GYS2(3), HRAS(2), IKBKB(3), INPP5D(6), INSR(7), IRS1(4), IRS2(2), IRS4(3), KRAS(1), LIPE(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK10(1), MAPK3(2), MAPK8(2), MAPK9(1), PCK1(3), PCK2(1), PDE3A(5), PDE3B(3), PDPK1(1), PFKL(2), PFKM(5), PFKP(2), PHKA1(4), PHKA2(4), PHKB(6), PHKG1(2), PHKG2(1), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PKLR(3), PKM2(1), PPARGC1A(5), PPP1CA(1), PPP1CB(1), PPP1CC(1), PPP1R3C(2), PPP1R3D(2), PRKAA2(2), PRKAB2(1), PRKACA(1), PRKACB(2), PRKACG(1), PRKAG2(4), PRKAG3(2), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCI(4), PRKX(1), PTPN1(1), PTPRF(7), PYGB(2), PYGM(6), RAF1(1), RAPGEF1(3), RHEB(1), RPS6(1), RPS6KB1(1), SHC1(1), SHC2(3), SHC3(3), SHC4(4), SLC2A4(2), SOCS2(1), SORBS1(5), SOS1(6), SOS2(4), SREBF1(3), TRIP10(2), TSC1(6), TSC2(6) 42874504 261 120 260 99 64 105 46 15 31 0 0.45 1.00 161 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 A1BG(1), AKT1(1), AKT3(2), BTK(5), GSK3A(4), GSK3B(1), IARS(3), INPP5D(6), PDK1(1), PPP1R13B(4), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KB1(1), SFN(2), SHC1(1), SOS1(6), SOS2(4), TEC(2), YWHAB(2), YWHAE(1), YWHAQ(1) 8850516 55 47 55 14 8 18 13 3 13 0 0.45 1.00 162 SA_G2_AND_M_PHASES Cdc25 activates the cdc2/cyclin B complex to induce the G2/M transition. CDC2, CDC25A, CDC25B, CDK7, CDKN1A, CHEK1, NEK1, WEE1 7 CDC25B(3), CDK7(1), CHEK1(4), NEK1(3), WEE1(2) 1979716 13 13 13 1 3 7 2 0 1 0 0.45 1.00 163 CIRCADIANPATHWAY A heterodimer composed of Bmal1 and Clock acts as a transcription factor for proteins that regulate circadian rhythms, such as Per and Cry. ARNTL, CLOCK, CRY1, CRY2, CSNK1E, PER1 6 ARNTL(2), CLOCK(5), CRY1(3), CRY2(2), PER1(6) 2337496 18 16 18 3 2 7 7 1 1 0 0.45 1.00 164 CCR3PATHWAY CCR3 is a G-protein coupled receptor that recruits eosinophils to inflammation sites via chemokine ligands. ARHA, CCL11, CCR3, CFL1, GNAQ, GNAS, GNB1, GNGT1, HRAS, LIMK1, MAP2K1, MAPK1, MAPK3, MYL2, NOX1, PIK3C2G, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2, RAF1, ROCK2 21 CCR3(1), CFL1(3), GNAS(4), GNB1(1), HRAS(2), LIMK1(1), MAP2K1(2), MAPK1(1), MAPK3(2), MYL2(1), NOX1(2), PIK3C2G(7), PLCB1(7), PPP1R12B(3), PRKCA(5), PTK2(3), RAF1(1), ROCK2(3) 6923488 49 41 49 18 15 20 7 3 4 0 0.45 1.00 165 BLYMPHOCYTEPATHWAY B cells express the major histocompatibility complex (class II MHC), immunoglobulins, adhesion proteins, and other factors on their cell surface. CD80, CR1, CR2, FCGR2B, HLA-DRA, HLA-DRB1, ICAM1, ITGAL, ITGB2, PTPRC, TNFRSF5 10 CD80(2), CR1(4), CR2(9), FCGR2B(2), HLA-DRA(1), HLA-DRB1(1), ICAM1(2), ITGAL(1), ITGB2(3), PTPRC(3) 4122124 28 26 28 13 8 9 4 5 2 0 0.46 1.00 166 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 30 ABP1(6), ADH1B(1), ADH1C(1), ADH4(2), ADH7(1), ADHFE1(2), ALDH3B2(2), AOC2(2), AOC3(3), AOX1(11), DBH(2), DCT(1), DDC(2), FAH(1), GOT1(2), GOT2(3), GSTZ1(2), HPD(3), PNMT(2), TAT(1), TH(2), TYR(3) 7878636 55 45 54 19 16 26 4 7 2 0 0.47 1.00 167 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(10), ASH2L(1), CARM1(1), CTCFL(2), DOT1L(5), EED(2), EHMT2(2), EZH1(4), EZH2(3), FBXO11(4), HSF4(1), JMJD6(1), KDM6A(3), MEN1(4), MLL(5), MLL3(22), MLL4(6), MLL5(4), NSD1(11), OGT(2), PPP1CA(1), PPP1CB(1), PPP1CC(1), PRDM2(6), PRDM9(11), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), RBBP5(1), SATB1(3), SETD1A(6), SETD2(5), SETD8(1), SETDB1(5), SMYD3(1), STK38(4), SUV39H1(1), SUV39H2(2), SUV420H1(1), SUZ12(2), WHSC1(2), WHSC1L1(12) 30009554 166 103 165 55 39 53 32 11 29 2 0.47 1.00 168 HSA00232_CAFFEINE_METABOLISM Genes involved in caffeine metabolism CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH 7 CYP1A2(1), CYP2A13(2), CYP2A6(3), NAT2(1), XDH(9) 2131550 16 14 16 7 4 8 1 1 2 0 0.47 1.00 169 PEPIPATHWAY Proepithelin (PEPI) induces epithelial cells to secrete IL-8, which promotes elastase secretion by neutrophils. ELA1, ELA2, ELA2A, ELA2B, ELA3B, GRN, IL8, SLPI 3 GRN(3) 455858 3 3 3 0 0 2 1 0 0 0 0.47 1.00 170 RANPATHWAY RanGEF (aka RCC1) and RanGFP regulate the GTP- or GDP-bound state of Ran, creating a Ran gradient across the nuclear membrane that is used in nuclear import. CHC1, RAN, RANBP1, RANBP2, RANGAP1 4 RAN(2), RANBP2(12), RANGAP1(4) 2248318 18 16 17 7 3 8 3 2 2 0 0.47 1.00 171 FREEPATHWAY Neutrophils release superoxide to induce lysis in invading bacteria; in neighboring endothelial cells, superoxide dismutase scavenges radicals but produces pro-apoptotic peroxides. GPX1, GSR, GSS, IL8, NFKB1, NOX1, RELA, SOD1, TNF, XDH 10 GSR(2), GSS(2), NFKB1(2), NOX1(2), RELA(3), XDH(9) 2705600 20 16 20 4 5 6 2 4 3 0 0.47 1.00 172 BBCELLPATHWAY Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 4 CD4(2), HLA-DRA(1), HLA-DRB1(1) 650412 4 4 4 1 1 1 0 0 2 0 0.48 1.00 173 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 11 AKT1(1), HRAS(2), KLK2(1), NTRK1(3), PIK3R1(1), PLCG1(2), PRKCA(5), SHC1(1), SOS1(6) 3626928 22 21 22 7 3 8 6 2 3 0 0.48 1.00 174 GANGLIOSIDE_BIOSYNTHESIS B3GALT4, GALGT, SIAT4A, SIAT4B, SIAT7B, SIAT7D, SIAT9, ST3GAL1, ST3GAL2, ST3GAL4, ST3GAL5, ST6GALNAC2, ST6GALNAC4, ST8SIA1 8 B3GALT4(1), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2), ST3GAL5(2), ST8SIA1(2) 1506770 10 10 9 7 2 4 3 0 1 0 0.48 1.00 175 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALE(1), GALT(1), TGDS(1), UGDH(3), UXS1(3) 1073162 9 7 9 1 0 5 2 1 1 0 0.48 1.00 176 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 7 FUT3(3), FUT5(4), FUT6(2) 1397656 9 8 9 3 2 3 3 1 0 0 0.49 1.00 177 CYANOAMINO_ACID_METABOLISM ATP6V0C, SHMT1, GBA3, GGT1, SHMT1, SHMT2 5 GBA3(6), GGT1(2) 1181208 8 7 8 7 1 2 3 1 1 0 0.49 1.00 178 TGFBPATHWAY The TGF-beta receptor responds to ligand binding by activating the SMAD family of transcriptional regulations, commonly blocking cell growth. APC, CDH1, CREBBP, EP300, MADH2, MADH3, MADH4, MADH7, MADHIP, MAP2K1, MAP3K7, MAP3K7IP1, MAPK3, SKIL, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2 13 APC(9), CDH1(4), CREBBP(12), EP300(5), MAP2K1(2), MAP3K7(3), MAPK3(2), TGFB1(1), TGFB2(1), TGFBR2(3) 6897500 42 38 41 11 8 15 10 3 6 0 0.49 1.00 179 GLOBOSIDE_METABOLISM A4GALT, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, ST8SIA1 13 FUT9(1), GBGT1(3), GLA(2), HEXA(6), NAGA(1), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2), ST8SIA1(2) 2748498 20 17 19 7 2 11 4 2 1 0 0.49 1.00 180 HSA04140_REGULATION_OF_AUTOPHAGY Genes involved in regulation of autophagy ATG12, ATG3, ATG5, ATG7, BECN1, GABARAP, GABARAPL1, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNG, INS, LOC441925, PIK3C3, PIK3R4, PRKAA1, PRKAA2, ULK1, ULK2, ULK3 29 ATG12(1), ATG3(1), ATG7(4), BECN1(1), GABARAP(1), IFNA1(1), IFNA10(1), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNG(1), PIK3C3(3), PIK3R4(6), PRKAA2(2), ULK1(1), ULK2(3) 5718962 34 31 34 10 10 9 11 1 3 0 0.49 1.00 181 HSA04514_CELL_ADHESION_MOLECULES Genes involved in cell adhesion molecules (CAMs) ALCAM, CADM1, CADM3, CD2, CD22, CD226, CD274, CD276, CD28, CD34, CD4, CD40, CD40LG, CD58, CD6, CD80, CD86, CD8A, CD8B, CD99, CDH1, CDH15, CDH2, CDH3, CDH4, CDH5, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CNTN1, CNTN2, CNTNAP1, CNTNAP2, CTLA4, ESAM, F11R, GLG1, HLA-A, HLA-A29.1, HLA-B, HLA-C, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-E, HLA-F, HLA-G, ICAM1, ICAM2, ICAM3, ICOS, ICOSLG, ITGA4, ITGA6, ITGA8, ITGA9, ITGAL, ITGAM, ITGAV, ITGB1, ITGB2, ITGB7, ITGB8, JAM2, JAM3, L1CAM, MADCAM1, MAG, MPZ, MPZL1, NCAM1, NCAM2, NEGR1, NEO1, NFASC, NLGN1, NLGN2, NLGN3, NRCAM, NRXN1, NRXN2, NRXN3, OCLN, PDCD1, PDCD1LG2, PECAM1, PTPRC, PTPRF, PTPRM, PVR, PVRL1, PVRL2, PVRL3, SDC1, SDC2, SDC3, SDC4, SELE, SELL, SELP, SELPLG, SIGLEC1, SPN, VCAM1, VCAN 124 ALCAM(3), CADM1(3), CADM3(3), CD2(1), CD22(5), CD226(3), CD276(1), CD34(3), CD4(2), CD40(1), CD40LG(2), CD58(1), CD6(1), CD80(2), CD86(1), CD8B(1), CDH1(4), CDH2(8), CDH3(1), CDH4(6), CDH5(2), CLDN1(2), CLDN10(4), CLDN16(4), CLDN17(1), CLDN19(1), CLDN2(1), CLDN22(1), CLDN3(1), CLDN6(1), CLDN8(2), CLDN9(3), CNTN1(9), CNTN2(1), CNTNAP1(7), ESAM(4), F11R(1), GLG1(3), HLA-B(1), HLA-C(1), HLA-DMA(1), HLA-DMB(1), HLA-DQA2(2), HLA-DRA(1), HLA-DRB1(1), HLA-DRB5(2), HLA-G(1), ICAM1(2), ICAM3(2), ICOS(2), ITGA4(5), ITGA6(6), ITGA8(9), ITGA9(1), ITGAL(1), ITGAM(3), ITGAV(3), ITGB1(4), ITGB2(3), ITGB7(1), ITGB8(3), L1CAM(2), MADCAM1(1), MAG(4), MPZ(2), NCAM1(5), NEGR1(2), NEO1(6), NFASC(6), NLGN1(5), NLGN2(1), NLGN3(4), NRCAM(4), NRXN2(8), NRXN3(9), PTPRC(3), PTPRF(7), PTPRM(6), PVRL1(3), PVRL3(2), SDC3(1), SELE(4), SELL(2), SELP(8), SELPLG(1), SIGLEC1(7), VCAM1(4), VCAN(16) 38466512 279 120 278 115 73 112 51 18 25 0 0.50 1.00 182 ACETYLCHOLINE_SYNTHESIS ACHE, CHAT, CHKA, PCYT1A, PDHA1, PDHA2, PEMT, SLC18A3 8 ACHE(2), CHAT(2), CHKA(2), PCYT1A(2), PDHA1(2), PDHA2(5) 1926672 15 14 15 4 4 7 3 1 0 0 0.50 1.00 183 UBIQUITIN_MEDIATED_PROTEOLYSIS CDC34, HIP2, NRF1, UBE1, UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2E1, UBE2E3, UBE2G1, UBE2G2, UBE2G2, TAX1BP3, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2L3, UBE2L6, UBE2M, UBE2N, UBE2S, UBE3A 23 NRF1(1), UBE2A(2), UBE2C(1), UBE2D1(1), UBE2D2(1), UBE2E3(1), UBE2G2(1), UBE2J1(3), UBE2J2(2), UBE2L6(1), UBE2M(1), UBE3A(4) 2847644 19 18 19 4 6 7 2 1 3 0 0.50 1.00 184 BETAOXIDATIONPATHWAY Beta-Oxidation of Fatty Acids ACADL, ACADM, ACADS, ACAT1, ECHS1, HADHA 6 ACADL(2), ACADM(1), ACADS(3), ACAT1(1), HADHA(2) 1468678 9 9 9 2 2 3 1 1 2 0 0.51 1.00 185 PTENPATHWAY PTEN suppresses AKT-induced cell proliferation and antagonizes the action of PI3K. AKT1, BCAR1, CDKN1B, FOXO3A, GRB2, ILK, ITGB1, MAPK1, MAPK3, PDK2, PDPK1, PIK3CA, PIK3R1, PTEN, PTK2, SHC1, SOS1, TNFSF6 14 AKT1(1), BCAR1(5), ILK(1), ITGB1(4), MAPK1(1), MAPK3(2), PDK2(2), PDPK1(1), PIK3R1(1), PTK2(3), SHC1(1), SOS1(6) 4492542 28 25 28 6 8 8 7 2 3 0 0.51 1.00 186 IL5PATHWAY Pro-inflammatory IL-5 is secretes by activated T cells, eosinophils, and mast cells, and stimulates the proliferation and activation of eosinophils in bone marrow. CCL11, CCR3, CD4, HLA-DRA, HLA-DRB1, IL1B, IL4, IL5, IL5RA, IL6 10 CCR3(1), CD4(2), HLA-DRA(1), HLA-DRB1(1), IL1B(1), IL4(2), IL5RA(2) 1438952 10 9 10 2 2 4 1 0 3 0 0.51 1.00 187 HSA00040_PENTOSE_AND_GLUCURONATE_INTERCONVERSIONS Genes involved in pentose and glucuronate interconversions AKR1B1, DCXR, GUSB, RPE, UGDH, UGP2, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, XYLB 25 GUSB(3), UGDH(3), UGP2(5), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4) 6739792 44 39 44 10 11 14 13 3 3 0 0.51 1.00 188 HSA00740_RIBOFLAVIN_METABOLISM Genes involved in riboflavin metabolism ACP1, ACP2, ACP5, ACP6, ACPP, ACPT, ENPP1, ENPP3, FLAD1, LHPP, MTMR1, MTMR2, MTMR6, PHPT1, RFK, TYR 16 ACP1(1), ACP6(3), ACPT(2), ENPP1(7), ENPP3(4), FLAD1(2), MTMR1(1), MTMR2(1), MTMR6(3), TYR(3) 4031522 27 24 27 8 7 11 4 0 5 0 0.52 1.00 189 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 8 HK1(4), KHK(1), MPI(1), PGM1(1), PYGM(6), TPI1(4), TREH(1) 2572278 18 17 17 6 6 5 5 0 2 0 0.52 1.00 190 LDLPATHWAY Low density lipoproteins (LDL) are present in blood plasma, contain cholesterol and triglycerides, and contribute to atherogenic plaque formation. ACAT1, CCL2, CSF1, IL6, LDLR, LPL 6 ACAT1(1), CSF1(2), LDLR(4), LPL(3) 1424534 10 10 10 2 5 4 1 0 0 0 0.52 1.00 191 PLCDPATHWAY Phospholipase C (PLC-d1) hydrolyzes the membrane lipid PIP2 to DAG and IP3, which induce calcium influx and activates protein kinase C. ADRA1B, PLCD1, PRKCA, PRKCB1, TGM2 4 ADRA1B(4), PRKCA(5), TGM2(1) 1368286 10 9 10 3 3 3 3 0 1 0 0.52 1.00 192 HSA00272_CYSTEINE_METABOLISM Genes involved in cysteine metabolism CARS, CARS2, CDO1, CTH, GOT1, GOT2, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, MPST, SDS, SULT1B1, SULT1C2, SULT1C4, SULT4A1 17 CARS(6), GOT1(2), GOT2(3), LDHAL6B(1), LDHB(2), LDHC(1), SDS(2), SULT1B1(3), SULT1C2(3), SULT1C4(2) 3393748 25 21 24 4 2 13 6 2 2 0 0.52 1.00 193 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 26 CCL3(2), CCR1(2), CCR3(1), CCR4(3), CD4(2), CXCR3(1), IFNG(1), IFNGR1(3), IFNGR2(1), IL12A(1), IL12B(3), IL12RB1(3), IL12RB2(3), IL18R1(2), IL4(2), TGFB1(1), TGFB2(1) 4906392 32 27 32 14 8 9 7 0 8 0 0.52 1.00 194 CARM1PATHWAY The methyltransferase CARM1 interacts with transcription factors such as CBP/p300 and methylates histones H3 and H4. CARM1, CREB1, CREBBP, EP300, NCOA3, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RARA, RXRA 13 CARM1(1), CREBBP(12), EP300(5), NCOA3(4), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), RARA(1), RXRA(1) 5467804 34 30 33 9 7 14 4 5 4 0 0.53 1.00 195 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 21 CDK5(2), CFL1(3), CHN1(2), LIMK1(1), MAP3K1(3), MYL2(1), MYLK(7), NCF2(5), PAK1(3), PDGFRA(8), PIK3R1(1), PLD1(10), PPP1R12B(3), RAC1(2), RALBP1(1), RPS6KB1(1), TRIO(7), VAV1(7) 8864578 67 48 65 26 17 27 13 7 3 0 0.53 1.00 196 PHOTOSYNTHESIS ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, FDXR 22 ATP6V0A1(4), ATP6V0A4(2), ATP6V0D1(1), ATP6V1A(3), ATP6V1B1(2), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4), FDXR(3) 4317924 25 22 25 11 9 3 7 1 5 0 0.53 1.00 197 KERATINOCYTEPATHWAY Keratinocyte differentiation, which models the differentiation of epidermal cells, requires the four main MAP kinase pathways. BCL2, CEBPA, CHUK, DAXX, EGF, EGFR, ETS1, ETS2, FOS, HOXA7, HRAS, IKBKB, JUN, MAP2K1, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K1, MAP3K14, MAP3K5, MAPK1, MAPK13, MAPK14, MAPK3, MAPK8, NFKB1, NFKBIA, PPP2CA, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCQ, RAF1, RELA, RIPK1, SP1, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TRAF2 43 CEBPA(1), CHUK(2), DAXX(3), EGF(6), EGFR(9), ETS1(2), FOS(1), HOXA7(3), HRAS(2), IKBKB(3), JUN(2), MAP2K1(2), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAP3K14(1), MAP3K5(3), MAPK1(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPK8(2), NFKB1(2), PRKCA(5), PRKCD(2), PRKCE(5), PRKCG(9), PRKCH(1), PRKCQ(4), RAF1(1), RELA(3), SP1(1), TNFRSF1A(2), TNFRSF1B(1) 13433838 92 65 91 24 26 35 14 6 11 0 0.53 1.00 198 EDG1PATHWAY The lipid S1P is an EDG1 ligand promoting chemotaxis via Rac1 and cell survival and proliferation via ERK activation. ADCY1, AKT1, ARHA, ASAH1, EDG1, GNAI1, GNB1, GNGT1, ITGAV, ITGB3, MAPK1, MAPK3, PDGFA, PDGFRA, PIK3CA, PIK3R1, PLCB1, PRKCA, PRKCB1, PTK2, RAC1, SKIP, SMPD1, SMPD2, SPHK1, SRC 21 ADCY1(8), AKT1(1), GNAI1(2), GNB1(1), ITGAV(3), ITGB3(3), MAPK1(1), MAPK3(2), PDGFRA(8), PIK3R1(1), PLCB1(7), PRKCA(5), PTK2(3), RAC1(2), SMPD1(3), SMPD2(2) 6767204 52 39 52 20 16 20 9 6 1 0 0.53 1.00 199 ERKPATHWAY Cell growth is promoted by Ras activation of the anti-apoptotic p44/42 MAP kinase pathway. DPM2, EGFR, ELK1, GNAS, GNB1, GNGT1, GRB2, HRAS, IGF1R, ITGB1, KLK2, MAP2K1, MAP2K2, MAPK1, MAPK3, MKNK1, MKNK2, MYC, NGFB, NGFR, PDGFRA, PPP2CA, PTPRR, RAF1, RPS6KA1, RPS6KA5, SHC1, SOS1, SRC, STAT3 29 EGFR(9), GNAS(4), GNB1(1), HRAS(2), IGF1R(1), ITGB1(4), KLK2(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), MYC(1), NGFR(1), PDGFRA(8), PTPRR(6), RAF1(1), RPS6KA1(4), RPS6KA5(3), SHC1(1), SOS1(6), STAT3(1) 9071948 61 50 60 18 18 18 18 3 4 0 0.53 1.00 200 HSA00471_D_GLUTAMINE_AND_D_GLUTAMATE_METABOLISM Genes involved in D-glutamine and D-glutamate metabolism GLS, GLS2, GLUD1, GLUD2 3 GLS(2), GLUD1(3) 848170 5 5 5 1 1 2 1 0 1 0 0.54 1.00 201 STREPTOMYCIN_BIOSYNTHESIS GCK, HK1, HK2, HK3, IMPA1, PGM1, PGM3, TGDS 8 GCK(1), HK1(4), HK2(6), HK3(7), IMPA1(1), PGM1(1), TGDS(1) 2756330 21 19 21 5 8 9 1 2 1 0 0.54 1.00 202 NUCLEAR_RECEPTORS ALK, AR, ESR1, ESR2, ESRRA, HNF4A, NPM1, NR0B1, NR1D2, NR1H2, NR1H3, NR1I2, NR1I3, NR2C2, NR2E1, NR2F1, NR2F2, NR2F6, NR3C1, NR4A1, NR4A2, NR5A1, NR5A2, PGR, PPARA, PPARD, PPARG, RARA, RARB, RARG, ROR1, RORA, RORC, RXRA, RXRB, RXRG, THRA, THRA, NR1D1, THRB, VDR 40 ALK(6), AR(4), ESR1(6), ESR2(1), HNF4A(2), NR0B1(4), NR1H3(2), NR1I2(1), NR1I3(1), NR2C2(1), NR2E1(4), NR2F6(1), NR4A1(4), NR4A2(4), NR5A2(4), PGR(3), PPARA(2), PPARD(2), RARA(1), RARB(2), RARG(3), ROR1(4), RORA(3), RORC(3), RXRA(1), RXRG(5), THRA(2), THRB(1), VDR(3) 11522474 80 57 80 26 23 29 14 4 10 0 0.54 1.00 203 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 108 ABL1(2), ANAPC1(4), ANAPC4(3), ANAPC5(3), ATM(7), ATR(11), BUB1(4), BUB1B(5), BUB3(1), CCNA1(1), CCNB1(1), CCNB3(9), CCND1(1), CCND2(3), CCND3(1), CCNE2(2), CDC25B(3), CDC25C(1), CDC27(3), CDC6(4), CDC7(1), CDK2(1), CDK7(1), CDKN2C(1), CDKN2D(1), CHEK1(4), CHEK2(3), CREBBP(12), CUL1(3), DBF4(4), E2F1(3), EP300(5), ESPL1(3), GADD45A(1), GADD45G(1), GSK3B(1), HDAC1(2), MAD1L1(5), MAD2L1(2), MCM2(1), MCM3(1), MCM4(4), MCM5(6), MCM6(2), MCM7(3), MDM2(1), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), PKMYT1(1), PLK1(1), PRKDC(15), PTTG1(1), PTTG2(2), RB1(7), RBL1(6), RBL2(5), RBX1(1), SFN(2), SKP1(1), SKP2(1), SMAD2(2), SMAD4(2), SMC1A(2), SMC1B(5), TGFB1(1), TGFB2(1), WEE1(2), YWHAB(2), YWHAE(1), YWHAQ(1) 36875548 207 112 205 58 50 74 37 18 28 0 0.54 1.00 204 PORPHYRIN_AND_CHLOROPHYLL_METABOLISM ALAD, BLVRA, BLVRB, CP, CPOX, EPRS, FECH, GUSB, HCCS, HMBS, HMOX1, HMOX2, PPOX, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4, UROD, UROS 26 BLVRA(2), CP(3), CPOX(3), EPRS(11), FECH(2), GUSB(3), HMBS(2), HMOX1(1), PPOX(1), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2B15(1), UGT2B4(4), UROD(1) 7022990 45 39 45 10 9 20 11 2 3 0 0.54 1.00 205 TOB1PATHWAY TGF-beta signaling activates SMADs, which interact with intracellular Tob to maintain unstimulated T cells by repressing IL-2 expression. CD28, CD3D, CD3E, CD3G, CD3Z, IFNG, IL2, IL2RA, IL4, MADH3, MADH4, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, TOB1, TOB2, TRA@, TRB@ 16 CD3D(1), IFNG(1), IL4(2), TGFB1(1), TGFB2(1), TGFBR2(3), TGFBR3(6), TOB2(2) 2875946 17 17 17 8 0 8 6 0 3 0 0.55 1.00 206 HSA02010_ABC_TRANSPORTERS_GENERAL Genes involved in ABC transporters - general ABCA1, ABCA10, ABCA12, ABCA13, ABCA2, ABCA3, ABCA4, ABCA5, ABCA6, ABCA7, ABCA8, ABCA9, ABCB1, ABCB10, ABCB11, ABCB4, ABCB5, ABCB6, ABCB7, ABCB8, ABCB9, ABCC1, ABCC10, ABCC11, ABCC12, ABCC2, ABCC3, ABCC4, ABCC5, ABCC6, ABCC8, ABCC9, ABCD1, ABCD2, ABCD3, ABCD4, ABCG1, ABCG2, ABCG4, ABCG5, ABCG8, CFTR, TAP1, TAP2 42 ABCA1(6), ABCA10(8), ABCA12(7), ABCA13(27), ABCA2(6), ABCA3(3), ABCA4(12), ABCA5(3), ABCA6(6), ABCA7(4), ABCA8(5), ABCA9(8), ABCB10(6), ABCB11(6), ABCB4(9), ABCB5(7), ABCB6(4), ABCB7(2), ABCB8(1), ABCB9(4), ABCC1(4), ABCC10(4), ABCC11(5), ABCC12(12), ABCC2(4), ABCC3(2), ABCC4(1), ABCC5(7), ABCC6(3), ABCC8(5), ABCC9(9), ABCD1(3), ABCD4(1), ABCG1(1), ABCG2(1), ABCG4(1), ABCG5(1), ABCG8(8), CFTR(4), TAP1(2) 31347224 212 110 210 83 51 83 43 11 24 0 0.55 1.00 207 PITX2PATHWAY The bicoid-related transcription factor Pitx2 is activated by Wnt binding to the Frizzled receptor and induces tissue-specific cell proliferation. APC, AXIN1, CREBBP, CTNNB1, DVL1, EP300, FZD1, GSK3B, HDAC1, HTATIP, LDB1, LEF1, PITX2, PPARBP, TRRAP, WNT1 14 APC(9), CREBBP(12), CTNNB1(3), DVL1(3), EP300(5), FZD1(1), GSK3B(1), HDAC1(2), LDB1(1), LEF1(3), PITX2(3), TRRAP(12) 8810288 55 46 54 19 10 18 17 3 7 0 0.55 1.00 208 HSA00565_ETHER_LIPID_METABOLISM Genes involved in ether lipid metabolism AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, AGPS, CHPT1, ENPP2, ENPP6, LYCAT, PAFAH1B1, PAFAH1B2, PAFAH1B3, PAFAH2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLD1, PLD2, PPAP2A, PPAP2B, PPAP2C 30 AGPAT3(1), AGPAT6(2), ENPP2(9), ENPP6(1), PAFAH1B1(1), PAFAH1B2(1), PAFAH2(1), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLD1(10), PLD2(4), PPAP2B(2) 6299776 52 37 50 21 16 22 7 1 6 0 0.55 1.00 209 CDMACPATHWAY Cadmium 2+ promotes cell proliferation in cultured macrophages by entering the cell via calcium channels and activating the MAP kinase pathway. CUZD1, FOS, HRAS, JUN, MAP2K1, MAPK1, MAPK3, MYC, NFKB1, NFKBIA, PLCB1, PRKCA, PRKCB1, RAF1, RELA, TNF 15 CUZD1(2), FOS(1), HRAS(2), JUN(2), MAP2K1(2), MAPK1(1), MAPK3(2), MYC(1), NFKB1(2), PLCB1(7), PRKCA(5), RAF1(1), RELA(3) 4191188 31 25 31 10 10 10 3 6 2 0 0.55 1.00 210 EXTRINSICPATHWAY The extrinsic prothrombin activation pathway requires the release of thromboplastin from damaged tissues to activate the blood clotting cascade. F10, F2, F2R, F3, F5, F7, FGA, FGB, FGG, PROC, PROS1, SERPINC1, TFPI 13 F10(3), F2R(2), F3(2), F5(15), FGA(5), FGB(3), FGG(1), SERPINC1(5) 4394464 36 26 36 8 5 15 13 2 1 0 0.56 1.00 211 CELLCYCLEPATHWAY Cyclins interact with cyclin-dependent kinases to form active kinase complexes that regulate progression through the cell cycle. CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNH, CDC2, CDC25A, CDK2, CDK4, CDK6, CDK7, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CDKN2D, E2F1, RB1, RBL1, TFDP1 21 CCNA1(1), CCNB1(1), CCND1(1), CCND2(3), CCND3(1), CDK2(1), CDK7(1), CDKN2C(1), CDKN2D(1), E2F1(3), RB1(7), RBL1(6) 4212192 27 23 27 6 4 9 4 3 7 0 0.56 1.00 212 HSA04070_PHOSPHATIDYLINOSITOL_SIGNALING_SYSTEM Genes involved in phosphatidylinositol signaling system CALM1, CALM2, CALM3, CALML3, CALML6, CARKL, CDIPT, CDS1, CDS2, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKI, DGKQ, DGKZ, FN3K, IMPA1, IMPA2, INPP1, INPP4A, INPP4B, INPP5A, INPP5B, INPP5D, INPP5E, INPPL1, ITGB1BP3, ITPK1, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, OCRL, PI4KA, PI4KB, PIB5PA, PIK3C2A, PIK3C2B, PIK3C2G, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCZ1, PRKCA, PRKCB1, PRKCG, PTEN, PTPMT1, SKIP, SYNJ1, SYNJ2 71 CDS1(2), DGKA(6), DGKB(4), DGKD(5), DGKE(2), DGKG(2), DGKI(7), DGKZ(3), IMPA1(1), INPP1(1), INPP4A(5), INPP4B(4), INPP5A(3), INPP5B(5), INPP5D(6), INPP5E(2), INPPL1(3), ITPKA(1), ITPKB(3), ITPR1(5), ITPR2(11), ITPR3(3), OCRL(5), PI4KA(4), PI4KB(2), PIK3C2A(4), PIK3C2B(7), PIK3C2G(7), PIK3C3(3), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PIP4K2A(2), PIP4K2B(3), PIP4K2C(3), PIP5K1A(4), PIP5K1B(1), PIP5K1C(2), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PLCD3(2), PLCE1(10), PLCG1(2), PLCG2(3), PLCZ1(3), PRKCA(5), PRKCG(9), SYNJ1(2), SYNJ2(5) 33604442 215 107 214 75 70 68 37 15 25 0 0.57 1.00 213 CARBON_FIXATION ALDOA, ALDOB, ALDOC, FBP1, FBP2, GOT1, GOT2, GPT, GPT2, MDH1, MDH2, ME1, ME2, ME3, PGK1, PKLR, PKM2, RPE, RPE, LOC440001, RPIA, TKT, TPI1 21 ALDOA(1), ALDOB(2), ALDOC(1), FBP2(1), GOT1(2), GOT2(3), GPT(1), GPT2(2), MDH1(1), MDH2(1), ME2(2), ME3(2), PGK1(1), PKLR(3), PKM2(1), RPIA(1), TKT(1), TPI1(4) 4743700 30 28 28 12 8 12 4 2 4 0 0.57 1.00 214 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@ 16 CD3D(1), CD80(2), CD86(1), HLA-DRA(1), HLA-DRB1(1), ICOS(2), ITK(2), LCK(2), PIK3R1(1), PTPN11(3) 2833226 16 16 16 7 2 7 3 2 2 0 0.57 1.00 215 SPPAPATHWAY Thrombin cleaves protease-activated receptors PAR1 and PAR4 to induce calcium influx and activate platelet aggregation, a process inhibited by aspirin. F2, F2R, F2RL3, GNAI1, GNB1, GNGT1, HRAS, ITGA1, ITGB1, MAP2K1, MAPK1, MAPK3, PLA2G4A, PLCB1, PRKCA, PRKCB1, PTGS1, PTK2, RAF1, SRC, SYK, TBXAS1 21 F2R(2), F2RL3(2), GNAI1(2), GNB1(1), HRAS(2), ITGA1(4), ITGB1(4), MAP2K1(2), MAPK1(1), MAPK3(2), PLA2G4A(5), PLCB1(7), PRKCA(5), PTGS1(2), PTK2(3), RAF1(1), SYK(1), TBXAS1(5) 6603266 51 37 49 15 13 22 8 3 5 0 0.57 1.00 216 ST_GA12_PATHWAY G-alpha-12 promotes cell survival and proliferation, is involved in the stress response, and activates JNK. BF, BTK, DLG4, EPHB2, F2, F2RL1, F2RL2, F2RL3, JUN, MAP2K5, MAPK1, MAPK7, MAPK8, MYEF2, PLD1, PLD2, PLD3, PTK2, RAF1, RASAL1, SRC, TEC, VAV1 22 BTK(5), DLG4(1), EPHB2(5), F2RL1(3), F2RL2(1), F2RL3(2), JUN(2), MAP2K5(2), MAPK1(1), MAPK7(1), MAPK8(2), MYEF2(3), PLD1(10), PLD2(4), PLD3(1), PTK2(3), RAF1(1), RASAL1(4), TEC(2), VAV1(7) 7510888 60 41 58 18 18 21 10 4 7 0 0.57 1.00 217 INFLAMPATHWAY Interleukins and TNF serve as signals to coordinate the inflammatory response, in which macrophages recruit and activate neutrophils, fibroblasts, and T cells. CD4, CSF1, CSF2, CSF3, HLA-DRA, HLA-DRB1, IFNA1, IFNB1, IFNG, IL10, IL11, IL12A, IL12B, IL13, IL15, IL1A, IL2, IL3, IL4, IL5, IL6, IL7, IL8, LTA, PDGFA, TGFB1, TGFB2, TGFB3, TNF 29 CD4(2), CSF1(2), HLA-DRA(1), HLA-DRB1(1), IFNA1(1), IFNB1(1), IFNG(1), IL10(1), IL12A(1), IL12B(3), IL4(2), LTA(3), TGFB1(1), TGFB2(1) 3596846 21 20 21 7 3 6 5 3 4 0 0.58 1.00 218 ST_INTERLEUKIN_4_PATHWAY Like IL-13, IL-4 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor. AKT1, AKT2, AKT3, CISH, GRB2, IARS, IL13RA1, IL2RG, IL4, IL4R, INPP5D, JAK1, JAK2, JAK3, NR0B2, PI3, PIK3CA, PPP1R13B, RPS6KB1, SERPINA4, SHC1, SOS1, SOS2, SRC, STAT6, TYK2 25 AKT1(1), AKT3(2), IARS(3), IL13RA1(2), IL2RG(1), IL4(2), INPP5D(6), JAK1(1), JAK2(3), JAK3(7), NR0B2(1), PI3(1), PPP1R13B(4), RPS6KB1(1), SERPINA4(4), SHC1(1), SOS1(6), SOS2(4), STAT6(1), TYK2(8) 9476898 59 48 59 17 8 23 15 4 9 0 0.58 1.00 219 ATP_SYNTHESIS ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP6V0A1(4), ATP6V0A4(2), ATP6V0D1(1), ATP6V1A(3), ATP6V1B1(2), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4) 4058222 22 20 22 11 7 2 7 1 5 0 0.58 1.00 220 FLAGELLAR_ASSEMBLY ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP6V0A1(4), ATP6V0A4(2), ATP6V0D1(1), ATP6V1A(3), ATP6V1B1(2), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4) 4058222 22 20 22 11 7 2 7 1 5 0 0.58 1.00 221 TYPE_III_SECRETION_SYSTEM ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP6V0A1(4), ATP6V0A4(2), ATP6V0D1(1), ATP6V1A(3), ATP6V1B1(2), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4) 4058222 22 20 22 11 7 2 7 1 5 0 0.58 1.00 222 