rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q 1 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(3), HLA-DRA(4), HLA-DRB1(1), IL3(3) 661548 11 11 10 2 5 1 0 3 0 2 0.00166 0.484 2 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 232 ADCYAP1R1(1), ADORA1(5), ADORA2A(3), ADORA2B(1), ADORA3(3), ADRA1A(5), ADRA1B(4), ADRA2A(3), ADRB1(2), ADRB3(1), AGTR1(3), AGTR2(4), AVPR1A(3), AVPR1B(3), AVPR2(6), BDKRB2(2), BRS3(1), C3AR1(2), C5AR1(2), CALCR(3), CALCRL(5), CCKAR(1), CCKBR(3), CGA(1), CHRM1(3), CHRM2(8), CHRM3(4), CHRM5(1), CNR1(3), CRHR1(1), CRHR2(4), CTSG(2), CYSLTR1(3), CYSLTR2(3), DRD1(1), DRD2(3), DRD3(3), DRD5(2), EDNRA(4), EDNRB(7), F2(2), F2RL2(2), FPR1(2), FSHB(1), FSHR(6), GABBR1(4), GABBR2(3), GABRA1(2), GABRA2(6), GABRA3(4), GABRA4(6), GABRA6(4), GABRB1(6), GABRB2(4), GABRB3(5), GABRE(5), GABRG1(7), GABRG2(8), GABRG3(5), GABRP(2), GABRQ(7), GABRR1(2), GABRR2(3), GALR1(1), GH1(1), GH2(1), GHR(6), GHRHR(2), GHSR(5), GLP1R(2), GLP2R(3), GLRA1(2), GLRA2(2), GLRA3(7), GLRB(6), GNRHR(4), GPR156(6), GPR50(5), GPR63(2), GPR83(1), GRIA2(10), GRIA3(5), GRIA4(12), GRID1(15), GRID2(10), GRIK1(5), GRIK2(10), GRIK4(11), GRIK5(5), GRIN1(1), GRIN2A(15), GRIN2B(8), GRIN2C(2), GRIN2D(3), GRIN3A(3), GRM1(9), GRM2(3), GRM3(5), GRM4(7), GRM5(8), GRM6(9), GRM7(8), GRM8(7), GRPR(3), GZMA(2), HCRTR1(1), HCRTR2(1), HRH1(1), HRH2(4), HRH4(2), HTR1A(3), HTR1B(3), HTR1D(2), HTR1E(5), HTR1F(2), HTR2A(2), HTR2B(1), HTR2C(6), HTR4(2), HTR5A(2), HTR7(6), LEP(1), LEPR(5), LHB(1), LHCGR(4), MAS1(1), MC2R(2), MC3R(1), MC4R(3), MC5R(4), MCHR1(6), MCHR2(2), MLNR(3), MTNR1B(3), NMUR1(4), NMUR2(6), NPBWR1(3), NPFFR2(3), NPY1R(4), NPY2R(5), NPY5R(1), NR3C1(3), NTSR1(1), NTSR2(4), OPRD1(1), OPRK1(5), OPRM1(1), OXTR(2), P2RX1(1), P2RX2(1), P2RX3(2), P2RX4(2), P2RX5(1), P2RX7(2), P2RY1(3), P2RY10(6), P2RY13(2), P2RY14(4), P2RY2(2), P2RY4(6), PARD3(5), PPYR1(1), PRL(2), PRLR(2), PRSS1(3), PRSS2(1), PRSS3(4), PTAFR(1), PTGER2(1), PTGER3(6), PTGFR(6), PTGIR(1), PTH2R(6), RXFP1(2), RXFP2(8), SCTR(3), SSTR1(4), SSTR2(2), SSTR4(2), TAAR1(3), TAAR2(2), TAAR5(5), TAAR6(2), TAAR8(1), TAAR9(1), TACR1(2), TACR2(1), TACR3(4), THRA(2), THRB(4), TRHR(6), TRPV1(3), TSHR(6), VIPR1(3), VIPR2(3) 48166910 709 118 706 266 272 154 15 210 58 0 0.00225 0.484 3 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 13 AXIN1(1), CREBBP(21), CTNNB1(8), EP300(13), GSK3B(7), HDAC1(2), LDB1(3), LEF1(4), PITX2(2), TRRAP(17), WNT1(1) 6009423 79 46 78 21 33 25 1 8 12 0 0.00281 0.484 4 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(21), EP300(13), ESR1(12), MAPK1(2), MAPK3(2), PELP1(2), SRC(3) 3251889 55 34 55 13 18 20 1 9 7 0 0.00324 0.484 5 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 CD28(1), CD3D(1), CD3G(2), CTLA4(1), GRB2(2), HLA-DRA(4), HLA-DRB1(1), ICOS(1), IL2(3), ITK(8), LCK(2), PIK3R1(5), PTPN11(2) 2385350 33 23 32 7 7 9 2 8 5 2 0.00436 0.484 6 GPCRDB_CLASS_A_RHODOPSIN_LIKE ADORA1, ADORA2A, ADORA2B, ADORA3, ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2C, ADRB1, ADRB2, ADRB3, AGTR1, AGTR2, AGTRL1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BLR1, BRS3, C3AR1, C5R1, CCBP2, CCKAR, CCKBR, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CCRL1, CCRL2, CHML, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CMKLR1, CMKOR1, CNR1, CNR2, CX3CR1, CXCR3, CXCR4, DRD1, DRD2, DRD3, DRD4, DRD5, EDNRA, EDNRB, ELA3A, F2R, F2RL1, F2RL2, F2RL3, FPR1, FPRL1, FPRL2, FSHR, GALR1, GALR2, GALR3, GALT, GHSR, GNB2L1, GPR10, GPR147, GPR17, GPR173, GPR174, GPR23, GPR24, GPR27, GPR3, GPR30, GPR35, GPR37, GPR37L1, GPR4, GPR44, GPR50, GPR6, GPR63, GPR74, GPR77, GPR83, GPR85, GPR87, GPR92, GRPR, HCRTR1, HCRTR2, HRH1, HRH2, HRH3, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, HTR7, LOC93164, IL8RA, IL8RB, LHCGR, LTB4R, MAS1, MC1R, MC3R, MC4R, MC5R, MLNR, MTNR1A, MTNR1B, NMBR, NMUR1, NMUR2, NPY1R, NPY2R, NPY5R, NPY6R, NTSR1, NTSR2, OPN1SW, OPN3, OPRD1, OPRK1, OPRL1, OPRM1, OR10A5, OR11A1, OR12D3, OR1C1, OR1F1, OR1Q1, OR2H1, OR5V1, OR5V1, OR12D3, OR7A5, OR7C1, OR8B8, OXTR, P2RY1, P2RY10, P2RY11, P2RY12, P2RY13, P2RY14, P2RY2, P2RY5, P2RY6, PPYR1, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, Rgr, RGR, RHO, RRH, SSTR1, SSTR2, SSTR3, SSTR4, SUCNR1, TBXA2R, TRHR 162 ADORA1(5), ADORA2A(3), ADORA2B(1), ADORA3(3), ADRA1A(5), ADRA1B(4), ADRA1D(2), ADRA2A(3), ADRB1(2), ADRB3(1), AGTR1(3), AGTR2(4), AVPR1A(3), AVPR1B(3), AVPR2(6), BDKRB2(2), BRS3(1), C3AR1(2), CCBP2(5), CCKAR(1), CCKBR(3), CCR1(5), CCR3(3), CCR5(1), CCR6(2), CCR7(1), CCR8(4), CCR9(4), CCRL1(2), CHML(4), CHRM1(3), CHRM2(8), CHRM3(4), CHRM5(1), CMKLR1(2), CNR1(3), CX3CR1(1), CXCR4(3), DRD1(1), DRD2(3), DRD3(3), DRD5(2), EDNRA(4), EDNRB(7), F2RL2(2), FPR1(2), FSHR(6), GALR1(1), GALT(2), GHSR(5), GPR17(1), GPR173(2), GPR174(2), GPR37(6), GPR37L1(3), GPR4(1), GPR50(5), GPR6(5), GPR63(2), GPR77(1), GPR83(1), GPR85(1), GPR87(4), GRPR(3), HCRTR1(1), HCRTR2(1), HRH1(1), HRH2(4), HTR1A(3), HTR1B(3), HTR1D(2), HTR1E(5), HTR1F(2), HTR2A(2), HTR2B(1), HTR2C(6), HTR4(2), HTR5A(2), HTR7(6), LHCGR(4), MAS1(1), MC3R(1), MC4R(3), MC5R(4), MLNR(3), MTNR1B(3), NMUR1(4), NMUR2(6), NPY1R(4), NPY2R(5), NPY5R(1), NTSR1(1), NTSR2(4), OPN1SW(3), OPN3(1), OPRD1(1), OPRK1(5), OPRM1(1), OR12D3(1), OR1C1(1), OR1F1(2), OR2H1(3), OR5V1(2), OR7A5(3), OR8B8(2), OXTR(2), P2RY1(3), P2RY10(6), P2RY12(3), P2RY13(2), P2RY14(4), P2RY2(2), PPYR1(1), PTAFR(1), PTGER2(1), PTGFR(6), PTGIR(1), RGR(2), RHO(2), RRH(2), SSTR1(4), SSTR2(2), SSTR4(2), TRHR(6) 26305643 350 94 351 123 144 85 5 90 26 0 0.00588 0.484 7 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 11 DNM1(8), GABRA1(2), GABRA2(6), GABRA3(4), GABRA4(6), GABRA6(4), GPHN(11), NSF(1), SRC(3), UBQLN1(2) 2538782 47 27 45 20 13 9 1 17 7 0 0.00682 0.484 8 1_AND_2_METHYLNAPHTHALENE_DEGRADATION ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 7 ADH1B(2), ADH1C(3), ADH4(1), ADH6(5), ADH7(2), ADHFE1(6) 1229065 19 16 19 5 3 4 1 11 0 0 0.00737 0.484 9 FLUMAZENILPATHWAY Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 8 GABRA1(2), GABRA2(6), GABRA3(4), GABRA4(6), GABRA6(4), GPX1(1), PRKCE(4) 1520965 27 19 27 5 9 5 0 10 3 0 0.00750 0.484 10 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(3), CFL1(1), GNAQ(3), GNAS(6), GNB1(1), LIMK1(4), MAP2K1(3), MAPK1(2), MAPK3(2), MYL2(1), NOX1(1), PIK3C2G(7), PLCB1(8), PPP1R12B(5), PRKCA(2), PTK2(5), RAF1(4), ROCK2(2) 5505383 60 39 58 11 24 8 2 17 9 0 0.00785 0.484 11 MONOAMINE_GPCRS ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2C, ADRB1, ADRB2, ADRB3, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, DRD1, DRD2, DRD3, DRD4, DRD5, HRH1, HRH2, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, HTR7, LOC93164 32 ADRA1A(5), ADRA1B(4), ADRA1D(2), ADRA2A(3), ADRB1(2), ADRB3(1), CHRM1(3), CHRM2(8), CHRM3(4), CHRM5(1), DRD1(1), DRD2(3), DRD3(3), DRD5(2), HRH1(1), HRH2(4), HTR1A(3), HTR1B(3), HTR1D(2), HTR1E(5), HTR1F(2), HTR2A(2), HTR2B(1), HTR2C(6), HTR4(2), HTR5A(2), HTR7(6) 5598144 81 46 81 31 37 22 1 12 9 0 0.00920 0.486 12 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(6), AGT(4), AGTR1(3), AGTR2(4), COL4A1(12), COL4A2(3), COL4A3(3), COL4A4(8), COL4A5(17), COL4A6(15), REN(3) 5623215 78 38 77 14 17 23 2 22 14 0 0.0103 0.486 13 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 79 ABL1(4), ABL2(5), AKT1(2), AKT2(5), ARAF(3), BAD(1), BTC(2), CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), CBL(2), CBLB(6), CDKN1A(1), CDKN1B(1), CRKL(2), EGF(3), EGFR(10), ERBB2(6), ERBB3(11), EREG(1), GAB1(6), GRB2(2), GSK3B(7), HBEGF(1), MAP2K1(3), MAPK1(2), MAPK10(4), MAPK3(2), MAPK8(2), MAPK9(3), NRG1(9), NRG2(4), NRG3(3), NRG4(1), PAK1(4), PAK2(2), PAK3(3), PAK6(1), PAK7(4), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PLCG1(4), PLCG2(9), PRKCA(2), PRKCG(8), PTK2(5), RAF1(4), RPS6KB1(3), RPS6KB2(1), SHC1(3), SHC3(1), SHC4(5), SOS1(5), SOS2(9), SRC(3), STAT5B(2) 21422571 222 77 216 71 77 54 9 52 30 0 0.0131 0.486 14 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(2), AXIN1(1), CD14(1), CTNNB1(8), GJA1(3), GNAI1(3), GSK3B(7), IRAK1(1), LBP(1), LEF1(4), LY96(2), MYD88(1), NFKB1(3), PDPK1(1), PIK3R1(5), PPP2CA(1), RELA(2), TIRAP(1), TLR4(7), TOLLIP(1), WNT1(1) 4870085 56 36 56 19 22 11 2 10 11 0 0.0144 0.486 15 HSA04540_GAP_JUNCTION Genes involved in gap junction ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADRB1, CDC2, CSNK1D, DRD1, DRD2, EDG2, EGF, EGFR, GJA1, GJD2, GNA11, GNAI1, GNAI2, GNAI3, GNAQ, GNAS, GRB2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, HTR2A, HTR2B, HTR2C, ITPR1, ITPR2, ITPR3, KRAS, LOC643224, LOC654264, MAP2K1, MAP2K2, MAP2K5, MAP3K2, MAPK1, MAPK3, MAPK7, NPR1, NPR2, NRAS, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PLCB1, PLCB2, PLCB3, PLCB4, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, PRKX, PRKY, RAF1, SOS1, SOS2, SRC, TJP1, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8 89 ADCY1(4), ADCY2(12), ADCY3(1), ADCY4(9), ADCY5(8), ADCY6(1), ADCY7(3), ADCY8(11), ADCY9(4), ADRB1(2), CSNK1D(3), DRD1(1), DRD2(3), EGF(3), EGFR(10), GJA1(3), GNA11(1), GNAI1(3), GNAQ(3), GNAS(6), GRB2(2), GRM1(9), GRM5(8), GUCY1A2(8), GUCY1B3(7), GUCY2C(7), GUCY2D(4), GUCY2F(7), HTR2A(2), HTR2B(1), HTR2C(6), ITPR1(11), ITPR2(12), ITPR3(11), MAP2K1(3), MAP2K5(2), MAP3K2(2), MAPK1(2), MAPK3(2), MAPK7(3), NPR1(6), NPR2(9), PDGFA(1), PDGFC(2), PDGFD(3), PDGFRA(13), PDGFRB(5), PLCB1(8), PLCB2(3), PLCB3(3), PLCB4(9), PRKACB(1), PRKACG(2), PRKCA(2), PRKCG(8), PRKG1(4), PRKG2(3), PRKX(2), RAF1(4), SOS1(5), SOS2(9), SRC(3), TJP1(5), TUBA3C(9), TUBA3D(2), TUBA3E(4), TUBA4A(1), TUBA8(1), TUBAL3(3), TUBB(1), TUBB1(2), TUBB2A(1), TUBB2B(3), TUBB3(1), TUBB4(2), TUBB4Q(2), TUBB6(3), TUBB8(2) 28303583 347 92 345 135 149 69 11 91 26 1 0.0149 0.486 16 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 ADCY1(4), CREM(4), FHL5(1), FSHB(1), FSHR(6), GNAS(6), XPO1(1) 2121753 23 20 23 8 9 5 2 5 2 0 0.0151 0.486 17 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 96 ADCY1(4), ADCY2(12), ADCY3(1), ADCY4(9), ADCY5(8), ADCY6(1), ADCY7(3), ADCY8(11), ADCY9(4), CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), CREB1(1), CREB3(2), CREB3L1(3), CREB3L2(3), CREB3L3(1), CREB3L4(1), CREBBP(21), CTNNB1(8), DCT(9), DVL2(8), DVL3(2), EDN1(1), EDNRB(7), EP300(13), FZD10(4), FZD2(2), FZD3(10), FZD4(1), FZD6(3), FZD7(3), FZD8(1), GNAI1(3), GNAO1(5), GNAQ(3), GNAS(6), GSK3B(7), KIT(6), KITLG(2), LEF1(4), MAP2K1(3), MAPK1(2), MAPK3(2), MITF(2), PLCB1(8), PLCB2(3), PLCB3(3), PLCB4(9), POMC(2), PRKACB(1), PRKACG(2), PRKCA(2), PRKCG(8), PRKX(2), RAF1(4), TCF7(3), TCF7L1(3), TYR(2), TYRP1(2), WNT1(1), WNT10B(3), WNT11(3), WNT16(2), WNT2B(1), WNT3(4), WNT3A(1), WNT4(1), WNT5A(3), WNT7A(2), WNT7B(2), WNT8A(1), WNT9A(2), WNT9B(1) 23644799 290 83 287 106 123 67 6 65 29 0 0.0154 0.486 18 GAMMA_HEXACHLOROCYCLOHEXANE_DEGRADATION ACP1, ACP2, ACP5, ACPP, ACPT, ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, CYP19A1, CYP1A1, CYP1A2, CYP2A6, CYP2A6, CYP2A7, CYP2A7P1, CYP2A13, CYP2B6, CYP2C18, CYP2C19, CYP2C19, CYP2C9, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP3A4, CYP3A5, CYP3A7, CYP4B1, CYP4F8, CYP51A1, PON1 31 ACP1(2), ACP2(2), ACP5(1), ACPP(3), ALPI(2), ALPL(1), ALPP(1), CYP19A1(5), CYP1A1(6), CYP1A2(2), CYP2A13(6), CYP2A6(3), CYP2A7(5), CYP2C19(4), CYP2C8(2), CYP2C9(4), CYP2E1(5), CYP2F1(3), CYP2J2(3), CYP3A4(1), CYP3A5(3), CYP3A7(4), CYP4B1(8), CYP4F8(4), CYP51A1(3), PON1(5) 6374104 88 43 87 18 32 18 4 24 9 1 0.0169 0.486 19 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(3), EGFR(10), ERBB3(11), NRG1(9), UBE2D1(1) 2348873 34 26 31 6 16 7 0 7 4 0 0.0176 0.486 20 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(4), CYP2C9(4) 461019 8 8 8 2 2 1 0 4 1 0 0.0187 0.486 21 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 190 ACTB(2), ACTN1(3), ACTN2(7), ACTN3(2), ACTN4(2), AKT1(2), AKT2(5), ARHGAP5(6), BAD(1), BCL2(1), BIRC2(2), BIRC3(2), CAPN2(5), CAV2(1), CAV3(2), CCND2(1), CCND3(1), CHAD(6), COL11A1(18), COL11A2(10), COL1A1(11), COL1A2(16), COL2A1(8), COL3A1(10), COL4A1(12), COL4A2(3), COL4A4(8), COL4A6(15), COL5A1(13), COL5A2(10), COL5A3(5), COL6A3(31), COL6A6(15), COMP(2), CRKL(2), CTNNB1(8), DIAPH1(1), DOCK1(5), EGF(3), EGFR(10), ERBB2(6), FARP2(5), FLNA(2), FLNB(14), FLNC(11), FLT1(9), FN1(17), FYN(4), GRB2(2), GRLF1(7), GSK3B(7), HGF(5), IBSP(3), IGF1(2), IGF1R(7), ITGA1(3), ITGA10(3), ITGA11(2), ITGA2(5), ITGA2B(2), ITGA3(4), ITGA4(3), ITGA5(7), ITGA6(3), ITGA7(6), ITGA8(5), ITGA9(4), ITGAV(1), ITGB1(6), ITGB3(7), ITGB4(2), ITGB5(5), ITGB6(6), ITGB7(4), ITGB8(4), KDR(8), LAMA1(22), LAMA2(22), LAMA3(12), LAMA4(9), LAMB1(8), LAMB2(2), LAMB3(9), LAMB4(12), LAMC1(7), LAMC2(7), LAMC3(6), MAP2K1(3), MAPK1(2), MAPK10(4), MAPK3(2), MAPK8(2), MAPK9(3), MET(4), MYL2(1), MYL7(1), MYLK(11), MYLK2(2), PAK1(4), PAK2(2), PAK3(3), PAK6(1), PAK7(4), PARVA(1), PARVB(5), PARVG(3), PDGFA(1), PDGFC(2), PDGFD(3), PDGFRA(13), PDGFRB(5), PDPK1(1), PGF(1), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PIP5K1C(3), PPP1CB(1), PPP1CC(1), PPP1R12A(2), PRKCA(2), PRKCG(8), PTEN(6), PTK2(5), RAF1(4), RAP1A(1), RAP1B(2), RAPGEF1(4), RELN(24), RHOA(4), ROCK1(8), ROCK2(2), SHC1(3), SHC3(1), SHC4(5), SOS1(5), SOS2(9), SPP1(1), SRC(3), THBS1(8), THBS2(10), THBS3(2), THBS4(1), TLN1(5), TLN2(5), TNC(13), TNN(15), TNR(19), TNXB(14), VASP(3), VAV1(11), VAV2(2), VAV3(10), VCL(1), VEGFA(2), VEGFB(2), VEGFC(3), VTN(3), VWF(10) 81004352 924 132 915 332 334 216 22 245 105 2 0.0190 0.486 22 HSA04020_CALCIUM_SIGNALING_PATHWAY Genes involved in calcium signaling pathway ADCY1, ADCY2, ADCY3, ADCY4, ADCY7, ADCY8, ADCY9, ADORA2A, ADORA2B, ADRA1A, ADRA1B, ADRA1D, ADRB1, ADRB2, ADRB3, AGTR1, ATP2A1, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, ATP2B4, AVPR1A, AVPR1B, BDKRB1, BDKRB2, BST1, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, CACNA1I, CACNA1S, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CCKAR, CCKBR, CD38, CHP, CHRM1, CHRM2, CHRM3, CHRM5, CHRNA7, CYSLTR1, CYSLTR2, DRD1, EDNRA, EDNRB, EGFR, ERBB2, ERBB3, ERBB4, F2R, GNA11, GNA14, GNA15, GNAL, GNAQ, GNAS, GRIN1, GRIN2A, GRIN2C, GRIN2D, GRM1, GRM5, GRPR, HRH1, HRH2, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, LHCGR, LTB4R2, MLCK, MYLK, MYLK2, NOS1, NOS2A, NOS3, NTSR1, OXTR, P2RX1, P2RX2, P2RX3, P2RX4, P2RX5, P2RX7, P2RXL1, PDE1A, PDE1B, PDE1C, PDGFRA, PDGFRB, PHKA1, PHKA2, PHKB, PHKG1, PHKG2, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCZ1, PLN, PPID, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PTAFR, PTGER1, PTGER3, PTGFR, PTK2B, RYR1, RYR2, RYR3, SLC25A4, SLC25A5, SLC25A6, SLC8A1, SLC8A2, SLC8A3, SPHK1, SPHK2, TACR1, TACR2, TACR3, TBXA2R, TNNC1, TNNC2, TRHR, TRPC1, VDAC1, VDAC2, VDAC3 166 ADCY1(4), ADCY2(12), ADCY3(1), ADCY4(9), ADCY7(3), ADCY8(11), ADCY9(4), ADORA2A(3), ADORA2B(1), ADRA1A(5), ADRA1B(4), ADRA1D(2), ADRB1(2), ADRB3(1), AGTR1(3), ATP2A1(6), ATP2A2(5), ATP2A3(3), ATP2B1(7), ATP2B2(7), ATP2B3(4), ATP2B4(5), AVPR1A(3), AVPR1B(3), BDKRB2(2), CACNA1A(8), CACNA1B(7), CACNA1C(10), CACNA1D(7), CACNA1E(15), CACNA1F(12), CACNA1G(10), CACNA1H(2), CACNA1I(3), CACNA1S(10), CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), CAMK4(2), CCKAR(1), CCKBR(3), CD38(1), CHRM1(3), CHRM2(8), CHRM3(4), CHRM5(1), CYSLTR1(3), CYSLTR2(3), DRD1(1), EDNRA(4), EDNRB(7), EGFR(10), ERBB2(6), ERBB3(11), GNA11(1), GNA14(5), GNA15(3), GNAL(3), GNAQ(3), GNAS(6), GRIN1(1), GRIN2A(15), GRIN2C(2), GRIN2D(3), GRM1(9), GRM5(8), GRPR(3), HRH1(1), HRH2(4), HTR2A(2), HTR2B(1), HTR2C(6), HTR4(2), HTR5A(2), HTR7(6), ITPKB(4), ITPR1(11), ITPR2(12), ITPR3(11), LHCGR(4), MYLK(11), MYLK2(2), NOS1(5), NOS3(2), NTSR1(1), OXTR(2), P2RX1(1), P2RX2(1), P2RX3(2), P2RX4(2), P2RX5(1), P2RX7(2), PDE1A(3), PDE1B(2), PDE1C(7), PDGFRA(13), PDGFRB(5), PHKA1(4), PHKA2(5), PHKB(4), PHKG2(2), PLCB1(8), PLCB2(3), PLCB3(3), PLCB4(9), PLCD1(6), PLCD3(2), PLCD4(2), PLCE1(7), PLCG1(4), PLCG2(9), PLCZ1(3), PPID(2), PPP3CA(1), PPP3CB(4), PPP3CC(3), PPP3R1(1), PPP3R2(1), PRKACB(1), PRKACG(2), PRKCA(2), PRKCG(8), PRKX(2), PTAFR(1), PTGER3(6), PTGFR(6), PTK2B(1), RYR1(19), RYR2(48), RYR3(31), SLC25A4(1), SLC25A5(1), SLC8A1(11), SLC8A2(3), SLC8A3(4), SPHK2(1), TACR1(2), TACR2(1), TACR3(4), TNNC2(1), TRHR(6), TRPC1(5), VDAC1(1), VDAC3(1) 56815715 711 122 705 284 301 162 17 171 58 2 0.0198 0.486 23 AKAPCENTROSOMEPATHWAY Protein Kinase A at the Centrosome AKAP9, ARHA, CDC2, MAP2, PCNT1, PCNT2, PPP1CA, PPP2CA, PRKACB, PRKACG, PRKAG1, PRKAR2A, PRKAR2B, PRKCE, PRKCL1 10 AKAP9(20), MAP2(21), PPP2CA(1), PRKACB(1), PRKACG(2), PRKAG1(1), PRKAR2B(2), PRKCE(4) 4045327 52 31 52 13 16 11 1 14 10 0 0.0202 0.486 24 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 DCN(3), FMOD(2), KERA(5), LUM(5) 806504 15 13 15 3 4 6 0 3 2 0 0.0204 0.486 25 ERKPATHWAY Cell growth is promoted by Ras activation of the anti-apoptotic p44/42 MAP kinase pathway. DPM2, EGFR, ELK1, GNAS, GNB1, GNGT1, GRB2, HRAS, IGF1R, ITGB1, KLK2, MAP2K1, MAP2K2, MAPK1, MAPK3, MKNK1, MKNK2, MYC, NGFB, NGFR, PDGFRA, PPP2CA, PTPRR, RAF1, RPS6KA1, RPS6KA5, SHC1, SOS1, SRC, STAT3 28 EGFR(10), GNAS(6), GNB1(1), GRB2(2), IGF1R(7), ITGB1(6), MAP2K1(3), MAPK1(2), MAPK3(2), MKNK1(1), MKNK2(2), NGFR(2), PDGFRA(13), PPP2CA(1), PTPRR(1), RAF1(4), RPS6KA1(1), RPS6KA5(3), SHC1(3), SOS1(5), SRC(3), STAT3(2) 7411213 80 47 78 30 30 16 6 20 7 1 0.0204 0.486 26 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(2), PIK3R1(5), PLCB1(8), PLCG1(4), PRKCA(2), VAV1(11) 2444739 32 26 32 9 13 4 2 8 5 0 0.0205 0.486 27 TUBBYPATHWAY Tubby is activated by phospholipase C activity and hydrolysis of PIP2, after which it enters the nucleus and regulates transcription. CHRM1, GNAQ, GNB1, GNGT1, HTR2C, PLCB1, TUB 7 CHRM1(3), GNAQ(3), GNB1(1), HTR2C(6), PLCB1(8), TUB(4) 1619755 25 18 25 7 13 3 1 5 3 0 0.0215 0.490 28 ALTERNATIVEPATHWAY The alternative complement pathway is an antibody-independent mechanism of immune activation that results in cell lysis via the membrane attack complex. BF, C3, C5, C6, C7, C8A, C9, DF, PFC 6 C3(10), C5(9), C6(10), C7(2), C8A(3), C9(4) 2805116 38 23 38 11 12 9 0 12 4 1 0.0250 0.551 29 ASBCELLPATHWAY B cells require interaction with helper T cells to produce antigen-specific immunoglobulins as a key element of the human immune response. CD28, CD4, CD80, HLA-DRA, HLA-DRB1, IL10, IL2, IL4, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 8 CD28(1), CD4(2), HLA-DRA(4), HLA-DRB1(1), IL10(1), IL2(3), IL4(3) 890834 15 12 15 8 6 4 0 3 0 2 0.0275 0.585 30 TGFBPATHWAY The TGF-beta receptor responds to ligand binding by activating the SMAD family of transcriptional regulations, commonly blocking cell growth. APC, CDH1, CREBBP, EP300, MADH2, MADH3, MADH4, MADH7, MADHIP, MAP2K1, MAP3K7, MAP3K7IP1, MAPK3, SKIL, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2 11 CDH1(4), CREBBP(21), EP300(13), MAP2K1(3), MAP3K7(2), MAPK3(2), TGFB1(1), TGFB2(5), TGFBR1(6) 4259312 57 33 56 15 22 18 2 7 8 0 0.0294 0.596 31 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(2), BAD(1), GRB2(2), IGF1R(7), IRS1(5), MAP2K1(3), MAPK1(2), MAPK3(2), PIK3R1(5), RAF1(4), SHC1(3), SOS1(5) 3739105 41 31 39 8 13 8 4 10 6 0 0.0300 0.596 32 ST_WNT_BETA_CATENIN_PATHWAY Beta-catenin is degraded in the absence of Wnt signaling; when extracellular Wnt binds Frizzled receptors, beta-catenin accumulates in the nucleus and may promote cell survival. AKT1, AKT2, AKT3, ANKRD6, APC, AXIN1, AXIN2, C22orf2, CER1, CSNK1A1, CTNNB1, DACT1, DKK1, DKK2, DKK3, DKK4, DVL1, FRAT1, FSTL1, GSK3A, GSK3B, IDAX, LAMR1, LRP1, MVP, NKD1, NKD2, PIN1, PSEN1, PTPRA, SENP2, SFRP1, TSHB, WIF1 28 AKT1(2), AKT2(5), ANKRD6(5), AXIN1(1), AXIN2(7), CER1(3), CSNK1A1(2), CTNNB1(8), DACT1(5), DKK1(3), DKK3(2), DKK4(4), FSTL1(5), GSK3A(2), GSK3B(7), LRP1(14), MVP(4), NKD1(3), NKD2(1), PIN1(1), PSEN1(3), PTPRA(2), SENP2(2), SFRP1(2), WIF1(2) 7411049 95 48 94 28 42 16 3 21 13 0 0.0313 0.603 33 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 31 AKT1(2), AR(4), ASAH1(3), CCL13(1), CCL15(1), DAG1(4), EGFR(10), GNA11(1), GNA15(3), GNAI1(3), GNAQ(3), ITPKB(4), ITPR1(11), ITPR2(12), ITPR3(11), KCNJ3(6), KCNJ5(3), KCNJ9(2), MAPK1(2), MAPK10(4), MAPK14(3), PHKA2(5), PIK3CD(2), PIK3R1(5), PITX2(2), PTX3(2), RAF1(4), SRC(3) 9491373 116 53 115 49 49 17 6 34 10 0 0.0346 0.626 34 PEPTIDE_GPCRS AGTR1, AGTR2, ATP8A1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BLR1, BRS3, C3AR1, C5R1, CCKAR, CCKBR, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CX3CR1, CXCR3, CXCR4, CXCR6, EDNRA, EDNRB, ELA3A, FPR1, FPRL1, FPRL2, FSHR, FY, GALR1, GALR2, GALR3, GALT, GHSR, GNB2L1, GNRHR, GPR77, GRPR, IL8RA, IL8RB, LHCGR, MC1R, MC2R, MC3R, MC4R, MC5R, NMBR, NPY1R, NPY2R, NPY5R, NPY6R, NTSR1, NTSR2, OPRD1, OPRK1, OPRL1, OPRM1, OXTR, PPYR1, SSTR1, SSTR2, SSTR3, SSTR4, TAC4, TACR1, TACR2, TACR3, TRHR, TSHR 66 AGTR1(3), AGTR2(4), ATP8A1(5), AVPR1A(3), AVPR1B(3), AVPR2(6), BDKRB2(2), BRS3(1), C3AR1(2), CCKAR(1), CCKBR(3), CCR1(5), CCR3(3), CCR5(1), CCR6(2), CCR7(1), CCR8(4), CX3CR1(1), CXCR4(3), EDNRA(4), EDNRB(7), FPR1(2), FSHR(6), GALR1(1), GALT(2), GHSR(5), GNRHR(4), GPR77(1), GRPR(3), LHCGR(4), MC2R(2), MC3R(1), MC4R(3), MC5R(4), NPY1R(4), NPY2R(5), NPY5R(1), NTSR1(1), NTSR2(4), OPRD1(1), OPRK1(5), OPRM1(1), OXTR(2), PPYR1(1), SSTR1(4), SSTR2(2), SSTR4(2), TAC4(1), TACR1(2), TACR2(1), TACR3(4), TRHR(6), TSHR(6) 11247469 155 61 156 61 58 36 3 50 8 0 0.0346 0.626 35 CALCIUM_REGULATION_IN_CARDIAC_CELLS ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADRA1A, ADRA1B, ADRA1D, ADRB1, ADRB2, ADRB3, ANXA6, ARRB1, ARRB2, ATP1A4, ATP1B1, ATP1B2, ATP1B3, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1S, CACNB1, CACNB3, CALM1, CALM2, CALM3, CALR, CAMK1, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CASQ1, CASQ2, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, FXYD2, GJA1, GJA12, GJA4, GJA5, GJB1, GJB2, GJB3, GJB4, GJB5, GJB6, GNA11, GNAI2, GNAI3, GNAO1, GNAQ, GNAZ, GNB1, GNB2, GNB3, GNB4, GNB5, GNG12, GNG13, GNG2, GNG3, GNG4, GNG5, GNG7, GNGT1, GRK4, GRK5, GRK6, ITPR1, ITPR2, ITPR3, KCNB1, KCNJ3, KCNJ5, MGC11266, MYCBP, NME7, PEA15, PKIA, PKIB, PKIG, PLCB3, PLN, PRKACA, PRKACB, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCQ, PRKCZ, PRKD1, RGS1, RGS10, RGS11, RGS14, RGS16, RGS17, RGS18, RGS19, RGS2, RGS20, RGS3, RGS4, RGS5, RGS6, RGS7, RGS9, RYR1, RYR2, RYR3, SARA1, SFN, SLC8A1, SLC8A3, USP5, YWHAB, YWHAH, YWHAQ, YWHAQ, MIB1 139 ADCY1(4), ADCY2(12), ADCY3(1), ADCY4(9), ADCY5(8), ADCY6(1), ADCY7(3), ADCY8(11), ADCY9(4), ADRA1A(5), ADRA1B(4), ADRA1D(2), ADRB1(2), ADRB3(1), ANXA6(2), ARRB1(1), ATP1A4(6), ATP1B1(1), ATP2A2(5), ATP2A3(3), ATP2B1(7), ATP2B2(7), ATP2B3(4), CACNA1A(8), CACNA1B(7), CACNA1C(10), CACNA1D(7), CACNA1E(15), CACNA1S(10), CACNB1(1), CACNB3(1), CAMK1(1), CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), CAMK4(2), CASQ1(1), CASQ2(1), CHRM1(3), CHRM2(8), CHRM3(4), CHRM5(1), GJA1(3), GJA4(2), GJA5(3), GJB1(3), GJB3(3), GJB4(1), GNA11(1), GNAO1(5), GNAQ(3), GNAZ(1), GNB1(1), GNB3(3), GNB4(3), GNB5(1), GNG3(2), GNG7(1), GRK4(5), GRK5(3), GRK6(3), ITPR1(11), ITPR2(12), ITPR3(11), KCNB1(2), KCNJ3(6), KCNJ5(3), NME7(3), PEA15(1), PKIA(1), PKIB(1), PLCB3(3), PRKACB(1), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PRKCA(2), PRKCD(3), PRKCE(4), PRKCG(8), PRKCH(2), PRKCQ(4), PRKD1(10), RGS1(1), RGS10(1), RGS14(2), RGS16(2), RGS17(1), RGS18(2), RGS2(1), RGS20(3), RGS3(8), RGS4(2), RGS6(3), RGS7(4), RGS9(4), RYR1(19), RYR2(48), RYR3(31), SLC8A1(11), SLC8A3(4), USP5(3), YWHAB(2), YWHAQ(1) 39826433 482 106 480 206 215 101 12 114 39 1 0.0356 0.626 36 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 21 AXIN1(1), BTRC(2), CREBBP(21), CSNK1A1(2), CSNK1D(3), CSNK2A1(4), CTBP1(1), CTNNB1(8), GSK3B(7), HDAC1(2), MAP3K7(2), NLK(1), PPARD(1), PPP2CA(1), TLE1(1), WIF1(2), WNT1(1) 5057069 60 38 60 18 21 15 1 13 10 0 0.0382 0.654 37 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 39 AKT1(2), ASAH1(3), ATF1(1), CREB1(1), CREB3(2), CREB5(2), CREBBP(21), CRKL(2), DAG1(4), EGR1(2), EGR2(6), EGR3(2), FRS2(2), GNAQ(3), MAP1B(18), MAPK1(2), MAPK10(4), MAPK3(2), MAPK8(2), MAPK8IP1(2), MAPK8IP3(1), MAPK9(3), NTRK1(6), PIK3C2G(7), PIK3CD(2), PIK3R1(5), PTPN11(2), RPS6KA3(3), SHC1(3), SRC(3), TERF2IP(1) 10374793 119 55 117 41 31 35 3 27 22 1 0.0406 0.665 38 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 ALDH1A1(3), ALDH1A2(6), BCMO1(4), RDH5(1) 874199 14 12 14 1 6 2 1 4 1 0 0.0421 0.665 39 ACETYLCHOLINE_SYNTHESIS ACHE, CHAT, CHKA, PCYT1A, PDHA1, PDHA2, PEMT, SLC18A3 8 CHAT(6), CHKA(2), PCYT1A(4), PDHA1(4), PDHA2(6), PEMT(1), SLC18A3(6) 1548475 29 20 29 13 11 10 0 6 2 0 0.0432 0.665 40 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 128 ALCAM(2), CADM1(8), CADM3(6), CD2(3), CD22(8), CD226(2), CD274(3), CD28(1), CD34(1), CD4(2), CD40LG(6), CD58(1), CD6(3), CD8B(2), CDH1(4), CDH2(16), CDH3(2), CDH4(7), CDH5(2), CLDN10(2), CLDN11(1), CLDN15(1), CLDN16(4), CLDN17(5), CLDN18(2), CLDN19(1), CLDN6(2), CLDN7(2), CLDN8(3), CLDN9(1), CNTN1(12), CNTN2(5), CNTNAP1(6), CNTNAP2(8), CTLA4(1), ESAM(3), F11R(1), GLG1(4), HLA-A(1), HLA-B(3), HLA-C(2), HLA-DMA(2), HLA-DOB(1), HLA-DPA1(1), HLA-DPB1(1), HLA-DQA1(1), HLA-DQA2(1), HLA-DRA(4), HLA-DRB1(1), HLA-E(1), HLA-F(1), HLA-G(1), ICAM1(2), ICAM2(1), ICOS(1), ITGA4(3), ITGA6(3), ITGA8(5), ITGA9(4), ITGAL(5), ITGAM(5), ITGAV(1), ITGB1(6), ITGB2(4), ITGB7(4), ITGB8(4), JAM3(3), L1CAM(2), MAG(5), MPZL1(1), NCAM1(2), NCAM2(9), NEGR1(4), NEO1(4), NFASC(13), NLGN1(4), NLGN2(1), NLGN3(4), NRCAM(6), NRXN2(5), NRXN3(16), OCLN(1), PDCD1LG2(1), PECAM1(1), PTPRC(9), PTPRF(8), PTPRM(19), PVR(1), PVRL1(4), PVRL2(3), PVRL3(1), SDC2(2), SDC3(2), SDC4(1), SELE(2), SELP(4), SELPLG(1), SIGLEC1(2), SPN(1), VCAM1(7), VCAN(23) 32428458 384 90 377 145 129 85 6 114 46 4 0.0435 0.665 41 BBCELLPATHWAY Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 4 CD28(1), CD4(2), HLA-DRA(4), HLA-DRB1(1) 521258 8 8 8 4 2 3 0 1 0 2 0.0443 0.665 42 ALKPATHWAY Activin receptor-like kinase 3 (ALK3) is required during gestation for cardiac muscle development. ACVR1, APC, ATF2, AXIN1, BMP10, BMP2, BMP4, BMP5, BMP7, BMPR1A, BMPR2, CHRD, CTNNB1, DVL1, FZD1, GATA4, GSK3B, MADH1, MADH4, MADH5, MADH6, MAP3K7, MEF2C, MYL2, NKX2-5, NOG, NPPA, NPPB, RFC1, TCF1, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, WNT1 30 ACVR1(3), AXIN1(1), BMP10(2), BMP4(1), BMP5(4), BMP7(5), BMPR1A(4), BMPR2(7), CHRD(5), CTNNB1(8), GATA4(1), GSK3B(7), MAP3K7(2), MEF2C(7), MYL2(1), NKX2-5(1), NPPA(1), RFC1(10), TGFB1(1), TGFB2(5), TGFBR1(6), TGFBR3(5), WNT1(1) 6406372 88 41 87 25 30 15 0 26 17 0 0.0478 0.702 43 CELL2CELLPATHWAY Epithelial cell adhesion proteins such as cadherins transduce signals into the cell via catenins, which alter cell shape and motility. ACTN1, ACTN2, ACTN3, BCAR1, CSK, CTNNA1, CTNNA2, CTNNB1, PECAM1, PTK2, PXN, SRC, VCL 13 ACTN1(3), ACTN2(7), ACTN3(2), CSK(1), CTNNA1(10), CTNNA2(10), CTNNB1(8), PECAM1(1), PTK2(5), SRC(3), VCL(1) 4387151 51 33 51 20 26 11 0 8 6 0 0.0503 0.713 44 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(10), AR(4), ESR1(12), ESR2(2), ESRRA(2), HNF4A(2), NR0B1(2), NR1D1(4), NR1D2(3), NR1H3(4), NR1I2(2), NR1I3(2), NR2C2(4), NR2E1(1), NR2F1(2), NR2F2(5), NR3C1(3), NR4A1(2), NR4A2(5), NR5A2(4), PGR(4), PPARA(1), PPARD(1), PPARG(1), RARB(7), RARG(5), ROR1(5), RORA(2), RORC(1), RXRA(1), RXRB(2), RXRG(3), THRA(2), THRB(4), VDR(1) 9434417 115 54 115 46 45 25 2 32 11 0 0.0513 0.713 45 GPCRDB_CLASS_C_METABOTROPIC_GLUTAMATE_PHEROMONE CASR, GABBR1, GPCR5A, GPR51, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GRM1, GRM2, GRM3, GRM4, GRM5, GRM7, GRM8 13 CASR(5), GABBR1(4), GPRC5A(2), GPRC5B(1), GPRC5C(1), GPRC5D(1), GRM1(9), GRM2(3), GRM3(5), GRM4(7), GRM5(8), GRM7(8), GRM8(7) 4608839 61 37 59 36 29 11 1 14 6 0 0.0526 0.713 46 HSA04512_ECM_RECEPTOR_INTERACTION Genes involved in ECM-receptor interaction AGRN, CD36, CD44, CD47, CHAD, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, DAG1, FN1, FNDC1, FNDC3A, FNDC4, FNDC5, GP1BA, GP1BB, GP5, GP6, GP9, HMMR, HSPG2, IBSP, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAV, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, RELN, SDC1, SDC2, SDC3, SDC4, SPP1, SV2A, SV2B, SV2C, THBS1, THBS2, THBS3, THBS4, TNC, TNN, TNR, TNXB, VTN, VWF 86 AGRN(1), CD36(1), CD44(3), CD47(3), CHAD(6), COL11A1(18), COL11A2(10), COL1A1(11), COL1A2(16), COL2A1(8), COL3A1(10), COL4A1(12), COL4A2(3), COL4A4(8), COL4A6(15), COL5A1(13), COL5A2(10), COL5A3(5), COL6A3(31), COL6A6(15), DAG1(4), FN1(17), FNDC1(15), FNDC3A(5), FNDC4(1), GP1BA(1), GP5(5), GP6(1), HMMR(4), HSPG2(9), IBSP(3), ITGA1(3), ITGA10(3), ITGA11(2), ITGA2(5), ITGA2B(2), ITGA3(4), ITGA4(3), ITGA5(7), ITGA6(3), ITGA7(6), ITGA8(5), ITGA9(4), ITGAV(1), ITGB1(6), ITGB3(7), ITGB4(2), ITGB5(5), ITGB6(6), ITGB7(4), ITGB8(4), LAMA1(22), LAMA2(22), LAMA3(12), LAMA4(9), LAMB1(8), LAMB2(2), LAMB3(9), LAMB4(12), LAMC1(7), LAMC2(7), LAMC3(6), RELN(24), SDC2(2), SDC3(2), SDC4(1), SPP1(1), SV2A(4), SV2B(4), SV2C(4), THBS1(8), THBS2(10), THBS3(2), THBS4(1), TNC(13), TNN(15), TNR(19), TNXB(14), VTN(3), VWF(10) 50004551 599 112 596 234 221 136 11 169 62 0 0.0539 0.713 47 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 CDK5R1(1), DAB1(4), FYN(4), LRP8(1), RELN(24), VLDLR(3) 3166952 37 25 36 14 10 8 3 11 5 0 0.0567 0.713 48 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_NEOLACTOSERIES ABO, B3GNT1, FUT1, FUT2, FUT9, GCNT2, ST8SIA1 7 ABO(2), B3GNT1(2), FUT1(1), FUT2(1), FUT9(4), GCNT2(9), ST8SIA1(3) 1350762 22 15 22 4 6 6 1 6 3 0 0.0584 0.713 49 HSA00430_TAURINE_AND_HYPOTAURINE_METABOLISM Genes involved in taurine and hypotaurine metabolism BAAT, CDO1, CSAD, GAD1, GAD2, GGT1, GGTL3, GGTL4 5 BAAT(2), CDO1(1), CSAD(1), GAD1(7), GAD2(4) 1079177 15 13 15 3 7 3 1 4 0 0 0.0610 0.713 50 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(2), ADH1C(3), ADH4(1), ADH5(1), ADH6(5), ADH7(2), ADHFE1(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(1), ALDH9A1(1) 2914856 40 26 40 10 12 11 1 16 0 0 0.0611 0.713 51 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(12), COL4A2(3), COL4A3(3), COL4A4(8), COL4A5(17), COL4A6(15), F10(1), F11(4), F12(2), F2(2), F5(14), F8(15), F9(6), FGA(11), FGB(1), FGG(4), KLKB1(4), PROC(1), PROS1(3), SERPINC1(3), SERPING1(3) 9953487 132 48 129 31 26 35 3 45 23 0 0.0614 0.713 52 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(3), CD4(2), HLA-DRA(4), HLA-DRB1(1), IL4(3), IL5RA(4), IL6(1) 1203207 18 13 18 5 7 3 0 6 0 2 0.0626 0.713 53 FIBRINOLYSISPATHWAY Thrombin cleavage of fibrinogen results in rapid formation of fibrin threads that form a mesh to capture platelets and other blood cells into a clot. CPB2, F13A1, F2, F2R, FGA, FGB, FGG, PLAT, PLAU, PLG, SERPINB2, SERPINE1 12 CPB2(1), F13A1(8), F2(2), FGA(11), FGB(1), FGG(4), PLAT(4), PLAU(2), PLG(7), SERPINB2(4), SERPINE1(1) 3039479 45 28 45 13 12 16 1 11 5 0 0.0631 0.713 54 COMPLEMENT_ACTIVATION_CLASSICAL C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C9, DAF, MASP1 12 C1QB(1), C1R(2), C1S(3), C3(10), C5(9), C6(10), C7(2), C8A(3), C9(4), MASP1(9) 4357879 53 29 53 21 17 10 1 16 8 1 0.0643 0.713 55 SA_BONE_MORPHOGENETIC Bone morphogenetic protein binds to its receptor to induce ectopic bone formation and promote development of the viscera. BMP1, BMPR1A, BMPR1B, BMPR2, MADH1, MADH4, MADH6 4 BMP1(4), BMPR1A(4), BMPR1B(9), BMPR2(7) 1406446 24 16 24 4 5 7 0 5 7 0 0.0648 0.713 56 HSA00534_HEPARAN_SULFATE_BIOSYNTHESIS Genes involved in heparan sulfate biosynthesis EXT1, EXT2, EXTL1, EXTL2, EXTL3, GLCE, HS2ST1, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, HS3ST5, HS6ST1, HS6ST2, HS6ST3, LOC728969, NDST1, NDST2, NDST3, NDST4 19 EXT1(10), EXTL1(3), EXTL2(3), EXTL3(7), GLCE(3), HS2ST1(3), HS3ST1(1), HS3ST2(1), HS3ST3B1(2), HS3ST5(4), HS6ST2(2), HS6ST3(2), NDST1(3), NDST2(5), NDST3(7), NDST4(4) 4602310 60 36 60 16 26 15 2 13 4 0 0.0660 0.713 57 HSA01430_CELL_COMMUNICATION Genes involved in cell communication ACTB, ACTG1, CHAD, COL11A1, COL11A2, COL17A1, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, COMP, DES, DSC1, DSC2, DSC3, DSG1, DSG2, DSG3, DSG4, FN1, GJA1, GJA10, GJA3, GJA4, GJA5, GJA8, GJA9, GJB1, GJB2, GJB3, GJB4, GJB5, GJB6, GJB7, GJC1, GJC2, GJC3, GJD2, GJD3, GJD4, IBSP, INA, ITGA6, ITGB4, KRT1, KRT10, KRT12, KRT13, KRT14, KRT15, KRT16, KRT17, KRT18, KRT19, KRT2, KRT20, KRT23, KRT24, KRT25, KRT27, KRT28, KRT3, KRT31, KRT32, KRT33A, KRT33B, KRT34, KRT35, KRT36, KRT37, KRT38, KRT39, KRT4, KRT40, KRT5, KRT6A, KRT6B, KRT6C, KRT7, KRT71, KRT72, KRT73, KRT74, KRT75, KRT76, KRT77, KRT78, KRT79, KRT8, KRT81, KRT82, KRT83, KRT84, KRT85, KRT86, KRT9, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, LMNA, LMNB1, LMNB2, LOC728760, NES, PRPH, RELN, SPP1, THBS1, THBS2, THBS3, THBS4, TNC, TNN, TNR, TNXB, VIM, VTN, VWF 135 ACTB(2), CHAD(6), COL11A1(18), COL11A2(10), COL17A1(6), COL1A1(11), COL1A2(16), COL2A1(8), COL3A1(10), COL4A1(12), COL4A2(3), COL4A4(8), COL4A6(15), COL5A1(13), COL5A2(10), COL5A3(5), COL6A3(31), COL6A6(15), COMP(2), DES(1), DSC1(7), DSC2(2), DSC3(3), DSG1(6), DSG2(5), DSG3(8), DSG4(5), FN1(17), GJA1(3), GJA10(5), GJA4(2), GJA5(3), GJA8(4), GJA9(3), GJB1(3), GJB3(3), GJB4(1), GJB7(1), GJC1(4), GJC2(1), GJC3(1), GJD4(2), IBSP(3), INA(2), ITGA6(3), ITGB4(2), KRT1(3), KRT10(2), KRT12(1), KRT13(4), KRT15(1), KRT16(2), KRT17(2), KRT18(2), KRT19(2), KRT2(1), KRT23(1), KRT24(1), KRT25(3), KRT27(1), KRT28(1), KRT3(5), KRT31(4), KRT32(1), KRT33A(2), KRT33B(4), KRT34(4), KRT35(1), KRT36(2), KRT37(3), KRT4(2), KRT5(3), KRT6A(3), KRT6B(2), KRT6C(2), KRT7(1), KRT71(3), KRT72(5), KRT73(2), KRT74(2), KRT75(5), KRT76(2), KRT77(1), KRT78(3), KRT79(2), KRT8(1), KRT81(1), KRT82(4), KRT83(1), KRT84(5), KRT85(5), KRT9(4), LAMA1(22), LAMA2(22), LAMA3(12), LAMA4(9), LAMB1(8), LAMB2(2), LAMB3(9), LAMB4(12), LAMC1(7), LAMC2(7), LAMC3(6), LMNB1(2), LMNB2(1), NES(6), PRPH(1), RELN(24), SPP1(1), THBS1(8), THBS2(10), THBS3(2), THBS4(1), TNC(13), TNN(15), TNR(19), TNXB(14), VIM(2), VTN(3), VWF(10) 54560808 661 118 658 247 264 152 9 177 59 0 0.0660 0.713 58 COMPPATHWAY Both the classic and alternative immune complement pathways promote inflammation, foreign cell lysis, and phagocytosis. BF, C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C9, DF, MASP1, MASP2, MBL2 14 C1QB(1), C1R(2), C1S(3), C3(10), C5(9), C6(10), C7(2), C8A(3), C9(4), MASP1(9), MASP2(4) 4746977 57 31 57 22 17 11 2 18 8 1 0.0676 0.718 59 HSA00520_NUCLEOTIDE_SUGARS_METABOLISM Genes involved in nucleotide sugars metabolism GALE, GALT, TGDS, UGDH, UGP2, UXS1 6 GALE(1), GALT(2), UGDH(3), UGP2(5), UXS1(6) 1094737 17 14 17 5 7 4 0 4 2 0 0.0711 0.730 60 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(2), ADH1C(3), ADH4(1), ADH5(1), ADH6(5), ADH7(2), ADHFE1(6), AKR1C2(3), AKR1C4(2), ALDH1A3(4), ALDH3A1(2), ALDH3B1(2), ALDH3B2(1), CYP1A1(6), CYP1A2(2), CYP1B1(2), CYP2C19(4), CYP2C8(2), CYP2C9(4), CYP2E1(5), CYP2F1(3), CYP2S1(3), CYP3A4(1), CYP3A5(3), CYP3A7(4), DHDH(1), EPHX1(5), GSTA1(1), GSTA3(3), GSTA5(1), GSTM2(2), GSTM3(2), GSTM4(2), GSTM5(1), GSTZ1(2), MGST1(2), MGST3(1), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(1), UGT1A5(3), UGT1A7(2), UGT1A9(5), UGT2A1(8), UGT2A3(5), UGT2B10(1), UGT2B11(4), UGT2B15(2), UGT2B17(4), UGT2B28(2), UGT2B4(2), UGT2B7(4) 12103139 143 52 142 33 39 30 4 52 17 1 0.0724 0.730 61 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(12), COL4A2(3), COL4A3(3), COL4A4(8), COL4A5(17), COL4A6(15), P4HB(2), SLC23A1(2), SLC23A2(6), SLC2A3(1) 5543856 69 34 68 15 16 17 2 20 14 0 0.0732 