Table 3.
KEGG pathways enriched by up and downregulated DEGs and the corresponding genes identified in pathway analysis (a) following perinatal alcohol exposure (b) following perinatal nicotine and alcohol exposure.
| Perinatal alcohol exposure | Perinatal nicotine-alcohol exposure | ||||
|---|---|---|---|---|---|
| KEGG term | P value | Genes | KEGG term | P value | Genes |
| Downregulated | Downregulated | ||||
| Glutamatergic synapse | 8.53E−04 | TRPC1, GRM2, HOMER3, GNG13, PRKCG, GRIA3, SLC38A1, GRIA4, SLC1A1 | MicroRNAs in cancer | 1.34E−02 | RECK, BAK1, NOTCH1, KRAS, PAK4, MDM4, PDCD4 |
| Protein processing in endoplasmic reticulum | 8.90E−03 | ATF6, UBE2E3, HERPUD1, UFD1L, RNF5, FBXO2, DNAJB12, SAR1B, EIF2AK4 | Metabolic pathways | 2.24E−02 | COASY, PPCS, HPRT1, EXTL1, ALDH3A2, HIBADH, GLDC, GOT2, CRYL1, AGPAT5, ST3GAL5, ST3GAL6, GGPS1, GALNT18, ATP6V0D1, IPMK, ALDOART2, SPTLC1, NME7, HYI, PGLS, PANK2, HSD11B1, LCLAT1, GPAM, SMPD3, UGP2 |
| MicroRNAs in cancer | 1.23E−02 | RECK, DNMT3A, NOTCH1, KRAS, PAK4, PRKCG, MDM4, PDCD4 | Pantothenate and CoA biosynthesis | 2.72E−02 | COASY, PANK2, PPCS |
| cAMP signaling pathway | 2.04E−02 | VAV3, RAC1, PPP1R12A, HTR4, NFKBIA, GRIA3, PAK1, GRIA4, VAV2 | Biosynthesis of antibiotics | 3.02E−02 | GOT2, ALDOART2, PGLS, GGPS1, UGP2, NME7, ALDH3A2, GLDC |
| Natural killer cell mediated cytotoxicity | 2.79E−02 | KRAS, VAV3, RAC1, PRKCG, PAK1, VAV2 | Signaling pathways regulating pluripotency of stem cells | 4.26E−02 | ACVR2A, WNT1, KRAS, SOX2, ID4, AXIN2 |
| Fc epsilon RI signaling pathway | 3.19E−02 | KRAS, VAV3, RAC1, PRKCG, VAV2 | Glycerolipid metabolism | 4.66E−02 | AGPAT5, LCLAT1, GPAM, ALDH3A2 |
| B cell receptor signaling pathway | 3.19E−02 | KRAS, VAV3, RAC1, NFKBIA, VAV2 | T cell receptor signaling pathway | 5.54E−02 | KRAS, PAK4, NFKBIA, PAK1, VAV2 |
| T cell receptor signaling pathway | 3.60E−02 | KRAS, VAV3, PAK4, NFKBIA, PAK1, VAV2 | Glutamatergic synapse | 7.24E−02 | TRPC1, GRM2, HOMER3, GRIA3, GRIA4 |
| Biosynthesis of antibiotics | 3.72E−02 | GOT2, ALDOART2, PGLS, HK2, GGPS1, UGP2, NME7, ALDH3A2, GLDC | Protein processing in endoplasmic reticulum | 8.00E−02 | ATF6, UBE2E3, BAK1, HERPUD1, FBXO2, DNAJB12 |