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), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), AKAP1(3), AKAP11(7), AKAP12(4), AKAP3(6), AKAP5(1), AKAP6(12), AKAP7(2), AKAP8(3), AKAP9(6), ARHGEF1(2), CHMP1B(1), GNA12(1), GNA13(1), GNA14(1), GNA15(1), GNAI3(1), GNAL(2), GNAZ(2), GNB1(1), GNB2(3), GNB3(2), GNB5(1), GNG12(1), GNG3(1), GNG4(2), GNG5(1), HRAS(2), ITPR1(5), KRAS(1), PDE1A(2), PDE1B(1), PDE4B(3), PDE4C(4), PDE4D(1), PDE7B(1), PDE8A(6), PDE8B(2), PLCB3(4), PPP3CA(2), PPP3CC(2), PRKACA(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), PRKCD(2), PRKCE(5), PRKCG(9), PRKCH(1), PRKCI(4), PRKCQ(4), PRKD1(9), PRKD3(2), SLC9A1(3), USP5(3) 30555480 203 100 202 57 65 66 33 17 22 0 0.58 1.00 223 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 13 ACTR2(1), ARPC1A(2), ARPC1B(1), CDC42(1), PAK1(3), PDGFRA(8), PIK3R1(1), RAC1(2), WASL(2) 2999656 21 19 21 7 7 7 4 3 0 0 0.59 1.00 224 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 68 AKT1(1), AKT3(2), CASP9(1), CDC42(1), CHP(2), HRAS(2), KDR(11), KRAS(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPKAPK2(1), NFAT5(3), NFATC2(5), NFATC3(3), NFATC4(2), NOS3(1), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLCG1(2), PLCG2(3), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKCA(5), PRKCG(9), PTK2(3), PXN(3), RAC1(2), RAF1(1), SHC2(3), SPHK2(1) 19311932 134 80 134 51 40 45 15 19 15 0 0.59 1.00 225 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 8 IFNG(1), IFNGR1(3), JAK1(1), JAK2(3), PLA2G2A(1), PTPRU(8), STAT1(2) 3011048 19 18 18 3 4 9 4 0 2 0 0.60 1.00 226 ST_ERK1_ERK2_MAPK_PATHWAY The Erk1 and Erk2 MAP kinase pathways are regulated by Raf, Mos, and Tpl-2. ARAF1, ATF1, BAD, BRAF, COPEB, CREB1, CREB3, CREB5, DUSP4, DUSP6, DUSP9, EEF2K, EIF4E, GRB2, HTATIP, MAP2K1, MAP2K2, MAP3K8, MAPK1, MAPK3, MKNK1, MKNK2, MOS, NFKB1, RAP1A, RPS6KA1, RPS6KA2, RPS6KA3, SHC1, SOS1, SOS2, TRAF3 29 BRAF(7), CREB3(2), CREB5(3), DUSP4(1), DUSP6(1), DUSP9(4), EEF2K(3), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), MOS(4), NFKB1(2), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), SHC1(1), SOS1(6), SOS2(4), TRAF3(1) 8109146 53 44 52 15 10 15 17 2 9 0 0.60 1.00 227 NKCELLSPATHWAY Natural killer (NK) lymphocytes are inhibited by MHC and activated by surface glycoproteins on tumor or virus-infected cells, which undergo perforin-mediated lysis. B2M, HLA-A, IL18, ITGB1, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LAT, MAP2K1, MAPK3, PAK1, PIK3CA, PIK3R1, PTK2B, PTPN6, RAC1, SYK, VAV1 18 B2M(1), ITGB1(4), KLRC1(1), KLRC3(1), LAT(1), MAP2K1(2), MAPK3(2), PAK1(3), PIK3R1(1), RAC1(2), SYK(1), VAV1(7) 4237290 26 24 26 8 9 6 5 4 2 0 0.60 1.00 228 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 15 B3GALT4(1), HEXA(6), SLC33A1(3), ST3GAL1(1), ST3GAL2(2), ST3GAL5(2), ST6GALNAC3(3), ST6GALNAC5(2), ST8SIA1(2) 3398732 22 21 21 10 7 8 4 0 3 0 0.60 1.00 229 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 19 CSNK2A1(2), FOS(1), HRAS(2), IGF1(2), IGF1R(1), IRS1(4), JUN(2), MAP2K1(2), MAPK3(2), MAPK8(2), PIK3R1(1), PTPN11(3), RAF1(1), RASA1(6), SHC1(1), SOS1(6), SRF(2) 6085998 40 35 40 7 12 13 6 4 5 0 0.61 1.00 230 PKCPATHWAY Gq-coupled receptors promote hydrolysis of PIP2 to DAG and IP3, which causes calcium influx and activates protein kinase C. GNAQ, NFKB1, NFKBIA, PLCB1, PRKCA, PRKCB1, RELA 6 NFKB1(2), PLCB1(7), PRKCA(5), RELA(3) 2235858 17 13 17 6 5 7 1 2 2 0 0.61 1.00 231 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 25 CSNK2A1(2), EGF(6), EGFR(9), FOS(1), HRAS(2), JAK1(1), JUN(2), MAP2K1(2), MAP3K1(3), MAPK3(2), MAPK8(2), PIK3R1(1), PLCG1(2), PRKCA(5), RAF1(1), RASA1(6), SHC1(1), SOS1(6), SRF(2), STAT1(2), STAT3(1), STAT5A(2) 9513210 61 48 60 14 18 20 10 4 9 0 0.61 1.00 232 BILE_ACID_BIOSYNTHESIS ACAA1, ACAA2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1C4, AKR1D1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, BAAT, CEL, CYP27A1, CYP7A1, HADHB, SOAT2, SRD5A1, SRD5A2 27 ACAA2(1), ADH1B(1), ADH1C(1), ADH4(2), ADH7(1), ADHFE1(2), AKR1C4(1), AKR1D1(4), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2), BAAT(3), CEL(5), CYP27A1(2), CYP7A1(3), HADHB(2), SOAT2(1), SRD5A1(2), SRD5A2(2) 6312592 44 36 42 13 9 21 6 4 4 0 0.61 1.00 233 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 19 ALDH18A1(4), ARG1(2), ASL(2), CKB(1), CKM(2), CKMT2(1), GATM(1), GLUD1(3), NAGS(1), ODC1(1), OTC(2), SMS(4) 3860642 24 21 24 6 4 10 5 0 5 0 0.62 1.00 234 GATA3PATHWAY GATA-3 is a transcription factor that promotes differentiation of helper T cells into Th2 cells, which secrete cytokines IL4, IL5, and IL13. GATA3, IL13, IL4, IL5, JUNB, MAF, MAP2K3, MAPK14, NFATC1, NFATC2, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 16 GATA3(5), IL4(2), MAF(1), MAP2K3(2), MAPK14(1), NFATC2(5), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 3260782 26 20 26 6 12 8 3 1 2 0 0.62 1.00 235 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 52 ABP1(6), ACAT1(1), ACMSD(1), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2), AOC2(2), AOC3(3), AOX1(11), CAT(1), CYP19A1(3), CYP1A2(1), CYP2A13(2), CYP2A6(3), CYP2B6(3), CYP2C19(6), CYP2C8(3), CYP2C9(2), CYP2D6(3), CYP2E1(1), CYP2F1(4), CYP2J2(2), CYP3A4(1), CYP3A7(1), CYP4B1(3), CYP4F8(1), DDC(2), EHHADH(1), GCDH(1), HAAO(2), HADHA(2), KMO(3), KYNU(3), SDS(2), TDO2(1), TPH1(1), WARS(4), WARS2(1) 14418534 98 71 97 48 27 39 19 7 6 0 0.62 1.00 236 FRUCTOSE_AND_MANNOSE_METABOLISM AKR1B1, ALDOA, ALDOB, ALDOC, FBP1, FBP2, FPGT, GCK, GMDS, GMPPA, GMPPB, HK1, HK2, HK3, KHK, MPI, PFKFB1, PFKFB3, PFKFB4, PFKM, PFKP, PMM1, PMM2, SORD, TPI1 25 ALDOA(1), ALDOB(2), ALDOC(1), FBP2(1), FPGT(2), GCK(1), GMPPA(1), HK1(4), HK2(6), HK3(7), KHK(1), MPI(1), PFKFB1(3), PFKM(5), PFKP(2), PMM1(1), TPI1(4) 6506434 43 36 41 15 17 11 8 4 3 0 0.63 1.00 237 GLUCONEOGENESIS ACYP1, ACYP2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GCK, GPI, HK1, HK2, HK3, LDHA, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKM, PFKP, PGAM1, PGK1, PGM1, PGM3, PKLR, PKM2, TPI1 53 ADH1B(1), ADH1C(1), ADH4(2), ADH7(1), ADHFE1(2), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH3B2(2), ALDH9A1(2), ALDOA(1), ALDOB(2), ALDOC(1), BPGM(2), DLAT(1), DLD(2), ENO2(2), ENO3(1), FBP2(1), G6PC(2), GAPDH(3), GCK(1), GPI(5), HK1(4), HK2(6), HK3(7), LDHB(2), LDHC(1), PDHA1(2), PDHA2(5), PFKM(5), PFKP(2), PGK1(1), PGM1(1), PKLR(3), PKM2(1), TPI1(4) 12973530 88 66 85 22 28 38 11 6 5 0 0.63 1.00 238 GLYCOLYSIS ACYP1, ACYP2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GCK, GPI, HK1, HK2, HK3, LDHA, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKM, PFKP, PGAM1, PGK1, PGM1, PGM3, PKLR, PKM2, TPI1 53 ADH1B(1), ADH1C(1), ADH4(2), ADH7(1), ADHFE1(2), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH3B2(2), ALDH9A1(2), ALDOA(1), ALDOB(2), ALDOC(1), BPGM(2), DLAT(1), DLD(2), ENO2(2), ENO3(1), FBP2(1), G6PC(2), GAPDH(3), GCK(1), GPI(5), HK1(4), HK2(6), HK3(7), LDHB(2), LDHC(1), PDHA1(2), PDHA2(5), PFKM(5), PFKP(2), PGK1(1), PGM1(1), PKLR(3), PKM2(1), TPI1(4) 12973530 88 66 85 22 28 38 11 6 5 0 0.63 1.00 239 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 60 AKT1(1), AKT3(2), BCL2L1(2), CDC42(1), CDK2(1), CREB3(2), CREB5(3), EBP(1), ERBB4(9), F2RL2(1), GAB1(2), GADD45A(1), GSK3A(4), GSK3B(1), IGF1(2), INPPL1(3), IRS1(4), IRS2(2), IRS4(3), MET(3), MYC(1), NOLC1(2), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PARD3(5), PARD6A(2), PDK1(1), PIK3CD(3), PPP1R13B(4), PREX1(12), PTK2(3), PTPN1(1), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KB1(1), SFN(2), SHC1(1), SLC2A4(2), SOS1(6), SOS2(4), TSC1(6), TSC2(6), YWHAB(2), YWHAE(1), YWHAQ(1) 20089970 135 82 135 45 26 53 28 9 19 0 0.63 1.00 240 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 6 ATM(7), ATR(11), CDC25C(1), CHEK1(4), CHEK2(3) 4065520 26 22 26 1 6 6 5 5 4 0 0.63 1.00 241 RBPATHWAY The ATM protein kinase recognizes DNA damage and blocks cell cycle progression by phosphorylating chk1 and p53, which normally inhibits Rb to allow G1/S transitions. ATM, CDC2, CDC25A, CDC25B, CDC25C, CDK2, CDK4, CHEK1, MYT1, RB1, TP53, WEE1, YWHAH 11 ATM(7), CDC25B(3), CDC25C(1), CDK2(1), CHEK1(4), RB1(7), WEE1(2) 4531524 25 22 25 3 4 10 2 1 8 0 0.64 1.00 242 HSA00730_THIAMINE_METABOLISM Genes involved in thiamine metabolism LHPP, MTMR1, MTMR2, MTMR6, NFS1, PHPT1, THTPA, TPK1 8 MTMR1(1), MTMR2(1), MTMR6(3), NFS1(3), TPK1(3) 1721082 11 11 11 3 2 4 4 0 1 0 0.64 1.00 243 RARRXRPATHWAY RXR and RAR suppress transcription in the absence of ligand and, on binding trans- or 9-cis-retinoic acid, are ubiquitinated to allow transcription to proceed. ERCC3, GTF2A1, GTF2B, GTF2E1, GTF2F1, HDAC3, NCOA1, NCOA2, NCOA3, NCOR2, PCAF, POLR2A, RARA, RXRA, TBP 14 ERCC3(2), GTF2A1(1), GTF2B(1), GTF2E1(1), HDAC3(1), NCOA1(6), NCOA2(10), NCOA3(4), NCOR2(6), POLR2A(2), RARA(1), RXRA(1), TBP(1) 6895008 37 34 37 18 8 15 5 2 7 0 0.64 1.00 244 GSK3PATHWAY Bacterial lipopolysaccharide activates AKT to promote the survival and activation of macrophages and inhibits Gsk3-beta to promote beta-catenin accumulation in the nucleus. AKT1, APC, AXIN1, CCND1, CD14, CTNNB1, DVL1, FZD1, GJA1, GNAI1, GSK3B, IRAK1, LBP, LEF1, LY96, MYD88, NFKB1, PDPK1, PIK3CA, PIK3R1, PPP2CA, PRKR, RELA, TIRAP, TLR4, TOLLIP, WNT1 24 AKT1(1), APC(9), CCND1(1), CD14(1), CTNNB1(3), DVL1(3), FZD1(1), GJA1(4), GNAI1(2), GSK3B(1), IRAK1(4), LBP(5), LEF1(3), NFKB1(2), PDPK1(1), PIK3R1(1), RELA(3), TOLLIP(1) 7187818 46 37 46 10 9 14 11 5 7 0 0.64 1.00 245 ETSPATHWAY The Ets transcription factors are activated by Ras and promote macrophage differentiation. CSF1, CSF1R, DDX20, E2F1, E2F4, ETS1, ETS2, ETV3, FOS, HDAC2, HDAC5, HRAS, JUN, NCOR2, RBL1, RBL2, SIN3A, SIN3B 18 CSF1(2), CSF1R(3), E2F1(3), ETS1(2), ETV3(2), FOS(1), HDAC5(1), HRAS(2), JUN(2), NCOR2(6), RBL1(6), RBL2(5), SIN3A(5), SIN3B(3) 7269342 43 37 43 11 6 18 7 7 5 0 0.64 1.00 246 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 24 ARNT(1), EIF2B1(1), EIF2B2(2), EIF2B3(1), EIF2B5(1), ELAVL1(1), FLT1(9), FLT4(3), HIF1A(1), HRAS(2), KDR(11), NOS3(1), PIK3R1(1), PLCG1(2), PRKCA(5), PTK2(3), PXN(3), SHC1(1), VHL(1) 8685154 50 43 50 22 12 17 6 9 6 0 0.65 1.00 247 HSA00625_TETRACHLOROETHENE_DEGRADATION Genes involved in tetrachloroethene degradation AKR1B10, EPHX2, HSD3B7, RDH11, RDH12, RDH13, RDH14 7 AKR1B10(1), EPHX2(2), RDH11(2), RDH12(2), RDH13(1) 1309724 8 8 8 2 3 2 0 2 1 0 0.66 1.00 248 HSA00480_GLUTATHIONE_METABOLISM Genes involved in glutathione metabolism ANPEP, G6PD, GCLC, GCLM, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GSR, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, OPLAH, TXNDC12 36 ANPEP(5), GCLC(2), GCLM(1), GGT1(2), GPX5(1), GPX6(2), GSR(2), GSS(2), GSTA2(1), GSTA4(2), GSTA5(2), GSTM3(1), GSTM4(3), GSTM5(2), GSTZ1(2), IDH1(2), MGST1(2), OPLAH(3) 6086710 37 34 37 15 8 17 7 4 1 0 0.66 1.00 249 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 71 B2M(1), CALR(1), CANX(1), CD4(2), CD8B(1), CIITA(4), CTSL1(2), CTSS(2), HLA-B(1), HLA-C(1), HLA-DMA(1), HLA-DMB(1), HLA-DQA2(2), HLA-DRA(1), HLA-DRB1(1), HLA-DRB5(2), HLA-G(1), HSP90AB1(2), HSPA5(2), IFNA1(1), IFNA10(1), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), KIR2DL1(3), KIR2DL3(4), KIR3DL1(6), KIR3DL2(1), KIR3DL3(1), KLRC1(1), KLRC3(1), LGMN(1), LTA(3), NFYB(1), PSME1(1), PSME2(1), RFX5(1), RFXAP(1), TAP1(2), TAPBP(3) 12369754 70 53 70 31 10 22 19 7 12 0 0.66 1.00 250 ARFPATHWAY Cyclin-dependent kinase inhibitor 2A is a tumor suppressor that induces G1 arrest and can activate the p53 pathway, leading to G2/M arrest. ABL1, CDKN2A, E2F1, MDM2, MYC, PIK3CA, PIK3R1, POLR1A, POLR1B, POLR1C, POLR1D, RAC1, RB1, TBX2, TP53, TWIST1 13 ABL1(2), E2F1(3), MDM2(1), MYC(1), PIK3R1(1), POLR1A(4), POLR1B(4), POLR1C(1), POLR1D(1), RAC1(2), RB1(7), TBX2(3), TWIST1(1) 4540424 31 24 31 10 7 13 0 4 7 0 0.67 1.00 251 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 5 C3(4), C5(1), C7(7), C8A(3), C9(2) 2928990 17 16 17 7 3 5 5 2 2 0 0.67 1.00 252 ST_G_ALPHA_S_PATHWAY The G-alpha-s protein activates adenylyl cyclases, which catalyze cAMP formation. ASAH1, BF, BFAR, BRAF, CAMP, CREB1, CREB3, CREB5, EPAC, GAS, GRF2, MAPK1, RAF1, SNX13, SRC, TERF2IP 12 BRAF(7), CREB3(2), CREB5(3), MAPK1(1), RAF1(1), SNX13(4) 3132622 18 18 18 7 4 4 8 0 2 0 0.67 1.00 253 PHENYLALANINE_METABOLISM ABP1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, DDC, EPX, GOT1, GOT2, HPD, LPO, MAOA, MAOB, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TAT, TPO 21 ABP1(6), ALDH3B2(2), AOC2(2), AOC3(3), DDC(2), EPX(5), GOT1(2), GOT2(3), HPD(3), LPO(2), MPO(3), PRDX1(1), PRDX6(1), TAT(1) 5494504 36 32 35 19 11 13 9 3 0 0 0.67 1.00 254 DREAMPATHWAY The transcription factor DREAM blocks expression of the prodynorphin gene, which encodes the ligand of an opioid receptor that blocks pain signaling. CREB1, CREM, CSEN, FOS, JUN, MAPK3, OPRK1, POLR2A, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 13 CREM(2), FOS(1), JUN(2), MAPK3(2), OPRK1(1), POLR2A(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3) 3384492 20 19 20 6 6 8 1 2 3 0 0.67 1.00 255 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 15 C3(4), C5(1), C7(7), ICAM1(2), ITGA4(5), ITGAL(1), ITGB1(4), ITGB2(3), SELP(8), SELPLG(1), VCAM1(4) 6211488 40 32 40 11 9 11 10 5 5 0 0.68 1.00 256 HSA00970_AMINOACYL_TRNA_BIOSYNTHESIS Genes involved in aminoacyl-tRNA biosynthesis AARS, AARS2, CARS, CARS2, DARS, DARS2, EARS2, EPRS, FARS2, FARSA, FARSB, GARS, HARS, HARS2, IARS, IARS2, KARS, LARS, LARS2, MARS, MARS2, MTFMT, NARS, NARS2, PARS2, QARS, RARS, RARS2, SARS, SARS2, TARS, TARS2, VARS, VARS2, WARS, WARS2, YARS, YARS2 38 AARS(2), AARS2(6), CARS(6), DARS(1), DARS2(5), EARS2(2), EPRS(11), FARS2(1), FARSA(2), GARS(1), HARS(2), HARS2(2), IARS(3), IARS2(4), KARS(3), LARS2(5), MARS(1), NARS(3), NARS2(2), PARS2(1), RARS(4), RARS2(2), SARS(2), SARS2(2), TARS(3), TARS2(2), VARS(4), VARS2(4), WARS(4), WARS2(1), YARS(1), YARS2(1) 14615580 93 66 93 32 15 40 24 5 9 0 0.68 1.00 257 HSA00603_GLYCOSPHINGOLIPID_BIOSYNTHESIS_GLOBOSERIES Genes involved in glycosphingolipid biosynthesis - globoseries A4GALT, B3GALNT1, B3GALT5, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, ST3GAL1, ST3GAL2, ST8SIA1 14 B3GALNT1(1), FUT9(1), GBGT1(3), GLA(2), HEXA(6), NAGA(1), ST3GAL1(1), ST3GAL2(2), ST8SIA1(2) 2913504 19 17 18 7 2 12 2 2 1 0 0.68 1.00 258 UBIQUINONE_BIOSYNTHESIS NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 14 NDUFB5(3), NDUFS1(4), NDUFV1(3), NDUFV2(2) 1823966 12 11 12 3 4 4 3 1 0 0 0.68 1.00 259 PDGFPATHWAY Platelet-derived growth factor (PDGF) receptor is phosphorylated on ligand binding and promotes cell proliferation. CSNK2A1, ELK1, FOS, GRB2, HRAS, JAK1, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, PDGFA, PDGFRA, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, SRF, STAT1, STAT3, STAT5A 25 CSNK2A1(2), FOS(1), HRAS(2), JAK1(1), JUN(2), MAP2K1(2), MAP3K1(3), MAPK3(2), MAPK8(2), PDGFRA(8), PIK3R1(1), PLCG1(2), PRKCA(5), RAF1(1), RASA1(6), SHC1(1), SOS1(6), SRF(2), STAT1(2), STAT3(1), STAT5A(2) 8769348 54 44 54 19 18 15 10 5 6 0 0.68 1.00 260 PANTOTHENATE_AND_COA_BIOSYNTHESIS BCAT1, COASY, DPYD, DPYS, ENPP1, ENPP3, PANK1, PANK2, PANK3, PANK4, PPCS, UPB1 12 BCAT1(1), COASY(2), DPYD(7), DPYS(4), ENPP1(7), ENPP3(4), PANK3(2), PANK4(1), PPCS(1) 3808488 29 22 29 10 8 12 4 2 3 0 0.68 1.00 261 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 88 ACVR1B(3), ACVR1C(3), ACVR2A(3), ACVR2B(1), ACVRL1(3), AMHR2(4), BMP4(2), BMP5(5), BMP7(1), BMPR1A(3), CHRD(2), COMP(2), CREBBP(12), CUL1(3), DCN(1), EP300(5), GDF5(4), GDF6(2), ID4(1), IFNG(1), INHBA(4), INHBC(1), LEFTY2(2), LTBP1(10), MAPK1(1), MAPK3(2), MYC(1), NODAL(3), PITX2(3), PPP2R1A(6), PPP2R1B(2), PPP2R2A(1), PPP2R2B(2), PPP2R2C(2), RBL1(6), RBL2(5), RBX1(1), ROCK1(5), ROCK2(3), RPS6KB1(1), SKP1(1), SMAD1(3), SMAD2(2), SMAD4(2), SMAD7(1), SMURF1(4), SMURF2(1), SP1(1), TGFB1(1), TGFB2(1), TGFBR2(3), THBS1(1), THBS3(4), ZFYVE16(3), ZFYVE9(5) 26483908 155 93 154 48 28 55 32 19 21 0 0.68 1.00 262 EEA1PATHWAY The FYVE-finger proteins EEA1 and HRS are localized to endosome membranes and regulate sorting and ubiquitination in the vesicle transport system. EEA1, EGF, EGFR, HGS, RAB5A, TF, TFRC 7 EGF(6), EGFR(9), TF(7), TFRC(2) 3479188 24 20 23 4 8 11 2 0 3 0 0.69 1.00 263 HCMVPATHWAY Cytomegalovirus activates MAP kinase pathways in the host cell, inducing transcription of viral genes. AKT1, CREB1, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NFKB1, PIK3CA, PIK3R1, RB1, RELA, SP1 15 AKT1(1), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAPK1(1), MAPK14(1), MAPK3(2), NFKB1(2), PIK3R1(1), RB1(7), RELA(3), SP1(1) 4701692 31 25 31 8 7 14 2 2 6 0 0.69 1.00 264 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 21 CSNK2A1(2), FOS(1), HRAS(2), JAK2(3), JUN(2), MAP2K1(2), MAPK3(2), MPL(3), PIK3R1(1), PLCG1(2), PRKCA(5), RAF1(1), RASA1(6), SHC1(1), SOS1(6), STAT1(2), STAT3(1), STAT5A(2), THPO(1) 7485434 45 38 45 9 13 12 8 4 8 0 0.69 1.00 265 AT1RPATHWAY Binding of angiotensin II to AT1-R activates Ca2+ signaling and the JNK pathway. AGT, AGTR1, ATF2, CALM1, CALM2, CALM3, EGFR, ELK1, GNAQ, GRB2, HRAS, JUN, MAP2K1, MAP2K2, MAP2K4, MAP3K1, MAPK1, MAPK3, MAPK8, MEF2A, MEF2B, MEF2C, MEF2D, PAK1, PRKCA, PRKCB1, PTK2, PTK2B, RAC1, RAF1, SHC1, SOS1, SRC, SYT1 33 AGT(1), AGTR1(3), ATF2(2), EGFR(9), HRAS(2), JUN(2), MAP2K1(2), MAP2K2(2), MAP3K1(3), MAPK1(1), MAPK3(2), MAPK8(2), MEF2A(2), MEF2C(2), MEF2D(2), PAK1(3), PRKCA(5), PTK2(3), RAC1(2), RAF1(1), SHC1(1), SOS1(6), SYT1(3) 9123746 61 48 60 23 19 19 12 6 5 0 0.69 1.00 266 HSA04670_LEUKOCYTE_TRANSENDOTHELIAL_MIGRATION Genes involved in Leukocyte transendothelial migration ACTN1, ACTN2, ACTN3, ACTN4, ARHGAP5, BCAR1, CD99, CDC42, CDH5, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTNND1, CXCL12, CXCR4, CYBA, CYBB, ESAM, EZR, F11R, GNAI1, GNAI2, GNAI3, GRLF1, ICAM1, ITGA4, ITGAL, ITGAM, ITGB1, ITGB2, ITK, JAM2, JAM3, MAPK11, MAPK12, MAPK13, MAPK14, MLLT4, MMP2, MMP9, MRCL3, MRLC2, MSN, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLPF, NCF1, NCF2, NCF4, NOX1, NOX3, OCLN, PECAM1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCG, PTK2, PTK2B, PTPN11, PXN, RAC1, RAC2, RAP1A, RAP1B, RAPGEF3, RAPGEF4, RASSF5, RHOA, RHOH, ROCK1, ROCK2, SIPA1, THY1, TXK, VASP, VAV1, VAV2, VAV3, VCAM1, VCL 105 ACTN1(2), ACTN2(6), ACTN3(2), ACTN4(5), BCAR1(5), CDC42(1), CDH5(2), CLDN1(2), CLDN10(4), CLDN16(4), CLDN17(1), CLDN19(1), CLDN2(1), CLDN22(1), CLDN3(1), CLDN6(1), CLDN8(2), CLDN9(3), CTNNB1(3), CTNND1(4), CYBB(6), ESAM(4), EZR(1), F11R(1), GNAI1(2), GNAI3(1), GRLF1(11), ICAM1(2), ITGA4(5), ITGAL(1), ITGAM(3), ITGB1(4), ITGB2(3), ITK(2), MAPK13(2), MAPK14(1), MLLT4(3), MMP2(4), MMP9(6), MSN(3), MYL2(1), MYLPF(1), NCF2(5), NCF4(1), NOX1(2), NOX3(5), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLCG1(2), PLCG2(3), PRKCA(5), PRKCG(9), PTK2(3), PTPN11(3), PXN(3), RAC1(2), RAPGEF4(5), RASSF5(2), RHOH(3), ROCK1(5), ROCK2(3), THY1(2), TXK(3), VASP(2), VAV1(7), VAV2(4), VAV3(1), VCAM1(4), VCL(2) 32525228 227 104 226 80 59 81 42 23 22 0 0.69 1.00 267 HSA00770_PANTOTHENATE_AND_COA_BIOSYNTHESIS Genes involved in pantothenate and CoA biosynthesis BCAT1, BCAT2, COASY, DPYD, DPYS, ENPP1, ENPP3, ILVBL, PANK1, PANK2, PANK3, PANK4, PPCDC, PPCS, UPB1, VNN1 16 BCAT1(1), BCAT2(3), COASY(2), DPYD(7), DPYS(4), ENPP1(7), ENPP3(4), ILVBL(2), PANK3(2), PANK4(1), PPCS(1), VNN1(2) 4731952 36 27 36 12 11 13 7 2 3 0 0.69 1.00 268 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 9 GPR37(2), SNCAIP(3), UBE2E2(1), UBE2G2(1), UBE2L6(1) 1465118 8 8 8 3 1 0 5 0 2 0 0.69 1.00 269 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), MYC(1), SP1(1), SP3(1), WT1(4) 1666614 9 9 9 4 2 1 4 2 0 0 0.70 1.00 270 GPCRPATHWAY G-protein coupled receptors activate adenylyl cyclase, which converts ATP to cAMP, to activate second messenger pathways. ADCY1, CALM1, CALM2, CALM3, CREB1, ELK1, FOS, GNAI1, GNAQ, GNAS, GNB1, GNGT1, HRAS, JUN, MAP2K1, MAPK3, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, RAF1, RPS6KA3, SYT1 34 ADCY1(8), FOS(1), GNAI1(2), GNAS(4), GNB1(1), HRAS(2), JUN(2), MAP2K1(2), MAPK3(2), NFATC2(5), NFATC3(3), NFATC4(2), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), RAF1(1), RPS6KA3(1), SYT1(3) 9434534 65 49 65 21 22 22 7 9 5 0 0.70 1.00 271 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 73 ACP1(1), ACTB(1), ACTN1(2), ACTN2(6), ACTN3(2), ACTN4(5), ACVR1B(3), ACVR1C(3), CDC42(1), CDH1(4), CREBBP(12), CSNK2A1(2), CTNNB1(3), CTNND1(4), EGFR(9), EP300(5), ERBB2(3), FARP2(6), FER(2), FGFR1(3), FYN(4), IGF1R(1), INSR(7), IQGAP1(6), LEF1(3), LMO7(7), MAP3K7(3), MAPK1(1), MAPK3(2), MET(3), MLLT4(3), NLK(2), PARD3(5), PTPN1(1), PTPRB(15), PTPRF(7), PTPRJ(3), PTPRM(6), PVRL1(3), PVRL3(2), PVRL4(5), RAC1(2), SMAD2(2), SMAD4(2), SNAI1(3), SNAI2(2), SORBS1(5), SSX2IP(1), TCF7(1), TGFBR2(3), TJP1(9), VCL(2), WAS(5), WASF3(1), WASL(2), YES1(1) 31278694 207 103 205 62 40 75 48 19 25 0 0.70 1.00 272 RELAPATHWAY Acetylated NF-kB proteins are immune to IkB regulation and promote transcription until the histone deacetylase HDAC3 deacetylates the RelA subunit of NF-kB. CHUK, CREBBP, EP300, FADD, HDAC3, IKBKB, IKBKG, NFKB1, NFKBIA, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF6 15 CHUK(2), CREBBP(12), EP300(5), FADD(1), HDAC3(1), IKBKB(3), NFKB1(2), RELA(3), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TRAF6(1) 6117860 34 29 33 10 7 10 6 4 7 0 0.71 1.00 273 HSA00010_GLYCOLYSIS_AND_GLUCONEOGENESIS Genes involved in glycolysis and gluconeogenesis ACSS1, ACSS2, ACYP1, ACYP2, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH7A1, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, G6PC2, GALM, GAPDH, GAPDHS, GCK, GPI, HK1, HK2, HK3, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKL, PFKM, PFKP, PGAM1, PGAM2, PGAM4, PGK1, PGK2, PGM1, PGM3, PKLR, PKM2, TPI1 63 ACSS1(3), ACSS2(2), ADH1B(1), ADH1C(1), ADH4(2), ADH5(2), ADH7(1), ADHFE1(2), ALDH1B1(3), ALDH2(2), ALDH3B2(2), ALDH7A1(1), ALDH9A1(2), ALDOA(1), ALDOB(2), ALDOC(1), BPGM(2), DLAT(1), DLD(2), ENO2(2), ENO3(1), FBP2(1), G6PC(2), G6PC2(2), GAPDH(3), GAPDHS(2), GCK(1), GPI(5), HK1(4), HK2(6), HK3(7), LDHAL6B(1), LDHB(2), LDHC(1), PDHA1(2), PDHA2(5), PFKL(2), PFKM(5), PFKP(2), PGAM2(1), PGK1(1), PGK2(5), PGM1(1), PKLR(3), PKM2(1), TPI1(4) 15403764 105 72 103 33 36 42 12 8 7 0 0.71 1.00 274 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 13 CCND1(1), CDK2(1), CFL1(3), E2F1(3), MDM2(1), PRB1(2) 1870246 11 11 11 7 1 8 0 1 1 0 0.71 1.00 275 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 41 CD3D(1), FOS(1), FYN(4), HRAS(2), JUN(2), LAT(1), LCK(2), MAP2K1(2), MAP3K1(3), MAPK3(2), MAPK8(2), NFATC2(5), NFATC3(3), NFATC4(2), NFKB1(2), PIK3R1(1), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKCA(5), RAC1(2), RAF1(1), RASA1(6), RELA(3), SHC1(1), SOS1(6), SYT1(3), VAV1(7), ZAP70(3) 12376696 83 58 83 19 24 25 12 13 9 0 0.71 1.00 276 HSA00900_TERPENOID_BIOSYNTHESIS Genes involved in terpenoid biosynthesis FDFT1, FDPS, GGPS1, IDI1, IDI2, SQLE 6 FDFT1(1), FDPS(1), GGPS1(1), IDI1(1), IDI2(1), SQLE(2) 1174622 7 7 7 0 2 3 1 1 0 0 0.71 1.00 277 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 GLUL(1), PGLYRP2(1) 506410 2 2 2 0 0 1 1 0 0 0 0.71 1.00 278 HSA00960_ALKALOID_BIOSYNTHESIS_II Genes involved in alkaloid biosynthesis II AADAC, ABP1, AOC2, AOC3, ARD1A, CES1, CES7, DDHD1, ESCO1, ESCO2, LIPA, LYCAT, MYST3, MYST4, NAT5, NAT6, PLA1A, PNPLA3, PPME1, PRDX6, SH3GLB1 18 AADAC(2), ABP1(6), AOC2(2), AOC3(3), CES1(2), CES7(1), DDHD1(4), ESCO1(1), LIPA(2), MYST3(11), MYST4(3), PLA1A(5), PNPLA3(1), PRDX6(1), SH3GLB1(1) 6849084 45 37 45 21 12 18 7 4 4 0 0.72 1.00 279 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3D(1) 303668 1 1 1 0 0 1 0 0 0 0 0.72 1.00 280 O_GLYCAN_BIOSYNTHESIS GALNT1, GALNT10, GALNT2, GALNT3, GALNT4, GALNT6, GALNT7, GALNT8, GALNT9, GCNT1, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, WBSCR17 13 GALNT1(1), GALNT10(2), GALNT2(4), GALNT3(2), GALNT6(2), GALNT7(1), GALNT8(2), GCNT1(3), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2) 3526536 22 18 20 6 3 10 6 1 2 0 0.72 1.00 281 LEPTINPATHWAY Leptin is a peptide secreted by adipose tissue that, in skeletal muscle, promotes fatty acid oxidation, decreases cells' lipid content, and promotes insulin sensitivity. ACACA, CPT1A, LEP, LEPR, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2 10 ACACA(4), CPT1A(3), LEPR(10), PRKAA2(2), PRKAB2(1), PRKAG2(4) 3886986 24 23 24 7 8 8 6 1 1 0 0.72 1.00 282 KERATAN_SULFATE_BIOSYNTHESIS B3GNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT5, FUT8, SIAT4A, SIAT4B, SIAT6, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 10 B4GALT1(1), B4GALT3(2), B4GALT5(3), FUT8(2), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2) 2168218 13 13 12 10 3 6 2 1 1 0 0.72 1.00 283 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 106 A4GNT(5), ALG1(1), ALG13(8), ALG2(2), ALG6(3), B3GALT6(1), B3GNT2(1), B3GNT6(1), B3GNT7(2), B4GALT1(1), B4GALT3(2), B4GALT4(1), B4GALT5(3), C1GALT1C1(1), CHPF(1), CHST1(2), CHST11(1), CHST12(1), CHST14(1), CHST2(4), CHST3(2), CHST4(2), CHST6(3), EXT1(2), EXT2(1), EXTL1(2), EXTL3(1), FUT8(2), GALNT1(1), GALNT10(2), GALNT11(2), GALNT12(3), GALNT14(4), GALNT2(4), GALNT3(2), GALNT5(6), GALNT6(2), GALNT7(1), GALNT8(2), GALNTL1(3), GALNTL2(1), GALNTL4(4), GALNTL5(3), GANAB(5), GCNT1(3), GCNT3(3), HS3ST2(1), HS3ST5(4), HS6ST1(2), HS6ST3(2), MAN1A1(3), MAN1A2(4), MAN1C1(3), MAN2A1(4), MGAT1(1), MGAT2(2), MGAT3(4), MGAT4A(2), MGAT4B(1), MGAT5(3), MGAT5B(4), NDST1(3), NDST2(1), NDST3(4), OGT(2), RPN1(1), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2), ST6GAL1(1), ST6GALNAC1(6), STT3B(1), XYLT1(4) 29176692 176 105 174 77 40 77 28 17 14 0 0.72 1.00 284 TCAPOPTOSISPATHWAY HIV infection