0.730 62 TH1TH2PATHWAY Helper T subtype Th1 produces pro-inflammatory cytokines that stimulate phagocytosis, while Th2 cells promote antibody production and activate eosinophils. CD28, CD86, HLA-DRA, HLA-DRB1, IFNG, IFNGR1, IFNGR2, IL12A, IL12B, IL12RB1, IL12RB2, IL18, IL18R1, IL2, IL2RA, IL4, IL4R, TNFRSF5, TNFSF5 17 CD28(1), HLA-DRA(4), HLA-DRB1(1), IFNG(1), IFNGR1(2), IFNGR2(1), IL12B(2), IL12RB1(2), IL12RB2(5), IL18R1(8), IL2(3), IL2RA(2), IL4(3), IL4R(1) 2810347 36 22 36 13 12 10 0 10 2 2 0.0734 0.730 63 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 19 B2M(3), HLA-A(1), ITGB1(6), KLRC3(2), KLRC4(1), KLRD1(1), MAP2K1(3), MAPK3(2), PAK1(4), PIK3R1(5), PTK2B(1), PTPN6(4), VAV1(11) 3661778 44 28 44 11 15 7 3 10 9 0 0.0789 0.771 64 INOSITOL_METABOLISM ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 5 ALDH6A1(3), ALDOA(1), ALDOB(5), ALDOC(1), TPI1(1) 847422 11 11 11 1 2 0 0 9 0 0 0.0827 0.782 65 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(3), ADCY1(4), CCNB1(2), CDC25C(3), GNAI1(3), GNAS(6), GNB1(1), MAPK1(2), MAPK3(2), MYT1(8), PIN1(1), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), RPS6KA1(1), SRC(3) 4486219 46 35 46 17 18 12 2 12 2 0 0.0831 0.782 66 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(4), CD3D(1), CD3G(2), CD4(2), CREBBP(21), CSK(1), GNAS(6), GNB1(1), HLA-DRA(4), HLA-DRB1(1), LCK(2), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PTPRC(9), ZAP70(4) 5055453 65 34 65 20 21 20 5 8 9 2 0.0852 0.782 67 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(4), CD3D(1), CD3G(2), CD4(2), CREBBP(21), CSK(1), GNAS(6), GNB1(1), HLA-DRA(4), HLA-DRB1(1), LCK(2), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PTPRC(9), ZAP70(4) 5055453 65 34 65 20 21 20 5 8 9 2 0.0852 0.782 68 SMOOTH_MUSCLE_CONTRACTION ACTA1, ACTA2, ACTC, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADM, ADMR, ARRB1, ARRB2, ATF1, ATF2, ATF3, ATF4, ATF5, ATP2A2, ATP2A3, CACNB3, CALCA, CALM1, CALM2, CALM3, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CMKOR1, CNN1, CNN2, CORIN, CREB3, CREBL1, CREBL1, TNXB, CRH, CRHR1, DGKZ, EDG2, ETS2, FOS, GABPA, GABPB2, GBA2, GJA1, GNAQ, GNB1, GNB2, GNB3, GNB4, GNB5, GNG12, GNG13, GNG2, GNG3, GNG4, GNG5, GNG7, GNGT1, GRK4, GRK5, GRK6, GSTO1, GUCA2A, GUCA2B, GUCY1A3, HEAB, IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP6, IL1B, IL6, ITPR1, ITPR2, ITPR3, JUN, LGR7, LGR8, MAFF, MGC11266, MYL2, MYL4, MYLK2, NFKB1, NOS1, NOS3, OXT, OXTR, PDE4B, PDE4D, PKIA, PKIB, PKIG, PLCB3, PLCD1, PLCG1, PLCG2, PRKACA, PRKACB, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCH, PRKCQ, PRKCZ, PRKD1, RAMP1, RAMP2, RAMP3, RCP9, RGS1, RGS10, RGS11, RGS14, RGS16, RGS17, RGS18, RGS19, RGS2, RGS20, RGS3, RGS4, RGS5, RGS6, RGS7, RGS9, RLN1, RYR1, RYR2, RYR3, SARA1, SFN, SLC8A1, SP1, USP5, YWHAB, YWHAH, YWHAQ, YWHAQ, MIB1 137 ACTA1(3), ACTA2(3), ADCY1(4), ADCY2(12), ADCY3(1), ADCY4(9), ADCY5(8), ADCY6(1), ADCY7(3), ADCY8(11), ADCY9(4), ADM(2), ARRB1(1), ATF1(1), ATF3(1), ATP2A2(5), ATP2A3(3), CACNB3(1), CALCA(4), CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), CORIN(10), CREB3(2), CRHR1(1), DGKZ(2), ETS2(2), GABPA(4), GABPB2(2), GBA2(5), GJA1(3), GNAQ(3), GNB1(1), GNB3(3), GNB4(3), GNB5(1), GNG3(2), GNG7(1), GRK4(5), GRK5(3), GRK6(3), GSTO1(1), GUCA2B(2), IGFBP1(2), IGFBP2(1), IGFBP3(2), IGFBP4(2), IL6(1), ITPR1(11), ITPR2(12), ITPR3(11), MYL2(1), MYLK2(2), NFKB1(3), NOS1(5), NOS3(2), OXTR(2), PDE4B(2), PDE4D(3), PKIA(1), PKIB(1), PLCB3(3), PLCD1(6), PLCG1(4), PLCG2(9), PRKACB(1), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PRKCA(2), PRKCD(3), PRKCE(4), PRKCH(2), PRKCQ(4), PRKD1(10), RAMP1(1), RAMP3(3), RGS1(1), RGS10(1), RGS14(2), RGS16(2), RGS17(1), RGS18(2), RGS2(1), RGS20(3), RGS3(8), RGS4(2), RGS6(3), RGS7(4), RGS9(4), RYR1(19), RYR2(48), RYR3(31), SLC8A1(11), SP1(2), TNXB(14), USP5(3), YWHAB(2), YWHAQ(1) 36386369 428 96 424 158 185 90 12 103 38 0 0.0863 0.782 69 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 10 AKT1(2), GRB2(2), NTRK1(6), PIK3R1(5), PLCG1(4), PRKCA(2), SHC1(3), SOS1(5) 2904153 29 24 28 8 5 6 3 9 6 0 0.0881 0.787 70 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(3), ACO2(2), FH(1), IDH1(3), IDH2(7), MDH1(1), MDH2(1), SDHB(2), SUCLA2(3) 2021902 23 20 23 4 9 4 0 7 3 0 0.0914 0.797 71 SETPATHWAY Cytotoxic T cells release perforin, which to allow entry into target cells of granzyme B, which activates caspases, and granzyme A, which induces caspase-independent apoptosis. ANP32A, APEX1, CREBBP, DFFA, DFFB, GZMA, GZMB, HMGB2, NME1, PRF1, SET 11 ANP32A(1), APEX1(2), CREBBP(21), DFFA(2), DFFB(2), GZMA(2), GZMB(1), HMGB2(1) 2302357 32 22 32 8 7 13 1 5 6 0 0.0930 0.797 72 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 18 AKT1(2), EIF2B5(5), EIF2S2(1), EIF2S3(1), GSK3B(7), IGF1(2), IGF1R(7), INPPL1(3), PDK2(1), PDPK1(1), PIK3R1(5), PPP2CA(1), PTEN(6), RPS6KB1(3) 3922083 45 28 44 10 17 8 3 6 10 1 0.0933 0.797 73 HSA04614_RENIN_ANGIOTENSIN_SYSTEM Genes involved in renin-angiotensin system ACE, ACE2, AGT, AGTR1, AGTR2, ANPEP, CMA1, CPA3, CTSA, CTSG, ENPEP, LNPEP, MAS1, MME, NLN, REN, THOP1 17 ACE(2), ACE2(6), AGT(4), AGTR1(3), AGTR2(4), ANPEP(5), CPA3(2), CTSA(3), CTSG(2), ENPEP(7), LNPEP(6), MAS1(1), MME(6), NLN(1), REN(3) 4795277 55 35 55 10 14 17 2 14 8 0 0.0945 0.797 74 NKTPATHWAY T cell differentiation into Th1 and Th2 cells occurs by differential chemokine receptor expression, which mediates tissue localization and immune response. CCL3, CCL4, CCR1, CCR2, CCR3, CCR4, CCR5, CCR7, CD28, CD4, CSF2, CXCR3, CXCR4, IFNG, IFNGR1, IFNGR2, IL12A, IL12B, IL12RB1, IL12RB2, IL18R1, IL2, IL4, IL4R, IL5, TGFB1, TGFB2, TGFB3, TNFSF5 28 CCR1(5), CCR3(3), CCR5(1), CCR7(1), CD28(1), CD4(2), CXCR4(3), IFNG(1), IFNGR1(2), IFNGR2(1), IL12B(2), IL12RB1(2), IL12RB2(5), IL18R1(8), IL2(3), IL4(3), IL4R(1), TGFB1(1), TGFB2(5) 4332673 50 29 51 27 13 17 0 15 5 0 0.0972 0.799 75 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(8), BDKRB2(2), C1QB(1), C1QC(3), C1R(2), C1S(3), C3(10), C3AR1(2), C4BPA(2), C5(9), C5AR1(2), C6(10), C7(2), C8A(3), C9(4), CD46(2), CD55(3), CFB(2), CFH(10), CFI(2), CPB2(1), CR1(7), CR2(9), F10(1), F11(4), F12(2), F13A1(8), F13B(3), F2(2), F3(1), F5(14), F7(2), F8(15), F9(6), FGA(11), FGB(1), FGG(4), KLKB1(4), KNG1(3), MASP1(9), MASP2(4), PLAT(4), PLAU(2), PLAUR(3), PLG(7), PROC(1), PROS1(3), SERPINA5(3), SERPINC1(3), SERPIND1(1), SERPINE1(1), SERPING1(3), THBD(2), VWF(10) 19751884 236 67 233 84 67 62 5 75 26 1 0.0973 0.799 76 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 145 AKT1(2), AKT2(5), BCL2L1(1), CBL(2), CBLB(6), CCND2(1), CCND3(1), CNTF(2), CNTFR(2), CREBBP(21), CSF2RB(7), CSF3R(9), EP300(13), GH1(1), GH2(1), GHR(6), GRB2(2), IFNA1(1), IFNA10(1), IFNA13(2), IFNA16(4), IFNA2(3), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), IFNAR1(3), IFNAR2(1), IFNB1(1), IFNG(1), IFNGR1(2), IFNGR2(1), IL10(1), IL10RA(1), IL10RB(4), IL11(1), IL11RA(1), IL12B(2), IL12RB1(2), IL12RB2(5), IL13(1), IL13RA1(1), IL13RA2(2), IL15(1), IL15RA(1), IL19(1), IL2(3), IL20(2), IL20RA(4), IL21(2), IL21R(3), IL22(2), IL22RA1(1), IL23R(2), IL24(2), IL26(3), IL28RA(3), IL2RA(2), IL2RB(1), IL3(3), IL4(3), IL4R(1), IL5RA(4), IL6(1), IL6R(2), IL6ST(2), IL7(1), IL7R(2), IL9(1), IRF9(3), JAK1(3), JAK2(6), JAK3(6), LEP(1), LEPR(5), LIFR(19), MPL(1), OSM(1), OSMR(4), PIAS1(3), PIAS2(2), PIAS3(4), PIAS4(1), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PIM1(1), PRL(2), PRLR(2), PTPN11(2), PTPN6(4), SOCS2(2), SOCS5(2), SOS1(5), SOS2(9), SPRED1(6), SPRED2(5), SPRY1(2), SPRY4(2), STAM(1), STAM2(2), STAT1(6), STAT2(5), STAT3(2), STAT5B(2), STAT6(2), TPO(8), TSLP(2), TYK2(1) 31279350 342 83 337 96 122 70 11 99 39 1 0.0987 0.800 77 RBPATHWAY The ATM protein kinase recognizes DNA damage and blocks cell cycle progression by phosphorylating chk1 and p53, which normally inhibits Rb to allow G1/S transitions. ATM, CDC2, CDC25A, CDC25B, CDC25C, CDK2, CDK4, CHEK1, MYT1, RB1, TP53, WEE1, YWHAH 10 CDC25A(2), CDC25B(5), CDC25C(3), CDK2(2), CDK4(2), CHEK1(1), MYT1(8), RB1(4), WEE1(3) 2404880 30 21 30 5 7 8 0 12 2 1 0.106 0.848 78 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 15 AKT1(2), CDKN1B(1), GRB2(2), ITGB1(6), MAPK1(2), MAPK3(2), PDK2(1), PDPK1(1), PIK3R1(5), PTEN(6), PTK2(5), SHC1(3), SOS1(5) 3845050 41 26 39 11 8 9 3 11 9 1 0.108 0.854 79 HSA04520_ADHERENS_JUNCTION Genes involved in adherens junction ACP1, ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, ACVR1B, ACVR1C, BAIAP2, CDC42, CDH1, CREBBP, CSNK2A1, CSNK2A2, CSNK2B, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTNND1, EGFR, EP300, ERBB2, FARP2, FER, FGFR1, FYN, IGF1R, INSR, IQGAP1, LEF1, LMO7, MAP3K7, MAPK1, MAPK3, MET, MLLT4, NLK, PARD3, PTPN1, PTPN6, PTPRB, PTPRF, PTPRJ, PTPRM, PVRL1, PVRL2, PVRL3, PVRL4, RAC1, RAC2, RAC3, RHOA, SMAD2, SMAD3, SMAD4, SNAI1, SNAI2, SORBS1, SRC, SSX2IP, TCF7, TCF7L1, TCF7L2, TGFBR1, TGFBR2, TJP1, VCL, WAS, WASF1, WASF2, WASF3, WASL, YES1 70 ACP1(2), ACTB(2), ACTN1(3), ACTN2(7), ACTN3(2), ACTN4(2), ACVR1C(2), CDH1(4), CREBBP(21), CSNK2A1(4), CSNK2A2(2), CSNK2B(2), CTNNA1(10), CTNNA2(10), CTNNA3(9), CTNNB1(8), CTNND1(5), EGFR(10), EP300(13), ERBB2(6), FARP2(5), FER(4), FGFR1(3), FYN(4), IGF1R(7), INSR(5), IQGAP1(10), LEF1(4), LMO7(18), MAP3K7(2), MAPK1(2), MAPK3(2), MET(4), MLLT4(3), NLK(1), PARD3(5), PTPN1(4), PTPN6(4), PTPRB(4), PTPRF(8), PTPRJ(3), PTPRM(19), PVRL1(4), PVRL2(3), PVRL3(1), PVRL4(4), RHOA(4), SMAD3(6), SNAI1(1), SNAI2(1), SORBS1(7), SRC(3), SSX2IP(3), TCF7(3), TCF7L1(3), TGFBR1(6), TJP1(5), VCL(1), WAS(1), WASF1(1), WASF2(2), WASF3(2), WASL(5), YES1(1) 24909130 312 79 308 94 113 82 4 80 33 0 0.113 0.868 80 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(4), CCNE1(3), CDK2(2), CUL1(7), RB1(4), SKP2(1), TFDP1(4) 2015990 25 19 25 4 6 3 1 11 3 1 0.113 0.868 81 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(2), CAT(2), GH1(1), GHR(6), IGF1(2), IGF1R(7), PIK3R1(5), SHC1(3), SOD2(4) 2486628 32 23 31 7 13 4 1 9 5 0 0.119 0.904 82 TCRAPATHWAY The kinases Lck and Fyn phosphorylate and activate the T cell receptor, which recognizes antigen-bound MHCII and leads to T cell activation. CD3D, CD3E, CD3G, CD3Z, CD4, FYN, HLA-DRA, HLA-DRB1, LCK, PTPRC, TRA@, TRB@, ZAP70 10 CD3D(1), CD3G(2), CD4(2), FYN(4), HLA-DRA(4), HLA-DRB1(1), LCK(2), PTPRC(9), ZAP70(4) 2046111 29 19 29 8 7 10 2 3 5 2 0.123 0.909 83 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 242 ACVR1(3), ACVR2B(3), AMHR2(2), BMP7(5), BMPR1A(4), BMPR1B(9), BMPR2(7), CCL13(1), CCL15(1), CCL18(1), CCL23(2), CCL27(3), CCL7(1), CCL8(1), CCR1(5), CCR3(3), CCR5(1), CCR6(2), CCR7(1), CCR8(4), CCR9(4), CD27(3), CD40LG(6), CD70(5), CNTF(2), CNTFR(2), CSF1(1), CSF1R(3), CSF2RB(7), CSF3R(9), CX3CR1(1), CXCL11(2), CXCL12(1), CXCL14(1), CXCL5(1), CXCL6(1), CXCL9(2), CXCR4(3), EDA(1), EDA2R(2), EDAR(1), EGF(3), EGFR(10), FASLG(1), FLT1(9), FLT3(3), FLT3LG(1), FLT4(4), GDF5(1), GH1(1), GH2(1), GHR(6), HGF(5), IFNA1(1), IFNA10(1), IFNA13(2), IFNA16(4), IFNA2(3), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), IFNAR1(3), IFNAR2(1), IFNB1(1), IFNG(1), IFNGR1(2), IFNGR2(1), IL10(1), IL10RA(1), IL10RB(4), IL11(1), IL11RA(1), IL12B(2), IL12RB1(2), IL12RB2(5), IL13(1), IL13RA1(1), IL15(1), IL15RA(1), IL17A(1), IL17RA(5), IL17RB(1), IL18R1(8), IL18RAP(2), IL19(1), IL1A(1), IL1R1(3), IL1R2(3), IL2(3), IL20(2), IL20RA(4), IL21(2), IL21R(3), IL22(2), IL22RA1(1), IL23R(2), IL24(2), IL25(1), IL26(3), IL28RA(3), IL2RA(2), IL2RB(1), IL3(3), IL4(3), IL4R(1), IL5RA(4), IL6(1), IL6R(2), IL6ST(2), IL7(1), IL7R(2), IL9(1), INHBB(1), INHBC(2), KDR(8), KIT(6), KITLG(2), LEP(1), LEPR(5), LIFR(19), LTB(1), LTBR(2), MET(4), MPL(1), NGFR(2), OSM(1), OSMR(4), PDGFC(2), PDGFRA(13), PDGFRB(5), PLEKHO2(5), PRL(2), PRLR(2), RELT(2), TGFB1(1), TGFB2(5), TGFBR1(6), TNFRSF10A(3), TNFRSF10B(2), TNFRSF11A(2), TNFRSF11B(4), TNFRSF13B(4), TNFRSF17(2), TNFRSF19(3), TNFRSF1A(1), TNFRSF21(4), TNFRSF4(1), TNFRSF8(1), TNFRSF9(2), TNFSF10(1), TNFSF11(1), TNFSF12(2), TNFSF13(2), TNFSF14(3), TNFSF15(3), TNFSF18(1), TNFSF4(1), TNFSF8(1), TPO(8), TSLP(2), VEGFA(2), VEGFB(2), VEGFC(3), XCL2(1) 38171456 452 94 446 155 151 100 7 136 57 1 0.123 0.909 84 ST_MYOCYTE_AD_PATHWAY Cardiac myocytes have a variety of adrenergic receptors that induce subtype-specific signaling effects. ADRB1, AKT1, APC, ASAH1, BF, CAMP, CAV3, DAG1, DLG4, EPHB2, GAS, GNAI1, GNAQ, HTATIP, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, PITX2, PLB, PTX1, PTX3, RAC1, RHO, RYR1 22 ADRB1(2), AKT1(2), ASAH1(3), CAV3(2), DAG1(4), DLG4(2), EPHB2(7), GNAI1(3), GNAQ(3), ITPR1(11), ITPR2(12), ITPR3(11), KCNJ3(6), KCNJ5(3), KCNJ9(2), MAPK1(2), PITX2(2), PTX3(2), RHO(2), RYR1(19) 8538809 100 48 99 45 50 16 4 22 8 0 0.125 0.909 85 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 ARFIP2(2), CDK5R1(1), CFL1(1), CHN1(1), LIMK1(4), MAP3K1(6), MYL2(1), MYLK(11), NCF2(1), PAK1(4), PDGFRA(13), PIK3R1(5), PLD1(8), PPP1R12B(5), RALBP1(4), RPS6KB1(3), TRIO(12), VAV1(11), WASF1(1) 7273111 94 42 93 28 31 26 3 16 17 1 0.126 0.909 86 TRYPTOPHAN_METABOLISM AANAT, ABP1, ACAT1, ACAT2, ACMSD, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, AOC2, AOC3, AOX1, ASMT, CAT, CYP19A1, CYP1A1, CYP1A2, CYP2A6, CYP2A6, CYP2A7, CYP2A7P1, CYP2A13, CYP2B6, CYP2C18, CYP2C19, CYP2C19, CYP2C9, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP3A4, CYP3A5, CYP3A7, CYP4B1, CYP4F8, CYP51A1, DDC, ECHS1, EHHADH, GCDH, HAAO, HADHA, INDO, KMO, KYNU, MAOA, MAOB, SDS, TDO2, TPH1, WARS, WARS2 53 ABP1(1), ACAT1(1), ACAT2(2), ACMSD(3), ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), AOC2(4), AOC3(4), AOX1(5), CAT(2), CYP19A1(5), CYP1A1(6), CYP1A2(2), CYP2A13(6), CYP2A6(3), CYP2A7(5), CYP2C19(4), CYP2C8(2), CYP2C9(4), CYP2E1(5), CYP2F1(3), CYP2J2(3), CYP3A4(1), CYP3A5(3), CYP3A7(4), CYP4B1(8), CYP4F8(4), CYP51A1(3), DDC(1), ECHS1(2), EHHADH(2), GCDH(3), HAAO(2), HADHA(2), KMO(3), KYNU(6), MAOA(2), SDS(2), TDO2(2), TPH1(1), WARS(1), WARS2(2) 12169758 152 54 152 38 57 36 2 45 11 1 0.127 0.909 87 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 ARHGAP5(6), DIAPH1(1), FYN(4), ITGA1(3), ITGB1(6), MAP2K1(3), MAPK1(2), MAPK3(2), MYL2(1), MYLK(11), PIK3R1(5), PTK2(5), RAF1(4), ROCK1(8), SHC1(3), SRC(3), TLN1(5) 7853675 72 43 69 19 21 18 2 17 14 0 0.129 0.912 88 CDC25PATHWAY The protein phosphatase Cdc25 is phosphorylated by Chk1 and activates Cdc2 to stimulate eukaryotic cells into M phase. ATM, CDC2, CDC25A, CDC25B, CDC25C, CHEK1, MYT1, WEE1, YWHAH 7 CDC25A(2), CDC25B(5), CDC25C(3), CHEK1(1), MYT1(8), WEE1(3) 1694314 22 17 22 3 6 6 0 8 2 0 0.130 0.913 89 SRCRPTPPATHWAY Activation of Src by Protein-tyrosine phosphatase alpha CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CSK, GRB2, PRKCA, PRKCB1, PTPRA, SRC 9 CCNB1(2), CDC25A(2), CDC25B(5), CDC25C(3), CSK(1), GRB2(2), PRKCA(2), PTPRA(2), SRC(3) 2105138 22 19 22 8 5 6 1 10 0 0 0.138 0.952 90 LAIRPATHWAY The local acute inflammatory response is mediated by activated macrophages and mast cells or by complement activation. BDK, C3, C5, C6, C7, ICAM1, IL1A, IL6, IL8, ITGA4, ITGAL, ITGB1, ITGB2, SELP, SELPLG, TNF, VCAM1 16 C3(10), C5(9), C6(10), C7(2), ICAM1(2), IL1A(1), IL6(1), ITGA4(3), ITGAL(5), ITGB1(6), ITGB2(4), SELP(4), SELPLG(1), VCAM1(7) 5463624 65 33 64 20 23 17 0 18 6 1 0.144 0.985 91 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 69 ARAF(3), C7orf16(4), CACNA1A(8), CRHR1(1), GNA11(1), GNA12(2), GNA13(2), GNAI1(3), GNAO1(5), GNAQ(3), GNAS(6), GNAZ(1), GRIA2(10), GRIA3(5), GRID2(10), GRM1(9), GRM5(8), GUCY1A2(8), GUCY1B3(7), GUCY2C(7), GUCY2D(4), GUCY2F(7), IGF1(2), IGF1R(7), ITPR1(11), ITPR2(12), ITPR3(11), LYN(4), MAP2K1(3), MAPK1(2), MAPK3(2), NOS1(5), NOS3(2), NPR1(6), NPR2(9), PLA2G1B(1), PLA2G2F(1), PLA2G4A(5), PLA2G6(2), PLCB1(8), PLCB2(3), PLCB3(3), PLCB4(9), PPP2CA(1), PPP2R1A(4), PPP2R1B(1), PPP2R2A(1), PPP2R2B(1), PPP2R2C(3), PRKCA(2), PRKCG(8), PRKG1(4), PRKG2(3), RAF1(4), RYR1(19) 22910303 273 79 270 106 117 64 6 66 20 0 0.151 1.000 92 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), IL12B(2), IL13(1), IL15(1), IL16(5), IL1A(1), IL2(3), IL3(3), IL4(3), IL6(1), IL9(1) 2172653 25 19 24 15 11 3 1 9 1 0 0.154 1.000 93 KREBPATHWAY The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain. ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2 8 ACO2(2), FH(1), IDH2(7), MDH1(1), OGDH(4), SDHA(5), SUCLA2(3) 2086712 23 20 23 6 11 4 0 4 4 0 0.157 1.000 94 RHOPATHWAY RhoA is a G protein whose active form stabilizes actin structures such as focal adhesions and activates Rock1, which phosphorylates myosin light chains. ACTR2, ACTR3, ARHA, ARHGAP1, ARHGAP4, ARHGAP5, ARHGAP6, ARHGEF1, ARHGEF11, ARHGEF5, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, BAIAP2, CFL1, DIAPH1, GSN, LIMK1, MYL2, MYLK, OPHN1, PFN1, PIP5K1A, PIP5K1B, PPP1R12B, ROCK1, SRC, TLN1, VCL 30 ACTR2(1), ACTR3(2), ARHGAP4(1), ARHGAP5(6), ARHGAP6(1), ARHGEF1(4), ARHGEF11(9), ARHGEF5(7), ARPC1A(5), ARPC1B(2), ARPC2(1), CFL1(1), DIAPH1(1), LIMK1(4), MYL2(1), MYLK(11), OPHN1(4), PIP5K1A(3), PIP5K1B(1), PPP1R12B(5), ROCK1(8), SRC(3), TLN1(5), VCL(1) 10247563 87 49 85 29 32 15 4 21 15 0 0.167 1.000 95 GLUTATHIONE_METABOLISM ANPEP, G6PD, GCLC, GCLM, GGT1, GPX1, GPX2, GPX3, GPX4, GPX5, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, PGD 28 ANPEP(5), G6PD(2), GCLC(4), GCLM(1), GPX1(1), GPX2(2), GPX3(1), GPX5(4), GSS(4), GSTA1(1), GSTA3(3), GSTM2(2), GSTM3(2), GSTM4(2), GSTM5(1), GSTZ1(2), IDH1(3), IDH2(7), MGST1(2), MGST3(1), PGD(1) 3787851 51 28 51 6 11 13 2 19 6 0 0.170 1.000 96 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 22 CXCL12(1), CXCR4(3), GNAI1(3), GNAQ(3), GNB1(1), MAP2K1(3), MAPK1(2), MAPK3(2), NFKB1(3), PIK3C2G(7), PIK3R1(5), PLCG1(4), PRKCA(2), PTK2(5), PTK2B(1), RAF1(4), RELA(2) 5630720 51 32 50 14 20 10 2 8 11 0 0.170 1.000 97 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(4), AKT1(2), BAD(1), BAX(1), BCL2(1), BCL2L1(1), CSF2RB(7), IGF1(2), IGF1R(7), IL3(3), KIT(6), KITLG(2), PIK3R1(5), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2) 4200105 49 32 48 14 21 10 2 9 7 0 0.171 1.000 98 P27PATHWAY p27 blocks the G1/S transition by inhibiting the checkpoint kinase cdk2/cyclin E and is inhibited by cdk2-mediated ubiquitination. CCNE1, CDK2, CDKN1B, CKS1B, CUL1, E2F1, NEDD8, RB1, RBX1, SKP1A, SKP2, TFDP1, UBE2M 12 CCNE1(3), CDK2(2), CDKN1B(1), CKS1B(1), CUL1(7), RB1(4), SKP2(1), TFDP1(4) 1979499 23 18 23 3 4 2 1 11 4 1 0.179 1.000 99 ST_G_ALPHA_S_PATHWAY The G-alpha-s protein activates adenylyl cyclases, which catalyze cAMP formation. ASAH1, BF, BFAR, BRAF, CAMP, CREB1, CREB3, CREB5, EPAC, GAS, GRF2, MAPK1, RAF1, SNX13, SRC, TERF2IP 11 ASAH1(3), BFAR(1), CREB1(1), CREB3(2), CREB5(2), MAPK1(2), RAF1(4), SNX13(6), SRC(3), TERF2IP(1) 2188441 25 16 24 11 7 8 0 5 5 0 0.180 1.000 100 MYOSINPATHWAY Myosin light chain kinase phosphorylates myosin and promotes muscle contraction and platelet formation; myosin phosphatase antagonizes these processes. ARHGAP5, ARHGEF1, GNA12, GNA13, GNAQ, GNB1, GNGT1, MYL2, MYLK, PLCB1, PPP1R12B, PRKCA, PRKCB1, PRKCL1, ROCK1 13 ARHGAP5(6), ARHGEF1(4), GNA12(2), GNA13(2), GNAQ(3), GNB1(1), MYL2(1), MYLK(11), PLCB1(8), PPP1R12B(5), PRKCA(2), ROCK1(8) 4650654 53 30 51 14 13 10 3 15 12 0 0.180 1.000 101 HSA00251_GLUTAMATE_METABOLISM Genes involved in glutamate metabolism ABAT, ADC, ALDH4A1, ALDH5A1, CAD, CPS1, EARS2, EPRS, GAD1, GAD2, GCLC, GCLM, GFPT1, GFPT2, GLS, GLS2, GLUD1, GLUD2, GLUL, GMPS, GNPNAT1, GOT1, GOT2, GPT, GPT2, GSR, GSS, NADSYN1, NAGK, PPAT, QARS 31 ABAT(5), ADC(1), ALDH4A1(2), ALDH5A1(4), CAD(10), CPS1(8), EPRS(10), GAD1(7), GAD2(4), GCLC(4), GCLM(1), GFPT1(3), GFPT2(3), GLS2(2), GLUD1(2), GLUD2(4), GLUL(3), GMPS(5), GOT1(5), GOT2(1), GPT2(2), GSR(1), GSS(4), NADSYN1(2), NAGK(2), PPAT(3), QARS(7) 8826901 105 45 105 24 39 28 2 29 7 0 0.181 1.000 102 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(4), GNAS(6), GNB1(1), PPP2CA(1), PRKAA1(2), PRKAA2(6), PRKAB1(1), PRKAB2(1), PRKACB(1), PRKACG(2), PRKAG1(1), PRKAG2(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2) 3353145 32 26 32 16 12 6 2 9 3 0 0.184 1.000 103 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(2), EGF(3), EGFR(10), GRB2(2), MAP2K1(3), MAPK1(2), MAPK3(2), PTPRB(4), RAF1(4), RASA1(5), SHC1(3), SOS1(5), SPRY1(2), SPRY4(2), SRC(3) 5246046 52 31 50 19 17 15 4 12 4 0 0.184 1.000 104 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 BCL2(1), CREBBP(21), EP300(13), FYN(4), IL7(1), IL7R(2), JAK1(3), JAK3(6), LCK(2), NMI(1), PIK3R1(5), PTK2B(1), STAT5B(2) 5811777 62 35 61 20 20 18 2 10 12 0 0.186 1.000 105 NUCLEOTIDE_GPCRS ADORA1, ADORA2A, ADORA2B, ADORA3, GPR23, LTB4R, P2RY1, P2RY2, P2RY5, P2RY6 8 ADORA1(5), ADORA2A(3), ADORA2B(1), ADORA3(3), P2RY1(3), P2RY2(2) 1250559 17 14 17 4 7 4 1 4 1 0 0.188 1.000 106 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 CR1(7), CR2(9), HLA-DRA(4), HLA-DRB1(1), ICAM1(2), ITGAL(5), ITGB2(4), PTPRC(9) 3166501 41 24 41 10 11 14 0 9 5 2 0.191 1.000 107 FCER1PATHWAY In mast cells, Fc epsilon receptor 1 activates BTK, PKC, and the MAP kinase pathway to promote degranulation and arachnidonic acid release. BTK, CALM1, CALM2, CALM3, ELK1, FCER1A, FCER1G, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP2K4, MAP2K7, MAP3K1, MAPK1, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, PAK2, PIK3CA, PIK3R1, PLA2G4A, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCB1, RAF1, SHC1, SOS1, SYK, SYT1, VAV1 35 BTK(6), FCER1A(2), GRB2(2), LYN(4), MAP2K1(3), MAP3K1(6), MAPK1(2), MAPK3(2), MAPK8(2), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), PAK2(2), PIK3R1(5), PLA2G4A(5), PLCG1(4), PPP3CA(1), PPP3CB(4), PPP3CC(3), RAF1(4), SHC1(3), SOS1(5), SYT1(1), VAV1(11) 8937546 89 43 87 22 33 19 5 18 14 0 0.191 1.000 108 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 16 CSNK2A1(4), GRB2(2), MAP2K1(3), MAPK3(2), MAPK8(2), NGFR(2), PIK3R1(5), PLCG1(4), RAF1(4), SHC1(3), SOS1(5) 3670516 36 24 34 7 10 9 4 8 5 0 0.191 1.000 109 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(4), AKT1(2), ASAH1(3), GNAI1(3), GNB1(1), ITGAV(1), ITGB3(7), MAPK1(2), MAPK3(2), PDGFA(1), PDGFRA(13), PIK3R1(5), PLCB1(8), PRKCA(2), PTK2(5), SMPD1(6), SRC(3) 5692241 68 33 68 23 22 17 3 16 9 1 0.194 1.000 110 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(1), HLA-DRA(4), HLA-DRB1(1), IFNA1(1), IFNB1(1), IFNG(1), IL10(1), IL11(1), IL12B(2), IL13(1), IL15(1), IL1A(1), IL2(3), IL3(3), IL4(3), IL6(1), IL7(1), PDGFA(1), TGFB1(1), TGFB2(5) 2979184 36 21 35 17 15 5 0 11 3 2 0.196 1.000 111 CDK5PATHWAY Cdk5, a regulatory kinase implicated in neuronal development, represses Mek1, which downregulates the MAP kinase pathway. CDK5, CDK5R1, DPM2, EGR1, HRAS, KLK2, MAP2K1, MAP2K2, MAPK1, MAPK3, NGFB, NGFR, RAF1 11 CDK5R1(1), EGR1(2), MAP2K1(3), MAPK1(2), MAPK3(2), NGFR(2), RAF1(4) 1650990 16 14 15 5 6 3 2 2 3 0 0.197 1.000 112 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 57 AXIN1(1), CCND2(1), CCND3(1), CTNNB1(8), DVL2(8), DVL3(2), FBXW2(2), FZD10(4), FZD2(2), FZD3(10), FZD6(3), FZD7(3), FZD8(1), GSK3B(7), LDLR(4), MAPK10(4), MAPK9(3), PAFAH1B1(3), PLAU(2), PPP2R5C(2), PPP2R5E(2), PRKCA(2), PRKCD(3), PRKCE(4), PRKCG(8), PRKCH(2), PRKCI(4), PRKCQ(4), PRKD1(10), RHOA(4), SFRP4(3), TCF7(3), WNT1(1), WNT10B(3), WNT11(3), WNT16(2), WNT2B(1), WNT3(4), WNT4(1), WNT5A(3), WNT7A(2), WNT7B(2) 11692277 142 58 140 44 63 28 2 34 15 0 0.202 1.000 113 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), ACTR3(2), ARPC1A(5), ARPC1B(2), ARPC2(1), PAK1(4), PDGFRA(13), PIK3R1(5), WASL(5) 2527942 38 18 38 11 9 8 2 10 8 1 0.205 1.000 114 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(4), GRB2(2), IGF1(2), IGF1R(7), IRS1(5), MAP2K1(3), MAPK3(2), MAPK8(2), PIK3R1(5), PTPN11(2), RAF1(4), RASA1(5), SHC1(3), SOS1(5), SRF(3) 5028300 54 32 52 10 15 13 3 16 7 0 0.213 1.000 115 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(4), AGTR2(4), CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), F2(2), FYN(4), GNA11(1), GNAI1(3), GNB1(1), GRB2(2), JAK2(6), MAP2K1(3), MAPK1(2), MAPK14(3), MAPK3(2), MAPK8(2), MAPT(4), MYLK(11), PLCG1(4), PRKCA(2), PTK2B(1), RAF1(4), SHC1(3), SOS1(5), STAT1(6), STAT3(2), SYT1(1) 9462747 89 42 87 27 25 24 9 21 9 1 0.216 1.000 116 BILE_ACID_BIOSYNTHESIS ACAA1, ACAA2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1C4, AKR1D1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, BAAT, CEL, CYP27A1, CYP7A1, HADHB, SOAT2, SRD5A1, SRD5A2 27 ACAA1(2), ADH1B(2), ADH1C(3), ADH4(1), ADH6(5), ADH7(2), ADHFE1(6), AKR1C4(2), ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), BAAT(2), CEL(1), CYP27A1(3), CYP7A1(4), HADHB(1), SOAT2(1), SRD5A1(1), SRD5A2(1) 5194000 65 33 65 11 20 18 1 23 3 0 0.216 1.000 117 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(2), AKT2(5), BAD(1), BCR(6), BTK(6), CD19(3), CSK(1), DAG1(4), EPHB2(7), GRB2(2), ITPKB(4), LYN(4), MAP2K1(3), MAPK1(2), NFAT5(5), NFKB1(3), NFKB2(2), NFKBIB(1), NFKBIE(2), PIK3CD(2), PIK3R1(5), PLCG2(9), PPP1R13B(5), RAF1(4), SERPINA4(2), SHC1(3), SOS1(5), SOS2(9), VAV1(11) 11259569 118 52 114 33 47 24 7 28 12 0 0.217 1.000 118 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 138 APC2(1), AXIN1(1), AXIN2(7), BTRC(2), CACYBP(1), CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), CCND2(1), CCND3(1), CER1(3), CHD8(4), CREBBP(21), CSNK1A1(2), CSNK1A1L(5), CSNK2A1(4), CSNK2A2(2), CSNK2B(2), CTBP1(1), CTBP2(2), CTNNB1(8), CTNNBIP1(1), CUL1(7), CXXC4(1), DAAM1(1), DAAM2(5), DKK1(3), DKK4(4), DVL2(8), DVL3(2), EP300(13), FBXW11(7), FZD10(4), FZD2(2), FZD3(10), FZD4(1), FZD6(3), FZD7(3), FZD8(1), GSK3B(7), LEF1(4), LRP5(5), LRP6(10), MAP3K7(2), MAPK10(4), MAPK8(2), MAPK9(3), MMP7(3), NFAT5(5), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), NKD1(3), NKD2(1), NLK(1), PLCB1(8), PLCB2(3), PLCB3(3), PLCB4(9), PORCN(2), PPARD(1), PPP2CA(1), PPP2R1A(4), PPP2R1B(1), PPP2R2A(1), PPP2R2B(1), PPP2R2C(3), PPP3CA(1), PPP3CB(4), PPP3CC(3), PPP3R1(1), PPP3R2(1), PRICKLE1(8), PRICKLE2(5), PRKACB(1), PRKACG(2), PRKCA(2), PRKCG(8), PRKX(2), PSEN1(3), RHOA(4), ROCK1(8), ROCK2(2), RUVBL1(6), SENP2(2), SFRP1(2), SFRP2(1), SFRP4(3), SFRP5(1), SIAH1(1), SKP1(1), SMAD3(6), SOX17(2), TBL1X(5), TBL1XR1(6), TCF7(3), TCF7L1(3), VANGL1(2), VANGL2(5), WIF1(2), WNT1(1), WNT10B(3), WNT11(3), WNT16(2), WNT2B(1), WNT3(4), WNT3A(1), WNT4(1), WNT5A(3), WNT7A(2), WNT7B(2), WNT8A(1), WNT9A(2), WNT9B(1) 33129819 383 89 379 111 154 84 7 93 45 0 0.221 1.000 119 FBW7PATHWAY Cyclin E interacts with cell cycle checkpoint kinase cdk2 to allow transcription of genes required for S phase, including transcription of additional cyclin E. CCNE1, CDC34, CDK2, CUL1, E2F1, FBXW7, RB1, SKP1A, TFDP1 7 CCNE1(3), CDK2(2), CUL1(7), RB1(4), TFDP1(4) 1565322 20 15 20 3 4 2 1 9 3 1 0.230 1.000 120 HSA00940_PHENYLPROPANOID_BIOSYNTHESIS Genes involved in phenylpropanoid biosynthesis EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO 7 EPX(6), GBA3(3), LPO(2), MPO(3), PRDX6(2), TPO(8) 1812945 24 20 23 10 13 3 0 4 4 0 0.234 1.000 121 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(4), CREBBP(21), EP300(13), HDAC3(2), IKBKB(2), NFKB1(3), RELA(2), RIPK1(2), TNFRSF1A(1), TRADD(1), TRAF6(4) 5112898 55 32 55 17 20 19 2 7 7 0 0.235 1.000 122 HSA00533_KERATAN_SULFATE_BIOSYNTHESIS Genes involved in keratan sulfate biosynthesis B3GNT1, B3GNT2, B3GNT7, B4GALT1, B4GALT2, B4GALT3, B4GALT4, CHST1, CHST2, CHST4, CHST6, FUT8, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 16 B3GNT1(2), B3GNT2(1), B3GNT7(4), B4GALT1(5), B4GALT2(3), B4GALT3(6), CHST1(6), CHST2(1), CHST4(5), FUT8(1), ST3GAL1(1), ST3GAL2(1), ST3GAL3(4), ST3GAL4(2) 2751228 42 27 42 12 25 7 0 7 3 0 0.238 1.000 123 HSA00720_REDUCTIVE_CARBOXYLATE_CYCLE Genes involved in reductive carboxylate cycle (CO2 fixation) ACLY, ACO1, ACO2, ACSS1, ACSS2, FH, IDH1, IDH2, LOC441996, MDH1, MDH2, SUCLA2 11 ACLY(4), ACO1(3), ACO2(2), ACSS1(3), ACSS2(5), FH(1), IDH1(3), IDH2(7), MDH1(1), MDH2(1), SUCLA2(3) 3020520 33 23 33 6 15 7 0 8 3 0 0.239 1.000 124 STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR 10 EPX(6), GBA3(3), LPO(2), MPO(3), PRDX6(2), TPO(8), TYR(2) 2094617 26 21 25 11 13 3 0 6 4 0 0.240 1.000 125 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 AHCY(3), BHMT(3), CBS(2), CTH(1), DNMT1(12), DNMT3A(7), DNMT3B(3), MARS(3), MAT1A(5), MAT2B(2), MTR(6) 3945731 47 29 44 10 23 8 1 8 7 0 0.247 1.000 126 CARM1PATHWAY The methyltransferase CARM1 interacts with transcription factors such as CBP/p300 and methylates histones H3 and H4. CARM1, CREB1, CREBBP, EP300, NCOA3, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RARA, RXRA 13 CARM1(2), CREB1(1), CREBBP(21), EP300(13), NCOA3(6), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), RXRA(1) 4603883 51 31 51 12 15 20 2 8 6 0 0.250 1.000 127 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 5 FOSB(2), GRIA2(10), PPP1R1B(1) 814862 13 11 13 3 6 3 0 3 1 0 0.252 1.000 128 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 BCR(6), GRB2(2), LYN(4), MAP2K1(3), MAP3K1(6), MAPK1(2), MAPK3(2), MAPK8IP3(1), PAPPA(13), RPS6KA1(1), RPS6KA3(3), SHC1(3), SOS1(5), VAV1(11), VAV2(2), VAV3(10) 7169485 74 38 72 20 30 13 5 20 6 0 0.253 1.000 129 CLASSICPATHWAY The classic complement pathway is initiated by antibodies and promotes phagocytosis and lysis of foreign cells as well as activating the inflammatory response. C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C9 11 C1QB(1), C1R(2), C1S(3), C3(10), C5(9), C6(10), C7(2), C8A(3), C9(4) 3887230 44 23 44 15 14 9 0 13 7 1 0.253 1.000 130 ST_WNT_CA2_CYCLIC_GMP_PATHWAY Some Wnt glycoprotein/Frizzled receptor interactions increase intracellular calcium and decrease cGMP. BF, CAMK2A, CAMK2B, CAMK2D, CAMK2G, DAG1, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, NFAT5, PDE6A, PDE6B, PDE6C, PDE6D, PDE6G, PDE6H, SLC6A13, TF 19 CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), DAG1(4), ITPKB(4), ITPR1(11), ITPR2(12), ITPR3(11), NFAT5(5), PDE6A(6), PDE6B(5), PDE6C(8), PDE6D(1), SLC6A13(5), TF(7) 7648862 86 38 86 26 35 13 7 23 8 0 0.254 1.000 131 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(3), ABAT(5), ACAT1(1), ACAT2(2), ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH5A1(4), ALDH9A1(1), ECHS1(2), EHHADH(2), GAD1(7), GAD2(4), HADHA(2), L2HGDH(3), OXCT1(3), PDHA1(4), PDHA2(6), PDHB(2), SDHB(2), SDS(2) 5884604 82 36 82 14 31 20 0 25 6 0 0.255 1.000 132 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(2), BAD(1), CHRNB1(3), CHRNG(2), MUSK(2), PIK3R1(5), PTK2(5), PTK2B(1), RAPSN(2), SRC(3), TERT(2) 3117935 28 23 28 14 9 6 1 3 9 0 0.255 1.000 133 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(4), FARSA(1), FARSB(7), GOT1(5), GOT2(1), PAH(4), TAT(3), YARS(2), YARS2(3) 1991988 30 18 30 5 10 6 1 8 5 0 0.255 1.000 134 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(2), BAD(1), BCL2L1(1), CASP9(2), CHUK(4), MAP2K1(3), MAPK3(2), NFKB1(3), PIK3R1(5), RAF1(4), RALBP1(4), RALGDS(1), RELA(2), RHOA(4) 3844131 38 26 37 8 17 8 3 3 7 0 0.258 1.000 135 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALE(1), GALT(2), UGDH(3), UXS1(6) 852892 12 10 12 4 5 3 0 3 1 0 0.260 1.000 136 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(6), AGT(4), AGTR2(4), EDN1(1), EDNRA(4), EDNRB(7), EGF(3), EGFR(10), NFKB1(3), PLCG1(4), PRKCA(2), RELA(2) 4651612 50 31 50 16 22 9 0 14 5 0 0.262 1.000 137 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 63 ADCY1(4), ADCY8(11), ARAF(3), CACNA1C(10), CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), CAMK4(2), CREBBP(21), EP300(13), GNAQ(3), GRIA2(10), GRIN1(1), GRIN2A(15), GRIN2B(8), GRIN2C(2), GRIN2D(3), GRM1(9), GRM5(8), ITPR1(11), ITPR2(12), ITPR3(11), MAP2K1(3), MAPK1(2), MAPK3(2), PLCB1(8), PLCB2(3), PLCB3(3), PLCB4(9), PPP1CB(1), PPP1CC(1), PPP1R12A(2), PPP3CA(1), PPP3CB(4), PPP3CC(3), PPP3R1(1), PPP3R2(1), PRKACB(1), PRKACG(2), PRKCA(2), PRKCG(8), PRKX(2), RAF1(4), RAP1A(1), RAP1B(2), RAPGEF3(3), RPS6KA1(1), RPS6KA2(8), RPS6KA3(3), RPS6KA6(5) 20936197 250 69 249 97 107 62 9 48 24 0 0.263 1.000 138 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 21 AKT1(2), EIF4A2(4), EIF4G1(8), EIF4G2(7), EIF4G3(8), GHR(6), IRS1(5), MAPK1(2), MAPK14(3), MAPK3(2), MKNK1(1), PABPC1(3), PDK2(1), PDPK1(1), PIK3R1(5), PRKCA(2), PTEN(6), RPS6KB1(3) 5790690 69 34 67 16 17 17 1 23 10 1 0.263 1.000 139 MALATEXPATHWAY The tricarboxylate transfer pathway shuttles acetyl groups of acetyl-CoA between mitochondria and the cytoplasm. ACLY, CS, MDH1, ME1, PC, PDHA1, SLC25A1, SLC25A11 8 ACLY(4), MDH1(1), ME1(7), PC(3), PDHA1(4), SLC25A11(1) 2053472 20 19 20 5 8 5 0 3 4 0 0.264 1.000 140 HSA00602_GLYCOSPHINGOLIPID_BIOSYNTHESIS_NEO_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - neo-lactoseries ABO, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALT1, B4GALT2, B4GALT3, B4GALT4, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GCNT2, ST3GAL6, ST8SIA1 21 ABO(2), B3GNT1(2), B3GNT2(1), B3GNT4(1), B3GNT5(1), B4GALT1(5), B4GALT2(3), B4GALT3(6), FUT1(1), FUT2(1), FUT3(3), FUT6(1), FUT9(4), GCNT2(9), ST3GAL6(4), ST8SIA1(3) 3496006 47 27 47 10 20 8 2 13 4 0 0.270 1.000 141 SA_TRKA_RECEPTOR The TrkA receptor binds nerve growth factor to activate MAP kinase pathways and promote cell growth. AKT1, AKT2, AKT3, ARHA, CDKN1A, ELK1, GRB2, HRAS, MAP2K1, MAP2K2, NGFB, NGFR, NTRK1, PIK3CA, PIK3CD, SHC1, SOS1 14 AKT1(2), AKT2(5), CDKN1A(1), GRB2(2), MAP2K1(3), NGFR(2), NTRK1(6), PIK3CD(2), SHC1(3), SOS1(5) 3156280 31 23 30 10 9 5 5 8 4 0 0.277 1.000 142 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(4), CCNB1(2), CCND2(1), CCND3(1), CCNE1(3), CCNH(2), CDC25A(2), CDK2(2), CDK4(2), CDK6(1), CDK7(1), CDKN1A(1), CDKN1B(1), CDKN2A(1), CDKN2C(1), RB1(4), RBL1(3), TFDP1(4) 3577268 36 26 36 9 11 7 1 13 3 1 0.278 1.000 143 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(2), CREB1(1), GRB2(2), MAPK1(2), MAPK3(2), MAPK7(3), MEF2A(3), MEF2C(7), MEF2D(1), NTRK1(6), PIK3R1(5), PLCG1(4), RPS6KA1(1), SHC1(3) 3666946 42 25 41 13 14 11 2 9 6 0 0.279 1.000 144 TYROSINE_METABOLISM ABP1, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, AOX1, COMT, DBH, DCT, DDC, FAH, GOT1, GOT2, GSTZ1, HGD, HPD, MAOA, MAOB, PNMT, TAT, TH, TPO, TYR 32 ABP1(1), ADH1B(2), ADH1C(3), ADH4(1), ADH6(5), ADH7(2), ADHFE1(6), ALDH1A3(4), ALDH3A1(2), ALDH3B1(2), ALDH3B2(1), AOC2(4), AOC3(4), AOX1(5), DBH(4), DCT(9), DDC(1), FAH(1), GOT1(5), GOT2(1), GSTZ1(2), HGD(1), HPD(3), MAOA(2), TAT(3), TPO(8), TYR(2) 6890114 84 40 83 35 35 19 2 25 3 0 0.279 1.000 145 HSA00272_CYSTEINE_METABOLISM Genes involved in cysteine metabolism CARS, CARS2, CDO1, CTH, GOT1, GOT2, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, MPST, SDS, SULT1B1, SULT1C2, SULT1C4, SULT4A1 17 CARS(5), CARS2(1), CDO1(1), CTH(1), GOT1(5), GOT2(1), LDHA(1), LDHAL6A(2), LDHAL6B(1), LDHB(1), LDHC(2), SDS(2), SULT1B1(3), SULT1C2(1), SULT1C4(3), SULT4A1(1) 2869834 31 20 29 3 13 7 1 7 3 0 0.283 1.000 146 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(7), BAD(1), BAK1(1), BAX(1), BCL10(3), BCL2(1), BCL2L1(1), BCL2L11(2), BID(1), CASP8AP2(12), CASP9(2), CES1(4) 2327323 36 21 36 8 11 5 0 13 7 0 0.285 1.000 147 IL3PATHWAY IL-3 promotes proliferation and differentiation of hematopoietic cells via a heterodimeric receptor that activates the Stat5 and MAP kinase pathways. CSF2RB, FOS, GRB2, HRAS, IL3, IL3RA, JAK2, MAP2K1, MAPK3, PTPN6, RAF1, SHC1, SOS1, STAT5A, STAT5B 14 CSF2RB(7), GRB2(2), IL3(3), JAK2(6), MAP2K1(3), MAPK3(2), PTPN6(4), RAF1(4), SHC1(3), SOS1(5), STAT5B(2) 