| Carbon metabolism | 5.98E−02 | GOT2, ALDOART2, PGLS, HK2, GLDC, PC | Hypertrophic cardiomyopathy (HCM) | 9.62E−02 | ACTC1, CACNG8, ITGB4, CACNB2 |
| Fc gamma R-mediated phagocytosis | 6.06E−02 | VAV3, RAC1, PRKCG, PAK1, VAV2 | Upregulated | ||
| Regulation of actin cytoskeleton | 8.43E−02 | KRAS, VAV3, PAK4, PIKFYVE, RAC1, PPP1R12A, PAK1, VAV2 | Hippo signaling pathway | 7.74E−05 | PARD3, YWHAZ, MOB1A, APC2, SOX2, BMPR2, TCF7L2, ACTG1, FRMD6, DLG4, LIMD1, YAP1, FGF1, BMP4, TGFBR1, SMAD1, TEAD3, PPP1CC, YWHAE, DVL1, PPP1CA, CCND1, YWHAH, YWHAQ, WNT7A, BMPR1A |
| MAPK signaling pathway | 1.56E−04 | FGFR2, FGFR1, FGFR3, GRB2, MRAS, MKNK2, PPP3R1, CACNB1, FASLG, SRF, CDC42, TNFRSF1A, MAPT, SOS2, FGF1, NFATC3, CHUK, CACNA2D1, NLK, MAP2K3, TGFBR1, TAB2, PRKCB, RPS6KA5, MAP4K3, MAPK1, MAP4K4, DUSP3, RPS6KA1, RASGRF1, MAPK14, NTRK2, PDGFRA, RAP1B, CACNA1B, DUSP6 | |||
| Chemokine signaling pathway | 8.84E−02 | KRAS, VAV3, RAC1, GNG13, NFKBIA, PAK1, VAV2 | Adherens junction | 1.64E−04 | PTPN6, FGFR1, PARD3, PTPRF, BAIAP2, TGFBR1, NLK, CREBBP, TCF7L2, IQGAP1, SRC, ACTG1, MAPK1, CDC42, PTPN1, SSX2IP |
| Ubiquitin mediated proteolysis | 9.72E−02 | UBE2E3, UBE2Z, FBXO2, RHOBTB1, CDC23, NEDD4L | Renal cell carcinoma | 2.64E−04 | GRB2, CREBBP, RBX1, CDC42, CUL2, MAPK1, HIF1A, ETS1, SOS2, SLC2A1, ARAF, VEGFA, TGFA, RAP1B, PIK3R2 |
| Upregulated | GABAergic synapse | 3.86E-04 | SLC38A5, GABRA2, GABRA1, GNAO1, GNAI2, SLC6A1, GABRB2, ADCY6, GABBR1, SRC, PRKCB, GNB2, TRAK2, GNB1, GLS, GNG5, CACNA1B | ||
| Endocytosis | 1.96E−06 | ARFGAP1, FGFR2, PARD3, FGFR3, CHMP5, CAPZA2, SNX2, VPS37B, VPS37C, SNX4, CLTC, SRC, CDC42, SMAP2, AP2B1, FOLR2, SH3GLB1, DNM3, RAB8A, PLD1, TGFBR1, RAB4A, RT1-A2, RT1-A1, ARPC1B, RAB31, PSD, ACAP3, IST1, ARPC5L, ARF3, IGF2R, RAB22A, PDGFRA, SH3KBP1, HGS, SNX32, SMURF1, BIN1, RT1-N2 | Endocytosis | 4.06E−04 | ARFGAP1, FGFR2, PARD3, FGFR3, CHMP5, CAPZA2, VPS37B, VPS37C, CYTH3, CLTC, SRC, CDC42, SMAP2, FOLR2, SH3GLB1, DNM3, RAB8A, PLD1, TGFBR1, RAB4A, RT1-A2, RT1-A1, ARPC1B, RAB31, CHMP1A, PSD, ACAP3, IST1, ARF3, IGF2R, RAB22A, PDGFRA, SH3KBP1, HGS, SMURF1, BIN1 |