upregulates Fas ligand in macrophages and CD4 in helper T cells, leading to widespread Fas-induced T cell apoptosis. CCR5, CD28, CD3D, CD3E, CD3G, CD3Z, CD4, TNFRSF6, TNFSF6, TRA@, TRB@ 5 CD3D(1), CD4(2) 675510 3 3 3 1 1 1 0 0 1 0 0.72 1.00 285 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 111 ATP12A(7), ATP4A(5), ATP5A1(2), ATP5B(1), ATP5C1(3), ATP5G2(3), ATP5G3(1), ATP5L(1), ATP6V0A1(4), ATP6V0A2(5), ATP6V0A4(2), ATP6V0D1(1), ATP6V0D2(2), ATP6V1A(3), ATP6V1B1(2), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4), COX10(1), COX4I1(1), COX4I2(1), COX6B1(2), COX7A2(1), CYC1(4), NDUFA13(2), NDUFA6(2), NDUFA7(1), NDUFAB1(1), NDUFB5(3), NDUFB8(1), NDUFS1(4), NDUFS6(1), NDUFS8(1), NDUFV1(3), NDUFV2(2), SDHA(1), SDHC(1), UQCRB(1), UQCRC2(1) 15069124 87 64 86 31 21 29 22 6 9 0 0.72 1.00 286 SA_TRKA_RECEPTOR The TrkA receptor binds nerve growth factor to activate MAP kinase pathways and promote cell growth. AKT1, AKT2, AKT3, ARHA, CDKN1A, ELK1, GRB2, HRAS, MAP2K1, MAP2K2, NGFB, NGFR, NTRK1, PIK3CA, PIK3CD, SHC1, SOS1 14 AKT1(1), AKT3(2), HRAS(2), MAP2K1(2), MAP2K2(2), NGFR(1), NTRK1(3), PIK3CD(3), SHC1(1), SOS1(6) 3889122 23 21 23 10 4 11 4 2 2 0 0.73 1.00 287 EIF4PATHWAY The eIF-4F complex recognizes 5' mRNA caps, recruits RNA helicases, and maintains mRNA-ribosome bridging. AKT1, EIF4A1, EIF4A2, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FRAP1, GHR, IRS1, MAPK1, MAPK14, MAPK3, MKNK1, PABPC1, PDK2, PDPK1, PIK3CA, PIK3R1, PRKCA, PRKCB1, PTEN, RPS6KB1 20 AKT1(1), EIF4A1(3), EIF4A2(3), EIF4G1(8), EIF4G2(4), EIF4G3(3), GHR(2), IRS1(4), MAPK1(1), MAPK14(1), MAPK3(2), PABPC1(1), PDK2(2), PDPK1(1), PIK3R1(1), PRKCA(5), RPS6KB1(1) 6769340 43 36 43 18 7 20 9 3 4 0 0.73 1.00 288 IFNAPATHWAY Interferon alpha, active in the immune response, binds to the IFN receptor and activates Jak1 and Tyk2, which phosphorylate Stat1 and Stat2. IFNA1, IFNAR1, IFNAR2, IFNB1, ISGF3G, JAK1, STAT1, STAT2, TYK2 8 IFNA1(1), IFNAR1(2), IFNB1(1), JAK1(1), STAT1(2), STAT2(2), TYK2(8) 2905494 17 17 17 5 6 6 1 3 1 0 0.73 1.00 289 PENTOSE_PHOSPHATE_PATHWAY ALDOA, ALDOB, ALDOC, FBP1, FBP2, G6PD, GPI, H6PD, PFKM, PFKP, PGD, PGLS, PGM1, PGM3, PRPS1, PRPS1L1, PRPS2, RBKS, RPE, RPE, LOC440001, RPIA, TAL1, TALDO1, TALDO1, HSUP1, TKT 23 ALDOA(1), ALDOB(2), ALDOC(1), FBP2(1), GPI(5), H6PD(4), PFKM(5), PFKP(2), PGLS(1), PGM1(1), PRPS1(1), PRPS1L1(1), PRPS2(1), RBKS(1), RPIA(1), TAL1(2), TALDO1(2), TKT(1) 5552176 33 29 32 14 11 10 3 3 6 0 0.73 1.00 290 HSA00680_METHANE_METABOLISM Genes involved in methane metabolism ADH5, CAT, EPX, LPO, MPO, MTHFR, PRDX6, SHMT1, SHMT2, TPO 9 ADH5(2), CAT(1), EPX(5), LPO(2), MPO(3), MTHFR(2), PRDX6(1) 2704176 16 16 16 9 3 6 6 1 0 0 0.73 1.00 291 SA_FAS_SIGNALING The TNF-type receptor Fas induces apoptosis on ligand binding. BCL2, CASP3, CASP8, CFL1, CFLAR, P11, PDE6D, TNFRSF6, TNFSF6 6 CASP8(1), CFL1(3), CFLAR(1) 1038452 5 5 5 2 0 4 0 0 1 0 0.73 1.00 292 TELPATHWAY Telomerase is a ribonucleotide protein that adds telomeric repeats to the 3' ends of chromosomes. AKT1, BCL2, EGFR, G22P1, HSPCA, IGF1R, KRAS2, MYC, POLR2A, PPP2CA, PRKCA, RB1, TEP1, TERF1, TERT, TNKS, TP53, XRCC5 14 AKT1(1), EGFR(9), IGF1R(1), MYC(1), POLR2A(2), PRKCA(5), RB1(7), TEP1(6), TERF1(2), TERT(5), TNKS(7), XRCC5(1) 7453394 47 35 46 13 9 20 5 3 10 0 0.73 1.00 293 HISTIDINE_METABOLISM ABP1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, AOC2, AOC3, ASPA, CNDP1, DDC, HAL, HARS, HARSL, HDC, HNMT, MAOA, MAOB, PRPS1, PRPS2 24 ABP1(6), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH3B2(2), ALDH9A1(2), AOC2(2), AOC3(3), ASPA(1), CNDP1(3), DDC(2), HARS(2), HDC(3), HNMT(1), PRPS1(1), PRPS2(1) 6575498 38 35 37 17 11 16 6 3 2 0 0.73 1.00 294 TCRAPATHWAY The kinases Lck and Fyn phosphorylate and activate the T cell receptor, which recognizes antigen-bound MHCII and leads to T cell activation. CD3D, CD3E, CD3G, CD3Z, CD4, FYN, HLA-DRA, HLA-DRB1, LCK, PTPRC, TRA@, TRB@, ZAP70 10 CD3D(1), CD4(2), FYN(4), HLA-DRA(1), HLA-DRB1(1), LCK(2), PTPRC(3), ZAP70(3) 2464054 17 14 17 6 4 8 2 1 2 0 0.73 1.00 295 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 10 C1QA(2), C1QB(2), C1R(2), C1S(4), C2(1), C3(4), C5(1), C7(7), C8A(3), C9(2) 4329494 28 23 28 12 6 11 6 2 3 0 0.73 1.00 296 HSA00051_FRUCTOSE_AND_MANNOSE_METABOLISM Genes involved in fructose and mannose metabolism AKR1B1, AKR1B10, ALDOA, ALDOB, ALDOC, FBP1, FBP2, FPGT, FUK, GMDS, GMPPA, GMPPB, HK1, HK2, HK3, HSD3B7, KHK, LHPP, MPI, MTMR1, MTMR2, MTMR6, PFKFB1, PFKFB2, PFKFB3, PFKFB4, PFKL, PFKM, PFKP, PGM2, PHPT1, PMM1, PMM2, RDH11, RDH12, RDH13, RDH14, SORD, TPI1, TSTA3, UGCGL1, UGCGL2 40 AKR1B10(1), ALDOA(1), ALDOB(2), ALDOC(1), FBP2(1), FPGT(2), FUK(1), GMPPA(1), HK1(4), HK2(6), HK3(7), KHK(1), MPI(1), MTMR1(1), MTMR2(1), MTMR6(3), PFKFB1(3), PFKFB2(1), PFKL(2), PFKM(5), PFKP(2), PGM2(5), PMM1(1), RDH11(2), RDH12(2), RDH13(1), TPI1(4) 10174124 62 51 60 18 22 16 10 7 7 0 0.74 1.00 297 EGFR_SMRTEPATHWAY EGF receptor activation inhibits SMRT, a transcriptional co-repressor that interacts with transcription factor complexes and gene silencers. EGF, EGFR, MAP2K1, MAP3K1, MAPK14, NCOR2, RARA, RXRA, THRA, THRB, ZNF145 10 EGF(6), EGFR(9), MAP2K1(2), MAP3K1(3), MAPK14(1), NCOR2(6), RARA(1), RXRA(1), THRA(2), THRB(1) 4792828 32 25 31 10 11 12 4 0 5 0 0.74 1.00 298 BCRPATHWAY B cell antigen receptors (BCRs) activate tyrosine kinases and transiently increase tyrosine phosphorylation on binding to antigen. BLNK, BTK, CALM1, CALM2, CALM3, CD79A, CD79B, ELK1, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP3K1, MAPK14, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, RAC1, RAF1, SHC1, SOS1, SYK, SYT1, VAV1 34 BLNK(1), BTK(5), CD79A(1), FOS(1), HRAS(2), JUN(2), LYN(1), MAP2K1(2), MAP3K1(3), MAPK14(1), MAPK3(2), MAPK8(2), NFATC2(5), NFATC3(3), NFATC4(2), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKCA(5), RAC1(2), RAF1(1), SHC1(1), SOS1(6), SYK(1), SYT1(3), VAV1(7) 10354616 70 52 70 22 21 20 12 10 7 0 0.74 1.00 299 NOTCHPATHWAY Proteolysis and Signaling Pathway of Notch ADAM17, DLL1, FURIN, NOTCH1, PSEN1, RBPSUH 5 DLL1(1), FURIN(1), NOTCH1(11), PSEN1(1) 2659320 14 12 14 6 2 5 0 1 6 0 0.75 1.00 300 S1PPATHWAY At low cholesterol concentrations, sterol-regulatory element binding proteins (SREBPs) act as transcription factors to promote cholesterol uptake and biosynthesis. EPLIN, HMGCS1, LDLR, MBTPS1, MBTPS2, SCAP, SREBF1, SREBF2 7 HMGCS1(1), LDLR(4), MBTPS1(3), MBTPS2(2), SCAP(4), SREBF1(3), SREBF2(2) 3331092 19 18 19 3 5 7 3 4 0 0 0.75 1.00 301 P35ALZHEIMERSPATHWAY p35, a neuron-specific activator of cyclin-dependent kinase 5, is cleaved to p25 in Alzheimer's disease and promotoes hyperphosphorylated tau formation and apoptosis. APP, CAPN1, CAPNS1, CAPNS2, CDK5, CDK5R1, CSNK1A1, CSNK1D, GSK3B, MAPT, PPP2CA 11 APP(1), CAPN1(2), CAPNS2(1), CDK5(2), CSNK1A1(1), GSK3B(1), MAPT(5) 2580466 13 13 13 5 2 5 0 1 5 0 0.75 1.00 302 STAT3PATHWAY The STAT transcription factors are phosphorylated and activated by JAK kinases in response to cytokine signaling. FRAP1, JAK1, JAK2, JAK3, MAPK1, MAPK3, STAT3, TYK2 7 JAK1(1), JAK2(3), JAK3(7), MAPK1(1), MAPK3(2), STAT3(1), TYK2(8) 3262918 23 18 23 4 5 12 4 1 1 0 0.75 1.00 303 HSA00030_PENTOSE_PHOSPHATE_PATHWAY Genes involved in pentose phosphate pathway ALDOA, ALDOB, ALDOC, DERA, FBP1, FBP2, G6PD, GPI, H6PD, PFKL, PFKM, PFKP, PGD, PGLS, PGM1, PGM3, PRPS1, PRPS1L1, PRPS2, RBKS, RPE, RPIA, TALDO1, TKT, TKTL1, TKTL2 25 ALDOA(1), ALDOB(2), ALDOC(1), DERA(1), FBP2(1), GPI(5), H6PD(4), PFKL(2), PFKM(5), PFKP(2), PGLS(1), PGM1(1), PRPS1(1), PRPS1L1(1), PRPS2(1), RBKS(1), RPIA(1), TALDO1(2), TKT(1), TKTL1(4) 6312058 38 34 35 14 14 12 4 2 6 0 0.75 1.00 304 TERPENOID_BIOSYNTHESIS FDFT1, FDPS, FDPS, LOC402397, IDI1, SQLE 4 FDFT1(1), FDPS(1), IDI1(1), SQLE(2) 887152 5 5 5 0 2 2 0 1 0 0 0.75 1.00 305 HSA00561_GLYCEROLIPID_METABOLISM Genes involved in glycerolipid metabolism ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AGK, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, AKR1A1, AKR1B1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, CEL, DAK, DGAT1, DGAT2, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKI, DGKQ, DGKZ, GK, GK2, GLA, GLB1, GPAM, LCT, LIPA, LIPC, LIPF, LIPG, LPL, LYCAT, MGLL, PNLIP, PNLIPRP1, PNLIPRP2, PNPLA3, PPAP2A, PPAP2B, PPAP2C, UGCGL1, UGCGL2 52 ADH1B(1), ADH1C(1), ADH4(2), ADH5(2), ADH7(1), ADHFE1(2), AGPAT3(1), AGPAT6(2), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), CEL(5), DAK(1), DGAT2(2), DGKA(6), DGKB(4), DGKD(5), DGKE(2), DGKG(2), DGKI(7), DGKZ(3), GK(4), GK2(5), GLA(2), GPAM(2), LIPA(2), LIPC(1), LIPF(1), LIPG(2), LPL(3), MGLL(1), PNLIPRP1(3), PNLIPRP2(2), PNPLA3(1), PPAP2B(2) 14585320 88 65 87 41 27 40 7 9 5 0 0.75 1.00 306 METPATHWAY The hepatocyte growth factor receptor c-Met stimulates proliferation and alters cell motility and adhesion on binding the ligand HGF. ACTA1, CRK, CRKL, DOCK1, ELK1, FOS, GAB1, GRB2, GRF2, HGF, HRAS, ITGA1, ITGB1, JUN, MAP2K1, MAP2K2, MAP4K1, MAPK1, MAPK3, MAPK8, MET, PAK1, PIK3CA, PIK3R1, PTEN, PTK2, PTK2B, PTPN11, PXN, RAF1, RAP1A, RAP1B, RASA1, SOS1, SRC, STAT3 33 ACTA1(2), CRKL(1), DOCK1(3), FOS(1), GAB1(2), HGF(6), HRAS(2), ITGA1(4), ITGB1(4), JUN(2), MAP2K1(2), MAP2K2(2), MAP4K1(2), MAPK1(1), MAPK3(2), MAPK8(2), MET(3), PAK1(3), PIK3R1(1), PTK2(3), PTPN11(3), PXN(3), RAF1(1), RASA1(6), SOS1(6), STAT3(1) 11291786 68 51 68 26 18 22 11 7 10 0 0.75 1.00 307 VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS BCAT1, IARS, LARS, LARS2, PDHA1, PDHA2, PDHB 7 BCAT1(1), IARS(3), LARS2(5), PDHA1(2), PDHA2(5) 2688156 16 15 16 3 2 8 4 1 1 0 0.75 1.00 308 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 ALDH1A2(4), BCMO1(1) 1037384 5 5 4 3 0 2 1 0 2 0 0.76 1.00 309 PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS ENO1, ENO2, ENO3, FARS2, FARSLB, GOT1, GOT2, PAH, TAT, YARS 9 ENO2(2), ENO3(1), FARS2(1), GOT1(2), GOT2(3), PAH(1), TAT(1), YARS(1) 2211650 12 12 11 5 5 4 1 1 1 0 0.76 1.00 310 HSA00521_STREPTOMYCIN_BIOSYNTHESIS Genes involved in streptomycin biosynthesis GCK, HK1, HK2, HK3, IMPA1, IMPA2, ISYNA1, PGM1, PGM3, TGDS 10 GCK(1), HK1(4), HK2(6), HK3(7), IMPA1(1), PGM1(1), TGDS(1) 3175520 21 19 21 5 8 9 1 2 1 0 0.76 1.00 311 BUTANOATE_METABOLISM AACS, ABAT, ACADS, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH5A1, ALDH9A1, BDH, BUCS1, ECHS1, EHHADH, GAD1, GAD2, HADHA, HMGCL, L2HGDH, OXCT1, PDHA1, PDHA2, PDHB, SDHB, SDS 27 AACS(2), ABAT(3), ACADS(3), ACAT1(1), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH5A1(1), ALDH9A1(2), EHHADH(1), GAD1(5), GAD2(5), HADHA(2), HMGCL(1), L2HGDH(1), OXCT1(2), PDHA1(2), PDHA2(5), SDS(2) 6966742 47 36 46 20 9 23 4 4 7 0 0.76 1.00 312 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 8 CAMK1G(2), MEF2A(2), MEF2C(2), MEF2D(2) 1618376 8 8 8 7 3 1 1 2 1 0 0.76 1.00 313 HSA00120_BILE_ACID_BIOSYNTHESIS Genes involved in bile acid biosynthesis ACAA1, ACAA2, ACAD8, ACAD9, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AKR1B10, AKR1C4, AKR1D1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, BAAT, CEL, CYP27A1, CYP7A1, HADHB, HSD3B7, LIPA, RDH11, RDH12, RDH13, RDH14, SLC27A5, SOAT1, SOAT2, SRD5A1, SRD5A2 38 ACAA2(1), ACAD8(2), ACAD9(3), ADH1B(1), ADH1C(1), ADH4(2), ADH5(2), ADH7(1), ADHFE1(2), AKR1B10(1), AKR1C4(1), AKR1D1(4), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), BAAT(3), CEL(5), CYP27A1(2), CYP7A1(3), HADHB(2), LIPA(2), RDH11(2), RDH12(2), RDH13(1), SLC27A5(4), SOAT2(1), SRD5A1(2), SRD5A2(2) 8668778 60 45 59 16 16 26 6 7 5 0 0.76 1.00 314 HSA04210_APOPTOSIS Genes involved in apoptosis AIFM1, AKT1, AKT2, AKT3, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CAPN1, CAPN2, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHP, CHUK, CSF2RB, CYCS, DFFA, DFFB, ENDOG, FADD, FAS, FASLG, IKBKB, IKBKG, IL1A, IL1B, IL1R1, IL1RAP, IL3, IL3RA, IRAK1, IRAK2, IRAK3, IRAK4, MAP3K14, MYD88, NFKB1, NFKB2, NFKBIA, NGFB, NTRK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RELA, RIPK1, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF1A, TNFSF10, TP53, TRADD, TRAF2 78 AIFM1(2), AKT1(1), AKT3(2), APAF1(1), ATM(7), BAX(1), BCL2L1(2), BID(1), BIRC3(3), CAPN1(2), CAPN2(2), CASP10(4), CASP6(1), CASP7(2), CASP8(1), CASP9(1), CFLAR(1), CHP(2), CHUK(2), CSF2RB(5), DFFA(1), DFFB(2), FADD(1), FAS(1), FASLG(1), IKBKB(3), IL1B(1), IL1RAP(2), IRAK1(4), IRAK2(1), IRAK3(3), MAP3K14(1), NFKB1(2), NFKB2(2), NTRK1(3), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKACA(1), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), RELA(3), TNFRSF10A(1), TNFRSF10B(1), TNFRSF10D(1), TNFRSF1A(2), TRADD(1) 21763526 127 80 127 49 38 45 10 17 17 0 0.76 1.00 315 WNT_SIGNALING Wnt signaling genes APC, ARHA, AXIN1, C2orf31, CCND1, CCND2, CCND3, CSNK1E, CSNK1E, LOC400927, CTNNB1, DIPA, DVL1, DVL2, DVL3, FBXW2, FOSL1, FRAT1, FZD1, FZD10, FZD2, FZD3, FZD5, FZD6, FZD7, FZD8, FZD9, GSK3B, JUN, LDLR, MAPK10, MAPK9, MYC, PAFAH1B1, PLAU, PPP2R5C, PPP2R5E, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCM, PRKCQ, PRKCZ, PRKD1, RAC1, RHOA, SFRP4, TCF7, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B 58 APC(9), CCND1(1), CCND2(3), CCND3(1), CTNNB1(3), DVL1(3), DVL3(3), FZD1(1), FZD10(2), FZD3(4), FZD6(1), FZD9(3), GSK3B(1), JUN(2), LDLR(4), MAPK10(1), MAPK9(1), MYC(1), PAFAH1B1(1), PLAU(2), PPP2R5C(7), PRKCA(5), PRKCD(2), PRKCE(5), PRKCG(9), PRKCH(1), PRKCI(4), PRKCQ(4), PRKD1(9), RAC1(2), SFRP4(3), TCF7(1), WNT10B(2), WNT11(2), WNT2(3), WNT2B(2), WNT3(2), WNT5A(1), WNT5B(1), WNT6(2), WNT7A(2), WNT7B(1) 16330076 117 72 117 34 36 44 21 10 6 0 0.77 1.00 316 MONOCYTEPATHWAY Monocytes are a class of immune phagocytes that can develop into macrophages and express LFA-1, CD44, and other surface signaling proteins. CD44, ICAM1, ITGA4, ITGAL, ITGAM, ITGB1, ITGB2, PECAM1, SELE, SELL, SELP 11 CD44(3), ICAM1(2), ITGA4(5), ITGAL(1), ITGAM(3), ITGB1(4), ITGB2(3), SELE(4), SELL(2), SELP(8) 4718780 35 24 35 7 9 10 9 2 5 0 0.77 1.00 317 HSA00363_BISPHENOL_A_DEGRADATION Genes involved in bisphenol A degradation AKR1B10, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, HSD3B7, PON1, PON2, PON3, RDH11, RDH12, RDH13, RDH14 13 AKR1B10(1), DHRS2(1), PON1(4), PON2(1), PON3(1), RDH11(2), RDH12(2), RDH13(1) 2268076 13 12 13 3 3 5 1 2 2 0 0.77 1.00 318 NITROGEN_METABOLISM AMT, ASNS, CA1, CA12, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA8, CA9, CPS1, CTH, GLS, GLS2, GLUD1, GLUL, HAL 20 ASNS(3), CA12(2), CA14(1), CA3(2), CA4(1), CA5A(1), CA5B(1), CA6(2), CA7(1), CA9(1), GLS(2), GLUD1(3), GLUL(1) 4193680 21 21 21 2 5 8 6 0 2 0 0.77 1.00 319 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 B2M(1), CD3D(1), GZMB(1), ICAM1(2), ITGAL(1), ITGB2(3), PRF1(2) 2139916 11 11 11 6 2 4 2 2 1 0 0.78 1.00 320 OVARIAN_INFERTILITY_GENES ATM, BMPR1B, CCND2, CDK4, CDKN1B, CEBPB, DAZL, DMC1, EGR1, ESR2, FSHR, GJA4, INHA, LHCGR, MLH1, MSH5, NCOR1, NR5A1, NRIP1, PGR, PRLR, PTGER2, SMPD1, VDR, ZP2 24 ATM(7), CCND2(3), DAZL(1), DMC1(1), EGR1(4), ESR2(1), INHA(3), LHCGR(8), MLH1(3), MSH5(5), NCOR1(4), NRIP1(3), PGR(3), PRLR(5), PTGER2(1), SMPD1(3), VDR(3), ZP2(2) 9107726 60 46 58 24 24 17 6 6 7 0 0.78 1.00 321 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 16 AKT1(1), HRAS(2), MAPK1(1), MAPK3(2), MAPK7(1), MEF2A(2), MEF2C(2), MEF2D(2), NTRK1(3), PIK3R1(1), PLCG1(2), RPS6KA1(4), SHC1(1) 4600410 24 24 24 11 7 9 3 3 2 0 0.78 1.00 322 METHANE_METABOLISM ADH5, ATP6V0C, SHMT1, CAT, EPX, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, SHMT1, SHMT2, TPO 12 ADH5(2), CAT(1), EPX(5), LPO(2), MPO(3), PRDX1(1), PRDX6(1) 2761848 15 15 15 10 3 4 7 1 0 0 0.78 1.00 323 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 AKT1(1), APC(9), CAV3(1), DAG1(1), DLG4(1), EPHB2(5), GNAI1(2), ITPR1(5), ITPR2(11), ITPR3(3), KCNJ5(2), KCNJ9(2), MAPK1(1), PITX2(3), PTX3(2), RAC1(2), RYR1(29) 12333620 80 58 80 22 21 31 14 6 8 0 0.78 1.00 324 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 17 CSNK2A1(2), FOS(1), HRAS(2), JUN(2), KLK2(1), MAP2K1(2), MAPK3(2), MAPK8(2), NGFR(1), PIK3R1(1), PLCG1(2), RAF1(1), SHC1(1), SOS1(6) 4595960 26 25 26 8 8 8 6 3 1 0 0.78 1.00 325 HSA00460_CYANOAMINO_ACID_METABOLISM Genes involved in cyanoamino acid metabolism ASRGL1, GBA, GBA3, GGT1, GGTL3, GGTL4, SHMT1, SHMT2 6 GBA3(6), GGT1(2) 1569604 8 7 8 9 1 2 3 1 1 0 0.78 1.00 326 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 5 ABCB11(6), ABCB4(9), ABCC1(4), ABCC3(2) 3186912 21 18 21 7 11 5 3 1 1 0 0.78 1.00 327 ST_IL_13_PATHWAY Like IL-4, IL-13 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor. IL13, IL13RA1, IL13RA2, IL4R, JAK1, JAK2, TYK2 7 IL13RA1(2), IL13RA2(1), JAK1(1), JAK2(3), TYK2(8) 2816850 15 15 15 6 3 6 4 1 1 0 0.79 1.00 328 ST_INTERLEUKIN_13_PATHWAY IL-13 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor. IL13, IL13RA1, IL13RA2, IL4R, JAK1, JAK2, TYK2 7 IL13RA1(2), IL13RA2(1), JAK1(1), JAK2(3), TYK2(8) 2816850 15 15 15 6 3 6 4 1 1 0 0.79 1.00 329 SIG_BCR_SIGNALING_PATHWAY Members of the BCR signaling pathway AKT1, AKT2, AKT3, BAD, BCL2, BCR, BLNK, BTK, CD19, CD22, CD81, CR2, CSK, DAG1, FLOT1, FLOT2, GRB2, GSK3A, GSK3B, INPP5D, ITPR1, ITPR2, ITPR3, LYN, MAP4K1, MAPK1, MAPK3, NFATC1, NFATC2, NR0B2, PDK1, PIK3CA, PIK3CD, PIK3R1, PLCG2, PPP1R13B, PPP3CA, PPP3CB, PPP3CC, PTPRC, RAF1, SHC1, SOS1, SOS2, SYK, VAV1 45 AKT1(1), AKT3(2), BCR(1), BLNK(1), BTK(5), CD19(2), CD22(5), CD81(1), CR2(9), DAG1(1), FLOT1(2), GSK3A(4), GSK3B(1), INPP5D(6), ITPR1(5), ITPR2(11), ITPR3(3), LYN(1), MAP4K1(2), MAPK1(1), MAPK3(2), NFATC2(5), NR0B2(1), PDK1(1), PIK3CD(3), PIK3R1(1), PLCG2(3), PPP1R13B(4), PPP3CA(2), PPP3CB(5), PPP3CC(2), PTPRC(3), RAF1(1), SHC1(1), SOS1(6), SOS2(4), SYK(1), VAV1(7) 19587120 116 74 116 45 32 36 18 12 18 0 0.79 1.00 330 IONPATHWAY Activated phospholipase C hydrolyzes the lipid PIP3 into second messengers DAG, which activates protein kinase C, and IP3, which induces calcium influx into the cytoplasm. P2RY2, PLCG1, PRKCA, PRKCB1, PTK2B 4 P2RY2(2), PLCG1(2), PRKCA(5) 1819516 9 9 9 5 2 5 1 0 1 0 0.79 1.00 331 NFATPATHWAY Cardiac hypertrophy is induced by NF-ATc4 and GATA4, which are stimulated through calcineurin activated by CaMK. ACTA1, AGT, AKT1, CALM1, CALM2, CALM3, CALR, CAMK1, CAMK1G, CAMK4, CREBBP, CSNK1A1, CTF1, DTR, EDN1, ELSPBP1, F2, FGF2, FKBP1A, GATA4, GSK3B, HAND1, HAND2, HRAS, IGF1, LIF, MAP2K1, MAPK1, MAPK14, MAPK3, MAPK8, MEF2C, MYH2, NFATC1, NFATC2, NFATC3, NFATC4, NKX2-5, NPPA, PIK3CA, PIK3R1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RAF1, RPS6KB1, SYT1 49 ACTA1(2), AGT(1), AKT1(1), CALR(1), CAMK1G(2), CAMK4(3), CREBBP(12), CSNK1A1(1), EDN1(1), ELSPBP1(1), FGF2(2), GSK3B(1), HAND1(1), HAND2(1), HRAS(2), IGF1(2), MAP2K1(2), MAPK1(1), MAPK14(1), MAPK3(2), MAPK8(2), MEF2C(2), NFATC2(5), NFATC3(3), NFATC4(2), NKX2-5(2), PIK3R1(1), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), RAF1(1), RPS6KB1(1), SYT1(3) 11982604 81 55 81 32 24 25 10 13 9 0 0.79 1.00 332 NTHIPATHWAY Hemophilus influenzae infections activate NF-kB via several pathways, inducing the inflammatory response. CHUK, CREBBP, DUSP1, EP300, IKBKB, IL1B, IL8, MADH3, MADH4, MAP2K3, MAP2K6, MAP3K14, MAP3K7, MAPK11, MAPK14, MYD88, NFKB1, NFKBIA, NR3C1, RELA, TGFBR1, TGFBR2, TLR2, TNF 22 CHUK(2), CREBBP(12), EP300(5), IKBKB(3), IL1B(1), MAP2K3(2), MAP2K6(3), MAP3K14(1), MAP3K7(3), MAPK14(1), NFKB1(2), RELA(3), TGFBR2(3), TLR2(3) 8069630 44 39 42 14 11 15 7 3 8 0 0.79 1.00 333 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 8 JAK1(1), JAK2(3), JAK3(7), PIAS1(3), PIAS3(4), PTPRU(8) 3736754 26 21 24 4 5 14 4 1 2 0 0.79 1.00 334 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 84 ABL1(2), ABL2(6), AKT1(1), AKT3(2), ARAF(3), AREG(2), BRAF(7), CAMK2B(2), CAMK2D(1), CBL(4), CBLB(4), CRKL(1), EGF(6), EGFR(9), ERBB2(3), ERBB3(3), ERBB4(9), EREG(1), GAB1(2), GSK3B(1), HBEGF(1), HRAS(2), JUN(2), KRAS(1), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK10(1), MAPK3(2), MAPK8(2), MAPK9(1), MYC(1), NCK1(3), NRG1(4), NRG2(2), NRG3(5), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLCG1(2), PLCG2(3), PRKCA(5), PRKCG(9), PTK2(3), RAF1(1), RPS6KB1(1), SHC1(1), SHC2(3), SHC3(3), SHC4(4), SOS1(6), SOS2(4), STAT5A(2), TGFA(1) 27584304 186 96 185 69 50 69 31 13 23 0 0.79 1.00 335 HSA00791_ATRAZINE_DEGRADATION Genes involved in atrazine degradation ADAR, APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3F, APOBEC3G, APOBEC4 8 ADAR(7), APOBEC2(1), APOBEC3F(2), APOBEC4(2) 1832866 12 10 12 3 5 3 1 1 2 0 0.79 1.00 336 EOSINOPHILSPATHWAY Recruitment of eosinophils in the inflammatory response observed in asthma occurs via the chemoattractant eotaxin binding to the CCR3 receptor. CCL11, CCL5, CCR3, CSF2, HLA-DRA, HLA-DRB1, IL3, IL5 8 CCR3(1), HLA-DRA(1), HLA-DRB1(1) 817376 3 3 3 2 0 1 0 0 2 0 0.79 1.00 337 IL17PATHWAY Activated T cells secrete IL-17, which stimulates fibroblasts and other cells to secrete inflammatory and hematopoietic cytokines. CD2, CD34, CD3D, CD3E, CD3G, CD3Z, CD4, CD58, CD8A, CSF3, IL17, IL3, IL6, IL8, KITLG, TRA@, TRB@ 13 CD2(1), CD34(3), CD3D(1), CD4(2), CD58(1) 1701146 8 8 8 7 3 3 0 0 2 0 0.80 1.00 338 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 20 AKT1(1), BCL2L1(2), CASP9(1), CDC42(1), CHUK(2), H2AFX(1), HRAS(2), MAP2K1(2), MAPK3(2), NFKB1(2), PIK3R1(1), RAC1(2), RAF1(1), RALA(2), RALBP1(1), RALGDS(1), RELA(3) 4640638 27 24 27 8 7 9 2 6 3 0 0.80 1.00 339 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 22 ASNS(3), CA12(2), CA13(1), CA14(1), CA3(2), CA4(1), CA5A(1), CA5B(1), CA6(2), CA7(1), CA9(1), GLS(2), GLUD1(3), GLUL(1) 4508384 22 22 22 4 5 9 6 0 2 0 0.80 1.00 340 ST_WNT_BETA_CATENIN_PATHWAY Beta-catenin is degraded in the absence of Wnt signaling; when extracellular Wnt binds Frizzled receptors, beta-catenin accumulates in the nucleus and may promote cell survival. AKT1, AKT2, AKT3, ANKRD6, APC, AXIN1, AXIN2, C22orf2, CER1, CSNK1A1, CTNNB1, DACT1, DKK1, DKK2, DKK3, DKK4, DVL1, FRAT1, FSTL1, GSK3A, GSK3B, IDAX, LAMR1, LRP1, MVP, NKD1, NKD2, PIN1, PSEN1, PTPRA, SENP2, SFRP1, TSHB, WIF1 30 AKT1(1), AKT3(2), APC(9), CSNK1A1(1), CTNNB1(3), DACT1(4), DKK1(3), DKK2(1), DKK4(1), DVL1(3), FSTL1(2), GSK3A(4), GSK3B(1), LRP1(14), MVP(3), NKD1(1), NKD2(2), PSEN1(1), SENP2(3), SFRP1(1), WIF1(4) 10938100 64 51 63 21 18 21 13 2 10 0 0.80 1.00 341 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 BCAR1(5), GNAI1(2), GNB1(1), HRAS(2), MAP2K1(2), MAPK1(1), MAPK3(2), NFKB1(2), PIK3C2G(7), PIK3R1(1), PLCG1(2), PRKCA(5), PTK2(3), PXN(3), RAF1(1), RELA(3) 6906222 42 35 42 17 12 17 5 5 3 0 0.80 1.00 342 BOTULINPATHWAY Blockade of Neurotransmitter Relase by Botulinum Toxin CHRM1, CHRNA1, SNAP25, STX1A, VAMP2 5 CHRNA1(2), SNAP25(2) 869530 4 4 4 6 1 2 1 0 0 0 0.80 1.00 343 HSA00072_SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES Genes involved in synthesis and degradation of ketone bodies ACAT1, ACAT2, BDH1, BDH2, HMGCL, HMGCS1, HMGCS2, OXCT1, OXCT2 9 ACAT1(1), BDH1(6), HMGCL(1), HMGCS1(1), HMGCS2(1), OXCT1(2) 1973842 12 11 12 6 4 6 1 1 0 0 0.80 1.00 344 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(5), AMY2B(5), ASCC3(9), ATP13A2(1), DDX18(2), DDX19A(2), DDX23(6), DDX4(1), DDX41(2), DDX50(1), DDX52(1), DDX54(3), DDX55(1), DDX56(1), ENPP1(7), ENPP3(4), ENTPD7(1), ERCC2(3), ERCC3(2), G6PC(2), G6PC2(2), GANC(3), GBA3(6), GBE1(1), GCK(1), GPI(5), GUSB(3), GYS1(1), GYS2(3), HK1(4), HK2(6), HK3(7), IFIH1(3), MGAM(5), NUDT8(1), PGM1(1), PYGB(2), PYGM(6), RAD54L(1), SETX(11), SKIV2L2(2), SMARCA2(3), TREH(1), UGDH(3), UGP2(5), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4), UXS1(3) 32156056 181 101 180 56 52 69 36 10 14 0 0.81 1.00 345 GLUTATHIONE_METABOLISM ANPEP, G6PD, GCLC, GCLM, GGT1, GPX1, GPX2, GPX3, GPX4, GPX5, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, PGD 30 ANPEP(5), GCLC(2), GCLM(1), GGT1(2), GPX5(1), GSS(2), GSTA2(1), GSTA4(2), GSTM3(1), GSTM4(3), GSTM5(2), GSTZ1(2), IDH1(2), MGST1(2) 4947866 28 27 28 13 8 13 4 3 0 0 0.81 1.00 346 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 61 APAF1(1), ATM(7), ATR(11), BAI1(8), BAX(1), BID(1), CASP8(1), CASP9(1), CCNB1(1), CCNB3(9), CCND1(1), CCND2(3), CCND3(1), CCNE2(2), CCNG1(1), CD82(1), CDK2(1), CHEK1(4), CHEK2(3), DDB2(4), EI24(1), FAS(1), GADD45A(1), GADD45G(1), GTSE1(2), IGF1(2), IGFBP3(1), MDM2(1), PPM1D(1), RFWD2(4), RPRM(1), RRM2B(2), SERPINB5(2), SERPINE1(2), SESN1(3), SESN2(3), SESN3(2), SFN(2), SIAH1(1), STEAP3(2), THBS1(1), TNFRSF10B(1), TSC2(6) 17264754 105 67 104 29 18 39 19 12 17 0 0.81 1.00 347 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 34 ARSD(1), ARSE(2), B4GALT6(2), CERK(3), ENPP7(4), GAL3ST1(1), GALC(2), GLA(2), NEU1(4), NEU2(2), NEU3(2), PPAP2B(2), SGMS1(2), SGMS2(1), SGPP1(2), SMPD1(3), SMPD2(2), SMPD3(3), SPHK2(1), SPTLC2(3), UGT8(6) 8350870 50 40 50 17 13 18 10 5 4 0 0.81 1.00 348 1_2_DICHLOROETHANE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2) 2153800 11 11 10 0 1 7 1 1 1 0 0.81 1.00 349 ASCORBATE_AND_ALDARATE_METABOLISM ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2) 2153800 11 11 10 0 1 7 1 1 1 0 0.81 1.00 350 HSA00590_ARACHIDONIC_ACID_METABOLISM Genes involved in arachidonic acid metabolism AKR1C3, ALOX12, ALOX12B, ALOX15, ALOX15B, ALOX5, CBR1, CBR3, CYP2B6, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2E1, CYP2J2, CYP2U1, CYP4A11, CYP4A22, CYP4F2, CYP4F3, DHRS4, EPHX2, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, LTA4H, LTC4S, PGDS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PTGDS, PTGES, PTGES2, PTGIS, PTGS1, PTGS2, TBXAS1 51 