3740633 41 24 38 9 17 7 4 8 4 1 0.288 1.000 148 HSA04640_HEMATOPOIETIC_CELL_LINEAGE Genes involved in hematopoietic cell lineage ANPEP, CD14, CD19, CD1A, CD1B, CD1C, CD1D, CD1E, CD2, CD22, CD24, CD33, CD34, CD36, CD37, CD38, CD3D, CD3E, CD3G, CD4, CD44, CD5, CD55, CD59, CD7, CD8A, CD8B, CD9, CR1, CR2, CSF1, CSF1R, CSF2, CSF2RA, CSF3, CSF3R, DNTT, EPO, EPOR, FCER2, FCGR1A, FLT3, FLT3LG, GP1BA, GP1BB, GP5, GP9, GYPA, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, IL11, IL11RA, IL1A, IL1B, IL1R1, IL1R2, IL2RA, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL7, IL7R, IL9R, ITGA1, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGAM, ITGB3, KIT, KITLG, MME, MS4A1, TFRC, THPO, TNF, TPO 81 ANPEP(5), CD14(1), CD19(3), CD1A(2), CD1D(1), CD1E(5), CD2(3), CD22(8), CD33(1), CD34(1), CD36(1), CD37(2), CD38(1), CD3D(1), CD3G(2), CD4(2), CD44(3), CD5(2), CD55(3), CD7(1), CD8B(2), CD9(1), CR1(7), CR2(9), CSF1(1), CSF1R(3), CSF3R(9), DNTT(5), FCER2(1), FCGR1A(1), FLT3(3), FLT3LG(1), GP1BA(1), GP5(5), GYPA(1), HLA-DRA(4), HLA-DRB1(1), IL11(1), IL11RA(1), IL1A(1), IL1R1(3), IL1R2(3), IL2RA(2), IL3(3), IL4(3), IL4R(1), IL5RA(4), IL6(1), IL6R(2), IL7(1), IL7R(2), ITGA1(3), ITGA2(5), ITGA2B(2), ITGA3(4), ITGA4(3), ITGA5(7), ITGA6(3), ITGAM(5), ITGB3(7), KIT(6), KITLG(2), MME(6), MS4A1(4), TFRC(2), THPO(1), TPO(8) 17773655 199 61 196 59 78 40 3 59 17 2 0.289 1.000 149 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(21), EP300(13), LPL(6), NCOA1(6), NCOA2(4), PPARG(1), RXRA(1) 3981028 52 26 52 18 13 20 3 9 7 0 0.290 1.000 150 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(4), GNAS(6), GNB1(1), PRKAR1A(1) 1425557 12 12 12 8 5 3 1 3 0 0 0.291 1.000 151 ST_JAK_STAT_PATHWAY The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway transduces extracellular signals to promote gene activation. CISH, JAK1, JAK2, JAK3, PIAS1, PIAS3, PTPRU, REG1A, SOAT1 9 JAK1(3), JAK2(6), JAK3(6), PIAS1(3), PIAS3(4), PTPRU(6), REG1A(3), SOAT1(1) 3010939 32 22 30 11 15 7 1 3 5 1 0.294 1.000 152 HSA00300_LYSINE_BIOSYNTHESIS Genes involved in lysine biosynthesis AADAT, AASDHPPT, AASS, KARS 4 AADAT(1), AASDHPPT(2), AASS(7), KARS(3) 1089983 13 10 13 2 4 2 0 5 2 0 0.295 1.000 153 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(5), ALDOC(1), FBP2(2), GOT1(5), GOT2(1), GPT2(2), MDH1(1), MDH2(1), ME1(7), ME2(3), ME3(4), PGK1(3), PKM2(2), RPE(2), RPIA(3), TKT(3), TPI1(1) 3973236 47 29 47 10 14 8 1 19 5 0 0.298 1.000 154 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(4), ABAT(5), ADSL(7), ADSS(1), AGXT2(5), ASNS(1), ASPA(3), CAD(10), CRAT(3), DARS(3), DDO(2), GAD1(7), GAD2(4), GOT1(5), GOT2(1), GPT2(2), NARS(2), PC(3) 5858433 68 38 68 18 31 16 0 17 4 0 0.299 1.000 155 GPCRDB_CLASS_B_SECRETIN_LIKE ADCYAP1R1, CALCR, CALCRL, CD97, CRHR1, CRHR2, ELTD1, EMR1, EMR2, GCGR, GHRHR, GIPR, GLP1R, GLP2R, GPR64, LPHN1, LPHN2, LPHN3, PTHR1, PTHR2, SCTR, VIPR1, VIPR2 20 ADCYAP1R1(1), CALCR(3), CALCRL(5), CD97(3), CRHR1(1), CRHR2(4), ELTD1(5), EMR1(5), EMR2(2), GHRHR(2), GLP1R(2), GLP2R(3), GPR64(5), LPHN1(3), LPHN2(10), LPHN3(10), SCTR(3), VIPR1(3), VIPR2(3) 5936337 73 35 71 25 25 14 1 24 9 0 0.300 1.000 156 SIG_CHEMOTAXIS Genes related to chemotaxis ACTR2, ACTR3, AKT1, AKT2, AKT3, ANGPTL2, ARHGAP1, ARHGAP4, ARHGEF11, BTK, CDC42, CFL1, CFL2, GDI1, GDI2, INPPL1, ITPR1, ITPR2, ITPR3, LIMK1, MYLK, MYLK2, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDK1, PIK3CA, PIK3CD, PIK3CG, PIK3R1, PITX2, PPP1R13B, PTEN, RACGAP1, RHO, ROCK1, ROCK2, RPS4X, SAG, WASF1, WASL 43 ACTR2(1), ACTR3(2), AKT1(2), AKT2(5), ANGPTL2(8), ARHGAP4(1), ARHGEF11(9), BTK(6), CFL1(1), GDI1(1), GDI2(1), INPPL1(3), ITPR1(11), ITPR2(12), ITPR3(11), LIMK1(4), MYLK(11), MYLK2(2), PAK1(4), PAK2(2), PAK3(3), PAK6(1), PAK7(4), PIK3CD(2), PIK3CG(12), PIK3R1(5), PITX2(2), PPP1R13B(5), PTEN(6), RACGAP1(2), RHO(2), ROCK1(8), ROCK2(2), RPS4X(1), SAG(1), WASF1(1), WASL(5) 14719075 159 56 158 52 54 34 6 44 20 1 0.303 1.000 157 HSA00232_CAFFEINE_METABOLISM Genes involved in caffeine metabolism CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH 7 CYP1A2(2), CYP2A13(6), CYP2A6(3), CYP2A7(5), XDH(7) 1773025 23 15 23 9 6 7 1 6 3 0 0.305 1.000 158 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(2), AGT(4), AGTR1(3), AGTR2(4), BDKRB2(2), KNG1(3), NOS3(2), REN(3) 2194883 23 19 23 5 8 5 0 6 4 0 0.307 1.000 159 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(1), IL11(1), IL2(3), IL3(3), IL4(3), IL6(1), IL7(1), IL9(1) 1411652 16 12 15 4 7 3 0 5 1 0 0.307 1.000 160 HSA01030_GLYCAN_STRUCTURES_BIOSYNTHESIS_1 Genes involved in glycan structures - biosynthesis 1 A4GNT, ALG1, ALG10, ALG10B, ALG11, ALG12, ALG13, ALG14, ALG2, ALG3, ALG6, ALG8, ALG9, B3GALT6, B3GNT1, B3GNT2, B3GNT6, B3GNT7, B4GALT1, B4GALT2, B4GALT3, B4GALT4, B4GALT5, B4GALT7, C1GALT1, C1GALT1C1, ChGn, CHPF, CHST1, CHST11, CHST12, CHST13, CHST14, CHST2, CHST3, CHST4, CHST6, CHST7, CHSY-2, CHSY1, CSGlcA-T, DAD1, DDOST, DPAGT1, EXT1, EXT2, EXTL1, EXTL2, EXTL3, FUT11, FUT8, GALNAC4S-6ST, GALNACT-2, GALNT1, GALNT10, GALNT11, GALNT12, GALNT13, GALNT14, GALNT17, GALNT2, GALNT3, GALNT4, GALNT5, GALNT6, GALNT7, GALNT8, GALNT9, GALNTL1, GALNTL2, GALNTL4, GALNTL5, GANAB, GCNT1, GCNT3, GCNT4, GCS1, HS2ST1, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, HS3ST5, HS6ST1, HS6ST2, HS6ST3, LOC728969, MAN1A1, MAN1A2, MAN1B1, MAN1C1, MAN2A1, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT5, MGAT5B, NDST1, NDST2, NDST3, NDST4, OGT, RPN1, RPN2, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST6GAL1, ST6GALNAC1, STT3B, UST, WBSCR17, XYLT1, XYLT2 108 A4GNT(2), ALG10(3), ALG10B(4), ALG11(1), ALG12(2), ALG13(1), ALG2(3), ALG3(1), ALG6(3), ALG8(5), ALG9(1), B3GNT1(2), B3GNT2(1), B3GNT7(4), B4GALT1(5), B4GALT2(3), B4GALT3(6), B4GALT5(2), C1GALT1C1(2), CHPF(3), CHST1(6), CHST11(2), CHST12(2), CHST13(1), CHST14(1), CHST2(1), CHST4(5), CHSY1(5), DAD1(2), DDOST(2), DPAGT1(1), EXT1(10), EXTL1(3), EXTL2(3), EXTL3(7), FUT8(1), GALNT1(2), GALNT10(5), GALNT11(4), GALNT12(1), GALNT13(5), GALNT14(9), GALNT2(3), GALNT3(4), GALNT5(6), GALNT6(2), GALNT7(2), GALNT8(1), GALNT9(2), GALNTL1(3), GALNTL2(6), GALNTL4(1), GALNTL5(5), GANAB(4), GCNT1(3), GCNT3(2), GCNT4(5), HS2ST1(3), HS3ST1(1), HS3ST2(1), HS3ST3B1(2), HS3ST5(4), HS6ST2(2), HS6ST3(2), MAN1A1(4), MAN1A2(2), MAN1B1(2), MAN1C1(4), MAN2A1(8), MGAT1(1), MGAT3(2), MGAT4A(2), MGAT4B(1), MGAT5(3), MGAT5B(2), NDST1(3), NDST2(5), NDST3(7), NDST4(4), OGT(4), ST3GAL1(1), ST3GAL2(1), ST3GAL3(4), ST3GAL4(2), ST6GAL1(1), ST6GALNAC1(2), STT3B(4), UST(1), XYLT1(4), XYLT2(2) 24224704 272 75 271 78 107 62 7 69 27 0 0.308 1.000 161 HSA00680_METHANE_METABOLISM Genes involved in methane metabolism ADH5, CAT, EPX, LPO, MPO, MTHFR, PRDX6, SHMT1, SHMT2, TPO 10 ADH5(1), CAT(2), EPX(6), LPO(2), MPO(3), MTHFR(6), PRDX6(2), SHMT1(1), SHMT2(2), TPO(8) 2537296 33 23 32 10 18 5 0 7 3 0 0.308 1.000 162 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(2) 166939 2 2 2 0 1 0 0 0 1 0 0.308 1.000 163 SA_DIACYLGLYCEROL_SIGNALING DAG (diacylglycerol) signaling activity ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP 10 ESR1(12), ESR2(2), PDE1A(3), PDE1B(2), PLCB1(8), PLCB2(3), PRL(2), TRH(1) 2504248 33 20 33 8 13 9 0 7 4 0 0.309 1.000 164 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), PLCD1(6), PRKCA(2), TGM2(4) 1129699 16 11 16 4 6 2 1 6 1 0 0.309 1.000 165 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 108 ACTN1(3), ACTN2(7), ACTN3(2), ACTN4(2), ARHGAP5(6), CDH5(2), CLDN10(2), CLDN11(1), CLDN15(1), CLDN16(4), CLDN17(5), CLDN18(2), CLDN19(1), CLDN6(2), CLDN7(2), CLDN8(3), CLDN9(1), CTNNA1(10), CTNNA2(10), CTNNA3(9), CTNNB1(8), CTNND1(5), CXCL12(1), CXCR4(3), CYBB(1), ESAM(3), EZR(2), F11R(1), GNAI1(3), GRLF1(7), ICAM1(2), ITGA4(3), ITGAL(5), ITGAM(5), ITGB1(6), ITGB2(4), ITK(8), JAM3(3), MAPK12(2), MAPK14(3), MLLT4(3), MMP2(2), MMP9(6), MSN(3), MYL2(1), MYL7(1), NCF1(1), NCF2(1), NCF4(2), NOX1(1), NOX3(5), OCLN(1), PECAM1(1), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PLCG1(4), PLCG2(9), PRKCA(2), PRKCG(8), PTK2(5), PTK2B(1), PTPN11(2), RAP1A(1), RAP1B(2), RAPGEF3(3), RAPGEF4(7), RASSF5(3), RHOA(4), RHOH(2), ROCK1(8), ROCK2(2), SIPA1(1), TXK(4), VASP(3), VAV1(11), VAV2(2), VAV3(10), VCAM1(7), VCL(1) 26878094 303 79 298 87 122 61 6 72 42 0 0.309 1.000 166 SPPAPATHWAY Thrombin cleaves protease-activated receptors PAR1 and PAR4 to induce calcium influx and activate platelet aggregation, a process inhibited by aspirin. F2, F2R, F2RL3, GNAI1, GNB1, GNGT1, HRAS, ITGA1, ITGB1, MAP2K1, MAPK1, MAPK3, PLA2G4A, PLCB1, PRKCA, PRKCB1, PTGS1, PTK2, RAF1, SRC, SYK, TBXAS1 21 F2(2), GNAI1(3), GNB1(1), ITGA1(3), ITGB1(6), MAP2K1(3), MAPK1(2), MAPK3(2), PLA2G4A(5), PLCB1(8), PRKCA(2), PTGS1(4), PTK2(5), RAF1(4), SRC(3), TBXAS1(5) 5577911 58 32 57 17 23 13 2 17 3 0 0.317 1.000 167 KERATAN_SULFATE_BIOSYNTHESIS B3GNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT5, FUT8, SIAT4A, SIAT4B, SIAT6, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 10 B3GNT1(2), B4GALT1(5), B4GALT2(3), B4GALT3(6), B4GALT5(2), FUT8(1), ST3GAL1(1), ST3GAL2(1), ST3GAL3(4), ST3GAL4(2) 1810012 27 19 27 4 14 6 0 5 2 0 0.322 1.000 168 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(14), CPT1A(5), LEP(1), LEPR(5), PRKAA1(2), PRKAA2(6), PRKAB1(1), PRKAB2(1), PRKAG1(1), PRKAG2(2) 3310353 38 23 38 13 13 8 0 12 5 0 0.322 1.000 169 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 ALDH6A1(3), TPI1(1) 351993 4 4 4 0 0 0 0 4 0 0 0.323 1.000 170 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 ATG5(3), ATG7(1), BECN1(2), IFNA1(1), IFNA10(1), IFNA13(2), IFNA16(4), IFNA2(3), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), IFNG(1), PIK3C3(5), PIK3R4(12), PRKAA1(2), PRKAA2(6), ULK2(4), ULK3(3) 4664018 59 28 59 14 11 17 2 26 3 0 0.326 1.000 171 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(1), F2(2), F3(1), F5(14), F7(2), FGA(11), FGB(1), FGG(4), PROC(1), PROS1(3), SERPINC1(3) 3699195 43 24 43 10 9 11 1 18 4 0 0.326 1.000 172 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 ACAD9(3), ADH1B(2), ADH1C(3), ADH4(1), ADH5(1), ADH6(5), ADH7(2), ADHFE1(6), DHRS1(1), DHRS2(2), DHRS3(2), ESCO1(7), ESCO2(3), MYST3(13), MYST4(5), PNPLA3(4), SH3GLB1(3) 5432175 63 31 63 22 22 16 3 18 4 0 0.329 1.000 173 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(4), AKT1(2), CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), CREB1(1), GNAS(6), GRB2(2), MAPK1(2), MAPK14(3), MAPK3(2), PIK3R1(5), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PRKCA(2), RPS6KA1(1), RPS6KA5(3), SOS1(5) 5999120 52 32 52 20 17 9 6 16 4 0 0.330 1.000 174 HSA00710_CARBON_FIXATION Genes involved in carbon fixation ALDOA, ALDOB, ALDOC, FBP1, FBP2, GOT1, GOT2, GPT, GPT2, MDH1, MDH2, ME1, ME3, PGK1, PGK2, PKLR, PKM2, RPE, RPIA, TKT, TKTL1, TKTL2, TPI1 23 ALDOA(1), ALDOB(5), ALDOC(1), FBP2(2), GOT1(5), GOT2(1), GPT2(2), MDH1(1), MDH2(1), ME1(7), ME3(4), PGK1(3), PGK2(6), PKM2(2), RPE(2), RPIA(3), TKT(3), TKTL1(4), TKTL2(5), TPI1(1) 4448432 59 32 59 14 19 11 0 23 6 0 0.330 1.000 175 GPCRDB_OTHER ADORA3, ALG6, C5R1, CCKBR, CCR2, CCR3, CCR5, CELSR1, CELSR2, CELSR3, CHRM2, CHRM3, CIDEB, CXCR3, DRD4, EBI2, EDG1, EDNRA, ELA3A, EMR2, EMR3, F2R, FSHR, FY, GHRHR, GNRHR, GPR, GPR116, GPR132, GPR133, GPR135, GPR143, GPR145, GPR17, GPR18, GPR55, GPR56, GPR61, GPR73L1, GPR77, GPR84, GPR88, GRCA, GRM1, GRPR, HRH4, IL8RA, IL8RB, LGR6, LGR7, LPHN2, LPHN3, LTB4R2, MASS1, NTSR1, OR2A9P, OR2M4, OR5E1P, OR7E19P, OR7E47P, OR7E37P, OR7E18P, OR7E35P, LOC441453, OR8G1, LOC442754, OR8G2, P2RY11, P2RY13, PTGFR, RLN3R1, SMO, SSTR2, TAAR5, TSHR, VN1R1 52 ADORA3(3), ALG6(3), CCKBR(3), CCR3(3), CCR5(1), CELSR1(8), CELSR2(8), CELSR3(5), CHRM2(8), CHRM3(4), EDNRA(4), EMR2(2), EMR3(7), FSHR(6), GHRHR(2), GNRHR(4), GPR116(7), GPR132(1), GPR133(7), GPR143(2), GPR17(1), GPR55(1), GPR56(1), GPR61(4), GPR77(1), GPR84(3), GPR88(1), GRM1(9), GRPR(3), HRH4(2), LPHN2(10), LPHN3(10), NTSR1(1), OR8G2(1), P2RY13(2), PTGFR(6), SSTR2(2), TAAR5(5), TSHR(6), VN1R1(4) 14332202 161 59 158 60 62 34 3 47 15 0 0.332 1.000 176 SA_REG_CASCADE_OF_CYCLIN_EXPR Expression of cyclins regulates progression through the cell cycle by activating cyclin-dependent kinases. CCNA1, CCNA2, CCND1, CCNE1, CCNE2, CDK2, CDK4, CDKN1B, CDKN2A, E2F1, E2F2, E2F4, PRB1 13 CCNA1(4), CCNA2(3), CCNE1(3), CCNE2(1), CDK2(2), CDK4(2), CDKN1B(1), CDKN2A(1), E2F2(1), E2F4(1) 1943874 19 16 19 4 6 3 0 9 1 0 0.333 1.000 177 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(4), CFTR(8), GNAS(6), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), SLC9A3R1(3) 2834468 28 23 28 10 10 4 1 10 3 0 0.333 1.000 178 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(3), ACTN1(3), ACTN2(7), ACTN3(2), BCR(6), CAPN1(2), CAPNS1(1), CAPNS2(1), CRKL(2), CSK(1), FYN(4), GRB2(2), ITGA1(3), ITGB1(6), MAP2K1(3), MAPK1(2), MAPK3(2), MAPK8(2), PPP1R12B(5), PTK2(5), RAF1(4), RAP1A(1), ROCK1(8), SHC1(3), SOS1(5), SRC(3), TLN1(5), VCL(1) 10350397 92 48 89 29 38 22 3 22 7 0 0.339 1.000 179 ACETAMINOPHENPATHWAY Acetaminophen selectively inhibits Cox-3, which is localized to the brain, and yields the toxic metabolite NAPQI when processed by CAR in the liver. CYP1A2, CYP2E1, CYP3A, NR1I3, PTGS1, PTGS2 5 CYP1A2(2), CYP2E1(5), NR1I3(2), PTGS1(4), PTGS2(2) 1190438 15 12 15 2 7 4 0 4 0 0 0.350 1.000 180 HSA03022_BASAL_TRANSCRIPTION_FACTORS Genes involved in basal transcription factors GTF2A1, GTF2A1L, GTF2A2, GTF2B, GTF2E1, GTF2E2, GTF2F1, GTF2F2, GTF2H1, GTF2H2, GTF2H3, GTF2H4, GTF2I, GTF2IRD1, LOC391764, STON1, TAF1, TAF10, TAF12, TAF13, TAF1L, TAF2, TAF4, TAF4B, TAF5, TAF5L, TAF6, TAF6L, TAF7, TAF7L, TAF9, TAF9B, TBPL1, TBPL2 33 GTF2A1(2), GTF2B(1), GTF2E1(5), GTF2F1(3), GTF2H1(2), GTF2H3(4), GTF2H4(1), GTF2IRD1(8), TAF1(7), TAF1L(16), TAF2(6), TAF4(4), TAF4B(4), TAF5(3), TAF5L(1), TAF6(2), TAF6L(2), TAF7(1), TAF7L(3), TAF9B(1), TBPL1(1), TBPL2(1) 8143764 78 41 78 21 30 17 1 24 6 0 0.350 1.000 181 ST_STAT3_PATHWAY The transcription factor STAT3 is involved in cell growth regulation and is commonly upregulated in tumors. CISH, IL6, IL6R, JAK1, JAK2, JAK3, PIAS3, PTPRU, REG1A, SRC, STAT3 11 IL6(1), IL6R(2), JAK1(3), JAK2(6), JAK3(6), PIAS3(4), PTPRU(6), REG1A(3), SRC(3), STAT3(2) 3429621 36 24 34 16 17 10 1 4 3 1 0.352 1.000 182 HSA00480_GLUTATHIONE_METABOLISM Genes involved in glutathione metabolism ANPEP, G6PD, GCLC, GCLM, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GSR, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, OPLAH, TXNDC12 34 ANPEP(5), G6PD(2), GCLC(4), GCLM(1), GPX1(1), GPX2(2), GPX3(1), GPX5(4), GPX6(2), GSR(1), GSS(4), GSTA1(1), GSTA3(3), GSTA5(1), GSTM2(2), GSTM3(2), GSTM4(2), GSTM5(1), GSTZ1(2), IDH1(3), IDH2(7), MGST1(2), MGST3(1) 4587593 54 29 54 8 11 13 2 21 7 0 0.355 1.000 183 HSA04612_ANTIGEN_PROCESSING_AND_PRESENTATION Genes involved in antigen processing and presentation B2M, CALR, CANX, CD4, CD74, CD8A, CD8B, CIITA, CREB1, CTSB, CTSL1, CTSS, HLA-A, HLA-A29.1, HLA-B, HLA-C, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-E, HLA-F, HLA-G, HSP90AA1, HSP90AB1, HSPA5, IFI30, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LGMN, LTA, NFYA, NFYB, NFYC, PDIA3, PSME1, PSME2, RFX5, RFXANK, RFXAP, TAP1, TAP2, TAPBP 73 B2M(3), CANX(2), CD4(2), CD74(1), CD8B(2), CIITA(6), CREB1(1), CTSB(2), CTSL1(3), CTSS(2), HLA-A(1), HLA-B(3), HLA-C(2), HLA-DMA(2), HLA-DOB(1), HLA-DPA1(1), HLA-DPB1(1), HLA-DQA1(1), HLA-DQA2(1), HLA-DRA(4), HLA-DRB1(1), HLA-E(1), HLA-F(1), HLA-G(1), HSP90AA1(2), HSP90AB1(1), IFI30(1), IFNA1(1), IFNA10(1), IFNA13(2), IFNA16(4), IFNA2(3), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), KIR2DL1(2), KIR2DL3(1), KIR2DL4(2), KIR3DL1(3), KIR3DL2(3), KIR3DL3(4), KLRC3(2), KLRC4(1), KLRD1(1), LGMN(1), NFYA(1), NFYB(1), NFYC(3), PDIA3(1), RFX5(1), RFXAP(1), TAP1(3), TAP2(4), TAPBP(3) 10267263 107 41 104 30 21 27 5 32 17 5 0.356 1.000 184 G1PATHWAY CDK4/6-cyclin D and CDK2-cyclin E phosphorylate Rb, which allows the transcription of genes needed for the G1/S cell cycle transition. ABL1, ATM, ATR, CCNA1, CCND1, CCNE1, CDC2, CDC25A, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, DHFR, E2F1, GSK3B, HDAC1, MADH3, MADH4, RB1, SKP2, TFDP1, TGFB1, TGFB2, TGFB3, TP53 22 ABL1(4), ATR(13), CCNA1(4), CCNE1(3), CDC25A(2), CDK2(2), CDK4(2), CDK6(1), CDKN1A(1), CDKN1B(1), CDKN2A(1), GSK3B(7), HDAC1(2), RB1(4), SKP2(1), TFDP1(4), TGFB1(1), TGFB2(5) 5148613 58 29 58 11 20 11 2 16 8 1 0.358 1.000 185 APOPTOSIS_KEGG APAF1, BAD, BAX, BCL2, BCL2A1, BCL2L1, BCL2L2, BOK, CASP1, CASP1, COPl, CASP10, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CD40, CD40LG, CRADD, CYCS, DAXX, DFFA, DFFB, FADD, FAS, FASLG, HRK, IKBKE, LTA, MCL1, NFKB1, NFKBIA, NGFB, NGFR, NR3C1, NTRK1, PTPN13, RIPK1, SFRS2IP, TFG, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF1, TRAF2, TRAF3, TRAF6 46 APAF1(7), BAD(1), BAX(1), BCL2(1), BCL2L1(1), BOK(1), CASP1(2), CASP10(2), CASP2(4), CASP3(1), CASP4(1), CASP6(1), CASP7(1), CASP9(2), CD40LG(6), CRADD(1), DFFA(2), DFFB(2), FASLG(1), IKBKE(3), NFKB1(3), NGFR(2), NR3C1(3), NTRK1(6), PTPN13(8), RIPK1(2), SFRS2IP(3), TFG(6), TNFRSF1A(1), TRADD(1), TRAF1(1), TRAF2(1), TRAF3(4), TRAF6(4) 9415263 86 44 85 40 27 16 4 27 11 1 0.359 1.000 186 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(4), GRB2(2), INSR(5), IRS1(5), MAP2K1(3), MAPK3(2), MAPK8(2), PIK3R1(5), PTPN11(2), RAF1(4), RASA1(5), SHC1(3), SLC2A4(3), SOS1(5), SRF(3) 5201403 53 32 51 16 12 14 3 17 7 0 0.359 1.000 187 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(2), CSF1R(3), EGF(3), EGFR(10), GRB2(2), MET(4), PDGFRA(13), PRKCA(2), SH3GLB1(3), SH3GLB2(2), SH3KBP1(4), SRC(3) 4379823 51 25 51 25 14 12 3 17 4 1 0.359 1.000 188 TALL1PATHWAY APRIL and BAFF bind to BCMA and TACI receptors on B cell surfaces, promoting immunoglobulin production and cell proliferation. CHUK, MAP3K14, MAPK14, MAPK8, NFKB1, RELA, TNFRSF13B, TNFRSF13C, TNFRSF17, TNFSF13, TNFSF13B, TRAF2, TRAF3, TRAF5, TRAF6 15 CHUK(4), MAP3K14(2), MAPK14(3), MAPK8(2), NFKB1(3), RELA(2), TNFRSF13B(4), TNFRSF17(2), TNFSF13(2), TRAF2(1), TRAF3(4), TRAF5(4), TRAF6(4) 3197661 37 25 36 11 17 6 0 8 6 0 0.366 1.000 189 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), IL12B(2), IL2(3) 665213 8 6 8 5 0 3 0 5 0 0 0.370 1.000 190 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 AKT1(2), GNAS(6), GNB1(1), NFKB1(3), NOS3(2), NPPA(1), NR3C1(3), PIK3R1(5), RELA(2), SYT1(1) 3517726 26 22 26 13 9 2 2 7 6 0 0.374 1.000 191 HSA04742_TASTE_TRANSDUCTION Genes involved in taste transduction ACCN1, ADCY4, ADCY6, ADCY8, CACNA1A, CACNA1B, GNAS, GNAT3, GNB1, GNB3, GNG13, GNG3, GRM4, ITPR3, KCNB1, PDE1A, PLCB2, PRKACA, PRKACB, PRKACG, PRKX, PRKY, SCNN1A, SCNN1B, SCNN1G, TAS1R1, TAS1R2, TAS1R3, TAS2R1, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R3, TAS2R38, TAS2R39, TAS2R4, TAS2R40, TAS2R41, TAS2R42, TAS2R43, TAS2R44, TAS2R45, TAS2R46, TAS2R48, TAS2R49, TAS2R5, TAS2R50, TAS2R60, TAS2R7, TAS2R8, TAS2R9, TRPM5 47 ACCN1(6), ADCY4(9), ADCY6(1), ADCY8(11), CACNA1A(8), CACNA1B(7), GNAS(6), GNAT3(1), GNB1(1), GNB3(3), GNG3(2), GRM4(7), ITPR3(11), KCNB1(2), PDE1A(3), PLCB2(3), PRKACB(1), PRKACG(2), PRKX(2), SCNN1A(3), SCNN1B(3), SCNN1G(2), TAS1R1(6), TAS1R2(5), TAS2R1(1), TAS2R10(3), TAS2R13(3), TAS2R16(1), TAS2R3(1), TAS2R38(2), TAS2R39(2), TAS2R4(1), TAS2R41(1), TAS2R46(1), TAS2R5(1), TAS2R50(4), TAS2R60(1), TAS2R8(1), TAS2R9(1) 11915572 129 53 129 46 52 24 3 40 10 0 0.375 1.000 192 PARKINPATHWAY In Parkinson's disease, dopaminergic neurons contain Lewy bodies consisting of alpha-synuclein and parkin, an E3 ubiquitin ligase that targets glycosylated alpha-synuclein. GPR37, PARK2, PNUTL1, SNCA, SNCAIP, UBE2E2, UBE2F, UBE2G1, UBE2G2, UBE2L3, UBE2L6, UBL1 10 GPR37(6), PARK2(4), SNCA(1), SNCAIP(1), UBE2F(1), UBE2G1(2), UBE2L3(2) 1454834 17 13 17 7 5 5 0 6 1 0 0.379 1.000 193 PDGFPATHWAY Platelet-derived growth factor (PDGF) receptor is phosphorylated on ligand binding and promotes cell proliferation. CSNK2A1, ELK1, FOS, GRB2, HRAS, JAK1, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, PDGFA, PDGFRA, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, SRF, STAT1, STAT3, STAT5A 24 CSNK2A1(4), GRB2(2), JAK1(3), MAP2K1(3), MAP3K1(6), MAPK3(2), MAPK8(2), PDGFA(1), PDGFRA(13), PIK3R1(5), PLCG1(4), PRKCA(2), RAF1(4), RASA1(5), SHC1(3), SOS1(5), SRF(3), STAT1(6), STAT3(2) 7087810 75 34 72 22 22 19 5 17 11 1 0.380 1.000 194 HSA02010_ABC_TRANSPORTERS_GENERAL Genes involved in ABC transporters - general ABCA1, ABCA10, ABCA12, ABCA13, ABCA2, ABCA3, ABCA4, ABCA5, ABCA6, ABCA7, ABCA8, ABCA9, ABCB1, ABCB10, ABCB11, ABCB4, ABCB5, ABCB6, ABCB7, ABCB8, ABCB9, ABCC1, ABCC10, ABCC11, ABCC12, ABCC2, ABCC3, ABCC4, ABCC5, ABCC6, ABCC8, ABCC9, ABCD1, ABCD2, ABCD3, ABCD4, ABCG1, ABCG2, ABCG4, ABCG5, ABCG8, CFTR, TAP1, TAP2 44 ABCA1(17), ABCA10(7), ABCA12(22), ABCA13(23), ABCA3(5), ABCA4(10), ABCA5(15), ABCA6(12), ABCA7(5), ABCA8(10), ABCA9(12), ABCB1(6), ABCB10(3), ABCB11(8), ABCB4(8), ABCB5(10), ABCB6(3), ABCB7(3), ABCB8(4), ABCB9(2), ABCC1(8), ABCC10(7), ABCC11(9), ABCC12(7), ABCC2(11), ABCC3(5), ABCC4(9), ABCC5(5), ABCC6(5), ABCC8(7), ABCC9(7), ABCD1(3), ABCD2(8), ABCD3(3), ABCD4(5), ABCG1(5), ABCG2(5), ABCG4(3), ABCG5(1), ABCG8(4), CFTR(8), TAP1(3), TAP2(4) 26106513 317 72 315 96 100 74 7 94 40 2 0.380 1.000 195 BIOGENIC_AMINE_SYNTHESIS AANAT, ACHE, CHAT, COMT, DBH, DDC, DXYS155E, GAD1, GAD2, HDC, MAOA, PAH, PNMT, SLC18A3, TH, TPH1 15 CHAT(6), DBH(4), DDC(1), GAD1(7), GAD2(4), HDC(3), MAOA(2), PAH(4), SLC18A3(6), TPH1(1) 3220226 38 26 38 18 16 10 1 10 1 0 0.381 1.000 196 HSA00791_ATRAZINE_DEGRADATION Genes involved in atrazine degradation ADAR, APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3F, APOBEC3G, APOBEC4 9 ADAR(6), APOBEC1(2), APOBEC2(1), APOBEC3A(1), APOBEC3C(3), APOBEC3F(1), APOBEC3G(2), APOBEC4(2) 1633065 18 14 18 3 7 4 0 5 2 0 0.381 1.000 197 HBXPATHWAY Hbx is a hepatitis B protein that activates a number of transcription factors, possibly by inducing calcium release from the mitochondrion to the cytoplasm. CREB1, GRB2, HBXIP, HRAS, PTK2B, SHC1, SOS1, SRC 8 CREB1(1), GRB2(2), HBXIP(2), PTK2B(1), SHC1(3), SOS1(5), SRC(3) 1995497 17 15 16 6 2 4 2 6 3 0 0.382 1.000 198 D4GDIPATHWAY D4-GDI inhibits the pro-apoptotic Rho GTPases and is cleaved by caspase-3. ADPRT, APAF1, ARHGAP5, ARHGDIB, CASP1, CASP10, CASP3, CASP8, CASP9, CYCS, GZMB, JUN, PRF1 11 APAF1(7), ARHGAP5(6), ARHGDIB(3), CASP1(2), CASP10(2), CASP3(1), CASP9(2), GZMB(1) 2588916 24 20 23 9 4 4 0 10 6 0 0.383 1.000 199 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(3), ACTR2(1), ACTR3(2), ARPC1A(5), ARPC1B(2), ARPC2(1), NCKAP1(8), NTRK1(6), WASF1(1), WASF2(2), WASF3(2), WASL(5) 3437407 38 24 38 9 12 9 2 11 4 0 0.383 1.000 200 HSA00271_METHIONINE_METABOLISM Genes involved in methionine metabolism AHCY, AMD1, BHMT, CBS, CTH, DNMT1, DNMT3A, DNMT3B, KIAA0828, MARS, MARS2, MAT1A, MAT2B, MTAP, MTFMT, MTR, SRM, TAT 17 AHCY(3), BHMT(3), CBS(2), CTH(1), DNMT1(12), DNMT3A(7), DNMT3B(3), MARS(3), MAT1A(5), MAT2B(2), MTFMT(1), MTR(6), TAT(3) 4665290 51 31 48 13 24 10 1 8 8 0 0.383 1.000 201 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(4), ARHGEF1(4), F2(2), GNA12(2), GNA13(2), GNAI1(3), GNAQ(3), GNB1(1), MAP3K7(2), PIK3R1(5), PLCB1(8), PPP1R12B(5), PRKCA(2), PTK2B(1), ROCK1(8) 5357040 52 29 51 17 16 7 2 17 10 0 0.388 1.000 202 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 70 AKT1(2), AKT2(5), BTK(6), FCER1A(2), FYN(4), GAB2(1), GRB2(2), IL13(1), IL3(3), IL4(3), INPP5D(2), LCP2(2), LYN(4), MAP2K1(3), MAP2K3(2), MAP2K6(2), MAPK1(2), MAPK10(4), MAPK12(2), MAPK14(3), MAPK3(2), MAPK8(2), MAPK9(3), MS4A2(1), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PLA2G1B(1), PLA2G2F(1), PLA2G4A(5), PLA2G6(2), PLCG1(4), PLCG2(9), PRKCA(2), PRKCD(3), PRKCE(4), RAF1(4), SOS1(5), SOS2(9), VAV1(11), VAV2(2), VAV3(10) 15222573 158 56 154 43 60 36 7 41 14 0 0.389 1.000 203 EPHA4PATHWAY Eph Kinases and ephrins support platelet aggregation ACTA1, EPHA4, EPHB1, FYN, ITGA1, ITGB1, L1CAM, LYN, RAP1B, SELP 10 ACTA1(3), EPHA4(4), EPHB1(6), FYN(4), ITGA1(3), ITGB1(6), L1CAM(2), LYN(4), RAP1B(2), SELP(4) 3376427 38 23 38 8 14 12 0 9 3 0 0.390 1.000 204 HSA04350_TGF_BETA_SIGNALING_PATHWAY Genes involved in TGF-beta signaling pathway ACVR1, ACVR1B, ACVR1C, ACVR2A, ACVR2B, ACVRL1, AMH, AMHR2, BMP2, BMP4, BMP5, BMP6, BMP7, BMP8A, BMP8B, BMPR1A, BMPR1B, BMPR2, CDKN2B, CHRD, COMP, CREBBP, CUL1, DCN, E2F4, E2F5, EP300, FST, GDF5, GDF6, GDF7, hCG_1982709, ID1, ID2, ID3, ID4, IFNG, INHBA, INHBB, INHBC, INHBE, LEFTY1, LEFTY2, LTBP1, MAPK1, MAPK3, MYC, NODAL, NOG, PITX2, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, RBL1, RBL2, RBX1, RHOA, ROCK1, ROCK2, RPS6KB1, RPS6KB2, SKP1, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6, SMAD7, SMAD9, SMURF1, SMURF2, SP1, TFDP1, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, THBS1, THBS2, THBS3, THBS4, TNF, ZFYVE16, ZFYVE9 82 ACVR1(3), ACVR1C(2), ACVR2B(3), ACVRL1(3), AMHR2(2), BMP4(1), BMP5(4), BMP6(3), BMP7(5), BMP8A(1), BMPR1A(4), BMPR1B(9), BMPR2(7), CHRD(5), COMP(2), CREBBP(21), CUL1(7), DCN(3), E2F4(1), E2F5(2), EP300(13), FST(2), GDF5(1), GDF6(2), IFNG(1), INHBB(1), INHBC(2), LTBP1(8), MAPK1(2), MAPK3(2), NODAL(1), PITX2(2), PPP2CA(1), PPP2R1A(4), PPP2R1B(1), PPP2R2A(1), PPP2R2B(1), PPP2R2C(3), RBL1(3), RBL2(8), RHOA(4), ROCK1(8), ROCK2(2), RPS6KB1(3), RPS6KB2(1), SKP1(1), SMAD1(2), SMAD3(6), SMAD9(2), SMURF1(1), SMURF2(2), SP1(2), TFDP1(4), TGFB1(1), TGFB2(5), TGFBR1(6), THBS1(8), THBS2(10), THBS3(2), THBS4(1), ZFYVE16(9), ZFYVE9(6) 20817952 233 67 230 91 79 61 3 56 34 0 0.390 1.000 205 OVARIAN_INFERTILITY_GENES ATM, BMPR1B, CCND2, CDK4, CDKN1B, CEBPB, DAZL, DMC1, EGR1, ESR2, FSHR, GJA4, INHA, LHCGR, MLH1, MSH5, NCOR1, NR5A1, NRIP1, PGR, PRLR, PTGER2, SMPD1, VDR, ZP2 24 BMPR1B(9), CCND2(1), CDK4(2), CDKN1B(1), DAZL(1), DMC1(3), EGR1(2), ESR2(2), FSHR(6), GJA4(2), INHA(2), LHCGR(4), MLH1(5), MSH5(4), NCOR1(7), NRIP1(5), PGR(4), PRLR(2), PTGER2(1), SMPD1(6), VDR(1), ZP2(6) 6470356 76 34 76 24 25 17 1 22 11 0 0.392 1.000 206 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 8 CARS(5), CTH(1), GOT1(5), GOT2(1), LDHA(1), LDHB(1), LDHC(2) 1549666 16 13 16 2 7 4 0 3 2 0 0.393 1.000 207 EIF2PATHWAY Eukaryotic initiation factor 2 (EIF2) initiates translation by transferring Met-tRNA to the 40S ribosome in a GTP-dependent process. EIF2AK3, EIF2AK4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF5, GSK3B, HRI, PPP1CA, PRKR 9 EIF2AK3(1), EIF2AK4(5), EIF2B5(5), EIF2S2(1), EIF2S3(1), EIF5(3), GSK3B(7) 2546207 23 17 23 3 6 7 2 3 5 0 0.396 1.000 208 ERYTHPATHWAY Erythropoietin selectively stimulates erythrocyte differentiation from CFU-GEMM cells in bone marrow. CCL3, CSF2, CSF3, EPO, FLT3, IGF1, IL11, IL1A, IL3, IL6, IL9, KITLG, TGFB1, TGFB2, TGFB3 15 FLT3(3), IGF1(2), IL11(1), IL1A(1), IL3(3), IL6(1), IL9(1), KITLG(2), TGFB1(1), TGFB2(5) 1903197 20 16 19 8 8 1 0 8 3 0 0.396 1.000 209 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 3 FAH(1), GSTZ1(2), HGD(1) 380018 4 3 4 3 0 1 0 2 1 0 0.406 1.000 210 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(6), DLG4(2), EPHB2(7), F2(2), F2RL2(2), MAP2K5(2), MAPK1(2), MAPK7(3), MAPK8(2), MYEF2(7), PLD1(8), PLD2(1), PLD3(5), PTK2(5), RAF1(4), RASAL1(1), SRC(3), TEC(1), VAV1(11) 6158399 74 36 72 24 36 18 1 14 5 0 0.407 1.000 211 SIG_PIP3_SIGNALING_IN_B_LYMPHOCYTES Genes related to PIP3 signaling in B lymphocytes AKT1, AKT2, AKT3, BCR, BTK, CD19, CDKN2A, DAPP1, FLOT1, FLOT2, FOXO3A, GAB1, ITPR1, ITPR2, ITPR3, LYN, NR0B2, P101-PI3K, PDK1, PHF11, PIK3CA, PITX2, PLCG2, PPP1R13B, PREX1, PSCD3, PTEN, PTPRC, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SAG, SYK, TEC, VAV1 32 AKT1(2), AKT2(5), BCR(6), BTK(6), CD19(3), CDKN2A(1), DAPP1(1), FLOT1(3), GAB1(6), ITPR1(11), ITPR2(12), ITPR3(11), LYN(4), PHF11(2), PITX2(2), PLCG2(9), PPP1R13B(5), PREX1(14), PTEN(6), PTPRC(9), RPS6KA1(1), RPS6KA2(8), RPS6KA3(3), RPS6KB1(3), SAG(1), TEC(1), VAV1(11) 11427664 146 49 143 46 58 33 4 33 17 1 0.412 1.000 212 HSA00730_THIAMINE_METABOLISM Genes involved in thiamine metabolism LHPP, MTMR1, MTMR2, MTMR6, NFS1, PHPT1, THTPA, TPK1 8 LHPP(1), MTMR1(4), MTMR2(1), MTMR6(4), NFS1(2), PHPT1(1), THTPA(1) 1454764 14 12 14 4 4 3 1 4 2 0 0.412 1.000 213 TERCPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. NFYA, NFYB, NFYC, RB1, SP1, SP3 6 NFYA(1), NFYB(1), NFYC(3), RB1(4), SP1(2), SP3(2) 1533323 13 11 13 3 2 4 1 5 0 1 0.415 1.000 214 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(2), CCNE1(3), CDK2(2), CDK4(2), CDK6(1), CDKN1A(1), CDKN1B(1), MAPK1(2), MAPK3(2), NFKB1(3), PAK1(4), PIK3R1(5), RAF1(4), RB1(4), RELA(2), TFDP1(4) 4122396 42 25 41 8 11 10 2 12 6 1 0.415 1.000 215 PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS ENO1, ENO2, ENO3, FARS2, FARSLB, GOT1, GOT2, PAH, TAT, YARS 9 ENO2(3), ENO3(3), FARS2(4), GOT1(5), GOT2(1), PAH(4), TAT(3), YARS(2) 1909324 25 17 25 5 8 8 0 6 3 0 0.417 1.000 216 CERAMIDEPATHWAY Ceramide is a lipid signaling molecule that can activate proliferative or apoptotic pathways, depending on signaling context, localization, and cell type. BAD, BAX, BCL2, CASP8, CYCS, FADD, MAP2K1, MAP2K4, MAP3K1, MAPK1, MAPK3, MAPK8, NFKB1, NSMAF, PDCD8, RAF1, RELA, RIPK1, SMPD1, TNFRSF1A, TRADD, TRAF2 19 BAD(1), BAX(1), BCL2(1), MAP2K1(3), MAP3K1(6), MAPK1(2), MAPK3(2), MAPK8(2), NFKB1(3), NSMAF(1), RAF1(4), RELA(2), RIPK1(2), SMPD1(6), TNFRSF1A(1), TRADD(1), TRAF2(1) 4171474 39 25 38 10 19 10 2 5 3 0 0.417 1.000 217 SIG_CD40PATHWAYMAP Genes related to CD40 signaling DUSP1, GORASP1, IKBKG, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MAPKAPK5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PIK3CA, PIK3CD, PIK3R1, SYT1, TNFRSF5, TRAF2, TRAF3, TRAF5, TRAF6 30 DUSP1(2), GORASP1(3), MAPK1(2), MAPK10(4), MAPK12(2), MAPK14(3), MAPK3(2), MAPK8(2), MAPK8IP1(2), MAPK8IP3(1), MAPK9(3), MAPKAPK5(1), NFKB1(3), NFKB2(2), NFKBIB(1), NFKBIE(2), PIK3CD(2), PIK3R1(5), SYT1(1), TRAF2(1), TRAF3(4), TRAF5(4), TRAF6(4) 6800824 56 36 56 19 15 11 0 19 11 0 0.417 1.000 218 LYSINE_BIOSYNTHESIS AADAT, AASDH, AASDHPPT, AASS, KARS 5 AADAT(1), AASDH(3), AASDHPPT(2), AASS(7), KARS(3) 1599415 16 12 16 5 5 3 0 6 2 0 0.418 1.000 219 HSA00512_O_GLYCAN_BIOSYNTHESIS Genes involved in O-glycan biosynthesis B3GNT6, B4GALT5, C1GALT1, C1GALT1C1, GALNT1, GALNT10, GALNT11, GALNT12, GALNT13, GALNT14, GALNT17, GALNT2, GALNT3, GALNT4, GALNT5, GALNT6, GALNT7, GALNT8, GALNT9, GALNTL1, GALNTL2, GALNTL4, GALNTL5, GCNT1, GCNT3, GCNT4, OGT, ST3GAL1, ST3GAL2, ST6GALNAC1, WBSCR17 29 B4GALT5(2), C1GALT1C1(2), GALNT1(2), GALNT10(5), GALNT11(4), GALNT12(1), GALNT13(5), GALNT14(9), GALNT2(3), GALNT3(4), GALNT5(6), GALNT6(2), GALNT7(2), GALNT8(1), GALNT9(2), GALNTL1(3), GALNTL2(6), GALNTL4(1), GALNTL5(5), GCNT1(3), GCNT3(2), GCNT4(5), OGT(4), ST3GAL1(1), ST3GAL2(1), ST6GALNAC1(2) 7013495 83 36 83 22 32 20 1 18 12 0 0.423 1.000 220 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(3), ESR1(12), GREB1(10), HSPB2(1), MTA1(1), PDZK1(1), TUBA8(1) 2305972 30 18 30 8 10 6 0 9 5 0 0.425 1.000 221 TOB1PATHWAY TGF-beta signaling activates SMADs, which interact with intracellular Tob to maintain unstimulated T cells by repressing IL-2 expression. CD28, CD3D, CD3E, CD3G, CD3Z, IFNG, IL2, IL2RA, IL4, MADH3, MADH4, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, TOB1, TOB2, TRA@, TRB@ 15 CD28(1), CD3D(1), CD3G(2), IFNG(1), IL2(3), IL2RA(2), IL4(3), TGFB1(1), TGFB2(5), TGFBR1(6), TGFBR3(5), TOB2(1) 2132631 31 16 30 11 14 4 0 9 4 0 0.426 1.000 222 ST_ERK1_ERK2_MAPK_PATHWAY The Erk1 and Erk2 MAP kinase pathways are regulated by Raf, Mos, and Tpl-2. ARAF1, ATF1, BAD, BRAF, COPEB, CREB1, CREB3, CREB5, DUSP4, DUSP6, DUSP9, EEF2K, EIF4E, GRB2, HTATIP, MAP2K1, MAP2K2, MAP3K8, MAPK1, MAPK3, MKNK1, MKNK2, MOS, NFKB1, RAP1A, RPS6KA1, RPS6KA2, RPS6KA3, SHC1, SOS1, SOS2, TRAF3 28 ATF1(1), BAD(1), CREB1(1), CREB3(2), CREB5(2), DUSP4(1), DUSP6(4), DUSP9(1), GRB2(2), MAP2K1(3), MAP3K8(2), MAPK1(2), MAPK3(2), MKNK1(1), MKNK2(2), MOS(2), NFKB1(3), RAP1A(1), RPS6KA1(1), RPS6KA2(8), RPS6KA3(3), SHC1(3), SOS1(5), SOS2(9), TRAF3(4) 6435621 66 34 65 21 20 16 3 16 11 0 0.426 1.000 223 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(1), GOT1(5), GOT2(1), TAT(3), TYR(2) 1077195 12 10 12 5 5 3 0 3 1 0 0.428 1.000 224 HSA00660_C5_BRANCHED_DIBASIC_ACID_METABOLISM Genes involved in C5-branched dibasic acid metabolism ILVBL, SUCLA2 2 ILVBL(2), SUCLA2(3) 471201 5 5 5 2 3 1 0 0 1 0 0.429 1.000 225 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 34 ACTA1(3), CRKL(2), DOCK1(5), GAB1(6), GRB2(2), HGF(5), ITGA1(3), ITGB1(6), MAP2K1(3), MAP4K1(2), MAPK1(2), MAPK3(2), MAPK8(2), MET(4), PAK1(4), PIK3R1(5), PTEN(6), PTK2(5), PTK2B(1), PTPN11(2), RAF1(4), RAP1A(1), RAP1B(2), RASA1(5), SOS1(5), SRC(3), STAT3(2) 9257961 92 39 90 24 22 29 3 25 12 1 0.436 1.000 226 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), ACTR3(2), AKT1(2), ANGPTL2(8), DAG1(4), DGKA(1), ETFA(2), ITGA9(4), ITPKB(4), ITPR1(11), ITPR2(12), ITPR3(11), MAP2K1(3), MAPK1(2), MAPK3(2), NR1I3(2), PAK1(4), PDE3A(5), PDE3B(2), PIK3C2G(7), PIK3CD(2), PIK3R1(5), PLDN(1), RIPK3(4), RPS4X(1), VASP(3) 9949411 105 44 105 34 38 21 6 22 18 0 0.438 1.000 227 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT1(5), GOT2(1), TAT(3) 607023 9 7 9 1 4 3 0 1 1 0 0.439 1.000 228 HSA00785_LIPOIC_ACID_METABOLISM Genes involved in lipoic acid metabolism LIAS, LIPT1, LOC387787 2 LIAS(3), LIPT1(2) 344910 5 4 5 0 0 2 0 2 1 0 0.441 1.000 229 HSA00780_BIOTIN_METABOLISM Genes involved in biotin metabolism BTD, HLCS, SPCS1, SPCS3 4 BTD(2), HLCS(4), SPCS1(1) 694979 7 7 6 2 4 0 0 1 2 0 0.441 1.000 230 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(2), CREB1(1), MAP2K1(3), MAP2K3(2), MAP2K6(2), MAP3K1(6), MAPK1(2), MAPK14(3), MAPK3(2), NFKB1(3), PIK3R1(5), RB1(4), RELA(2), SP1(2) 3898591 39 22 39 10 12 9 3 8 6 1 0.442 1.000 231 ERBB4PATHWAY ErbB4 (aka HER4) is a receptor tyrosine kinase that binds neuregulins as well as members of the EGF family, which also target EGF receptors. ADAM17, ERBB4, NRG2, NRG3, PRKCA, PRKCB1, PSEN1 5 ADAM17(6), NRG2(4), NRG3(3), PRKCA(2), PSEN1(3) 1439981 18 13 18 2 6 5 0 4 3 0 0.442 1.000 232 RECKPATHWAY RECK is a membrane-anchored inhibitor of matrix metalloproteinases, which are expressed by tumor cells and promote metastasis. HRAS, MMP14, MMP2, MMP9, RECK, TIMP1, TIMP2, TIMP3, TIMP4 9 MMP14(4), MMP2(2), MMP9(6), RECK(3), TIMP1(1), TIMP2(2), TIMP3(2), TIMP4(2) 1689618 22 16 22 5 13 3 2 4 0 0 0.445 1.000 233 ST_T_CELL_SIGNAL_TRANSDUCTION On activation of the T cell receptor, phospholipase C is activated to produce second messengers DAG and PIP3, both required for T cell activation. CBL, CD28, CD3D, CSK, CTLA4, DAG1, DTYMK, EPHB2, FBXW7, GRAP2, GRB2, ITK, ITPKA, ITPKB, LAT, LCK, LCP2, MAPK1, NCK1, NFAT5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PAG, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PLCG1, PTPRC, RAF1, RASGRP1, RASGRP2, RASGRP3, RASGRP4, SOS1, SOS2, VAV1, ZAP70 43 CBL(2), CD28(1), CD3D(1), CSK(1), CTLA4(1), DAG1(4), EPHB2(7), GRAP2(2), GRB2(2), ITK(8), ITPKB(4), LCK(2), LCP2(2), MAPK1(2), NFAT5(5), NFKB1(3), NFKB2(2), NFKBIB(1), NFKBIE(2), PAK1(4), PAK2(2), PAK3(3), PAK6(1), PAK7(4), PLCG1(4), PTPRC(9), RAF1(4), RASGRP1(2), RASGRP2(5), RASGRP3(4), RASGRP4(1), SOS1(5), SOS2(9), VAV1(11), ZAP70(4) 11944552 124 48 121 48 47 29 8 32 8 0 0.445 1.000 234 HSA00471_D_GLUTAMINE_AND_D_GLUTAMATE_METABOLISM