| MicroRNAs in cancer | 4.80E−05 | DNMT3A, FGFR3, GRB2, CREBBP, BMPR2, TP63, ZEB2, UBE2I, CCNG1, PRKCB, DDIT4, RPS6KA5, SPRY2, EZR, CDKN1B, GLS, SOS2, NOTCH4, VEGFA, PDGFRA, PDGFRB, SHC1, ABL1, BMF | MicroRNAs in cancer | 4.92E−04 | DNMT3A, FGFR3, APC2, GRB2, CREBBP, BMPR2, TP63, ZEB2, UBE2I, CCNG1, PRKCB, DDIT4, RPS6KA5, CCND1, EZR, CDKN1B, GLS, SOS2, VEGFA, PDGFRA, SHC1, ABL1, BMF |
| MAPK signaling pathway | 5.85E−05 | FGFR2, FGFR1, FGFR3, GRB2, MRAS, MKNK2, PPP3R1, CACNB1, MAPKAPK2, SRF, CDC42, TNFRSF1A, MAPT, SOS2, FGF1, NFATC3, CHUK, CACNA2D1, LAMTOR3, MAP2K3, TGFBR1, TAB2, PRKCB, RPS6KA5, MAPK1, MAP4K4, DUSP3, RPS6KA1, RASGRF1, MAPK14, NTRK2, PDGFRA, PDGFRB, RAP1B, DUSP6 | Pathways in cancer | 1.21E−03 | FGFR2, FGFR1, FGFR3, APC2, GNAI2, GRB2, ADCY6, MITF, FOXO1, TFG, FASLG, ITGB1, TCF7L2, SUFU, TPM3, RBX1, EDNRB, CUL2, CDC42, SLC2A1, SOS2, TGFA, FGF1, GNG5, CHUK, TRAF3, PIK3R2, BMP4, CTBP1, RALBP1, TGFBR1, CREBBP, DVL1, PRKCB, MAPK1, CCND1, HIF1A, CDKN1B, GNB2, GNB1, VEGFA, ARAF, PDGFRA, GNAS, ABL1, WNT7A |
| Adherens junction | 2.26E−04 | PTPN6, FGFR1, PARD3, PTPRF, BAIAP2, TGFBR1, CREBBP, TCF7L2, IQGAP1, SRC, ACTG1, MAPK1, CDC42, PTPN1, SSX2IP | Neurotrophin signaling Pathway | 1.49E−03 | GRB2, FASLG, FOXO3, KIDINS220, YWHAE, RPS6KA5, CDC42, MAPK1, RPS6KA1, MAPK14, SOS2, NTRK2, PSEN2, SH2B3, SHC1, RAP1B, ABL1, ARHGDIA, ARHGDIB, PIK3R2 |
| Pathways in cancer | 3.30E−04 | FGFR2, FGFR1, FGFR3, GNAI2, GRB2, MITF, FOXO1, TFG, HDAC1L, ITGB1, TCF7L2, SUFU, TPM3, RBX1, EDNRB, CUL2, CDC42, SLC2A1, SOS2, TGFA, PLCB1, FGF1, TRAF4, CHUK, TRAF3, BMP4, CTBP1, RALBP1, TGFBR1, CREBBP, CDK2, DVL1, PRKCB, MAPK1, HIF1A, CDKN1B, GNB2, GNB1, VEGFA, ARAF, PDGFRA, PDGFRB, GNAS, ABL1, WNT7A | Central carbon metabolism in cancer | 1.70E−03 | FGFR2, FGFR1, FGFR3, PFKL, PGAM1, SIRT6, SIRT3, MAPK1, HIF1A, GLS, SLC2A1, PDGFRA, PIK3R2 |
| Hippo signaling pathway | 3.70E−04 | BMP4, YWHAZ, PARD3, TGFBR1, SOX2, BMPR2, TEAD3, SMAD1, PPP1CC, TCF7L2, YWHAE, DVL1, ACTG1, PPP1CA, YWHAH, FRMD6, CSNK1D, YWHAQ, DLG4, YAP1, FGF1, WNT7A, BMPR1A | Proteoglycans in cancer | 2.26E−03 | FGFR1, GRB2, MRAS, PPP1R12C, FASLG, ITGB1, IQGAP1, SRC, PXN, ACTG1, CDC42, EZR, ANK1, SOS2, PIK3R2, PTPN6, PPP1CC, DDX5, PRKCB, MAPK1, PPP1CA, CCND1, HIF1A, MAPK14, VEGFA, ARAF, WNT7A |