AKR1C3(1), ALOX12B(1), ALOX15(2), ALOX15B(1), CYP2B6(3), CYP2C19(6), CYP2C8(3), CYP2C9(2), CYP2E1(1), CYP2J2(2), CYP4A22(1), CYP4F2(3), CYP4F3(3), EPHX2(2), GGT1(2), GPX5(1), GPX6(2), LTA4H(2), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PTGES(1), PTGS1(2), TBXAS1(5) 10638882 66 50 64 32 18 18 19 3 8 0 0.81 1.00 351 G2PATHWAY Activated Cdc2-cyclin B kinase regulates the G2/M transition; DNA damage stimulates the DNA-PK/ATM/ATR kinases, which inactivate Cdc2. ATM, ATR, BRCA1, CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CDC34, CDKN1A, CDKN2D, CHEK1, CHEK2, EP300, GADD45A, MDM2, MYT1, PLK, PRKDC, RPS6KA1, TP53, WEE1, YWHAH, YWHAQ 21 ATM(7), ATR(11), BRCA1(6), CCNB1(1), CDC25B(3), CDC25C(1), CDKN2D(1), CHEK1(4), CHEK2(3), EP300(5), GADD45A(1), MDM2(1), PRKDC(15), RPS6KA1(4), WEE1(2), YWHAQ(1) 11367080 66 52 64 8 15 22 13 9 7 0 0.82 1.00 352 HSA04660_T_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in T cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, CARD11, CBL, CBLB, CBLC, CD247, CD28, CD3D, CD3E, CD3G, CD4, CD40LG, CD8A, CD8B, CDC42, CDK4, CHP, CHUK, CSF2, CTLA4, FOS, FYN, GRAP2, GRB2, HRAS, ICOS, IFNG, IKBKB, IKBKG, IL10, IL2, IL4, IL5, ITK, JUN, KRAS, LAT, LCK, LCP2, MALT1, MAP3K14, MAP3K8, NCK1, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDCD1, PDK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCQ, PTPN6, PTPRC, RASGRP1, RHOA, SOS1, SOS2, TEC, TNF, VAV1, VAV2, VAV3, ZAP70 91 AKT1(1), AKT3(2), CARD11(3), CBL(4), CBLB(4), CD3D(1), CD4(2), CD40LG(2), CD8B(1), CDC42(1), CHP(2), CHUK(2), FOS(1), FYN(4), GRAP2(1), HRAS(2), ICOS(2), IFNG(1), IKBKB(3), IL10(1), IL4(2), ITK(2), JUN(2), KRAS(1), LAT(1), LCK(2), LCP2(2), MALT1(2), MAP3K14(1), NCK1(3), NFAT5(3), NFATC2(5), NFATC3(3), NFATC4(2), NFKB1(2), NFKB2(2), NFKBIB(1), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PDK1(1), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PPP3R1(1), PPP3R2(3), PRKCQ(4), PTPRC(3), RASGRP1(1), SOS1(6), SOS2(4), TEC(2), VAV1(7), VAV2(4), VAV3(1), ZAP70(3) 27075046 164 92 164 53 43 52 28 20 21 0 0.82 1.00 353 ACTINYPATHWAY The Arp 2/3 complex localizes to the Y-junction of polymerizing actin fibers that enable lamellipod extension and consequent cell motility. ABI-2, ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, NCK1, NCKAP1, NTRK1, PIR, PSMA7, RAC1, WASF1, WASF2, WASF3, WASL 18 ACTA1(2), ACTR2(1), ARPC1A(2), ARPC1B(1), NCK1(3), NCKAP1(5), NTRK1(3), RAC1(2), WASF3(1), WASL(2) 4129422 22 21 22 15 3 11 2 2 4 0 0.82 1.00 354 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 21 AKT1(1), CCND1(1), CDK2(1), E2F1(3), HRAS(2), MAPK1(1), MAPK3(2), NFKB1(2), PAK1(3), PIK3R1(1), RAC1(2), RAF1(1), RB1(7), RELA(3) 4943950 30 24 30 5 6 12 1 4 7 0 0.82 1.00 355 SARSPATHWAY The SARS coronavirus has a 30kb RNA genome containing rep, a large gene encoding viral protease Mpro. ANPEP, CKM, EIF4E, FBL, GPT, LDHA, LDHB, LDHC, MAPK14, NCL 10 ANPEP(5), CKM(2), FBL(1), GPT(1), LDHB(2), LDHC(1), MAPK14(1), NCL(1) 2415104 14 12 14 5 2 7 2 1 2 0 0.82 1.00 356 PAR1PATHWAY Activated extracellular thrombin cleaves and activates the G-protein coupled receptors PAR1 and PAR4, which activate platelets. ADCY1, ARHA, ARHGEF1, F2, F2R, F2RL3, GNA12, GNA13, GNAI1, GNAQ, GNB1, GNGT1, MAP3K7, PIK3CA, PIK3R1, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2B, ROCK1 18 ADCY1(8), ARHGEF1(2), F2R(2), F2RL3(2), GNA12(1), GNA13(1), GNAI1(2), GNB1(1), MAP3K7(3), PIK3R1(1), PLCB1(7), PPP1R12B(3), PRKCA(5), ROCK1(5) 6447694 43 34 43 11 11 19 7 4 2 0 0.82 1.00 357 METHIONINEPATHWAY Catabolic Pathways for Methionine, Isoleucine, Threonine and Valine BCKDHB, BCKDK, CBS, CTH, MUT 5 BCKDHB(2), CBS(4), MUT(1) 1333932 7 6 7 1 0 5 0 0 2 0 0.82 1.00 358 TNFR2PATHWAY Tumor necrosis factor beta, produced by activated lymphocytes, binds to its receptor TNFR2 to induce activation in immune cells and apoptosis in many other cells. CHUK, DUSP1, IKBKAP, IKBKB, IKBKG, LTA, MAP3K1, MAP3K14, NFKB1, NFKBIA, RELA, RIPK1, TANK, TNFAIP3, TNFRSF1B, TRAF1, TRAF2, TRAF3 17 CHUK(2), IKBKAP(2), IKBKB(3), LTA(3), MAP3K1(3), MAP3K14(1), NFKB1(2), RELA(3), TANK(4), TNFAIP3(4), TNFRSF1B(1), TRAF1(4), TRAF3(1) 6090804 33 26 33 14 5 9 6 5 8 0 0.82 1.00 359 FCER1PATHWAY In mast cells, Fc epsilon receptor 1 activates BTK, PKC, and the MAP kinase pathway to promote degranulation and arachnidonic acid release. BTK, CALM1, CALM2, CALM3, ELK1, FCER1A, FCER1G, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP2K4, MAP2K7, MAP3K1, MAPK1, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, PAK2, PIK3CA, PIK3R1, PLA2G4A, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCB1, RAF1, SHC1, SOS1, SYK, SYT1, VAV1 36 BTK(5), FCER1A(1), FOS(1), HRAS(2), JUN(2), LYN(1), MAP2K1(2), MAP3K1(3), MAPK1(1), MAPK3(2), MAPK8(2), NFATC2(5), NFATC3(3), NFATC4(2), PAK2(1), PIK3R1(1), PLA2G4A(5), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), RAF1(1), SHC1(1), SOS1(6), SYK(1), SYT1(3), VAV1(7) 11048638 69 53 69 29 20 20 12 11 6 0 0.82 1.00 360 P53PATHWAY p53 induces cell cycle arrest or apoptosis under conditions of DNA damage. APAF1, ATM, BAX, BCL2, CCND1, CCNE1, CDK2, CDK4, CDKN1A, E2F1, GADD45A, MDM2, PCNA, RB1, TIMP3, TP53 15 APAF1(1), ATM(7), BAX(1), CCND1(1), CDK2(1), E2F1(3), GADD45A(1), MDM2(1), RB1(7) 4723408 23 21 23 4 3 9 2 2 7 0 0.82 1.00 361 1_AND_2_METHYLNAPHTHALENE_DEGRADATION ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 7 ADH1B(1), ADH1C(1), ADH4(2), ADH7(1), ADHFE1(2) 1501074 7 7 7 4 3 4 0 0 0 0 0.83 1.00 362 SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES ACAT1, ACAT2, BDH, HMGCL, OXCT1 4 ACAT1(1), HMGCL(1), OXCT1(2) 901926 4 4 4 3 3 1 0 0 0 0 0.83 1.00 363 AHSPPATHWAY Alpha-hemoglobin stabilizing protein (AHSP) prevents precitipation of hemoglobin alpha-subunits. ALAD, ALAS1, ALAS2, CPO, ERAF, FECH, GATA1, HBA1, HBA2, HBB, HMBS, UROD, UROS 12 ALAS1(2), CPO(1), FECH(2), GATA1(3), HBB(2), HMBS(2), UROD(1) 2209870 13 12 13 3 4 6 0 1 2 0 0.83 1.00 364 HSA00400_PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS Genes involved in phenylalanine, tyrosine and tryptophan biosynthesis FARS2, FARSA, FARSB, GOT1, GOT2, PAH, TAT, YARS, YARS2 9 FARS2(1), FARSA(2), GOT1(2), GOT2(3), PAH(1), TAT(1), YARS(1), YARS2(1) 2348888 12 12 11 8 6 4 0 1 1 0 0.83 1.00 365 HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - lactoseries ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 10 B3GALT1(2), B3GALT2(2), FUT3(3), ST3GAL4(2) 1955330 9 9 9 5 3 0 5 1 0 0 0.83 1.00 366 RABPATHWAY Rab family GTPases regulate vesicle transport, endocytosis and exocytosis, and vesicle docking via interactions with the rabphilins. ACTA1, MEL, RAB11A, RAB1A, RAB2, RAB27A, RAB3A, RAB4A, RAB5A, RAB6A, RAB7, RAB9A 9 ACTA1(2), RAB4A(3) 1158068 5 5 5 10 3 2 0 0 0 0 0.83 1.00 367 CELL_CYCLE_KEGG ABL1, ASK, ATM, BUB1, BUB1B, BUB3, CCNA1, CCNA2, CCNB1, CCNB2, CCNB3, CCND2, CCND3, CCNE1, CCNE2, CCNH, CDAN1, CDC14A, CDC14B, CDC14B, CDC14C, CDC2, CDC20, CDC25A, CDC25B, CDC25C, CDC45L, CDC6, CDC7, CDH1, CDK2, CDK4, CDKN1A, CDKN2A, CHEK1, CHEK2, DTX4, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, EP300, ESPL1, FLJ14001, GADD45A, GSK3B, HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7A, HDAC8, MAD1L1, MAD2L1, MAD2L2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MPEG1, MPL, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, PLK1, PRKDC, PTPRA, PTTG1, PTTG2, PTTG3, RB1, RBL1, SKP2, SMAD4, SMC1L1, TBC1D8, TFDP1, TGFB1, TP53, WEE1 80 ABL1(2), ATM(7), BUB1(4), BUB1B(5), BUB3(1), CCNA1(1), CCNB1(1), CCNB3(9), CCND2(3), CCND3(1), CCNE2(2), CDAN1(3), CDC25B(3), CDC25C(1), CDC6(4), CDC7(1), CDH1(4), CDK2(1), CHEK1(4), CHEK2(3), DTX4(2), E2F1(3), EP300(5), ESPL1(3), GADD45A(1), GSK3B(1), HDAC1(2), HDAC3(1), HDAC4(5), HDAC5(1), MAD1L1(5), MAD2L1(2), MCM2(1), MCM3(1), MCM4(4), MCM5(6), MCM6(2), MCM7(3), MDM2(1), MPEG1(5), MPL(3), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), PLK1(1), PRKDC(15), PTTG1(1), PTTG2(2), RB1(7), RBL1(6), SKP2(1), SMAD4(2), TBC1D8(2), TGFB1(1), WEE1(2) 29837428 161 96 159 50 34 62 30 11 24 0 0.83 1.00 368 AKAPCENTROSOMEPATHWAY Protein Kinase A at the Centrosome AKAP9, ARHA, CDC2, MAP2, PCNT1, PCNT2, PPP1CA, PPP2CA, PRKACB, PRKACG, PRKAG1, PRKAR2A, PRKAR2B, PRKCE, PRKCL1 10 AKAP9(6), MAP2(9), PPP1CA(1), PRKACB(2), PRKACG(1), PRKAR2B(3), PRKCE(5) 4900162 27 24 27 11 8 5 9 3 2 0 0.83 1.00 369 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 244 ACVR1B(3), ACVR2A(3), ACVR2B(1), AMHR2(4), BMP7(1), BMPR1A(3), CCL14(2), CCL16(1), CCL20(1), CCL26(2), CCL3(2), CCR1(2), CCR3(1), CCR4(3), CCR6(2), CCR8(3), CD27(2), CD40(1), CD40LG(2), CNTFR(1), CSF1(2), CSF1R(3), CSF2RB(5), CSF3R(5), CX3CR1(3), CXCL5(2), CXCR3(1), EDA2R(1), EGF(6), EGFR(9), EPOR(2), FAS(1), FASLG(1), FLT1(9), FLT3(4), FLT4(3), GDF5(4), GH1(1), GH2(2), GHR(2), HGF(6), IFNA1(1), IFNA10(1), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNAR1(2), IFNB1(1), IFNG(1), IFNGR1(3), IFNGR2(1), IL10(1), IL10RA(1), IL11RA(2), IL12A(1), IL12B(3), IL12RB1(3), IL12RB2(3), IL13RA1(2), IL17A(1), IL17RA(3), IL17RB(2), IL18R1(2), IL18RAP(2), IL1B(1), IL1R2(3), IL1RAP(2), IL20(1), IL20RA(1), IL21(1), IL21R(2), IL22(1), IL22RA1(1), IL22RA2(1), IL23R(1), IL26(1), IL28B(1), IL2RB(2), IL2RG(1), IL4(2), IL5RA(2), IL6R(1), IL7R(3), INHBA(4), INHBC(1), KDR(11), KIT(6), LEPR(10), LIFR(4), LTA(3), LTB(1), LTBR(1), MET(3), MPL(3), NGFR(1), OSMR(4), PDGFB(1), PDGFC(1), PDGFRA(8), PDGFRB(5), PF4(1), PLEKHO2(5), PRL(1), PRLR(5), TGFB1(1), TGFB2(1), TGFBR2(3), TNFRSF10A(1), TNFRSF10B(1), TNFRSF10D(1), TNFRSF11A(1), TNFRSF11B(1), TNFRSF13B(2), TNFRSF14(1), TNFRSF18(1), TNFRSF19(1), TNFRSF1A(2), TNFRSF1B(1), TNFRSF21(3), TNFRSF6B(1), TNFRSF9(1), TNFSF11(1), TNFSF13(1), TNFSF14(2), TNFSF18(1), VEGFC(4), XCL1(1), XCR1(1) 46629236 297 120 295 134 81 110 52 18 36 0 0.84 1.00 370 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 30 AKT1(1), AKT3(2), BCR(1), BTK(5), CD19(2), FLOT1(2), GAB1(2), ITPR1(5), ITPR2(11), ITPR3(3), LYN(1), NR0B2(1), PDK1(1), PHF11(2), PITX2(3), PLCG2(3), PPP1R13B(4), PREX1(12), PTPRC(3), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KB1(1), SYK(1), TEC(2), VAV1(7) 14183574 82 60 82 37 20 29 13 7 13 0 0.84 1.00 371 BIOPEPTIDESPATHWAY Extracellular signaling peptides exert biological effects via G-protein coupled receptors (GPCRs), which activate intracellular GTPases. AGT, AGTR2, BDK, CALM1, CALM2, CALM3, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CDK5, F2, FYN, GNA11, GNAI1, GNB1, GNGT1, GRB2, HRAS, JAK2, MAP2K1, MAP2K2, MAPK1, MAPK14, MAPK3, MAPK8, MAPT, MYLK, PLCG1, PRKCA, PRKCB1, PTK2B, RAF1, SHC1, SOS1, STAT1, STAT3, STAT5A, SYT1 37 AGT(1), AGTR2(4), CAMK2B(2), CAMK2D(1), CDK5(2), FYN(4), GNAI1(2), GNB1(1), HRAS(2), JAK2(3), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK14(1), MAPK3(2), MAPK8(2), MAPT(5), MYLK(7), PLCG1(2), PRKCA(5), RAF1(1), SHC1(1), SOS1(6), STAT1(2), STAT3(1), STAT5A(2), SYT1(3) 11315994 67 54 67 20 14 28 13 5 7 0 0.84 1.00 372 N_GLYCAN_DEGRADATION AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 12 AGA(2), FUCA1(1), HEXA(6), MAN2C1(5), MANBA(2), NEU1(4), NEU2(2), NEU3(2) 3513542 24 17 24 6 4 11 7 0 2 0 0.84 1.00 373 HSA00052_GALACTOSE_METABOLISM Genes involved in galactose metabolism AKR1B1, AKR1B10, B4GALT1, B4GALT2, G6PC, G6PC2, GAA, GALE, GALK1, GALK2, GALT, GANC, GCK, GLA, GLB1, HK1, HK2, HK3, HSD3B7, LALBA, LCT, MGAM, PFKL, PFKM, PFKP, PGM1, PGM3, RDH11, RDH12, RDH13, RDH14, UGP2 31 AKR1B10(1), B4GALT1(1), G6PC(2), G6PC2(2), GALE(1), GALK2(1), GALT(1), GANC(3), GCK(1), GLA(2), HK1(4), HK2(6), HK3(7), MGAM(5), PFKL(2), PFKM(5), PFKP(2), PGM1(1), RDH11(2), RDH12(2), RDH13(1), UGP2(5) 9542224 57 48 56 20 21 22 4 6 4 0 0.84 1.00 374 ALKPATHWAY Activin receptor-like kinase 3 (ALK3) is required during gestation for cardiac muscle development. ACVR1, APC, ATF2, AXIN1, BMP10, BMP2, BMP4, BMP5, BMP7, BMPR1A, BMPR2, CHRD, CTNNB1, DVL1, FZD1, GATA4, GSK3B, MADH1, MADH4, MADH5, MADH6, MAP3K7, MEF2C, MYL2, NKX2-5, NOG, NPPA, NPPB, RFC1, TCF1, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, WNT1 32 APC(9), ATF2(2), BMP10(1), BMP4(2), BMP5(5), BMP7(1), BMPR1A(3), CHRD(2), CTNNB1(3), DVL1(3), FZD1(1), GSK3B(1), MAP3K7(3), MEF2C(2), MYL2(1), NKX2-5(2), RFC1(1), TGFB1(1), TGFB2(1), TGFBR2(3), TGFBR3(6) 9785906 53 43 53 18 10 16 14 7 6 0 0.84 1.00 375 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(1), ACO2(2), FH(2), IDH1(2), MDH1(1), MDH2(1), SUCLA2(2) 2378792 11 11 11 4 1 7 1 1 1 0 0.84 1.00 376 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 38 AKT1(1), AKT3(2), BCR(1), BLNK(1), BTK(5), CD19(2), DAG1(1), EPHB2(5), ITPKA(1), ITPKB(3), LYN(1), MAP2K1(2), MAP2K2(2), MAPK1(1), NFAT5(3), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), PI3(1), PIK3CD(3), PIK3R1(1), PLCG2(3), PPP1R13B(4), RAF1(1), SERPINA4(4), SHC1(1), SOS1(6), SOS2(4), SYK(1), VAV1(7) 13747830 78 56 78 31 17 26 15 9 11 0 0.84 1.00 377 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 30 ACP1(1), ACPT(2), ALPI(1), ALPL(3), ALPP(1), ALPPL2(1), CYP19A1(3), CYP1A2(1), CYP2A13(2), CYP2A6(3), CYP2B6(3), CYP2C19(6), CYP2C8(3), CYP2C9(2), CYP2D6(3), CYP2E1(1), CYP2F1(4), CYP2J2(2), CYP3A4(1), CYP3A7(1), CYP4B1(3), CYP4F8(1), PON1(4) 7658806 52 39 52 28 20 13 13 3 3 0 0.85 1.00 378 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 49 ALG6(3), CCKBR(1), CCR3(1), CELSR1(10), CELSR2(7), CELSR3(9), CHRM2(6), CHRM3(5), CXCR3(1), DRD4(1), EDNRA(2), EMR2(5), EMR3(3), F2R(2), GHRHR(3), GPR116(4), GPR132(1), GPR133(2), GPR143(2), GPR17(5), GPR18(1), GPR55(1), GPR56(1), GPR61(2), GPR77(4), GPR84(1), GRPR(2), HRH4(3), LGR6(2), LPHN2(6), LTB4R2(1), NTSR1(3), OR8G2(1), P2RY13(1), PTGFR(2), SMO(1), SSTR2(2), TAAR5(5), TSHR(1), VN1R1(2) 16444886 115 68 115 52 36 40 21 5 13 0 0.85 1.00 379 IL3PATHWAY IL-3 promotes proliferation and differentiation of hematopoietic cells via a heterodimeric receptor that activates the Stat5 and MAP kinase pathways. CSF2RB, FOS, GRB2, HRAS, IL3, IL3RA, JAK2, MAP2K1, MAPK3, PTPN6, RAF1, SHC1, SOS1, STAT5A, STAT5B 14 CSF2RB(5), FOS(1), HRAS(2), JAK2(3), MAP2K1(2), MAPK3(2), RAF1(1), SHC1(1), SOS1(6), STAT5A(2) 4575846 25 24 25 5 7 9 5 1 3 0 0.85 1.00 380 GLYCEROLIPID_METABOLISM ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AKR1A1, AKR1B1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, CEL, DGAT1, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKQ, DGKZ, GK, GLA, GLB1, LCT, LIPC, LIPF, LIPG, LPL, PNLIP, PNLIPRP1, PNLIPRP2, PPAP2A, PPAP2B, PPAP2C 42 ADH1B(1), ADH1C(1), ADH4(2), ADH7(1), ADHFE1(2), AGPAT3(1), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2), CEL(5), DGKA(6), DGKB(4), DGKD(5), DGKE(2), DGKG(2), DGKZ(3), GK(4), GLA(2), LIPC(1), LIPF(1), LIPG(2), LPL(3), PNLIPRP1(3), PNLIPRP2(2), PPAP2B(2) 11725394 66 53 64 32 18 33 5 5 5 0 0.85 1.00 381 GLYCEROPHOSPHOLIPID_METABOLISM ACHE, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPS, CDIPT, CDS1, CDS2, CHAT, CHKA, CHKB, CHKB, CPT1B, CLC, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKQ, DGKZ, ETNK1, GNPAT, GPD1, GPD2, LCAT, LGALS13, LYPLA1, LYPLA2, LYPLA2, LYPLA2P1, LOC388499, LYPLA3, PAFAH1B1, PAFAH2, PCYT1A, PCYT1B, PEMT, PISD, PLA2G1B, PLA2G2A, PLA2G2E, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCB2, PLCG1, PLCG2, PPAP2A, PPAP2B, PPAP2C 49 ACHE(2), AGPAT3(1), CDS1(2), CHAT(2), CHKA(2), DGKA(6), DGKB(4), DGKD(5), DGKE(2), DGKG(2), DGKZ(3), ETNK1(3), GPD1(2), GPD2(2), LYPLA1(5), PAFAH1B1(1), PAFAH2(1), PCYT1A(2), PCYT1B(1), PISD(1), PLA2G2A(1), PLA2G2E(2), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLCB2(5), PLCG1(2), PLCG2(3), PPAP2B(2) 13840390 80 60 80 34 22 32 13 5 8 0 0.85 1.00 382 SULFUR_METABOLISM BPNT1, PAPSS1, PAPSS2, SULT1A2, SULT1A3, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SUOX 7 BPNT1(1), PAPSS2(1), SULT1A2(2), SULT1E1(1), SULT2A1(3) 1626208 8 8 8 3 3 2 2 0 1 0 0.85 1.00 383 PS1PATHWAY Presenilin is required for gamma-secretase activity to activate Notch signaling; presenilin also inhibits beta-catenin in the Wnt/Frizzled pathway. ADAM17, APC, AXIN1, BTRC, CTNNB1, DLL1, DVL1, FZD1, GSK3B, NOTCH1, PSEN1, RBPSUH, TCF1, WNT1 12 APC(9), BTRC(1), CTNNB1(3), DLL1(1), DVL1(3), FZD1(1), GSK3B(1), NOTCH1(11), PSEN1(1) 5808318 31 27 31 8 6 11 5 1 8 0 0.85 1.00 384 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 24 GH1(1), GHR(2), HRAS(2), INSR(7), IRS1(4), JAK2(3), MAP2K1(2), MAPK1(1), MAPK3(2), PIK3R1(1), PLCG1(2), PRKCA(5), RAF1(1), RPS6KA1(4), SHC1(1), SLC2A4(2), SOS1(6), SRF(2), STAT5A(2) 8349802 50 41 50 15 10 21 11 4 4 0 0.85 1.00 385 HSA00310_LYSINE_DEGRADATION Genes involved in lysine degradation AADAT, AASDHPPT, AASS, ACAT1, ACAT2, AKR1B10, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, BBOX1, DLST, DOT1L, ECHS1, EHHADH, EHMT1, EHMT2, GCDH, HADH, HADHA, HSD17B10, HSD17B4, HSD3B7, NSD1, OGDH, OGDHL, PIPOX, PLOD1, PLOD2, PLOD3, RDH11, RDH12, RDH13, RDH14, SETD1A, SETD7, SETDB1, SHMT1, SHMT2, SPCS1, SPCS3, SUV39H1, SUV39H2, TMLHE 47 AADAT(1), AASDHPPT(1), AASS(6), ACAT1(1), AKR1B10(1), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), BBOX1(2), DLST(1), DOT1L(5), EHHADH(1), EHMT2(2), GCDH(1), HADH(1), HADHA(2), HSD17B4(1), NSD1(11), OGDH(3), OGDHL(4), PIPOX(1), PLOD1(2), PLOD2(4), PLOD3(4), RDH11(2), RDH12(2), RDH13(1), SETD1A(6), SETDB1(5), SPCS1(1), SPCS3(2), SUV39H1(1), SUV39H2(2) 15838974 85 64 85 46 12 30 21 8 14 0 0.85 1.00 386 HSA03320_PPAR_SIGNALING_PATHWAY Genes involved in PPAR signaling pathway ACAA1, ACADL, ACADM, ACOX1, ACOX2, ACOX3, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADIPOQ, ANGPTL4, APOA1, APOA2, APOA5, APOC3, AQP7, CD36, CPT1A, CPT1B, CPT1C, CPT2, CYP27A1, CYP4A11, CYP4A22, CYP7A1, CYP8B1, DBI, EHHADH, FABP1, FABP2, FABP3, FABP4, FABP5, FABP5L1, FABP6, FABP7, FADS2, GK, GK2, HMGCS2, ILK, LOC642956, LPL, ME1, MMP1, NR1H3, OLR1, PCK1, PCK2, PDPK1, PLIN, PLTP, PPARA, PPARD, PPARG, RXRA, RXRB, RXRG, SCD, SCP2, SLC27A1, SLC27A2, SLC27A4, SLC27A5, SLC27A6, SORBS1, UBC, UCP1 65 ACADL(2), ACADM(1), ACOX1(2), ACOX3(4), ACSL1(2), ACSL3(1), ACSL5(1), ACSL6(2), ADIPOQ(1), ANGPTL4(1), APOA2(1), APOA5(3), AQP7(2), CD36(1), CPT1A(3), CPT1C(5), CPT2(2), CYP27A1(2), CYP4A22(1), CYP7A1(3), DBI(1), EHHADH(1), FABP5(1), FABP6(1), FABP7(1), FADS2(1), GK(4), GK2(5), HMGCS2(1), ILK(1), LPL(3), MMP1(3), NR1H3(2), PCK1(3), PCK2(1), PDPK1(1), PLTP(2), PPARA(2), PPARD(2), RXRA(1), RXRG(5), SCD(1), SCP2(1), SLC27A1(1), SLC27A2(2), SLC27A4(1), SLC27A5(4), SLC27A6(3), SORBS1(5), UBC(1), UCP1(2) 17498112 103 71 103 54 26 36 26 6 9 0 0.86 1.00 387 IFNGPATHWAY IFN gamma signaling pathway IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 6 IFNG(1), IFNGR1(3), IFNGR2(1), JAK1(1), JAK2(3), STAT1(2) 2203818 11 10 11 2 2 4 4 0 1 0 0.86 1.00 388 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 41 AKT1(1), BRAF(7), CREB3(2), CREB5(3), CREBBP(12), CRKL(1), DAG1(1), EGR1(4), EGR2(6), EGR3(1), FRS2(3), JUN(2), MAP1B(4), MAPK1(1), MAPK10(1), MAPK3(2), MAPK8(2), MAPK8IP1(2), MAPK8IP3(6), MAPK9(1), NTRK1(3), OPN1LW(2), PIK3C2G(7), PIK3CD(3), PIK3R1(1), PTPN11(3), RPS6KA3(1), SHC1(1), TH(2) 13677876 85 61 84 34 29 30 14 6 6 0 0.87 1.00 389 ST_T_CELL_SIGNAL_TRANSDUCTION On activation of the T cell receptor, phospholipase C is activated to produce second messengers DAG and PIP3, both required for T cell activation. CBL, CD28, CD3D, CSK, CTLA4, DAG1, DTYMK, EPHB2, FBXW7, GRAP2, GRB2, ITK, ITPKA, ITPKB, LAT, LCK, LCP2, MAPK1, NCK1, NFAT5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PAG, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PLCG1, PTPRC, RAF1, RASGRP1, RASGRP2, RASGRP3, RASGRP4, SOS1, SOS2, VAV1, ZAP70 42 CBL(4), CD3D(1), DAG1(1), EPHB2(5), GRAP2(1), ITK(2), ITPKA(1), ITPKB(3), LAT(1), LCK(2), LCP2(2), MAPK1(1), NCK1(3), NFAT5(3), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PLCG1(2), PTPRC(3), RAF1(1), RASGRP1(1), RASGRP3(8), RASGRP4(4), SOS1(6), SOS2(4), VAV1(7), ZAP70(3) 14819924 94 64 94 32 28 33 18 5 10 0 0.87 1.00 390 ST_GRANULE_CELL_SURVIVAL_PATHWAY The survival and differentiation of granule cells in the brain is controlled by pro-growth PACAP and pro-apoptotic ceramides. ADPRT, APC, ASAH1, CAMP, CASP3, CERK, CREB1, CREB3, CREB5, CXCL2, DAG1, EPHB2, FOS, GNAQ, IL8RB, ITPKA, ITPKB, JUN, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, PACAP 25 APC(9), CERK(3), CREB3(2), CREB5(3), DAG1(1), EPHB2(5), FOS(1), ITPKA(1), ITPKB(3), JUN(2), MAPK1(1), MAPK10(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(6), MAPK9(1) 7865998 43 37 43 11 11 15 10 2 5 0 0.87 1.00 391 HSA00650_BUTANOATE_METABOLISM Genes involved in butanoate metabolism AACS, AADAC, ABAT, ACADS, ACAT1, ACAT2, ACSM1, AKR1B10, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH5A1, ALDH7A1, ALDH9A1, BDH1, BDH2, DDHD1, ECHS1, EHHADH, GAD1, GAD2, HADH, HADHA, HMGCL, HMGCS1, HMGCS2, HSD17B10, HSD17B4, HSD3B7, ILVBL, L2HGDH, OXCT1, OXCT2, PDHA1, PDHA2, PDHB, PLA1A, PPME1, PRDX6, RDH11, RDH12, RDH13, RDH14 45 AACS(2), AADAC(2), ABAT(3), ACADS(3), ACAT1(1), ACSM1(6), AKR1B10(1), ALDH1B1(3), ALDH2(2), ALDH5A1(1), ALDH7A1(1), ALDH9A1(2), BDH1(6), DDHD1(4), EHHADH(1), GAD1(5), GAD2(5), HADH(1), HADHA(2), HMGCL(1), HMGCS1(1), HMGCS2(1), HSD17B4(1), ILVBL(2), L2HGDH(1), OXCT1(2), PDHA1(2), PDHA2(5), PLA1A(5), PRDX6(1), RDH11(2), RDH12(2), RDH13(1) 11071778 78 49 78 30 18 33 8 10 9 0 0.87 1.00 392 PROTEASOMEPATHWAY Ubiquitinated proteins are targeted for proteolytic degradation by the proteasome, where they are unfolded and degraded to small peptides in an ATP-dependent process. PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMC3, PSMD14, RPN1, RPN2, UBE1, UBE2A, UBE3A 20 PSMA4(1), PSMA5(1), PSMB3(1), PSMB4(2), PSMB6(1), PSMC3(1), PSMD14(3), RPN1(1), UBE2A(2), UBE3A(4) 3479544 17 17 17 6 4 8 3 0 2 0 0.87 1.00 393 TUBBYPATHWAY Tubby is activated by phospholipase C activity and hydrolysis of PIP2, after which it enters the nucleus and regulates transcription. CHRM1, GNAQ, GNB1, GNGT1, HTR2C, PLCB1, TUB 7 GNB1(1), HTR2C(3), PLCB1(7) 1924358 11 10 11 5 4 5 0 2 0 0 0.87 1.00 394 HSA00062_FATTY_ACID_ELONGATION_IN_MITOCHONDRIA Genes involved in fatty acid elongation in mitochondria ACAA2, ECHS1, HADH, HADHA, HADHB, HSD17B10, HSD17B4, MECR, PPT1, PPT2 10 ACAA2(1), HADH(1), HADHA(2), HADHB(2), HSD17B4(1), MECR(1), PPT1(1), PPT2(1) 2306524 10 10 10 2 2 1 2 3 2 0 0.88 1.00 395 HSA00340_HISTIDINE_METABOLISM Genes involved in histidine metabolism ABP1, ACY3, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH7A1, ALDH9A1, AMDHD1, AOC2, AOC3, ASPA, CARM1, CNDP1, DDC, FTCD, HAL, HARS, HARS2, HDC, HEMK1, HNMT, LCMT1, LCMT2, MAOA, MAOB, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, PRPS1, PRPS2, UROC1, WBSCR22 41 ABP1(6), ACY3(2), ALDH1B1(3), ALDH2(2), ALDH3B2(2), ALDH7A1(1), ALDH9A1(2), AMDHD1(2), AOC2(2), AOC3(3), ASPA(1), CARM1(1), CNDP1(3), DDC(2), HARS(2), HARS2(2), HDC(3), HNMT(1), LCMT1(2), LCMT2(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), PRPS1(1), PRPS2(1), UROC1(3), WBSCR22(4) 10716134 61 50 61 24 23 22 8 4 4 0 0.88 1.00 396 LYMPHOCYTEPATHWAY B and T cell lymphocytes interact with other cells via transmembrane adhesion proteins such as CD44, which interacts with endothelial cells. CD44, ICAM1, ITGA4, ITGAL, ITGB1, ITGB2, PECAM1, SELE, SELL 9 CD44(3), ICAM1(2), ITGA4(5), ITGAL(1), ITGB1(4), ITGB2(3), SELE(4), SELL(2) 3655764 24 17 24 3 6 7 7 2 2 0 0.88 1.00 397 APOPTOSIS_KEGG APAF1, BAD, BAX, BCL2, BCL2A1, BCL2L1, BCL2L2, BOK, CASP1, CASP1, COPl, CASP10, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CD40, CD40LG, CRADD, CYCS, DAXX, DFFA, DFFB, FADD, FAS, FASLG, HRK, IKBKE, LTA, MCL1, NFKB1, NFKBIA, NGFB, NGFR, NR3C1, NTRK1, PTPN13, RIPK1, SFRS2IP, TFG, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF1, TRAF2, TRAF3, TRAF6 47 APAF1(1), BAX(1), BCL2A1(1), BCL2L1(2), CASP1(2), CASP10(4), CASP2(1), CASP4(3), CASP6(1), CASP7(2), CASP8(1), CASP9(1), CD40(1), CD40LG(2), CRADD(1), DAXX(3), DFFA(1), DFFB(2), FADD(1), FAS(1), FASLG(1), IKBKE(3), LTA(3), MCL1(2), NFKB1(2), NGFR(1), NTRK1(3), PTPN13(3), SFRS2IP(3), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TRAF1(4), TRAF3(1), TRAF6(1) 12079436 63 49 63 27 14 24 6 7 12 0 0.88 1.00 398 SALMONELLAPATHWAY Salmonella induces membrane ruffling in infected cells via bacterial proteins including SipA, SipC, and SopE, which alter actin structure. ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, RAC1, WASF1, WASL 12 ACTA1(2), ACTR2(1), ARPC1A(2), ARPC1B(1), CDC42(1), RAC1(2), WASL(2) 2180856 11 11 11 7 1 7 2 1 0 0 0.88 1.00 399 HSA00602_GLYCOSPHINGOLIPID_BIOSYNTHESIS_NEO_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - neo-lactoseries ABO, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALT1, B4GALT2, B4GALT3, B4GALT4, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GCNT2, ST3GAL6, ST8SIA1 21 B3GNT2(1), B3GNT3(4), B3GNT4(1), B4GALT1(1), B4GALT3(2), B4GALT4(1), FUT3(3), FUT5(4), FUT6(2), FUT9(1), GCNT2(1), ST3GAL6(1), ST8SIA1(2) 4446796 24 20 24 19 8 7 6 2 1 0 0.88 1.00 400 GLYCOSAMINOGLYCAN_DEGRADATION ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, IDS, IDUA, LCT, NAGLU 10 ARSB(2), GNS(1), GUSB(3), HEXA(6), IDS(1), IDUA(2) 2919378 15 13 15 2 2 6 3 1 3 0 0.88 1.00 401 VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION ACAA1, ACAA2, ACADL, ACADM, ACADS, ACADSB, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH9A1, AOX1, BCAT1, BCKDHA, BCKDHB, ECHS1, EHHADH, HADHA, HADHB, HIBADH, HMGCL, IVD, MCCC1, MCCC2, MCEE, MUT, OXCT1, PCCA, PCCB, SDS 36 ACAA2(1), ACADL(2), ACADM(1), ACADS(3), ACAT1(1), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH6A1(2), ALDH9A1(2), AOX1(11), BCAT1(1), BCKDHB(2), EHHADH(1), HADHA(2), HADHB(2), HMGCL(1), MCCC1(7), MUT(1), OXCT1(2), PCCA(2), PCCB(6), SDS(2) 9687116 61 43 60 19 9 25 12 8 7 0 0.88 1.00 402 PYRUVATE_METABOLISM ACACA, ACAS2, ACAS2L, ACAT1, ACAT2, ACYP1, ACYP2, ADH5, AKR1B1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, CACH_1, DLAT, DLD, GLO1, GRHPR, HAGH, HAGHL, LDHA, LDHB, LDHC, LDHD, MDH1, MDH2, ME1, ME2, ME3, PC, PCK1, PDHA1, PDHA2, PDHB, PKLR, PKM2 37 ACACA(4), ACAT1(1), ADH5(2), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2), DLAT(1), DLD(2), GRHPR(1), HAGHL(1), LDHB(2), LDHC(1), LDHD(6), MDH1(1), MDH2(1), ME2(2), ME3(2), PC(4), PCK1(3), PDHA1(2), PDHA2(5), PKLR(3), PKM2(1) 9947530 56 46 55 21 12 28 6 4 6 0 0.88 1.00 403 CALCINEURIN_NF_AT_SIGNALING Mouse genes associated with signal transduction through calcium, calcineurin, and NF-AT. ACTB, BAD, BCL2, CABIN1, CALM1, CALM2, CALM3, CAMK2B, CAMK4, CD3E, CD3G, CD3Z, CD69, CDKN1A, CEBPB, CNR1, CREBBP, CSF2, CSNK2A1, CSNK2B, CTLA4, EGR2, EGR3, EP300, FCER1A, FCGR3A, FKBP1B, FLJ14639, FOS, FOSL1, GAPD, GATA3, GATA4, GRLF1, GSK3A, GSK3B, HRAS, ICOS, IFNA1, IFNB1, IFNG, IL10, IL13, IL1B, IL2, IL2RA, IL3, IL4, IL6, IL8, IL8RA, ITK, JUNB, KPNA5, KPNB3, MAP2K7, MAPK14, MAPK8, MAPK9, MEF2A, MEF2B, MEF2D, MYF5, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB2, NFKBIB, NFKBIE, NPPB, NUP214, OPRD1, P2RX7, PAK1, PIN1, PPIA, PPP3CB, PPP3CC, PPP3R1, PTPRC, RELA, RPL13A, SFN, SLA, SP1, SP3, TGFB1, TNF, TNFSF5, TNFSF6, TRAF2, TRPV6, VAV1, VAV2, VAV3, VEGF, XPO5 92 ACTB(1), CABIN1(5), CAMK2B(2), CAMK4(3), CNR1(3), CREBBP(12), CSNK2A1(2), EGR2(6), EGR3(1), EP300(5), FCER1A(1), FCGR3A(3), FKBP1B(1), FOS(1), GATA3(5), GRLF1(11), GSK3A(4), GSK3B(1), HRAS(2), ICOS(2), IFNA1(1), IFNB1(1), IFNG(1), IL10(1), IL1B(1), IL4(2), ITK(2), KPNA5(2), MAPK14(1), MAPK8(2), MAPK9(1), MEF2A(2), MEF2D(2), MYF5(3), NFAT5(3), NFATC2(5), NFATC3(3), NFATC4(2), NFKB2(2), NFKBIB(1), NUP214(5), OPRD1(2), P2RX7(1), PAK1(3), PPP3CB(5), PPP3CC(2), PPP3R1(1), PTPRC(3), RELA(3), SFN(2), SLA(2), SP1(1), SP3(1), TGFB1(1), TRPV6(5), VAV1(7), VAV2(4), VAV3(1), XPO5(3) 24820854 161 87 160 55 50 46 28 17 20 0 0.88 1.00 404 SA_MMP_CYTOKINE_CONNECTION Cytokines can induce activation of matrix metalloproteinases, which degrade extracellular matrix. ACE, CD44, CSF1, FCGR3A, IL1B, IL6R, SELL, SPN, TGFB1, TGFB2, TNF, TNFRSF1A, TNFRSF1B, TNFRSF8, TNFSF8 15 ACE(4), CD44(3), CSF1(2), FCGR3A(3), IL1B(1), IL6R(1), SELL(2), TGFB1(1), TGFB2(1), TNFRSF1A(2), TNFRSF1B(1) 3779118 21 17 21 9 6 5 5 2 3 0 0.88 1.00 405 SA_CASPASE_CASCADE Apoptosis is mediated by caspases, cysteine proteases arranged in a proteolytic cascade. ADPRT, APAF1, BIRC2, BIRC3, BIRC4, CASP10, CASP3, CASP7, CASP8, CASP9, DFFA, DFFB, GZMB, PRF1, SCAP, SREBF1, SREBF2, TNFRSF6, TNFSF6 15 APAF1(1), BIRC3(3), CASP10(4), CASP7(2), CASP8(1), CASP9(1), DFFA(1), DFFB(2), GZMB(1), PRF1(2), SCAP(4), SREBF1(3), SREBF2(2) 5027432 27 24 27 11 7 11 4 3 2 0 0.88 1.00 406 THELPERPATHWAY Helper T cells coordinate the actions of B cells, macrophages, and other immune cells via surface molecules such as T cell receptor/CD3 and their characteristic marker CD4. CD2, CD28, CD3D, CD3E, CD3G, CD3Z, CD4, ICAM1, ITGAL, ITGB2, PTPRC, THY1, TRA@, TRB@ 11 CD2(1), CD3D(1), CD4(2), ICAM1(2), ITGAL(1), ITGB2(3), PTPRC(3), THY1(2) 3034544 15 15 15 8 3 8 1 2 1 0 0.89 1.00 407 KREBS_TCA_CYCLE ACO2, CGI_48, CS, DLAT, DLD, DLST, DLST, DLSTP, FH, IDH2, IDH3A, IDH3B, IDH3G, KIAA1348, MDH1, MDH2, OGDH, PC, PDHA1, PDHA2, PDHB, PDHX, PDK1, PDK2, PDK3, PDK4, PDP2, PPM2C, SDHA, SDHA, SDHAL2, SDHB, SDHC, SDHD, SUCLA2, SUCLG1, SUCLG2, WDR50 30 ACO2(2), DLAT(1), DLD(2), DLST(1), FH(2), IDH3A(2), IDH3B(3), MDH1(1), MDH2(1), OGDH(3), PC(4), PDHA1(2), PDHA2(5), PDK1(1), PDK2(2), PDK3(2), PDK4(2), PDP2(4), SDHA(1), SDHC(1), SUCLA2(2), SUCLG2(1) 7678564 45 36 45 16 5 21 7 6 6 0 0.89 1.00 408 RIBOSOMAL_PROTEINS ANK2, APG10L, RPS23, B3GALT4, CDR1, DGKI, FAU, IL6ST, KIAA1394, LOC133957, MRPL19, NET_5, PIGK, RPL10, RPL11, RPL12, RPL13, RPL13, LOC388344, RPL13A, RPL13A, LOC283340, LOC387930, RPL14, RPL14, RPL14L, RPL15, RPL15, LOC136321, LOC402694, RPL17, RPL17, dJ612B15.1, RPL18, RPL18A, LOC285053, LOC347544, LOC390354, RPL18A, LOC390354, RPL19, RPL21, RPL21, LOC387753, LOC388143, LOC388532, LOC388621, LOC389156, LOC390488, LOC402336, LOC440487, LOC440575, RPL21, LOC387753, LOC388143, LOC388532, LOC388621, LOC389156, LOC390488, LOC440487, LOC440575, RPL22, RPL23, RPL24, RPL24, SLC36A2, RPL26, LOC391126, LOC392501, LOC400055, LOC441073, LOC441533, RPL27, RPL27A, RPL27A, LOC389435, RPL28, RPL29, RPL29, LOC283412, LOC284064, LOC389655, LOC391738, LOC401911, RPL3, RPL30, RPL31, RPL32, RPL34, LOC342994, RPL35, RPL35A, RPL36, RPL37, RPL38, RPL39, RPL3L, RPL4, RPL41, RPL5, RPL5, LOC388907, RPL5, RNU66, LOC388907, RPL6, RPL7, RPL7, LOC389305, RPL7, LOC90193, LOC388401, LOC389305, LOC392550, LOC439954, RPL7A, RPL7A, LOC133748, LOC388474, RPL7A, RNU36B, LOC133748, LOC388474, RPL8, RPL9, RPLP0, RPLP0, RPLP0_like, RPLP1, RPLP2, RPS10, RPS10, LOC158104, LOC388885, LOC389127, LOC390842, LOC401817, RPS10, LOC388885, RPS11, RPS12, RPS13, RPS14, RPS15, RPS16, RPS16, LOC441876, RPS17, RPS17, LOC402057, RPS18, RPS19, RPS2, RPS2, LOC91561, LOC148430, LOC286444, LOC400963, LOC440589, RPS20, RPS21, RPS23, RPS24, RPS25, RPS26, RPS26L, LOC440440, RPS27, RPS27A, RPS27A, LOC388720, LOC389425, RPS28, RPS29, RPS3, RPS3A, RPS3A, LOC146053, LOC400652, LOC401016, LOC439992, RPS4X, RPS4Y1, RPS5, RPS6, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6, RPS6KB1, RPS6KB2, RPS7, RPS8, RPS9, RPSA, LOC388524, LOC388654, SCDR10, TBC1D10C, TSPAN9, UBA52, UBB, UBC 93 ANK2(24), B3GALT4(1), CDR1(2), DGKI(7), MRPL19(1), PIGK(1), RPL14(1), RPL19(1), RPL28(1), RPL30(1), RPL32(1), RPL37(1), RPL3L(1), RPL4(1), RPL5(2), RPL7(1), RPL8(4), RPLP0(2), RPS11(1), RPS18(2), RPS2(1), RPS21(1), RPS26(1), RPS6(1), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KA6(3), RPS6KB1(1), RPS8(1), SLC36A2(1), TBC1D10C(1), TSPAN9(1), UBB(1), UBC(1) 14395750 77 62 77 43 22 21 22 10 2 0 0.89 1.00 409 VOBESITYPATHWAY The adipose tissue of obese individuals overexpresses a key glucocorticoid-metabolizing enzyme, activating inactive circulating corticosteroids and inducing insulin resistance. APM1, HSD11B1, LPL, NR3C1, PPARG, RETN, RXRA, TNF 7 HSD11B1(3), LPL(3), RXRA(1) 1557322 7 7 7 4 2 4 0 1 0 0 0.89 1.00 410 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(1), INPP1(1), INPP4A(5), INPP4B(4), INPP5A(3), INPP5B(5), INPP5E(2), INPPL1(3), IPMK(1), ITPKA(1), ITPKB(3), OCRL(5), PI4KA(4), PI4KB(2), PIK3C3(3), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIP4K2A(2), PIP4K2B(3), PIP4K2C(3), PIP5K1A(4), PIP5K1B(1), PIP5K1C(2), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), PLCD3(2), PLCE1(10), PLCG1(2), PLCG2(3), PLCZ1(3), SYNJ1(2), SYNJ2(5) 19558106 119 75 118 43 38 38 20 10 13 0 0.89 1.00 411 HEME_BIOSYNTHESIS ALAD, ALAS1, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, UROS 9 ALAS1(2), CPOX(3), FECH(2), HMBS(2), PPOX(1), UROD(1) 2065156 11 10 11 1 2 7 0 1 1 0 0.89 1.00 412 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 31 GORASP1(1), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPK8(2), MAPK8IP1(2), MAPK8IP3(6), MAPK9(1), MAPKAPK5(4), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), PIK3CD(3), PIK3R1(1), SYT1(3), TRAF3(1), TRAF5(2), TRAF6(1) 8770594 45 38 45 12 13 16 3 7 6 0 0.89 1.00 413 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 33 ACTR2(1), AKT1(1), CDC42(1), CFL1(3), CFL2(1), FLNA(9), FLNC(13), FSCN3(1), GDI1(2), GDI2(1), LIMK1(1), MYLK(7), MYLK2(2), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), ROCK1(5), ROCK2(3), VASP(2), WASL(2) 11843586 69 53 69 31 16 32 11 3 7 0 0.89 1.00 414 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 23 B4GALT1(1), FBP2(1), G6PC(2), GALE(1), GALK2(1), GALT(1), GANAB(5), GCK(1), GLA(2), HK1(4), HK2(6), HK3(7), MGAM(5), PFKM(5), PFKP(2), PGM1(1) 7869914 45 39 44 19 16 21 2 4 2 0 0.89 1.00 415 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 54 ABP1(6), ADH1B(1), ADH1C(1), ADH4(2), ADH5(2), ADH7(1), ADHFE1(2), ALDH3B2(2), AOC2(2), AOC3(3), AOX1(11), CARM1(1), DBH(2), DCT(1), DDC(2), ECH1(1), ESCO1(1), FAH(1), GOT1(2), GOT2(3), GSTZ1(2), HPD(3), LCMT1(2), LCMT2(1), MYST3(11), MYST4(3), PNMT(2), PNPLA3(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), SH3GLB1(1), TAT(1), TH(2), TYR(3), TYRP1(2), WBSCR22(4) 15374572 94 65 93 30 28 39 9 10 8 0 0.89 1.00 416 VIPPATHWAY Apoptosis of activated T cells is inhibited by vasoactive intestinal peptide (VIP) and its relative PACAP. CALM1, CALM2, CALM3, CHUK, EGR2, EGR3, GNAQ, MAP3K1, MYC, NFATC1, NFATC2, NFKB1, NFKBIA, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RELA, SYT1, VIP, VIPR2 27 CHUK(2), EGR2(6), EGR3(1), MAP3K1(3), MYC(1), NFATC2(5), NFKB1(2), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), RELA(3), SYT1(3), VIP(2) 7466566 49 34 49 15 16 14 5 8 6 0 0.89 1.00 417 NEUTROPHILPATHWAY Neutrophils are phagocytotic leukocytes that destroy foreign cells with reactive oxygen species or enzymatic digestion and express CD11 and CD18. CD44, ICAM1, ITGAL, ITGAM, ITGB2, PECAM1, SELE, SELL 8 CD44(3), ICAM1(2), ITGAL(1), ITGAM(3), ITGB2(3), SELE(4), SELL(2) 3233726 18 16 18 5 5 5 5 2 1 0 0.89 1.00 418 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 29 ADCY3(5), CAMK2B(2), CAMK2D(1), CLCA1(6), CLCA2(3), CLCA4(2), CNGA3(3), CNGA4(5), CNGB1(5), GNAL(2), GUCA1A(2), PRKACA(1), PRKACB(2), PRKACG(1), PRKG1(5), PRKG2(5), PRKX(1) 7900530 51 38 51 13 18 16 5 5 7 0 0.89 1.00 419 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 98 ADCY1(8), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADCY9(4), CAMK2B(2), CAMK2D(1), CREB3(2), CREB3L2(2), CREB3L3(1), CREB3L4(2), CREBBP(12), CTNNB1(3), DCT(1), DVL1(3), DVL3(3), EDN1(1), EDNRB(5), EP300(5), FZD1(1), FZD10(2), FZD3(4), FZD4(1), FZD6(1), FZD9(3), GNAI1(2), GNAI3(1), GNAS(4), GSK3B(1), HRAS(2), KIT(6), KRAS(1), LEF1(3), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), POMC(2), PRKACA(1), PRKACB(2), PRKACG(1), PRKCA(5), PRKCG(9), PRKX(1), RAF1(1), TCF7(1), TYR(3), TYRP1(2), WNT10B(2), WNT11(2), WNT2(3), WNT2B(2), WNT3(2), WNT3A(1), WNT5A(1), WNT5B(1), WNT6(2), WNT7A(2), WNT7B(1), WNT9A(1), WNT9B(2) 29302182 193 97 192 69 59 73 30 17 14 0 0.89 1.00 420 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ5(2), COQ7(2), NDUFA13(2) 1115170 6 6 6 2 2 3 1 0 0 0 0.90 1.00 421 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 32 AKT1(1), APC(9), AR(4), BRAF(7), CCL16(1), DAG1(1), EGFR(9), GNA15(1), GNAI1(2), ITPKA(1), ITPKB(3), ITPR1(5), ITPR2(11), ITPR3(3), KCNJ5(2), KCNJ9(2), MAPK1(1), MAPK10(1), MAPK14(1), PHKA2(4), PIK3CD(3), PIK3R1(1), PITX2(3), PTX3(2), RAF1(1) 13775954 79 59 78 24 23 27 16 5 8 0 0.90 1.00 422 CARM_ERPATHWAY Methyltransferase CARM1 methylates CBP and co-activates estrogen receptors via Grip1. BRCA1, CARM1, CCND1, CREBBP, EP300, ERCC3, ESR1, GRIP1, GTF2A1, GTF2E1, GTF2F1, HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HIST2H3C, MEF2C, NCOR2, NR0B1, NRIP1, PELP1, POLR2A, PPARBP, PPARGC1, REA, SHARP, SRA1, TBP 25 BRCA1(6), CARM1(1), CCND1(1), CREBBP(12), EP300(5), ERCC3(2), ESR1(6), GRIP1(5), GTF2A1(1), GTF2E1(1), HDAC1(2), HDAC3(1), HDAC4(5), HDAC5(1), MEF2C(2), NCOR2(6), NR0B1(4), NRIP1(3), PELP1(1), POLR2A(2), TBP(1) 12822586 68 54 67 24 20 19 13 7 9 0 0.90 1.00 423 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 28 AGA(2), ARSB(2), FUCA1(1), GNS(1), GUSB(3), HEXA(6), HGSNAT(2), HPSE(3), HPSE2(4), HYAL1(4), IDS(1), IDUA(2), MAN2B1(1), MAN2B2(3), MAN2C1(5), MANBA(2), NEU1(4), NEU2(2), NEU3(2), SPAM1(3) 8481878 53 36 52 14 7 24 14 1 7 0 0.90 1.00 424 KREBPATHWAY The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain. ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2 8 ACO2(2), FH(2), MDH1(1), OGDH(3), SDHA(1), SUCLA2(2) 2517098 11 11 11 8 0 5 2 3 1 0 0.90 1.00 425 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 10 IL6R(1), JAK1(1), JAK2(3), JAK3(7), PIAS3(4), PTPRU(8), STAT3(1) 4136186 25 21 23 4 6 13 3 1 2 0 0.90 1.00 426 PENTOSE_AND_GLUCURONATE_INTERCONVERSIONS AKR1B1, DCXR, GUSB, RPE, RPE, LOC440001, UCHL1, UCHL3, UGDH, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4 18 GUSB(3), UGDH(3), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2B15(1), UGT2B4(4) 4394820 22 20 22 5 6 8 6 1 1 0 0.90 1.00 427 CAPROLACTAM_DEGRADATION AKR1A1, ECHS1, EHHADH, HADHA, SDS 5 EHHADH(1), HADHA(2), SDS(2) 1318802 5 5 5 7 0 2 1 0 2 0 0.90 1.00 428 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 BGN(1), DCN(1), FMOD(1), LUM(1) 967608 4 4 4 2 0 3 1 0 0 0 0.90 1.00 429 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 AHCY(1), CBS(4), DNMT1(4), DNMT3A(6), DNMT3B(3), MARS(1), MAT1A(1), MTR(5) 4733020 25 22 25 17 5 11 6 1 2 0 0.90 1.00 430 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 14 AKT1(1), HRAS(2), IGF1R(1), IRS1(4), MAP2K1(2), MAPK1(1), MAPK3(2), PIK3R1(1), RAF1(1), SHC1(1), SOS1(6) 4499306 22 22 22 4 6 8 5 2 1 0 0.91 1.00 431 IL2PATHWAY IL-2 promotes proliferation via JAK and MAP kinase and has surface receptors on activated B cells, LPS-treated monocytes, and many T cells. CSNK2A1, ELK1, FOS, GRB2, HRAS, IL2, IL2RA, IL2RB, IL2RG, JAK1, JAK3, JUN, LCK, MAP2K1, MAPK3, MAPK8, RAF1, SHC1, SOS1, STAT5A, STAT5B, SYK 22 CSNK2A1(2), FOS(1), HRAS(2), IL2RB(2), IL2RG(1), JAK1(1), JAK3(7), JUN(2), LCK(2), MAP2K1(2), MAPK3(2), MAPK8(2), RAF1(1), SHC1(1), SOS1(6), STAT5A(2), SYK(1) 6428648 37 31 37 13 10 14 8 2 3 0 0.91 1.00 432 PYK2PATHWAY Pyk2 and Rac1 stimulate the JNK cascade and activate MKK3, which activates p38. BCAR1, CALM1, CALM2, CALM3, CRKL, GNAQ, GRB2, HRAS, JUN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP3K1, MAPK1, MAPK14, MAPK3, MAPK8, PAK1, PLCG1, PRKCA, PRKCB1, PTK2B, RAC1, RAF1, SHC1, SOS1, SRC, SYT1 28 BCAR1(5), CRKL(1), HRAS(2), JUN(2), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP3K1(3), MAPK1(1), MAPK14(1), MAPK3(2), MAPK8(2), PAK1(3), PLCG1(2), PRKCA(5), RAC1(2), RAF1(1), SHC1(1), SOS1(6), SYT1(3) 7794620 48 39 48 14 18 14 9 5 2 0 0.91 1.00 433 FOLATE_BIOSYNTHESIS ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, DHFR, FPGS, GCH1, GGH, SPR 9 ALPI(1), ALPL(3), ALPP(1), ALPPL2(1), GCH1(2), SPR(1) 1834468 9 9 9 3 4 4 0 1 0 0 0.91 1.00 434 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(6), ADC(1), ALDH18A1(4), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), AMD1(1), AOC2(2), AOC3(3), ARG1(2), ASL(2), ASS1(4), GATM(1), NAGS(1), ODC1(1), OTC(2), SMS(4) 7199388 42 34 40 13 11 20 6 2 3 0 0.91 1.00 435 HSA00641_3_CHLOROACRYLIC_ACID_DEGRADATION Genes involved in 3-chloroacrylic acid degradation ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1 15 ADH1B(1), ADH1C(1), ADH4(2), ADH5(2), ADH7(1), ADHFE1(2), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2) 3593286 17 17 17 5 6 9 0 2 0 0 0.91 1.00 436 HSA00053_ASCORBATE_AND_ALDARATE_METABOLISM Genes involved in ascorbate and aldarate metabolism ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, MIOX, UGDH 9 ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), UGDH(3) 2317560 11 11 11 1 2 8 0 1 0 0 0.91 1.00 437 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(1), AKT3(2), BPNT1(1), ILK(1), MAPK1(1), MAPK3(2), PDK1(1), PIK3CD(3), RBL2(5), SHC1(1), SOS1(6) 4702582 24 21 24 6 5 7 6 3 3 0 0.91 1.00 438 SRCRPTPPATHWAY Activation of Src by Protein-tyrosine phosphatase alpha CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CSK, GRB2, PRKCA, PRKCB1, PTPRA, SRC 9 CCNB1(1), CDC25B(3), CDC25C(1), PRKCA(5) 2502858 10 10 10 4 1 6 1 1 1 0 0.91 1.00 439 MITOCHONDRIAL_FATTY_ACID_BETAOXIDATION ACADL, ACADM, ACADS, ACADVL, ACSL1, ACSL3, ACSL4, CPT1A, CPT2, DCI, EHHADH, HADHA, HADHSC, MGC5139, PECR, SCP2, SLC25A20 15 ACADL(2), ACADM(1), ACADS(3), ACADVL(1), ACSL1(2), ACSL3(1), CPT1A(3), CPT2(2), DCI(1), EHHADH(1), HADHA(2), PECR(1), SCP2(1), SLC25A20(1) 4528320 22 22 22 12 4 9 5 1 3 0 0.91 1.00 440 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 12 AKT1(1), CHRNB1(2), CHRNG(4), MUSK(3), PIK3R1(1), PTK2(3), RAPSN(3), TERT(5) 3938606 22 20 22 12 11 7 1 1 2 0 0.91 1.00 441 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 15 FOS(1), JUN(2), MAPK14(1), MAPK8(2), PLCG1(2), PRKCA(5), SYT1(3) 3344976 16 16 16 8 6 4 2 3 1 0 0.92 1.00 442 HSA00290_VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS Genes involved in valine, leucine and isoleucine biosynthesis BCAT1, BCAT2, IARS, IARS2, ILVBL, LARS, LARS2, PDHA1, PDHA2, PDHB, VARS, VARS2 12 BCAT1(1), BCAT2(3), IARS(3), IARS2(4), ILVBL(2), LARS2(5), PDHA1(2), PDHA2(5), VARS(4), VARS2(4) 5037400 33 24 33 10 5 18 6 1 3 0 0.92 1.00 443 STRESSPATHWAY Tumor necrosis factor receptor TNFR1 promotes apoptosis and activates the pro-inflammatory NF-kB, while TNFR2 activates stress-activated protein kinases (SAPKs). ATF1, CASP2, CHUK, CRADD, IKBKB, IKBKG, JUN, LTA, MAP2K3, MAP2K4, MAP2K6, MAP3K1, MAP3K14, MAP4K2, MAPK14, MAPK8, NFKB1, NFKBIA, RELA, RIPK1, TANK, TNF, TNFRSF1A, TRADD, TRAF2 24 CASP2(1), CHUK(2), CRADD(1), IKBKB(3), JUN(2), LTA(3), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAP3K14(1), MAP4K2(1), MAPK14(1), MAPK8(2), NFKB1(2), RELA(3), TANK(4), TNFRSF1A(2), TRADD(1) 6698318 37 29 37 12 8 13 6 3 7 0 0.92 1.00 444 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 15 CREBBP(12), EP300(5), FYN(4), IL2RG(1), IL7R(3), JAK1(1), JAK3(7), LCK(2), NMI(1), PIK3R1(1), STAT5A(2) 7041502 39 31 38 14 6 15 9 4 5 0 0.92 1.00 445 FATTY_ACID_BIOSYNTHESIS_PATH_2 ACAA1, ACAA2, ACAT1, ACAT2, ECHS1, EHHADH, HADHA, HADHB, SDS 9 ACAA2(1), ACAT1(1), EHHADH(1), HADHA(2), HADHB(2), SDS(2) 2252946 9 9 9 9 1 2 2 2 2 0 0.92 1.00 446 MEF2DPATHWAY Mef2 transcription factors promote calcium-induced apoptosis in T cells and are regulated by MAP kinases and histone deacetylases. CABIN1, CALM1, CALM2, CALM3, CAPN2, CAPNS1, CAPNS2, EP300, HDAC1, HDAC2, MEF2D, NFATC1, NFATC2, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, SYT1, TRA@, TRB@ 18 CABIN1(5), CAPN2(2), CAPNS2(1), EP300(5), HDAC1(2), MEF2D(2), NFATC2(5), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKCA(5), SYT1(3) 6598994 39 30 38 12 12 11 6 6 4 0 0.92 1.00 447 HSA00360_PHENYLALANINE_METABOLISM Genes involved in phenylalanine metabolism ABP1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, ARD1A, DDC, EPX, ESCO1, ESCO2, GOT1, GOT2, HPD, LPO, LYCAT, MAOA, MAOB, MIF, MPO, MYST3, MYST4, NAT5, NAT6, PNPLA3, PRDX6, SH3GLB1, TAT, TPO 26 ABP1(6), ALDH3B2(2), AOC2(2), AOC3(3), DDC(2), EPX(5), ESCO1(1), GOT1(2), GOT2(3), HPD(3), LPO(2), MPO(3), MYST3(11), MYST4(3), PNPLA3(1), PRDX6(1), SH3GLB1(1), TAT(1) 8770238 52 42 51 25 15 19 11 4 3 0 0.92 1.00 448 CDC25PATHWAY The protein phosphatase Cdc25 is phosphorylated by Chk1 and activates Cdc2 to stimulate eukaryotic cells into M phase. ATM, CDC2, CDC25A, CDC25B, CDC25C, CHEK1, MYT1, WEE1, YWHAH 8 ATM(7), CDC25B(3), CDC25C(1), CHEK1(4), WEE1(2) 3709342 17 16 17 1 4 8 2 1 2 0 0.92 1.00 449 HSA05120_EPITHELIAL_CELL_SIGNALING_IN_HELICOBACTER_PYLORI_INFECTION Genes involved in epithelial cell signaling in Helicobacter pylori infection ADAM10, ADAM17, ATP6AP1, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E1, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, CASP3, CCL5, CDC42, CHUK, CSK, CXCL1, EGFR, F11R, GIT1, HBEGF, IGSF5, IKBKB, IKBKG, IL8, IL8RA, IL8RB, JAM2, JAM3, JUN, LYN, MAP2K4, MAP3K14, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK8, MAPK9, MET, NFKB1, NFKB2, NFKBIA, NOD1, PAK1, PLCG1, PLCG2, PTPN11, PTPRZ1, RAC1, RELA, SRC, TCIRG1, TJP1 65 ADAM10(4), ATP6V0A1(4), ATP6V0A2(5), ATP6V0A4(2), ATP6V0D1(1), ATP6V0D2(2), ATP6V1A(3), ATP6V1B1(2), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4), CDC42(1), CHUK(2), EGFR(9), F11R(1), GIT1(1), HBEGF(1), IGSF5(1), IKBKB(3), JUN(2), LYN(1), MAP3K14(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK8(2), MAPK9(1), MET(3), NFKB1(2), NFKB2(2), NOD1(5), PAK1(3), PLCG1(2), PLCG2(3), PTPN11(3), PTPRZ1(8), RAC1(2), RELA(3), TJP1(9) 19090856 108 66 107 28 32 29 19 10 18 0 0.93 1.00 450 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 48 ACOX1(2), APOA2(1), CD36(1), CREBBP(12), EHHADH(1), EP300(5), HSD17B4(1), JUN(2), LPL(3), MAPK1(1), MAPK3(2), MYC(1), NCOA1(6), NCOR1(4), NCOR2(6), NR0B2(1), NR1H3(2), NRIP1(3), PIK3R1(1), PPARA(2), PRKACB(2), PRKACG(1), PRKAR1A(3), PRKAR1B(1), PRKAR2B(3), PRKCA(5), RB1(7), RELA(3), RXRA(1), SP1(1), STAT5A(2) 16377780 86 61 85 40 18 31 13 9 15 0 0.93 1.00 451 HSA00564_GLYCEROPHOSPHOLIPID_METABOLISM Genes involved in glycerophospholipid metabolism ACHE, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, ARD1A, CDIPT, CDS1, CDS2, CHAT, CHKA, CHKB, CHPT1, CRLS1, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKI, DGKQ, DGKZ, ESCO1, ESCO2, ETNK1, ETNK2, GNPAT, GPAM, GPD1, GPD1L, GPD2, LCAT, LYCAT, LYPLA1, LYPLA2, LYPLA3, MYST3, MYST4, NAT5, NAT6, PCYT1A, PCYT1B, PEMT, PHOSPHO1, PISD, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLD1, PLD2, PNPLA3, PPAP2A, PPAP2B, PPAP2C, PTDSS1, PTDSS2, SH3GLB1 64 ACHE(2), AGPAT3(1), AGPAT6(2), CDS1(2), CHAT(2), CHKA(2), CRLS1(1), DGKA(6), DGKB(4), DGKD(5), DGKE(2), DGKG(2), DGKI(7), DGKZ(3), ESCO1(1), ETNK1(3), GPAM(2), GPD1(2), GPD1L(1), GPD2(2), LYPLA1(5), MYST3(11), MYST4(3), PCYT1A(2), PCYT1B(1), PISD(1), PLA2G2A(1), PLA2G2E(2), PLA2G2F(1), PLA2G3(2), PLA2G4A(5), PLA2G5(3), PLA2G6(6), PLD1(10), PLD2(4), PNPLA3(1), PPAP2B(2), PTDSS1(1), SH3GLB1(1) 18095124 114 70 112 48 34 44 16 7 13 0 0.93 1.00 452 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 23 ABL1(2), ATM(7), ATR(11), CCNA1(1), CCND1(1), CDK2(1), E2F1(3), GSK3B(1), HDAC1(2), RB1(7), SKP2(1), TGFB1(1), TGFB2(1) 7767920 39 33 39 11 9 12 6 3 9 0 0.93 1.00 453 FMLPPATHWAY The fMLP receptor is a G-protein coupled receptor in neutrophils that recognizes formylated bacterial peptides and activates NADPH oxidase. CALM1, CALM2, CALM3, CAMK1, CAMK1G, ELK1, FPR1, GNA15, GNB1, GNGT1, HRAS, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NCF1, NCF2, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKBIA, PAK1, PIK3C2G, PLCB1, PPP3CA, PPP3CB, PPP3CC, RAC1, RAF1, RELA, SYT1 37 CAMK1G(2), FPR1(1), GNA15(1), GNB1(1), HRAS(2), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAPK1(1), MAPK14(1), MAPK3(2), NCF2(5), NFATC2(5), NFATC3(3), NFATC4(2), NFKB1(2), PAK1(3), PIK3C2G(7), PLCB1(7), PPP3CA(2), PPP3CB(5), PPP3CC(2), RAC1(2), RAF1(1), RELA(3), SYT1(3) 10537956 75 50 74 26 26 29 6 10 4 0 0.93 1.00 454 PTDINSPATHWAY Phosphoinositide 3 kinase (PI3K) phosphorylate inositol rings of phosphoinositide lipids, influencing vesicle trafficking, cell proliferation, and migration. AKT1, AP2A1, AP2M1, ARF1, BAD, BTK, EEA1, GRASP, GSK3A, GSK3B, LYN, PDPK1, PFKL, PFKM, PFKP, PFKX, PLCG1, PRKCE, PRKCZ, RAB5A, RAC1, RPS6KB1, VAV2 22 AKT1(1), AP2A1(3), BTK(5), GSK3A(4), GSK3B(1), LYN(1), PDPK1(1), PFKL(2), PFKM(5), PFKP(2), PLCG1(2), PRKCE(5), RAC1(2), RPS6KB1(1), VAV2(4) 6962292 39 30 38 16 11 9 8 3 8 0 0.93 1.00 455 CALCINEURINPATHWAY Increased intracellular calcium activates the phosphatase calcineurin in differentiating keratinocytes. CALM1, CALM2, CALM3, CDKN1A, GNAQ, MARCKS, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, SP1, SP3, SYT1 18 MARCKS(1), NFATC2(5), NFATC3(3), NFATC4(2), PLCG1(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), PRKCA(5), SP1(1), SP3(1), SYT1(3) 5691372 32 27 32 11 11 11 2 5 3 0 0.93 1.00 456 HSA00440_AMINOPHOSPHONATE_METABOLISM Genes involved in aminophosphonate metabolism CARM1, CHPT1, HEMK1, LCMT1, LCMT2, METTL2B, METTL6, PCYT1A, PCYT1B, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, WBSCR22 16 CARM1(1), LCMT1(2), LCMT2(1), PCYT1A(2), PCYT1B(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), WBSCR22(4) 3831272 20 18 20 5 8 7 2 1 2 0 0.93 1.00 457 TSP1PATHWAY Thrombospondin-1 (TSP-1) inhibits angiogenesis by inducing caspase-dependent apoptosis in microvascular endothelial cells. CASP3, CD36, FOS, FYN, JUN, MAPK14, THBS1 7 CD36(1), FOS(1), FYN(4), JUN(2), MAPK14(1), THBS1(1) 1984344 10 9 10 1 2 2 4 2 0 0 0.93 1.00 458 TNFR1PATHWAY Tumor necrosis factor alpha binds to its receptor TNFR1 and induces caspase-dependent apoptosis. ADPRT, ARHGDIB, BAG4, CASP2, CASP3, CASP8, CRADD, DFFA, DFFB, FADD, JUN, LMNA, LMNB1, LMNB2, MADD, MAP2K4, MAP3K1, MAP3K7, MAPK8, PAK1, PAK2, PRKDC, RB1, RIPK1, SPTAN1, TNF, TNFRSF1A, TRADD, TRAF2 28 ARHGDIB(1), BAG4(1), CASP2(1), CASP8(1), CRADD(1), DFFA(1), DFFB(2), FADD(1), JUN(2), MADD(3), MAP3K1(3), MAP3K7(3), MAPK8(2), PAK1(3), PAK2(1), PRKDC(15), RB1(7), SPTAN1(2), TNFRSF1A(2), TRADD(1) 10863874 53 45 52 20 13 21 5 1 13 0 0.93 1.00 459 HSA00920_SULFUR_METABOLISM Genes involved in sulfur metabolism BPNT1, CHST11, CHST12, CHST13, PAPSS1, PAPSS2, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SULT2B1, SUOX 12 BPNT1(1), CHST11(1), CHST12(1), PAPSS2(1), SULT1A1(1), SULT1A2(2), SULT1E1(1), SULT2A1(3) 2544332 11 11 11 6 3 3 2 1 2 0 0.93 1.00 460 HSA00271_METHIONINE_METABOLISM Genes involved in methionine metabolism AHCY, AMD1, BHMT, CBS, CTH, DNMT1, DNMT3A, DNMT3B, KIAA0828, MARS, MARS2, MAT1A, MAT2B, MTAP, MTFMT, MTR, SRM, TAT 17 AHCY(1), AMD1(1), CBS(4), DNMT1(4), DNMT3A(6), DNMT3B(3), MARS(1), MAT1A(1), MTAP(1), MTR(5), TAT(1) 5640642 28 25 28 19 6 12 6 1 3 0 0.94 1.00 461 ST_G_ALPHA_I_PATHWAY Gi and Go proteins are members of the same family that transduce cellular signals through both their alpha and beta