Genes involved in D-glutamine and D-glutamate metabolism GLS, GLS2, GLUD1, GLUD2 4 GLS2(2), GLUD1(2), GLUD2(4) 960843 8 8 8 5 6 1 0 1 0 0 0.446 1.000 235 SA_FAS_SIGNALING The TNF-type receptor Fas induces apoptosis on ligand binding. BCL2, CASP3, CASP8, CFL1, CFLAR, P11, PDE6D, TNFRSF6, TNFSF6 5 BCL2(1), CASP3(1), CFL1(1), CFLAR(2), PDE6D(1) 598787 6 6 6 2 2 0 0 4 0 0 0.450 1.000 236 HSA00053_ASCORBATE_AND_ALDARATE_METABOLISM Genes involved in ascorbate and aldarate metabolism ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, MIOX, UGDH 9 ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(1), ALDH9A1(1), MIOX(1), UGDH(3) 1916590 24 17 24 5 9 7 0 6 2 0 0.458 1.000 237 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 5 ATR(13), CDC25C(3), CHEK1(1), CHEK2(1) 2051792 18 13 18 1 6 3 2 4 3 0 0.460 1.000 238 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(32), B3GALT4(1), CDR1(1), DGKI(6), IL6ST(2), MRPL19(1), PIGK(3), RPL18A(1), RPL21(1), RPL22(2), RPL24(1), RPL28(1), RPL3(2), RPL31(2), RPL32(1), RPL35(1), RPL39(1), RPL3L(1), RPL4(2), RPL6(1), RPL7(1), RPL9(3), RPLP0(2), RPS11(1), RPS13(1), RPS16(1), RPS18(1), RPS20(1), RPS23(4), RPS3(1), RPS4X(1), RPS6KA1(1), RPS6KA2(8), RPS6KA3(3), RPS6KA6(5), RPS6KB1(3), RPS6KB2(1), RPS9(2), RPSA(1), SLC36A2(1), TBC1D10C(2), TSPAN9(2), UBA52(2), UBB(1) 11427799 112 48 111 28 39 24 1 30 18 0 0.462 1.000 239 HSA05130_PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EHEC Genes involved in pathogenic Escherichia coli infection - EHEC ABL1, ACTB, ACTG1, ARHGEF2, ARPC5, ARPC5L, CD14, CDC42, CDH1, CLDN1, CTNNB1, CTTN, EZR, FYN, HCLS1, ITGB1, KRT18, LOC643224, LOC654264, LY96, NCK1, NCK2, NCL, OCLN, PRKCA, RHOA, ROCK1, ROCK2, TLR4, TLR5, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8, WAS, WASL, YWHAQ, YWHAZ 51 ABL1(4), ACTB(2), ARHGEF2(4), ARPC5(1), ARPC5L(1), CD14(1), CDH1(4), CTNNB1(8), EZR(2), FYN(4), HCLS1(7), ITGB1(6), KRT18(2), LY96(2), NCL(2), OCLN(1), PRKCA(2), RHOA(4), ROCK1(8), ROCK2(2), TLR4(7), TLR5(3), TUBA3C(9), TUBA3D(2), TUBA3E(4), TUBA4A(1), TUBA8(1), TUBAL3(3), TUBB(1), TUBB1(2), TUBB2A(1), TUBB2B(3), TUBB3(1), TUBB4(2), TUBB4Q(2), TUBB6(3), TUBB8(2), WAS(1), WASL(5), YWHAQ(1) 11374491 121 47 120 44 44 24 2 38 13 0 0.466 1.000 240 HSA05131_PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EPEC Genes involved in pathogenic Escherichia coli infection - EPEC ABL1, ACTB, ACTG1, ARHGEF2, ARPC5, ARPC5L, CD14, CDC42, CDH1, CLDN1, CTNNB1, CTTN, EZR, FYN, HCLS1, ITGB1, KRT18, LOC643224, LOC654264, LY96, NCK1, NCK2, NCL, OCLN, PRKCA, RHOA, ROCK1, ROCK2, TLR4, TLR5, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8, WAS, WASL, YWHAQ, YWHAZ 51 ABL1(4), ACTB(2), ARHGEF2(4), ARPC5(1), ARPC5L(1), CD14(1), CDH1(4), CTNNB1(8), EZR(2), FYN(4), HCLS1(7), ITGB1(6), KRT18(2), LY96(2), NCL(2), OCLN(1), PRKCA(2), RHOA(4), ROCK1(8), ROCK2(2), TLR4(7), TLR5(3), TUBA3C(9), TUBA3D(2), TUBA3E(4), TUBA4A(1), TUBA8(1), TUBAL3(3), TUBB(1), TUBB1(2), TUBB2A(1), TUBB2B(3), TUBB3(1), TUBB4(2), TUBB4Q(2), TUBB6(3), TUBB8(2), WAS(1), WASL(5), YWHAQ(1) 11374491 121 47 120 44 44 24 2 38 13 0 0.466 1.000 241 GLUTAMATE_METABOLISM ABAT, ALDH4A1, ALDH5A1, CAD, CPS1, EPRS, GAD1, GAD2, GCLC, GCLM, GFPT1, GLS, GLS2, GLUD1, GLUL, GMPS, GOT1, GOT2, GPT, GPT2, GSS, NADSYN1, PPAT, QARS 24 ABAT(5), ALDH4A1(2), ALDH5A1(4), CAD(10), CPS1(8), EPRS(10), GAD1(7), GAD2(4), GCLC(4), GCLM(1), GFPT1(3), GLS2(2), GLUD1(2), GLUL(3), GMPS(5), GOT1(5), GOT2(1), GPT2(2), GSS(4), NADSYN1(2), PPAT(3), QARS(7) 7443276 94 37 94 17 31 26 2 28 7 0 0.466 1.000 242 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 11 ADAM17(6), AXIN1(1), BTRC(2), CTNNB1(8), DLL1(1), GSK3B(7), PSEN1(3), WNT1(1) 3302540 29 20 29 9 11 7 0 5 6 0 0.467 1.000 243 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(3), ACTR2(1), ACTR3(2), ARPC1A(5), ARPC1B(2), ARPC2(1), WASF1(1), WASL(5) 1805655 20 15 20 5 7 5 1 6 1 0 0.468 1.000 244 1_2_DICHLOROETHANE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1) 1805955 28 17 28 3 12 8 0 8 0 0 0.479 1.000 245 ASCORBATE_AND_ALDARATE_METABOLISM ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1) 1805955 28 17 28 3 12 8 0 8 0 0 0.479 1.000 246 HSA04660_T_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in T cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, CARD11, CBL, CBLB, CBLC, CD247, CD28, CD3D, CD3E, CD3G, CD4, CD40LG, CD8A, CD8B, CDC42, CDK4, CHP, CHUK, CSF2, CTLA4, FOS, FYN, GRAP2, GRB2, HRAS, ICOS, IFNG, IKBKB, IKBKG, IL10, IL2, IL4, IL5, ITK, JUN, KRAS, LAT, LCK, LCP2, MALT1, MAP3K14, MAP3K8, NCK1, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDCD1, PDK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCQ, PTPN6, PTPRC, RASGRP1, RHOA, SOS1, SOS2, TEC, TNF, VAV1, VAV2, VAV3, ZAP70 89 AKT1(2), AKT2(5), BCL10(3), CARD11(6), CBL(2), CBLB(6), CD247(2), CD28(1), CD3D(1), CD3G(2), CD4(2), CD40LG(6), CD8B(2), CDK4(2), CHUK(4), CTLA4(1), FYN(4), GRAP2(2), GRB2(2), ICOS(1), IFNG(1), IKBKB(2), IL10(1), IL2(3), IL4(3), ITK(8), LCK(2), LCP2(2), MALT1(6), MAP3K14(2), MAP3K8(2), NFAT5(5), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), NFKB1(3), NFKB2(2), NFKBIB(1), NFKBIE(2), PAK1(4), PAK2(2), PAK3(3), PAK6(1), PAK7(4), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PLCG1(4), PPP3CA(1), PPP3CB(4), PPP3CC(3), PPP3R1(1), PPP3R2(1), PRKCQ(4), PTPN6(4), PTPRC(9), RASGRP1(2), RHOA(4), SOS1(5), SOS2(9), TEC(1), VAV1(11), VAV2(2), VAV3(10), ZAP70(4) 21911612 229 66 227 85 85 48 10 60 26 0 0.482 1.000 247 PKCPATHWAY Gq-coupled receptors promote hydrolysis of PIP2 to DAG and IP3, which causes calcium influx and activates protein kinase C. GNAQ, NFKB1, NFKBIA, PLCB1, PRKCA, PRKCB1, RELA 6 GNAQ(3), NFKB1(3), PLCB1(8), PRKCA(2), RELA(2) 1890394 18 14 18 5 6 3 0 6 3 0 0.484 1.000 248 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(2), BAD(1), BCL2(1), CABIN1(9), CAMK2B(2), CAMK4(2), CD3G(2), CDKN1A(1), CNR1(3), CREBBP(21), CSNK2A1(4), CSNK2B(2), CTLA4(1), EGR2(6), EGR3(2), EP300(13), FCER1A(2), GATA3(4), GATA4(1), GRLF1(7), GSK3A(2), GSK3B(7), ICOS(1), IFNA1(1), IFNB1(1), IFNG(1), IL10(1), IL13(1), IL2(3), IL2RA(2), IL3(3), IL4(3), IL6(1), ITK(8), KPNA5(4), MAPK14(3), MAPK8(2), MAPK9(3), MEF2A(3), MEF2D(1), MYF5(2), NFAT5(5), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), NFKB2(2), NFKBIB(1), NFKBIE(2), NUP214(4), OPRD1(1), P2RX7(2), PAK1(4), PIN1(1), PPP3CB(4), PPP3CC(3), PPP3R1(1), PTPRC(9), RELA(2), SLA(4), SP1(2), SP3(2), TGFB1(1), TRAF2(1), TRPV6(9), VAV1(11), VAV2(2), VAV3(10) 19966925 234 64 230 77 84 63 6 53 28 0 0.484 1.000 249 HSA00120_BILE_ACID_BIOSYNTHESIS Genes involved in bile acid biosynthesis ACAA1, ACAA2, ACAD8, ACAD9, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AKR1B10, AKR1C4, AKR1D1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, BAAT, CEL, CYP27A1, CYP7A1, HADHB, HSD3B7, LIPA, RDH11, RDH12, RDH13, RDH14, SLC27A5, SOAT1, SOAT2, SRD5A1, SRD5A2 38 ACAA1(2), ACAD9(3), ADH1B(2), ADH1C(3), ADH4(1), ADH5(1), ADH6(5), ADH7(2), ADHFE1(6), AKR1C4(2), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(1), ALDH9A1(1), BAAT(2), CEL(1), CYP27A1(3), CYP7A1(4), HADHB(1), HSD3B7(2), LIPA(1), RDH12(2), RDH13(1), SLC27A5(3), SOAT1(1), SOAT2(1), SRD5A1(1), SRD5A2(1) 7061346 71 36 71 20 20 21 2 23 5 0 0.492 1.000 250 TERTPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. HDAC1, MAX, MYC, SP1, SP3, TP53, WT1, ZNF42 6 HDAC1(2), MAX(1), SP1(2), SP3(2), WT1(4) 1394754 11 10 11 3 6 3 1 1 0 0 0.495 1.000 251 SA_PTEN_PATHWAY PTEN is a tumor suppressor that dephosphorylates the lipid messenger phosphatidylinositol triphosphate. AKT1, AKT2, AKT3, BPNT1, GRB2, ILK, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIP3-E, PTEN, PTK2B, RBL2, SHC1, SOS1 15 AKT1(2), AKT2(5), BPNT1(1), GRB2(2), MAPK1(2), MAPK3(2), PIK3CD(2), PTEN(6), PTK2B(1), RBL2(8), SHC1(3), SOS1(5) 4085447 39 22 37 11 11 7 3 9 8 1 0.496 1.000 252 TSP1PATHWAY Thrombospondin-1 (TSP-1) inhibits angiogenesis by inducing caspase-dependent apoptosis in microvascular endothelial cells. CASP3, CD36, FOS, FYN, JUN, MAPK14, THBS1 7 CASP3(1), CD36(1), FYN(4), MAPK14(3), THBS1(8) 1625380 17 14 17 7 5 6 0 4 2 0 0.501 1.000 253 SIG_BCR_SIGNALING_PATHWAY Members of the BCR signaling pathway AKT1, AKT2, AKT3, BAD, BCL2, BCR, BLNK, BTK, CD19, CD22, CD81, CR2, CSK, DAG1, FLOT1, FLOT2, GRB2, GSK3A, GSK3B, INPP5D, ITPR1, ITPR2, ITPR3, LYN, MAP4K1, MAPK1, MAPK3, NFATC1, NFATC2, NR0B2, PDK1, PIK3CA, PIK3CD, PIK3R1, PLCG2, PPP1R13B, PPP3CA, PPP3CB, PPP3CC, PTPRC, RAF1, SHC1, SOS1, SOS2, SYK, VAV1 45 AKT1(2), AKT2(5), BAD(1), BCL2(1), BCR(6), BTK(6), CD19(3), CD22(8), CR2(9), CSK(1), DAG1(4), FLOT1(3), GRB2(2), GSK3A(2), GSK3B(7), INPP5D(2), ITPR1(11), ITPR2(12), ITPR3(11), LYN(4), MAP4K1(2), MAPK1(2), MAPK3(2), NFATC1(1), NFATC2(3), PIK3CD(2), PIK3R1(5), PLCG2(9), PPP1R13B(5), PPP3CA(1), PPP3CB(4), PPP3CC(3), PTPRC(9), RAF1(4), SHC1(3), SOS1(5), SOS2(9), VAV1(11) 15494572 180 56 177 48 68 39 7 41 25 0 0.503 1.000 254 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(6), GRB2(2), INSR(5), IRS1(5), JAK2(6), MAP2K1(3), MAPK1(2), MAPK3(2), PIK3R1(5), PLCG1(4), PRKCA(2), PTPN6(4), RAF1(4), RPS6KA1(1), SHC1(3), SLC2A4(3), SOS1(5), SRF(3), STAT5B(2) 6929739 68 34 66 25 24 11 4 22 6 1 0.503 1.000 255 ST_G_ALPHA_I_PATHWAY Gi and Go proteins are members of the same family that transduce cellular signals through both their alpha and beta subunits. AKT1, AKT2, AKT3, ASAH1, BF, BRAF, DAG1, DRD2, EGFR, EPHB2, GRB2, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, PI3, PIK3CB, PITX2, PLCB1, PLCB2, PLCB3, PLCB4, RAF1, RAP1GA1, RGS20, SHC1, SOS1, SOS2, SRC, STAT3, TERF2IP 33 AKT1(2), AKT2(5), ASAH1(3), DAG1(4), DRD2(3), EGFR(10), EPHB2(7), GRB2(2), ITPKB(4), ITPR1(11), ITPR2(12), ITPR3(11), KCNJ3(6), KCNJ5(3), KCNJ9(2), MAPK1(2), PIK3CB(2), PITX2(2), PLCB1(8), PLCB2(3), PLCB3(3), PLCB4(9), RAF1(4), RGS20(3), SHC1(3), SOS1(5), SOS2(9), SRC(3), STAT3(2), TERF2IP(1) 12452362 144 52 141 48 58 30 7 38 11 0 0.504 1.000 256 ALKALOID_BIOSYNTHESIS_II ABP1, AOC2, AOC3, CES1, ESD 5 ABP1(1), AOC2(4), AOC3(4), CES1(4) 1267882 13 12 13 4 6 3 0 4 0 0 0.506 1.000 257 IL12PATHWAY IL12 and Stat4 Dependent Signaling Pathway in Th1 Development CCR5, CD3D, CD3E, CD3G, CD3Z, CXCR3, ETV5, IFNG, IL12A, IL12B, IL12RB1, IL12RB2, IL18, IL18R1, JAK2, JUN, MAP2K6, MAPK14, MAPK8, STAT4, TRA@, TRB@, TYK2 20 CCR5(1), CD3D(1), CD3G(2), ETV5(5), IFNG(1), IL12B(2), IL12RB1(2), IL12RB2(5), IL18R1(8), JAK2(6), MAP2K6(2), MAPK14(3), MAPK8(2), TYK2(1) 4079903 41 24 42 20 9 15 1 9 6 1 0.508 1.000 258 HSA00150_ANDROGEN_AND_ESTROGEN_METABOLISM Genes involved in androgen and estrogen metabolism AKR1C4, AKR1D1, ARSD, ARSE, CARM1, CYP11B1, CYP11B2, CYP19A1, HEMK1, HSD11B1, HSD11B2, HSD17B1, HSD17B12, HSD17B2, HSD17B3, HSD17B7, HSD17B8, HSD3B1, HSD3B2, LCMT1, LCMT2, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, SRD5A1, SRD5A2, STS, SULT1E1, SULT2A1, SULT2B1, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, WBSCR22 54 AKR1C4(2), ARSD(3), ARSE(2), CARM1(2), CYP11B1(5), CYP11B2(5), CYP19A1(5), HSD11B1(1), HSD17B12(2), HSD17B2(1), HSD17B3(1), HSD17B8(1), HSD3B1(2), LCMT1(1), LCMT2(2), METTL2B(1), METTL6(5), PRMT2(1), PRMT3(2), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(3), SRD5A1(1), SRD5A2(1), STS(6), SULT1E1(1), SULT2A1(1), SULT2B1(1), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(1), UGT1A5(3), UGT1A7(2), UGT1A9(5), UGT2A1(8), UGT2A3(5), UGT2B10(1), UGT2B11(4), UGT2B15(2), UGT2B17(4), UGT2B28(2), UGT2B4(2), UGT2B7(4), WBSCR22(1) 10482985 110 44 109 24 35 26 3 30 16 0 0.510 1.000 259 BOTULINPATHWAY Blockade of Neurotransmitter Relase by Botulinum Toxin CHRM1, CHRNA1, SNAP25, STX1A, VAMP2 5 CHRM1(3), CHRNA1(2), SNAP25(1), STX1A(2) 729912 8 8 8 4 6 1 0 1 0 0 0.515 1.000 260 ST_GRANULE_CELL_SURVIVAL_PATHWAY The survival and differentiation of granule cells in the brain is controlled by pro-growth PACAP and pro-apoptotic ceramides. ADPRT, APC, ASAH1, CAMP, CASP3, CERK, CREB1, CREB3, CREB5, CXCL2, DAG1, EPHB2, FOS, GNAQ, IL8RB, ITPKA, ITPKB, JUN, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, PACAP 23 ASAH1(3), CASP3(1), CERK(1), CREB1(1), CREB3(2), CREB5(2), DAG1(4), EPHB2(7), GNAQ(3), ITPKB(4), MAPK1(2), MAPK10(4), MAPK8(2), MAPK8IP1(2), MAPK8IP3(1), MAPK9(3) 4882114 42 26 41 18 12 10 2 12 6 0 0.515 1.000 261 LIMONENE_AND_PINENE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ECHS1, EHHADH, HADHA, SDS 12 ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), ECHS1(2), EHHADH(2), HADHA(2), SDS(2) 2761561 36 21 36 4 15 10 0 8 3 0 0.518 1.000 262 G_PROTEIN_SIGNALING ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, AKAP1, AKAP10, AKAP11, AKAP12, AKAP2, PALM2_AKAP2, AKAP3, AKAP4, AKAP5, AKAP6, AKAP7, AKAP8, AKAP9, ARHGEF1, CALM1, CALM2, CALM3, CHMP1B, GNA11, GNA12, GNA13, GNA14, GNA15, GNAI2, GNAI3, GNAL, GNAO1, GNAQ, GNAZ, GNB1, GNB2, GNB3, GNB5, GNG10, GNG10, LOC552891, GNG12, GNG13, GNG3, GNG4, GNG5, GNG7, GNGT1, GNGT2, HRAS, IL18BP, ITPR1, KCNJ3, KRAS, MGC11266, NRAS, PALM2, PALM2_AKAP2, PALM2_AKAP2, PDE1A, PDE1B, PDE1C, PDE4A, PDE4B, PDE4C, PDE4D, PDE7A, PDE7B, PDE8A, PDE8B, PLCB3, PPP3CA, PPP3CC, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCQ, PRKCZ, PRKD1, PRKD3, RHOA, RRAS, SARA1, SLC9A1, USP5 90 ADCY1(4), ADCY2(12), ADCY3(1), ADCY4(9), ADCY5(8), ADCY6(1), ADCY7(3), ADCY8(11), ADCY9(4), AKAP10(2), AKAP11(4), AKAP12(11), AKAP3(6), AKAP4(2), AKAP5(3), AKAP6(10), AKAP7(2), AKAP8(3), AKAP9(20), ARHGEF1(4), GNA11(1), GNA12(2), GNA13(2), GNA14(5), GNA15(3), GNAL(3), GNAO1(5), GNAQ(3), GNAZ(1), GNB1(1), GNB3(3), GNB5(1), GNG3(2), GNG7(1), ITPR1(11), KCNJ3(6), PDE1A(3), PDE1B(2), PDE1C(7), PDE4A(4), PDE4B(2), PDE4C(2), PDE4D(3), PDE7A(3), PDE7B(3), PDE8A(1), PDE8B(6), PLCB3(3), PPP3CA(1), PPP3CC(3), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PRKCA(2), PRKCD(3), PRKCE(4), PRKCG(8), PRKCH(2), PRKCI(4), PRKCQ(4), PRKD1(10), PRKD3(6), RHOA(4), SLC9A1(2), USP5(3) 25696558 272 71 268 108 107 58 10 65 31 1 0.519 1.000 263 AGPCRPATHWAY G-protein coupled receptors (GPCRs) transduce extracellular signals across the plasma membrane; attenuation occurs by signal molecule degradation or receptor-mediated endocytosis. ARRB1, GNAS, GNB1, GNGT1, GPRK2L, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1 11 ARRB1(1), GNAS(6), GNB1(1), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PRKCA(2) 2085116 17 16 17 6 7 1 2 6 1 0 0.521 1.000 264 TCRPATHWAY T cell receptors bind to foreign peptides presented by MHC molecules and induce T cell activation. CALM1, CALM2, CALM3, CD3D, CD3E, CD3G, CD3Z, ELK1, FOS, FYN, GRB2, HRAS, JUN, LAT, LCK, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKBIA, PIK3CA, PIK3R1, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, PTPN7, RAC1, RAF1, RASA1, RELA, SHC1, SOS1, SYT1, TRA@, TRB@, VAV1, ZAP70 40 CD3D(1), CD3G(2), FYN(4), GRB2(2), LCK(2), MAP2K1(3), MAP3K1(6), MAPK3(2), MAPK8(2), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), NFKB1(3), PIK3R1(5), PLCG1(4), PPP3CA(1), PPP3CB(4), PPP3CC(3), PRKCA(2), PTPN7(1), RAF1(4), RASA1(5), RELA(2), SHC1(3), SOS1(5), SYT1(1), VAV1(11), ZAP70(4) 10000745 94 42 92 29 36 16 6 17 19 0 0.522 1.000 265 HSA00603_GLYCOSPHINGOLIPID_BIOSYNTHESIS_GLOBOSERIES Genes involved in glycosphingolipid biosynthesis - globoseries A4GALT, B3GALNT1, B3GALT5, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, ST3GAL1, ST3GAL2, ST8SIA1 14 A4GALT(3), B3GALNT1(3), B3GALT5(2), FUT1(1), FUT2(1), FUT9(4), GLA(4), HEXB(1), NAGA(1), ST3GAL1(1), ST3GAL2(1), ST8SIA1(3) 2387145 25 16 25 8 8 6 0 6 5 0 0.523 1.000 266 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(1), IL6(1), LDLR(4), LPL(6) 1189147 13 10 13 2 3 3 0 5 2 0 0.523 1.000 267 HSA00290_VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS Genes involved in valine, leucine and isoleucine biosynthesis BCAT1, BCAT2, IARS, IARS2, ILVBL, LARS, LARS2, PDHA1, PDHA2, PDHB, VARS, VARS2 12 BCAT1(1), BCAT2(1), IARS(5), IARS2(6), ILVBL(2), LARS(4), LARS2(2), PDHA1(4), PDHA2(6), PDHB(2), VARS(1), VARS2(6) 4151357 40 25 40 8 18 10 0 6 6 0 0.523 1.000 268 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(4), FBL(3), LDHA(1), LDHB(1), LDHC(2), MAPK14(3), NCL(2) 2012341 21 16 21 10 9 4 1 6 1 0 0.525 1.000 269 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(2), BAD(1), CASP9(2), CHUK(4), GH1(1), GHR(6), NFKB1(3), PDPK1(1), PIK3R1(5), PPP2CA(1), RELA(2) 2731547 28 18 28 8 9 5 1 8 5 0 0.528 1.000 270 EGFPATHWAY The epidermal growth factor (EGF) peptide stimulates the EGF receptor to promote cell proliferation via the MAP kinase and Ras pathways. CSNK2A1, EGF, EGFR, ELK1, FOS, GRB2, HRAS, JAK1, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, SRF, STAT1, STAT3, STAT5A 24 CSNK2A1(4), EGF(3), EGFR(10), GRB2(2), JAK1(3), MAP2K1(3), MAP3K1(6), MAPK3(2), MAPK8(2), PIK3R1(5), PLCG1(4), PRKCA(2), RAF1(4), RASA1(5), SHC1(3), SOS1(5), SRF(3), STAT1(6), STAT3(2) 7715443 74 36 71 21 27 17 4 18 8 0 0.528 1.000 271 HSA04320_DORSO_VENTRAL_AXIS_FORMATION Genes involved in dorso-ventral axis formation BRAF, CPEB1, EGFR, ERBB2, ERBB4, ETS1, ETS2, ETV6, ETV7, FMN2, GRB2, KRAS, MAP2K1, MAPK1, MAPK3, NOTCH1, NOTCH2, NOTCH3, NOTCH4, PIWIL1, PIWIL2, PIWIL3, PIWIL4, RAF1, SOS1, SOS2, SPIRE1, SPIRE2 25 CPEB1(2), EGFR(10), ERBB2(6), ETS2(2), ETV6(4), FMN2(4), GRB2(2), MAP2K1(3), MAPK1(2), MAPK3(2), NOTCH2(11), NOTCH3(12), NOTCH4(3), PIWIL1(5), PIWIL2(6), PIWIL3(8), PIWIL4(6), RAF1(4), SOS1(5), SOS2(9), SPIRE1(2), SPIRE2(1) 10813674 109 49 107 35 41 27 3 32 6 0 0.532 1.000 272 VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS BCAT1, IARS, LARS, LARS2, PDHA1, PDHA2, PDHB 7 BCAT1(1), IARS(5), LARS(4), LARS2(2), PDHA1(4), PDHA2(6), PDHB(2) 2253000 24 15 24 4 9 6 0 5 4 0 0.533 1.000 273 FREEPATHWAY Neutrophils release superoxide to induce lysis in invading bacteria; in neighboring endothelial cells, superoxide dismutase scavenges radicals but produces pro-apoptotic peroxides. GPX1, GSR, GSS, IL8, NFKB1, NOX1, RELA, SOD1, TNF, XDH 10 GPX1(1), GSR(1), GSS(4), NFKB1(3), NOX1(1), RELA(2), XDH(7) 2280177 19 15 19 6 5 7 1 3 3 0 0.533 1.000 274 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(4), GRB2(2), JAK2(6), MAP2K1(3), MAPK3(2), MPL(1), PIK3R1(5), PLCG1(4), PRKCA(2), RAF1(4), RASA1(5), SHC1(3), SOS1(5), STAT1(6), STAT3(2), STAT5B(2), THPO(1) 6264598 57 29 55 17 16 11 5 16 8 1 0.540 1.000 275 NTHIPATHWAY Hemophilus influenzae infections activate NF-kB via several pathways, inducing the inflammatory response. CHUK, CREBBP, DUSP1, EP300, IKBKB, IL1B, IL8, MADH3, MADH4, MAP2K3, MAP2K6, MAP3K14, MAP3K7, MAPK11, MAPK14, MYD88, NFKB1, NFKBIA, NR3C1, RELA, TGFBR1, TGFBR2, TLR2, TNF 21 CHUK(4), CREBBP(21), DUSP1(2), EP300(13), IKBKB(2), MAP2K3(2), MAP2K6(2), MAP3K14(2), MAP3K7(2), MAPK14(3), MYD88(1), NFKB1(3), NR3C1(3), RELA(2), TGFBR1(6), TLR2(2) 6394503 70 33 69 25 24 18 3 18 7 0 0.542 1.000 276 GLYCOLYSISPATHWAY Glycolysis is an evolutionarily conserved pathway by which one glucose molecule is converted to two pyruvate molecules for a gain of 2 ATP. ALDOB, ENO1, GAPD, GPI, HK1, PFKL, PGAM1, PGK1, PKLR, TPI1 9 ALDOB(5), GPI(1), HK1(6), PFKL(1), PGAM1(3), PGK1(3), TPI1(1) 1983193 20 19 19 10 9 1 0 10 0 0 0.542 1.000 277 P53HYPOXIAPATHWAY Hypoxia induces p53 accumulation and consequent apoptosis with p53-mediated cell cycle arrest, which is present under conditions of DNA damage. ABCB1, AKT1, ATM, BAX, CDKN1A, CPB2, CSNK1A1, CSNK1D, FHL2, GADD45A, HIC1, HIF1A, HSPA1A, HSPCA, IGFBP3, MAPK8, MDM2, NFKBIB, NQO1, TP53 16 ABCB1(6), AKT1(2), BAX(1), CDKN1A(1), CPB2(1), CSNK1A1(2), CSNK1D(3), FHL2(1), HIF1A(1), IGFBP3(2), MAPK8(2), MDM2(4), NFKBIB(1), NQO1(1) 2962226 28 20 28 4 4 11 1 11 1 0 0.542 1.000 278 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(5), CARM1(2), CREBBP(21), EP300(13), ERCC3(6), ESR1(12), GRIP1(7), GTF2A1(2), GTF2E1(5), GTF2F1(3), HDAC1(2), HDAC2(2), HDAC3(2), HDAC4(5), HDAC5(1), HDAC6(4), MEF2C(7), NCOR2(2), NR0B1(2), NRIP1(5), PELP1(2), POLR2A(6), TBP(1) 10316344 117 46 117 24 45 34 2 21 15 0 0.544 1.000 279 TIDPATHWAY On ligand binding, interferon gamma receptors stimulate JAK2 kinase to phosphorylate STAT transcription factors, which promote expression of interferon responsive genes. DNAJA3, HSPA1A, IFNG, IFNGR1, IFNGR2, IKBKB, JAK2, LIN7A, NFKB1, NFKBIA, RB1, RELA, TIP-1, TNF, TNFRSF1A, TNFRSF1B, TP53, USH1C, WT1 16 DNAJA3(3), IFNG(1), IFNGR1(2), IFNGR2(1), IKBKB(2), JAK2(6), LIN7A(2), NFKB1(3), RB1(4), RELA(2), TNFRSF1A(1), USH1C(5), WT1(4) 3974272 36 21 36 13 12 4 3 11 4 2 0.547 1.000 280 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(1), F11(4), F12(2), F13B(3), F2(2), F5(14), F7(2), F8(15), F9(6), FGA(11), FGB(1), FGG(4), LPA(9), PLAT(4), PLAU(2), PLG(7), SERPINB2(4), SERPINE1(1), VWF(10) 7871547 102 36 100 31 23 29 3 33 14 0 0.547 1.000 281 SMALL_LIGAND_GPCRS C9orf47, CNR1, CNR2, DNMT1, EDG1, EDG2, EDG5, EDG6, MTNR1A, MTNR1B, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, TBXA2R 13 C9orf47(1), CNR1(3), DNMT1(12), MTNR1B(3), PTAFR(1), PTGER2(1), PTGFR(6), PTGIR(1) 2492801 28 19 25 7 11 3 1 12 1 0 0.554 1.000 282 METHANE_METABOLISM ADH5, ATP6V0C, SHMT1, CAT, EPX, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, SHMT1, SHMT2, TPO 13 ADH5(1), CAT(2), EPX(6), LPO(2), MPO(3), PRDX6(2), SHMT1(1), SHMT2(2), TPO(8) 2574833 27 21 26 9 17 3 0 4 3 0 0.555 1.000 283 ST_TYPE_I_INTERFERON_PATHWAY Type I interferon is an antiviral cytokine that induces a JAK-STAT type pathway leading to ISGF3 activation and a cellular antiviral response. IFNAR1, IFNB1, ISGF3G, JAK1, PTPRU, REG1A, STAT1, STAT2, TYK2 8 IFNAR1(3), IFNB1(1), JAK1(3), PTPRU(6), REG1A(3), STAT1(6), STAT2(5), TYK2(1) 2752150 28 19 26 7 13 6 1 5 3 0 0.555 1.000 284 IL6PATHWAY IL-6 binding to its receptor activates JAK kinases and a variety of transcription factors, with effects in neuronal differentiation, bone loss, and inflammation. CEBPB, CSNK2A1, ELK1, FOS, GRB2, HRAS, IL6, IL6R, IL6ST, JAK1, JAK2, JAK3, JUN, MAP2K1, MAPK3, PTPN11, RAF1, SHC1, SOS1, SRF, STAT3 21 CSNK2A1(4), GRB2(2), IL6(1), IL6R(2), IL6ST(2), JAK1(3), JAK2(6), JAK3(6), MAP2K1(3), MAPK3(2), PTPN11(2), RAF1(4), SHC1(3), SOS1(5), SRF(3), STAT3(2) 5376589 50 28 47 13 16 10 4 14 5 1 0.562 1.000 285 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(4), ACTN1(3), ACTR2(1), ACTR3(2), AKT1(2), AKT2(5), ANGPTL2(8), ARHGEF6(7), ARHGEF7(8), CDKN2A(1), CSE1L(4), DOCK1(5), EPHB2(7), FYN(4), GRB2(2), GRB7(1), GRLF1(7), ITGA1(3), ITGA10(3), ITGA11(2), ITGA2(5), ITGA3(4), ITGA4(3), ITGA5(7), ITGA6(3), ITGA7(6), ITGA8(5), ITGA9(4), ITGB3BP(1), MAP3K11(4), MAPK1(2), MAPK10(4), MAPK8(2), MAPK8IP1(2), MAPK8IP3(1), MAPK9(3), MRAS(1), MYLK(11), MYLK2(2), P4HB(2), PAK1(4), PAK2(2), PAK3(3), PAK6(1), PAK7(4), PIK3CB(2), PLCG1(4), PLCG2(9), PTEN(6), PTK2(5), RAF1(4), RHO(2), ROCK1(8), ROCK2(2), SHC1(3), SOS1(5), SOS2(9), SRC(3), TERF2IP(1), TLN1(5), TLN2(5), VASP(3), WAS(1) 25995429 242 72 236 92 87 56 6 59 33 1 0.562 1.000 286 PLCEPATHWAY Gs-coupled receptors activate adenylyl cyclase, which activates Epac1, leading to the stimulation of PLC and subsequent DAG and IP3 production. ADCY1, ADRB2, GNAS, PLCE1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTGER1, RAP2B 11 ADCY1(4), GNAS(6), PLCE1(7), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2) 3074220 24 20 24 9 10 4 2 5 3 0 0.563 1.000 287 NO1PATHWAY Shear stress in endothelial cells increases cytoplasmic calcium, which activates nitric oxide synthase III to release NO, which in turn regulates cardiac contractions. ACTA1, AKT1, BDK, BDKRB2, CALM1, CALM2, CALM3, CAV1, CHRM1, CHRNA1, FLT1, FLT4, HSPCA, KDR, NOS3, PDE2A, PDE3A, PDE3B, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKG1, PRKG2, RYR2, SLC7A1, SYT1, TNNI1, VEGF 28 ACTA1(3), AKT1(2), BDKRB2(2), CHRM1(3), CHRNA1(2), FLT1(9), FLT4(4), KDR(8), NOS3(2), PDE3A(5), PDE3B(2), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PRKG1(4), PRKG2(3), RYR2(48), SLC7A1(2), SYT1(1), TNNI1(2) 8582717 109 41 109 44 39 26 4 30 10 0 0.563 1.000 288 IFNGPATHWAY IFN gamma signaling pathway IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 6 IFNG(1), IFNGR1(2), IFNGR2(1), JAK1(3), JAK2(6), STAT1(6) 1835289 19 13 18 6 7 1 2 7 1 1 0.567 1.000 289 HSA04912_GNRH_SIGNALING_PATHWAY Genes involved in GnRH signaling pathway ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ATF4, CACNA1C, CACNA1D, CACNA1F, CACNA1S, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CDC42, CGA, EGFR, ELK1, FSHB, GNA11, GNAQ, GNAS, GNRH1, GNRH2, GNRHR, GRB2, HBEGF, HRAS, ITPR1, ITPR2, ITPR3, JUN, KRAS, LHB, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K1, MAP3K2, MAP3K3, MAP3K4, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK7, MAPK8, MAPK9, MMP14, MMP2, NRAS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCB1, PLCB2, PLCB3, PLCB4, PLD1, PLD2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCD, PRKX, PRKY, PTK2B, RAF1, SOS1, SOS2, SRC 92 ADCY1(4), ADCY2(12), ADCY3(1), ADCY4(9), ADCY5(8), ADCY6(1), ADCY7(3), ADCY8(11), ADCY9(4), CACNA1C(10), CACNA1D(7), CACNA1F(12), CACNA1S(10), CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), CGA(1), EGFR(10), FSHB(1), GNA11(1), GNAQ(3), GNAS(6), GNRHR(4), GRB2(2), HBEGF(1), ITPR1(11), ITPR2(12), ITPR3(11), LHB(1), MAP2K1(3), MAP2K3(2), MAP2K6(2), MAP3K1(6), MAP3K2(2), MAP3K3(2), MAP3K4(15), MAPK1(2), MAPK10(4), MAPK12(2), MAPK14(3), MAPK3(2), MAPK7(3), MAPK8(2), MAPK9(3), MMP14(4), MMP2(2), PLA2G1B(1), PLA2G2F(1), PLA2G4A(5), PLA2G6(2), PLCB1(8), PLCB2(3), PLCB3(3), PLCB4(9), PLD1(8), PLD2(1), PRKACB(1), PRKACG(2), PRKCA(2), PRKCD(3), PRKX(2), PTK2B(1), RAF1(4), SOS1(5), SOS2(9), SRC(3) 27836425 295 75 292 115 116 63 10 82 24 0 0.567 1.000 290 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(4), AARS2(6), ABAT(5), ADSL(7), ADSS(1), AGXT2(5), ASNS(1), ASPA(3), ASS1(1), CAD(10), CRAT(3), DARS(3), DARS2(2), DDO(2), DLAT(2), GAD1(7), GAD2(4), GOT1(5), GOT2(1), GPT2(2), NARS(2), NARS2(3), PC(3), PDHA1(4), PDHA2(6), PDHB(2) 8525697 94 43 94 23 41 23 0 21 9 0 0.568 1.000 291 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 BTK(6), CD79A(3), GRB2(2), LYN(4), MAP2K1(3), MAP3K1(6), MAPK14(3), MAPK3(2), MAPK8(2), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), PLCG1(4), PPP3CA(1), PPP3CB(4), PPP3CC(3), PRKCA(2), RAF1(4), SHC1(3), SOS1(5), SYT1(1), VAV1(11) 8524594 81 38 79 23 34 15 4 17 11 0 0.568 1.000 292 PEPIPATHWAY Proepithelin (PEPI) induces epithelial cells to secrete IL-8, which promotes elastase secretion by neutrophils. ELA1, ELA2, ELA2A, ELA2B, ELA3B, GRN, IL8, SLPI 3 GRN(2) 363274 2 2 2 3 0 0 0 1 1 0 0.569 1.000 293 PROSTAGLANDIN_SYNTHESIS_REGULATION ANXA1, ANXA2, ANXA3, ANXA4, ANXA5, ANXA6, ANXA8, CYP11A1, EDN1, EDNRA, EDNRB, HPGD, HSD11B1, HSD11B2, PLA2G4A, PRL, PTGDR, PTGDS, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, PTGIS, PTGS1, PTGS2, S100A6, SCGB1A1, TBXAS1 27 ANXA2(2), ANXA3(1), ANXA4(4), ANXA5(1), ANXA6(2), CYP11A1(2), EDN1(1), EDNRA(4), EDNRB(7), HSD11B1(1), PLA2G4A(5), PRL(2), PTGER2(1), PTGFR(6), PTGIR(1), PTGIS(4), PTGS1(4), PTGS2(2), TBXAS1(5) 4589791 55 26 55 14 22 7 0 21 5 0 0.570 1.000 294 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(2), AKT2(5), BAD(1), BCL2(1), GRB2(2), GSK3A(2), GSK3B(7), IL4R(1), IRS1(5), JAK1(3), JAK3(6), MAP4K1(2), MAPK1(2), MAPK3(2), PIK3CD(2), PIK3R1(5), PPP1R13B(5), RAF1(4), SHC1(3), SOS1(5), SOS2(9), STAT6(2) 7662901 76 38 73 20 24 16 3 19 14 0 0.570 1.000 295 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), MAP2K1(3), MAPK1(2), MAPK3(2), NFKB1(3), PLCB1(8), PRKCA(2), RAF1(4), RELA(2) 3476261 28 20 27 9 11 6 1 7 3 0 0.571 1.000 296 HSA00040_PENTOSE_AND_GLUCURONATE_INTERCONVERSIONS Genes involved in pentose and glucuronate interconversions AKR1B1, DCXR, GUSB, RPE, UGDH, UGP2, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, XYLB 25 AKR1B1(2), GUSB(2), RPE(2), UGDH(3), UGP2(5), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(1), UGT1A5(3), UGT1A7(2), UGT1A9(5), UGT2A1(8), UGT2A3(5), UGT2B10(1), UGT2B11(4), UGT2B15(2), UGT2B17(4), UGT2B28(2), UGT2B4(2), UGT2B7(4), XYLB(2) 5482237 63 27 62 15 16 17 1 18 11 0 0.572 1.000 297 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(4), EIF2B1(2), EIF2B3(2), EIF2B5(5), EIF2S2(1), EIF2S3(1), ELAVL1(3), FLT1(9), FLT4(4), HIF1A(1), KDR(8), NOS3(2), PIK3R1(5), PLCG1(4), PRKCA(2), PTK2(5), SHC1(3) 7148961 61 36 60 21 19 15 2 14 11 0 0.572 1.000 298 AT1RPATHWAY Binding of angiotensin II to AT1-R activates Ca2+ signaling and the JNK pathway. AGT, AGTR1, ATF2, CALM1, CALM2, CALM3, EGFR, ELK1, GNAQ, GRB2, HRAS, JUN, MAP2K1, MAP2K2, MAP2K4, MAP3K1, MAPK1, MAPK3, MAPK8, MEF2A, MEF2B, MEF2C, MEF2D, PAK1, PRKCA, PRKCB1, PTK2, PTK2B, RAC1, RAF1, SHC1, SOS1, SRC, SYT1 32 AGT(4), AGTR1(3), EGFR(10), GNAQ(3), GRB2(2), MAP2K1(3), MAP3K1(6), MAPK1(2), MAPK3(2), MAPK8(2), MEF2A(3), MEF2C(7), MEF2D(1), PAK1(4), PRKCA(2), PTK2(5), PTK2B(1), RAF1(4), SHC1(3), SOS1(5), SRC(3), SYT1(1) 7310068 76 35 74 26 25 20 3 19 9 0 0.573 1.000 299 MITRPATHWAY The MyoD/MEF2 transcription factors induce muscle cell differentiation and are repressed by the transcriptional repressor MITR. CAMK1, CAMK1G, HDAC9, MEF2A, MEF2B, MEF2C, MEF2D, MYOD1, YWHAH 9 CAMK1(1), CAMK1G(3), HDAC9(11), MEF2A(3), MEF2C(7), MEF2D(1) 1545529 26 13 26 12 8 7 0 11 0 0 0.573 1.000 300 PROPANOATE_METABOLISM ABAT, ACACA, ACADL, ACADM, ACADSB, ACAS2, ACAS2L, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH9A1, ECHS1, EHHADH, HADHA, LDHA, LDHB, LDHC, MCEE, MLYCD, MUT, PCCA, PCCB, SDS, SUCLA2, SUCLG1, SUCLG2 31 ABAT(5), ACACA(14), ACADM(3), ACADSB(5), ACAT1(1), ACAT2(2), ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH6A1(3), ALDH9A1(1), ECHS1(2), EHHADH(2), HADHA(2), LDHA(1), LDHB(1), LDHC(2), MCEE(1), MLYCD(1), MUT(3), PCCA(3), PCCB(3), SDS(2), SUCLA2(3), SUCLG1(1) 7531279 88 35 88 16 33 22 0 23 10 0 0.574 1.000 301 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(4), CREB1(1), GNAI1(3), GNAQ(3), GNAS(6), GNB1(1), MAP2K1(3), MAPK3(2), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), PLCG1(4), PPP3CA(1), PPP3CB(4), PPP3CC(3), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PRKCA(2), RAF1(4), RPS6KA3(3), SYT1(1) 7702126 64 39 63 23 30 9 3 14 8 0 0.575 1.000 302 MRPPATHWAY Cancer cells resistant to numerous drugs are called multidrug-resistant (MDR) and express ATP-binding cassette transporter proteins that pump the drugs out of cells. ABCB1, ABCB11, ABCB4, ABCC1, ABCC3, GSTP1 6 ABCB1(6), ABCB11(8), ABCB4(8), ABCC1(8), ABCC3(5) 3055796 35 21 35 10 5 14 0 10 6 0 0.582 1.000 303 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(3), NDUFA1(1), SDHA(5), SDHB(2), SDHD(1), UQCRC1(2) 1443707 16 11 16 3 5 5 0 5 1 0 0.582 1.000 304 ST_INTERFERON_GAMMA_PATHWAY The interferon gamma pathway resembles the JAK-STAT pathway and activates STAT transcription factors. CISH, IFNG, IFNGR1, JAK1, JAK2, PLA2G2A, PTPRU, REG1A, STAT1, STATIP1 9 IFNG(1), IFNGR1(2), JAK1(3), JAK2(6), PTPRU(6), REG1A(3), STAT1(6) 2538159 27 16 25 9 11 4 2 7 2 1 0.583 1.000 305 GLOBOSIDE_METABOLISM A4GALT, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, ST8SIA1 13 A4GALT(3), FUT1(1), FUT2(1), FUT9(4), GLA(4), HEXB(1), NAGA(1), ST3GAL1(1), ST3GAL2(1), ST3GAL4(2), ST8SIA1(3) 2244093 22 15 22 8 5 6 0 6 5 0 0.585 1.000 306 HSA00640_PROPANOATE_METABOLISM Genes involved in propanoate metabolism ABAT, ACACA, ACACB, ACADM, ACAT1, ACAT2, ACSS1, ACSS2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH7A1, ALDH9A1, ECHS1, EHHADH, HADHA, HIBCH, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, LOC283398, MCEE, MLYCD, MUT, PCCA, PCCB, SUCLA2, SUCLG1, SUCLG2 33 ABAT(5), ACACA(14), ACACB(14), ACADM(3), ACAT1(1), ACAT2(2), ACSS1(3), ACSS2(5), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH6A1(3), ALDH7A1(1), ALDH9A1(1), ECHS1(2), EHHADH(2), HADHA(2), LDHA(1), LDHAL6A(2), LDHAL6B(1), LDHB(1), LDHC(2), MCEE(1), MLYCD(1), MUT(3), PCCA(3), PCCB(3), SUCLA2(3), SUCLG1(1) 9043186 98 40 98 23 37 23 0 28 10 0 0.586 1.000 307 SA_G2_AND_M_PHASES Cdc25 activates the cdc2/cyclin B complex to induce the G2/M transition. CDC2, CDC25A, CDC25B, CDK7, CDKN1A, CHEK1, NEK1, WEE1 7 CDC25A(2), CDC25B(5), CDK7(1), CDKN1A(1), CHEK1(1), NEK1(7), WEE1(3) 1497944 20 12 19 7 7 4 0 8 1 0 0.588 1.000 308 PHENYLALANINE_METABOLISM ABP1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, DDC, EPX, GOT1, GOT2, HPD, LPO, MAOA, MAOB, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TAT, TPO 22 ABP1(1), ALDH1A3(4), ALDH3A1(2), ALDH3B1(2), ALDH3B2(1), AOC2(4), AOC3(4), DDC(1), EPX(6), GOT1(5), GOT2(1), HPD(3), LPO(2), MAOA(2), MPO(3), PRDX6(2), TAT(3), TPO(8) 4837673 54 33 53 16 29 12 0 10 3 0 0.589 1.000 309 IL4PATHWAY IL-4 promotes Th2 cell differentiation via a heterodimeric receptor that activates Stat6/JAK and MAP kinase pathways. AKT1, GRB2, IL2RG, IL4, IL4R, IRS1, JAK1, JAK3, RPS6KB1, SHC1, STAT6 11 AKT1(2), GRB2(2), IL4(3), IL4R(1), IRS1(5), JAK1(3), JAK3(6), RPS6KB1(3), SHC1(3), STAT6(2) 3273899 30 21 28 10 10 7 2 6 5 0 0.590 1.000 310 MITOCHONDRIAPATHWAY Pro-apoptotic signaling induces mitochondria to release cytochrome c, which stimulates Apaf-1 to activate caspase 9. APAF1, BAK1, BAX, BCL2, BCL2L1, BID, BIK, BIRC2, BIRC3, BIRC4, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, DFFA, DFFB, DIABLO, ENDOG, PDCD8 18 APAF1(7), BAK1(1), BAX(1), BCL2(1), BCL2L1(1), BID(1), BIK(1), BIRC2(2), BIRC3(2), CASP3(1), CASP6(1), CASP7(1), CASP9(2), DFFA(2), DFFB(2), DIABLO(1) 2837574 27 21 27 8 8 7 0 10 2 0 0.591 1.000 311 HSA00020_CITRATE_CYCLE Genes involved in citrate cycle (TCA cycle) ACLY, ACO1, ACO2, CLYBL, CS, DLD, DLST, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, LOC283398, LOC441996, MDH1, MDH2, OGDH, OGDHL, PC, PCK1, PCK2, SDHA, SDHB, SDHC, SDHD, SUCLA2, SUCLG1, SUCLG2 27 ACLY(4), ACO1(3), ACO2(2), CLYBL(5), FH(1), IDH1(3), IDH2(7), IDH3A(1), IDH3G(2), MDH1(1), MDH2(1), OGDH(4), OGDHL(8), PC(3), PCK2(3), SDHA(5), SDHB(2), SDHD(1), SUCLA2(3), SUCLG1(1) 6634216 60 36 60 19 27 14 0 14 5 0 0.594 1.000 312 HSA00440_AMINOPHOSPHONATE_METABOLISM Genes involved in aminophosphonate metabolism CARM1, CHPT1, HEMK1, LCMT1, LCMT2, METTL2B, METTL6, PCYT1A, PCYT1B, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, WBSCR22 16 CARM1(2), LCMT1(1), LCMT2(2), METTL2B(1), METTL6(5), PCYT1A(4), PCYT1B(5), PRMT2(1), PRMT3(2), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(3), WBSCR22(1) 3059338 31 21 31 14 9 9 0 11 2 0 0.600 1.000 313 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ2(2), COQ6(1), COQ7(1), NDUFA12(2), NDUFA13(1) 914763 7 7 7 2 1 2 0 2 2 0 0.605 1.000 314 CYANOAMINO_ACID_METABOLISM ATP6V0C, SHMT1, GBA3, GGT1, SHMT1, SHMT2 4 GBA3(3), SHMT1(1), SHMT2(2) 641894 6 6 6 3 2 1 0 0 3 0 0.608 1.000 315 GLEEVECPATHWAY The drug Gleevec specifically targets the abnormal bcr-abl protein, an apoptosis inhibitor present in chronic myeloid leukemia. AKT1, BCL2, BCR, CRKL, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, MYC, PIK3CA, PIK3R1, RAF1, SOS1, STAT1, STAT5A, STAT5B 20 AKT1(2), BCL2(1), BCR(6), CRKL(2), GRB2(2), JAK2(6), MAP2K1(3), MAP3K1(6), MAPK3(2), MAPK8(2), PIK3R1(5), RAF1(4), SOS1(5), STAT1(6), STAT5B(2) 5504413 54 28 53 13 20 12 6 10 5 1 0.613 1.000 316 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3D(1), CD3G(2) 266355 3 2 3 1 1 1 0 0 1 0 0.615 1.000 317 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 20 