| Renal cell carcinoma | 3.88E−04 | GRB2, CREBBP, RBX1, CDC42, CUL2, MAPK1, HIF1A, ETS1, SOS2, SLC2A1, ARAF, VEGFA, TGFA, RAP1B | Retrograde endocannabinoid signaling | 2.52E−03 | GABRA2, GABRA1, GNAO1, GNAI2, GABRB2, ADCY6, GRIA4, PRKCB, MAPK1, DAGLA, SLC17A6, GNB2, GNB1, MAPK14, MGLL, GNG5, CACNA1B |
| Glutamatergic synapse | 4.42E−04 | DLGAP1, PLD1, GNAO1, GNAI2, GRIK1, PPP3R1, GRIN3A, GRIA4, KCNJ3, SHANK3, PRKCB, MAPK1, SLC17A6, GNB2, GNB1, GLS, DLG4, GNAS, PLCB1 | Glycerophospholipid metabolism | 2.89E−03 | PLD3, CHKA, CRLS1, CDIPT, PLD1, PLA2G15, CHKB, TAZ, LYPLA2, CHPT1, DGKE, DGKG, PLA2G3, AGPAT4, PTDSS1, AGPAT3 |
| Gap junction | 5.20E−04 | GNAI2, GRB2, TUBA3B, GJA1, SRC, PRKCB, MAPK1, CSNK1D, SOS2, TUBB5, PDGFRA, PDGFRB, GNAS, PLCB1, TUBA1A, TUBA1B | Glutamatergic synapse | 3.21E−03 | PLD1, GNAO1, GNAI2, GRIK1, ADCY6, PPP3R1, GRIN3A, GRIA4, SHANK3, PRKCB, MAPK1, SLC17A6, GNB2, GNB1, GLS, DLG4, GNAS, GNG5 |
| Central carbon metabolism in cancer | 7.74E−04 | FGFR2, FGFR1, FGFR3, PFKL, PGAM1, SIRT6, SIRT3, MAPK1, HIF1A, GLS, SLC2A1, PDGFRA, PDGFRB | Regulation of actin cytoskeleton | 6.40E−03 | FGFR2, FGFR1, FGFR3, APC2, MRAS, SSH3, PPP1R12C, ABI2, ITGB1, IQGAP1, SRC, PXN, ACTG1, CDC42, EZR, SOS2, BRK1, FGF1, PIK3R2, LIMK2, BAIAP2, PPP1CC, MAPK1, ARPC1B, PPP1CA, ARAF, PDGFRA |
| Regulation of actin cytoskeleton | 8.87E−04 | FGFR2, FGFR1, ENAH, FGFR3, SSH3, MRAS, PPP1R12C, ABI2, ITGB1, PXN, IQGAP1, SRC, ACTG1, CDC42, EZR, SOS2, BRK1, FGF1, LIMK2, BAIAP2, PPP1CC, MAPK1, ARPC1B, PPP1CA, ARPC5L, ARAF, PDGFRA, PDGFRB | Spliceosome | 8.06E−03 | SRSF10, TRA2B, DDX5, RBMX, HNRNPU, SF3A3, SMNDC1, HNRNPA3, HNRNPM, SRSF2, SRSF5, SRSF4, SRSF7, SRSF6, USP39, SNRNP70, HNRNPC, ACIN1, DDX42 |
| Glycerophospholipid metabolism | 3.32E−03 | PLD3, CHKA, CRLS1, CDIPT, PLD1, CHKB, TAZ, LYPLA2, CHPT1, DGKE, DGKG, PLA2G3, AGPAT4, PTDSS1, AGPAT3 | Axon guidance | 9.55E−03 | ABLIM2, GNAI2, LIMK2, PPP3R1, L1CAM, DPYSL2, ITGB1, SLIT1, EPHA5, MAPK1, CDC42, SEMA6B, SEMA6D, UNC5A, SEMA4B, SEMA4D, ABL1, NFATC3 |
| Neurotrophin signaling pathway | 3.33E−03 | GRB2, MAPKAPK2, FOXO3, YWHAE, RPS6KA5, CDC42, MAPK1, RPS6KA1, MAPK14, SOS2, NTRK2, PSEN2, CALM3, SHC1, RAP1B, ABL1, ARHGDIA, ARHGDIB | Ubiquitin mediated proteolysis | 1.08E−02 | SYVN1, UBE4A, ANAPC5, UBE2G1, UBE2G2, UBE2J1, BIRC6, UBE2I, CDC34, UBE2H, UBOX5, RBX1, CUL3, CUL2, PIAS4, UBE2K, KLHL9, SMURF1, TRIP12 |