subunits. AKT1, AKT2, AKT3, ASAH1, BF, BRAF, DAG1, DRD2, EGFR, EPHB2, GRB2, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, PI3, PIK3CB, PITX2, PLCB1, PLCB2, PLCB3, PLCB4, RAF1, RAP1GA1, RGS20, SHC1, SOS1, SOS2, SRC, STAT3, TERF2IP 33 AKT1(1), AKT3(2), BRAF(7), DAG1(1), DRD2(2), EGFR(9), EPHB2(5), ITPKA(1), ITPKB(3), ITPR1(5), ITPR2(11), ITPR3(3), KCNJ5(2), KCNJ9(2), MAPK1(1), PI3(1), PIK3CB(1), PITX2(3), PLCB1(7), PLCB2(5), PLCB3(4), PLCB4(4), RAF1(1), RGS20(1), SHC1(1), SOS1(6), SOS2(4), STAT3(1) 15750330 94 66 93 28 27 33 18 5 11 0 0.94 1.00 462 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 21 DIAPH1(1), FYN(4), GSN(2), HRAS(2), ITGA1(4), ITGB1(4), MAP2K1(2), MAPK1(1), MAPK3(2), MYL2(1), MYLK(7), PIK3R1(1), PTK2(3), PXN(3), RAF1(1), ROCK1(5), SHC1(1), TLN1(8) 9542402 52 42 51 16 10 20 9 9 4 0 0.94 1.00 463 HSA00930_CAPROLACTAM_DEGRADATION Genes involved in caprolactam degradation AKR1A1, ASAHL, ECHS1, EHHADH, HADH, HADHA, HSD17B10, HSD17B4, NTAN1, SIRT1, SIRT2, SIRT5, SIRT7, VNN2, VNN3 13 EHHADH(1), HADH(1), HADHA(2), HSD17B4(1), SIRT1(1), SIRT2(2), VNN2(5) 3154338 13 12 13 9 1 4 3 1 4 0 0.94 1.00 464 HSA00720_REDUCTIVE_CARBOXYLATE_CYCLE Genes involved in reductive carboxylate cycle (CO2 fixation) ACLY, ACO1, ACO2, ACSS1, ACSS2, FH, IDH1, IDH2, LOC441996, MDH1, MDH2, SUCLA2 11 ACO1(1), ACO2(2), ACSS1(3), ACSS2(2), FH(2), IDH1(2), MDH1(1), MDH2(1), SUCLA2(2) 3552346 16 15 16 10 3 8 2 2 1 0 0.94 1.00 465 CITRATE_CYCLE_TCA_CYCLE ACO1, ACO2, CS, DLD, DLST, DLSTP, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, MDH1, MDH2, PC, PCK1, SDHA, SDHA, SDHAL2, SDHB, SUCLA2, SUCLG1, SUCLG2 20 ACO1(1), ACO2(2), DLD(2), DLST(1), FH(2), IDH1(2), IDH3A(2), IDH3B(3), MDH1(1), MDH2(1), PC(4), PCK1(3), SDHA(1), SUCLA2(2), SUCLG2(1) 5541852 28 24 28 10 6 11 3 3 5 0 0.94 1.00 466 HIVNEFPATHWAY HIV-infected CD4 helper T cells may express Fas ligand, which binds to the Fas receptors of uninfected cells and induces apoptosis. ACTG1, ADPRT, APAF1, ARHGDIB, BAG4, BCL2, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CDC2L1, CDC2L2, CFLAR, CHUK, CRADD, CYCS, DAXX, DFFA, DFFB, FADD, GSN, LMNA, LMNB1, LMNB2, MAP2K7, MAP3K1, MAP3K14, MAP3K5, MAPK8, MDM2, NFKB1, NFKBIA, NUMA1, PAK2, PRKCD, PRKDC, PSEN1, PSEN2, PTK2, RASA1, RB1, RELA, RIPK1, SPTAN1, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TRADD, TRAF1, TRAF2 52 APAF1(1), ARHGDIB(1), BAG4(1), BID(1), BIRC3(3), CASP2(1), CASP6(1), CASP7(2), CASP8(1), CASP9(1), CFLAR(1), CHUK(2), CRADD(1), DAXX(3), DFFA(1), DFFB(2), FADD(1), GSN(2), MAP3K1(3), MAP3K14(1), MAP3K5(3), MAPK8(2), MDM2(1), NFKB1(2), NUMA1(3), PAK2(1), PRKCD(2), PRKDC(15), PSEN1(1), PSEN2(2), PTK2(3), RASA1(6), RB1(7), RELA(3), SPTAN1(2), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TRAF1(4) 19149418 91 66 90 32 18 33 10 7 23 0 0.94 1.00 467 LIMONENE_AND_PINENE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ECHS1, EHHADH, HADHA, SDS 12 ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2), EHHADH(1), HADHA(2), SDS(2) 3292822 16 14 15 7 1 9 2 1 3 0 0.94 1.00 468 HSA00361_GAMMA_HEXACHLOROCYCLOHEXANE_DEGRADATION Genes involved in gamma-hexachlorocyclohexane degradation ACP1, ACP2, ACP5, ACP6, ACPP, ACPT, ALPI, ALPL, ALPP, ALPPL2, CMBL, CYP3A4, CYP3A43, CYP3A5, CYP3A7, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, PON1, PON2, PON3 22 ACP1(1), ACP6(3), ACPT(2), ALPI(1), ALPL(3), ALPP(1), ALPPL2(1), CMBL(1), CYP3A4(1), CYP3A43(3), CYP3A7(1), DHRS2(1), PON1(4), PON2(1), PON3(1) 4730528 25 21 25 9 8 8 3 2 4 0 0.94 1.00 469 CASPASEPATHWAY Caspases are cysteine proteases active in apoptosis; caspase-8 and 9 cleave and activate other caspases, while 3, 6, and 7 cleave cellular targets. ADPRT, APAF1, ARHGDIB, BIRC2, BIRC3, BIRC4, CASP1, CASP10, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CYCS, DFFA, DFFB, GZMB, LMNA, LMNB1, LMNB2, PRF1 21 APAF1(1), ARHGDIB(1), BIRC3(3), CASP1(2), CASP10(4), CASP2(1), CASP4(3), CASP6(1), CASP7(2), CASP8(1), CASP9(1), DFFA(1), DFFB(2), GZMB(1), PRF1(2) 5233378 26 23 26 11 6 10 3 2 5 0 0.94 1.00 470 TCYTOTOXICPATHWAY Cytotoxic T cells release perforin and granzyme to lyse foreign cell targets and express Fas ligand to promote Fas-induced apoptosis. CD2, CD28, CD3D, CD3E, CD3G, CD3Z, CD8A, ICAM1, ITGAL, ITGB2, PTPRC, THY1, TRA@, TRB@ 11 CD2(1), CD3D(1), ICAM1(2), ITGAL(1), ITGB2(3), PTPRC(3), THY1(2) 2883956 13 13 13 7 2 8 1 2 0 0 0.94 1.00 471 INTEGRIN_MEDIATED_CELL_ADHESION_KEGG AKT1, AKT3, BCAR1, CAPN1, CAPN10, CAPN11, CAPN2, CAPN3, CAPN5, CAPN6, CAPN7, CAPN9, CAPNS1, CAV1, CAV2, CAV3, CDC42, CRK, CSK, DKFZp434E1119, DOCK1, FLJ14825, FLJ40125, FYN, GIT2, GRB2, ILK, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, LOC283874, PDPK1, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAPK10, MAPK12, MAPK4, MAPK6, MAPK7, MGC17301, MYLK2, PAK1, PAK2, PAK3, PAK4, PAK6, PDPK1, PIK3R2, PTK2, PXN, RAC1, RAC2, RAC3, RAP1B, RAPGEF1, RHO, ROCK1, ROCK2, SDCCAG8, SEPP1, SHC1, SHC3, SORBS1, SOS1, SRC, TLN1, TNS, TNS1, VASP, VAV2, VAV3, VCL, ZYX 90 AKT1(1), AKT3(2), BCAR1(5), CAPN1(2), CAPN10(3), CAPN11(2), CAPN2(2), CAPN3(6), CAPN5(2), CAPN6(8), CAPN7(1), CAPN9(1), CAV2(1), CAV3(1), CDC42(1), DOCK1(3), FYN(4), ILK(1), ITGA10(6), ITGA11(3), ITGA2(5), ITGA2B(1), ITGA3(2), ITGA4(5), ITGA5(1), ITGA6(6), ITGA7(3), ITGA8(9), ITGA9(1), ITGAD(6), ITGAE(3), ITGAL(1), ITGAM(3), ITGAV(3), ITGAX(9), ITGB1(4), ITGB2(3), ITGB3(3), ITGB4(9), ITGB5(2), ITGB6(2), ITGB7(1), ITGB8(3), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K6(3), MAPK10(1), MAPK4(1), MAPK6(2), MAPK7(1), MYLK2(2), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PDPK1(1), PIK3R2(4), PTK2(3), PXN(3), RAC1(2), RAPGEF1(3), ROCK1(5), ROCK2(3), SDCCAG8(5), SHC1(1), SHC3(3), SORBS1(5), SOS1(6), TLN1(8), TNS1(8), VASP(2), VAV2(4), VAV3(1), VCL(2) 36879464 235 108 232 81 60 98 41 14 22 0 0.94 1.00 472 APOPTOSIS APAF1, BAD, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BCL2L11, BID, BIRC2, BIRC3, BIRC4, BIRC5, BNIP3L, CASP1, CASP10, CASP1, COPl, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CHUK, CYCS, DFFA, DFFB, FADD, FAS, FASLG, GZMB, HELLS, HRK, IKBKB, IKBKG, IRF1, IRF2, IRF3, IRF4, IRF5, IRF6, IRF7, JUN, LTA, MAP2K4, MAP3K1, MAPK10, MDM2, MYC, NFKB1, NFKBIA, NFKBIB, NFKBIE, PRF1, RELA, RIPK1, TNF, TNFRSF10B, TNFRSF1A, TNFRSF1B, TNFRSF21, TNFRSF25, TNFRSF25, PLEKHG5, TNFSF10, TP53, TP73, TRADD, TRAF1, TRAF2, TRAF3 65 APAF1(1), BAK1(1), BAX(1), BCL2L1(2), BID(1), BIRC3(3), BNIP3L(1), CASP1(2), CASP10(4), CASP2(1), CASP4(3), CASP6(1), CASP7(2), CASP8(1), CASP9(1), CHUK(2), DFFA(1), DFFB(2), FADD(1), FAS(1), FASLG(1), GZMB(1), IKBKB(3), IRF1(1), IRF3(1), IRF4(3), IRF6(5), JUN(2), LTA(3), MAP3K1(3), MAPK10(1), MDM2(1), MYC(1), NFKB1(2), NFKBIB(1), PLEKHG5(1), PRF1(2), RELA(3), TNFRSF10B(1), TNFRSF1A(2), TNFRSF1B(1), TNFRSF21(3), TRADD(1), TRAF1(4), TRAF3(1) 15460190 80 58 80 34 16 26 13 10 15 0 0.94 1.00 473 ST_GA13_PATHWAY G-alpha-13 influences the actin cytoskeleton and activates protein kinase D, PI3K, and Pyk2. AKT1, AKT2, AKT3, ARHGEF11, BCL2, BF, CDC42, DLG4, GNA13, IKBKG, LPA, MAP2K4, MAP3K1, MAP3K5, MAPK8, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PDK1, PHKA2, PI3, PIK3CB, PLD1, PLD2, PLD3, PRKCM, PTK2, RDX, ROCK1, ROCK2, SERPINA4, SRF, TBXA2R 34 AKT1(1), AKT3(2), ARHGEF11(7), CDC42(1), DLG4(1), GNA13(1), LPA(11), MAP3K1(3), MAP3K5(3), MAPK8(2), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), PDK1(1), PHKA2(4), PI3(1), PIK3CB(1), PLD1(10), PLD2(4), PLD3(1), PTK2(3), RDX(1), ROCK1(5), ROCK2(3), SERPINA4(4), SRF(2), TBXA2R(2) 13379548 85 57 82 30 17 37 15 10 6 0 0.94 1.00 474 HSA00511_N_GLYCAN_DEGRADATION Genes involved in N-glycan degradation AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2B1, MAN2B2, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 14 AGA(2), FUCA1(1), HEXA(6), MAN2B1(1), MAN2B2(3), MAN2C1(5), MANBA(2), NEU1(4), NEU2(2), NEU3(2) 4558580 28 19 28 9 4 14 8 0 2 0 0.94 1.00 475 ERYTHPATHWAY Erythropoietin selectively stimulates erythrocyte differentiation from CFU-GEMM cells in bone marrow. CCL3, CSF2, CSF3, EPO, FLT3, IGF1, IL11, IL1A, IL3, IL6, IL9, KITLG, TGFB1, TGFB2, TGFB3 15 CCL3(2), FLT3(4), IGF1(2), TGFB1(1), TGFB2(1) 2290504 10 10 10 10 2 4 4 0 0 0 0.94 1.00 476 D4GDIPATHWAY D4-GDI inhibits the pro-apoptotic Rho GTPases and is cleaved by caspase-3. ADPRT, APAF1, ARHGAP5, ARHGDIB, CASP1, CASP10, CASP3, CASP8, CASP9, CYCS, GZMB, JUN, PRF1 12 APAF1(1), ARHGDIB(1), CASP1(2), CASP10(4), CASP8(1), CASP9(1), GZMB(1), JUN(2), PRF1(2) 3454802 15 15 15 10 5 4 2 2 2 0 0.95 1.00 477 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 144 AKT1(1), AKT3(2), BCL2L1(2), CBL(4), CBLB(4), CCND1(1), CCND2(3), CCND3(1), CNTFR(1), CREBBP(12), CSF2RB(5), CSF3R(5), EP300(5), EPOR(2), GH1(1), GH2(2), GHR(2), IFNA1(1), IFNA10(1), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNAR1(2), IFNB1(1), IFNG(1), IFNGR1(3), IFNGR2(1), IL10(1), IL10RA(1), IL11RA(2), IL12A(1), IL12B(3), IL12RB1(3), IL12RB2(3), IL13RA1(2), IL13RA2(1), IL20(1), IL20RA(1), IL21(1), IL21R(2), IL22(1), IL22RA1(1), IL22RA2(1), IL23R(1), IL26(1), IL28B(1), IL2RB(2), IL2RG(1), IL4(2), IL5RA(2), IL6R(1), IL7R(3), JAK1(1), JAK2(3), JAK3(7), LEPR(10), LIFR(4), MPL(3), MYC(1), OSMR(4), PIAS1(3), PIAS2(2), PIAS3(4), PIAS4(3), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), PIM1(2), PRL(1), PRLR(5), PTPN11(3), SOCS2(1), SOCS5(3), SOS1(6), SOS2(4), SPRED1(1), SPRED2(2), STAM(1), STAM2(2), STAT1(2), STAT2(2), STAT3(1), STAT4(4), STAT5A(2), STAT6(1), TYK2(8) 37361666 229 108 227 97 56 86 45 20 22 0 0.95 1.00 478 HBXPATHWAY Hbx is a hepatitis B protein that activates a number of transcription factors, possibly by inducing calcium release from the mitochondrion to the cytoplasm. CREB1, GRB2, HBXIP, HRAS, PTK2B, SHC1, SOS1, SRC 8 HRAS(2), SHC1(1), SOS1(6) 2388582 9 9 9 2 1 2 4 1 1 0 0.95 1.00 479 OXIDATIVE_PHOSPHORYLATION ATP12A, ATP4B, ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ATP7A, ATP7B, COX10, COX4I1, COX5A, COX5B, COX6A1, COX6A2, COX6B1, COX6C, COX7A1, COX7A2, COX7B, COX7C, COX8A, NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2, PP, PPA2, SDHA, SDHA, SDHAL2, SDHB, UQCRB, UQCRC1, UQCRFS1, UQCRH 58 ATP12A(7), ATP6V0A1(4), ATP6V0A4(2), ATP6V0D1(1), ATP6V1A(3), ATP6V1B1(2), ATP6V1B2(1), ATP6V1C1(1), ATP6V1C2(1), ATP6V1G1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(4), ATP7B(1), COX10(1), COX4I1(1), COX6B1(2), COX7A2(1), NDUFB5(3), NDUFS1(4), NDUFV1(3), NDUFV2(2), SDHA(1), UQCRB(1) 9402494 49 38 48 20 15 13 12 3 6 0 0.95 1.00 480 LYSINE_DEGRADATION AADAT, AASDH, AASDHPPT, AASS, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ATP6V0C, SHMT1, BAT8, BBOX1, DLST, DLSTP, DOT1L, ECHS1, EHHADH, EHMT1, EHMT2, GCDH, HADHA, PLOD1, PLOD2, PLOD3, SDS, SHMT1, SHMT2, TMLHE 31 AADAT(1), AASDH(6), AASDHPPT(1), AASS(6), ACAT1(1), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH9A1(2), BBOX1(2), DLST(1), DOT1L(5), EHHADH(1), EHMT2(2), GCDH(1), HADHA(2), PLOD1(2), PLOD2(4), PLOD3(4), SDS(2) 10099720 52 42 51 28 5 21 15 4 7 0 0.95 1.00 481 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 ADH1B(1), ADH1C(1), ADH4(2), ADH5(2), ADH7(1), ADHFE1(2), AKR1C2(1), AKR1C3(1), AKR1C4(1), ALDH3B2(2), CYP1A2(1), CYP2B6(3), CYP2C19(6), CYP2C8(3), CYP2C9(2), CYP2E1(1), CYP2F1(4), CYP2S1(1), CYP3A4(1), CYP3A43(3), CYP3A7(1), GSTA2(1), GSTA4(2), GSTA5(2), GSTM3(1), GSTM4(3), GSTM5(2), GSTZ1(2), MGST1(2), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2), UGT2A1(2), UGT2A3(5), UGT2B10(3), UGT2B11(3), UGT2B15(1), UGT2B28(4), UGT2B4(4) 14629286 88 61 88 37 29 25 23 7 4 0 0.95 1.00 482 SODDPATHWAY Some members of the tumor necrosis factor receptor family have cytoplasmic death domains that promote apoptosis when active and are repressed by silencers called SODDs. BAG4, BIRC3, CASP8, FADD, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF2 10 BAG4(1), BIRC3(3), CASP8(1), FADD(1), TNFRSF1A(2), TNFRSF1B(1), TRADD(1) 2346218 10 8 10 5 3 2 0 2 3 0 0.95 1.00 483 UCALPAINPATHWAY Calpains promote formation of integrin adhesion clusters which recruit Rac to enable the formation of mature focal adhesions that do not contain calpain. ACTA1, ACTN1, ACTN2, ACTN3, ARHA, CAPN1, CAPNS1, CAPNS2, ITGA1, ITGB1, ITGB3, PTK2, PXN, RAC1, SPTAN1, SRC, TLN1, VIL2 16 ACTA1(2), ACTN1(2), ACTN2(6), ACTN3(2), CAPN1(2), CAPNS2(1), ITGA1(4), ITGB1(4), ITGB3(3), PTK2(3), PXN(3), RAC1(2), SPTAN1(2), TLN1(8) 7784474 44 33 43 22 13 15 5 6 5 0 0.95 1.00 484 41BBPATHWAY TNF-type receptor 4-1BB is bound by TRAF1 to activate the MAP kinase pathway in activated T cells. ATF2, CHUK, IFNG, IKBKB, IL2, IL4, JUN, MAP3K1, MAP3K5, MAP4K5, MAPK14, MAPK8, NFKB1, NFKBIA, RELA, TNFRSF9, TNFSF9, TRAF2 18 ATF2(2), CHUK(2), IFNG(1), IKBKB(3), IL4(2), JUN(2), MAP3K1(3), MAP3K5(3), MAP4K5(1), MAPK14(1), MAPK8(2), NFKB1(2), RELA(3), TNFRSF9(1) 5344806 28 23 28 12 5 8 9 2 4 0 0.95 1.00 485 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 55 AADAT(1), ABP1(6), ACAT1(1), ACMSD(1), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), AOC2(2), AOC3(3), AOX1(11), CARM1(1), CAT(1), CYP1A2(1), DDC(2), EHHADH(1), GCDH(1), HAAO(2), HADH(1), HADHA(2), HSD17B4(1), INMT(3), KMO(3), KYNU(3), LCMT1(2), LCMT2(1), LNX1(2), NFX1(1), OGDH(3), OGDHL(4), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), TDO2(1), TPH1(1), WARS(4), WARS2(1), WBSCR22(4) 15662042 88 64 88 40 23 38 12 8 7 0 0.96 1.00 486 EPOPATHWAY Erythropoietin, which activates the MAPK pathway, stimulates erythrocyte production and is an effective treatment for anemia. CSNK2A1, ELK1, EPO, EPOR, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAPK3, MAPK8, PLCG1, PTPN6, RAF1, SHC1, SOS1, STAT5A, STAT5B 19 CSNK2A1(2), EPOR(2), FOS(1), HRAS(2), JAK2(3), JUN(2), MAP2K1(2), MAPK3(2), MAPK8(2), PLCG1(2), RAF1(1), SHC1(1), SOS1(6), STAT5A(2) 5861184 30 27 30 8 9 10 6 2 3 0 0.96 1.00 487 MYOSINPATHWAY Myosin light chain kinase phosphorylates myosin and promotes muscle contraction and platelet formation; myosin phosphatase antagonizes these processes. ARHGAP5, ARHGEF1, GNA12, GNA13, GNAQ, GNB1, GNGT1, MYL2, MYLK, PLCB1, PPP1R12B, PRKCA, PRKCB1, PRKCL1, ROCK1 13 ARHGEF1(2), GNA12(1), GNA13(1), GNB1(1), MYL2(1), MYLK(7), PLCB1(7), PPP1R12B(3), PRKCA(5), ROCK1(5) 5569976 33 26 33 11 6 16 6 3 2 0 0.96 1.00 488 INTEGRINPATHWAY Integrins are cell surface receptors commonly present at focal adhensions that interact with the extracellular matrix and transduce extracellular signaling. ACTA1, ACTN1, ACTN2, ACTN3, ARHA, BCAR1, BCR, CAPN1, CAPNS1, CAPNS2, CAV1, CRKL, CSK, FYN, GRB2, GRF2, HRAS, ITGA1, ITGB1, JUN, MAP2K1, MAP2K2, MAPK1, MAPK3, MAPK8, PPP1R12B, PTK2, PXN, RAF1, RAP1A, ROCK1, SHC1, SOS1, SRC, TLN1, TNS, VCL, ZYX 35 ACTA1(2), ACTN1(2), ACTN2(6), ACTN3(2), BCAR1(5), BCR(1), CAPN1(2), CAPNS2(1), CRKL(1), FYN(4), HRAS(2), ITGA1(4), ITGB1(4), JUN(2), MAP2K1(2), MAP2K2(2), MAPK1(1), MAPK3(2), MAPK8(2), PPP1R12B(3), PTK2(3), PXN(3), RAF1(1), ROCK1(5), SHC1(1), SOS1(6), TLN1(8), VCL(2) 12940422 79 54 78 27 19 29 15 10 6 0 0.96 1.00 489 HSA04620_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY Genes involved in Toll-like receptor signaling pathway AKT1, AKT2, AKT3, CASP8, CCL3, CCL4, CCL5, CD14, CD40, CD80, CD86, CHUK, CXCL10, CXCL11, CXCL9, FADD, FOS, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IKBKB, IKBKE, IKBKG, IL12A, IL12B, IL1B, IL6, IL8, IRAK1, IRAK4, IRF3, IRF5, IRF7, JUN, LBP, LY96, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K8, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK9, MYD88, NFKB1, NFKB2, NFKBIA, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, RAC1, RELA, RIPK1, SPP1, STAT1, TBK1, TICAM1, TICAM2, TIRAP, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TNF, TOLLIP, TRAF3, TRAF6 97 AKT1(1), AKT3(2), CASP8(1), CCL3(2), CD14(1), CD40(1), CD80(2), CD86(1), CHUK(2), FADD(1), FOS(1), IFNA1(1), IFNA10(1), IFNA14(1), IFNA16(2), IFNA17(1), IFNA4(1), IFNA6(1), IFNA8(2), IFNAR1(2), IFNB1(1), IKBKB(3), IKBKE(3), IL12A(1), IL12B(3), IL1B(1), IRAK1(4), IRF3(1), JUN(2), LBP(5), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K6(3), MAP3K7(3), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPK8(2), MAPK9(1), NFKB1(2), NFKB2(2), PIK3CB(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PIK3R2(4), PIK3R3(2), PIK3R5(2), RAC1(2), RELA(3), STAT1(2), TBK1(3), TICAM1(1), TLR1(3), TLR2(3), TLR3(2), TLR5(3), TLR7(3), TLR8(2), TLR9(1), TOLLIP(1), TRAF3(1), TRAF6(1) 23394718 131 78 130 41 35 43 22 15 16 0 0.96 1.00 490 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 12 CCNA1(1), CCND1(1), CCNE2(2), CDK2(1), E2F1(3), PRB1(2) 2268254 10 10 10 5 2 7 0 0 1 0 0.96 1.00 491 HSA00626_NAPHTHALENE_AND_ANTHRACENE_DEGRADATION Genes involved in naphthalene and anthracene degradation CARM1, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, HEMK1, LCMT1, LCMT2, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, WBSCR22 17 CARM1(1), DHRS2(1), LCMT1(2), LCMT2(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), WBSCR22(4) 3890012 18 17 18 4 8 5 2 1 2 0 0.96 1.00 492 HSA00280_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION Genes involved in valine, leucine and isoleucine degradation ABAT, ACAA1, ACAA2, ACADM, ACADS, ACAT1, ACAT2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH7A1, ALDH9A1, AOX1, AUH, BCAT1, BCAT2, BCKDHA, BCKDHB, DBT, DLD, ECHS1, EHHADH, HADH, HADHA, HADHB, HIBADH, HIBCH, HMGCL, HMGCS1, HMGCS2, HSD17B10, HSD17B4, IVD, MCCC1, MCCC2, MCEE, MUT, OXCT1, OXCT2, PCCA, PCCB 44 ABAT(3), ACAA2(1), ACADM(1), ACADS(3), ACAT1(1), ALDH1B1(3), ALDH2(2), ALDH6A1(2), ALDH7A1(1), ALDH9A1(2), AOX1(11), AUH(1), BCAT1(1), BCAT2(3), BCKDHB(2), DBT(1), DLD(2), EHHADH(1), HADH(1), HADHA(2), HADHB(2), HIBCH(1), HMGCL(1), HMGCS1(1), HMGCS2(1), HSD17B4(1), MCCC1(7), MUT(1), OXCT1(2), PCCA(2), PCCB(6) 11653660 69 48 69 22 15 23 13 10 8 0 0.96 1.00 493 MSPPATHWAY Macrophage stimulating protein is synthesized as pro-MSP by the liver and, on proteolysis, binds to monocyte receptor kinase RON to induce macrophage development. CCL2, CSF1, IL1B, MST1, MST1R, TNF 6 CSF1(2), IL1B(1), MST1(2), MST1R(1) 1782314 6 6 6 3 2 3 1 0 0 0 0.96 1.00 494 NFKBPATHWAY Inactive nuclear factor kB (NF-kB) is inhibited by the IkB family in the cytoplasm; active NF-kB is localized in the nucleus and regulates transcription of a variety of genes. CHUK, FADD, IKBKB, IKBKG, IL1A, IL1R1, IRAK1, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MYD88, NFKB1, NFKBIA, RELA, RIPK1, TLR4, TNF, TNFAIP3, TNFRSF1A, TNFRSF1B, TRADD, TRAF6 20 CHUK(2), FADD(1), IKBKB(3), IRAK1(4), MAP3K1(3), MAP3K14(1), MAP3K7(3), NFKB1(2), RELA(3), TNFAIP3(4), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TRAF6(1) 6253140 31 25 31 12 8 11 4 3 5 0 0.96 1.00 495 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 108 ADCY1(8), ADCY3(5), ADCY4(4), ADCY5(3), ADCY7(4), ADCY8(13), ADSL(1), ADSS(1), AK5(2), AMPD1(4), AMPD2(1), AMPD3(6), ATP5A1(2), ATP5B(1), ATP5C1(3), ATP5G2(3), ATP5G3(1), CANT1(3), DCK(1), ENPP1(7), ENPP3(4), ENTPD1(1), ENTPD2(1), GART(2), GDA(6), GUCY1A3(6), GUCY1B3(3), GUCY2C(4), GUCY2D(1), GUCY2F(8), GUK1(1), HPRT1(1), IMPDH1(2), NPR1(2), NPR2(5), NT5E(2), PAPSS2(1), PDE1A(2), PDE4B(3), PDE4C(4), PDE4D(1), PDE5A(3), PDE6B(3), PDE7B(1), PDE8A(6), PDE9A(2), PFAS(5), PKLR(3), PKM2(1), POLB(1), POLD1(2), POLG(2), POLL(1), POLQ(18), POLR1B(4), POLR2A(2), POLR2B(2), POLR2D(1), POLR2E(1), POLR2H(1), PPAT(1), PRPS1(1), PRPS1L1(1), PRPS2(1), RRM1(2) 34217830 198 104 194 73 58 83 27 12 18 0 0.96 1.00 496 PGC1APATHWAY PCG-1a is expressed in skeletal muscle, heart muscle, and brown fat, and is a coactivator for receptors such as glucocorticoid receptor and thyroid hormone receptor. CALM1, CALM2, CALM3, CAMK1, CAMK1G, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, ESRRA, HDAC5, MEF2A, MEF2B, MEF2C, MEF2D, PPARA, PPARGC1, PPP3CA, PPP3CB, PPP3CC, SLC2A4, SYT1, YWHAH 23 CAMK1G(2), CAMK2B(2), CAMK2D(1), CAMK4(3), HDAC5(1), MEF2A(2), MEF2C(2), MEF2D(2), PPARA(2), PPP3CA(2), PPP3CB(5), PPP3CC(2), SLC2A4(2), SYT1(3) 5542920 31 23 31 11 11 6 3 7 4 0 0.96 1.00 497 GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM ACO1, ACO2, CS, GRHPR, HAO1, HAO2, HYI, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 11 ACO1(1), ACO2(2), GRHPR(1), MDH1(1), MDH2(1), MTHFD1(3), MTHFD1L(2), MTHFD2(3) 3225182 14 13 14 2 3 6 4 1 0 0 0.96 1.00 498 PTC1PATHWAY The binding of extracellular signaling protein Sonic hedgehog to the Patched receptor (Ptc1) allows progression through G1 and may inhibit the G2/M transition. CCNB1, CCNH, CDC2, CDC25A, CDC25B, CDC25C, CDK7, MNAT1, PTCH, SHH, XPO1 9 CCNB1(1), CDC25B(3), CDC25C(1), CDK7(1), XPO1(2) 2376300 8 8 8 5 0 4 1 3 0 0 0.96 1.00 499 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 30 GTF2A1(1), GTF2B(1), GTF2E1(1), GTF2H2(1), GTF2H4(1), GTF2I(1), GTF2IRD1(4), TAF1(11), TAF2(5), TAF4(1), TAF4B(6), TAF5(2), TAF5L(3), TAF6L(2), TAF7L(1), TAF9(2), TBPL2(1) 8734104 44 37 44 18 13 13 6 5 7 0 0.96 1.00 500 STATIN_PATHWAY_PHARMGKB ABCA1, APOA1, APOA1, LOC440837, APOA4, APOC1, APOC2, APOC3, APOC3, LOC440838, APOE, CETP, CYP7A1, DGAT1, HMGCR, LCAT, LDLR, LIPC, LPL, LRP1, SCARB1, SOAT1 14 ABCA1(6), APOC2(2), CYP7A1(3), HMGCR(2), LDLR(4), LIPC(1), LPL(3), LRP1(14), SCARB1(3) 6764356 38 32 37 22 16 15 5 0 2 0 0.97 1.00 501 ETCPATHWAY Energy is extracted from carbohydrates via oxidation and transferred to the mitochondrial electron transport chain, which couples ATP synthesis to the reduction of oxygen to water. ATP5A1, CYCS, GPD2, MTCO1, NDUFA1, SDHA, SDHB, SDHC, SDHD, UQCRC1 9 ATP5A1(2), GPD2(2), SDHA(1), SDHC(1) 1766116 6 6 6 2 0 3 1 2 0 0 0.97 1.00 502 DNAFRAGMENTPATHWAY DNA fragmentation during apoptosis is effected by DFF, a caspase-activated DNAse, and by endonuclease G. CASP3, CASP7, DFFA, DFFB, ENDOG, GZMB, HMGB1, HMGB2, TOP2A, TOP2B 10 CASP7(2), DFFA(1), DFFB(2), GZMB(1), TOP2A(3), TOP2B(3) 2721976 12 11 12 5 1 5 4 1 1 0 0.97 1.00 503 PROPANOATE_METABOLISM ABAT, ACACA, ACADL, ACADM, ACADSB, ACAS2, ACAS2L, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH9A1, ECHS1, EHHADH, HADHA, LDHA, LDHB, LDHC, MCEE, MLYCD, MUT, PCCA, PCCB, SDS, SUCLA2, SUCLG1, SUCLG2 31 ABAT(3), ACACA(4), ACADL(2), ACADM(1), ACAT1(1), ALDH1A2(4), ALDH1B1(3), ALDH2(2), ALDH6A1(2), ALDH9A1(2), EHHADH(1), HADHA(2), LDHB(2), LDHC(1), MLYCD(2), MUT(1), PCCA(2), PCCB(6), SDS(2), SUCLA2(2), SUCLG2(1) 8878106 46 37 45 16 8 22 7 3 6 0 0.97 1.00 504 BENZOATE_DEGRADATION_VIA_COA_LIGATION ACAT1, ACAT2, ACYP1, ACYP2, ECHS1, EHHADH, GCDH, HADHA, SDHB, SDS 10 ACAT1(1), EHHADH(1), GCDH(1), HADHA(2), SDS(2) 2113928 7 7 7 10 1 2 2 0 2 0 0.97 1.00 505 P53HYPOXIAPATHWAY Hypoxia induces p53 accumulation and consequent apoptosis with p53-mediated cell cycle arrest, which is present under conditions of DNA damage. ABCB1, AKT1, ATM, BAX, CDKN1A, CPB2, CSNK1A1, CSNK1D, FHL2, GADD45A, HIC1, HIF1A, HSPA1A, HSPCA, IGFBP3, MAPK8, MDM2, NFKBIB, NQO1, TP53 17 AKT1(1), ATM(7), BAX(1), CPB2(2), CSNK1A1(1), FHL2(2), GADD45A(1), HIF1A(1), IGFBP3(1), MAPK8(2), MDM2(1), NFKBIB(1) 4744590 21 19 21 4 5 7 4 3 2 0 0.97 1.00 506 IL6PATHWAY IL-6 binding to its receptor activates JAK kinases and a variety of transcription factors, with effects in neuronal differentiation, bone loss, and inflammation. CEBPB, CSNK2A1, ELK1, FOS, GRB2, HRAS, IL6, IL6R, IL6ST, JAK1, JAK2, JAK3, JUN, MAP2K1, MAPK3, PTPN11, RAF1, SHC1, SOS1, SRF, STAT3 21 CSNK2A1(2), FOS(1), HRAS(2), IL6R(1), JAK1(1), JAK2(3), JAK3(7), JUN(2), MAP2K1(2), MAPK3(2), PTPN11(3), RAF1(1), SHC1(1), SOS1(6), SRF(2), STAT3(1) 6555740 37 30 37 9 9 15 8 3 2 0 0.97 1.00 507 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 13 AKT1(1), CASP9(1), CHUK(2), GH1(1), GHR(2), NFKB1(2), PDPK1(1), PIK3R1(1), RELA(3) 3258112 14 12 14 9 1 6 1 4 2 0 0.97 1.00 508 SA_PROGRAMMED_CELL_DEATH Programmed cell death, or apoptosis, eliminates damaged or unneeded cells. APAF1, BAD, BAK1, BAX, BCL10, BCL2, BCL2L1, BCL2L11, BID, CASP8AP2, CASP9, CES1 12 APAF1(1), BAK1(1), BAX(1), BCL2L1(2), BID(1), CASP8AP2(6), CASP9(1), CES1(2) 3102540 15 12 15 7 4 4 4 2 1 0 0.97 1.00 509 RANKLPATHWAY RANK is a TNF-type receptor that promotes osteoclast differentiation and consequent bone resorbtion on binding RANK ligand produced by osteoblasts. FOS, FOSL1, FOSL2, IFNAR1, IFNAR2, IFNB1, ISGF3G, MAPK8, NFKB1, PRKR, RELA, TNFRSF11A, TNFSF11, TRAF6 12 FOS(1), FOSL2(1), IFNAR1(2), IFNB1(1), MAPK8(2), NFKB1(2), RELA(3), TNFRSF11A(1), TNFSF11(1), TRAF6(1) 3013540 15 12 15 3 5 5 0 3 2 0 0.97 1.00 510 ST_DICTYOSTELIUM_DISCOIDEUM_CAMP_CHEMOTAXIS_PATHWAY The fungus Dictyostelium discoideum is a model system for cytoskeletal organization during chemotaxis. ACTR2, ACTR3, AKT1, ANGPTL2, BF, DAG1, DGKA, ETFA, GCA, ITGA9, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, MAP2K1, MAPK1, MAPK3, NR1I3, PAK1, PDE3A, PDE3B, PI3, PIK3C2G, PIK3CA, PIK3CD, PIK3R1, PLDN, PSME1, RIPK3, RPS4X, SGCB, VASP 31 ACTR2(1), AKT1(1), DAG1(1), DGKA(6), ETFA(2), GCA(1), ITGA9(1), ITPKA(1), ITPKB(3), ITPR1(5), ITPR2(11), ITPR3(3), MAP2K1(2), MAPK1(1), MAPK3(2), NR1I3(1), PAK1(3), PDE3A(5), PDE3B(3), PI3(1), PIK3C2G(7), PIK3CD(3), PIK3R1(1), PSME1(1), RIPK3(1), SGCB(1), VASP(2) 12846260 70 53 70 27 27 21 11 3 8 0 0.97 1.00 511 P38MAPKPATHWAY The Rho family GTPases activate the p38 MAPKs under environmental stress or in the presence of pro-inflammatory cytokines. ATF2, CDC42, CREB1, DAXX, DDIT3, ELK1, GRB2, HMGN1, HRAS, HSPB1, HSPB2, MAP2K4, MAP2K6, MAP3K1, MAP3K5, MAP3K7, MAP3K9, MAPK14, MAPKAPK2, MAPKAPK5, MAX, MEF2A, MEF2B, MEF2C, MEF2D, MKNK1, MYC, PDZGEF1, PLA2G4A, RAC1, RIPK1, RPS6KA5, SHC1, STAT1, TGFB1, TGFB2, TGFB3, TGFBR1, TRADD, TRAF2 39 