AKT1(2), EIF4A2(4), EIF4B(1), EIF4G1(8), EIF4G2(7), EIF4G3(8), MKNK1(1), PDK2(1), PDPK1(1), PIK3R1(5), PPP2CA(1), PTEN(6), RPS6KB1(3), TSC1(3), TSC2(1) 5654666 52 28 50 17 15 14 1 11 10 1 0.615 1.000 318 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(21), PAX3(5), PML(3), RB1(4), SIRT1(4), SP100(4), TNFRSF1A(1) 4066331 42 24 41 18 13 12 3 8 5 1 0.616 1.000 319 ST_PHOSPHOINOSITIDE_3_KINASE_PATHWAY The phosphoinositide-3 kinase pathway produces the lipid second messenger PIP3 and regulates cell growth, survival, and movement. A1BG, AKT1, AKT2, AKT3, BAD, BTK, CDKN2A, CSL4, DAF, DAPP1, FOXO1A, GRB2, GSK3A, GSK3B, IARS, IGFBP1, INPP5D, P14, PDK1, PIK3CA, PPP1R13B, PSCD3, PTEN, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SOS1, SOS2, TEC, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 32 AKT1(2), AKT2(5), BAD(1), BTK(6), CDKN2A(1), DAPP1(1), GRB2(2), GSK3A(2), GSK3B(7), IARS(5), IGFBP1(2), INPP5D(2), PPP1R13B(5), PTEN(6), RPS6KA1(1), RPS6KA2(8), RPS6KA3(3), RPS6KB1(3), SHC1(3), SOS1(5), SOS2(9), TEC(1), YWHAB(2), YWHAE(3), YWHAQ(1) 7466549 86 34 84 21 27 17 3 24 14 1 0.620 1.000 320 P53PATHWAY p53 induces cell cycle arrest or apoptosis under conditions of DNA damage. APAF1, ATM, BAX, BCL2, CCND1, CCNE1, CDK2, CDK4, CDKN1A, E2F1, GADD45A, MDM2, PCNA, RB1, TIMP3, TP53 14 APAF1(7), BAX(1), BCL2(1), CCNE1(3), CDK2(2), CDK4(2), CDKN1A(1), MDM2(4), PCNA(2), RB1(4), TIMP3(2) 2528786 29 17 29 6 7 6 0 14 1 1 0.623 1.000 321 CK1PATHWAY Caseine kinase 1 (CK1) and cdk5 phosphorylate DARPP32 in the dopamine signaling pathway. CDK5, CDK5R1, CSNK1D, DRD1, DRD2, GRM1, PLCB1, PPP1CA, PPP1R1B, PPP2CA, PPP3CA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 17 CDK5R1(1), CSNK1D(3), DRD1(1), DRD2(3), GRM1(9), PLCB1(8), PPP1R1B(1), PPP2CA(1), PPP3CA(1), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2) 3496532 35 25 35 13 14 7 1 8 5 0 0.623 1.000 322 HSA05050_DENTATORUBROPALLIDOLUYSIAN_ATROPHY Genes involved in dentatorubropallidoluysian atrophy (DRPLA) ATN1, BAIAP2, CASP1, CASP3, CASP7, CASP8, GAPDH, INS, INSR, ITCH, MAGI1, MAGI2, RERE, WWP1, WWP2 14 ATN1(3), CASP1(2), CASP3(1), CASP7(1), INSR(5), ITCH(3), MAGI1(10), MAGI2(6), RERE(3), WWP1(5), WWP2(4) 5036174 43 32 43 19 15 9 0 13 6 0 0.624 1.000 323 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(4), CDKN1A(1), GRIN1(1), HIF1A(1), JAK2(6), NFKB1(3), RELA(2), SOD2(4) 2875583 22 18 22 5 6 6 1 6 2 1 0.625 1.000 324 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(3), ACTN1(3), ACTN2(7), ACTN3(2), CAPN1(2), CAPNS1(1), CAPNS2(1), ITGA1(3), ITGB1(6), ITGB3(7), PTK2(5), SPTAN1(9), SRC(3), TLN1(5) 6192956 57 33 57 25 28 11 0 15 2 1 0.627 1.000 325 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(7), POLR1B(6), POLR1C(2), POLR1D(2), POLR2A(6), POLR2B(5), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLR3A(7), POLR3B(6), POLR3GL(1), POLR3H(1) 5246792 47 28 47 9 17 17 1 9 3 0 0.627 1.000 326 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(17), APOE(1), CETP(6), CYP7A1(4), HMGCR(2), LCAT(1), LDLR(4), LIPC(3), LPL(6), LRP1(14), SOAT1(1) 5645238 59 31 59 18 22 14 2 16 5 0 0.628 1.000 327 HSA00590_ARACHIDONIC_ACID_METABOLISM Genes involved in arachidonic acid metabolism AKR1C3, ALOX12, ALOX12B, ALOX15, ALOX15B, ALOX5, CBR1, CBR3, CYP2B6, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2E1, CYP2J2, CYP2U1, CYP4A11, CYP4A22, CYP4F2, CYP4F3, DHRS4, EPHX2, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, LTA4H, LTC4S, PGDS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PTGDS, PTGES, PTGES2, PTGIS, PTGS1, PTGS2, TBXAS1 50 ALOX12(2), ALOX12B(2), ALOX15B(5), ALOX5(4), CYP2C19(4), CYP2C8(2), CYP2C9(4), CYP2E1(5), CYP2J2(3), CYP2U1(1), CYP4A11(2), CYP4A22(2), CYP4F2(8), CYP4F3(2), EPHX2(1), GPX1(1), GPX2(2), GPX3(1), GPX5(4), GPX6(2), PLA2G1B(1), PLA2G2F(1), PLA2G4A(5), PLA2G6(2), PTGIS(4), PTGS1(4), PTGS2(2), TBXAS1(5) 8543568 81 41 81 28 30 12 0 34 5 0 0.636 1.000 328 HSA00561_GLYCEROLIPID_METABOLISM Genes involved in glycerolipid metabolism ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AGK, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, AKR1A1, AKR1B1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, CEL, DAK, DGAT1, DGAT2, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKI, DGKQ, DGKZ, GK, GK2, GLA, GLB1, GPAM, LCT, LIPA, LIPC, LIPF, LIPG, LPL, LYCAT, MGLL, PNLIP, PNLIPRP1, PNLIPRP2, PNPLA3, PPAP2A, PPAP2B, PPAP2C, UGCGL1, UGCGL2 54 ADH1B(2), ADH1C(3), ADH4(1), ADH5(1), ADH6(5), ADH7(2), ADHFE1(6), AGK(2), AGPAT1(1), AGPAT3(3), AGPAT4(6), AGPAT6(1), AKR1B1(2), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(1), ALDH9A1(1), CEL(1), DAK(3), DGAT2(3), DGKA(1), DGKB(7), DGKD(9), DGKE(1), DGKG(3), DGKH(5), DGKI(6), DGKZ(2), GK(3), GK2(3), GLA(4), GLB1(3), GPAM(2), LCT(15), LIPA(1), LIPC(3), LIPF(1), LIPG(2), LPL(6), PNLIP(5), PNLIPRP1(4), PNLIPRP2(1), PNPLA3(4), PPAP2B(1) 12987826 154 50 153 50 49 32 2 59 12 0 0.641 1.000 329 IFNAPATHWAY Interferon alpha, active in the immune response, binds to the IFN receptor and activates Jak1 and Tyk2, which phosphorylate Stat1 and Stat2. IFNA1, IFNAR1, IFNAR2, IFNB1, ISGF3G, JAK1, STAT1, STAT2, TYK2 8 IFNA1(1), IFNAR1(3), IFNAR2(1), IFNB1(1), JAK1(3), STAT1(6), STAT2(5), TYK2(1) 2374004 21 16 20 4 10 3 1 5 2 0 0.642 1.000 330 ST_PAC1_RECEPTOR_PATHWAY The signaling peptide PACAP binds to its receptor, PAC1R, which activates adenylyl cyclase and phospholipase C. ASAH1, CAMP, DAG1, GAS, GNAQ, ITPKA, ITPKB, PACAP 6 ASAH1(3), DAG1(4), GNAQ(3), ITPKB(4) 1356844 14 10 14 5 5 3 2 2 2 0 0.643 1.000 331 GANGLIOSIDE_BIOSYNTHESIS B3GALT4, GALGT, SIAT4A, SIAT4B, SIAT7B, SIAT7D, SIAT9, ST3GAL1, ST3GAL2, ST3GAL4, ST3GAL5, ST6GALNAC2, ST6GALNAC4, ST8SIA1 8 B3GALT4(1), ST3GAL1(1), ST3GAL2(1), ST3GAL4(2), ST6GALNAC2(1), ST6GALNAC4(1), ST8SIA1(3) 1240596 10 9 10 2 2 2 1 3 2 0 0.643 1.000 332 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(3), GPR161(5), GPR171(3), GPR34(5), GPR39(2), GPR45(4), GPR75(1) 2160775 26 17 26 9 12 4 1 7 2 0 0.644 1.000 333 HSA00363_BISPHENOL_A_DEGRADATION Genes involved in bisphenol A degradation AKR1B10, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, HSD3B7, PON1, PON2, PON3, RDH11, RDH12, RDH13, RDH14 13 DHRS1(1), DHRS2(2), DHRS3(2), HSD3B7(2), PON1(5), PON2(1), PON3(2), RDH12(2), RDH13(1) 1878267 18 14 18 7 7 3 1 3 4 0 0.645 1.000 334 HSA00604_GLYCOSPHINGOLIPID_BIOSYNTHESIS_GANGLIOSERIES Genes involved in glycosphingolipid biosynthesis - ganglioseries B3GALT4, B4GALNT1, GLB1, HEXA, HEXB, LCT, SLC33A1, ST3GAL1, ST3GAL2, ST3GAL5, ST6GALNAC3, ST6GALNAC4, ST6GALNAC5, ST6GALNAC6, ST8SIA1, ST8SIA5 16 B3GALT4(1), B4GALNT1(3), GLB1(3), HEXB(1), LCT(15), SLC33A1(1), ST3GAL1(1), ST3GAL2(1), ST6GALNAC3(3), ST6GALNAC4(1), ST6GALNAC5(4), ST6GALNAC6(3), ST8SIA1(3), ST8SIA5(4) 3657306 44 25 44 15 20 8 2 9 5 0 0.647 1.000 335 PYK2PATHWAY Pyk2 and Rac1 stimulate the JNK cascade and activate MKK3, which activates p38. BCAR1, CALM1, CALM2, CALM3, CRKL, GNAQ, GRB2, HRAS, JUN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP3K1, MAPK1, MAPK14, MAPK3, MAPK8, PAK1, PLCG1, PRKCA, PRKCB1, PTK2B, RAC1, RAF1, SHC1, SOS1, SRC, SYT1 27 CRKL(2), GNAQ(3), GRB2(2), MAP2K1(3), MAP2K3(2), MAP3K1(6), MAPK1(2), MAPK14(3), MAPK3(2), MAPK8(2), PAK1(4), PLCG1(4), PRKCA(2), PTK2B(1), RAF1(4), SHC1(3), SOS1(5), SRC(3), SYT1(1) 6232939 54 29 52 20 15 13 4 15 7 0 0.651 1.000 336 HSA00750_VITAMIN_B6_METABOLISM Genes involved in vitamin B6 metabolism AOX1, PDXK, PDXP, PNPO, PSAT1 5 AOX1(5), PNPO(1), PSAT1(3) 1106092 9 8 9 5 4 4 0 0 1 0 0.654 1.000 337 LYMPHOCYTEPATHWAY B and T cell lymphocytes interact with other cells via transmembrane adhesion proteins such as CD44, which interacts with endothelial cells. CD44, ICAM1, ITGA4, ITGAL, ITGB1, ITGB2, PECAM1, SELE, SELL 9 CD44(3), ICAM1(2), ITGA4(3), ITGAL(5), ITGB1(6), ITGB2(4), PECAM1(1), SELE(2) 2841027 26 18 25 8 8 9 0 7 2 0 0.655 1.000 338 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 ALG10(3), ALG10B(4), ALG11(1), ALG12(2), ALG13(1), ALG2(3), ALG3(1), ALG5(2), ALG6(3), ALG8(5), ALG9(1), B4GALT1(5), B4GALT2(3), B4GALT3(6), DAD1(2), DDOST(2), DPAGT1(1), DPM1(1), FUT8(1), GANAB(4), MAN1A1(4), MAN1A2(2), MAN1B1(2), MAN1C1(4), MAN2A1(8), MGAT1(1), MGAT3(2), MGAT4A(2), MGAT4B(1), MGAT5(3), MGAT5B(2), ST6GAL1(1), STT3B(4) 9381957 87 44 86 17 30 17 2 33 5 0 0.656 1.000 339 SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES ACAT1, ACAT2, BDH, HMGCL, OXCT1 4 ACAT1(1), ACAT2(2), OXCT1(3) 773281 6 6 6 2 1 1 0 4 0 0 0.662 1.000 340 TCAPOPTOSISPATHWAY HIV infection upregulates Fas ligand in macrophages and CD4 in helper T cells, leading to widespread Fas-induced T cell apoptosis. CCR5, CD28, CD3D, CD3E, CD3G, CD3Z, CD4, TNFRSF6, TNFSF6, TRA@, TRB@ 6 CCR5(1), CD28(1), CD3D(1), CD3G(2), CD4(2) 642460 7 6 8 5 2 4 0 0 1 0 0.664 1.000 341 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 14 ABL1(4), CDKN2A(1), MDM2(4), PIK3R1(5), POLR1A(7), POLR1B(6), POLR1C(2), POLR1D(2), RB1(4) 3751265 35 21 35 6 7 15 0 8 4 1 0.665 1.000 342 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 CAPN1(2), CAPNS1(1), CAPNS2(1), CDK5R1(1), CSNK1A1(2), CSNK1D(3), GSK3B(7), MAPT(4), PPP2CA(1) 1918009 22 14 22 4 9 6 0 4 3 0 0.667 1.000 343 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 48 AKT1(2), AKT2(5), BRD4(4), CBL(2), CDKN2A(1), F2RL2(2), FLOT1(3), GRB2(2), GSK3A(2), GSK3B(7), IGFBP1(2), INPPL1(3), IRS1(5), IRS4(11), LNPEP(6), MAPK1(2), MAPK3(2), PARD3(5), PIK3CD(2), PIK3R1(5), PPYR1(1), PTEN(6), PTPN1(4), RAF1(4), RPS6KA1(1), RPS6KA2(8), RPS6KA3(3), RPS6KB1(3), SERPINB6(1), SHC1(3), SLC2A4(3), SORBS1(7), SOS1(5), SOS2(9), YWHAB(2), YWHAE(3), YWHAQ(1) 12733833 137 49 133 42 44 29 4 42 17 1 0.669 1.000 344 HSA05110_CHOLERA_INFECTION Genes involved in cholera - infection ACTG1, ACTG2, ADCY3, ADCY9, AK1, ARF1, ARF3, ARF4, ARF5, ARF6, ARL4D, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E1, ATP6V1A, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ERO1L, GNAS, PDIA4, PLCG1, PLCG2, PRKCA, SEC61A1, SEC61A2, SEC61B, SEC61G, TRIM23 41 ACTG2(3), ADCY3(1), ADCY9(4), ARF4(2), ARF6(1), ARL4D(1), ATP6V0A1(2), ATP6V0A2(2), ATP6V0A4(4), ATP6V0D1(2), ATP6V0D2(6), ATP6V1A(2), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1E2(2), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(2), ERO1L(1), GNAS(6), PDIA4(4), PLCG1(4), PLCG2(9), PRKCA(2), SEC61A1(5), SEC61A2(1), SEC61B(1), TRIM23(5) 8288239 79 39 75 27 38 19 3 13 6 0 0.673 1.000 345 G2PATHWAY Activated Cdc2-cyclin B kinase regulates the G2/M transition; DNA damage stimulates the DNA-PK/ATM/ATR kinases, which inactivate Cdc2. ATM, ATR, BRCA1, CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CDC34, CDKN1A, CDKN2D, CHEK1, CHEK2, EP300, GADD45A, MDM2, MYT1, PLK, PRKDC, RPS6KA1, TP53, WEE1, YWHAH, YWHAQ 20 ATR(13), BRCA1(5), CCNB1(2), CDC25A(2), CDC25B(5), CDC25C(3), CDKN1A(1), CHEK1(1), CHEK2(1), EP300(13), MDM2(4), MYT1(8), PRKDC(13), RPS6KA1(1), WEE1(3), YWHAQ(1) 7576009 76 34 76 19 22 24 3 19 8 0 0.676 1.000 346 GLYCOSAMINOGLYCAN_DEGRADATION ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, IDS, IDUA, LCT, NAGLU 11 ARSB(5), GALNS(4), GLB1(3), GNS(1), GUSB(2), HEXB(1), IDS(2), IDUA(1), LCT(15), NAGLU(3) 3254815 37 22 37 10 16 6 2 9 4 0 0.679 1.000 347 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(5), ABP1(1), ACADM(3), ACADSB(5), ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), AOC2(4), AOC3(4), CNDP1(3), DPYD(8), DPYS(6), ECHS1(2), EHHADH(2), GAD1(7), GAD2(4), HADHA(2), MLYCD(1), SDS(2), SMS(2), UPB1(3) 6527462 92 34 92 16 34 25 1 25 7 0 0.680 1.000 348 PTC1PATHWAY The binding of extracellular signaling protein Sonic hedgehog to the Patched receptor (Ptc1) allows progression through G1 and may inhibit the G2/M transition. CCNB1, CCNH, CDC2, CDC25A, CDC25B, CDC25C, CDK7, MNAT1, PTCH, SHH, XPO1 9 CCNB1(2), CCNH(2), CDC25A(2), CDC25B(5), CDC25C(3), CDK7(1), MNAT1(1), XPO1(1) 2008281 17 12 17 7 5 5 0 6 1 0 0.681 1.000 349 METHIONINEPATHWAY Catabolic Pathways for Methionine, Isoleucine, Threonine and Valine BCKDHB, BCKDK, CBS, CTH, MUT 5 BCKDHB(1), BCKDK(2), CBS(2), CTH(1), MUT(3) 1117684 9 8 9 1 4 2 0 0 3 0 0.681 1.000 350 C21_STEROID_HORMONE_METABOLISM AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 AKR1C4(2), CYP11A1(2), CYP11B1(5), CYP11B2(5), CYP17A1(2), HSD11B1(1), HSD3B1(2) 1955432 19 14 19 6 11 4 0 4 0 0 0.682 1.000 351 HSA00140_C21_STEROID_HORMONE_METABOLISM Genes involved in C21-steroid hormone metabolism AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 AKR1C4(2), CYP11A1(2), CYP11B1(5), CYP11B2(5), CYP17A1(2), HSD11B1(1), HSD3B1(2) 1955432 19 14 19 6 11 4 0 4 0 0 0.682 1.000 352 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(2), AP2A1(2), AP2M1(4), BAD(1), BTK(6), EEA1(5), GRASP(1), GSK3A(2), GSK3B(7), LYN(4), PDPK1(1), PFKL(1), PFKM(1), PFKP(2), PLCG1(4), PRKCE(4), RPS6KB1(3), VAV2(2) 5563795 52 29 52 12 21 14 1 7 8 1 0.682 1.000 353 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(7), ATR(13), BAI1(2), BAX(1), BID(1), CASP3(1), CASP9(2), CCNB1(2), CCNB2(2), CCNB3(4), CCND2(1), CCND3(1), CCNE1(3), CCNE2(1), CCNG1(2), CDK2(2), CDK4(2), CDK6(1), CDKN1A(1), CDKN2A(1), CHEK1(1), CHEK2(1), IGF1(2), IGFBP3(2), MDM2(4), MDM4(2), PPM1D(4), PTEN(6), RCHY1(2), RFWD2(4), RPRM(1), RRM2(2), SERPINE1(1), SESN1(2), SESN2(3), SESN3(5), SIAH1(1), STEAP3(1), THBS1(8), TNFRSF10B(2), TSC2(1), ZMAT3(3) 12643349 108 47 107 29 30 27 4 34 12 1 0.683 1.000 354 ANDROGEN_AND_ESTROGEN_METABOLISM AKR1C4, AKR1D1, ARSB, ARSD, ARSE, CYP11B1, CYP11B2, HSD11B1, HSD11B2, HSD17B2, HSD17B3, HSD17B8, HSD3B1, HSD3B2, SRD5A1, SRD5A2, STS, SULT1E1, SULT2A1, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4 30 AKR1C4(2), ARSB(5), ARSD(3), ARSE(2), CYP11B1(5), CYP11B2(5), HSD11B1(1), HSD17B2(1), HSD17B3(1), HSD17B8(1), HSD3B1(2), SRD5A1(1), SRD5A2(1), STS(6), SULT1E1(1), SULT2A1(1), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(1), UGT1A5(3), UGT1A7(2), UGT1A9(5), UGT2B15(2), UGT2B4(2) 5811271 57 29 57 8 29 10 1 10 7 0 0.689 1.000 355 IL2PATHWAY IL-2 promotes proliferation via JAK and MAP kinase and has surface receptors on activated B cells, LPS-treated monocytes, and many T cells. CSNK2A1, ELK1, FOS, GRB2, HRAS, IL2, IL2RA, IL2RB, IL2RG, JAK1, JAK3, JUN, LCK, MAP2K1, MAPK3, MAPK8, RAF1, SHC1, SOS1, STAT5A, STAT5B, SYK 22 CSNK2A1(4), GRB2(2), IL2(3), IL2RA(2), IL2RB(1), JAK1(3), JAK3(6), LCK(2), MAP2K1(3), MAPK3(2), MAPK8(2), RAF1(4), SHC1(3), SOS1(5), STAT5B(2) 5226699 44 26 41 16 14 11 4 12 3 0 0.689 1.000 356 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 6 DBH(4), GAD1(7), HDC(3), TPH1(1) 1334752 15 12 15 6 6 2 1 6 0 0 0.690 1.000 357 HSA00350_TYROSINE_METABOLISM Genes involved in tyrosine metabolism ABP1, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, AOX1, ARD1A, CARM1, COMT, DBH, DCT, DDC, ECH1, ESCO1, ESCO2, FAH, GOT1, GOT2, GSTZ1, HEMK1, HGD, HPD, LCMT1, LCMT2, LYCAT, MAOA, MAOB, METTL2B, METTL6, MIF, MYST3, MYST4, NAT5, NAT6, PNMT, PNPLA3, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, SH3GLB1, TAT, TH, TPO, TYR, TYRP1, WBSCR22 56 ABP1(1), ADH1B(2), ADH1C(3), ADH4(1), ADH5(1), ADH6(5), ADH7(2), ADHFE1(6), ALDH1A3(4), ALDH3A1(2), ALDH3B1(2), ALDH3B2(1), AOC2(4), AOC3(4), AOX1(5), CARM1(2), DBH(4), DCT(9), DDC(1), ECH1(1), ESCO1(7), ESCO2(3), FAH(1), GOT1(5), GOT2(1), GSTZ1(2), HGD(1), HPD(3), LCMT1(1), LCMT2(2), MAOA(2), METTL2B(1), METTL6(5), MYST3(13), MYST4(5), PNPLA3(4), PRMT2(1), PRMT3(2), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(3), SH3GLB1(3), TAT(3), TPO(8), TYR(2), TYRP1(2), WBSCR22(1) 12994415 145 49 144 56 58 37 3 40 7 0 0.691 1.000 358 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(5), ITGAM(5), ITGB2(4), PECAM1(1), SELE(2) 2380691 22 16 22 6 8 8 0 4 2 0 0.695 1.000 359 BENZOATE_DEGRADATION_VIA_COA_LIGATION ACAT1, ACAT2, ACYP1, ACYP2, ECHS1, EHHADH, GCDH, HADHA, SDHB, SDS 10 ACAT1(1), ACAT2(2), ACYP1(1), ECHS1(2), EHHADH(2), GCDH(3), HADHA(2), SDHB(2), SDS(2) 1765483 17 11 17 1 5 3 0 5 4 0 0.695 1.000 360 HSA04662_B_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in B cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, BLNK, BTK, CARD11, CD19, CD22, CD72, CD79A, CD79B, CD81, CHP, CHUK, CR2, FCGR2B, FOS, GSK3B, HRAS, IFITM1, IKBKB, IKBKG, INPP5D, JUN, KRAS, LILRB3, LYN, MALT1, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCB1, PTPN6, RAC1, RAC2, RAC3, RASGRP3, SYK, VAV1, VAV2, VAV3 59 AKT1(2), AKT2(5), BCL10(3), BTK(6), CARD11(6), CD19(3), CD22(8), CD72(3), CD79A(3), CHUK(4), CR2(9), GSK3B(7), IFITM1(1), IKBKB(2), INPP5D(2), LILRB3(1), LYN(4), MALT1(6), NFAT5(5), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), NFKB1(3), NFKB2(2), NFKBIB(1), NFKBIE(2), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PLCG2(9), PPP3CA(1), PPP3CB(4), PPP3CC(3), PPP3R1(1), PPP3R2(1), PTPN6(4), RASGRP3(4), VAV1(11), VAV2(2), VAV3(10) 15721559 173 55 171 46 74 31 4 44 20 0 0.700 1.000 361 SA_G1_AND_S_PHASES Cdk2, 4, and 6 bind cyclin D in G1, while cdk2/cyclin E promotes the G1/S transition. ARF1, ARF3, CCND1, CDK2, CDK4, CDKN1A, CDKN1B, CDKN2A, CFL1, E2F1, E2F2, MDM2, NXT1, PRB1, TP53 14 CDK2(2), CDK4(2), CDKN1A(1), CDKN1B(1), CDKN2A(1), CFL1(1), E2F2(1), MDM2(4), NXT1(1) 1550562 14 10 14 4 2 4 0 7 1 0 0.700 1.000 362 HSA03050_PROTEASOME Genes involved in proteasome PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMC2, PSMC3, PSMD1, PSMD11, PSMD12, PSMD13, PSMD2, PSMD6 22 PSMA1(1), PSMA2(1), PSMA3(2), PSMA4(2), PSMA5(1), PSMB2(2), PSMB5(2), PSMB6(2), PSMC2(1), PSMC3(3), PSMD1(4), PSMD11(3), PSMD12(2), PSMD13(1), PSMD2(3), PSMD6(2) 3679575 32 22 32 15 10 7 2 10 3 0 0.701 1.000 363 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 123 ABL1(4), ABLIM1(5), ABLIM2(4), ABLIM3(5), ARHGEF12(7), CFL1(1), CXCL12(1), CXCR4(3), DCC(14), DPYSL2(3), DPYSL5(1), EFNA3(1), EFNA4(1), EFNA5(2), EFNB1(3), EFNB3(2), EPHA1(3), EPHA2(5), EPHA4(4), EPHA5(11), EPHA6(5), EPHA7(7), EPHA8(5), EPHB1(6), EPHB2(7), EPHB3(2), EPHB4(2), EPHB6(4), FYN(4), GNAI1(3), GSK3B(7), ITGB1(6), L1CAM(2), LIMK1(4), LIMK2(4), LRRC4C(6), MAPK1(2), MAPK3(2), MET(4), NFAT5(5), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), NGEF(1), NRP1(1), NTN1(4), NTN4(4), NTNG1(2), PAK1(4), PAK2(2), PAK3(3), PAK6(1), PAK7(4), PLXNA1(2), PLXNA2(5), PLXNA3(1), PLXNB1(3), PLXNB2(2), PLXNB3(2), PLXNC1(7), PPP3CA(1), PPP3CB(4), PPP3CC(3), PPP3R1(1), PPP3R2(1), PTK2(5), RASA1(5), RGS3(8), RHOA(4), RND1(1), ROBO2(15), ROBO3(2), ROCK1(8), ROCK2(2), SEMA3A(6), SEMA3B(1), SEMA3C(2), SEMA3D(9), SEMA3E(5), SEMA3F(1), SEMA3G(3), SEMA4A(2), SEMA4B(1), SEMA4D(12), SEMA4F(5), SEMA4G(5), SEMA5A(7), SEMA5B(7), SEMA6A(2), SEMA6C(2), SEMA6D(5), SEMA7A(2), SLIT1(9), SLIT2(12), SLIT3(7), SRGAP1(7), SRGAP2(3), SRGAP3(3), UNC5A(1), UNC5B(5), UNC5C(9), UNC5D(9) 41561322 429 94 424 148 172 88 4 109 56 0 0.703 1.000 364 CASPASEPATHWAY Caspases are cysteine proteases active in apoptosis; caspase-8 and 9 cleave and activate other caspases, while 3, 6, and 7 cleave cellular targets. ADPRT, APAF1, ARHGDIB, BIRC2, BIRC3, BIRC4, CASP1, CASP10, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CYCS, DFFA, DFFB, GZMB, LMNA, LMNB1, LMNB2, PRF1 20 APAF1(7), ARHGDIB(3), BIRC2(2), BIRC3(2), CASP1(2), CASP10(2), CASP2(4), CASP3(1), CASP4(1), CASP6(1), CASP7(1), CASP9(2), DFFA(2), DFFB(2), GZMB(1), LMNB1(2), LMNB2(1) 4102067 36 24 36 12 8 8 1 16 3 0 0.705 1.000 365 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 50 ACTA1(3), AGT(4), AKT1(2), CAMK1(1), CAMK1G(3), CAMK4(2), CREBBP(21), CSNK1A1(2), EDN1(1), ELSPBP1(1), F2(2), GATA4(1), GSK3B(7), HAND1(1), HAND2(1), IGF1(2), MAP2K1(3), MAPK1(2), MAPK14(3), MAPK3(2), MAPK8(2), MEF2C(7), MYH2(9), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), NKX2-5(1), NPPA(1), PIK3R1(5), PPP3CA(1), PPP3CB(4), PPP3CC(3), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), RAF1(4), RPS6KB1(3), SYT1(1) 10588366 124 44 123 32 43 34 4 24 19 0 0.711 1.000 366 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(4), CARS(5), DARS(3), EPRS(10), FARS2(4), GARS(3), HARS(2), IARS(5), KARS(3), LARS(4), LARS2(2), MARS(3), NARS(2), QARS(7), RARS(2), SARS(1), TARS(3), WARS(1), WARS2(2), YARS(2) 7296707 68 33 68 11 27 15 1 18 7 0 0.711 1.000 367 EEA1PATHWAY The FYVE-finger proteins EEA1 and HRS are localized to endosome membranes and regulate sorting and ubiquitination in the vesicle transport system. EEA1, EGF, EGFR, HGS, RAB5A, TF, TFRC 7 EEA1(5), EGF(3), EGFR(10), TF(7), TFRC(2) 2953464 27 18 27 6 14 4 1 5 2 1 0.712 1.000 368 DREAMPATHWAY The transcription factor DREAM blocks expression of the prodynorphin gene, which encodes the ligand of an opioid receptor that blocks pain signaling. CREB1, CREM, CSEN, FOS, JUN, MAPK3, OPRK1, POLR2A, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 13 CREB1(1), CREM(4), MAPK3(2), OPRK1(5), POLR2A(6), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2) 2819144 25 18 25 5 12 6 1 5 1 0 0.714 1.000 369 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(5), ALAS2(5), CPO(3), FECH(2), GATA1(4), HBB(2), HMBS(2), UROS(1) 1854085 24 14 24 5 13 5 0 5 1 0 0.714 1.000 370 HSA00591_LINOLEIC_ACID_METABOLISM Genes involved in linoleic acid metabolism AKR1B10, ALOX15, ALOX5, CYP1A2, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2E1, CYP2J2, CYP3A4, CYP3A43, CYP3A5, CYP3A7, HSD3B7, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, RDH11, RDH12, RDH13, RDH14 31 ALOX5(4), CYP1A2(2), CYP2C19(4), CYP2C8(2), CYP2C9(4), CYP2E1(5), CYP2J2(3), CYP3A4(1), CYP3A5(3), CYP3A7(4), HSD3B7(2), PLA2G1B(1), PLA2G2F(1), PLA2G4A(5), PLA2G6(2), RDH12(2), RDH13(1) 5411937 46 26 46 22 17 10 1 15 2 1 0.716 1.000 371 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(3), UBE2A(2), UBE2B(2), UBE2C(2), UBE2D1(1), UBE2E1(3), UBE2G1(2), UBE2I(1), UBE2J2(1), UBE2L3(2), UBE3A(6) 2340485 25 14 25 10 7 2 2 9 5 0 0.717 1.000 372 HSA00360_PHENYLALANINE_METABOLISM Genes involved in phenylalanine metabolism ABP1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, ARD1A, DDC, EPX, ESCO1, ESCO2, GOT1, GOT2, HPD, LPO, LYCAT, MAOA, MAOB, MIF, MPO, MYST3, MYST4, NAT5, NAT6, PNPLA3, PRDX6, SH3GLB1, TAT, TPO 27 ABP1(1), ALDH1A3(4), ALDH3A1(2), ALDH3B1(2), ALDH3B2(1), AOC2(4), AOC3(4), DDC(1), EPX(6), ESCO1(7), ESCO2(3), GOT1(5), GOT2(1), HPD(3), LPO(2), MAOA(2), MPO(3), MYST3(13), MYST4(5), PNPLA3(4), PRDX6(2), SH3GLB1(3), TAT(3), TPO(8) 7618227 89 39 88 26 45 22 1 16 5 0 0.717 1.000 373 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 7 ABO(2), FUT1(1), FUT2(1), FUT3(3), FUT6(1), ST3GAL3(4) 1019671 12 9 12 4 7 2 0 3 0 0 0.718 1.000 374 STREPTOMYCIN_BIOSYNTHESIS GCK, HK1, HK2, HK3, IMPA1, PGM1, PGM3, TGDS 8 GCK(1), HK1(6), HK2(3), HK3(4), IMPA1(2), PGM1(2), PGM3(4) 2304758 22 16 22 11 6 6 0 10 0 0 0.718 1.000 375 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 141 ADA(2), ADCY1(4), ADCY2(12), ADCY3(1), ADCY4(9), ADCY5(8), ADCY6(1), ADCY7(3), ADCY8(11), ADCY9(4), ADK(1), ADSL(7), ADSS(1), AK5(4), AK7(5), ALLC(3), AMPD1(7), AMPD2(4), AMPD3(2), ATIC(4), DCK(1), ENPP1(4), ENPP3(3), ENTPD1(2), ENTPD3(5), ENTPD4(5), ENTPD5(1), ENTPD6(1), FHIT(1), GART(3), GMPR(1), GMPR2(2), GMPS(5), GUCY1A2(8), GUCY1B3(7), GUCY2C(7), GUCY2D(4), GUCY2F(7), HPRT1(2), IMPDH1(1), IMPDH2(1), ITPA(2), NME6(3), NME7(3), NPR1(6), NPR2(9), NT5C1A(1), NT5C1B(9), NT5C2(3), NT5C3(2), NT5E(2), NT5M(1), NUDT9(2), PAPSS1(1), PAPSS2(2), PDE10A(6), PDE11A(7), PDE1A(3), PDE1C(7), PDE3B(2), PDE4A(4), PDE4B(2), PDE4C(2), PDE4D(3), PDE5A(3), PDE6D(1), PDE7A(3), PDE7B(3), PDE8A(1), PDE8B(6), PDE9A(5), PFAS(1), PKM2(2), PNPT1(5), POLA1(5), POLA2(2), POLD1(5), POLD2(1), POLD3(2), POLE(17), POLE3(1), POLR1A(7), POLR1B(6), POLR1C(2), POLR1D(2), POLR2A(6), POLR2B(5), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLR3A(7), POLR3B(6), POLR3GL(1), POLR3H(1), PPAT(3), PRIM2(6), PRPS1L1(1), PRPS2(2), RFC5(2), RRM1(1), RRM2(2), XDH(7) 36444503 380 81 377 122 124 103 11 91 51 0 0.719 1.000 376 HSA00521_STREPTOMYCIN_BIOSYNTHESIS Genes involved in streptomycin biosynthesis GCK, HK1, HK2, HK3, IMPA1, IMPA2, ISYNA1, PGM1, PGM3, TGDS 10 GCK(1), HK1(6), HK2(3), HK3(4), IMPA1(2), IMPA2(2), PGM1(2), PGM3(4) 2615706 24 18 24 11 7 6 0 10 1 0 0.719 1.000 377 TELPATHWAY Telomerase is a ribonucleotide protein that adds telomeric repeats to the 3' ends of chromosomes. AKT1, BCL2, EGFR, G22P1, HSPCA, IGF1R, KRAS2, MYC, POLR2A, PPP2CA, PRKCA, RB1, TEP1, TERF1, TERT, TNKS, TP53, XRCC5 14 AKT1(2), BCL2(1), EGFR(10), IGF1R(7), POLR2A(6), PPP2CA(1), PRKCA(2), RB1(4), TEP1(7), TERT(2), TNKS(4), XRCC5(4) 6198051 50 33 50 15 24 7 1 14 3 1 0.720 1.000 378 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(1), BMP5(4), BMP6(3), BMP7(5), BMP8A(1), BTRC(2), CSNK1A1(2), CSNK1A1L(5), CSNK1D(3), CSNK1G1(1), CSNK1G3(2), DHH(1), FBXW11(7), GLI1(3), GLI2(2), GLI3(9), GSK3B(7), HHIP(4), IHH(1), LRP2(39), PRKACB(1), PRKACG(2), PRKX(2), PTCH1(8), PTCH2(4), RAB23(1), STK36(4), SUFU(4), WNT1(1), WNT10B(3), WNT11(3), WNT16(2), WNT2B(1), WNT3(4), WNT3A(1), WNT4(1), WNT5A(3), WNT7A(2), WNT7B(2), WNT8A(1), WNT9A(2), WNT9B(1), ZIC2(1) 13405539 156 56 155 70 71 33 2 32 18 0 0.721 1.000 379 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(3), RAB27A(2), RAB3A(2), RAB4A(1), RAB6A(2) 939684 10 8 10 2 3 6 0 1 0 0 0.731 1.000 380 PROTEASOME PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB10, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMB8, PSMB9 17 PSMA1(1), PSMA2(1), PSMA3(2), PSMA4(2), PSMA5(1), PSMB2(2), PSMB5(2), PSMB6(2), PSMB9(4) 1998179 17 14 17 6 6 3 2 3 3 0 0.737 1.000 381 HSA01040_POLYUNSATURATED_FATTY_ACID_BIOSYNTHESIS Genes involved in polyunsaturated fatty acid biosynthesis ACAA1, ACOX1, ACOX3, ELOVL2, ELOVL5, ELOVL6, FADS1, FADS2, FASN, GPSN2, HADHA, HSD17B12, PECR, SCD 13 ACAA1(2), ACOX1(3), ACOX3(5), ELOVL2(3), ELOVL5(1), ELOVL6(1), FADS2(3), FASN(1), HADHA(2), HSD17B12(2), SCD(2) 3282086 25 19 25 4 11 6 1 4 3 0 0.738 1.000 382 HSA00530_AMINOSUGARS_METABOLISM Genes involved in aminosugars metabolism AMDHD2, CHIA, CHIT1, CMAS, CTBS, CYB5R1, CYB5R3, GFPT1, GFPT2, GNE, GNPDA1, GNPDA2, GNPNAT1, HEXA, HEXB, HK1, HK2, HK3, LHPP, MTMR1, MTMR2, MTMR6, NAGK, NANS, NPL, PGM3, PHPT1, RENBP, UAP1 29 CHIA(5), CHIT1(4), CMAS(5), CTBS(4), CYB5R1(1), CYB5R3(1), GFPT1(3), GFPT2(3), GNE(2), GNPDA2(1), HEXB(1), HK1(6), HK2(3), HK3(4), LHPP(1), MTMR1(4), MTMR2(1), MTMR6(4), NAGK(2), NPL(2), PGM3(4), PHPT1(1), RENBP(1) 6495567 63 33 63 17 25 17 0 16 5 0 0.739 1.000 383 IL17PATHWAY Activated T cells secrete IL-17, which stimulates fibroblasts and other cells to secrete inflammatory and hematopoietic cytokines. CD2, CD34, CD3D, CD3E, CD3G, CD3Z, CD4, CD58, CD8A, CSF3, IL17, IL3, IL6, IL8, KITLG, TRA@, TRB@ 13 CD2(3), CD34(1), CD3D(1), CD3G(2), CD4(2), CD58(1), IL3(3), IL6(1), KITLG(2) 1443001 16 10 15 6 5 6 0 4 1 0 0.740 1.000 384 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 64 ADAM10(1), ADAM17(6), ATP6AP1(2), ATP6V0A1(2), ATP6V0A2(2), ATP6V0A4(4), ATP6V0D1(2), ATP6V0D2(6), ATP6V1A(2), ATP6V1B1(4), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1E2(2), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(2), CASP3(1), CHUK(4), CSK(1), EGFR(10), F11R(1), GIT1(2), HBEGF(1), IGSF5(6), IKBKB(2), JAM3(3), LYN(4), MAP3K14(2), MAPK10(4), MAPK12(2), MAPK14(3), MAPK8(2), MAPK9(3), MET(4), NFKB1(3), NFKB2(2), NOD1(3), PAK1(4), PLCG1(4), PLCG2(9), PTPN11(2), PTPRZ1(12), RELA(2), SRC(3), TCIRG1(2), TJP1(5) 15505644 149 51 147 41 56 37 3 38 15 0 0.743 1.000 385 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(4), ASPH(2), CREB1(1), EDN1(1), EP300(13), HIF1A(1), LDHA(1), NOS3(2), P4HB(2) 3793446 27 21 27 10 8 11 0 6 2 0 0.749 1.000 386 HEME_BIOSYNTHESIS ALAD, ALAS1, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, UROS 9 ALAS1(5), ALAS2(5), FECH(2), HMBS(2), PPOX(3), UROS(1) 1751382 18 12 18 3 10 3 0 4 1 0 0.750 1.000 387 DNAFRAGMENTPATHWAY DNA fragmentation during apoptosis is effected by DFF, a caspase-activated DNAse, and by endonuclease G. CASP3, CASP7, DFFA, DFFB, ENDOG, GZMB, HMGB1, HMGB2, TOP2A, TOP2B 10 CASP3(1), CASP7(1), DFFA(2), DFFB(2), GZMB(1), HMGB1(1), HMGB2(1), TOP2A(2), TOP2B(5) 1842185 16 12 15 4 3 4 0 8 1 0 0.750 1.000 388 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), ATIC(4), FTCD(2), GART(3), MTFMT(1), MTHFD1(6), MTHFD1L(6), MTHFR(6), MTHFS(1), MTR(6), SHMT1(1), SHMT2(2), TYMS(2) 4240150 43 25 43 11 18 9 0 11 5 0 0.752 1.000 389 HISTIDINE_METABOLISM ABP1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, AOC2, AOC3, ASPA, CNDP1, DDC, HAL, HARS, HARSL, HDC, HNMT, MAOA, MAOB, PRPS1, PRPS2 24 ABP1(1), ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH3B1(2), ALDH3B2(1), ALDH9A1(1), AOC2(4), AOC3(4), ASPA(3), CNDP1(3), DDC(1), HAL(3), HARS(2), HDC(3), HNMT(4), MAOA(2), PRPS2(2) 5415728 63 31 63 15 26 19 0 17 1 0 0.752 1.000 390 HSA00930_CAPROLACTAM_DEGRADATION Genes involved in caprolactam degradation AKR1A1, ASAHL, ECHS1, EHHADH, HADH, HADHA, HSD17B10, HSD17B4, NTAN1, SIRT1, SIRT2, SIRT5, SIRT7, VNN2, VNN3 13 ECHS1(2), EHHADH(2), HADH(1), HADHA(2), HSD17B10(1), HSD17B4(3), NTAN1(3), SIRT1(4), SIRT2(1), SIRT5(1), SIRT7(1), VNN2(1) 2666211 22 17 22 8 8 7 0 2 5 0 0.755 1.000 391 GLYCEROLIPID_METABOLISM ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AKR1A1, AKR1B1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, CEL, DGAT1, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKQ, DGKZ, GK, GLA, GLB1, LCT, LIPC, LIPF, LIPG, LPL, PNLIP, PNLIPRP1, PNLIPRP2, PPAP2A, PPAP2B, PPAP2C 44 ADH1B(2), ADH1C(3), ADH4(1), ADH6(5), ADH7(2), ADHFE1(6), AGPAT1(1), AGPAT3(3), AGPAT4(6), AKR1B1(2), ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), CEL(1), DGKA(1), DGKB(7), DGKD(9), DGKE(1), DGKG(3), DGKH(5), DGKZ(2), GK(3), GLA(4), GLB1(3), LCT(15), LIPC(3), LIPF(1), LIPG(2), LPL(6), PNLIP(5), PNLIPRP1(4), PNLIPRP2(1), PPAP2B(1) 10636871 136 43 135 36 43 31 2 49 11 0 0.755 1.000 392 VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION ACAA1, ACAA2, ACADL, ACADM, ACADS, ACADSB, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH9A1, AOX1, BCAT1, BCKDHA, BCKDHB, ECHS1, EHHADH, HADHA, HADHB, HIBADH, HMGCL, IVD, MCCC1, MCCC2, MCEE, MUT, OXCT1, PCCA, PCCB, SDS 36 ACAA1(2), ACADM(3), ACADSB(5), ACAT1(1), ACAT2(2), ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH6A1(3), ALDH9A1(1), AOX1(5), BCAT1(1), BCKDHA(3), BCKDHB(1), ECHS1(2), EHHADH(2), HADHA(2), HADHB(1), MCCC1(7), MCCC2(2), MCEE(1), MUT(3), OXCT1(3), PCCA(3), PCCB(3), SDS(2) 8179982 85 37 85 18 33 19 0 24 9 0 0.762 1.000 393 FMLPPATHWAY The fMLP receptor is a G-protein coupled receptor in neutrophils that recognizes formylated bacterial peptides and activates NADPH oxidase. CALM1, CALM2, CALM3, CAMK1, CAMK1G, ELK1, FPR1, GNA15, GNB1, GNGT1, HRAS, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NCF1, NCF2, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKBIA, PAK1, PIK3C2G, PLCB1, PPP3CA, PPP3CB, PPP3CC, RAC1, RAF1, RELA, SYT1 37 CAMK1(1), CAMK1G(3), FPR1(2), GNA15(3), GNB1(1), MAP2K1(3), MAP2K3(2), MAP2K6(2), MAP3K1(6), MAPK1(2), MAPK14(3), MAPK3(2), NCF1(1), NCF2(1), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), NFKB1(3), PAK1(4), PIK3C2G(7), PLCB1(8), PPP3CA(1), PPP3CB(4), PPP3CC(3), RAF1(4), RELA(2), SYT1(1) 8462003 81 37 80 27 31 16 3 16 15 0 0.768 1.000 394 TCYTOTOXICPATHWAY Cytotoxic T cells release perforin and granzyme to lyse foreign cell targets and express Fas ligand to promote Fas-induced apoptosis. CD2, CD28, CD3D, CD3E, CD3G, CD3Z, CD8A, ICAM1, ITGAL, ITGB2, PTPRC, THY1, TRA@, TRB@ 11 CD2(3), CD28(1), CD3D(1), CD3G(2), ICAM1(2), ITGAL(5), ITGB2(4), PTPRC(9) 2394233 27 17 27 9 6 10 0 6 5 0 0.771 1.000 395 HSA00642_ETHYLBENZENE_DEGRADATION Genes involved in ethylbenzene degradation ARD1A, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ESCO1, ESCO2, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1 11 DHRS1(1), DHRS2(2), DHRS3(2), ESCO1(7), ESCO2(3), MYST3(13), MYST4(5), PNPLA3(4), SH3GLB1(3) 3609005 40 21 40 13 19 10 1 6 4 0 0.772 1.000 396 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 FOSL2(1), IFNAR1(3), IFNAR2(1), IFNB1(1), MAPK8(2), NFKB1(3), RELA(2), TNFRSF11A(2), TNFSF11(1), TRAF6(4) 2474213 20 14 20 7 7 7 0 1 5 0 0.772 1.000 397 THELPERPATHWAY Helper T cells coordinate the actions of B cells, macrophages, and other immune cells via surface molecules such as T cell receptor/CD3 and their characteristic marker CD4. CD2, CD28, CD3D, CD3E, CD3G, CD3Z, CD4, ICAM1, ITGAL, ITGB2, PTPRC, THY1, TRA@, TRB@ 11 CD2(3), CD28(1), CD3D(1), CD3G(2), CD4(2), ICAM1(2), ITGAL(5), ITGB2(4), PTPRC(9) 2530710 29 18 29 11 6 12 0 6 5 0 0.773 1.000 398 CITRATE_CYCLE_TCA_CYCLE ACO1, ACO2, CS, DLD, DLST, DLSTP, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, MDH1, MDH2, PC, PCK1, SDHA, SDHA, SDHAL2, SDHB, SUCLA2, SUCLG1, SUCLG2 20 ACO1(3), ACO2(2), FH(1), IDH1(3), IDH2(7), IDH3A(1), IDH3G(2), MDH1(1), MDH2(1), PC(3), SDHA(5), SDHB(2), SUCLA2(3), SUCLG1(1) 4559430 35 25 35 13 17 7 0 7 4 0 0.774 1.000 399 HSA04650_NATURAL_KILLER_CELL_MEDIATED_CYTOTOXICITY Genes involved in natural killer cell mediated cytotoxicity ARAF, BID, BRAF, CASP3, CD244, CD247, CD48, CHP, CSF2, FAS, FASLG, FCER1G, FCGR3A, FCGR3B, FYN, GRB2, GZMB, HCST, HLA-A, HLA-B, HLA-C, HLA-E, HLA-G, HRAS, ICAM1, ICAM2, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNG, IFNGR1, IFNGR2, ITGAL, ITGB2, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DS1, KIR2DS2, KIR3DL1, KIR3DL2, KLRC1, KLRC2, KLRC3, KLRD1, KLRK1, KRAS, LAT, LCK, LCP2, LOC652578, MAP2K1, MAP2K2, MAPK1, MAPK3, MICA, MICB, NCR1, NCR2, NCR3, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NRAS, PAK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRF1, PRKCA, PRKCB1, PRKCG, PTK2B, PTPN11, PTPN6, RAC1, RAC2, RAC3, RAF1, SH2D1A, SH2D1B, SH3BP2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SYK, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFSF10, TYROBP, ULBP1, ULBP2, ULBP3, VAV1, VAV2, VAV3, ZAP70 120 ARAF(3), BID(1), CASP3(1), CD244(3), CD247(2), FASLG(1), FYN(4), GRB2(2), GZMB(1), HLA-A(1), HLA-B(3), HLA-C(2), HLA-E(1), HLA-G(1), ICAM1(2), ICAM2(1), IFNA1(1), IFNA10(1), IFNA13(2), IFNA16(4), IFNA2(3), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), IFNAR1(3), IFNAR2(1), IFNB1(1), IFNG(1), IFNGR1(2), IFNGR2(1), ITGAL(5), ITGB2(4), KIR2DL1(2), KIR2DL3(1), KIR2DL4(2), KIR3DL1(3), KIR3DL2(3), KLRC3(2), KLRD1(1), KLRK1(3), LCK(2), LCP2(2), MAP2K1(3), MAPK1(2), MAPK3(2), MICB(1), NCR1(1), NCR3(1), NFAT5(5), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), PAK1(4), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PLCG1(4), PLCG2(9), PPP3CA(1), PPP3CB(4), PPP3CC(3), PPP3R1(1), PPP3R2(1), PRKCA(2), PRKCG(8), PTK2B(1), PTPN11(2), PTPN6(4), RAF1(4), SH2D1A(2), SH2D1B(1), SHC1(3), SHC3(1), SHC4(5), SOS1(5), SOS2(9), TNFRSF10A(3), TNFRSF10B(2), TNFSF10(1), ULBP1(2), ULBP2(2), VAV1(11), VAV2(2), VAV3(10), ZAP70(4) 24031129 249 61 244 69 81 57 10 69 30 2 0.774 1.000 400 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(4), DYRK1B(4), GLI2(2), GLI3(9), GSK3B(7), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), SUFU(4) 3624283 37 23 37 21 18 9 2 3 5 0 0.776 1.000 401 UREACYCLEPATHWAY Ammonia released from amino acid deamination is used to produce carbamoyl phosphate, which is used to convert ornithine to citrulline, from which urea is eventually formed. ARG1, ASL, ASS, CPS1, GLS, GLUD1, GOT1 6 ARG1(1), CPS1(8), GLUD1(2), GOT1(5) 1722990 16 10 16 4 4 5 0 4 3 0 0.777 1.000 402 TERPENOID_BIOSYNTHESIS