| Rap1 signaling pathway | 3.68E−03 | FGFR2, FGFR1, PARD3, FGFR3, GNAI2, MRAS, ITGB1, APBB1IP, SRC, ACTG1, CDC42, PLCB1, FGF1, GNAO1, MAP2K3, PRKCB, MAPK1, MAPK14, VEGFA, PDGFRA, CALM3, PDGFRB, GNAS, RAP1B, EFNA4, PRKD3 | Oxytocin signaling pathway | 1.20E−02 | MYL6, CACNA2D1, CAMK1G, GNAO1, GNAI2, ADCY6, PPP1R12C, CACNB1, PPP3R1, NPR1, PPP1CC, SRC, PRKCB, ACTG1, MAPK1, PPP1CA, CCND1, PRKAA1, GNAS, NFATC3 |
| Axon guidance | 3.93E−03 | ABLIM2, GNAI2, LIMK2, PPP3R1, DPYSL2, ITGB1, SLIT1, EPHA5, MAPK1, CDC42, SEMA6B, SEMA6D, UNC5A, SEMA4B, EFNA4, SEMA4D, ABL1, NFATC3 | Morphine addiction | 1.35E−02 | GABRA2, GABRA1, GNAO1, GNAI2, GABRB2, ADCY6, GABBR1, PRKCB, GNB2, PDE2A, GNB1, GNAS, GNG5, CACNA1B |
| Ras signaling pathway | 4.51E−03 | FGFR2, FGFR1, FGFR3, GRB2, MRAS, CDC42, SOS2, SHC1, FGF1, CHUK, PLD1, RALBP1, PRKCB, MAPK1, GNB2, ETS1, GNB1, RASGRF1, VEGFA, PDGFRA, PDGFRB, CALM3, RAP1B, EFNA4, ABL1, KSR1, PLA2G3 | Ras signaling pathway | 1.40E−02 | FGFR2, FGFR1, FGFR3, GRB2, MRAS, FASLG, CDC42, SOS2, SHC1, FGF1, GNG5, CHUK, PIK3R2, PLD1, RALBP1, PRKCB, MAPK1, GNB2, ETS1, GNB1, RASGRF1, VEGFA, PDGFRA, RAP1B, PLA2G3, ABL1, KSR1 |
| Oxytocin signaling pathway | 4.69E−03 | MYL6, CACNA2D1, GNAO1, GNAI2, PPP1R12C, CACNB1, PPP3R1, NPR1, PPP1CC, KCNJ3, SRC, PRKCB, ACTG1, MAPK1, PPP1CA, CALM3, PRKAA1, GNAS, PLCB1, NFATC3 | Alcoholism | 1.41E−02 | HIST2H2AA3, GNAO1, GNAI2, GRB2, LOC684797, HDAC10, GRIN3A, PPP1CC, HIST2H4, MAPK1, PPP1CA, GNB2, GNB1, HIST1H4B, SOS2, ARAF, NTRK2, H2AFY, SHC1, H3F3B, GNAS, GNG5 |
| Proteoglycans in cancer | 6.01E−03 | PTPN6, FGFR1, GRB2, MRAS, PPP1R12C, PPP1CC, DDX5, ITGB1, PXN, SRC, IQGAP1, PRKCB, ACTG1, CDC42, MAPK1, PPP1CA, EZR, HIF1A, ANK3, MAPK14, SOS2, ARAF, VEGFA, WNT7A | Protein processing in endoplasmic reticulum | 1.67E−02 | SYVN1, DERL1, UBE2G1, ERP29, UBE2G2, UBE2J1, MAN1B1, CALR, SEC63, SSR1, RBX1, HYOU1, ATXN3, STT3A, HSPA5, SEC24C, UGGT1, SSR2, DNAJC1, SEC61G, SEC61A2 |
| Notch signaling pathway | 6.01E−03 | DTX4, CTBP1, APH1A, DTX2, PSEN2, NOTCH4, CREBBP, HDAC1L, NCOR2, DVL1 | FoxO signaling pathway | 1.69E−02 | GRB2, NLK, TGFBR1, CREBBP, FASLG, FOXO1, FOXO3, MAPK1, PRMT1, CCND1, CDKN1B, MAPK14, SOS2, ARAF, PRKAA1, BCL6, CHUK, PIK3R2 |