ATF2(2), CDC42(1), DAXX(3), HRAS(2), HSPB2(1), MAP2K6(3), MAP3K1(3), MAP3K5(3), MAP3K7(3), MAP3K9(4), MAPK14(1), MAPKAPK2(1), MAPKAPK5(4), MEF2A(2), MEF2C(2), MEF2D(2), MYC(1), PLA2G4A(5), RAC1(2), RPS6KA5(3), SHC1(1), STAT1(2), TGFB1(1), TGFB2(1), TRADD(1) 9996480 54 42 54 21 11 20 12 5 6 0 0.97 1.00 512 PROTEASOME PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB10, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMB8, PSMB9 17 PSMA4(1), PSMA5(1), PSMB3(1), PSMB4(2), PSMB6(1), PSMB8(3), PSMB9(2) 2341234 11 10 10 6 5 4 1 0 1 0 0.97 1.00 513 FASPATHWAY Binding of the Fas ligand to the Fas receptor induces caspase activation and consequent apoptosis in the Fas-expressing cell. ADPRT, ARHGDIB, CASP10, CASP3, CASP6, CASP7, CASP8, CFLAR, DAXX, DFFA, DFFB, FADD, FAF1, JUN, LMNA, LMNB1, LMNB2, MAP2K4, MAP3K1, MAP3K7, MAPK8, PAK1, PAK2, PRKDC, PTPN13, RB1, RIPK2, SPTAN1, TNFRSF6, TNFSF6 27 ARHGDIB(1), CASP10(4), CASP6(1), CASP7(2), CASP8(1), CFLAR(1), DAXX(3), DFFA(1), DFFB(2), FADD(1), FAF1(1), JUN(2), MAP3K1(3), MAP3K7(3), MAPK8(2), PAK1(3), PAK2(1), PRKDC(15), PTPN13(3), RB1(7), RIPK2(1), SPTAN1(2) 11532976 60 46 59 14 15 27 6 1 11 0 0.97 1.00 514 IL22BPPATHWAY IL-22 is produced by T cells and induces the acute phase inflammatory response in hepatocytes. IL10RA, IL22, IL22RA1, IL22RA2, JAK1, JAK2, JAK3, SOCS3, STAT1, STAT3, STAT5A, STAT5B, TYK2 13 IL10RA(1), IL22(1), IL22RA1(1), IL22RA2(1), JAK1(1), JAK2(3), JAK3(7), STAT1(2), STAT3(1), STAT5A(2), TYK2(8) 5072466 28 22 28 9 9 12 4 1 2 0 0.97 1.00 515 HSA00620_PYRUVATE_METABOLISM Genes involved in pyruvate metabolism ACACA, ACACB, ACAT1, ACAT2, ACOT12, ACSS1, ACSS2, ACYP1, ACYP2, AKR1B1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, DLAT, DLD, GLO1, GRHPR, HAGH, HAGHL, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, LDHD, MDH1, MDH2, ME1, ME2, ME3, PC, PCK1, PCK2, PDHA1, PDHA2, PDHB, PKLR, PKM2 42 ACACA(4), ACACB(8), ACAT1(1), ACOT12(1), ACSS1(3), ACSS2(2), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), DLAT(1), DLD(2), GRHPR(1), HAGHL(1), LDHAL6B(1), LDHB(2), LDHC(1), LDHD(6), MDH1(1), MDH2(1), ME2(2), ME3(2), PC(4), PCK1(3), PCK2(1), PDHA1(2), PDHA2(5), PKLR(3), PKM2(1) 12575344 67 52 67 32 19 32 6 4 6 0 0.97 1.00 516 MITOCHONDRIAPATHWAY Pro-apoptotic signaling induces mitochondria to release cytochrome c, which stimulates Apaf-1 to activate caspase 9. APAF1, BAK1, BAX, BCL2, BCL2L1, BID, BIK, BIRC2, BIRC3, BIRC4, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, DFFA, DFFB, DIABLO, ENDOG, PDCD8 19 APAF1(1), BAK1(1), BAX(1), BCL2L1(2), BID(1), BIRC3(3), CASP6(1), CASP7(2), CASP8(1), CASP9(1), DFFA(1), DFFB(2) 3689762 17 15 17 8 3 7 2 2 3 0 0.97 1.00 517 HSA04340_HEDGEHOG_SIGNALING_PATHWAY Genes involved in Hedgehog signaling pathway BMP2, BMP4, BMP5, BMP6, BMP7, BMP8A, BMP8B, BTRC, CSNK1A1, CSNK1A1L, CSNK1D, CSNK1E, CSNK1G1, CSNK1G2, CSNK1G3, DHH, FBXW11, GAS1, GLI1, GLI2, GLI3, GSK3B, HHIP, IHH, LRP2, PRKACA, PRKACB, PRKACG, PRKX, PRKY, PTCH1, PTCH2, RAB23, SHH, SMO, STK36, SUFU, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B, ZIC2 55 BMP4(2), BMP5(5), BMP7(1), BTRC(1), CSNK1A1(1), CSNK1A1L(5), CSNK1G1(2), DHH(1), GLI1(3), GLI2(5), GLI3(6), GSK3B(1), HHIP(1), IHH(1), PRKACA(1), PRKACB(2), PRKACG(1), PRKX(1), PTCH1(6), PTCH2(6), SMO(1), STK36(3), SUFU(3), WNT10B(2), WNT11(2), WNT2(3), WNT2B(2), WNT3(2), WNT3A(1), WNT5A(1), WNT5B(1), WNT6(2), WNT7A(2), WNT7B(1), WNT9A(1), WNT9B(2) 14282186 81 57 81 34 22 28 12 11 8 0 0.97 1.00 518 HSA01031_GLYCAN_STRUCTURES_BIOSYNTHESIS_2 Genes involved in glycan structures - biosynthesis 2 A4GALT, ABO, B3GALNT1, B3GALT1, B3GALT2, B3GALT4, B3GALT5, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT4, B4GALT6, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GBGT1, GCNT2, PIGA, PIGB, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGU, PIGV, PIGX, PIGZ, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST3GAL5, ST3GAL6, ST6GALNAC3, ST6GALNAC4, ST6GALNAC5, ST6GALNAC6, ST8SIA1, ST8SIA5, UGCG, UGCGL1, UGCGL2 60 B3GALNT1(1), B3GALT1(2), B3GALT2(2), B3GALT4(1), B3GNT2(1), B3GNT3(4), B3GNT4(1), B4GALT1(1), B4GALT3(2), B4GALT4(1), B4GALT6(2), FUT3(3), FUT5(4), FUT6(2), FUT9(1), GBGT1(3), GCNT2(1), PIGA(1), PIGB(1), PIGF(1), PIGG(4), PIGH(1), PIGK(1), PIGL(2), PIGM(1), PIGN(2), PIGO(2), PIGQ(1), PIGS(1), PIGX(1), PIGZ(3), ST3GAL1(1), ST3GAL2(2), ST3GAL4(2), ST3GAL5(2), ST3GAL6(1), ST6GALNAC3(3), ST6GALNAC5(2), ST8SIA1(2) 13400908 69 54 68 41 17 22 17 6 7 0 0.97 1.00 519 LONGEVITYPATHWAY Caloric restriction in animals often increases lifespan, which may occur via decreased IGF receptor expression and consequent expression of stress-resistance proteins. AKT1, CAT, FOXO3A, GH1, GHR, HRAS, IGF1, IGF1R, PIK3CA, PIK3R1, SHC1, SOD1, SOD2, SOD3 12 AKT1(1), CAT(1), GH1(1), GHR(2), HRAS(2), IGF1(2), IGF1R(1), PIK3R1(1), SHC1(1), SOD2(1) 3007310 13 12 13 5 3 7 1 2 0 0 0.98 1.00 520 EICOSANOID_SYNTHESIS ALOX12, ALOX15, ALOX15B, ALOX5, ALOX5AP, DPEP1, GGT1, IPLA2(GAMMA), LTA4H, LTC4S, PLA2G2A, PLA2G6, PTGDS, PTGES, PTGIS, PTGS1, PTGS2, TBXAS1 17 ALOX15(2), ALOX15B(1), GGT1(2), LTA4H(2), PLA2G2A(1), PLA2G6(6), PTGES(1), PTGS1(2), TBXAS1(5) 4144552 22 17 20 7 4 12 4 1 1 0 0.98 1.00 521 HSA00532_CHONDROITIN_SULFATE_BIOSYNTHESIS Genes involved in chondroitin sulfate biosynthesis B3GALT6, B3GAT1, B3GAT2, B3GAT3, B4GALT7, ChGn, CHPF, CHST11, CHST12, CHST13, CHST14, CHST3, CHST7, CHSY-2, CHSY1, CSGlcA-T, DSE, GALNAC4S-6ST, GALNACT-2, UST, XYLT1, XYLT2 17 B3GALT6(1), B3GAT1(2), B3GAT2(2), CHPF(1), CHST11(1), CHST12(1), CHST14(1), CHST3(2), DSE(1), XYLT1(4) 4030810 16 15 16 13 2 7 3 2 2 0 0.98 1.00 522 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 26 AKT1(1), AKT3(2), GSK3A(4), GSK3B(1), IRS1(4), IRS2(2), JAK1(1), JAK3(7), MAP4K1(2), MAPK1(1), MAPK3(2), PDK1(1), PIK3CD(3), PIK3R1(1), PPP1R13B(4), RAF1(1), SHC1(1), SOS1(6), SOS2(4), STAT6(1) 9492028 49 38 49 21 9 20 10 4 6 0 0.98 1.00 523 SIG_CHEMOTAXIS Genes related to chemotaxis ACTR2, ACTR3, AKT1, AKT2, AKT3, ANGPTL2, ARHGAP1, ARHGAP4, ARHGEF11, BTK, CDC42, CFL1, CFL2, GDI1, GDI2, INPPL1, ITPR1, ITPR2, ITPR3, LIMK1, MYLK, MYLK2, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDK1, PIK3CA, PIK3CD, PIK3CG, PIK3R1, PITX2, PPP1R13B, PTEN, RACGAP1, RHO, ROCK1, ROCK2, RPS4X, SAG, WASF1, WASL 42 ACTR2(1), AKT1(1), AKT3(2), ARHGAP1(1), ARHGAP4(1), ARHGEF11(7), BTK(5), CDC42(1), CFL1(3), CFL2(1), GDI1(2), GDI2(1), INPPL1(3), ITPR1(5), ITPR2(11), ITPR3(3), LIMK1(1), MYLK(7), MYLK2(2), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PDK1(1), PIK3CD(3), PIK3CG(10), PIK3R1(1), PITX2(3), PPP1R13B(4), RACGAP1(1), ROCK1(5), ROCK2(3), WASL(2) 18413388 105 67 104 44 25 37 18 10 15 0 0.98 1.00 524 HSA05050_DENTATORUBROPALLIDOLUYSIAN_ATROPHY Genes involved in dentatorubropallidoluysian atrophy (DRPLA) ATN1, BAIAP2, CASP1, CASP3, CASP7, CASP8, GAPDH, INS, INSR, ITCH, MAGI1, MAGI2, RERE, WWP1, WWP2 15 ATN1(2), CASP1(2), CASP7(2), CASP8(1), GAPDH(3), INSR(7), ITCH(2), MAGI1(5), MAGI2(7), RERE(3), WWP1(1), WWP2(1) 6378808 36 25 36 13 8 12 6 3 7 0 0.98 1.00 525 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 12 ACO1(1), ACO2(2), GRHPR(1), MDH1(1), MDH2(1), MTHFD1(3), MTHFD1L(2), MTHFD2(3) 3388586 14 13 14 2 3 6 4 1 0 0 0.98 1.00 526 IL1RPATHWAY The cytokine IL-1 stimulates its primary receptor, IL-1R1, which induces transcription of inflammation-related genes such as interferons. CHUK, IFNA1, IFNB1, IKBKB, IL1A, IL1B, IL1R1, IL1RAP, IL1RN, IL6, IRAK1, IRAK2, IRAK3, JUN, MAP2K3, MAP2K6, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MAPK14, MAPK8, MYD88, NFKB1, NFKBIA, RELA, SITPEC, TGFB1, TGFB2, TGFB3, TNF, TOLLIP, TRAF6 31 CHUK(2), IFNA1(1), IFNB1(1), IKBKB(3), IL1B(1), IL1RAP(2), IL1RN(1), IRAK1(4), IRAK2(1), IRAK3(3), JUN(2), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAP3K14(1), MAP3K7(3), MAPK14(1), MAPK8(2), NFKB1(2), RELA(3), TGFB1(1), TGFB2(1), TOLLIP(1), TRAF6(1) 8061264 45 34 45 18 14 16 6 5 4 0 0.98 1.00 527 TALL1PATHWAY APRIL and BAFF bind to BCMA and TACI receptors on B cell surfaces, promoting immunoglobulin production and cell proliferation. CHUK, MAP3K14, MAPK14, MAPK8, NFKB1, RELA, TNFRSF13B, TNFRSF13C, TNFRSF17, TNFSF13, TNFSF13B, TRAF2, TRAF3, TRAF5, TRAF6 15 CHUK(2), MAP3K14(1), MAPK14(1), MAPK8(2), NFKB1(2), RELA(3), TNFRSF13B(2), TNFSF13(1), TRAF3(1), TRAF5(2), TRAF6(1) 3974740 18 15 18 9 6 4 1 1 6 0 0.98 1.00 528 HSA00624_1_AND_2_METHYLNAPHTHALENE_DEGRADATION Genes involved in 1- and 2-methylnaphthalene degradation ACAD8, ACAD9, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ARD1A, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ESCO1, ESCO2, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1 21 ACAD8(2), ACAD9(3), ADH1B(1), ADH1C(1), ADH4(2), ADH5(2), ADH7(1), ADHFE1(2), DHRS2(1), ESCO1(1), MYST3(11), MYST4(3), PNPLA3(1), SH3GLB1(1) 6562148 32 28 32 12 11 11 4 2 4 0 0.98 1.00 529 APOPTOSIS_GENMAPP APAF1, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, FADD, FAS, FASLG, GZMB, IKBKG, JUN, MAP2K4, MAP3K1, MAP3K14, MAPK10, MCL1, MDM2, MYC, NFKB1, NFKBIA, PARP1, PRF1, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TNFSF10, TP53, TRADD, TRAF1, TRAF2 40 APAF1(1), BAK1(1), BAX(1), BCL2L1(2), BID(1), BIRC3(3), CASP2(1), CASP6(1), CASP7(2), CASP8(1), CASP9(1), FADD(1), FAS(1), FASLG(1), GZMB(1), JUN(2), MAP3K1(3), MAP3K14(1), MAPK10(1), MCL1(2), MDM2(1), MYC(1), NFKB1(2), PARP1(3), PRF1(2), RELA(3), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TRAF1(4) 10022112 48 38 48 27 11 16 5 8 8 0 0.98 1.00 530 DNA_POLYMERASE POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLS 7 POLB(1), POLD1(2), POLG(2), POLL(1), POLQ(18) 4560360 24 20 22 4 6 11 3 3 1 0 0.98 1.00 531 HSA00640_PROPANOATE_METABOLISM Genes involved in propanoate metabolism ABAT, ACACA, ACACB, ACADM, ACAT1, ACAT2, ACSS1, ACSS2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH7A1, ALDH9A1, ECHS1, EHHADH, HADHA, HIBCH, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, LOC283398, MCEE, MLYCD, MUT, PCCA, PCCB, SUCLA2, SUCLG1, SUCLG2 33 ABAT(3), ACACA(4), ACACB(8), ACADM(1), ACAT1(1), ACSS1(3), ACSS2(2), ALDH1B1(3), ALDH2(2), ALDH6A1(2), ALDH7A1(1), ALDH9A1(2), EHHADH(1), HADHA(2), HIBCH(1), LDHAL6B(1), LDHB(2), LDHC(1), MLYCD(2), MUT(1), PCCA(2), PCCB(6), SUCLA2(2), SUCLG2(1) 10649918 54 43 54 24 15 23 6 4 6 0 0.98 1.00 532 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 18 EXT1(2), EXT2(1), EXTL1(2), EXTL3(1), HS3ST2(1), HS3ST5(4), HS6ST1(2), HS6ST3(2), NDST1(3), NDST2(1), NDST3(4) 5246906 23 21 23 13 2 12 4 5 0 0 0.98 1.00 533 STEMPATHWAY In the absence of infection, bone marrow stromal cells release hematopoietic cytokines; activated macrophages and Th cells induce hematopoiesis during infection. CD4, CD8A, CSF1, CSF2, CSF3, EPO, IL11, IL2, IL3, IL4, IL5, IL6, IL7, IL8, IL9 15 CD4(2), CSF1(2), IL4(2) 1697764 6 5 6 6 2 2 1 0 1 0 0.98 1.00 534 NUCLEOTIDE_METABOLISM ADSL, ADSS, DHFR, HPRT1, IMPDH1, MTHFD2, NME2, OAZ1, POLA, POLB, POLD1, POLG, PRPS2, RRM1, SAT, SRM 14 ADSL(1), ADSS(1), HPRT1(1), IMPDH1(2), MTHFD2(3), POLB(1), POLD1(2), POLG(2), PRPS2(1), RRM1(2) 3494318 16 14 16 5 5 6 3 1 1 0 0.98 1.00 535 HYPERTROPHY_MODEL ADAM10, ANKRD1, ATF3, CYR61, DUSP14, EIF4E, EIF4EBP1, GDF8, HBEGF, IFNG, IFRD1, IL18, IL1A, IL1R1, JUND, MYOG, NR4A3, TCF8, VEGF, WDR1 17 ADAM10(4), HBEGF(1), IFNG(1), NR4A3(2), WDR1(2) 2985950 10 10 10 8 1 4 1 2 2 0 0.98 1.00 536 N_GLYCAN_BIOSYNTHESIS ALG3, ALG5, B4GALT1, B4GALT2, B4GALT3, B4GALT5, DDOST, DPAGT1, DPM1, FUT8, GCS1, MAN1A1, MAN1B1, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT5, RPN1, RPN2, ST6GAL1 21 ALG5(1), B4GALT1(1), B4GALT3(2), B4GALT5(3), FUT8(2), MAN1A1(3), MGAT1(1), MGAT2(2), MGAT3(4), MGAT4A(2), MGAT4B(1), MGAT5(3), RPN1(1), ST6GAL1(1) 5405504 27 22 27 18 11 8 2 3 3 0 0.99 1.00 537 IL4PATHWAY IL-4 promotes Th2 cell differentiation via a heterodimeric receptor that activates Stat6/JAK and MAP kinase pathways. AKT1, GRB2, IL2RG, IL4, IL4R, IRS1, JAK1, JAK3, RPS6KB1, SHC1, STAT6 11 AKT1(1), IL2RG(1), IL4(2), IRS1(4), JAK1(1), JAK3(7), RPS6KB1(1), SHC1(1), STAT6(1) 4071928 19 16 19 9 3 10 5 0 1 0 0.99 1.00 538 IRINOTECAN_PATHWAY_PHARMGKB ABCC1, ABCC2, ABCG2, BCHE, CES1, CES2, CES4, CYP3A4, CYP3A5, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6 16 ABCC1(4), ABCC2(4), ABCG2(1), CES1(2), CES2(1), CYP3A4(1), UGT1A10(2), UGT1A3(1), UGT1A5(3), UGT1A6(1), UGT1A7(1), UGT1A8(1), UGT1A9(2) 5763106 24 22 24 10 7 10 4 2 1 0 0.99 1.00 539 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(2), FOS(1), IKBKB(3), IRAK1(4), JUN(2), MAP2K3(2), MAP2K6(3), MAP3K1(3), MAP3K14(1), MAP3K7(3), MAPK14(1), MAPK8(2), NFKB1(2), PPARA(2), RELA(3), TLR2(3), TLR3(2), TLR7(3), TLR9(1), TOLLIP(1), TRAF6(1) 9458386 46 38 45 13 17 14 5 4 6 0 0.99 1.00 540 HSA04710_CIRCADIAN_RHYTHM Genes involved in circadian rhythm ARNTL, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, NPAS2, NR1D1, PER1, PER2, PER3 11 ARNTL(2), CLOCK(5), CRY1(3), CRY2(2), NPAS2(1), PER1(6), PER2(3), PER3(1) 4651140 23 19 23 11 4 10 7 1 1 0 0.99 1.00 541 HSA00020_CITRATE_CYCLE Genes involved in citrate cycle (TCA cycle) ACLY, ACO1, ACO2, CLYBL, CS, DLD, DLST, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, LOC283398, LOC441996, MDH1, MDH2, OGDH, OGDHL, PC, PCK1, PCK2, SDHA, SDHB, SDHC, SDHD, SUCLA2, SUCLG1, SUCLG2 27 ACO1(1), ACO2(2), DLD(2), DLST(1), FH(2), IDH1(2), IDH3A(2), IDH3B(3), MDH1(1), MDH2(1), OGDH(3), OGDHL(4), PC(4), PCK1(3), PCK2(1), SDHA(1), SDHC(1), SUCLA2(2), SUCLG2(1) 8013026 37 31 37 25 8 15 4 4 6 0 0.99 1.00 542 EIF2PATHWAY Eukaryotic initiation factor 2 (EIF2) initiates translation by transferring Met-tRNA to the 40S ribosome in a GTP-dependent process. EIF2AK3, EIF2AK4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF5, GSK3B, HRI, PPP1CA, PRKR 9 EIF2AK3(7), EIF2AK4(2), EIF2B5(1), EIF5(1), GSK3B(1), PPP1CA(1) 3140988 13 13 13 6 5 6 1 0 1 0 0.99 1.00 543 HSA00563_GLYCOSYLPHOSPHATIDYLINOSITOL_ANCHOR_BIOSYNTHESIS Genes involved in glycosylphosphatidylinositol(GPI)-anchor biosynthesis GPAA1, GPLD1, PGAP1, PIGA, PIGB, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGU, PIGV, PIGW, PIGX, PIGZ 23 GPAA1(3), PGAP1(3), PIGA(1), PIGB(1), PIGF(1), PIGG(4), PIGH(1), PIGK(1), PIGL(2), PIGM(1), PIGN(2), PIGO(2), PIGQ(1), PIGS(1), PIGX(1), PIGZ(3) 6629788 28 25 28 18 6 7 5 6 4 0 0.99 1.00 544 HSA00450_SELENOAMINO_ACID_METABOLISM Genes involved in selenoamino acid metabolism AHCY, CARM1, CBS, CTH, GGT1, GGTL3, GGTL4, HEMK1, KIAA0828, LCMT1, LCMT2, MARS, MARS2, MAT1A, MAT2B, METTL2B, METTL6, PAPSS1, PAPSS2, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, SCLY, SEPHS1, SEPHS2, WBSCR22 26 AHCY(1), CARM1(1), CBS(4), GGT1(2), LCMT1(2), LCMT2(1), MARS(1), MAT1A(1), PAPSS2(1), PRMT3(2), PRMT5(1), PRMT6(2), PRMT7(3), PRMT8(1), SEPHS1(3), WBSCR22(4) 6761864 30 27 30 15 11 11 2 2 4 0 0.99 1.00 545 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_NEOLACTOSERIES ABO, B3GNT1, FUT1, FUT2, FUT9, GCNT2, ST8SIA1 7 FUT9(1), GCNT2(1), ST8SIA1(2) 1700256 4 4 4 4 1 1 1 0 1 0 0.99 1.00 546 ATMPATHWAY The tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair. ABL1, ATM, BRCA1, CDKN1A, CHEK1, CHEK2, GADD45A, JUN, MAPK8, MDM2, MRE11A, NBS1, NFKB1, NFKBIA, RAD50, RAD51, RBBP8, RELA, TP53, TP73 18 ABL1(2), ATM(7), BRCA1(6), CHEK1(4), CHEK2(3), GADD45A(1), JUN(2), MAPK8(2), MDM2(1), MRE11A(2), NFKB1(2), RAD50(3), RAD51(1), RBBP8(1), RELA(3) 7873474 40 30 40 9 7 15 4 8 6 0 0.99 1.00 547 HSA04920_ADIPOCYTOKINE_SIGNALING_PATHWAY Genes involved in adipocytokine signaling pathway ACACB, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADIPOQ, ADIPOR1, ADIPOR2, AGRP, AKT1, AKT2, AKT3, CAMKK1, CAMKK2, CD36, CHUK, CPT1A, CPT1B, CPT1C, CPT2, FRAP1, G6PC, G6PC2, IKBKB, IKBKG, IRS1, IRS2, IRS4, JAK1, JAK2, JAK3, LEP, LEPR, MAPK10, MAPK8, MAPK9, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NPY, PCK1, PCK2, POMC, PPARA, PPARGC1A, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3, PRKCQ, PTPN11, RELA, RXRA, RXRB, RXRG, SLC2A1, SLC2A4, SOCS3, STAT3, STK11, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF2, TYK2 70 ACACB(8), ACSL1(2), ACSL3(1), ACSL5(1), ACSL6(2), ADIPOQ(1), ADIPOR1(1), ADIPOR2(2), AKT1(1), AKT3(2), CD36(1), CHUK(2), CPT1A(3), CPT1C(5), CPT2(2), G6PC(2), G6PC2(2), IKBKB(3), IRS1(4), IRS2(2), IRS4(3), JAK1(1), JAK2(3), JAK3(7), LEPR(10), MAPK10(1), MAPK8(2), MAPK9(1), NFKB1(2), NFKB2(2), NFKBIB(1), PCK1(3), PCK2(1), POMC(2), PPARA(2), PPARGC1A(5), PRKAA2(2), PRKAB2(1), PRKAG2(4), PRKAG3(2), PRKCQ(4), PTPN11(3), RELA(3), RXRA(1), RXRG(5), SLC2A4(2), STAT3(1), STK11(3), TNFRSF1A(2), TNFRSF1B(1), TRADD(1), TYK2(8) 22732024 136 79 135 49 42 55 20 7 12 0 0.99 1.00 548 ST_INTEGRIN_SIGNALING_PATHWAY Integrins are transmembrane receptors that mediate cell growth, survival, and migration by binding to ligands in the extracellular matrix. ABL1, ACK1, ACTN1, ACTR2, ACTR3, AKT1, AKT2, AKT3, ANGPTL2, ARHGEF6, ARHGEF7, BCAR1, BRAF, CAV1, CDC42, CDKN2A, CRK, CSE1L, DDEF1, DOCK1, EPHB2, FYN, GRAF, GRB2, GRB7, GRF2, GRLF1, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGB3BP, MAP2K4, MAP2K7, MAP3K11, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MRAS, MYLK, MYLK2, P4HB, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PIK3CA, PIK3CB, PKLR, PLCG1, PLCG2, PTEN, PTK2, RAF1, RALA, RHO, ROCK1, ROCK2, SHC1, SOS1, SOS2, SRC, TERF2IP, TLN1, TLN2, VASP, WAS, ZYX 75 ABL1(2), ACTN1(2), ACTR2(1), AKT1(1), AKT3(2), ARHGEF6(2), ARHGEF7(3), BCAR1(5), BRAF(7), CDC42(1), CSE1L(3), DOCK1(3), EPHB2(5), FYN(4), GRLF1(11), ILK(1), ITGA1(4), ITGA10(6), ITGA11(3), ITGA2(5), ITGA3(2), ITGA4(5), ITGA5(1), ITGA6(6), ITGA7(3), ITGA8(9), ITGA9(1), ITGB3BP(1), MAP3K11(2), MAPK1(1), MAPK10(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(6), MAPK9(1), MRAS(3), MYLK(7), MYLK2(2), PAK1(3), PAK2(1), PAK3(3), PAK4(1), PAK6(2), PAK7(4), PIK3CB(1), PKLR(3), PLCG1(2), PLCG2(3), PTK2(3), RAF1(1), RALA(2), ROCK1(5), ROCK2(3), SHC1(1), SOS1(6), SOS2(4), TLN1(8), TLN2(11), VASP(2), WAS(5) 32546588 200 98 198 70 47 84 36 9 24 0 0.99 1.00 549 CD40PATHWAY The CD40 receptor is a TNF-type receptor that regulates immunoglobulin expression in B cells and moderates T cell activation via T-cell expression of its ligand. CHUK, DUSP1, IKBKAP, IKBKB, IKBKG, MAP3K1, MAP3K14, NFKB1, NFKBIA, RELA, TNFAIP3, TNFRSF5, TNFSF5, TRAF3, TRAF6 12 CHUK(2), IKBKAP(2), IKBKB(3), MAP3K1(3), MAP3K14(1), NFKB1(2), RELA(3), TNFAIP3(4), TRAF3(1), TRAF6(1) 4931312 22 17 22 10 5 6 4 2 5 0 0.99 1.00 550 ST_PAC1_RECEPTOR_PATHWAY The signaling peptide PACAP binds to its receptor, PAC1R, which activates adenylyl cyclase and phospholipase C. ASAH1, CAMP, DAG1, GAS, GNAQ, ITPKA, ITPKB, PACAP 6 DAG1(1), ITPKA(1), ITPKB(3) 1687262 5 5 5 3 3 1 1 0 0 0 0.99 1.00 551 CELL2CELLPATHWAY Epithelial cell adhesion proteins such as cadherins transduce signals into the cell via catenins, which alter cell shape and motility. ACTN1, ACTN2, ACTN3, BCAR1, CSK, CTNNA1, CTNNA2, CTNNB1, PECAM1, PTK2, PXN, SRC, VCL 12 ACTN1(2), ACTN2(6), ACTN3(2), BCAR1(5), CTNNB1(3), PTK2(3), PXN(3), VCL(2) 5192438 26 19 26 18 7 9 4 5 1 0 0.99 1.00 552 ST_GAQ_PATHWAY G-alpha-q activates phospholipase C, resulting in calcium influx and increasing protein kinase C activity. ADRBK1, AKT1, AKT2, AKT3, BF, DAG1, GNAQ, IKBKG, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PDK1, PHKA2, PIK3CB, PITX2, PLD1, PLD2, PLD3, VN1R1 26 ADRBK1(2), AKT1(1), AKT3(2), DAG1(1), ITPKA(1), ITPKB(3), ITPR1(5), ITPR2(11), ITPR3(3), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), PDK1(1), PHKA2(4), PIK3CB(1), PITX2(3), PLD1(10), PLD2(4), PLD3(1), VN1R1(2) 12327212 66 48 64 21 18 29 7 6 6 0 0.99 1.00 553 HSA00903_LIMONENE_AND_PINENE_DEGRADATION Genes involved in limonene and pinene degradation ACOT11, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, ARD1A, CYP2C19, CYP2C9, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ECHS1, EHHADH, ESCO1, ESCO2, HADHA, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1, YOD1 25 ACOT11(1), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), CYP2C19(6), CYP2C9(2), DHRS2(1), EHHADH(1), ESCO1(1), HADHA(2), MYST3(11), MYST4(3), PNPLA3(1), SH3GLB1(1) 8198324 38 33 38 17 10 14 6 2 6 0 0.99 1.00 554 ACETAMINOPHENPATHWAY Acetaminophen selectively inhibits Cox-3, which is localized to the brain, and yields the toxic metabolite NAPQI when processed by CAR in the liver. CYP1A2, CYP2E1, CYP3A, NR1I3, PTGS1, PTGS2 5 CYP1A2(1), CYP2E1(1), NR1I3(1), PTGS1(2) 1417058 5 4 5 4 1 3 0 1 0 0 0.99 1.00 555 HSA04130_SNARE_INTERACTIONS_IN_VESICULAR_TRANSPORT Genes involved in SNARE interactions in vesicular transport BET1, BET1L, BNIP1, C1orf142, GOSR1, GOSR2, SEC22B, SNAP23, SNAP25, SNAP29, STX10, STX11, STX12, STX16, STX17, STX18, STX19, STX2, STX3, STX4, STX5, STX6, STX7, STX8, TSNARE1, USE1, VAMP1, VAMP2, VAMP3, VAMP4, VAMP5, VAMP7, VAMP8, VTI1A, VTI1B, YKT6 34 BNIP1(2), GOSR1(1), SEC22B(4), SNAP23(1), SNAP25(2), STX10(1), STX11(1), STX5(2), STX7(1), TSNARE1(2), USE1(1), YKT6(1) 4427750 19 18 19 11 6 6 4 2 1 0 0.99 1.00 556 HSA01040_POLYUNSATURATED_FATTY_ACID_BIOSYNTHESIS Genes involved in polyunsaturated fatty acid biosynthesis ACAA1, ACOX1, ACOX3, ELOVL2, ELOVL5, ELOVL6, FADS1, FADS2, FASN, GPSN2, HADHA, HSD17B12, PECR, SCD 13 ACOX1(2), ACOX3(4), ELOVL5(2), ELOVL6(1), FADS1(1), FADS2(1), HADHA(2), HSD17B12(1), PECR(1), SCD(1) 4036862 16 14 16 4 3 3 4 2 4 0 0.99 1.00 557 ONE_CARBON_POOL_BY_FOLATE ALDH1L1, AMT, ATIC, ATP6V0C, SHMT1, DHFR, GART, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 15 ALDH1L1(3), GART(2), MTHFD1(3), MTHFD1L(2), MTHFD2(3), MTHFR(2), MTR(5), TYMS(1) 4817926 21 19 21 13 4 6 8 2 1 0 0.99 1.00 558 HSA04330_NOTCH_SIGNALING_PATHWAY Genes involved in Notch signaling pathway ADAM17, APH1A, CIR, CREBBP, CTBP1, CTBP2, DLL1, DLL3, DLL4, DTX1, DTX2, DTX3, DTX3L, DTX4, DVL1, DVL2, DVL3, EP300, GCN5L2, HDAC1, HDAC2, HES1, JAG1, JAG2, LFNG, LOC652788, MAML1, MAML2, MAML3, MFNG, NCOR2, NCSTN, NOTCH1, NOTCH2, NOTCH3, NOTCH4, NUMB, NUMBL, PCAF, PSEN1, PSEN2, PSENEN, PTCRA, RBPJ, RBPJL, RFNG, SNW1 43 CREBBP(12), CTBP1(1), DLL1(1), DLL3(1), DLL4(2), DTX2(2), DTX3(2), DTX3L(1), DTX4(2), DVL1(3), DVL3(3), EP300(5), HDAC1(2), JAG2(1), LFNG(1), MAML1(2), MAML2(6), MAML3(2), MFNG(2), NCOR2(6), NCSTN(3), NOTCH1(11), NOTCH2(7), NOTCH3(5), NOTCH4(3), PSEN1(1), PSEN2(2), PSENEN(2), SNW1(2) 19396660 93 68 92 34 27 26 15 6 19 0 0.99 1.00 559 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 16 ADRB2(3), AKT1(1), GNAS(4), GNB1(1), NFKB1(2), NOS3(1), PIK3R1(1), RELA(3), SYT1(3) 4352634 19 15 19 11 5 5 4 4 1 0 0.99 1.00 560 ATRBRCAPATHWAY BRCA1 and 2 block cell cycle progression in response to DNA damage and promote double-stranded break repair; mutations induce breast cancer susceptibility. ATM, ATR, BRCA1, BRCA2, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, HUS1, MRE11A, NBS1, RAD1, RAD17, RAD50, RAD51, RAD9A, TP53, TREX1 20 ATM(7), ATR(11), BRCA1(6), BRCA2(7), CHEK1(4), CHEK2(3), FANCC(2), FANCE(1), FANCF(3), FANCG(2), MRE11A(2), RAD1(1), RAD17(2), RAD50(3), RAD51(1), RAD9A(1), TREX1(1) 11625002 57 44 57 10 14 17 10 8 8 0 0.99 1.00 561 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 45 ACCN1(4), ADCY4(4), ADCY8(13), CACNA1A(8), CACNA1B(1), GNAS(4), GNAT3(1), GNB1(1), GNB3(2), GNG3(1), GRM4(1), ITPR3(3), KCNB1(1), PDE1A(2), PLCB2(5), PRKACA(1), PRKACB(2), PRKACG(1), PRKX(1), SCNN1B(2), SCNN1G(3), TAS1R1(2), TAS2R1(3), TAS2R10(3), TAS2R38(2), TAS2R39(2), TAS2R4(1), TAS2R40(2), TAS2R41(5), TAS2R42(1), TAS2R5(1), TAS2R7(1), TAS2R8(1), TAS2R9(3) 15132492 88 57 88 38 27 32 16 6 7 0 0.99 1.00 562 CHONDROITIN B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 HS3ST2(1), XYLT1(4) 1890716 5 5 5 7 1 3 1 0 0 0 0.99 1.00 563 HEPARAN_SULFATE_BIOSYNTHESIS B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 HS3ST2(1), XYLT1(4) 1890716 5 5 5 7 1 3 1 0 0 0 0.99 1.00 564 ARAPPATHWAY ADP-ribosylation factors (ARFs), members of the Ras superfamily, regulate eukaryotic vesicular trafficking and activate phospholipase D's. ARF1, ARFGAP1, ARFGAP3, ARFGEF2, BIG1, CENTD1, CENTD2, CLTA, CLTB, COP, COPA, DDEF1, DDEF2, GBF1, GPLD1, KDELR1, KDELR2, KDELR3, PSCD1, PSCD2, PSCD3, PSCD4 12 ARFGAP1(1), ARFGAP3(1), ARFGEF2(1), CLTB(2), COPA(8), GBF1(3), KDELR2(2) 4367764 18 17 17 8 8 4 4 1 1 0 0.99 1.00 565 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 22 ARSB(2), ARSD(1), ARSE(2), GAL3ST1(1), GALC(2), GLA(2), NEU1(4), NEU2(2), NEU3(2), PPAP2B(2), SMPD1(3), SMPD2(2), SPTLC2(3) 5598812 28 23 28 10 8 13 4 2 1 0 0.99 1.00 566 SELENOAMINO_ACID_METABOLISM AHCY, CBS, CTH, GGT1, MARS, MARS2, MAT1A, MAT2B, PAPSS1, PAPSS2, SCLY, SEPHS1 12 AHCY(1), CBS(4), GGT1(2), MARS(1), MAT1A(1), PAPSS2(1), SEPHS1(3) 3369540 13 11 13 11 4 6 0 1 2 0 0.99 1.00 567 CHEMICALPATHWAY DNA damage promotes Bid cleavage, which stimulates mitochondrial cytochrome c release and consequent caspase activation, resulting in apoptosis. ADPRT, AKT1, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, CASP3, CASP6, CASP7, CASP9, CYCS, EIF2S1, PRKCA, PRKCB1, PTK2, PXN, STAT1, TLN1, TP53 19 AKT1(1), APAF1(1), ATM(7), BAX(1), BCL2L1(2), BID(1), CASP6(1), CASP7(2), CASP9(1), PRKCA(5), PTK2(3), PXN(3), STAT1(2), TLN1(8) 7230004 38 29 37 12 9 17 6 4 2 0 0.99 1.00 568 HSA00510_N_GLYCAN_BIOSYNTHESIS Genes involved in N-glycan biosynthesis ALG1, ALG10, ALG10B, ALG11, ALG12, ALG13, ALG14, ALG2, ALG3, ALG5, ALG6, ALG8, ALG9, B4GALT1, B4GALT2, B4GALT3, DAD1, DDOST, DHDDS, DOLPP1, DPAGT1, DPM1, FUT8, GANAB, GCS1, MAN1A1, MAN1A2, MAN1B1, MAN1C1, MAN2A1, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT5, MGAT5B, RFT1, RPN1, RPN2, ST6GAL1, STT3B 