FDFT1, FDPS, FDPS, LOC402397, IDI1, SQLE 4 FDFT1(2), IDI1(1), SQLE(1) 671672 4 4 4 3 1 2 0 0 1 0 0.778 1.000 403 SIG_PIP3_SIGNALING_IN_CARDIAC_MYOCTES Genes related to PIP3 signaling in cardiac myocytes AKT1, AKT2, AKT3, BAD, BCL2L1, CDC42, CDK2, CDKN1B, CDKN2A, CREB1, CREB3, CREB5, EBP, ERBB4, F2RL2, FOXO3A, FRAP1, GAB1, GADD45A, GRB2, GSK3A, GSK3B, IFI27, IGF1, IGFBP1, INPPL1, IRS1, IRS2, IRS4, MET, MYC, NOLC1, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARD3, PARD6A, PDK1, PIK3CA, PIK3CD, PPP1R13B, PREX1, PSCD3, PTEN, PTK2, PTPN1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SLC2A4, SOS1, SOS2, TSC1, TSC2, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 61 AKT1(2), AKT2(5), BAD(1), BCL2L1(1), CDK2(2), CDKN1B(1), CDKN2A(1), CREB1(1), CREB3(2), CREB5(2), EBP(2), F2RL2(2), GAB1(6), GRB2(2), GSK3A(2), GSK3B(7), IGF1(2), IGFBP1(2), INPPL1(3), IRS1(5), IRS4(11), MET(4), NOLC1(7), PAK1(4), PAK2(2), PAK3(3), PAK6(1), PAK7(4), PARD3(5), PIK3CD(2), PPP1R13B(5), PREX1(14), PTEN(6), PTK2(5), PTPN1(4), RPS6KA1(1), RPS6KA2(8), RPS6KA3(3), RPS6KB1(3), SHC1(3), SLC2A4(3), SOS1(5), SOS2(9), TSC1(3), TSC2(1), YWHAB(2), YWHAE(3), YWHAQ(1) 16036497 173 53 169 64 60 36 5 48 23 1 0.778 1.000 404 EGFR_SMRTEPATHWAY EGF receptor activation inhibits SMRT, a transcriptional co-repressor that interacts with transcription factor complexes and gene silencers. EGF, EGFR, MAP2K1, MAP3K1, MAPK14, NCOR2, RARA, RXRA, THRA, THRB, ZNF145 10 EGF(3), EGFR(10), MAP2K1(3), MAP3K1(6), MAPK14(3), NCOR2(2), RXRA(1), THRA(2), THRB(4) 3852603 34 21 34 13 17 7 2 6 2 0 0.779 1.000 405 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(4), AARS2(6), CARS(5), CARS2(1), DARS(3), DARS2(2), EPRS(10), FARS2(4), FARSA(1), FARSB(7), GARS(3), HARS(2), HARS2(2), IARS(5), IARS2(6), KARS(3), LARS(4), LARS2(2), MARS(3), MTFMT(1), NARS(2), NARS2(3), QARS(7), RARS(2), RARS2(3), SARS(1), SARS2(2), TARS(3), TARS2(4), VARS(1), VARS2(6), WARS(1), WARS2(2), YARS(2), YARS2(3) 12243810 116 44 116 19 45 23 2 30 16 0 0.779 1.000 406 NOS1PATHWAY Glutamate stimulates NMDA-mediates calcium influx, which promotes nitric oxide synthesis from arginine by neuronal nitric oxide synthase, activating guanylate cyclase. CALM1, CALM2, CALM3, DLG4, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, NOS1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, SYT1 21 DLG4(2), GRIN1(1), GRIN2A(15), GRIN2B(8), GRIN2C(2), GRIN2D(3), NOS1(5), PPP3CA(1), PPP3CB(4), PPP3CC(3), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PRKCA(2), SYT1(1) 5585619 54 29 54 31 25 12 1 9 7 0 0.787 1.000 407 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 34 AKT1(2), ATF1(1), CREB1(1), CREB3(2), CREB5(2), DUSP1(2), DUSP10(4), IL1R1(3), MAP2K3(2), MAP2K6(2), MAP3K10(2), MAP3K4(15), MAP3K5(5), MAP3K7(2), MAPK1(2), MAPK12(2), MAPK14(3), MAPKAPK2(3), MAPKAPK5(1), MKNK1(1), MKNK2(2), MYEF2(7), NFKB1(3), NR2C2(4), SRF(3), TRAF6(4) 7488839 80 36 79 22 25 19 2 22 12 0 0.789 1.000 408 IL10PATHWAY The cytokine IL-10 inhibits the inflammatory response by macrophages via activation of heme oxygenase 1. BLVRA, BLVRB, HMOX1, IL10, IL10RA, IL10RB, IL1A, IL6, JAK1, STAT1, STAT3, STAT5A, TNF 13 BLVRA(2), BLVRB(1), HMOX1(2), IL10(1), IL10RA(1), IL10RB(4), IL1A(1), IL6(1), JAK1(3), STAT1(6), STAT3(2) 2708425 24 16 22 16 10 4 1 8 1 0 0.790 1.000 409 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 RANBP1(1), RANBP2(8), RANGAP1(1) 1717595 10 8 10 1 4 1 1 0 4 0 0.793 1.000 410 NUCLEOTIDE_METABOLISM ADSL, ADSS, DHFR, HPRT1, IMPDH1, MTHFD2, NME2, OAZ1, POLA, POLB, POLD1, POLG, PRPS2, RRM1, SAT, SRM 14 ADSL(7), ADSS(1), HPRT1(2), IMPDH1(1), POLB(1), POLD1(5), POLG(4), PRPS2(2), RRM1(1) 2788374 24 19 24 9 11 5 0 7 1 0 0.793 1.000 411 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 198 ACTN1(3), ACTN2(7), ACTN3(2), ACTN4(2), APC2(1), ARAF(3), ARHGEF1(4), ARHGEF12(7), ARHGEF4(3), ARHGEF6(7), ARHGEF7(8), ARPC1A(5), ARPC1B(2), ARPC2(1), ARPC5(1), ARPC5L(1), BDKRB2(2), CD14(1), CFL1(1), CHRM1(3), CHRM2(8), CHRM3(4), CHRM5(1), CRKL(2), CSK(1), CYFIP1(5), CYFIP2(4), DIAPH1(1), DIAPH2(9), DIAPH3(3), DOCK1(5), EGF(3), EGFR(10), EZR(2), F2(2), FGD1(6), FGD3(1), FGF1(2), FGF11(2), FGF12(2), FGF13(2), FGF14(5), FGF17(1), FGF20(1), FGF21(1), FGF23(1), FGF3(1), FGF5(2), FGF6(3), FGF7(1), FGF8(1), FGF9(1), FGFR1(3), FGFR2(1), FGFR3(2), FGFR4(2), FN1(17), GIT1(2), GNA12(2), GNA13(2), GRLF1(7), IQGAP1(10), IQGAP2(9), IQGAP3(11), ITGA1(3), ITGA10(3), ITGA11(2), ITGA2(5), ITGA2B(2), ITGA3(4), ITGA4(3), ITGA5(7), ITGA6(3), ITGA7(6), ITGA8(5), ITGA9(4), ITGAD(7), ITGAE(5), ITGAL(5), ITGAM(5), ITGAV(1), ITGAX(4), ITGB1(6), ITGB2(4), ITGB3(7), ITGB4(2), ITGB5(5), ITGB6(6), ITGB7(4), ITGB8(4), LIMK1(4), LIMK2(4), MAP2K1(3), MAPK1(2), MAPK3(2), MOS(2), MRAS(1), MSN(3), MYH10(8), MYH14(9), MYH9(9), MYL2(1), MYL7(1), MYLK(11), MYLK2(2), NCKAP1(8), NCKAP1L(7), PAK1(4), PAK2(2), PAK3(3), PAK6(1), PAK7(4), PDGFA(1), PDGFRA(13), PDGFRB(5), PFN2(1), PFN4(1), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PIP4K2A(2), PIP4K2B(2), PIP4K2C(3), PIP5K1A(3), PIP5K1B(1), PIP5K1C(3), PPP1CB(1), PPP1CC(1), PPP1R12A(2), PPP1R12B(5), PTK2(5), RAF1(4), RDX(2), RHOA(4), ROCK1(8), ROCK2(2), RRAS2(1), SCIN(2), SLC9A1(2), SOS1(5), SOS2(9), SSH1(4), SSH2(4), TIAM1(12), TIAM2(14), TMSL3(1), VAV1(11), VAV2(2), VAV3(10), VCL(1), WAS(1), WASF1(1), WASF2(2), WASL(5) 58759654 607 104 600 203 248 119 21 159 58 2 0.793 1.000 412 ST_JNK_MAPK_PATHWAY JNKs are MAP kinases regulated by several levels of kinases (MAPKK, MAPKKK) and phosphorylate transcription factors and regulatory proteins. AKT1, ATF2, CDC42, DLD, DUSP10, DUSP4, DUSP8, GAB1, GADD45A, GCK, IL1R1, JUN, MAP2K4, MAP2K5, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K9, MAPK10, MAPK7, MAPK8, MAPK9, MYEF2, NFATC3, NR2C2, PAPPA, SHC1, TP53, TRAF6, ZAK 36 AKT1(2), DUSP10(4), DUSP4(1), GAB1(6), GCK(1), IL1R1(3), MAP2K5(2), MAP3K1(6), MAP3K10(2), MAP3K11(4), MAP3K12(4), MAP3K13(8), MAP3K2(2), MAP3K3(2), MAP3K4(15), MAP3K5(5), MAP3K7(2), MAP3K9(2), MAPK10(4), MAPK7(3), MAPK8(2), MAPK9(3), MYEF2(7), NFATC3(4), NR2C2(4), PAPPA(13), SHC1(3), TRAF6(4), ZAK(4) 10933243 122 44 120 31 44 25 2 33 18 0 0.794 1.000 413 HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - lactoseries ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 10 ABO(2), B3GALT1(1), B3GALT2(3), B3GALT5(2), B3GNT5(1), FUT1(1), FUT2(1), FUT3(3), ST3GAL3(4), ST3GAL4(2) 1559353 20 13 20 3 9 4 0 5 2 0 0.795 1.000 414 HSA00531_GLYCOSAMINOGLYCAN_DEGRADATION Genes involved in glycosaminoglycan degradation ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, HGSNAT, HPSE, HPSE2, HYAL1, HYAL2, IDS, IDUA, LCT, NAGLU, SPAM1 17 ARSB(5), GALNS(4), GLB1(3), GNS(1), GUSB(2), HEXB(1), HGSNAT(6), HPSE(2), HPSE2(9), IDS(2), IDUA(1), LCT(15), NAGLU(3), SPAM1(1) 4565629 55 26 54 15 20 9 2 17 7 0 0.796 1.000 415 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(5), ABP1(1), ACADM(3), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(1), ALDH9A1(1), AOC2(4), AOC3(4), CNDP1(3), DPYD(8), DPYS(6), ECHS1(2), EHHADH(2), GAD1(7), GAD2(4), HADHA(2), MLYCD(1), SMS(2), UPB1(3) 6061630 77 31 77 17 28 21 1 21 6 0 0.796 1.000 416 KERATINOCYTEPATHWAY Keratinocyte differentiation, which models the differentiation of epidermal cells, requires the four main MAP kinase pathways. BCL2, CEBPA, CHUK, DAXX, EGF, EGFR, ETS1, ETS2, FOS, HOXA7, HRAS, IKBKB, JUN, MAP2K1, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K1, MAP3K14, MAP3K5, MAPK1, MAPK13, MAPK14, MAPK3, MAPK8, NFKB1, NFKBIA, PPP2CA, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCQ, RAF1, RELA, RIPK1, SP1, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TRAF2 41 BCL2(1), CHUK(4), EGF(3), EGFR(10), ETS2(2), HOXA7(1), IKBKB(2), MAP2K1(3), MAP2K3(2), MAP2K6(2), MAP3K1(6), MAP3K14(2), MAP3K5(5), MAPK1(2), MAPK14(3), MAPK3(2), MAPK8(2), NFKB1(3), PPP2CA(1), PRKCA(2), PRKCD(3), PRKCE(4), PRKCG(8), PRKCH(2), PRKCQ(4), RAF1(4), RELA(2), RIPK1(2), SP1(2), TNFRSF1A(1), TRAF2(1) 10732034 91 45 90 30 44 22 3 19 3 0 0.798 1.000 417 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(5), ACYP1(1), ADH1B(2), ADH1C(3), ADH4(1), ADH5(1), ADH6(5), ADH7(2), ADHFE1(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH3B1(2), ALDH3B2(1), ALDH7A1(1), ALDH9A1(1), ALDOA(1), ALDOB(5), ALDOC(1), DLAT(2), ENO2(3), ENO3(3), FBP2(2), G6PC(3), GALM(2), GCK(1), GPI(1), HK1(6), HK2(3), HK3(4), LDHA(1), LDHAL6A(2), LDHAL6B(1), LDHB(1), LDHC(2), PDHA1(4), PDHA2(6), PDHB(2), PFKL(1), PFKM(1), PFKP(2), PGAM1(3), PGAM2(1), PGK1(3), PGK2(6), PGM1(2), PGM3(4), PKM2(2), TPI1(1) 12729919 134 49 133 40 46 33 1 46 8 0 0.799 1.000 418 INOSITOL_PHOSPHATE_METABOLISM IMPA1, INPP1, INPP4A, INPP4B, INPP5A, INPPL1, ITPKA, ITPKB, MIOX, OCRL, PIK3C2A, PIK3C2B, PIK3C2G, PIK3CA, PIK3CB, PIK3CG, PIK4CA, PIK4CA, LOC220686, PIP5K2B, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCG1, PLCG2 22 IMPA1(2), INPP1(2), INPP4A(2), INPP4B(5), INPP5A(2), INPPL1(3), ITPKB(4), MIOX(1), OCRL(5), PIK3C2A(2), PIK3C2B(3), PIK3C2G(7), PIK3CB(2), PIK3CG(12), PLCB1(8), PLCB2(3), PLCB3(3), PLCB4(9), PLCD1(6), PLCG1(4), PLCG2(9) 9369516 94 40 93 23 41 22 2 21 8 0 0.805 1.000 419 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(14), ACAT1(1), ACAT2(2), ACYP1(1), ADH5(1), AKR1B1(2), ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), DLAT(2), LDHA(1), LDHB(1), LDHC(2), LDHD(1), MDH1(1), MDH2(1), ME1(7), ME2(3), ME3(4), PC(3), PDHA1(4), PDHA2(6), PDHB(2), PKM2(2) 8286323 89 36 89 22 32 23 1 23 10 0 0.805 1.000 420 HSA00910_NITROGEN_METABOLISM Genes involved in nitrogen metabolism AMT, ASNS, ASRGL1, CA1, CA12, CA13, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA8, CA9, CPS1, CTH, GLS, GLS2, GLUD1, GLUD2, GLUL, HAL 24 ASNS(1), CA1(1), CA13(1), CA14(2), CA2(1), CA3(1), CA4(1), CA5A(1), CA6(2), CA8(2), CA9(2), CPS1(8), CTH(1), GLS2(2), GLUD1(2), GLUD2(4), GLUL(3), HAL(3) 4751377 38 25 38 20 16 10 0 5 7 0 0.809 1.000 421 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(8), AMY2A(3), ENPP1(4), ENPP3(3), G6PC(3), GANAB(4), GBA3(3), GBE1(4), GCK(1), GPI(1), GUSB(2), GYS1(1), GYS2(8), HK1(6), HK2(3), HK3(4), MGAM(9), PGM1(2), PGM3(4), PYGB(4), PYGL(2), PYGM(2), SI(12), UCHL1(1), UCHL3(1), UGDH(3), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(1), UGT1A5(3), UGT1A7(2), UGT1A9(5), UGT2B15(2), UGT2B4(2), UXS1(6) 12134352 123 47 123 44 42 34 0 32 15 0 0.812 1.000 422 PURINE_METABOLISM 1_Sep, ADA, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADK, ADSL, ADSS, AK1, AK2, AK5, ALLC, AMPD1, AMPD2, AMPD3, APRT, ATIC, ATP1B1, ATP5A1, ATP5B, ATP5C1, ATP5D, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP5I, ATP5J, ATP5J2, CANT1, DCK, DGUOK, ECGF1, ENPP1, ENPP3, ENTPD1, ENTPD2, FHIT, GART, GDA, GMPS, GUCY1A2, GUCY1A3, GUCY1B2, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, GUK1, HPRT1, IMPDH1, IMPDH2, ITPA, NME1, NME2, NP, NPR1, NPR2, NT5C, NT5E, NT5M, NUDT2, PAICS, PAPSS1, PAPSS2, PDE1A, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A, PDE6B, PDE6C, PDE6G, PDE7B, PDE8A, PDE9A, PFAS, PKLR, PKM2, POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT, POLS, PPAT, PRPS1, PRPS1L1, PRPS2, PRUNE, RRM1, RRM2, SAC 109 ADA(2), ADCY1(4), ADCY2(12), ADCY3(1), ADCY4(9), ADCY5(8), ADCY6(1), ADCY7(3), ADCY8(11), ADK(1), ADSL(7), ADSS(1), AK5(4), ALLC(3), AMPD1(7), AMPD2(4), AMPD3(2), ATIC(4), ATP1B1(1), ATP5A1(2), ATP5B(4), ATP5C1(2), ATP5D(1), ATP5F1(1), ATP5G3(1), ATP5J2(1), DCK(1), ENPP1(4), ENPP3(3), ENTPD1(2), FHIT(1), GART(3), GMPS(5), GUCY1A2(8), GUCY1B3(7), GUCY2C(7), GUCY2D(4), GUCY2F(7), HPRT1(2), IMPDH1(1), IMPDH2(1), ITPA(2), NPR1(6), NPR2(9), NT5E(2), NT5M(1), PAPSS1(1), PAPSS2(2), PDE1A(3), PDE4A(4), PDE4B(2), PDE4C(2), PDE4D(3), PDE5A(3), PDE6B(5), PDE6C(8), PDE7B(3), PDE8A(1), PDE9A(5), PFAS(1), PKM2(2), POLB(1), POLD1(5), POLD2(1), POLE(17), POLG(4), POLQ(8), POLR1B(6), POLR2A(6), POLR2B(5), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLRMT(1), PPAT(3), PRPS1L1(1), PRPS2(2), RRM1(1), RRM2(2) 28421001 285 71 281 80 98 68 8 76 35 0 0.812 1.000 423 CAPROLACTAM_DEGRADATION AKR1A1, ECHS1, EHHADH, HADHA, SDS 5 ECHS1(2), EHHADH(2), HADHA(2), SDS(2) 1109940 8 6 8 1 3 2 0 0 3 0 0.819 1.000 424 O_GLYCAN_BIOSYNTHESIS GALNT1, GALNT10, GALNT2, GALNT3, GALNT4, GALNT6, GALNT7, GALNT8, GALNT9, GCNT1, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, WBSCR17 13 GALNT1(2), GALNT10(5), GALNT2(3), GALNT3(4), GALNT6(2), GALNT7(2), GALNT8(1), GALNT9(2), GCNT1(3), ST3GAL1(1), ST3GAL2(1), ST3GAL4(2) 2910158 28 17 28 12 10 8 0 4 6 0 0.819 1.000 425 DCPATHWAY Dendritic cells internalize and present antigen, after which they migrate to lymphocyte-rich tissues and induce T and B cell differentiation. ANPEP, CD2, CD33, CD5, CD7, CSF2, IFNA1, IFNB1, IFNG, IL10, IL12A, IL12B, IL13, IL3, IL4, IL5, ITGAX, TLR2, TLR4, TLR7, TLR9, TNFRSF5 21 ANPEP(5), CD2(3), CD33(1), CD5(2), CD7(1), IFNA1(1), IFNB1(1), IFNG(1), IL10(1), IL12B(2), IL13(1), IL3(3), IL4(3), ITGAX(4), TLR2(2), TLR4(7), TLR7(4), TLR9(4) 4101271 46 22 45 19 18 7 4 15 2 0 0.820 1.000 426 HSA00632_BENZOATE_DEGRADATION_VIA_COA_LIGATION Genes involved in benzoate degradation via CoA ligation ACAT1, ACAT2, ACOT11, ACYP1, ACYP2, ARD1A, CARKL, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ECHS1, EHHADH, ESCO1, ESCO2, FN3K, GCDH, HADHA, ITGB1BP3, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1, YOD1 23 ACAT1(1), ACAT2(2), ACOT11(3), ACYP1(1), DHRS1(1), DHRS2(2), DHRS3(2), ECHS1(2), EHHADH(2), ESCO1(7), ESCO2(3), GCDH(3), HADHA(2), ITGB1BP3(1), MYST3(13), MYST4(5), PNPLA3(4), SH3GLB1(3), YOD1(1) 5735998 58 29 58 16 25 14 1 10 8 0 0.828 1.000 427 MONOCYTEPATHWAY Monocytes are a class of immune phagocytes that can develop into macrophages and express LFA-1, CD44, and other surface signaling proteins. CD44, ICAM1, ITGA4, ITGAL, ITGAM, ITGB1, ITGB2, PECAM1, SELE, SELL, SELP 11 CD44(3), ICAM1(2), ITGA4(3), ITGAL(5), ITGAM(5), ITGB1(6), ITGB2(4), PECAM1(1), SELE(2), SELP(4) 3585058 35 19 34 10 12 10 0 10 3 0 0.829 1.000 428 HSA04130_SNARE_INTERACTIONS_IN_VESICULAR_TRANSPORT Genes involved in SNARE interactions in vesicular transport BET1, BET1L, BNIP1, C1orf142, GOSR1, GOSR2, SEC22B, SNAP23, SNAP25, SNAP29, STX10, STX11, STX12, STX16, STX17, STX18, STX19, STX2, STX3, STX4, STX5, STX6, STX7, STX8, TSNARE1, USE1, VAMP1, VAMP2, VAMP3, VAMP4, VAMP5, VAMP7, VAMP8, VTI1A, VTI1B, YKT6 34 BET1(1), BNIP1(1), GOSR1(2), GOSR2(2), SEC22B(2), SNAP23(1), SNAP25(1), SNAP29(3), STX11(1), STX12(3), STX16(3), STX19(1), STX2(2), STX3(2), STX4(2), STX5(3), STX6(1), STX7(2), STX8(2), TSNARE1(1), VAMP1(1), VAMP3(1), VAMP4(2), VAMP5(2), VAMP8(1), VTI1A(1), VTI1B(1) 3656686 45 22 44 14 19 4 0 12 10 0 0.830 1.000 429 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 ECHS1(2), HADH(1), HADHA(2), HADHB(1), HSD17B10(1), HSD17B4(3), MECR(1), PPT2(1) 1955404 12 10 12 5 2 2 0 3 5 0 0.831 1.000 430 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 GLUL(3) 406881 3 3 3 2 2 0 0 0 1 0 0.833 1.000 431 EPOPATHWAY Erythropoietin, which activates the MAPK pathway, stimulates erythrocyte production and is an effective treatment for anemia. CSNK2A1, ELK1, EPO, EPOR, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAPK3, MAPK8, PLCG1, PTPN6, RAF1, SHC1, SOS1, STAT5A, STAT5B 19 CSNK2A1(4), GRB2(2), JAK2(6), MAP2K1(3), MAPK3(2), MAPK8(2), PLCG1(4), PTPN6(4), RAF1(4), SHC1(3), SOS1(5), STAT5B(2) 4816101 41 22 39 11 16 8 4 9 3 1 0.833 1.000 432 MITOCHONDRIAL_FATTY_ACID_BETAOXIDATION ACADL, ACADM, ACADS, ACADVL, ACSL1, ACSL3, ACSL4, CPT1A, CPT2, DCI, EHHADH, HADHA, HADHSC, MGC5139, PECR, SCP2, SLC25A20 15 ACADM(3), ACADVL(1), ACSL1(3), ACSL3(6), ACSL4(4), CPT1A(5), CPT2(1), EHHADH(2), HADHA(2), SCP2(3), SLC25A20(1) 3827170 31 19 31 11 9 8 0 10 4 0 0.836 1.000 433 CALCINEURINPATHWAY Increased intracellular calcium activates the phosphatase calcineurin in differentiating keratinocytes. CALM1, CALM2, CALM3, CDKN1A, GNAQ, MARCKS, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, SP1, SP3, SYT1 18 CDKN1A(1), GNAQ(3), MARCKS(1), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), PLCG1(4), PPP3CA(1), PPP3CB(4), PPP3CC(3), PRKCA(2), SP1(2), SP3(2), SYT1(1) 4644159 36 26 36 12 14 4 0 10 8 0 0.838 1.000 434 GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM ACO1, ACO2, CS, GRHPR, HAO1, HAO2, HYI, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 12 ACO1(3), ACO2(2), HAO1(5), HAO2(3), HYI(1), MDH1(1), MDH2(1), MTHFD1(6), MTHFD1L(6) 2897069 28 17 27 8 11 5 0 10 2 0 0.838 1.000 435 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(3), ACTA2(3), ACTN2(7), ACTN3(2), ACTN4(2), DES(1), FAM48A(4), MYBPC1(5), MYBPC2(4), MYBPC3(2), MYH3(9), MYH6(8), MYH7(7), MYH8(17), MYL1(1), MYL2(1), MYOM1(8), NEB(38), TMOD1(2), TNNC2(1), TNNI1(2), TNNI3(1), TNNT2(3), TPM1(2), TPM2(5), TPM3(2), TPM4(3), VIM(2) 11470307 145 46 139 51 62 28 1 42 12 0 0.840 1.000 436 HSA00592_ALPHA_LINOLENIC_ACID_METABOLISM Genes involved in alpha-Linolenic acid metabolism ACOX1, ACOX3, FADS2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6 15 ACOX1(3), ACOX3(5), FADS2(3), PLA2G1B(1), PLA2G2F(1), PLA2G4A(5), PLA2G6(2) 2336103 20 13 20 6 8 5 1 4 2 0 0.841 1.000 437 CTLPATHWAY Cytotoxic T lymphocytes induce apoptosis in infected cells presenting antigen-MHC-I complexes via the perforin and Fas/Fas ligand pathways. B2M, CD3D, CD3E, CD3G, CD3Z, GZMB, HLA-A, ICAM1, ITGAL, ITGB2, PRF1, TNFRSF6, TNFSF6, TRA@, TRB@ 10 B2M(3), CD3D(1), CD3G(2), GZMB(1), HLA-A(1), ICAM1(2), ITGAL(5), ITGB2(4) 1874734 19 14 19 5 5 5 0 3 6 0 0.843 1.000 438 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(3), AADAC(2), ABAT(5), ACAT1(1), ACAT2(2), ACSM1(3), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH5A1(4), ALDH7A1(1), ALDH9A1(1), BDH1(1), DDHD1(1), ECHS1(2), EHHADH(2), GAD1(7), GAD2(4), HADH(1), HADHA(2), HMGCS1(1), HSD17B10(1), HSD17B4(3), HSD3B7(2), ILVBL(2), L2HGDH(3), OXCT1(3), OXCT2(1), PDHA1(4), PDHA2(6), PDHB(2), PLA1A(3), PPME1(2), PRDX6(2), RDH12(2), RDH13(1) 9221022 98 39 98 27 41 25 0 23 9 0 0.846 1.000 439 BETAOXIDATIONPATHWAY Beta-Oxidation of Fatty Acids ACADL, ACADM, ACADS, ACAT1, ECHS1, HADHA 6 ACADM(3), ACAT1(1), ECHS1(2), HADHA(2) 1230053 8 6 8 2 0 2 0 2 4 0 0.846 1.000 440 FEEDERPATHWAY Sugars such as mannose, galactose, and fructose are enzymatically converted to glucose via feeder pathways that lead to glycolysis. HK1, KHK, LCT, MPI, PGM1, PYGL, PYGM, TPI1, TREH 9 HK1(6), KHK(1), LCT(15), MPI(1), PGM1(2), PYGL(2), PYGM(2), TPI1(1), TREH(2) 2956045 32 21 32 13 10 10 1 11 0 0 0.847 1.000 441 HSA03320_PPAR_SIGNALING_PATHWAY Genes involved in PPAR signaling pathway ACAA1, ACADL, ACADM, ACOX1, ACOX2, ACOX3, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADIPOQ, ANGPTL4, APOA1, APOA2, APOA5, APOC3, AQP7, CD36, CPT1A, CPT1B, CPT1C, CPT2, CYP27A1, CYP4A11, CYP4A22, CYP7A1, CYP8B1, DBI, EHHADH, FABP1, FABP2, FABP3, FABP4, FABP5, FABP5L1, FABP6, FABP7, FADS2, GK, GK2, HMGCS2, ILK, LOC642956, LPL, ME1, MMP1, NR1H3, OLR1, PCK1, PCK2, PDPK1, PLIN, PLTP, PPARA, PPARD, PPARG, RXRA, RXRB, RXRG, SCD, SCP2, SLC27A1, SLC27A2, SLC27A4, SLC27A5, SLC27A6, SORBS1, UBC, UCP1 65 ACAA1(2), ACADM(3), ACOX1(3), ACOX2(2), ACOX3(5), ACSL1(3), ACSL3(6), ACSL4(4), ACSL5(4), ACSL6(5), ADIPOQ(4), APOA2(1), APOA5(1), AQP7(1), CD36(1), CPT1A(5), CPT1B(5), CPT2(1), CYP27A1(3), CYP4A11(2), CYP4A22(2), CYP7A1(4), CYP8B1(2), EHHADH(2), FABP1(1), FABP2(1), FABP3(1), FABP4(1), FABP5(1), FABP6(1), FADS2(3), GK(3), GK2(3), LPL(6), ME1(7), MMP1(1), NR1H3(4), OLR1(1), PCK2(3), PDPK1(1), PLTP(5), PPARA(1), PPARD(1), PPARG(1), RXRA(1), RXRB(2), RXRG(3), SCD(2), SCP2(3), SLC27A1(2), SLC27A2(2), SLC27A4(1), SLC27A5(3), SLC27A6(4), SORBS1(7), UCP1(1) 14600391 148 52 147 48 42 39 3 48 16 0 0.849 1.000 442 ONE_CARBON_POOL_BY_FOLATE ALDH1L1, AMT, ATIC, ATP6V0C, SHMT1, DHFR, GART, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 15 ALDH1L1(3), ATIC(4), GART(3), MTHFD1(6), MTHFD1L(6), MTHFR(6), MTHFS(1), MTR(6), SHMT1(1), SHMT2(2), TYMS(2) 4047718 40 23 40 10 17 9 0 11 3 0 0.849 1.000 443 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(9), CAPN2(5), CAPNS1(1), CAPNS2(1), EP300(13), HDAC1(2), HDAC2(2), MEF2D(1), NFATC1(1), NFATC2(3), PPP3CA(1), PPP3CB(4), PPP3CC(3), PRKCA(2), SYT1(1) 5422412 49 27 49 12 20 12 1 7 9 0 0.850 1.000 444 HSA04110_CELL_CYCLE Genes involved in cell cycle ABL1, ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, ATM, ATR, BUB1, BUB1B, BUB3, CCNA1, CCNA2, CCNB1, CCNB2, CCNB3, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNH, CDC14A, CDC14B, CDC16, CDC2, CDC20, CDC23, CDC25A, CDC25B, CDC25C, CDC26, CDC27, CDC45L, CDC6, CDC7, CDK2, CDK4, CDK6, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CHEK1, CHEK2, CREBBP, CUL1, DBF4, E2F1, E2F2, E2F3, EP300, ESPL1, FZR1, GADD45A, GADD45B, GADD45G, GSK3B, hCG_1982709, HDAC1, HDAC2, LOC440917, LOC728919, MAD1L1, MAD2L1, MAD2L2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, PKMYT1, PLK1, PRKDC, PTTG1, PTTG2, RB1, RBL1, RBL2, RBX1, SFN, SKP1, SKP2, SMAD2, SMAD3, SMAD4, SMC1A, SMC1B, TFDP1, TGFB1, TGFB2, TGFB3, TP53, WEE1, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 104 ABL1(4), ANAPC1(3), ANAPC10(2), ANAPC2(1), ANAPC4(1), ANAPC5(2), ANAPC7(4), ATR(13), BUB1(4), BUB1B(3), BUB3(2), CCNA1(4), CCNA2(3), CCNB1(2), CCNB2(2), CCNB3(4), CCND2(1), CCND3(1), CCNE1(3), CCNE2(1), CCNH(2), CDC14A(1), CDC14B(3), CDC16(3), CDC20(3), CDC23(6), CDC25A(2), CDC25B(5), CDC25C(3), CDC27(9), CDC7(2), CDK2(2), CDK4(2), CDK6(1), CDK7(1), CDKN1A(1), CDKN1B(1), CDKN2A(1), CDKN2C(1), CHEK1(1), CHEK2(1), CREBBP(21), CUL1(7), DBF4(2), E2F2(1), E2F3(1), EP300(13), ESPL1(8), GSK3B(7), HDAC1(2), HDAC2(2), MAD1L1(1), MAD2L1(1), MAD2L2(1), MCM3(1), MCM4(4), MCM5(3), MCM6(3), MCM7(2), MDM2(4), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(2), PKMYT1(1), PLK1(6), PRKDC(13), PTTG1(1), RB1(4), RBL1(3), RBL2(8), SKP1(1), SKP2(1), SMAD3(6), SMC1A(10), SMC1B(4), TFDP1(4), TGFB1(1), TGFB2(5), WEE1(3), YWHAB(2), YWHAE(3), YWHAQ(1) 28129910 278 68 275 70 84 65 8 79 41 1 0.851 1.000 445 ST_IL_13_PATHWAY Like IL-4, IL-13 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor. IL13, IL13RA1, IL13RA2, IL4R, JAK1, JAK2, TYK2 7 IL13(1), IL13RA1(1), IL13RA2(2), IL4R(1), JAK1(3), JAK2(6), TYK2(1) 2300981 15 13 14 6 7 0 2 4 1 1 0.851 1.000 446 ST_INTERLEUKIN_13_PATHWAY IL-13 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor. IL13, IL13RA1, IL13RA2, IL4R, JAK1, JAK2, TYK2 7 IL13(1), IL13RA1(1), IL13RA2(2), IL4R(1), JAK1(3), JAK2(6), TYK2(1) 2300981 15 13 14 6 7 0 2 4 1 1 0.851 1.000 447 GLUCONEOGENESIS ACYP1, ACYP2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GCK, GPI, HK1, HK2, HK3, LDHA, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKM, PFKP, PGAM1, PGK1, PGM1, PGM3, PKLR, PKM2, TPI1 53 ACYP1(1), ADH1B(2), ADH1C(3), ADH4(1), ADH6(5), ADH7(2), ADHFE1(6), ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH3B1(2), ALDH3B2(1), ALDH9A1(1), ALDOA(1), ALDOB(5), ALDOC(1), DLAT(2), ENO2(3), ENO3(3), FBP2(2), G6PC(3), GCK(1), GPI(1), HK1(6), HK2(3), HK3(4), LDHA(1), LDHB(1), LDHC(2), PDHA1(4), PDHA2(6), PDHB(2), PFKM(1), PFKP(2), PGAM1(3), PGK1(3), PGM1(2), PGM3(4), PKM2(2), TPI1(1) 10780789 120 44 119 32 40 31 1 42 6 0 0.852 1.000 448 GLYCOLYSIS ACYP1, ACYP2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GCK, GPI, HK1, HK2, HK3, LDHA, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKM, PFKP, PGAM1, PGK1, PGM1, PGM3, PKLR, PKM2, TPI1 53 ACYP1(1), ADH1B(2), ADH1C(3), ADH4(1), ADH6(5), ADH7(2), ADHFE1(6), ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH3B1(2), ALDH3B2(1), ALDH9A1(1), ALDOA(1), ALDOB(5), ALDOC(1), DLAT(2), ENO2(3), ENO3(3), FBP2(2), G6PC(3), GCK(1), GPI(1), HK1(6), HK2(3), HK3(4), LDHA(1), LDHB(1), LDHC(2), PDHA1(4), PDHA2(6), PDHB(2), PFKM(1), PFKP(2), PGAM1(3), PGK1(3), PGM1(2), PGM3(4), PKM2(2), TPI1(1) 10780789 120 44 119 32 40 31 1 42 6 0 0.852 1.000 449 SA_MMP_CYTOKINE_CONNECTION Cytokines can induce activation of matrix metalloproteinases, which degrade extracellular matrix. ACE, CD44, CSF1, FCGR3A, IL1B, IL6R, SELL, SPN, TGFB1, TGFB2, TNF, TNFRSF1A, TNFRSF1B, TNFRSF8, TNFSF8 15 ACE(2), CD44(3), CSF1(1), IL6R(2), SPN(1), TGFB1(1), TGFB2(5), TNFRSF1A(1), TNFRSF8(1), TNFSF8(1) 2999410 18 13 18 10 5 4 1 4 4 0 0.852 1.000 450 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(3), CAPN1(2), CAPN2(5), CAPNS1(1), CAPNS2(1), EGF(3), EGFR(10), ITGA1(3), ITGB1(6), MAPK1(2), MAPK3(2), MYL2(1), MYLK(11), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PTK2(5), TLN1(5) 7238657 67 34 67 18 28 18 2 15 4 0 0.852 1.000 451 N_GLYCAN_BIOSYNTHESIS ALG3, ALG5, B4GALT1, B4GALT2, B4GALT3, B4GALT5, DDOST, DPAGT1, DPM1, FUT8, GCS1, MAN1A1, MAN1B1, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT5, RPN1, RPN2, ST6GAL1 21 ALG3(1), ALG5(2), B4GALT1(5), B4GALT2(3), B4GALT3(6), B4GALT5(2), DDOST(2), DPAGT1(1), DPM1(1), FUT8(1), MAN1A1(4), MAN1B1(2), MGAT1(1), MGAT3(2), MGAT4A(2), MGAT4B(1), MGAT5(3), ST6GAL1(1) 4429180 40 26 40 10 18 8 2 11 1 0 0.855 1.000 452 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 86 AICDA(3), AK3(1), CAD(10), CDA(1), CTPS(3), CTPS2(4), DCK(1), DCTD(3), DHODH(3), DPYD(8), DPYS(6), ENTPD1(2), ENTPD3(5), ENTPD4(5), ENTPD5(1), ENTPD6(1), ITPA(2), NME6(3), NME7(3), NT5C1A(1), NT5C1B(9), NT5C2(3), NT5C3(2), NT5E(2), NT5M(1), PNPT1(5), POLA1(5), POLA2(2), POLD1(5), POLD2(1), POLD3(2), POLE(17), POLE3(1), POLR1A(7), POLR1B(6), POLR1C(2), POLR1D(2), POLR2A(6), POLR2B(5), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLR3A(7), POLR3B(6), POLR3GL(1), POLR3H(1), PRIM2(6), RFC5(2), RRM1(1), RRM2(2), TK1(1), TXNRD1(2), TXNRD2(2), TYMS(2), UCK2(1), UPB1(3), UPP2(1), UPRT(3) 18261551 194 57 193 47 55 57 4 56 22 0 0.855 1.000 453 PROTEASOMEPATHWAY Ubiquitinated proteins are targeted for proteolytic degradation by the proteasome, where they are unfolded and degraded to small peptides in an ATP-dependent process. PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMC3, PSMD14, RPN1, RPN2, UBE1, UBE2A, UBE3A 20 PSMA1(1), PSMA2(1), PSMA3(2), PSMA4(2), PSMA5(1), PSMB2(2), PSMB5(2), PSMB6(2), PSMC3(3), UBE2A(2), UBE3A(6) 2930348 24 15 24 11 8 5 2 6 3 0 0.855 1.000 454 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(3), JAK2(6), JAK3(6), MAPK1(2), MAPK3(2), STAT3(2), TYK2(1) 2633821 22 15 21 9 9 4 1 5 2 1 0.857 1.000 455 HSA00361_GAMMA_HEXACHLOROCYCLOHEXANE_DEGRADATION Genes involved in gamma-hexachlorocyclohexane degradation ACP1, ACP2, ACP5, ACP6, ACPP, ACPT, ALPI, ALPL, ALPP, ALPPL2, CMBL, CYP3A4, CYP3A43, CYP3A5, CYP3A7, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, PON1, PON2, PON3 22 ACP1(2), ACP2(2), ACP5(1), ACPP(3), ALPI(2), ALPL(1), ALPP(1), CYP3A4(1), CYP3A5(3), CYP3A7(4), DHRS1(1), DHRS2(2), DHRS3(2), PON1(5), PON2(1), PON3(2) 3868730 33 19 32 13 13 5 4 6 4 1 0.860 1.000 456 HSA04710_CIRCADIAN_RHYTHM Genes involved in circadian rhythm ARNTL, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, NPAS2, NR1D1, PER1, PER2, PER3 11 ARNTL(7), CLOCK(5), CRY1(2), CRY2(1), CSNK1D(3), NPAS2(5), NR1D1(4), PER1(1), PER2(2), PER3(7) 3847778 37 22 36 8 18 7 0 10 2 0 0.860 1.000 457 PPARAPATHWAY Peroxisome proliferators regulate gene expression via PPAR/RXR heterodimers which bind to peroxisome-proliferator response elements (PPREs). ACOX1, APOA1, APOA2, CD36, CITED2, CPT1B, CREBBP, DUSP1, DUT, EHHADH, EP300, FABP1, FAT, FRA8B, HSD17B4, HSPA1A, HSPCA, INS, JUN, LPL, MAPK1, MAPK3, ME1, MRPL11, MYC, NCOA1, NCOR1, NCOR2, NFKBIA, NOS2A, NR0B2, NR1H3, NR2F1, NRIP1, PDGFA, PIK3CA, PIK3R1, PPARA, PPARBP, PPARGC1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PTGS2, RB1, RELA, RXRA, SP1, SRA1, STAT5A, STAT5B, TNF 47 ACOX1(3), APOA2(1), CD36(1), CITED2(1), CPT1B(5), CREBBP(21), DUSP1(2), EHHADH(2), EP300(13), FABP1(1), HSD17B4(3), LPL(6), MAPK1(2), MAPK3(2), ME1(7), NCOA1(6), NCOR1(7), NCOR2(2), NR1H3(4), NR2F1(2), NRIP1(5), PDGFA(1), PIK3R1(5), PPARA(1), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PRKCA(2), PTGS2(2), RB1(4), RELA(2), RXRA(1), SP1(2), STAT5B(2) 13500963 125 45 125 41 34 34 4 32 20 1 0.862 1.000 458 CACAMPATHWAY Calcium functions as a second messenger activating the calcium/calmodulin-dependent kinases, which phosphorylate targets such as CREB. CALM1, CALM2, CALM3, CAMK1, CAMK1G, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CAMKK1, CAMKK2, CREB1, SYT1 14 CAMK1(1), CAMK1G(3), CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), CAMK4(2), CAMKK1(1), CAMKK2(1), CREB1(1), SYT1(1) 2649326 17 13 17 12 6 5 2 3 1 0 0.863 1.000 459 HSA00380_TRYPTOPHAN_METABOLISM Genes involved in tryptophan metabolism AADAT, AANAT, ABP1, ACAT1, ACAT2, ACMSD, AFMID, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, AOC2, AOC3, AOX1, ASMT, CARM1, CAT, CYP1A1, CYP1A2, CYP1B1, DDC, ECHS1, EHHADH, GCDH, HAAO, HADH, HADHA, HEMK1, HSD17B10, HSD17B4, INDO, INDOL1, INMT, KMO, KYNU, LCMT1, LCMT2, LNX1, MAOA, MAOB, METTL2B, METTL6, NFX1, OGDH, OGDHL, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, TDO2, TPH1, TPH2, WARS, WARS2, WBSCR22 57 AADAT(1), ABP1(1), ACAT1(1), ACAT2(2), ACMSD(3), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(1), ALDH9A1(1), AOC2(4), AOC3(4), AOX1(5), CARM1(2), CAT(2), CYP1A1(6), CYP1A2(2), CYP1B1(2), DDC(1), ECHS1(2), EHHADH(2), GCDH(3), HAAO(2), HADH(1), HADHA(2), HSD17B10(1), HSD17B4(3), INMT(1), KMO(3), KYNU(6), LCMT1(1), LCMT2(2), LNX1(7), MAOA(2), METTL2B(1), METTL6(5), NFX1(5), OGDH(4), OGDHL(8), PRMT2(1), PRMT3(2), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(3), TDO2(2), TPH1(1), TPH2(5), WARS(1), WARS2(2), WBSCR22(1) 13417652 139 51 139 42 53 37 0 38 11 0 0.864 1.000 460 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 AKT1(2), AKT2(5), DAG1(4), GNAQ(3), ITPKB(4), ITPR1(11), ITPR2(12), ITPR3(11), NFKB1(3), NFKB2(2), NFKBIB(1), NFKBIE(2), PHKA2(5), PIK3CB(2), PITX2(2), PLD1(8), PLD2(1), PLD3(5), VN1R1(4) 9605968 87 39 87 36 36 19 5 20 7 0 0.865 1.000 461 AMINOSUGARS_METABOLISM CMAS, CYB5R3, GCK, GFPT1, GNE, GNPDA1, GNPDA2, HEXA, HEXB, HK1, HK2, HK3, PGM3, RENBP, UAP1 15 CMAS(5), CYB5R3(1), GCK(1), GFPT1(3), GNE(2), GNPDA2(1), HEXB(1), HK1(6), HK2(3), HK3(4), PGM3(4), RENBP(1) 3860620 32 22 32 12 11 9 0 11 1 0 0.865 1.000 462 HSA00903_LIMONENE_AND_PINENE_DEGRADATION Genes involved in limonene and pinene degradation ACOT11, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, ARD1A, CYP2C19, CYP2C9, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ECHS1, EHHADH, ESCO1, ESCO2, HADHA, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1, YOD1 25 ACOT11(3), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(1), ALDH9A1(1), CYP2C19(4), CYP2C9(4), DHRS1(1), DHRS2(2), DHRS3(2), ECHS1(2), EHHADH(2), ESCO1(7), ESCO2(3), HADHA(2), MYST3(13), MYST4(5), PNPLA3(4), SH3GLB1(3), YOD1(1) 6880810 78 30 78 21 33 20 1 16 8 0 0.866 1.000 463 HSA00900_TERPENOID_BIOSYNTHESIS Genes involved in terpenoid biosynthesis FDFT1, FDPS, GGPS1, IDI1, IDI2, SQLE 6 FDFT1(2), IDI1(1), IDI2(1), SQLE(1) 920154 5 5 5 4 1 2 0 0 2 0 0.867 1.000 464 HSA00071_FATTY_ACID_METABOLISM Genes involved in fatty acid metabolism ACAA1, ACAA2, ACADL, ACADM, ACADS, ACADSB, ACADVL, ACAT1, ACAT2, ACOX1, ACOX3, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, CPT1A, CPT1B, CPT1C, CPT2, CYP4A11, CYP4A22, DCI, ECHS1, EHHADH, GCDH, HADH, HADHA, HADHB, HSD17B10, HSD17B4, PECI 47 ACAA1(2), ACADM(3), ACADSB(5), ACADVL(1), ACAT1(1), ACAT2(2), ACOX1(3), ACOX3(5), ACSL1(3), ACSL3(6), ACSL4(4), ACSL5(4), ACSL6(5), ADH1B(2), ADH1C(3), ADH4(1), ADH5(1), ADH6(5), ADH7(2), ADHFE1(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(1), ALDH9A1(1), CPT1A(5), CPT1B(5), CPT2(1), CYP4A11(2), CYP4A22(2), ECHS1(2), EHHADH(2), GCDH(3), HADH(1), HADHA(2), HADHB(1), HSD17B10(1), HSD17B4(3), PECI(1) 10960377 115 40 115 32 34 29 3 38 11 0 0.867 1.000 465 ST_INTERLEUKIN_4_PATHWAY Like IL-13, IL-4 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor. AKT1, AKT2, AKT3, CISH, GRB2, IARS, IL13RA1, IL2RG, IL4, IL4R, INPP5D, JAK1, JAK2, JAK3, NR0B2, PI3, PIK3CA, PPP1R13B, RPS6KB1, SERPINA4, SHC1, SOS1, SOS2, SRC, STAT6, TYK2 25 AKT1(2), AKT2(5), GRB2(2), IARS(5), IL13RA1(1), IL4(3), IL4R(1), INPP5D(2), JAK1(3), JAK2(6), JAK3(6), PPP1R13B(5), RPS6KB1(3), SERPINA4(2), SHC1(3), SOS1(5), SOS2(9), SRC(3), STAT6(2), TYK2(1) 7666023 69 33 67 29 21 12 4 21 10 1 0.875 1.000 466 GALACTOSE_METABOLISM AKR1B1, B4GALT1, B4GALT2, FBP2, G6PC, GAA, GALE, GALK1, GALK2, GALT, GANAB, GCK, GLA, GLB1, HK1, HK2, HK3, LALBA, LCT, MGAM, PFKM, PFKP, PGM1, PGM3 24 AKR1B1(2), B4GALT1(5), B4GALT2(3), FBP2(2), G6PC(3), GALE(1), GALK2(2), GALT(2), GANAB(4), GCK(1), GLA(4), GLB1(3), HK1(6), HK2(3), HK3(4), LCT(15), MGAM(9), PFKM(1), PFKP(2), PGM1(2), PGM3(4) 7106413 78 35 78 28 34 22 1 19 2 0 0.875 1.000 467 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 ALOX12(2), ALOX5(4), CYP4F2(8), CYP4F3(2), EPX(6), LPO(2), MPO(3), PLA2G1B(1), PLA2G4A(5), PLA2G6(2), PRDX6(2), PTGIS(4), PTGS1(4), PTGS2(2), TBXAS1(5), TPO(8) 6015049 60 32 59 20 30 10 0 16 4 0 0.877 1.000 468 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(1), AOC2(4), AOC3(4), CES1(4), DDHD1(1), ESCO1(7), ESCO2(3), LIPA(1), MYST3(13), MYST4(5), PLA1A(3), PNPLA3(4), PPME1(2), PRDX6(2), SH3GLB1(3) 5626099 59 27 59 18 26 17 1 10 5 0 0.878 1.000 469 OXIDATIVE_PHOSPHORYLATION ATP12A, ATP4B, ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ATP7A, ATP7B, COX10, COX4I1, COX5A, COX5B, COX6A1, COX6A2, COX6B1, COX6C, COX7A1, COX7A2, COX7B, COX7C, COX8A, NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2, PP, PPA2, SDHA, SDHA, SDHAL2, SDHB, UQCRB, UQCRC1, UQCRFS1, UQCRH 60 ATP12A(13), ATP4B(1), ATP5O(2), ATP6AP1(2), ATP6V0A1(2), ATP6V0A4(4), ATP6V0D1(2), ATP6V1A(2), ATP6V1B1(4), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(2), ATP7A(5), ATP7B(4), COX10(2), COX4I1(2), COX6A2(1), COX6C(1), COX7A1(1), NDUFA1(1), NDUFA10(2), NDUFA4(1), NDUFB2(1), NDUFB6(1), NDUFS1(4), NDUFV1(2), PPA2(1), SDHA(5), SDHB(2), SHMT1(1), UQCRB(2), UQCRC1(2), UQCRFS1(1), UQCRH(1) 8133318 85 35 84 22 34 28 1 16 6 0 0.881 1.000 470 HSA00630_GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM Genes involved in glyoxylate and dicarboxylate metabolism ACO1, ACO2, AFMID, CS, GRHPR, HAO1, HAO2, HYI, LOC441996, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 13 ACO1(3), ACO2(2), HAO1(5), HAO2(3), HYI(1), MDH1(1), MDH2(1), MTHFD1(6), MTHFD1L(6) 3033890 28 17 27 8 11 5 0 10 2 0 0.881 1.000 471 FRUCTOSE_AND_MANNOSE_METABOLISM AKR1B1, ALDOA, ALDOB, ALDOC, FBP1, FBP2, FPGT, GCK, GMDS, GMPPA, GMPPB, HK1, HK2, HK3, KHK, MPI, PFKFB1, PFKFB3, PFKFB4, PFKM, PFKP, PMM1, PMM2, SORD, TPI1 25 AKR1B1(2), ALDOA(1), ALDOB(5), ALDOC(1), FBP2(2), FPGT(3), GCK(1), GMDS(1), GMPPA(6), HK1(6), HK2(3), HK3(4), KHK(1), MPI(1), PFKFB1(6), PFKFB4(2), PFKM(1), PFKP(2), PMM1(1), TPI1(1) 5398793 50 31 50 22 19 11 0 17 3 0 0.882 1.000 472 CCR5PATHWAY CCR5 is a G-protein coupled receptor expressed in macrophages that recognizes chemokine ligands and is targeted by the HIV envelope protein GP120. CALM1, CALM2, CALM3, CCL2, CCL4, CCR5, CXCL12, CXCR4, FOS, GNAQ, JUN, MAPK14, MAPK8, PLCG1, PRKCA, PRKCB1, PTK2B, SYT1 17 CCR5(1), CXCL12(1), CXCR4(3), GNAQ(3), MAPK14(3), MAPK8(2), PLCG1(4), PRKCA(2), PTK2B(1), SYT1(1) 2998488 21 17 22 9 6 6 0 5 4 0 0.882 1.000 473 