| Long-term potentiation | 9.06E−03 | MAPK1, PPP1CA, RPS6KA1, ARAF, CREBBP, PPP3R1, CALM3, RAP1B, PPP1CC, PLCB1, PRKCB | Chronic myeloid leukemia | 1.71E−02 | MAPK1, CTBP1, CCND1, CDKN1B, GRB2, TGFBR1, SOS2, ARAF, SHC1, ABL1, CHUK, PIK3R2 |
| cGMP-PKG signaling pathway | 9.26E−03 | KCNMA1, ATP1B1, GNAI2, SLC25A5, PPP3R1, NPR1, PPP1CC, SRF, VDAC1, ATP2B1, EDNRB, MAPK1, PPP1CA, ATP2A2, PDE2A, GTF2IRD1, CALM3, ADRA2B, PLCB1, NFATC3 | Phosphatidylinositol signaling system | 1.88E−02 | INPP1, CDIPT, IMPAD1, PIK3C2A, TMEM55B, PRKCB, MTMR2, MTMR3, MTMR14, DGKE, DGKG, SYNJ2, PLCD4, PIK3R2 |
| Choline metabolism in cancer | 1.41E−02 | CHKA, PLD1, SLC44A1, GRB2, CHKB, CHPT1, PRKCB, MAPK1, HIF1A, DGKE, DGKG, SOS2, PDGFRA, PDGFRB | Rap1 signaling pathway | 2.05E−02 | FGFR2, FGFR1, TLN1, PARD3, FGFR3, GNAI2, MRAS, ADCY6, ITGB1, APBB1IP, SRC, ACTG1, CDC42, RAPGEF6, FGF1, PIK3R2, GNAO1, MAP2K3, PRKCB, MAPK1, MAPK14, VEGFA, PDGFRA, GNAS, RAP1B |
| Spliceosome | 1.57E−02 | SRSF10, TRA2B, WBP11, DDX5, RBMX, HNRNPU, SMNDC1, HNRNPM, SRSF2, SRSF5, SRSF4, SRSF7, SRSF6, USP39, ACIN1, SNRNP70, DDX42 | Signaling pathways regulating pluripotency of stem cells | 2.19E−02 | BMP4, FGFR2, SMARCAD1, FGFR1, FGFR3, APC2, GRB2, SOX2, BMPR2, SMAD1, DVL1, MAPK1, MAPK14, PCGF6, WNT7A, PIK3R2, KAT6A, BMPR1A |
| Retrograde endocannabinoid signaling | 1.64E−02 | GABRA2, GNAO1, GNAI2, GRIA4, KCNJ3, PRKCB, MAPK1, DAGLA, SLC17A6, GNB2, GNB1, MAPK14, MGLL, PLCB1 | cGMP-PKG signaling pathway | 2.23E−02 | ATP1B1, GNAI2, SLC25A4, SLC25A5, ADCY6, PPP3R1, NPR1, PPP1CC, SRF, VDAC1, ATP2B1, EDNRB, MAPK1, PPP1CA, ATP2A2, PDE2A, GTF2I, GTF2IRD1, ADRA2B, NFATC3 |
| Alcoholism | 2.10E−02 | HIST2H2AA3, GNAO1, GNAI2, GRB2, LOC684797, HDAC1L, GRIN3A, PPP1CC, MAPK1, PPP1CA, GNB2, GNB1, SOS2, ARAF, NTRK2, H2AFY, CALM3, SHC1, H3F3B, GNAS | Gap junction | 2.23E−02 | GNAI2, GRB2, TUBA3B, ADCY6, GJA1, SRC, PRKCB, MAPK1, SOS2, PDGFRA, GNAS, TUBA1A, TUBA1B |
| Phosphatidylinositol signaling system | 2.21E−02 | INPP1, MTMR3, MTMR14, IMPAD1, CDIPT, DGKE, DGKG, CALM3, PLCD4, SYNJ2, PLCB1, TMEM55B, PRKCB | Choline metabolism in cancer | 2.75E−02 | CHKA, PLD1, SLC44A1, GRB2, CHKB, CHPT1, PRKCB, MAPK1, HIF1A, DGKE, DGKG, SOS2, PDGFRA, PIK3R2 |