41 ALG1(1), ALG13(8), ALG2(2), ALG5(1), ALG6(3), B4GALT1(1), B4GALT3(2), DHDDS(2), DOLPP1(1), FUT8(2), GANAB(5), MAN1A1(3), MAN1A2(4), MAN1C1(3), MAN2A1(4), MGAT1(1), MGAT2(2), MGAT3(4), MGAT4A(2), MGAT4B(1), MGAT5(3), MGAT5B(4), RPN1(1), ST6GAL1(1), STT3B(1) 11591360 62 45 62 25 23 22 5 6 6 0 0.99 1.00 569 CACAMPATHWAY Calcium functions as a second messenger activating the calcium/calmodulin-dependent kinases, which phosphorylate targets such as CREB. CALM1, CALM2, CALM3, CAMK1, CAMK1G, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CAMKK1, CAMKK2, CREB1, SYT1 14 CAMK1G(2), CAMK2B(2), CAMK2D(1), CAMK4(3), SYT1(3) 3177478 11 10 11 6 4 1 1 4 1 0 0.99 1.00 570 HIFPATHWAY Under normal conditions, hypoxia inducible factor HIF-1 is degraded; under hypoxic conditions, it activates transcription of genes controlled by hpoxic response elements (HREs). ARNT, ASPH, COPS5, CREB1, EDN1, EP300, EPO, HIF1A, HSPCA, JUN, LDHA, NOS3, P4HB, VEGF, VHL 13 ARNT(1), ASPH(3), COPS5(3), EDN1(1), EP300(5), HIF1A(1), JUN(2), NOS3(1), VHL(1) 4582432 18 16 17 10 3 5 6 3 1 0 0.99 1.00 571 BIOSYNTHESIS_OF_STEROIDS DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, IDI1, LSS, MVD, MVK, NQO1, NQO2, PMVK, SC5DL, SQLE, VKORC1 14 DHCR7(2), FDFT1(1), FDPS(1), HMGCR(2), IDI1(1), MVD(1), PMVK(1), SC5DL(1), SQLE(2) 3072458 12 11 12 5 3 6 2 1 0 0 0.99 1.00 572 SIG_INSULIN_RECEPTOR_PATHWAY_IN_CARDIAC_MYOCYTES Genes related to the insulin receptor pathway AKT1, AKT2, AKT3, BRD4, CAP1, CBL, CDC42, CDKN2A, F2RL2, FLOT1, FLOT2, FOXO1A, GRB2, GSK3A, GSK3B, IGFBP1, INPPL1, IRS1, IRS2, IRS4, LNPEP, MAPK1, MAPK3, PARD3, PARD6A, PDK1, PIK3CA, PIK3CD, PIK3R1, PPYR1, PSCD3, PTEN, PTPN1, RAF1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SERPINB6, SFN, SHC1, SLC2A4, SORBS1, SOS1, SOS2, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 46 AKT1(1), AKT3(2), BRD4(2), CAP1(1), CBL(4), CDC42(1), F2RL2(1), FLOT1(2), GSK3A(4), GSK3B(1), INPPL1(3), IRS1(4), IRS2(2), IRS4(3), LNPEP(2), MAPK1(1), MAPK3(2), PARD3(5), PARD6A(2), PDK1(1), PIK3CD(3), PIK3R1(1), PPYR1(3), PTPN1(1), RAF1(1), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KB1(1), SERPINB6(4), SFN(2), SHC1(1), SLC2A4(2), SORBS1(5), SOS1(6), SOS2(4), YWHAB(2), YWHAE(1), YWHAQ(1) 15227900 89 56 89 27 18 32 20 7 12 0 0.99 1.00 573 HSA00071_FATTY_ACID_METABOLISM Genes involved in fatty acid metabolism ACAA1, ACAA2, ACADL, ACADM, ACADS, ACADSB, ACADVL, ACAT1, ACAT2, ACOX1, ACOX3, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, CPT1A, CPT1B, CPT1C, CPT2, CYP4A11, CYP4A22, DCI, ECHS1, EHHADH, GCDH, HADH, HADHA, HADHB, HSD17B10, HSD17B4, PECI 47 ACAA2(1), ACADL(2), ACADM(1), ACADS(3), ACADVL(1), ACAT1(1), ACOX1(2), ACOX3(4), ACSL1(2), ACSL3(1), ACSL5(1), ACSL6(2), ADH1B(1), ADH1C(1), ADH4(2), ADH5(2), ADH7(1), ADHFE1(2), ALDH1B1(3), ALDH2(2), ALDH7A1(1), ALDH9A1(2), CPT1A(3), CPT1C(5), CPT2(2), CYP4A22(1), DCI(1), EHHADH(1), GCDH(1), HADH(1), HADHA(2), HADHB(2), HSD17B4(1), PECI(1) 13166660 59 50 59 30 12 25 9 8 5 0 0.99 1.00 574 HSP27PATHWAY Hsp27 oligomers have molecular chaperone activity and protect heat-stressed cells against apoptosis. ACTA1, APAF1, BCL2, CASP3, CASP9, CYCS, DAXX, FAS, FASLG, HSPB1, HSPB2, IL1A, MAPKAPK2, MAPKAPK3, TNF, TNFRSF6 15 ACTA1(2), APAF1(1), CASP9(1), DAXX(3), FAS(1), FASLG(1), HSPB2(1), MAPKAPK2(1) 3068186 11 10 11 11 4 4 1 1 1 0 0.99 1.00 575 MALATEXPATHWAY The tricarboxylate transfer pathway shuttles acetyl groups of acetyl-CoA between mitochondria and the cytoplasm. ACLY, CS, MDH1, ME1, PC, PDHA1, SLC25A1, SLC25A11 8 MDH1(1), PC(4), PDHA1(2) 2508910 7 7 7 7 0 4 0 1 2 0 0.99 1.00 576 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 29 AKT1(1), CABIN1(5), CAMK1G(2), HDAC5(1), IGF1(2), IGF1R(1), INSR(7), MAP2K6(3), MAPK14(1), MAPK7(1), MEF2A(2), MEF2C(2), MEF2D(2), NFATC2(5), PIK3R1(1), PPP3CA(2), PPP3CB(5), PPP3CC(2), SYT1(3) 8922784 48 34 48 17 13 16 7 8 4 0 0.99 1.00 577 ST_P38_MAPK_PATHWAY p38 is a MAP kinase regulated by cytokines and cellular stress. AKT1, ATF1, CDC42, CREB1, CREB3, CREB5, DUSP1, DUSP10, EEF2K, EIF4E, ELK1, GADD45A, HSPB1, IL1R1, MAP2K3, MAP2K4, MAP2K6, MAP3K10, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAPK1, MAPK11, MAPK12, MAPK13, MAPK14, MAPKAPK2, MAPKAPK5, MKNK1, MKNK2, MYEF2, NFKB1, NR2C2, SRF, TRAF6 35 AKT1(1), CDC42(1), CREB3(2), CREB5(3), DUSP10(3), EEF2K(3), GADD45A(1), MAP2K3(2), MAP2K6(3), MAP3K4(4), MAP3K5(3), MAP3K7(3), MAPK1(1), MAPK13(2), MAPK14(1), MAPKAPK2(1), MAPKAPK5(4), MYEF2(3), NFKB1(2), NR2C2(1), SRF(2), TRAF6(1) 9192632 47 35 47 18 6 18 13 5 5 0 0.99 1.00 578 HSA00260_GLYCINE_SERINE_AND_THREONINE_METABOLISM Genes involved in glycine, serine and threonine metabolism ABP1, AGXT, AGXT2, AKR1B10, ALAS1, ALAS2, AMT, AOC2, AOC3, BHMT, CBS, CHDH, CHKA, CHKB, CTH, DAO, DLD, DMGDH, GAMT, GARS, GATM, GCAT, GLDC, GNMT, HSD3B7, MAOA, MAOB, PEMT, PHGDH, PIPOX, PISD, PSAT1, PSPH, RDH11, RDH12, RDH13, RDH14, SARDH, SARS, SARS2, SDS, SHMT1, SHMT2, TARS, TARS2 45 ABP1(6), AGXT2(2), AKR1B10(1), ALAS1(2), AOC2(2), AOC3(3), CBS(4), CHKA(2), DAO(1), DLD(2), DMGDH(2), GARS(1), GATM(1), GLDC(3), GNMT(1), PHGDH(2), PIPOX(1), PISD(1), PSPH(1), RDH11(2), RDH12(2), RDH13(1), SARDH(4), SARS(2), SARS2(2), SDS(2), TARS(3), TARS2(2) 11695846 58 44 58 25 13 25 12 4 4 0 1.00 1.00 579 CERAMIDEPATHWAY Ceramide is a lipid signaling molecule that can activate proliferative or apoptotic pathways, depending on signaling context, localization, and cell type. BAD, BAX, BCL2, CASP8, CYCS, FADD, MAP2K1, MAP2K4, MAP3K1, MAPK1, MAPK3, MAPK8, NFKB1, NSMAF, PDCD8, RAF1, RELA, RIPK1, SMPD1, TNFRSF1A, TRADD, TRAF2 21 BAX(1), CASP8(1), FADD(1), MAP2K1(2), MAP3K1(3), MAPK1(1), MAPK3(2), MAPK8(2), NFKB1(2), NSMAF(3), RAF1(1), RELA(3), SMPD1(3), TNFRSF1A(2), TRADD(1) 5630140 28 20 28 13 9 9 5 2 3 0 1.00 1.00 580 HSA00061_FATTY_ACID_BIOSYNTHESIS Genes involved in fatty acid biosynthesis ACACA, ACACB, FASN, MCAT, OLAH, OXSM 6 ACACA(4), ACACB(8), MCAT(4), OLAH(1), OXSM(1) 4429352 18 17 17 11 6 10 1 0 1 0 1.00 1.00 581 HSA03060_PROTEIN_EXPORT Genes involved in protein export OXA1L, SEC61A2, SRP19, SRP54, SRP68, SRP72, SRP9, SRPR 8 SEC61A2(1), SRP54(1), SRP68(1), SRP72(1), SRPR(1) 2013536 5 5 5 4 1 2 2 0 0 0 1.00 1.00 582 CHOLESTEROL_BIOSYNTHESIS C10orf110, CYP51A1, DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, HMGCS1, IDI1, LSS, MVD, MVK, NSDHL, PMVK, SC4MOL, SC5DL, SQLE 15 DHCR7(2), FDFT1(1), FDPS(1), HMGCR(2), HMGCS1(1), IDI1(1), MVD(1), NSDHL(1), PMVK(1), SC5DL(1), SQLE(2) 3632980 14 13 14 5 3 7 2 2 0 0 1.00 1.00 583 HSA03010_RIBOSOME Genes involved in ribosome C15orf15, FAU, hCG_1644323, hCG_1984468, hCG_2041321, hCG_21078, hCG_26523, LOC283412, LOC284064, LOC284230, LOC284288, LOC284393, LOC285053, LOC342994, LOC347292, LOC388720, LOC389342, LOC390876, LOC391656, LOC400652, LOC402057, LOC439992, LOC440055, LOC440589, LOC440733, LOC440737, LOC441377, LOC441876, LOC441907, MRPL13, MRPS7, RPL10A, RPL10L, RPL11, RPL12, RPL13, RPL13A, RPL14, RPL18, RPL18A, RPL19, RPL21, RPL22L1, RPL23A, RPL23AP2, RPL24, RPL26, RPL27, RPL27A, RPL28, RPL29, RPL3, RPL30, RPL31, RPL32, RPL34, RPL35, RPL35A, RPL36A, RPL36AL, RPL37, RPL37A, RPL38, RPL39, RPL3L, RPL41, RPL6, RPL7, RPL8, RPL9, RPS10, RPS11, RPS12, RPS13, RPS15A, RPS16, RPS18, RPS2, RPS20, RPS21, RPS23, RPS24, RPS25, RPS26, RPS26P10, RPS27, RPS28, RPS29, RPS3, RPS3A, RPS4Y1, RPS5, RPS6, RPS7, RPS8, RPS9, RPSA, tcag7.23 67 MRPS7(2), RPL10L(4), RPL14(1), RPL19(1), RPL28(1), RPL30(1), RPL32(1), RPL37(1), RPL3L(1), RPL7(1), RPL8(4), RPS11(1), RPS18(2), RPS2(1), RPS21(1), RPS26(1), RPS6(1), RPS8(1) 6262930 26 23 25 12 5 10 6 3 2 0 1.00 1.00 584 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(2), MAP3K14(1), NFKB1(2), RELA(3) 2511402 8 6 8 2 1 2 1 1 3 0 1.00 1.00 585 HSA00670_ONE_CARBON_POOL_BY_FOLATE Genes involved in one carbon pool by folate ALDH1L1, AMT, ATIC, DHFR, FTCD, GART, MTFMT, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 16 ALDH1L1(3), GART(2), MTHFD1(3), MTHFD1L(2), MTHFD2(3), MTHFR(2), MTR(5), TYMS(1) 5119102 21 19 21 13 4 6 8 2 1 0 1.00 1.00 586 ST_TUMOR_NECROSIS_FACTOR_PATHWAY Tumor necrosis factor is a pro-inflammatory cytokine that activates NF-kB and c-Jun. BAG4, BIRC2, BIRC3, CASP3, CASP8, CFLAR, FADD, HRB, IKBKG, JUN, MAP2K4, MAP3K3, MAP3K7, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, NR2C2, RALBP1, RIPK1, TNF, TNFAIP3, TNFRSF1A, TNFRSF1B, TRADD, TRAF2 27 BAG4(1), BIRC3(3), CASP8(1), CFLAR(1), FADD(1), JUN(2), MAP3K7(3), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), NR2C2(1), RALBP1(1), TNFAIP3(4), TNFRSF1A(2), TNFRSF1B(1), TRADD(1) 7490062 33 26 33 15 7 11 4 7 4 0 1.00 1.00 587 ST_WNT_CA2_CYCLIC_GMP_PATHWAY Some Wnt glycoprotein/Frizzled receptor interactions increase intracellular calcium and decrease cGMP. BF, CAMK2A, CAMK2B, CAMK2D, CAMK2G, DAG1, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, NFAT5, PDE6A, PDE6B, PDE6C, PDE6D, PDE6G, PDE6H, SLC6A13, TF 19 CAMK2B(2), CAMK2D(1), DAG1(1), ITPKA(1), ITPKB(3), ITPR1(5), ITPR2(11), ITPR3(3), NFAT5(3), PDE6A(3), PDE6B(3), PDE6H(2), SLC6A13(4), TF(7) 9814920 49 39 49 15 20 14 8 1 6 0 1.00 1.00 588 HSA00642_ETHYLBENZENE_DEGRADATION Genes involved in ethylbenzene degradation ARD1A, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ESCO1, ESCO2, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1 11 DHRS2(1), ESCO1(1), MYST3(11), MYST4(3), PNPLA3(1), SH3GLB1(1) 4289088 18 15 18 8 5 6 3 1 3 0 1.00 1.00 589 IGF1MTORPATHWAY Growth factor IGF-1 activates AKT, Gsk3-beta, and mTOR to promote muscle hypertrophy. AKT1, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF4E, EIF4EBP1, FRAP1, GSK3B, IGF1, IGF1R, INPPL1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1 17 AKT1(1), EIF2B5(1), GSK3B(1), IGF1(2), IGF1R(1), INPPL1(3), PDK2(2), PDPK1(1), PIK3R1(1), RPS6(1), RPS6KB1(1) 4542560 15 15 15 8 1 5 2 3 4 0 1.00 1.00 590 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 21 AKT1(1), BCR(1), CRKL(1), FOS(1), HRAS(2), JAK2(3), JUN(2), MAP2K1(2), MAP3K1(3), MAPK3(2), MAPK8(2), MYC(1), PIK3R1(1), RAF1(1), SOS1(6), STAT1(2), STAT5A(2) 6979024 33 27 33 7 9 10 8 4 2 0 1.00 1.00 591 MAPKPATHWAY The mitogen-activated protein (MAP) kinase pathway is a common signaling mechanism and has four main sub-pathways: Erk, JNK/SAPK, p53, and ERK5. ARAF1, ATF2, BRAF, CEBPA, CHUK, CREB1, DAXX, ELK1, FOS, GRB2, HRAS, IKBKB, JUN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K14, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8, MAP3K9, MAP4K1, MAP4K2, MAP4K3, MAP4K4, MAP4K5, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK4, MAPK6, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, MAPKAPK5, MAX, MEF2A, MEF2B, MEF2C, MEF2D, MKNK1, MKNK2, MYC, NFKB1, NFKBIA, PAK1, PAK2, PDZGEF1, RAC1, RAF1, RELA, RIPK1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KA5, RPS6KB1, RPS6KB2, SHC1, SP1, STAT1, TGFB1, TGFB2, TGFB3, TGFBR1, TRADD, TRAF2 85 ATF2(2), BRAF(7), CEBPA(1), CHUK(2), DAXX(3), FOS(1), HRAS(2), IKBKB(3), JUN(2), MAP2K1(2), MAP2K2(2), MAP2K3(2), MAP2K5(2), MAP2K6(3), MAP3K1(3), MAP3K11(2), MAP3K12(2), MAP3K13(5), MAP3K14(1), MAP3K4(4), MAP3K5(3), MAP3K6(1), MAP3K7(3), MAP3K9(4), MAP4K1(2), MAP4K2(1), MAP4K3(5), MAP4K4(6), MAP4K5(1), MAPK1(1), MAPK10(1), MAPK13(2), MAPK14(1), MAPK3(2), MAPK4(1), MAPK6(2), MAPK7(1), MAPK8(2), MAPK9(1), MAPKAPK2(1), MAPKAPK5(4), MEF2A(2), MEF2C(2), MEF2D(2), MYC(1), NFKB1(2), PAK1(3), PAK2(1), RAC1(2), RAF1(1), RELA(3), RPS6KA1(4), RPS6KA2(2), RPS6KA3(1), RPS6KA4(3), RPS6KA5(3), RPS6KB1(1), SHC1(1), SP1(1), STAT1(2), TGFB1(1), TGFB2(1), TRADD(1) 26589284 136 80 135 53 34 46 26 12 18 0 1.00 1.00 592 SA_BONE_MORPHOGENETIC Bone morphogenetic protein binds to its receptor to induce ectopic bone formation and promote development of the viscera. BMP1, BMPR1A, BMPR1B, BMPR2, MADH1, MADH4, MADH6 4 BMPR1A(3) 1683524 3 3 3 1 2 0 0 1 0 0 1.00 1.00 593 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(3), CAD(10), CANT1(3), CDA(1), CTPS(2), CTPS2(2), DCK(1), DPYD(7), DPYS(4), ENTPD1(1), ENTPD3(1), ENTPD5(1), ENTPD6(3), NME4(1), NME7(2), NT5C1A(2), NT5C1B(2), NT5C2(3), NT5C3(4), NT5E(2), PNPT1(2), POLA1(5), POLA2(3), POLD1(2), POLD3(1), POLE2(2), POLE4(1), POLR1A(4), POLR1B(4), POLR1C(1), POLR1D(1), POLR2A(2), POLR2B(2), POLR2D(1), POLR2E(1), POLR2H(1), POLR3A(3), POLR3B(2), POLR3G(1), POLR3H(1), PRIM1(2), RFC5(2), RRM1(2), RRM2B(2), TK2(1), TXNRD1(2), TXNRD2(3), TYMS(1), UMPS(1), UPP1(3), UPP2(1), UPRT(1) 21837574 116 72 114 62 27 48 20 6 15 0 1.00 1.00 594 HSA03050_PROTEASOME Genes involved in proteasome PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMC2, PSMC3, PSMD1, PSMD11, PSMD12, PSMD13, PSMD2, PSMD6 22 PSMA4(1), PSMA5(1), PSMB3(1), PSMB4(2), PSMB6(1), PSMC2(4), PSMC3(1), PSMD1(2), PSMD11(1), PSMD12(1), PSMD13(1) 4277518 16 15 16 12 5 8 2 0 1 0 1.00 1.00 595 EPONFKBPATHWAY The cytokine erythropoietin (Epo) prevents stress-induced neuronal apoptosis by stimulating anti-apoptotic pathways through JAK2 kinase and NF-kB. ARNT, CDKN1A, EPO, EPOR, GRIN1, HIF1A, JAK2, NFKB1, NFKBIA, RELA, SOD2 11 ARNT(1), EPOR(2), GRIN1(1), HIF1A(1), JAK2(3), NFKB1(2), RELA(3), SOD2(1) 3452132 14 10 14 2 3 5 2 1 3 0 1.00 1.00 596 G1_TO_S_CELL_CYCLE_REACTOME ATM, CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNG2, CCNH, CDC25A, CDC45L, CDK2, CDK4, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CREB3, CREB3L1, CREB3L3, CREB3L4, CREBL1, CREBL1, TNXB, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, FLJ14001, GADD45A, GBA2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MNAT1, MYC, MYT1, NACA, NACA, FKSG17, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, POLA2, POLE, POLE2, PRIM1, PRIM2A, RB1, RBL1, RPA1, RPA2, RPA3, TFDP1, TFDP2, TP53, WEE1 63 ATM(7), CCNA1(1), CCNB1(1), CCND1(1), CCND2(3), CCND3(1), CCNE2(2), CDK2(1), CDK7(1), CDKN2C(1), CDKN2D(1), CREB3(2), CREB3L3(1), CREB3L4(2), E2F1(3), GADD45A(1), GBA2(2), MCM2(1), MCM3(1), MCM4(4), MCM5(6), MCM6(2), MCM7(3), MDM2(1), MYC(1), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), POLA2(3), POLE2(2), PRIM1(2), RB1(7), RBL1(6), TFDP2(1), TNXB(16), WEE1(2) 20615604 93 68 93 28 21 38 14 7 13 0 1.00 1.00 597 IL10PATHWAY The cytokine IL-10 inhibits the inflammatory response by macrophages via activation of heme oxygenase 1. BLVRA, BLVRB, HMOX1, IL10, IL10RA, IL10RB, IL1A, IL6, JAK1, STAT1, STAT3, STAT5A, TNF 13 BLVRA(2), HMOX1(1), IL10(1), IL10RA(1), JAK1(1), STAT1(2), STAT3(1), STAT5A(2) 3285880 11 10 11 8 3 5 2 1 0 0 1.00 1.00 598 IL2RBPATHWAY The beta subunit of the IL-2 receptor is required for IL-2 and IL-15 signal recognition and activates JAK kinase on ligand binding. AKT1, BAD, BCL2, BCL2L1, CBL, CFLAR, CRKL, E2F1, FOS, GRB2, HRAS, IL2RA, IL2RB, IL2RG, IRS1, JAK1, JAK3, MAPK1, MAPK3, MYC, NMI, PIK3CA, PIK3R1, PPIA, PTPN6, RAF1, RPS6KB1, SHC1, SOCS1, SOCS3, SOS1, STAT5A, STAT5B, SYK, TNFRSF6, TNFSF6, ZNFN1A3 33 AKT1(1), BCL2L1(2), CBL(4), CFLAR(1), CRKL(1), E2F1(3), FOS(1), HRAS(2), IL2RB(2), IL2RG(1), IRS1(4), JAK1(1), JAK3(7), MAPK1(1), MAPK3(2), MYC(1), NMI(1), PIK3R1(1), RAF1(1), RPS6KB1(1), SHC1(1), SOS1(6), STAT5A(2), SYK(1) 9289642 48 35 48 16 10 22 9 3 4 0 1.00 1.00 599 TRANSLATION_FACTORS ANKHD1, ANKHD1, MASK_BP3, EEF1A2, EEF1B2, EEF1D, EEF1G, EEF2, EEF2K, EIF1AX, EIF1AY, EIF2AK1, EIF2AK2, EIF2AK3, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF3S1, EIF3S10, EIF3S2, EIF3S3, EIF3S4, EIF3S5, EIF3S6, EIF3S7, EIF3S8, EIF3S9, EIF4A1, EIF4A2, EIF4E, EIF4EBP1, EIF4EBP2, EIF4G1, EIF4G3, EIF5, EIF5A, EIF5B, ETF1, GSPT2, ITGB4BP, KIAA0664, PABPC1, PABPC3, PABPC1, LOC341315, PAIP1, PAIP1, LOC388345, SLC35A4, SUI1, WBSCR1 37 EEF1A2(2), EEF1B2(1), EEF1D(1), EEF1G(2), EEF2(1), EEF2K(3), EIF2AK3(7), EIF2B1(1), EIF2B2(2), EIF2B3(1), EIF2B5(1), EIF4A1(3), EIF4A2(3), EIF4G1(8), EIF4G3(3), EIF5(1), EIF5B(1), ETF1(2), KIAA0664(1), PABPC1(1), PABPC3(7), PAIP1(1) 12059144 53 44 53 29 10 21 15 2 5 0 1.00 1.00 600 GLYCINE_SERINE_AND_THREONINE_METABOLISM ABP1, AGXT, AGXT2, ALAS1, ALAS2, AMT, AOC2, AOC3, ATP6V0C, SHMT1, BHMT, CBS, CHDH, CHKA, CHKB, CHKB, CPT1B, CTH, DAO, DLD, DMGDH, GAMT, GARS, GATM, GCAT, GLDC, MAOA, MAOB, PEMT, PISD, PLCB2, PLCG1, PLCG2, PSPH, SARDH, SARS, SHMT1, SHMT2, TARS 37 ABP1(6), AGXT2(2), ALAS1(2), AOC2(2), AOC3(3), CBS(4), CHKA(2), DAO(1), DLD(2), DMGDH(2), GARS(1), GATM(1), GLDC(3), PISD(1), PLCB2(5), PLCG1(2), PLCG2(3), PSPH(1), SARDH(4), SARS(2), TARS(3) 11524254 52 40 52 23 13 21 11 3 4 0 1.00 1.00 601 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 37 AKT1(1), ATF2(2), CDC42(1), DLD(2), DUSP10(3), DUSP4(1), GAB1(2), GADD45A(1), GCK(1), JUN(2), MAP2K5(2), MAP3K1(3), MAP3K11(2), MAP3K12(2), MAP3K13(5), MAP3K4(4), MAP3K5(3), MAP3K7(3), MAP3K9(4), MAPK10(1), MAPK7(1), MAPK8(2), MAPK9(1), MYEF2(3), NFATC3(3), NR2C2(1), PAPPA(8), SHC1(1), TRAF6(1), ZAK(1) 13536722 67 49 67 25 18 26 13 6 4 0 1.00 1.00 602 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 58 ALG2(2), BAK1(1), BAX(1), BTK(5), CAD(10), CASP10(4), CASP8(1), CASP8AP2(6), CDK2AP1(1), CSNK1A1(1), DAXX(3), DFFA(1), EGFR(9), EPHB2(5), FADD(1), FAF1(1), FAIM2(1), MAP3K1(3), MAP3K5(3), MAPK1(1), MAPK10(1), MAPK8(2), MAPK8IP1(2), MAPK8IP3(6), MAPK9(1), MET(3), NFAT5(3), NFKB1(2), NFKB2(2), NFKBIB(1), NFKBIL1(1), NFKBIL2(5), NR0B2(1), PTPN13(3), RALBP1(1), ROCK1(5), SMPD1(3), TNFRSF6B(1), TPX2(1), TUFM(1) 20075552 105 64 104 32 27 40 18 7 13 0 1.00 1.00 603 RNA_POLYMERASE POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT 14 POLR1B(4), POLR2A(2), POLR2B(2), POLR2D(1), POLR2E(1), POLR2H(1) 3743518 11 10 11 5 3 4 0 1 3 0 1.00 1.00 604 MRNA_PROCESSING_REACTOME BRUNOL4, C10orf9, C20orf14, CD2BP2, CDC40, CLK2, CLK3, CLK4, COL2A1, CPSF1, CPSF2, CPSF3, CPSF4, CSTF1, CSTF2, CSTF2T, CSTF3, CUGBP1, CUGBP2, DDIT3, DDX1, DDX20, DHX15, DHX16, DHX38, DHX8, DHX9, DICER1, DNAJC8, FLJ10748, FNBP3, FUS, FUSIP1, GIPC1, HEAB, HNRPA2B1, HNRPA3, HNRPA3P1, HNRPA3, LOC387933, HNRPA3P1, HNRPA3, LOC389395, HNRPAB, HNRPC, HNRPC, HNRPCL1, LOC390615, LOC440563, HNRPD, HNRPH1, HNRPH2, HNRPL, HNRPR, HNRPU, HRMT1L2, LSM2, LSM7, METTL3, NCBP1, NCBP2, NONO, NUDT21, NXF1, PABPN1, PAPOLA, PHF5A, POLR2A, PPM1G, PRPF18, PRPF3, PRPF4, PRPF4B, PRPF8, PSKH1, PTBP1, PTBP2, RBM17, RBM5, RNGTT, RNMT, RNPC2, RNPS1, SF3A1, SF3A2, SF3A3, SF3B1, SF3B2, SF3B4, SF3B5, SF4, SFRS10, SFRS12, SFRS14, SFRS16, SFRS2, SFRS4, SFRS5, SFRS6, SFRS7, SFRS8, SFRS9, SMC1L1, SNRP70, SNRPA, SNRPA1, SNRPB, SNRPB2, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, SNRPN, SNRPN, PAR1, SNRPN, SNURF, SPOP, SRPK1, SRPK2, SRRM1, SUPT5H, TMP21, TXNL4A, U2AF1, U2AF2, WDR57, XRN2 91 CD2BP2(2), CDC40(2), CLK2(2), CLK3(2), CLK4(2), COL2A1(8), CPSF1(3), CPSF2(2), CPSF3(1), CPSF4(4), CSTF2(2), CSTF2T(2), CSTF3(2), DDX1(5), DHX15(2), DHX16(2), DHX8(2), DHX9(7), DICER1(7), FUS(1), METTL3(1), NCBP1(2), NONO(1), NXF1(2), PAPOLA(1), POLR2A(2), PRPF3(1), PRPF4(3), PRPF4B(4), PRPF8(9), PSKH1(1), PTBP2(1), RBM17(1), RBM5(1), RNGTT(1), RNPS1(1), SF3A2(2), SF3A3(1), SF3B1(3), SF3B2(2), SF3B4(1), SF4(3), SFRS12(1), SFRS14(6), SFRS2(2), SFRS4(1), SFRS6(3), SFRS8(3), SNRPA(1), SNRPB(3), SNRPD1(1), SNRPD2(2), SNRPN(1), SPOP(1), SRPK1(2), SRPK2(1), SRRM1(2), SUPT5H(3), U2AF2(1), XRN2(4) 28537138 142 82 136 48 36 53 32 10 11 0 1.00 1.00 605 DNA_REPLICATION_REACTOME ASK, CDC45L, CDC6, CDC7, CDK2, CDT1, DIAPH2, GMNN, MCM10, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, NACA, NACA, FKSG17, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, POLA, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, PRIM1, PRIM2A, RFC1, RFC2, RFC3, RFC4, RFC5, RPA1, RPA2, RPA3, RPA4, RPS27A, RPS27A, LOC388720, LOC389425, UBA52, UBB, UBC 42 CDC6(4), CDC7(1), CDK2(1), GMNN(2), MCM10(4), MCM2(1), MCM3(1), MCM4(4), MCM5(6), MCM6(2), MCM7(3), ORC1L(1), ORC2L(1), ORC3L(1), ORC5L(1), POLA2(3), POLD1(2), POLD3(1), POLE2(2), PRIM1(2), RFC1(1), RFC4(4), RFC5(2), RPA4(2), UBB(1), UBC(1) 13878660 54 45 54 24 13 18 13 1 9 0 1.00 1.00 606 HSA00100_BIOSYNTHESIS_OF_STEROIDS Genes involved in biosynthesis of steroids CYP27B1, CYP51A1, DHCR24, DHCR7, EBP, FDFT1, FDPS, GGCX, GGPS1, HMGCR, HSD17B7, IDI1, IDI2, LSS, MVD, MVK, NQO1, NSDHL, PMVK, SC4MOL, SC5DL, SQLE, TM7SF2, VKORC1 24 DHCR7(2), EBP(1), FDFT1(1), FDPS(1), GGPS1(1), HMGCR(2), HSD17B7(1), IDI1(1), IDI2(1), MVD(1), NSDHL(1), PMVK(1), SC5DL(1), SQLE(2), TM7SF2(2) 5284998 19 17 19 8 4 10 4 1 0 0 1.00 1.00 607 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(5), POLA2(3), POLB(1), POLD1(2), POLD3(1), POLE2(2), POLE4(1), POLG(2), POLG2(1), POLI(2), POLK(3), POLL(1), POLM(1), POLQ(18), PRIM1(2), REV1(5), REV3L(4), RFC5(2) 10953230 56 39 54 14 16 19 13 4 4 0 1.00 1.00 608 RHOPATHWAY RhoA is a G protein whose active form stabilizes actin structures such as focal adhesions and activates Rock1, which phosphorylates myosin light chains. ACTR2, ACTR3, ARHA, ARHGAP1, ARHGAP4, ARHGAP5, ARHGAP6, ARHGEF1, ARHGEF11, ARHGEF5, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, BAIAP2, CFL1, DIAPH1, GSN, LIMK1, MYL2, MYLK, OPHN1, PFN1, PIP5K1A, PIP5K1B, PPP1R12B, ROCK1, SRC, TLN1, VCL 30 ACTR2(1), ARHGAP1(1), ARHGAP4(1), ARHGAP6(5), ARHGEF1(2), ARHGEF11(7), ARHGEF5(1), ARPC1A(2), ARPC1B(1), CFL1(3), DIAPH1(1), GSN(2), LIMK1(1), MYL2(1), MYLK(7), OPHN1(1), PIP5K1A(4), PIP5K1B(1), PPP1R12B(3), ROCK1(5), TLN1(8), VCL(2) 12577124 60 43 58 20 10 28 13 6 3 0 1.00 1.00 609 HSA03020_RNA_POLYMERASE Genes involved in RNA polymerase POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, ZNRD1 23 POLR1A(4), POLR1B(4), POLR1C(1), POLR1D(1), POLR2A(2), POLR2B(2), POLR2D(1), POLR2E(1), POLR2H(1), POLR3A(3), POLR3B(2), POLR3G(1), POLR3H(1) 6292478 24 20 23 20 7 11 1 2 3 0 1.00 1.00 610 HSA00632_BENZOATE_DEGRADATION_VIA_COA_LIGATION Genes involved in benzoate degradation via CoA ligation ACAT1, ACAT2, ACOT11, ACYP1, ACYP2, ARD1A, CARKL, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ECHS1, EHHADH, ESCO1, ESCO2, FN3K, GCDH, HADHA, ITGB1BP3, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1, YOD1 23 ACAT1(1), ACOT11(1), DHRS2(1), EHHADH(1), ESCO1(1), GCDH(1), HADHA(2), MYST3(11), MYST4(3), PNPLA3(1), SH3GLB1(1) 6846592 24 21 24 16 6 8 4 1 5 0 1.00 1.00 611 HSA04120_UBIQUITIN_MEDIATED_PROTEOLYSIS Genes involved in ubiquitin mediated proteolysis ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, BTRC, CDC16, CDC20, CDC23, CDC26, CDC27, CUL1, CUL2, CUL3, FBXW11, FBXW7, FZR1, ITCH, LOC728919, RBX1, SKP1, SKP2, SMURF1, SMURF2, TCEB1, TCEB2, UBA1, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2D4, UBE2E1, UBE2E2, UBE2E3, VHL, WWP1, WWP2 37 ANAPC1(4), ANAPC4(3), ANAPC5(3), BTRC(1), CDC27(3), CUL1(3), ITCH(2), RBX1(1), SKP1(1), SKP2(1), SMURF1(4), SMURF2(1), UBA1(5), UBE2C(1), UBE2D1(1), UBE2D2(1), UBE2E2(1), UBE2E3(1), VHL(1), WWP1(1), WWP2(1) 10101144 40 33 40 11 12 12 5 6 5 0 1.00 1.00 612 PYRIMIDINE_METABOLISM AK3, AK3L1, AK3L1, AK3L2, CAD, CANT1, CDA, CMPK, CTPS, CTPS2, DCK, DCTD, DHODH, DPYD, DPYS, DTYMK, DUT, ECGF1, ENTPD1, ITPA, NME1, NME2, NP, NT5C, NT5E, NT5M, NUDT2, POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT, POLS, RRM1, RRM2, TK1, TK2, TXNRD1, TYMS, UCK1, UCK2, UMPS, UNG, UPB1, UPP1 54 CAD(10), CANT1(3), CDA(1), CTPS(2), CTPS2(2), DCK(1), DPYD(7), DPYS(4), ENTPD1(1), NT5E(2), POLB(1), POLD1(2), POLG(2), POLL(1), POLQ(18), POLR1B(4), POLR2A(2), POLR2B(2), POLR2D(1), POLR2E(1), POLR2H(1), RRM1(2), TK2(1), TXNRD1(2), TYMS(1), UMPS(1), UPP1(3) 15680732 78 53 76 30 16 36 11 6 9 0 1.00 1.00 613 DEATHPATHWAY Death receptors such as Fas and DR3, 4, and 5 transduce pro-apoptotic signaling by oligomerizing to activate the caspase cascade. APAF1, BCL2, BID, BIRC2, BIRC3, BIRC4, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHUK, CYCS, DFFA, DFFB, FADD, GAS2, LMNA, MAP3K14, NFKB1, NFKBIA, RELA, RIPK1, SPTAN1, TNFRSF10A, TNFRSF10B, TNFRSF25, TNFSF10, TNFSF12, TRADD, TRAF2 32 APAF1(1), BID(1), BIRC3(3), CASP10(4), CASP6(1), CASP7(2), CASP8(1), CASP9(1), CFLAR(1), CHUK(2), DFFA(1), DFFB(2), FADD(1), GAS2(2), MAP3K14(1), NFKB1(2), RELA(3), SPTAN1(2), TNFRSF10A(1), TNFRSF10B(1), TRADD(1) 9154184 34 27 34 14 9 12 2 4 7 0 1.00 1.00 614 RNA_TRANSCRIPTION_REACTOME CCNH, CDK7, ERCC3, GTF2A2, GTF2B, GTF2E1, GTF2E2, GTF2F2, GTF2H1, GTF2H2, GTF2H4, ILK, MGC9850, MNAT1, POLR1A, POLR1B, POLR2A, POLR2B, POLR2C, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR3B, POLR3D, POLR3E, POLR3H, POLR3K, TAF12, TAF13, TAF5, TAF6, TAF7, TAF9, TBP, VARS2L 36 CDK7(1), ERCC3(2), GTF2B(1), GTF2E1(1), GTF2H2(1), GTF2H4(1), ILK(1), POLR1A(4), POLR1B(4), POLR2A(2), POLR2B(2), POLR2E(1), POLR2H(1), POLR3B(2), POLR3D(1), POLR3E(2), POLR3H(1), TAF5(2), TAF9(2), TBP(1) 9538486 33 26 33 22 11 9 3 3 7 0 1.00 1.00 615 HSA00790_FOLATE_BIOSYNTHESIS Genes involved in folate biosynthesis ALPI, ALPL, ALPP, ALPPL2, ASCC3, ASCC3L1, ATP13A2, DDX18, DDX19A, DDX23, DDX4, DDX41, DDX47, DDX50, DDX51, DDX52, DDX54, DDX55, DDX56, DHFR, DHX58, ENTPD7, EP400, ERCC2, ERCC3, FPGS, GCH1, GGH, IFIH1, MOV10L1, NUDT5, NUDT8, PTS, QDPR, RAD54B, RAD54L, RUVBL2, SETX, SKIV2L2, SMARCA2, SMARCA5, SPR 41 ALPI(1), ALPL(3), ALPP(1), ALPPL2(1), ASCC3(9), ATP13A2(1), DDX18(2), DDX19A(2), DDX23(6), DDX4(1), DDX41(2), DDX50(1), DDX52(1), DDX54(3), DDX55(1), DDX56(1), ENTPD7(1), ERCC2(3), ERCC3(2), GCH1(2), IFIH1(3), NUDT8(1), RAD54L(1), SETX(11), SKIV2L2(2), SMARCA2(3), SPR(1) 17193732 66 45 66 24 18 29 12 3 4 0 1.00 1.00 616 HSA00785_LIPOIC_ACID_METABOLISM Genes involved in lipoic acid metabolism LIAS, LIPT1, LOC387787 2 407442 0 0 0 0 0 0 0 0 0 0 1.00 1.00