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(5), ALAS2(5), BLVRA(2), BLVRB(1), COX10(2), COX15(1), CP(3), EPRS(10), FECH(2), FTMT(3), GUSB(2), HCCS(1), HMBS(2), HMOX1(2), HMOX2(1), MMAB(1), PPOX(3), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(1), UGT1A5(3), UGT1A7(2), UGT1A9(5), UGT2A1(8), UGT2A3(5), UGT2B10(1), UGT2B11(4), UGT2B15(2), UGT2B17(4), UGT2B28(2), UGT2B4(2), UGT2B7(4), UROS(1) 8879587 94 34 92 21 25 26 1 32 10 0 0.884 1.000 474 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(1), DPYD(8), DPYS(6), ENPP1(4), ENPP3(3), ILVBL(2), PANK1(2), PANK3(2), PANK4(1), PPCS(1), UPB1(3), VNN1(5) 3874437 39 21 39 11 10 14 2 10 3 0 0.885 1.000 475 SIG_REGULATION_OF_THE_ACTIN_CYTOSKELETON_BY_RHO_GTPASES Genes related to regulation of the actin cytoskeleton ACTG1, ACTG2, ACTR2, ACTR3, AKT1, ANGPTL2, CDC42, CFL1, CFL2, FLNA, FLNC, FSCN1, FSCN2, FSCN3, GDI1, GDI2, LIMK1, MYH2, MYLK, MYLK2, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PFN1, PFN2, RHO, ROCK1, ROCK2, RPS4X, VASP, WASF1, WASL 35 ACTG2(3), ACTR2(1), ACTR3(2), AKT1(2), ANGPTL2(8), CFL1(1), FLNA(2), FLNC(11), FSCN3(2), GDI1(1), GDI2(1), LIMK1(4), MYH2(9), MYLK(11), MYLK2(2), PAK1(4), PAK2(2), PAK3(3), PAK6(1), PAK7(4), PFN2(1), RHO(2), ROCK1(8), ROCK2(2), RPS4X(1), VASP(3), WASF1(1), WASL(5) 10466462 97 40 97 31 28 25 4 28 12 0 0.885 1.000 476 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 56 ALG2(3), BAK1(1), BAX(1), BFAR(1), BTK(6), CAD(10), CASP10(2), CASP3(1), CASP8AP2(12), CD7(1), CSNK1A1(2), DFFA(2), DIABLO(1), EGFR(10), EPHB2(7), FAF1(4), FAIM2(3), IL1A(1), MAP3K1(6), MAP3K5(5), MAPK1(2), MAPK10(4), MAPK8(2), MAPK8IP1(2), MAPK8IP3(1), MAPK9(3), MET(4), NFAT5(5), NFKB1(3), NFKB2(2), NFKBIB(1), NFKBIE(2), PFN2(1), PTPN13(8), RALBP1(4), RIPK1(2), ROCK1(8), SMPD1(6), TPX2(7), TRAF2(1), TUFM(1) 15229964 148 49 146 42 51 29 0 53 14 1 0.886 1.000 477 PENTOSE_AND_GLUCURONATE_INTERCONVERSIONS AKR1B1, DCXR, GUSB, RPE, RPE, LOC440001, UCHL1, UCHL3, UGDH, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4 18 AKR1B1(2), GUSB(2), RPE(2), UCHL1(1), UCHL3(1), UGDH(3), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(1), UGT1A5(3), UGT1A7(2), UGT1A9(5), UGT2B15(2), UGT2B4(2) 3633569 30 18 30 10 13 8 0 4 5 0 0.886 1.000 478 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(14), ACACB(14), ACAT1(1), ACAT2(2), ACOT12(6), ACSS1(3), ACSS2(5), ACYP1(1), AKR1B1(2), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(1), ALDH9A1(1), DLAT(2), LDHA(1), LDHAL6A(2), LDHAL6B(1), LDHB(1), LDHC(2), LDHD(1), MDH1(1), MDH2(1), ME1(7), ME2(3), ME3(4), PC(3), PCK2(3), PDHA1(4), PDHA2(6), PDHB(2), PKM2(2) 10568226 114 41 114 31 42 27 1 30 14 0 0.886 1.000 479 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), NR1H3(4), NR1H4(1), RXRA(1) 1186453 11 9 11 7 4 6 0 1 0 0 0.887 1.000 480 HSA00450_SELENOAMINO_ACID_METABOLISM Genes involved in selenoamino acid metabolism AHCY, CARM1, CBS, CTH, GGT1, GGTL3, GGTL4, HEMK1, KIAA0828, LCMT1, LCMT2, MARS, MARS2, MAT1A, MAT2B, METTL2B, METTL6, PAPSS1, PAPSS2, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, SCLY, SEPHS1, SEPHS2, WBSCR22 25 AHCY(3), CARM1(2), CBS(2), CTH(1), LCMT1(1), LCMT2(2), MARS(3), MAT1A(5), MAT2B(2), METTL2B(1), METTL6(5), PAPSS1(1), PAPSS2(2), PRMT2(1), PRMT3(2), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(3), SCLY(1), SEPHS1(1), SEPHS2(3), WBSCR22(1) 5239724 46 26 46 17 18 11 1 13 3 0 0.887 1.000 481 HSA00565_ETHER_LIPID_METABOLISM Genes involved in ether lipid metabolism AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, AGPS, CHPT1, ENPP2, ENPP6, LYCAT, PAFAH1B1, PAFAH1B2, PAFAH1B3, PAFAH2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLD1, PLD2, PPAP2A, PPAP2B, PPAP2C 30 AGPAT1(1), AGPAT3(3), AGPAT4(6), AGPAT6(1), AGPS(2), ENPP2(10), ENPP6(1), PAFAH1B1(3), PLA2G1B(1), PLA2G2F(1), PLA2G4A(5), PLA2G6(2), PLD1(8), PLD2(1), PPAP2B(1) 5336176 46 26 45 21 17 13 1 12 3 0 0.889 1.000 482 SELENOAMINO_ACID_METABOLISM AHCY, CBS, CTH, GGT1, MARS, MARS2, MAT1A, MAT2B, PAPSS1, PAPSS2, SCLY, SEPHS1 11 AHCY(3), CBS(2), CTH(1), MARS(3), MAT1A(5), MAT2B(2), PAPSS1(1), PAPSS2(2), SCLY(1), SEPHS1(1) 2566548 21 14 21 8 11 4 1 4 1 0 0.889 1.000 483 VOBESITYPATHWAY The adipose tissue of obese individuals overexpresses a key glucocorticoid-metabolizing enzyme, activating inactive circulating corticosteroids and inducing insulin resistance. APM1, HSD11B1, LPL, NR3C1, PPARG, RETN, RXRA, TNF 7 HSD11B1(1), LPL(6), NR3C1(3), PPARG(1), RXRA(1) 1298420 12 8 12 9 1 2 0 7 2 0 0.890 1.000 484 FASPATHWAY Binding of the Fas ligand to the Fas receptor induces caspase activation and consequent apoptosis in the Fas-expressing cell. ADPRT, ARHGDIB, CASP10, CASP3, CASP6, CASP7, CASP8, CFLAR, DAXX, DFFA, DFFB, FADD, FAF1, JUN, LMNA, LMNB1, LMNB2, MAP2K4, MAP3K1, MAP3K7, MAPK8, PAK1, PAK2, PRKDC, PTPN13, RB1, RIPK2, SPTAN1, TNFRSF6, TNFSF6 25 ARHGDIB(3), CASP10(2), CASP3(1), CASP6(1), CASP7(1), CFLAR(2), DFFA(2), DFFB(2), FAF1(4), LMNB1(2), LMNB2(1), MAP3K1(6), MAP3K7(2), MAPK8(2), PAK1(4), PAK2(2), PRKDC(13), PTPN13(8), RB1(4), RIPK2(3), SPTAN1(9) 8239813 74 33 74 28 16 21 1 23 10 3 0.891 1.000 485 HSA00740_RIBOFLAVIN_METABOLISM Genes involved in riboflavin metabolism ACP1, ACP2, ACP5, ACP6, ACPP, ACPT, ENPP1, ENPP3, FLAD1, LHPP, MTMR1, MTMR2, MTMR6, PHPT1, RFK, TYR 16 ACP1(2), ACP2(2), ACP5(1), ACPP(3), ENPP1(4), ENPP3(3), FLAD1(1), LHPP(1), MTMR1(4), MTMR2(1), MTMR6(4), PHPT1(1), TYR(2) 3411607 29 18 28 13 10 7 1 8 3 0 0.891 1.000 486 PHOSPHATIDYLINOSITOL_SIGNALING_SYSTEM ACVR1, ACVR1B, ACVRL1, AKT1, AURKB, BMPR1A, BMPR2, BUB1, CDC2L5, CDIPT, CDKL1, CDKL2, CDS1, CDS2, CLK1, CLK2, CLK4, COL4A3BP, CSNK2A1, CSNK2A1, CSNK2A1P, CSNK2A2, CSNK2B, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKQ, DGKZ, IMPA1, INPP1, INPP4A, INPP4B, INPP5A, INPPL1, ITPKA, ITPKB, MAP3K10, MOS, NEK1, NEK3, OCRL, PAK4, PCTK1, PCTK2, PIK3C2A, PIK3C2B, PIK3C2G, PIK3CA, PIK3CB, PIK3CG, PIK4CA, PIK4CA, LOC220686, PIM2, PIP5K2B, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCG1, PLCG2, PLK3, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCQ, PRKCZ, PRKD1, PRKG1, RAF1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KB1, STK11, TGFBR1, VRK1 80 ACVR1(3), ACVRL1(3), AKT1(2), AURKB(1), BMPR1A(4), BMPR2(7), BUB1(4), CDKL1(2), CDKL2(4), CDS1(1), CDS2(4), CLK1(5), CLK4(2), COL4A3BP(3), CSNK2A1(4), CSNK2A2(2), CSNK2B(2), DGKA(1), DGKB(7), DGKD(9), DGKE(1), DGKG(3), DGKH(5), DGKZ(2), IMPA1(2), INPP1(2), INPP4A(2), INPP4B(5), INPP5A(2), INPPL1(3), ITPKB(4), MAP3K10(2), MOS(2), NEK1(7), NEK3(4), OCRL(5), PIK3C2A(2), PIK3C2B(3), PIK3C2G(7), PIK3CB(2), PIK3CG(12), PIM2(1), PLCB1(8), PLCB2(3), PLCB3(3), PLCB4(9), PLCD1(6), PLCG1(4), PLCG2(9), PLK3(2), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PRKCA(2), PRKCD(3), PRKCE(4), PRKCG(8), PRKCH(2), PRKCQ(4), PRKD1(10), PRKG1(4), RAF1(4), RPS6KA1(1), RPS6KA2(8), RPS6KA3(3), RPS6KB1(3), TGFBR1(6), VRK1(3) 24419008 264 68 260 75 110 58 6 68 22 0 0.892 1.000 487 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 72 CDS1(1), CDS2(4), DGKA(1), DGKB(7), DGKD(9), DGKE(1), DGKG(3), DGKH(5), DGKI(6), DGKZ(2), IMPA1(2), IMPA2(2), INPP1(2), INPP4A(2), INPP4B(5), INPP5A(2), INPP5B(1), INPP5D(2), INPPL1(3), ITGB1BP3(1), ITPK1(2), ITPKB(4), ITPR1(11), ITPR2(12), ITPR3(11), OCRL(5), PI4KA(11), PI4KB(2), PIK3C2A(2), PIK3C2B(3), PIK3C2G(7), PIK3C3(5), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PIP4K2A(2), PIP4K2B(2), PIP4K2C(3), PIP5K1A(3), PIP5K1B(1), PIP5K1C(3), PLCB1(8), PLCB2(3), PLCB3(3), PLCB4(9), PLCD1(6), PLCD3(2), PLCD4(2), PLCE1(7), PLCG1(4), PLCG2(9), PLCZ1(3), PRKCA(2), PRKCG(8), PTEN(6), PTPMT1(2), SYNJ1(8), SYNJ2(5) 26627877 260 68 256 77 109 52 8 59 31 1 0.892 1.000 488 HSA00460_CYANOAMINO_ACID_METABOLISM Genes involved in cyanoamino acid metabolism ASRGL1, GBA, GBA3, GGT1, GGTL3, GGTL4, SHMT1, SHMT2 5 GBA3(3), SHMT1(1), SHMT2(2) 958802 6 6 6 5 2 1 0 0 3 0 0.893 1.000 489 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP1(2), ACP2(2), ACP5(1), ACPP(3), ENPP1(4), ENPP3(3), FLAD1(1), TYR(2) 2184890 18 12 17 7 7 5 1 4 1 0 0.895 1.000 490 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(3), APAF1(7), BCL2(1), CASP3(1), CASP9(2), FASLG(1), HSPB2(1), IL1A(1), MAPKAPK2(3), MAPKAPK3(1) 2536946 21 15 21 10 6 6 0 6 3 0 0.897 1.000 491 RNA_TRANSCRIPTION_REACTOME CCNH, CDK7, ERCC3, GTF2A2, GTF2B, GTF2E1, GTF2E2, GTF2F2, GTF2H1, GTF2H2, GTF2H4, ILK, MGC9850, MNAT1, POLR1A, POLR1B, POLR2A, POLR2B, POLR2C, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR3B, POLR3D, POLR3E, POLR3H, POLR3K, TAF12, TAF13, TAF5, TAF6, TAF7, TAF9, TBP, VARS2L 37 CCNH(2), CDK7(1), ERCC3(6), GTF2B(1), GTF2E1(5), GTF2H1(2), GTF2H4(1), MNAT1(1), POLR1A(7), POLR1B(6), POLR2A(6), POLR2B(5), POLR2E(1), POLR2H(1), POLR2I(1), POLR3B(6), POLR3D(3), POLR3E(3), POLR3H(1), TAF5(3), TAF6(2), TAF7(1), TBP(1) 7988114 66 33 66 22 23 23 1 14 5 0 0.898 1.000 492 PANTOTHENATE_AND_COA_BIOSYNTHESIS BCAT1, COASY, DPYD, DPYS, ENPP1, ENPP3, PANK1, PANK2, PANK3, PANK4, PPCS, UPB1 12 BCAT1(1), DPYD(8), DPYS(6), ENPP1(4), ENPP3(3), PANK1(2), PANK3(2), PANK4(1), PPCS(1), UPB1(3) 3111342 31 17 31 7 6 12 1 9 3 0 0.898 1.000 493 CHEMICALPATHWAY DNA damage promotes Bid cleavage, which stimulates mitochondrial cytochrome c release and consequent caspase activation, resulting in apoptosis. ADPRT, AKT1, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, CASP3, CASP6, CASP7, CASP9, CYCS, EIF2S1, PRKCA, PRKCB1, PTK2, PXN, STAT1, TLN1, TP53 18 AKT1(2), APAF1(7), BAD(1), BAX(1), BCL2(1), BCL2L1(1), BID(1), CASP3(1), CASP6(1), CASP7(1), CASP9(2), PRKCA(2), PTK2(5), STAT1(6), TLN1(5) 4577281 37 24 37 14 14 7 2 11 3 0 0.899 1.000 494 FATTY_ACID_BIOSYNTHESIS_PATH_2 ACAA1, ACAA2, ACAT1, ACAT2, ECHS1, EHHADH, HADHA, HADHB, SDS 9 ACAA1(2), ACAT1(1), ACAT2(2), ECHS1(2), EHHADH(2), HADHA(2), HADHB(1), SDS(2) 1911177 14 10 14 2 3 5 0 3 3 0 0.901 1.000 495 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(2), FH(1), IDH2(7), IDH3A(1), IDH3G(2), MDH1(1), MDH2(1), OGDH(4), PC(3), PDHA1(4), PDHA2(6), PDHB(2), PDHX(2), PDK2(1), PDK4(2), SDHA(5), SDHB(2), SDHD(1), SUCLA2(3), SUCLG1(1) 6350188 53 29 53 17 25 11 0 8 9 0 0.903 1.000 496 HSA00626_NAPHTHALENE_AND_ANTHRACENE_DEGRADATION Genes involved in naphthalene and anthracene degradation CARM1, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, HEMK1, LCMT1, LCMT2, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, WBSCR22 17 CARM1(2), DHRS1(1), DHRS2(2), DHRS3(2), LCMT1(1), LCMT2(2), METTL2B(1), METTL6(5), PRMT2(1), PRMT3(2), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(3), WBSCR22(1) 3101478 27 17 27 12 9 6 0 8 4 0 0.903 1.000 497 N_GLYCAN_DEGRADATION AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 13 AGA(3), FUCA1(1), GLB1(3), HEXB(1), LCT(15), MAN2C1(6), MANBA(6), NEU2(1), NEU3(1) 3666155 37 22 37 12 15 12 1 8 1 0 0.904 1.000 498 PGC1APATHWAY PCG-1a is expressed in skeletal muscle, heart muscle, and brown fat, and is a coactivator for receptors such as glucocorticoid receptor and thyroid hormone receptor. CALM1, CALM2, CALM3, CAMK1, CAMK1G, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, ESRRA, HDAC5, MEF2A, MEF2B, MEF2C, MEF2D, PPARA, PPARGC1, PPP3CA, PPP3CB, PPP3CC, SLC2A4, SYT1, YWHAH 23 CAMK1(1), CAMK1G(3), CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), CAMK4(2), ESRRA(2), HDAC5(1), MEF2A(3), MEF2C(7), MEF2D(1), PPARA(1), PPP3CA(1), PPP3CB(4), PPP3CC(3), SLC2A4(3), SYT1(1) 4466644 40 22 40 22 16 9 2 8 5 0 0.905 1.000 499 HSA03030_DNA_POLYMERASE Genes involved in DNA polymerase POLA1, POLA2, POLB, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLG, POLG2, POLH, POLI, POLK, POLL, POLM, POLQ, POLS, PRIM1, PRIM2, REV1, REV3L, RFC5 24 POLA1(5), POLA2(2), POLB(1), POLD1(5), POLD2(1), POLD3(2), POLE(17), POLE3(1), POLG(4), POLG2(1), POLH(4), POLI(7), POLK(2), POLM(1), POLQ(8), PRIM2(6), REV1(4), REV3L(15), RFC5(2) 9226370 88 34 86 25 23 24 0 30 10 1 0.906 1.000 500 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 96 AKT1(2), AKT2(5), CD14(1), CHUK(4), CXCL11(2), CXCL9(2), IFNA1(1), IFNA10(1), IFNA13(2), IFNA16(4), IFNA2(3), IFNA21(1), IFNA4(2), IFNA5(1), IFNA6(3), IFNA7(1), IFNA8(1), IFNAR1(3), IFNAR2(1), IFNB1(1), IKBKB(2), IKBKE(3), IL12B(2), IL6(1), IRAK1(1), IRAK4(2), IRF5(3), LBP(1), LY96(2), MAP2K1(3), MAP2K3(2), MAP2K6(2), MAP3K7(2), MAP3K8(2), MAPK1(2), MAPK10(4), MAPK12(2), MAPK14(3), MAPK3(2), MAPK8(2), MAPK9(3), MYD88(1), NFKB1(3), NFKB2(2), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), RELA(2), RIPK1(2), SPP1(1), STAT1(6), TBK1(5), TICAM1(1), TIRAP(1), TLR1(2), TLR2(2), TLR3(4), TLR4(7), TLR5(3), TLR6(2), TLR7(4), TLR8(3), TLR9(4), TOLLIP(1), TRAF3(4), TRAF6(4) 19125946 174 53 174 57 46 39 9 59 21 0 0.906 1.000 501 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(4), DUSP1(2), IKBKAP(2), IKBKB(2), MAP3K1(6), MAP3K14(2), NFKB1(3), RELA(2), TNFAIP3(2), TRAF3(4), TRAF6(4) 3976714 33 20 33 13 17 3 0 8 5 0 0.908 1.000 502 CHONDROITIN B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 HS3ST1(1), HS3ST2(1), HS3ST3B1(2), XYLT1(4), XYLT2(2) 1413911 10 9 10 12 4 1 1 3 1 0 0.908 1.000 503 HEPARAN_SULFATE_BIOSYNTHESIS B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 HS3ST1(1), HS3ST2(1), HS3ST3B1(2), XYLT1(4), XYLT2(2) 1413911 10 9 10 12 4 1 1 3 1 0 0.908 1.000 504 HSA00340_HISTIDINE_METABOLISM Genes involved in histidine metabolism ABP1, ACY3, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH7A1, ALDH9A1, AMDHD1, AOC2, AOC3, ASPA, CARM1, CNDP1, DDC, FTCD, HAL, HARS, HARS2, HDC, HEMK1, HNMT, LCMT1, LCMT2, MAOA, MAOB, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, PRPS1, PRPS2, UROC1, WBSCR22 41 ABP1(1), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH3B1(2), ALDH3B2(1), ALDH7A1(1), ALDH9A1(1), AMDHD1(4), AOC2(4), AOC3(4), ASPA(3), CARM1(2), CNDP1(3), DDC(1), FTCD(2), HAL(3), HARS(2), HARS2(2), HDC(3), HNMT(4), LCMT1(1), LCMT2(2), MAOA(2), METTL2B(1), METTL6(5), PRMT2(1), PRMT3(2), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(3), PRPS2(2), UROC1(1), WBSCR22(1) 8678763 86 37 86 30 32 26 0 23 5 0 0.909 1.000 505 UBIQUINONE_BIOSYNTHESIS NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 15 NDUFA1(1), NDUFA10(2), NDUFA4(1), NDUFB2(1), NDUFB6(1), NDUFS1(4), NDUFV1(2) 1567225 12 10 12 4 4 3 0 4 1 0 0.911 1.000 506 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 63 APAF1(7), BAD(1), BAK1(1), BAX(1), BCL2(1), BCL2L1(1), BCL2L11(2), BID(1), BIRC2(2), BIRC3(2), BNIP3L(3), CASP1(2), CASP10(2), CASP2(4), CASP3(1), CASP4(1), CASP6(1), CASP7(1), CASP9(2), CHUK(4), DFFA(2), DFFB(2), FASLG(1), GZMB(1), HELLS(4), IKBKB(2), IRF1(1), IRF2(3), IRF4(1), IRF5(3), IRF6(2), MAP3K1(6), MAPK10(4), MDM2(4), NFKB1(3), NFKBIB(1), NFKBIE(2), RELA(2), RIPK1(2), TNFRSF10B(2), TNFRSF1A(1), TNFRSF21(4), TNFSF10(1), TRADD(1), TRAF1(1), TRAF2(1), TRAF3(4) 12214370 101 44 101 36 32 25 2 31 11 0 0.912 1.000 507 HSA00562_INOSITOL_PHOSPHATE_METABOLISM Genes involved in inositol phosphate metabolism CARKL, FN3K, IMPA1, IMPA2, INPP1, INPP4A, INPP4B, INPP5A, INPP5B, INPP5E, INPPL1, IPMK, ISYNA1, ITGB1BP3, ITPK1, ITPKA, ITPKB, MINPP1, MIOX, OCRL, PI4KA, PI4KB, PIB5PA, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCZ1, PTEN, PTPMT1, SKIP, SYNJ1, SYNJ2 46 IMPA1(2), IMPA2(2), INPP1(2), INPP4A(2), INPP4B(5), INPP5A(2), INPP5B(1), INPPL1(3), IPMK(2), ITGB1BP3(1), ITPK1(2), ITPKB(4), MIOX(1), OCRL(5), PI4KA(11), PI4KB(2), PIK3C3(5), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIP4K2A(2), PIP4K2B(2), PIP4K2C(3), PIP5K1A(3), PIP5K1B(1), PIP5K1C(3), PLCB1(8), PLCB2(3), PLCB3(3), PLCB4(9), PLCD1(6), PLCD3(2), PLCD4(2), PLCE1(7), PLCG1(4), PLCG2(9), PLCZ1(3), PTEN(6), PTPMT1(2), SYNJ1(8), SYNJ2(5) 15792659 159 50 155 39 69 33 6 31 18 2 0.912 1.000 508 SULFUR_METABOLISM BPNT1, PAPSS1, PAPSS2, SULT1A2, SULT1A3, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SUOX 7 BPNT1(1), PAPSS1(1), PAPSS2(2), SULT1A2(1), SULT1E1(1), SULT2A1(1), SUOX(2) 1367733 9 7 9 1 5 0 0 1 3 0 0.914 1.000 509 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(5), SCAP(1), SREBF1(1), SREBF2(2) 2711560 14 13 14 10 4 6 1 0 3 0 0.915 1.000 510 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(4), PRKCA(2), PTK2B(1) 1526248 9 8 9 3 4 1 1 2 1 0 0.916 1.000 511 GATA3PATHWAY GATA-3 is a transcription factor that promotes differentiation of helper T cells into Th2 cells, which secrete cytokines IL4, IL5, and IL13. GATA3, IL13, IL4, IL5, JUNB, MAF, MAP2K3, MAPK14, NFATC1, NFATC2, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 16 GATA3(4), IL13(1), IL4(3), MAF(1), MAP2K3(2), MAPK14(3), NFATC1(1), NFATC2(3), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2) 2630285 25 18 25 7 15 2 2 4 2 0 0.917 1.000 512 HSA00760_NICOTINATE_AND_NICOTINAMIDE_METABOLISM Genes involved in nicotinate and nicotinamide metabolism AOX1, BST1, C9orf95, CD38, ENPP1, ENPP3, NADK, NADSYN1, NMNAT1, NMNAT2, NMNAT3, NNMT, NNT, NP, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT12, PBEF1, QPRT 22 AOX1(5), C9orf95(1), CD38(1), ENPP1(4), ENPP3(3), NADK(1), NADSYN1(2), NMNAT1(1), NMNAT2(1), NMNAT3(2), NNMT(1), NNT(1), NT5C1A(1), NT5C1B(9), NT5C2(3), NT5C3(2), NT5E(2), NT5M(1), NUDT12(2), QPRT(1) 4949432 44 26 44 17 15 15 0 9 5 0 0.918 1.000 513 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 66 AKT1(2), AKT2(5), BAD(1), CASP9(2), KDR(8), MAP2K1(3), MAPK1(2), MAPK12(2), MAPK14(3), MAPK3(2), MAPKAPK2(3), MAPKAPK3(1), NFAT5(5), NFATC1(1), NFATC2(3), NFATC3(4), NFATC4(4), NOS3(2), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PLA2G1B(1), PLA2G2F(1), PLA2G4A(5), PLA2G6(2), PLCG1(4), PLCG2(9), PPP3CA(1), PPP3CB(4), PPP3CC(3), PPP3R1(1), PPP3R2(1), PRKCA(2), PRKCG(8), PTGS2(2), PTK2(5), RAF1(4), SH2D2A(1), SPHK2(1), SRC(3), VEGFA(2) 15464931 136 51 134 47 60 24 3 30 19 0 0.921 1.000 514 SA_CASPASE_CASCADE Apoptosis is mediated by caspases, cysteine proteases arranged in a proteolytic cascade. ADPRT, APAF1, BIRC2, BIRC3, BIRC4, CASP10, CASP3, CASP7, CASP8, CASP9, DFFA, DFFB, GZMB, PRF1, SCAP, SREBF1, SREBF2, TNFRSF6, TNFSF6 14 APAF1(7), BIRC2(2), BIRC3(2), CASP10(2), CASP3(1), CASP7(1), CASP9(2), DFFA(2), DFFB(2), GZMB(1), SCAP(1), SREBF1(1), SREBF2(2) 3868815 26 19 26 14 5 6 1 10 4 0 0.922 1.000 515 HSA04740_OLFACTORY_TRANSDUCTION Genes involved in olfactory transduction ADCY3, ADRBK2, ARRB2, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CLCA1, CLCA2, CLCA4, CNGA3, CNGA4, CNGB1, GNAL, GUCA1A, GUCA1B, GUCA1C, PDC, PDE1C, PRKACA, PRKACB, PRKACG, PRKG1, PRKG2, PRKX, PRKY 30 ADCY3(1), ADRBK2(1), CAMK2A(1), CAMK2B(2), CAMK2D(2), CAMK2G(2), CLCA1(4), CLCA2(4), CLCA4(5), CNGA3(5), CNGA4(5), CNGB1(7), GNAL(3), GUCA1A(1), GUCA1B(2), PDC(2), PDE1C(7), PRKACB(1), PRKACG(2), PRKG1(4), PRKG2(3), PRKX(2) 6875932 66 29 65 30 22 14 2 20 8 0 0.923 1.000 516 HSA04120_UBIQUITIN_MEDIATED_PROTEOLYSIS Genes involved in ubiquitin mediated proteolysis ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, BTRC, CDC16, CDC20, CDC23, CDC26, CDC27, CUL1, CUL2, CUL3, FBXW11, FBXW7, FZR1, ITCH, LOC728919, RBX1, SKP1, SKP2, SMURF1, SMURF2, TCEB1, TCEB2, UBA1, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2D4, UBE2E1, UBE2E2, UBE2E3, VHL, WWP1, WWP2 38 ANAPC1(3), ANAPC10(2), ANAPC2(1), ANAPC4(1), ANAPC5(2), ANAPC7(4), BTRC(2), CDC16(3), CDC20(3), CDC23(6), CDC27(9), CUL1(7), CUL2(4), CUL3(1), FBXW11(7), ITCH(3), SKP1(1), SKP2(1), SMURF1(1), SMURF2(2), UBA1(1), UBE2C(2), UBE2D1(1), UBE2D4(1), UBE2E1(3), WWP1(5), WWP2(4) 8728214 80 37 76 28 23 14 2 28 13 0 0.923 1.000 517 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(6), GTF2A1(2), GTF2B(1), GTF2E1(5), GTF2F1(3), HDAC3(2), NCOA1(6), NCOA2(4), NCOA3(6), NCOR2(2), POLR2A(6), RXRA(1), TBP(1) 5500768 45 26 45 17 15 15 2 11 2 0 0.924 1.000 518 HYPERTROPHY_MODEL ADAM10, ANKRD1, ATF3, CYR61, DUSP14, EIF4E, EIF4EBP1, GDF8, HBEGF, IFNG, IFRD1, IL18, IL1A, IL1R1, JUND, MYOG, NR4A3, TCF8, VEGF, WDR1 17 ADAM10(1), ANKRD1(4), ATF3(1), CYR61(2), HBEGF(1), IFNG(1), IFRD1(2), IL1A(1), IL1R1(3), NR4A3(2), WDR1(3) 2390028 21 13 21 5 5 9 0 5 2 0 0.924 1.000 519 ATP_SYNTHESIS ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP5O(2), ATP6AP1(2), ATP6V0A1(2), ATP6V0A4(4), ATP6V0D1(2), ATP6V1A(2), ATP6V1B1(4), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(2), SHMT1(1) 3448610 29 19 28 8 11 11 1 3 3 0 0.925 1.000 520 FLAGELLAR_ASSEMBLY ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP5O(2), ATP6AP1(2), ATP6V0A1(2), ATP6V0A4(4), ATP6V0D1(2), ATP6V1A(2), ATP6V1B1(4), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(2), SHMT1(1) 3448610 29 19 28 8 11 11 1 3 3 0 0.925 1.000 521 TYPE_III_SECRETION_SYSTEM ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP5O(2), ATP6AP1(2), ATP6V0A1(2), ATP6V0A4(4), ATP6V0D1(2), ATP6V1A(2), ATP6V1B1(4), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(2), SHMT1(1) 3448610 29 19 28 8 11 11 1 3 3 0 0.925 1.000 522 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 79 ABL1(4), BUB1(4), BUB1B(3), BUB3(2), CCNA1(4), CCNA2(3), CCNB1(2), CCNB2(2), CCNB3(4), CCND2(1), CCND3(1), CCNE1(3), CCNE2(1), CCNH(2), CDAN1(1), CDC14A(1), CDC14B(3), CDC20(3), CDC25A(2), CDC25B(5), CDC25C(3), CDC7(2), CDH1(4), CDK2(2), CDK4(2), CDKN1A(1), CDKN2A(1), CHEK1(1), CHEK2(1), DTX4(3), E2F2(1), E2F3(1), E2F4(1), E2F5(2), EP300(13), ESPL1(8), GSK3B(7), HDAC1(2), HDAC2(2), HDAC3(2), HDAC4(5), HDAC5(1), HDAC6(4), MAD1L1(1), MAD2L1(1), MAD2L2(1), MCM3(1), MCM4(4), MCM5(3), MCM6(3), MCM7(2), MDM2(4), MPEG1(2), MPL(1), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(2), PLK1(6), PRKDC(13), PTPRA(2), PTTG1(1), RB1(4), RBL1(3), SKP2(1), TBC1D8(5), TFDP1(4), TGFB1(1), WEE1(3) 22437469 192 58 192 52 51 56 4 55 25 1 0.925 1.000 523 HSA04330_NOTCH_SIGNALING_PATHWAY Genes involved in Notch signaling pathway ADAM17, APH1A, CIR, CREBBP, CTBP1, CTBP2, DLL1, DLL3, DLL4, DTX1, DTX2, DTX3, DTX3L, DTX4, DVL1, DVL2, DVL3, EP300, GCN5L2, HDAC1, HDAC2, HES1, JAG1, JAG2, LFNG, LOC652788, MAML1, MAML2, MAML3, MFNG, NCOR2, NCSTN, NOTCH1, NOTCH2, NOTCH3, NOTCH4, NUMB, NUMBL, PCAF, PSEN1, PSEN2, PSENEN, PTCRA, RBPJ, RBPJL, RFNG, SNW1 43 ADAM17(6), CREBBP(21), CTBP1(1), CTBP2(2), DLL1(1), DLL3(2), DLL4(1), DTX1(4), DTX2(3), DTX3L(3), DTX4(3), DVL2(8), DVL3(2), EP300(13), HDAC1(2), HDAC2(2), HES1(1), JAG1(7), MAML1(1), MAML2(3), MAML3(1), NCOR2(2), NCSTN(5), NOTCH2(11), NOTCH3(12), NOTCH4(3), NUMB(2), NUMBL(3), PSEN1(3), PSEN2(2), PTCRA(1), RBPJ(1), RBPJL(3), SNW1(4) 15056595 139 51 138 54 48 42 1 27 21 0 0.929 1.000 524 GLYCOSPHINGOLIPID_METABOLISM ARSA, ARSB, ARSD, ARSE, ASAH1, GAL3ST1, GALC, GBA, GBAP, GLA, GLB1, LCT, NEU1, NEU2, NEU3, NEU4, PPAP2A, PPAP2B, PPAP2C, SMPD1, SMPD2, SPTLC1, SPTLC2, UGCG 23 ARSA(1), ARSB(5), ARSD(3), ARSE(2), ASAH1(3), GALC(1), GLA(4), GLB1(3), LCT(15), NEU2(1), NEU3(1), PPAP2B(1), SMPD1(6), SPTLC1(4), SPTLC2(2), UGCG(2) 5281950 54 25 54 17 19 14 2 16 3 0 0.930 1.000 525 EICOSANOID_SYNTHESIS ALOX12, ALOX15, ALOX15B, ALOX5, ALOX5AP, DPEP1, GGT1, IPLA2(GAMMA), LTA4H, LTC4S, PLA2G2A, PLA2G6, PTGDS, PTGES, PTGIS, PTGS1, PTGS2, TBXAS1 16 ALOX12(2), ALOX15B(5), ALOX5(4), ALOX5AP(1), DPEP1(1), PLA2G6(2), PTGIS(4), PTGS1(4), PTGS2(2), TBXAS1(5) 3191198 30 19 30 8 11 6 0 12 1 0 0.931 1.000 526 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(2), IL22RA1(1), JAK1(3), JAK2(6), JAK3(6), STAT1(6), STAT3(2), STAT5B(2), TYK2(1) 4123712 30 20 29 14 12 6 2 7 2 1 0.931 1.000 527 GLUCOCORTICOID_MINERALOCORTICOID_METABOLISM CPN2, CYP11A1, CYP11B2, CYP17A1, HSD11B1, HSD11B2, HSD3B1, HSD3B2 8 CPN2(1), CYP11A1(2), CYP11B2(5), CYP17A1(2), HSD11B1(1), HSD3B1(2) 1499829 13 9 13 6 6 3 0 4 0 0 0.932 1.000 528 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(2), CABIN1(9), CAMK1(1), CAMK1G(3), HDAC5(1), IGF1(2), IGF1R(7), INSR(5), MAP2K6(2), MAPK14(3), MAPK7(3), MEF2A(3), MEF2C(7), MEF2D(1), NFATC1(1), NFATC2(3), PIK3R1(5), PPP3CA(1), PPP3CB(4), PPP3CC(3), SYT1(1) 7145769 67 34 67 27 31 12 2 12 10 0 0.934 1.000 529 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), BLVRB(1), CP(3), EPRS(10), FECH(2), GUSB(2), HCCS(1), HMBS(2), HMOX1(2), HMOX2(1), PPOX(3), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(1), UGT1A5(3), UGT1A7(2), UGT1A9(5), UGT2B15(2), UGT2B4(2), UROS(1) 5872591 49 26 48 16 17 12 0 15 5 0 0.936 1.000 530 HSA01031_GLYCAN_STRUCTURES_BIOSYNTHESIS_2 Genes involved in glycan structures - biosynthesis 2 A4GALT, ABO, B3GALNT1, B3GALT1, B3GALT2, B3GALT4, B3GALT5, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT4, B4GALT6, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GBGT1, GCNT2, PIGA, PIGB, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGU, PIGV, PIGX, PIGZ, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST3GAL5, ST3GAL6, ST6GALNAC3, ST6GALNAC4, ST6GALNAC5, ST6GALNAC6, ST8SIA1, ST8SIA5, UGCG, UGCGL1, UGCGL2 60 A4GALT(3), ABO(2), B3GALNT1(3), B3GALT1(1), B3GALT2(3), B3GALT4(1), B3GALT5(2), B3GNT1(2), B3GNT2(1), B3GNT4(1), B3GNT5(1), B4GALNT1(3), B4GALT1(5), B4GALT2(3), B4GALT3(6), B4GALT6(5), FUT1(1), FUT2(1), FUT3(3), FUT6(1), FUT9(4), GCNT2(9), PIGA(1), PIGB(1), PIGG(1), PIGK(3), PIGM(1), PIGN(1), PIGO(2), PIGQ(1), PIGS(2), PIGT(2), PIGX(2), ST3GAL1(1), ST3GAL2(1), ST3GAL3(4), ST3GAL4(2), ST3GAL6(4), ST6GALNAC3(3), ST6GALNAC4(1), ST6GALNAC5(4), ST6GALNAC6(3), ST8SIA1(3), ST8SIA5(4), UGCG(2) 10749110 110 40 110 30 45 21 4 23 17 0 0.938 1.000 531 IRINOTECAN_PATHWAY_PHARMGKB ABCC1, ABCC2, ABCG2, BCHE, CES1, CES2, CES4, CYP3A4, CYP3A5, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6 17 ABCC1(8), ABCC2(11), ABCG2(5), BCHE(7), CES1(4), CES2(1), CYP3A4(1), CYP3A5(3), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(1), UGT1A5(3), UGT1A7(2), UGT1A9(5) 5140080 55 23 55 18 21 11 0 16 7 0 0.939 1.000 532 HSA00220_UREA_CYCLE_AND_METABOLISM_OF_AMINO_GROUPS Genes involved in urea cycle and metabolism of amino groups ABP1, ACY1, ADC, AGMAT, ALDH18A1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, AMD1, AOC2, AOC3, ARG1, ARG2, ASL, ASS1, CPS1, GATM, MAOA, MAOB, NAGS, ODC1, OTC, SAT1, SAT2, SMS, SRM 30 ABP1(1), ACY1(2), ADC(1), ALDH18A1(5), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(1), ALDH9A1(1), AOC2(4), AOC3(4), ARG1(1), ARG2(4), ASS1(1), CPS1(8), GATM(1), MAOA(2), ODC1(2), OTC(4), SAT1(4), SAT2(1), SMS(2) 6651692 67 31 65 23 21 21 0 17 8 0 0.942 1.000 533 NO2IL12PATHWAY Macrophages activate NK cells by releasing IL-12, which induces NK cytotoxic activity in coordination with NO produced by inducible nitric oxide synthase II. CCR5, CD2, CD3D, CD3E, CD3G, CD3Z, CD4, CXCR3, IFNG, IL12A, IL12B, IL12RB1, IL12RB2, JAK2, NOS2A, STAT4, TYK2 15 CCR5(1), CD2(3), CD3D(1), CD3G(2), CD4(2), IFNG(1), IL12B(2), IL12RB1(2), IL12RB2(5), JAK2(6), TYK2(1) 3225578 26 15 27 17 5 10 1 6 3 1 0.942 1.000 534 PENTOSE_PHOSPHATE_PATHWAY ALDOA, ALDOB, ALDOC, FBP1, FBP2, G6PD, GPI, H6PD, PFKM, PFKP, PGD, PGLS, PGM1, PGM3, PRPS1, PRPS1L1, PRPS2, RBKS, RPE, RPE, LOC440001, RPIA, TAL1, TALDO1, TALDO1, HSUP1, TKT 23 ALDOA(1), ALDOB(5), ALDOC(1), FBP2(2), G6PD(2), GPI(1), H6PD(3), PFKM(1), PFKP(2), PGD(1), PGM1(2), PGM3(4), PRPS1L1(1), PRPS2(2), RPE(2), RPIA(3), TALDO1(3), TKT(3) 4495812 39 26 39 14 15 8 0 15 1 0 0.942 1.000 535 NITROGEN_METABOLISM AMT, ASNS, CA1, CA12, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA8, CA9, CPS1, CTH, GLS, GLS2, GLUD1, GLUL, HAL 21 ASNS(1), CA1(1), CA14(2), CA2(1), CA3(1), CA4(1), CA5A(1), CA6(2), CA8(2), CA9(2), CPS1(8), CTH(1), GLS2(2), GLUD1(2), GLUL(3), HAL(3) 4253878 33 20 33 18 13 9 0 5 6 0 0.943 1.000 536 UREA_CYCLE_AND_METABOLISM_OF_AMINO_GROUPS ACY1, ALDH18A1, ARG1, ARG2, ASL, ASS, CKB, CKM, CKMT1, CKMT1B, CKMT1A, CKMT2, CPS1, GAMT, GATM, GLUD1, NAGS, OAT, ODC1, OTC, PYCR1, SMS 20 ACY1(2), ALDH18A1(5), ARG1(1), ARG2(4), CKM(4), CKMT1B(1), CKMT2(2), CPS1(8), GAMT(1), GATM(1), GLUD1(2), ODC1(2), OTC(4), SMS(2) 3891102 39 21 39 14 11 12 0 9 7 0 0.945 1.000 537 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(2), BAD(1), BCL2(1), BCL2L1(1), CBL(2), CFLAR(2), CRKL(2), GRB2(2), IL2RA(2), IL2RB(1), IRS1(5), JAK1(3), JAK3(6), MAPK1(2), MAPK3(2), NMI(1), PIK3R1(5), PTPN6(4), RAF1(4), RPS6KB1(3), SHC1(3), SOS1(5), STAT5B(2) 7540908 61 31 58 23 21 12 3 17 8 0 0.945 1.000 538 HSA00280_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION Genes involved in valine, leucine and isoleucine degradation ABAT, ACAA1, ACAA2, ACADM, ACADS, ACAT1, ACAT2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH7A1, ALDH9A1, AOX1, AUH, BCAT1, BCAT2, BCKDHA, BCKDHB, DBT, DLD, ECHS1, EHHADH, HADH, HADHA, HADHB, HIBADH, HIBCH, HMGCL, HMGCS1, HMGCS2, HSD17B10, HSD17B4, IVD, MCCC1, MCCC2, MCEE, MUT, OXCT1, OXCT2, PCCA, PCCB 44 ABAT(5), ACAA1(2), ACADM(3), ACAT1(1), ACAT2(2), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH6A1(3), ALDH7A1(1), ALDH9A1(1), AOX1(5), AUH(1), BCAT1(1), BCAT2(1), BCKDHA(3), BCKDHB(1), ECHS1(2), EHHADH(2), HADH(1), HADHA(2), HADHB(1), HMGCS1(1), HSD17B10(1), HSD17B4(3), MCCC1(7), MCCC2(2), MCEE(1), MUT(3), OXCT1(3), OXCT2(1), PCCA(3), PCCB(3) 9836332 84 38 84 23 35 19 0 21 9 0 0.947 1.000 539 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 128 ACTB(2), ACTN1(3), ACTN2(7), ACTN3(2), ACTN4(2), AKT1(2), AKT2(5), AMOTL1(10), ASH1L(17), CASK(3), CDK4(2), CGN(6), CLDN10(2), CLDN11(1), CLDN15(1), CLDN16(4), CLDN17(5), CLDN18(2), CLDN19(1), CLDN6(2), CLDN7(2), CLDN8(3), CLDN9(1), CSDA(2), CSNK2A1(4), CSNK2A2(2), CSNK2B(2), CTNNA1(10), CTNNA2(10), CTNNA3(9), CTNNB1(8), EPB41(3), EPB41L1(8), EPB41L2(6), EPB41L3(15), EXOC4(4), F11R(1), GNAI1(3), HCLS1(7), IGSF5(6), INADL(3), JAM3(3), LLGL1(1), MAGI1(10), MAGI2(6), MAGI3(4), MLLT4(3), MPDZ(7), MPP5(3), MRAS(1), MYH1(8), MYH10(8), MYH11(22), MYH13(10), MYH14(9), MYH15(8), MYH2(9), MYH3(9), MYH4(11), MYH6(8), MYH7(7), MYH7B(4), MYH8(17), MYH9(9), MYL2(1), MYL7(1), OCLN(1), PARD3(5), PARD6G(1), PPP2CA(1), PPP2R1A(4), PPP2R1B(1), PPP2R2A(1), PPP2R2B(1), PPP2R2C(3), PPP2R3A(3), PRKCA(2), PRKCD(3), PRKCE(4), PRKCG(8), PRKCH(2), PRKCI(4), PRKCQ(4), PTEN(6), RAB3B(1), RHOA(4), RRAS2(1), SPTAN1(9), SRC(3), SYMPK(5), TJP1(5), TJP2(5), TJP3(1), YES1(1), ZAK(4) 42152446 460 84 453 145 202 94 10 106 45 3 0.950 1.000 540 IL1RPATHWAY The cytokine IL-1 stimulates its primary receptor, IL-1R1, which induces transcription of inflammation-related genes such as interferons. CHUK, IFNA1, IFNB1, IKBKB, IL1A, IL1B, IL1R1, IL1RAP, IL1RN, IL6, IRAK1, IRAK2, IRAK3, JUN, MAP2K3, MAP2K6, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MAPK14, MAPK8, MYD88, NFKB1, NFKBIA, RELA, SITPEC, TGFB1, TGFB2, TGFB3, TNF, TOLLIP, TRAF6 31 CHUK(4), IFNA1(1), IFNB1(1), IKBKB(2), IL1A(1), IL1R1(3), IL1RN(2), IL6(1), IRAK1(1), IRAK2(8), IRAK3(1), MAP2K3(2), MAP2K6(2), MAP3K1(6), MAP3K14(2), MAP3K7(2), MAPK14(3), MAPK8(2), MYD88(1), NFKB1(3), RELA(2), TGFB1(1), TGFB2(5), TOLLIP(1), TRAF6(4) 6521723 61 27 61 18 26 9 1 18 7 0 0.950 1.000 541 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 CHUK(4), IFNG(1), IKBKB(2), IL2(3), IL4(3), MAP3K1(6), MAP3K5(5), MAP4K5(2), MAPK14(3), MAPK8(2), NFKB1(3), RELA(2), TNFRSF9(2), TRAF2(1) 4337863 39 20 39 11 17 8 1 11 2 0 0.951 1.000 542 HSA00600_SPHINGOLIPID_METABOLISM Genes involved in sphingolipid metabolism ARSA, ARSD, ARSE, ASAH1, ASAH3L, B4GALT6, CERK, DEGS1, DEGS2, ENPP7, FVT1, GAL3ST1, GALC, GBA, GLA, GLB1, LCT, NEU1, NEU2, NEU3, NEU4, PHCA, PPAP2A, PPAP2B, PPAP2C, SGMS1, SGMS2, SGPP1, SGPP2, SMPD1, SMPD2, SMPD3, SMPD4, SPHK1, SPHK2, SPTLC1, SPTLC2, UGCG, UGT8 36 ARSA(1), ARSD(3), ARSE(2), ASAH1(3), B4GALT6(5), CERK(1), DEGS1(1), ENPP7(1), GALC(1), GLA(4), GLB1(3), LCT(15), NEU2(1), NEU3(1), PPAP2B(1), SGMS1(2), SGMS2(4), SGPP2(2), SMPD1(6), SMPD3(3), SMPD4(1), SPHK2(1), SPTLC1(4), SPTLC2(2), UGCG(2), UGT8(6) 7755348 76 34 75 26 25 23 2 21 5 0 0.951 1.000 543 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(4), IKBKB(2), IRAK1(1), LY96(2), MAP2K3(2), MAP2K6(2), MAP3K1(6), MAP3K14(2), MAP3K7(2), MAPK14(3), MAPK8(2), MYD88(1), NFKB1(3), PPARA(1), RELA(2), TIRAP(1), TLR10(1), TLR2(2), TLR3(4), TLR4(7), TLR6(2), TLR7(4), TLR9(4), TOLLIP(1), TRAF6(4) 7790703 66 31 66 26 25 11 4 19 7 0 0.952 1.000 544 PHOTOSYNTHESIS ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, FDXR 22 ATP5O(2), ATP6AP1(2), ATP6V0A1(2), ATP6V0A4(4), ATP6V0D1(2), ATP6V1A(2), ATP6V1B1(4), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(2), FDXR(1), SHMT1(1) 3646018 30 19 29 9 11 11 1 4 3 0 0.953 1.000 545 SODDPATHWAY Some members of the tumor necrosis factor receptor family have cytoplasmic death domains that promote apoptosis when active and are repressed by silencers called SODDs. BAG4, BIRC3, CASP8, FADD, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF2 9 BAG4(2), BIRC3(2), RIPK1(2), TNFRSF1A(1), TRADD(1), TRAF2(1) 1653269 9 9 9 4 3 2 1 3 0 0 0.955 1.000 546 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 75 AIFM1(1), AKT1(2), AKT2(5), APAF1(7), BAD(1), BAX(1), BCL2(1), BCL2L1(1), BID(1), BIRC2(2), BIRC3(2), CAPN1(2), CAPN2(5), CASP10(2), CASP3(1), CASP6(1), CASP7(1), CASP9(2), CFLAR(2), CHUK(4), CSF2RB(7), DFFA(2), DFFB(2), FASLG(1), IKBKB(2), IL1A(1), IL1R1(3), IL3(3), IRAK1(1), IRAK2(8), IRAK3(1), IRAK4(2), MAP3K14(2), MYD88(1), NFKB1(3), NFKB2(2), NTRK1(6), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PPP3CA(1), PPP3CB(4), PPP3CC(3), PPP3R1(1), PPP3R2(1), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), RELA(2), RIPK1(2), TNFRSF10A(3), TNFRSF10B(2), TNFRSF1A(1), TNFSF10(1), TRADD(1), TRAF2(1) 16085517 144 50 143 45 52 32 4 38 18 0 0.958 1.000 547 NOTCHPATHWAY Proteolysis and Signaling Pathway of Notch ADAM17, DLL1, FURIN, NOTCH1, PSEN1, RBPSUH 5 ADAM17(6), DLL1(1), FURIN(2), PSEN1(3) 2035925 12 10 12 2 5 4 0 0 3 0 0.959 1.000 548 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(2), CAPN1(2), CAPN10(3), CAPN11(1), CAPN2(5), CAPN3(6), CAPN5(5), CAPN6(2), CAPN7(3), CAPN9(1), CAPNS1(1), CAV2(1), CAV3(2), CSK(1), DOCK1(5), FYN(4), GIT2(6), GRB2(2), ITGA10(3), ITGA11(2), ITGA2(5), ITGA2B(2), ITGA3(4), ITGA4(3), ITGA5(7), ITGA6(3), ITGA7(6), ITGA8(5), ITGA9(4), ITGAD(7), ITGAE(5), ITGAL(5), ITGAM(5), ITGAV(1), ITGAX(4), ITGB1(6), ITGB2(4), ITGB3(7), ITGB4(2), ITGB5(5), ITGB6(6), ITGB7(4), ITGB8(4), MAP2K1(3), MAP2K3(2), MAP2K6(2), MAPK10(4), MAPK12(2), MAPK4(1), MAPK6(2), MAPK7(3), MYLK2(2), PAK1(4), PAK2(2), PAK3(3), PAK6(1), PDPK1(1), PIK3R2(1), PTK2(5), RAP1B(2), RAPGEF1(4), RHO(2), ROCK1(8), ROCK2(2), SHC1(3), SHC3(1), SORBS1(7), SOS1(5), SRC(3), TLN1(5), TNS1(11), VASP(3), VAV2(2), VAV3(10), VCL(1) 29475050 268 71 264 105 97 50 7 83 31 0 0.960 1.000 549 VIPPATHWAY Apoptosis of activated T cells is inhibited by vasoactive intestinal peptide (VIP) and its relative PACAP. CALM1, CALM2, CALM3, CHUK, EGR2, EGR3, GNAQ, MAP3K1, MYC, NFATC1, NFATC2, NFKB1, NFKBIA, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RELA, SYT1, VIP, VIPR2 27 CHUK(4), EGR2(6), EGR3(2), GNAQ(3), MAP3K1(6), NFATC1(1), NFATC2(3), NFKB1(3), PLCG1(4), PPP3CA(1), PPP3CB(4), PPP3CC(3), PRKACB(1), PRKACG(2), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), RELA(2), SYT1(1), VIPR2(3) 6108680 53 29 52 16 25 9 2 8 9 0 0.962 1.000 550 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(2), ARG1(1), GLUD1(2) 1206787 5 5 5 2 3 2 0 0 0 0 0.962 1.000 551 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 61 CCNA1(4), CCNB1(2), CCND2(1), CCND3(1), CCNE1(3), CCNE2(1), CCNH(2), CDC25A(2), CDK2(2), CDK4(2), CDK7(1), CDKN1A(1), CDKN1B(1), CDKN2A(1), CDKN2C(1), CREB3(2), CREB3L1(3), CREB3L3(1), CREB3L4(1), E2F2(1), E2F3(1), E2F4(1), E2F5(2), GBA2(5), MCM3(1), MCM4(4), MCM5(3), MCM6(3), MCM7(2), MDM2(4), MNAT1(1), MYT1(8), NACA(5), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(2), POLA2(2), POLE(17), RB1(4), RBL1(3), RPA1(2), RPA2(1), TFDP1(4), TFDP2(1), TNXB(14), WEE1(3) 