| PI3K-Akt signaling pathway | 2.22E−02 | PHLPP1, CSF3, FGFR2, FGFR1, YWHAZ, FGFR3, GRB2, PPP2R5C, FOXO3, ITGB1, CDC37, SOS2, GYS1, PRKAA1, MLST8, FGF1, CHUK, IL7, PKN2, COL5A3, YWHAE, CDK2, DDIT4, MAPK1, YWHAH, CDKN1B, GNB2, GNB1, VEGFA, YWHAQ, PDGFRA, PDGFRB, EFNA4 | Notch signaling pathway | 3.03E−02 | DTX4, CTBP1, APH1A, DTX2, PSEN2, CREBBP, RBPJ, NCOR2, DVL1 |
| Chronic myeloid leukemia | 2.35E−02 | MAPK1, CTBP1, CDKN1B, GRB2, TGFBR1, SOS2, ARAF, SHC1, HDAC1L, ABL1, CHUK | Endometrial cancer | 3.03E−02 | MAPK1, CCND1, APC2, GRB2, SOS2, ARAF, FOXO3, TCF7L2, PIK3R2 |
| Circadian entrainment | 2.38E−02 | GNAO1, GNAI2, ADCYAP1R1, GRIA4, KCNJ3, PRKCB, RPS6KA5, MAPK1, GNB2, GNB1, CALM3, GNAS, PLCB1 | Protein export | 3.47E−02 | MGC109340, HSPA5, SRPRB, SEC63, SEC61G, SEC61A2 |
| Glioma | 2.47E−02 | MAPK1, GRB2, SOS2, ARAF, PDGFRA, CALM3, TGFA, PDGFRB, SHC1, PRKCB | Lysosome | 3.73E−02 | PLA2G15, AP4E1, ACP2, CD164, CLTC, M6PR, DNASE2, SLC11A2, SLC17A5, GNPTAB, IGF2R, CTSD, CTSB, GGA1, GGA3, IDUA |
| GABAergic synapse | 2.58E−02 | SLC38A5, GABRA2, GNAO1, GNB2, GNAI2, TRAK2, SLC6A1, GNB1, GLS, GABBR1, SRC, PRKCB | Pancreatic cancer | 3.75E−02 | MAPK1, CDC42, CCND1, RALBP1, TGFBR1, VEGFA, ARAF, TGFA, CHUK, PIK3R2 |
| Melanogenesis | 2.75E−02 | MAPK1, EDNRB, GNAO1, GNAI2, CREBBP, MITF, CALM3, GNAS, PLCB1, TCF7L2, WNT7A, DVL1, PRKCB | Basal transcription factors | 3.93E−02 | TAF5L, GTF2I, GTF2IRD1, TAF8, TAF9B, GTF2H4, ERCC3, ERCC2 |
| Glucagon signaling pathway | 2.94E−02 | LDHB, CREBBP, PGAM1, PPP3R1, ACACA, FOXO1, PRMT1, SLC2A1, GYS1, CALM3, PRKAA1, GNAS, PLCB1 | Hepatitis B | 3.96E−02 | YWHAZ, GRB2, TGFBR1, CREBBP, FASLG, SRC, STAT2, PRKCB, IKBKE, MAPK1, CCND1, CDKN1B, YWHAQ, TICAM2, NFATC3, CHUK, PIK3R2 |
| GnRH signaling pathway | 3.70E−02 | MAPK1, CDC42, PLD1, GRB2, MAP2K3, MAPK14, SOS2, CALM3, GNAS, PLCB1, SRC, PRKCB | Glioma | 4.09E−02 | MAPK1, CCND1, GRB2, SOS2, ARAF, PDGFRA, TGFA, SHC1, PRKCB, PIK3R2 |
| Ubiquitin mediated proteolysis | 3.98E−02 | UBE4A, ANAPC5, UBE2G1, UBE2G2, UBE2J1, BIRC6, UBE2I, CDC34, UBE2H, UBOX5, RBX1, CUL3, CUL2, UBE2K, SMURF1, TRIP12 | Non-small cell lung cancer | 4.46E−02 | MAPK1, CCND1, GRB2, SOS2, ARAF, TGFA, FOXO3, PRKCB, PIK3R2 |