14909750 130 45 129 29 38 32 1 44 14 1 0.962 1.000 552 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(14), ACSL1(3), ACSL3(6), ACSL4(4), ACSL5(4), ACSL6(5), ADIPOQ(4), ADIPOR1(1), ADIPOR2(2), AKT1(2), AKT2(5), CAMKK1(1), CAMKK2(1), CD36(1), CHUK(4), CPT1A(5), CPT1B(5), CPT2(1), G6PC(3), IKBKB(2), IRS1(5), IRS4(11), JAK1(3), JAK2(6), JAK3(6), LEP(1), LEPR(5), MAPK10(4), MAPK8(2), MAPK9(3), NFKB1(3), NFKB2(2), NFKBIB(1), NFKBIE(2), NPY(1), PCK2(3), POMC(2), PPARA(1), PPARGC1A(5), PRKAA1(2), PRKAA2(6), PRKAB1(1), PRKAB2(1), PRKAG1(1), PRKAG2(2), PRKAG3(4), PRKCQ(4), PTPN11(2), RELA(2), RXRA(1), RXRB(2), RXRG(3), SLC2A4(3), STAT3(2), TNFRSF1A(1), TRADD(1), TRAF2(1), TYK2(1) 18673754 179 55 178 65 55 48 4 54 17 1 0.963 1.000 553 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(2), AASS(7), ACAT1(1), ACAT2(2), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH7A1(1), ALDH9A1(1), BBOX1(1), DOT1L(3), ECHS1(2), EHHADH(2), EHMT1(2), EHMT2(1), GCDH(3), HADH(1), HADHA(2), HSD17B10(1), HSD17B4(3), HSD3B7(2), NSD1(11), OGDH(4), OGDHL(8), PIPOX(4), PLOD1(3), PLOD2(4), PLOD3(3), RDH12(2), RDH13(1), SETD1A(7), SETD7(2), SETDB1(7), SHMT1(1), SHMT2(2), SPCS1(1), SUV39H1(1), SUV39H2(2), TMLHE(1) 13066752 120 46 120 33 50 22 0 32 16 0 0.964 1.000 554 DNA_POLYMERASE POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLS 7 POLB(1), POLD1(5), POLD2(1), POLE(17), POLG(4), POLQ(8) 3767056 36 19 34 9 15 6 0 12 3 0 0.964 1.000 555 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(6), GNA12(2), PRKACB(1), PRKACG(2), PRKAG1(1), PRKAR2B(2) 2305248 14 11 14 10 4 3 0 2 5 0 0.965 1.000 556 ARAPPATHWAY ADP-ribosylation factors (ARFs), members of the Ras superfamily, regulate eukaryotic vesicular trafficking and activate phospholipase D's. ARF1, ARFGAP1, ARFGAP3, ARFGEF2, BIG1, CENTD1, CENTD2, CLTA, CLTB, COP, COPA, DDEF1, DDEF2, GBF1, GPLD1, KDELR1, KDELR2, KDELR3, PSCD1, PSCD2, PSCD3, PSCD4 12 ARFGAP1(1), ARFGAP3(3), ARFGEF2(5), CLTA(1), COPA(1), GBF1(11), GPLD1(4), KDELR1(2), KDELR3(1) 3720912 29 20 29 12 12 7 0 8 2 0 0.966 1.000 557 HSA00330_ARGININE_AND_PROLINE_METABOLISM Genes involved in arginine and proline metabolism ALDH4A1, ARG1, ARG2, ASL, ASS1, CKB, CKM, CKMT1A, CKMT1B, CKMT2, CPS1, DAO, EPRS, GAMT, GATM, GLUD1, GLUD2, GOT1, GOT2, LAP3, NOS1, NOS2A, NOS3, OAT, OTC, P4HA1, P4HA2, P4HA3, PARS2, PRODH, PYCR1, PYCR2, PYCRL, RARS, RARS2 34 ALDH4A1(2), ARG1(1), ARG2(4), ASS1(1), CKM(4), CKMT1B(1), CKMT2(2), CPS1(8), DAO(2), EPRS(10), GAMT(1), GATM(1), GLUD1(2), GLUD2(4), GOT1(5), GOT2(1), LAP3(1), NOS1(5), NOS3(2), OTC(4), P4HA2(2), P4HA3(1), RARS(2), RARS2(3) 8004672 69 31 69 25 22 19 0 17 11 0 0.966 1.000 558 HSA00190_OXIDATIVE_PHOSPHORYLATION Genes involved in oxidative phosphorylation ATP12A, ATP4A, ATP4B, ATP5A1, ATP5B, ATP5C1, ATP5D, ATP5E, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP5I, ATP5J, ATP5J2, ATP5L, ATP5O, ATP6, ATP6AP1, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E1, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ATP8, COX1, COX10, COX15, COX17, COX2, COX3, COX4I1, COX4I2, COX5A, COX5B, COX6A1, COX6A2, COX6B1, COX6B2, COX6C, COX7A1, COX7A2, COX7B, COX7B2, COX7C, COX8A, COX8C, CYC1, CYTB, LHPP, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA1, NDUFA10, NDUFA11, NDUFA12, NDUFA13, NDUFA2, NDUFA3, NDUFA4, NDUFA4L2, NDUFA5, NDUFA6, NDUFA7, NDUFA8, NDUFA9, NDUFAB1, NDUFB1, NDUFB10, NDUFB11, NDUFB2, NDUFB3, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFB8, NDUFB9, NDUFC1, NDUFC2, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS5, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NDUFV3, PPA1, PPA2, SDHA, SDHB, SDHC, SDHD, TCIRG1, UCRC, UQCR, UQCRB, UQCRC1, UQCRC2, UQCRFS1, UQCRH, UQCRQ 113 ATP12A(13), ATP4A(8), ATP4B(1), ATP5A1(2), ATP5B(4), ATP5C1(2), ATP5D(1), ATP5F1(1), ATP5G3(1), ATP5J2(1), ATP5O(2), ATP6AP1(2), ATP6V0A1(2), ATP6V0A2(2), ATP6V0A4(4), ATP6V0D1(2), ATP6V0D2(6), ATP6V1A(2), ATP6V1B1(4), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1E1(1), ATP6V1E2(2), ATP6V1G2(1), ATP6V1G3(1), ATP6V1H(2), COX10(2), COX15(1), COX17(1), COX4I1(2), COX4I2(2), COX6A2(1), COX6C(1), COX7A1(1), COX7B2(1), COX8C(1), CYC1(1), LHPP(1), NDUFA1(1), NDUFA10(2), NDUFA12(2), NDUFA13(1), NDUFA4(1), NDUFA9(2), NDUFB1(1), NDUFB2(1), NDUFB3(1), NDUFB6(1), NDUFB9(1), NDUFC2(1), NDUFS1(4), NDUFS3(2), NDUFS6(2), NDUFV1(2), PPA1(2), PPA2(1), SDHA(5), SDHB(2), SDHD(1), TCIRG1(2), UQCRB(2), UQCRC1(2), UQCRC2(2), UQCRFS1(1), UQCRH(1) 12651670 133 44 132 32 55 36 1 29 12 0 0.969 1.000 559 DEATHPATHWAY Death receptors such as Fas and DR3, 4, and 5 transduce pro-apoptotic signaling by oligomerizing to activate the caspase cascade. APAF1, BCL2, BID, BIRC2, BIRC3, BIRC4, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHUK, CYCS, DFFA, DFFB, FADD, GAS2, LMNA, MAP3K14, NFKB1, NFKBIA, RELA, RIPK1, SPTAN1, TNFRSF10A, TNFRSF10B, TNFRSF25, TNFSF10, TNFSF12, TRADD, TRAF2 31 APAF1(7), BCL2(1), BID(1), BIRC2(2), BIRC3(2), CASP10(2), CASP3(1), CASP6(1), CASP7(1), CASP9(2), CFLAR(2), CHUK(4), DFFA(2), DFFB(2), GAS2(2), MAP3K14(2), NFKB1(3), RELA(2), RIPK1(2), SPTAN1(9), TNFRSF10A(3), TNFRSF10B(2), TNFSF10(1), TNFSF12(2), TRADD(1), TRAF2(1) 7256651 60 31 60 27 22 15 0 18 4 1 0.970 1.000 560 NICOTINATE_AND_NICOTINAMIDE_METABOLISM AOX1, CD38, ENPP1, ENPP3, NADSYN1, NMNAT1, NMNAT2, NNMT, NNT, NP, NT5C, NT5E, NT5M, QPRT 13 AOX1(5), CD38(1), ENPP1(4), ENPP3(3), NADSYN1(2), NMNAT1(1), NMNAT2(1), NNMT(1), NNT(1), NT5E(2), NT5M(1), QPRT(1) 3362885 23 16 23 11 9 8 0 4 2 0 0.970 1.000 561 ST_GA13_PATHWAY G-alpha-13 influences the actin cytoskeleton and activates protein kinase D, PI3K, and Pyk2. AKT1, AKT2, AKT3, ARHGEF11, BCL2, BF, CDC42, DLG4, GNA13, IKBKG, LPA, MAP2K4, MAP3K1, MAP3K5, MAPK8, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PDK1, PHKA2, PI3, PIK3CB, PLD1, PLD2, PLD3, PRKCM, PTK2, RDX, ROCK1, ROCK2, SERPINA4, SRF, TBXA2R 33 AKT1(2), AKT2(5), ARHGEF11(9), BCL2(1), DLG4(2), GNA13(2), LPA(9), MAP3K1(6), MAP3K5(5), MAPK8(2), NFKB1(3), NFKB2(2), NFKBIB(1), NFKBIE(2), PHKA2(5), PIK3CB(2), PLD1(8), PLD2(1), PLD3(5), PTK2(5), RDX(2), ROCK1(8), ROCK2(2), SERPINA4(2), SRF(3) 10647426 94 39 94 34 40 17 1 25 11 0 0.971 1.000 562 ARENRF2PATHWAY Nrf1 and nrf2 are transcription factors that bind to antioxidant response elements (AREs), promoters of genes involved in oxidative damage control. CREB1, FOS, FXYD2, JUN, KEAP1, MAFF, MAFG, MAFK, MAPK1, MAPK14, MAPK8, NFE2L2, PRKCA, PRKCB1 12 CREB1(1), KEAP1(3), MAPK1(2), MAPK14(3), MAPK8(2), NFE2L2(1), PRKCA(2) 1909327 14 9 14 3 2 5 0 7 0 0 0.973 1.000 563 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 AGPAT1(1), AGPAT3(3), AGPAT4(6), AGPAT6(1), CDS1(1), CDS2(4), CHAT(6), CHKA(2), DGKA(1), DGKB(7), DGKD(9), DGKE(1), DGKG(3), DGKH(5), DGKI(6), DGKZ(2), ESCO1(7), ESCO2(3), ETNK1(2), ETNK2(1), GNPAT(1), GPAM(2), GPD1(1), GPD1L(2), GPD2(3), LCAT(1), MYST3(13), MYST4(5), PCYT1A(4), PCYT1B(5), PEMT(1), PLA2G1B(1), PLA2G2F(1), PLA2G4A(5), PLA2G6(2), PLD1(8), PLD2(1), PNPLA3(4), PPAP2B(1), PTDSS1(4), SH3GLB1(3) 14992014 139 47 138 56 50 38 1 40 10 0 0.974 1.000 564 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(3), AASDHPPT(2), AASS(7), ACAT1(1), ACAT2(2), ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH9A1(1), BBOX1(1), DOT1L(3), ECHS1(2), EHHADH(2), EHMT1(2), EHMT2(1), GCDH(3), HADHA(2), PLOD1(3), PLOD2(4), PLOD3(3), SDS(2), SHMT1(1), SHMT2(2), TMLHE(1) 8307032 76 34 76 17 29 17 0 20 10 0 0.974 1.000 565 STRESSPATHWAY Tumor necrosis factor receptor TNFR1 promotes apoptosis and activates the pro-inflammatory NF-kB, while TNFR2 activates stress-activated protein kinases (SAPKs). ATF1, CASP2, CHUK, CRADD, IKBKB, IKBKG, JUN, LTA, MAP2K3, MAP2K4, MAP2K6, MAP3K1, MAP3K14, MAP4K2, MAPK14, MAPK8, NFKB1, NFKBIA, RELA, RIPK1, TANK, TNF, TNFRSF1A, TRADD, TRAF2 23 ATF1(1), CASP2(4), CHUK(4), CRADD(1), IKBKB(2), MAP2K3(2), MAP2K6(2), MAP3K1(6), MAP3K14(2), MAPK14(3), MAPK8(2), NFKB1(3), RELA(2), RIPK1(2), TANK(3), TNFRSF1A(1), TRADD(1), TRAF2(1) 5189587 42 22 42 18 18 11 4 6 3 0 0.974 1.000 566 HSA00625_TETRACHLOROETHENE_DEGRADATION Genes involved in tetrachloroethene degradation AKR1B10, EPHX2, HSD3B7, RDH11, RDH12, RDH13, RDH14 7 EPHX2(1), HSD3B7(2), RDH12(2), RDH13(1) 1067763 6 5 6 3 3 1 0 2 0 0 0.975 1.000 567 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 127 ACACA(14), ACACB(14), AKT1(2), AKT2(5), ARAF(3), BAD(1), CBL(2), CBLB(6), CRKL(2), EXOC7(1), FASN(1), FBP2(2), FLOT1(3), FOXO1(1), G6PC(3), GCK(1), GRB2(2), GSK3B(7), GYS1(1), GYS2(8), IKBKB(2), INPP5D(2), INSR(5), IRS1(5), IRS4(11), LIPE(3), MAP2K1(3), MAPK1(2), MAPK10(4), MAPK3(2), MAPK8(2), MAPK9(3), MKNK1(1), MKNK2(2), PCK2(3), PDE3A(5), PDE3B(2), PDPK1(1), PFKL(1), PFKM(1), PFKP(2), PHKA1(4), PHKA2(5), PHKB(4), PHKG2(2), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PKM2(2), PPARGC1A(5), PPP1CB(1), PPP1CC(1), PPP1R3A(8), PPP1R3B(1), PPP1R3C(2), PPP1R3D(1), PRKAA1(2), PRKAA2(6), PRKAB1(1), PRKAB2(1), PRKACB(1), PRKACG(2), PRKAG1(1), PRKAG2(2), PRKAG3(4), PRKAR1A(1), PRKAR1B(1), PRKAR2B(2), PRKCI(4), PRKX(2), PTPN1(4), PTPRF(8), PYGB(4), PYGL(2), PYGM(2), RAF1(4), RAPGEF1(4), RPS6KB1(3), RPS6KB2(1), SHC1(3), SHC3(1), SHC4(5), SLC2A4(3), SOCS2(2), SORBS1(7), SOS1(5), SOS2(9), SREBF1(1), TSC1(3), TSC2(1) 34862232 302 75 298 119 105 71 8 87 31 0 0.975 1.000 568 HSA00030_PENTOSE_PHOSPHATE_PATHWAY Genes involved in pentose phosphate pathway ALDOA, ALDOB, ALDOC, DERA, FBP1, FBP2, G6PD, GPI, H6PD, PFKL, PFKM, PFKP, PGD, PGLS, PGM1, PGM3, PRPS1, PRPS1L1, PRPS2, RBKS, RPE, RPIA, TALDO1, TKT, TKTL1, TKTL2 26 ALDOA(1), ALDOB(5), ALDOC(1), DERA(1), FBP2(2), G6PD(2), GPI(1), H6PD(3), PFKL(1), PFKM(1), PFKP(2), PGD(1), PGM1(2), PGM3(4), PRPS1L1(1), PRPS2(2), RPE(2), RPIA(3), TALDO1(3), TKT(3), TKTL1(4), TKTL2(5) 5372056 50 28 50 16 20 12 0 16 2 0 0.976 1.000 569 TNFR1PATHWAY Tumor necrosis factor alpha binds to its receptor TNFR1 and induces caspase-dependent apoptosis. ADPRT, ARHGDIB, BAG4, CASP2, CASP3, CASP8, CRADD, DFFA, DFFB, FADD, JUN, LMNA, LMNB1, LMNB2, MADD, MAP2K4, MAP3K1, MAP3K7, MAPK8, PAK1, PAK2, PRKDC, RB1, RIPK1, SPTAN1, TNF, TNFRSF1A, TRADD, TRAF2 26 ARHGDIB(3), BAG4(2), CASP2(4), CASP3(1), CRADD(1), DFFA(2), DFFB(2), LMNB1(2), LMNB2(1), MADD(13), MAP3K1(6), MAP3K7(2), MAPK8(2), PAK1(4), PAK2(2), PRKDC(13), RB1(4), RIPK1(2), SPTAN1(9), TNFRSF1A(1), TRADD(1), TRAF2(1) 7973716 78 31 78 31 23 20 4 19 10 2 0.976 1.000 570 NFKBPATHWAY Inactive nuclear factor kB (NF-kB) is inhibited by the IkB family in the cytoplasm; active NF-kB is localized in the nucleus and regulates transcription of a variety of genes. CHUK, FADD, IKBKB, IKBKG, IL1A, IL1R1, IRAK1, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MYD88, NFKB1, NFKBIA, RELA, RIPK1, TLR4, TNF, TNFAIP3, TNFRSF1A, TNFRSF1B, TRADD, TRAF6 21 CHUK(4), IKBKB(2), IL1A(1), IL1R1(3), IRAK1(1), MAP3K1(6), MAP3K14(2), MAP3K7(2), MYD88(1), NFKB1(3), RELA(2), RIPK1(2), TLR4(7), TNFAIP3(2), TNFRSF1A(1), TRADD(1), TRAF6(4) 5376907 44 21 44 15 18 7 2 12 5 0 0.977 1.000 571 HSA00072_SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES Genes involved in synthesis and degradation of ketone bodies ACAT1, ACAT2, BDH1, BDH2, HMGCL, HMGCS1, HMGCS2, OXCT1, OXCT2 9 ACAT1(1), ACAT2(2), BDH1(1), HMGCS1(1), OXCT1(3), OXCT2(1) 1654560 9 8 9 3 4 1 0 4 0 0 0.978 1.000 572 HSA00500_STARCH_AND_SUCROSE_METABOLISM Genes involved in starch and sucrose metabolism AGL, AMY1A, AMY1B, AMY1C, AMY2A, AMY2B, ASCC3, ASCC3L1, ATP13A2, DDX18, DDX19A, DDX23, DDX4, DDX41, DDX47, DDX50, DDX51, DDX52, DDX54, DDX55, DDX56, DHX58, ENPP1, ENPP3, ENTPD7, EP400, ERCC2, ERCC3, G6PC, G6PC2, GAA, GANC, GBA, GBA3, GBE1, GCK, GPI, GUSB, GYS1, GYS2, HK1, HK2, HK3, IFIH1, LYZL1, MGAM, MOV10L1, NUDT5, NUDT8, PGM1, PGM3, PYGB, PYGL, PYGM, RAD54B, RAD54L, RUVBL2, SETX, SI, SKIV2L2, SMARCA2, SMARCA5, TREH, UGDH, UGP2, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, UXS1 80 AGL(8), AMY2A(3), ASCC3(14), ATP13A2(3), DDX18(2), DDX19A(2), DDX23(4), DDX4(2), DDX41(2), DDX47(3), DDX50(2), DDX52(1), DDX54(5), DDX55(2), DDX56(3), DHX58(2), ENPP1(4), ENPP3(3), ENTPD7(4), EP400(18), ERCC2(4), ERCC3(6), G6PC(3), GANC(2), GBA3(3), GBE1(4), GCK(1), GPI(1), GUSB(2), GYS1(1), GYS2(8), HK1(6), HK2(3), HK3(4), IFIH1(5), MGAM(9), MOV10L1(6), PGM1(2), PGM3(4), PYGB(4), PYGL(2), PYGM(2), RAD54B(6), RAD54L(3), RUVBL2(1), SETX(11), SI(12), SKIV2L2(2), SMARCA2(8), SMARCA5(3), TREH(2), UGDH(3), UGP2(5), UGT1A1(1), UGT1A10(1), UGT1A3(2), UGT1A4(1), UGT1A5(3), UGT1A7(2), UGT1A9(5), UGT2A1(8), UGT2A3(5), UGT2B10(1), UGT2B11(4), UGT2B15(2), UGT2B17(4), UGT2B28(2), UGT2B4(2), UGT2B7(4), UXS1(6) 26917431 278 64 274 85 96 76 3 69 33 1 0.978 1.000 573 HSA00061_FATTY_ACID_BIOSYNTHESIS Genes involved in fatty acid biosynthesis ACACA, ACACB, FASN, MCAT, OLAH, OXSM 6 ACACA(14), ACACB(14), FASN(1), MCAT(1), OLAH(1), OXSM(4) 3645065 35 18 35 8 13 10 0 10 2 0 0.978 1.000 574 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(2), CHST12(2), CHST13(1), PAPSS1(1), PAPSS2(2), SULT1A1(2), SULT1A2(1), SULT1E1(1), SULT2A1(1), SULT2B1(1), SUOX(2) 2068896 17 11 17 3 9 2 0 3 3 0 0.979 1.000 575 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(4), DUSP1(2), IKBKAP(2), IKBKB(2), MAP3K1(6), MAP3K14(2), NFKB1(3), RELA(2), RIPK1(2), TANK(3), TNFAIP3(2), TRAF1(1), TRAF2(1), TRAF3(4) 4932283 36 21 36 13 19 6 0 7 4 0 0.980 1.000 576 HSA00511_N_GLYCAN_DEGRADATION Genes involved in N-glycan degradation AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2B1, MAN2B2, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 15 AGA(3), FUCA1(1), GLB1(3), HEXB(1), LCT(15), MAN2B1(4), MAN2B2(1), MAN2C1(6), MANBA(6), NEU2(1), NEU3(1) 4503008 42 23 42 15 15 14 1 11 1 0 0.982 1.000 577 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 42 AKT1(2), AKT2(5), EIF4B(1), HIF1A(1), IGF1(2), MAPK1(2), MAPK3(2), PDPK1(1), PGF(1), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(5), PIK3R2(1), PIK3R5(1), PRKAA1(2), PRKAA2(6), RICTOR(10), RPS6KA1(1), RPS6KA2(8), RPS6KA3(3), RPS6KA6(5), RPS6KB1(3), RPS6KB2(1), TSC1(3), TSC2(1), ULK2(4), ULK3(3), VEGFA(2), VEGFB(2), VEGFC(3) 11043171 97 37 96 28 34 21 2 24 16 0 0.982 1.000 578 ATRBRCAPATHWAY BRCA1 and 2 block cell cycle progression in response to DNA damage and promote double-stranded break repair; mutations induce breast cancer susceptibility. ATM, ATR, BRCA1, BRCA2, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, HUS1, MRE11A, NBS1, RAD1, RAD17, RAD50, RAD51, RAD9A, TP53, TREX1 19 ATR(13), BRCA1(5), BRCA2(11), CHEK1(1), CHEK2(1), FANCA(5), FANCC(3), FANCD2(7), FANCF(1), FANCG(2), HUS1(1), MRE11A(3), RAD1(1), RAD17(2), RAD50(5), TREX1(2) 8371032 63 26 63 12 21 10 5 16 11 0 0.982 1.000 579 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(7), CLOCK(5), CRY1(2), CRY2(1), PER1(1) 1928382 16 10 16 4 7 2 0 5 2 0 0.982 1.000 580 BIOSYNTHESIS_OF_STEROIDS DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, IDI1, LSS, MVD, MVK, NQO1, NQO2, PMVK, SC5DL, SQLE, VKORC1 14 DHCR7(2), FDFT1(2), HMGCR(2), IDI1(1), LSS(1), MVK(1), NQO1(1), PMVK(1), SC5DL(1), SQLE(1) 2478269 13 12 13 6 7 4 0 1 1 0 0.983 1.000 581 RNAPATHWAY dsRNA-activated protein kinase phosphorylates elF2a, which generally inhibits translation, and activates NF-kB to provoke inflammation. CHUK, DNAJC3, EIF2S1, EIF2S2, MAP3K14, NFKB1, NFKBIA, PRKR, RELA, TP53 8 CHUK(4), DNAJC3(1), EIF2S2(1), MAP3K14(2), NFKB1(3), RELA(2) 1979947 13 7 13 5 8 2 0 1 2 0 0.984 1.000 582 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(4), CDC40(3), CLK3(2), CLK4(2), COL2A1(8), CPSF1(4), CPSF2(1), CPSF3(1), CPSF4(3), CSTF1(1), CSTF2T(5), CSTF3(2), DDX1(4), DDX20(3), DHX15(1), DHX16(6), DHX38(10), DHX8(6), DHX9(4), DICER1(7), DNAJC8(2), METTL3(3), NCBP1(4), NCBP2(1), NONO(1), NUDT21(1), NXF1(5), PABPN1(1), PAPOLA(2), PHF5A(1), POLR2A(6), PPM1G(1), PRPF18(3), PRPF3(1), PRPF4(4), PRPF4B(3), PRPF8(9), PSKH1(1), PTBP1(1), PTBP2(3), RBM17(2), RBM5(1), RNGTT(6), RNMT(3), SF3A1(2), SF3A2(1), SF3A3(1), SF3B1(9), SF3B2(2), SF3B4(4), SFRS14(2), SFRS4(2), SNRPB2(1), SNRPE(2), SNRPN(2), SNURF(1), SPOP(2), SRPK1(7), SRPK2(2), SRRM1(8), SUPT5H(10), TXNL4A(1), U2AF1(1), U2AF2(2), XRN2(6) 23732676 210 63 210 60 69 53 3 51 34 0 0.985 1.000 583 NDKDYNAMINPATHWAY Endocytotic role of NDK, Phosphins and Dynamin AMPH, AP2A1, AP2M1, BIN1, CALM1, CALM2, CALM3, DNM1, EPN1, EPS15, NME1, NME2, PICALM, PPP3CA, PPP3CB, PPP3CC, SYNJ1, SYNJ2, SYT1 19 AMPH(7), AP2A1(2), AP2M1(4), BIN1(1), DNM1(8), EPN1(1), EPS15(4), PICALM(2), PPP3CA(1), PPP3CB(4), PPP3CC(3), SYNJ1(8), SYNJ2(5), SYT1(1) 4961899 51 22 49 22 14 11 1 13 12 0 0.986 1.000 584 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 RPL10A(1), RPL10L(2), RPL18A(1), RPL21(1), RPL22L1(1), RPL24(1), RPL28(1), RPL3(2), RPL31(2), RPL32(1), RPL35(1), RPL39(1), RPL3L(1), RPL6(1), RPL7(1), RPL9(3), RPS11(1), RPS13(1), RPS16(1), RPS18(1), RPS20(1), RPS23(4), RPS3(1), RPS9(2), RPSA(1) 4720501 34 21 34 10 14 7 0 10 3 0 0.986 1.000 585 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 55 AK3(1), CAD(10), CDA(1), CTPS(3), CTPS2(4), DCK(1), DCTD(3), DHODH(3), DPYD(8), DPYS(6), ENTPD1(2), ITPA(2), NT5E(2), NT5M(1), POLB(1), POLD1(5), POLD2(1), POLE(17), POLG(4), POLQ(8), POLR1B(6), POLR2A(6), POLR2B(5), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLRMT(1), RRM1(1), RRM2(2), TK1(1), TXNRD1(2), TYMS(2), UCK2(1), UNG(1), UPB1(3) 12889515 118 42 116 30 36 34 3 36 9 0 0.987 1.000 586 HSA01032_GLYCAN_STRUCTURES_DEGRADATION Genes involved in degradation of glycan structures AGA, ARSB, FLJ21865, FUCA1, FUCA2, GALNS, GBA, GLB1, GNS, GUSB, HEXA, HEXB, HGSNAT, HPSE, HPSE2, HYAL1, HYAL2, IDS, IDUA, LCT, MAN2B1, MAN2B2, MAN2C1, MANBA, NAGLU, NEU1, NEU2, NEU3, NEU4, SPAM1 29 AGA(3), ARSB(5), FUCA1(1), GALNS(4), GLB1(3), GNS(1), GUSB(2), HEXB(1), HGSNAT(6), HPSE(2), HPSE2(9), IDS(2), IDUA(1), LCT(15), MAN2B1(4), MAN2B2(1), MAN2C1(6), MANBA(6), NAGLU(3), NEU2(1), NEU3(1), SPAM1(1) 7626724 78 31 77 26 27 18 2 23 8 0 0.988 1.000 587 TRANSLATION_FACTORS ANKHD1, ANKHD1, MASK_BP3, EEF1A2, EEF1B2, EEF1D, EEF1G, EEF2, EEF2K, EIF1AX, EIF1AY, EIF2AK1, EIF2AK2, EIF2AK3, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF3S1, EIF3S10, EIF3S2, EIF3S3, EIF3S4, EIF3S5, EIF3S6, EIF3S7, EIF3S8, EIF3S9, EIF4A1, EIF4A2, EIF4E, EIF4EBP1, EIF4EBP2, EIF4G1, EIF4G3, EIF5, EIF5A, EIF5B, ETF1, GSPT2, ITGB4BP, KIAA0664, PABPC1, PABPC3, PABPC1, LOC341315, PAIP1, PAIP1, LOC388345, SLC35A4, SUI1, WBSCR1 37 EEF1A2(1), EEF1G(1), EEF2(3), EIF2AK1(5), EIF2AK3(1), EIF2B1(2), EIF2B3(2), EIF2B5(5), EIF2S2(1), EIF2S3(1), EIF4A2(4), EIF4G1(8), EIF4G3(8), EIF5(3), EIF5A(1), EIF5B(4), ETF1(2), KIAA0664(4), PABPC1(3), PABPC3(4), PAIP1(1), SLC35A4(2) 9672283 66 34 65 19 21 15 2 18 10 0 0.990 1.000 588 GLYCOLYSIS_AND_GLUCONEOGENESIS Genes involved in glycolysis and gluconeogenesis ALDOA, ALDOB, ALDOC, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GAPDHS, GAPDS, GCK, GOT1, GOT2, GPI, HK1, HK2, HK3, LDHA, LDHAL6B, LDHB, LDHC, MDH1, MDH2, PC, PCK1, PDHA1, PDHA2, PDHB, PDHX, PFKL, PFKM, PFKP, PGAM1, PGAM2, PGK1, PGK2, PKLR, PKM2, TNFAIP1, TPI1 43 ALDOA(1), ALDOB(5), ALDOC(1), DLAT(2), ENO2(3), ENO3(3), FBP2(2), G6PC(3), GCK(1), GOT1(5), GOT2(1), GPI(1), HK1(6), HK2(3), HK3(4), LDHA(1), LDHAL6B(1), LDHB(1), LDHC(2), MDH1(1), MDH2(1), PC(3), PDHA1(4), PDHA2(6), PDHB(2), PDHX(2), PFKL(1), PFKM(1), PFKP(2), PGAM1(3), PGAM2(1), PGK1(3), PGK2(6), PKM2(2), TNFAIP1(3), TPI1(1) 9359869 88 36 87 30 38 17 1 25 7 0 0.990 1.000 589 HSA00100_BIOSYNTHESIS_OF_STEROIDS Genes involved in biosynthesis of steroids CYP27B1, CYP51A1, DHCR24, DHCR7, EBP, FDFT1, FDPS, GGCX, GGPS1, HMGCR, HSD17B7, IDI1, IDI2, LSS, MVD, MVK, NQO1, NSDHL, PMVK, SC4MOL, SC5DL, SQLE, TM7SF2, VKORC1 24 CYP27B1(3), CYP51A1(3), DHCR24(2), DHCR7(2), EBP(2), FDFT1(2), GGCX(2), HMGCR(2), IDI1(1), IDI2(1), LSS(1), MVK(1), NQO1(1), NSDHL(2), PMVK(1), SC5DL(1), SQLE(1) 4305366 28 19 28 9 10 7 1 6 4 0 0.990 1.000 590 GLYCINE_SERINE_AND_THREONINE_METABOLISM ABP1, AGXT, AGXT2, ALAS1, ALAS2, AMT, AOC2, AOC3, ATP6V0C, SHMT1, BHMT, CBS, CHDH, CHKA, CHKB, CHKB, CPT1B, CTH, DAO, DLD, DMGDH, GAMT, GARS, GATM, GCAT, GLDC, MAOA, MAOB, PEMT, PISD, PLCB2, PLCG1, PLCG2, PSPH, SARDH, SARS, SHMT1, SHMT2, TARS 37 ABP1(1), AGXT2(5), ALAS1(5), ALAS2(5), AOC2(4), AOC3(4), BHMT(3), CBS(2), CHDH(1), CHKA(2), CPT1B(5), CTH(1), DAO(2), DMGDH(5), GAMT(1), GARS(3), GATM(1), GLDC(2), MAOA(2), PEMT(1), PLCB2(3), PLCG1(4), PLCG2(9), SARDH(7), SARS(1), SHMT1(1), SHMT2(2), TARS(3) 9396084 85 36 84 30 38 22 0 14 11 0 0.991 1.000 591 HSA00052_GALACTOSE_METABOLISM Genes involved in galactose metabolism AKR1B1, AKR1B10, B4GALT1, B4GALT2, G6PC, G6PC2, GAA, GALE, GALK1, GALK2, GALT, GANC, GCK, GLA, GLB1, HK1, HK2, HK3, HSD3B7, LALBA, LCT, MGAM, PFKL, PFKM, PFKP, PGM1, PGM3, RDH11, RDH12, RDH13, RDH14, UGP2 32 AKR1B1(2), B4GALT1(5), B4GALT2(3), G6PC(3), GALE(1), GALK2(2), GALT(2), GANC(2), GCK(1), GLA(4), GLB1(3), HK1(6), HK2(3), HK3(4), HSD3B7(2), LCT(15), MGAM(9), PFKL(1), PFKM(1), PFKP(2), PGM1(2), PGM3(4), RDH12(2), RDH13(1), UGP2(5) 8464403 85 33 85 31 39 23 1 19 3 0 0.991 1.000 592 HSA03060_PROTEIN_EXPORT Genes involved in protein export OXA1L, SEC61A2, SRP19, SRP54, SRP68, SRP72, SRP9, SRPR 8 OXA1L(2), SEC61A2(1), SRP19(1), SRP54(1), SRP68(1), SRP72(3) 1699033 9 8 9 4 4 2 0 3 0 0 0.991 1.000 593 ETSPATHWAY The Ets transcription factors are activated by Ras and promote macrophage differentiation. CSF1, CSF1R, DDX20, E2F1, E2F4, ETS1, ETS2, ETV3, FOS, HDAC2, HDAC5, HRAS, JUN, NCOR2, RBL1, RBL2, SIN3A, SIN3B 18 CSF1(1), CSF1R(3), DDX20(3), E2F4(1), ETS2(2), HDAC2(2), HDAC5(1), NCOR2(2), RBL1(3), RBL2(8), SIN3A(4), SIN3B(3) 5863448 33 20 33 18 10 6 0 9 8 0 0.991 1.000 594 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 AGPAT1(1), AGPAT3(3), AGPAT4(6), AGPS(2), CDS1(1), CDS2(4), CHAT(6), CHKA(2), CLC(2), CPT1B(5), DGKA(1), DGKB(7), DGKD(9), DGKE(1), DGKG(3), DGKH(5), DGKZ(2), ETNK1(2), GNPAT(1), GPD1(1), GPD2(3), LCAT(1), PAFAH1B1(3), PCYT1A(4), PCYT1B(5), PEMT(1), PLA2G1B(1), PLA2G4A(5), PLA2G6(2), PLCB2(3), PLCG1(4), PLCG2(9), PPAP2B(1) 11282175 106 40 104 41 40 25 1 29 11 0 0.992 1.000 595 ARGININE_AND_PROLINE_METABOLISM ABP1, AGMAT, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH4A1, ALDH9A1, AMD1, AOC2, AOC3, ARG1, ARG2, ASL, ASS, CKB, CKM, CKMT1, CKMT1B, CKMT1A, CKMT2, CPS1, DAO, GAMT, GATM, GLUD1, GOT1, GOT2, MAOA, MAOB, NOS1, NOS2A, NOS3, OAT, ODC1, OTC, P4HA1, P4HA2, P4HA3, P4HB, PYCR1, RARS, SAT, SMS 43 ABP1(1), ALDH1A1(3), ALDH1A2(6), ALDH1A3(4), ALDH1B1(5), ALDH2(3), ALDH3A1(2), ALDH3A2(4), ALDH4A1(2), ALDH9A1(1), AOC2(4), AOC3(4), ARG1(1), ARG2(4), CKM(4), CKMT1B(1), CKMT2(2), CPS1(8), DAO(2), GAMT(1), GATM(1), GLUD1(2), GOT1(5), GOT2(1), MAOA(2), NOS1(5), NOS3(2), ODC1(2), OTC(4), P4HA2(2), P4HA3(1), P4HB(2), RARS(2), SMS(2) 9781881 95 35 95 32 36 27 0 22 10 0 0.992 1.000 596 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(17), ASH2L(2), C17orf79(1), CARM1(2), CTCFL(7), DOT1L(3), EED(2), EHMT1(2), EHMT2(1), EZH1(4), EZH2(4), FBXO11(4), JMJD6(2), KDM6A(1), MEN1(1), MLL(15), MLL2(14), MLL3(10), MLL4(8), MLL5(11), NSD1(11), OGT(4), PAXIP1(5), PPP1CB(1), PPP1CC(1), PRDM2(13), PRDM7(1), PRMT1(1), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(3), RBBP5(2), SATB1(1), SETD1A(7), SETD2(10), SETD7(2), SETD8(2), SETDB1(7), SETDB2(1), SMYD3(2), STK38(1), SUV39H1(1), SUV39H2(2), SUV420H1(5), SUZ12(2), WHSC1(6), WHSC1L1(4) 25649276 210 56 207 70 85 40 2 55 27 1 0.992 1.000 597 CHOLESTEROL_BIOSYNTHESIS C10orf110, CYP51A1, DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, HMGCS1, IDI1, LSS, MVD, MVK, NSDHL, PMVK, SC4MOL, SC5DL, SQLE 15 CYP51A1(3), DHCR7(2), FDFT1(2), HMGCR(2), HMGCS1(1), IDI1(1), LSS(1), MVK(1), NSDHL(2), PMVK(1), SC5DL(1), SQLE(1) 2946365 18 13 18 7 8 5 0 3 2 0 0.992 1.000 598 ST_TUMOR_NECROSIS_FACTOR_PATHWAY Tumor necrosis factor is a pro-inflammatory cytokine that activates NF-kB and c-Jun. BAG4, BIRC2, BIRC3, CASP3, CASP8, CFLAR, FADD, HRB, IKBKG, JUN, MAP2K4, MAP3K3, MAP3K7, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, NR2C2, RALBP1, RIPK1, TNF, TNFAIP3, TNFRSF1A, TNFRSF1B, TRADD, TRAF2 25 BAG4(2), BIRC2(2), BIRC3(2), CASP3(1), CFLAR(2), MAP3K3(2), MAP3K7(2), NFKB1(3), NFKB2(2), NFKBIB(1), NFKBIE(2), NR2C2(4), RALBP1(4), RIPK1(2), TNFAIP3(2), TNFRSF1A(1), TRADD(1), TRAF2(1) 5658027 36 22 36 10 12 10 1 12 1 0 0.993 1.000 599 HSA00532_CHONDROITIN_SULFATE_BIOSYNTHESIS Genes involved in chondroitin sulfate biosynthesis B3GALT6, B3GAT1, B3GAT2, B3GAT3, B4GALT7, ChGn, CHPF, CHST11, CHST12, CHST13, CHST14, CHST3, CHST7, CHSY-2, CHSY1, CSGlcA-T, DSE, GALNAC4S-6ST, GALNACT-2, UST, XYLT1, XYLT2 17 B3GAT1(1), CHPF(3), CHST11(2), CHST12(2), CHST13(1), CHST14(1), CHSY1(5), DSE(2), UST(1), XYLT1(4), XYLT2(2) 3125802 24 15 24 21 8 7 2 5 2 0 0.993 1.000 600 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 CDC7(2), CDK2(2), DIAPH2(9), GMNN(1), MCM10(6), MCM3(1), MCM4(4), MCM5(3), MCM6(3), MCM7(2), NACA(5), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(2), POLA2(2), POLD1(5), POLD2(1), POLD3(2), POLE(17), RFC1(10), RFC4(3), RFC5(2), RPA1(2), RPA2(1), RPA4(2), UBA52(2), UBB(1) 11275109 94 37 93 21 22 23 0 36 13 0 0.993 1.000 601 RNA_POLYMERASE POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT 14 POLR1B(6), POLR2A(6), POLR2B(5), POLR2D(1), POLR2E(1), POLR2H(1), POLR2I(1), POLRMT(1) 3030829 22 12 22 3 7 8 1 5 1 0 0.993 1.000 602 P38MAPKPATHWAY The Rho family GTPases activate the p38 MAPKs under environmental stress or in the presence of pro-inflammatory cytokines. ATF2, CDC42, CREB1, DAXX, DDIT3, ELK1, GRB2, HMGN1, HRAS, HSPB1, HSPB2, MAP2K4, MAP2K6, MAP3K1, MAP3K5, MAP3K7, MAP3K9, MAPK14, MAPKAPK2, MAPKAPK5, MAX, MEF2A, MEF2B, MEF2C, MEF2D, MKNK1, MYC, PDZGEF1, PLA2G4A, RAC1, RIPK1, RPS6KA5, SHC1, STAT1, TGFB1, TGFB2, TGFB3, TGFBR1, TRADD, TRAF2 38 CREB1(1), GRB2(2), HSPB2(1), MAP2K6(2), MAP3K1(6), MAP3K5(5), MAP3K7(2), MAP3K9(2), MAPK14(3), MAPKAPK2(3), MAPKAPK5(1), MAX(1), MEF2A(3), MEF2C(7), MEF2D(1), MKNK1(1), PLA2G4A(5), RIPK1(2), RPS6KA5(3), SHC1(3), STAT1(6), TGFB1(1), TGFB2(5), TGFBR1(6), TRADD(1), TRAF2(1) 7903522 74 27 72 25 29 19 2 16 8 0 0.994 1.000 603 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 38 APAF1(7), BAK1(1), BAX(1), BCL2(1), BCL2L1(1), BID(1), BIRC2(2), BIRC3(2), CASP2(4), CASP3(1), CASP6(1), CASP7(1), CASP9(2), FASLG(1), GZMB(1), MAP3K1(6), MAP3K14(2), MAPK10(4), MDM2(4), NFKB1(3), PARP1(4), RELA(2), RIPK1(2), TNFRSF1A(1), TNFSF10(1), TRADD(1), TRAF1(1), TRAF2(1) 7652944 59 29 59 25 23 16 2 15 3 0 0.994 1.000 604 MSPPATHWAY Macrophage stimulating protein is synthesized as pro-MSP by the liver and, on proteolysis, binds to monocyte receptor kinase RON to induce macrophage development. CCL2, CSF1, IL1B, MST1, MST1R, TNF 6 CSF1(1), MST1(1), MST1R(1) 1358366 3 3 3 1 1 1 0 1 0 0 0.995 1.000 605 STEROID_BIOSYNTHESIS CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 9 CYP17A1(2), F13B(3), HSD17B2(1), HSD17B3(1), HSD17B4(3), HSD3B1(2) 1844290 12 8 12 2 4 4 0 3 1 0 0.995 1.000 606 HSA00051_FRUCTOSE_AND_MANNOSE_METABOLISM Genes involved in fructose and mannose metabolism AKR1B1, AKR1B10, ALDOA, ALDOB, ALDOC, FBP1, FBP2, FPGT, FUK, GMDS, GMPPA, GMPPB, HK1, HK2, HK3, HSD3B7, KHK, LHPP, MPI, MTMR1, MTMR2, MTMR6, PFKFB1, PFKFB2, PFKFB3, PFKFB4, PFKL, PFKM, PFKP, PGM2, PHPT1, PMM1, PMM2, RDH11, RDH12, RDH13, RDH14, SORD, TPI1, TSTA3, UGCGL1, UGCGL2 40 AKR1B1(2), ALDOA(1), ALDOB(5), ALDOC(1), FBP2(2), FPGT(3), FUK(1), GMDS(1), GMPPA(6), HK1(6), HK2(3), HK3(4), HSD3B7(2), KHK(1), LHPP(1), MPI(1), MTMR1(4), MTMR2(1), MTMR6(4), PFKFB1(6), PFKFB4(2), PFKL(1), PFKM(1), PFKP(2), PHPT1(1), PMM1(1), RDH12(2), RDH13(1), TPI1(1), TSTA3(1) 8400861 68 33 68 32 27 14 0 22 5 0 0.996 1.000 607 FOLATE_BIOSYNTHESIS ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, DHFR, FPGS, GCH1, GGH, SPR 9 ALPI(2), ALPL(1), ALPP(1), GGH(1) 1353847 5 5 5 1 2 1 1 1 0 0 0.996 1.000 608 MAPKPATHWAY The mitogen-activated protein (MAP) kinase pathway is a common signaling mechanism and has four main sub-pathways: Erk, JNK/SAPK, p53, and ERK5. ARAF1, ATF2, BRAF, CEBPA, CHUK, CREB1, DAXX, ELK1, FOS, GRB2, HRAS, IKBKB, JUN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K14, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8, MAP3K9, MAP4K1, MAP4K2, MAP4K3, MAP4K4, MAP4K5, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK4, MAPK6, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, MAPKAPK5, MAX, MEF2A, MEF2B, MEF2C, MEF2D, MKNK1, MKNK2, MYC, NFKB1, NFKBIA, PAK1, PAK2, PDZGEF1, RAC1, RAF1, RELA, RIPK1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KA5, RPS6KB1, RPS6KB2, SHC1, SP1, STAT1, TGFB1, TGFB2, TGFB3, TGFBR1, TRADD, TRAF2 82 CHUK(4), CREB1(1), GRB2(2), IKBKB(2), MAP2K1(3), MAP2K3(2), MAP2K5(2), MAP2K6(2), MAP3K1(6), MAP3K10(2), MAP3K11(4), MAP3K12(4), MAP3K13(8), MAP3K14(2), MAP3K2(2), MAP3K3(2), MAP3K4(15), MAP3K5(5), MAP3K6(6), MAP3K7(2), MAP3K8(2), MAP3K9(2), MAP4K1(2), MAP4K3(3), MAP4K4(5), MAP4K5(2), MAPK1(2), MAPK10(4), MAPK12(2), MAPK14(3), MAPK3(2), MAPK4(1), MAPK6(2), MAPK7(3), MAPK8(2), MAPK9(3), MAPKAPK2(3), MAPKAPK3(1), MAPKAPK5(1), MAX(1), MEF2A(3), MEF2C(7), MEF2D(1), MKNK1(1), MKNK2(2), NFKB1(3), PAK1(4), PAK2(2), RAF1(4), RELA(2), RIPK1(2), RPS6KA1(1), RPS6KA2(8), RPS6KA3(3), RPS6KA5(3), RPS6KB1(3), RPS6KB2(1), SHC1(3), SP1(2), STAT1(6), TGFB1(1), TGFB2(5), TGFBR1(6), TRADD(1), TRAF2(1) 20608939 197 53 193 60 74 44 5 51 23 0 0.996 1.000 609 HSA00260_GLYCINE_SERINE_AND_THREONINE_METABOLISM Genes involved in glycine, serine and threonine metabolism ABP1, AGXT, AGXT2, AKR1B10, ALAS1, ALAS2, AMT, AOC2, AOC3, BHMT, CBS, CHDH, CHKA, CHKB, CTH, DAO, DLD, DMGDH, GAMT, GARS, GATM, GCAT, GLDC, GNMT, HSD3B7, MAOA, MAOB, PEMT, PHGDH, PIPOX, PISD, PSAT1, PSPH, RDH11, RDH12, RDH13, RDH14, SARDH, SARS, SARS2, SDS, SHMT1, SHMT2, TARS, TARS2 45 ABP1(1), AGXT2(5), ALAS1(5), ALAS2(5), AOC2(4), AOC3(4), BHMT(3), CBS(2), CHDH(1), CHKA(2), CTH(1), DAO(2), DMGDH(5), GAMT(1), GARS(3), GATM(1), GLDC(2), GNMT(1), HSD3B7(2), MAOA(2), PEMT(1), PHGDH(2), PIPOX(4), PSAT1(3), RDH12(2), RDH13(1), SARDH(7), SARS(1), SARS2(2), SDS(2), SHMT1(1), SHMT2(2), TARS(3), TARS2(4) 9632105 87 35 87 31 35 22 0 19 11 0 0.997 1.000 610 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 240 ACVR1C(2), AKT1(2), AKT2(5), ARRB1(1), BDNF(1), CACNA1A(8), CACNA1B(7), CACNA1C(10), CACNA1D(7), CACNA1E(15), CACNA1F(12), CACNA1G(10), CACNA1H(2), CACNA1I(3), CACNA1S(10), CACNA2D1(8), CACNA2D2(1), CACNA2D3(3), CACNA2D4(3), CACNB1(1), CACNB2(5), CACNB3(1), CACNG1(2), CACNG2(2), CACNG3(5), CACNG4(2), CACNG5(5), CACNG7(3), CACNG8(1), CASP3(1), CD14(1), CDC25B(5), CHUK(4), CRKL(2), DUSP1(2), DUSP10(4), DUSP16(3), DUSP3(1), DUSP4(1), DUSP5(1), DUSP6(4), DUSP7(1), DUSP9(1), ECSIT(2), EGF(3), EGFR(10), ELK4(1), FASLG(1), FGF1(2), FGF11(2), FGF12(2), FGF13(2), FGF14(5), FGF17(1), FGF20(1), FGF21(1), FGF23(1), FGF3(1), FGF5(2), FGF6(3), FGF7(1), FGF8(1), FGF9(1), FGFR1(3), FGFR2(1), FGFR3(2), FGFR4(2), FLNA(2), FLNB(14), FLNC(11), GNA12(2), GRB2(2), IKBKB(2), IL1A(1), IL1R1(3), IL1R2(3), MAP2K1(3), MAP2K3(2), MAP2K5(2), MAP2K6(2), MAP3K1(6), MAP3K10(2), MAP3K12(4), MAP3K13(8), MAP3K14(2), MAP3K2(2), MAP3K3(2), MAP3K4(15), MAP3K5(5), MAP3K6(6), MAP3K7(2), MAP3K8(2), MAP4K1(2), MAP4K3(3), MAP4K4(5), MAPK1(2), MAPK10(4), MAPK12(2), MAPK14(3), MAPK3(2), MAPK7(3), MAPK8(2), MAPK8IP1(2), MAPK8IP3(1), MAPK9(3), MAPKAPK2(3), MAPKAPK3(1), MAPKAPK5(1), MAPT(4), MAX(1), MEF2C(7), MKNK1(1), MKNK2(2), MOS(2), MRAS(1), NF1(5), NFATC2(3), NFATC4(4), NFKB1(3), NFKB2(2), NLK(1), NR4A1(2), NTF3(1), NTRK1(6), NTRK2(3), PAK1(4), PAK2(2), PDGFA(1), PDGFRA(13), PDGFRB(5), PLA2G1B(1), PLA2G2F(1), PLA2G4A(5), PLA2G6(2), PPM1A(7), PPM1B(1), PPP3CA(1), PPP3CB(4), PPP3CC(3), PPP3R1(1), PPP3R2(1), PPP5C(2), PRKACB(1), PRKACG(2), PRKCA(2), PRKCG(8), PRKX(2), PTPN5(1), PTPN7(1), PTPRR(1), RAF1(4), RAP1A(1), RAP1B(2), RAPGEF2(8), RASA1(5), RASA2(1), RASGRF1(9), RASGRF2(5), RASGRP1(2), RASGRP2(5), RASGRP3(4), RASGRP4(1), RPS6KA1(1), RPS6KA2(8), RPS6KA3(3), RPS6KA5(3), RPS6KA6(5), RRAS2(1), SOS1(5), SOS2(9), SRF(3), STK3(3), STK4(3), STMN1(1), TAOK1(5), TAOK2(2), TAOK3(4), TGFB1(1), TGFB2(5), TGFBR1(6), TNFRSF1A(1), TRAF2(1), TRAF6(4), ZAK(4) 60802963 608 96 599 229 253 127 12 151 63 2 0.997 1.000 611 HSA00790_FOLATE_BIOSYNTHESIS Genes involved in folate biosynthesis ALPI, ALPL, ALPP, ALPPL2, ASCC3, ASCC3L1, ATP13A2, DDX18, DDX19A, DDX23, DDX4, DDX41, DDX47, DDX50, DDX51, DDX52, DDX54, DDX55, DDX56, DHFR, DHX58, ENTPD7, EP400, ERCC2, ERCC3, FPGS, GCH1, GGH, IFIH1, MOV10L1, NUDT5, NUDT8, PTS, QDPR, RAD54B, RAD54L, RUVBL2, SETX, SKIV2L2, SMARCA2, SMARCA5, SPR 41 ALPI(2), ALPL(1), ALPP(1), ASCC3(14), ATP13A2(3), DDX18(2), DDX19A(2), DDX23(4), DDX4(2), DDX41(2), DDX47(3), DDX50(2), DDX52(1), DDX54(5), DDX55(2), DDX56(3), DHX58(2), ENTPD7(4), EP400(18), ERCC2(4), ERCC3(6), GGH(1), IFIH1(5), MOV10L1(6), RAD54B(6), RAD54L(3), RUVBL2(1), SETX(11), SKIV2L2(2), SMARCA2(8), SMARCA5(3) 14115773 129 40 126 38 54 35 3 24 12 1 0.997 1.000 612 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(7), AZIN1(2), BTG1(1), CBX3(1), CLOCK(5), CRY1(2), CRY2(1), DNAJA1(1), EIF4G2(7), ETV6(4), GFRA1(3), GSTM3(2), HERPUD1(1), HSPA8(3), IDI1(1), MYF6(1), NCKAP1(8), NCOA4(3), NR1D2(3), PER1(1), PER2(2), PPP1R3C(2), PSMA4(2), SF3A3(1), SUMO3(1), TUBB3(1), UCP3(2), UGP2(5), ZFR(1) 8255610 74 29 72 17 33 14 3 16 8 0 0.997 1.000 613 HIVNEFPATHWAY HIV-infected CD4 helper T cells may express Fas ligand, which binds to the Fas receptors of uninfected cells and induces apoptosis. ACTG1, ADPRT, APAF1, ARHGDIB, BAG4, BCL2, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CDC2L1, CDC2L2, CFLAR, CHUK, CRADD, CYCS, DAXX, DFFA, DFFB, FADD, GSN, LMNA, LMNB1, LMNB2, MAP2K7, MAP3K1, MAP3K14, MAP3K5, MAPK8, MDM2, NFKB1, NFKBIA, NUMA1, PAK2, PRKCD, PRKDC, PSEN1, PSEN2, PTK2, RASA1, RB1, RELA, RIPK1, SPTAN1, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TRADD, TRAF1, TRAF2 51 APAF1(7), ARHGDIB(3), BAG4(2), BCL2(1), BID(1), BIRC2(2), BIRC3(2), CASP2(4), CASP3(1), CASP6(1), CASP7(1), CASP9(2), CFLAR(2), CHUK(4), CRADD(1), DFFA(2), DFFB(2), LMNB1(2), LMNB2(1), MAP3K1(6), MAP3K14(2), MAP3K5(5), MAPK8(2), MDM2(4), NFKB1(3), NUMA1(8), PAK2(2), PRKCD(3), PRKDC(13), PSEN1(3), PSEN2(2), PTK2(5), RASA1(5), RB1(4), RELA(2), RIPK1(2), SPTAN1(9), TNFRSF1A(1), TRADD(1), TRAF1(1), TRAF2(1) 14812128 125 41 125 44 40 33 5 33 12 2 0.999 1.000 614 ATMPATHWAY The tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair. ABL1, ATM, BRCA1, CDKN1A, CHEK1, CHEK2, GADD45A, JUN, MAPK8, MDM2, MRE11A, NBS1, NFKB1, NFKBIA, RAD50, RAD51, RBBP8, RELA, TP53, TP73 17 ABL1(4), BRCA1(5), CDKN1A(1), CHEK1(1), CHEK2(1), MAPK8(2), MDM2(4), MRE11A(3), NFKB1(3), RAD50(5), RBBP8(2), RELA(2) 5127746 33 17 33 7 9 12 2 6 4 0 0.999 1.000 615 HSA00563_GLYCOSYLPHOSPHATIDYLINOSITOL_ANCHOR_BIOSYNTHESIS Genes involved in glycosylphosphatidylinositol(GPI)-anchor biosynthesis GPAA1, GPLD1, PGAP1, PIGA, PIGB, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGU, PIGV, PIGW, PIGX, PIGZ 23 GPAA1(3), GPLD1(4), PGAP1(6), PIGA(1), PIGB(1), PIGG(1), PIGK(3), PIGM(1), PIGN(1), PIGO(2), PIGQ(1), PIGS(2), PIGT(2), PIGW(1), PIGX(2) 5321874 31 18 31 13 10 6 1 9 5 0 1.000 1.000 616 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 117141 0 0 0 1 0 0 0 0 0 0 1.000 1.000