| VEGF signaling pathway | 4.04E−02 | MAPK1, CDC42, MAPK14, VEGFA, PPP3R1, MAPKAPK2, PXN, SRC, PRKCB | Mucin type O-Glycan biosynthesis | 4.61E−02 | GALNT2, GALNT1, C1GALT1C1, GALNT7, GALNT14, B4GALT5 |
| Phagosome | 4.78E−02 | DYNC1LI2, TUBA3B, MRC2, CALR, ITGB1, CANX, M6PR, ACTG1, RT1-A2, RT1-A1, CORO1A, TUBB5, HGS, SCARB1, TUBA1A, TUBA1B, DYNC1I2, SEC61G, SEC61A2, RT1-N2 | Platelet activation | 5.85E−02 | TLN1, GNAI2, ADCY6, COL5A3, PPP1CC, ITGB1, APBB1IP, SRC, ACTG1, MAPK1, PPP1CA, GP1BB, MAPK14, RAP1B, GNAS, PIK3R2 |
| FoxO signaling pathway | 6.05E−02 | GRB2, TGFBR1, CREBBP, FOXO1, FOXO3, CDK2, MAPK1, PRMT1, CDKN1B, MAPK14, SOS2, ARAF, PRKAA1, BCL6, CHUK | VEGF signaling pathway | 6.28E−02 | MAPK1, CDC42, MAPK14, VEGFA, PPP3R1, PXN, SRC, PRKCB, PIK3R2 |
| Adrenergic signaling in cardiomyocytes | 6.67E−02 | ATP1B1, CACNA2D1, GNAI2, PPP2R5C, CACNB1, PPP1CC, TPM3, RPS6KA5, ATP2B1, MAPK1, PPP1CA, MAPK14, CALM3, GNAS, PLCB1 | Nicotine addiction | 6.31E−02 | GABRA2, GABRA1, SLC17A6, GABRB2, GRIA4, GRIN3A, CACNA1B |
| Hepatitis B | 7.00E−02 | YWHAZ, GRB2, TGFBR1, CREBBP, CDK2, SRC, PRKCB, STAT2, IKBKE, MAPK1, CDKN1B, YWHAQ, TICAM2, NFATC3, CHUK | Bladder cancer | 6.31E−02 | RPS6KA5, MAPK1, CCND1, FGFR3, VEGFA, ARAF, SRC |
| Signaling pathways regulating pluripotency of stem cells | 7.34E−02 | BMP4, FGFR2, FGFR1, FGFR3, GRB2, IL6ST, SOX2, BMPR2, SMAD1, DVL1, MAPK1, MAPK14, WNT7A, KAT6A, BMPR1A | Influenza A | 6.34E−02 | AGFG1, MAP2K3, CREBBP, FASLG, NLRX1, TRIM25, NXF1, STAT2, VDAC1, PRKCB, ACTG1, TNFRSF1A, IKBKE, MAPK1, HNRNPUL1, MAPK14, CPSF4, IFNGR1, PIK3R2 |
| Dorso-ventral axis formation | 7.68E−02 | MAPK1, ETS1, GRB2, SOS2, NOTCH4 | PI3K-Akt signaling pathway | 6.42E−02 | PHLPP1, CSF3, FGFR2, FGFR1, YWHAZ, FGFR3, GRB2, PPP2R5C, FASLG, FOXO3, ITGB1, CDC37, SOS2, PRKAA1, MLST8, FGF1, GNG5, CHUK, PIK3R2, IL7, PKN2, COL5A3, YWHAE, DDIT4, MAPK1, CCND1, CDKN1B, YWHAH, GNB2, GNB1, VEGFA, YWHAQ, PDGFRA |
| Dopaminergic synapse | 7.85E−02 | GNAO1, GNAI2, PPP2R5C, GRIA4, PPP1CC, KCNJ3, PRKCB, PPP1CA, GNB2, GNB1, MAPK14, CALM3, GNAS, PLCB1 | mRNA surveillance pathway | 6.75E−02 | PPP1CA, SMG5, NUDT21, PPP2R5C, CPSF6, PELO, CPSF4, ACIN1, PABPC1, NXF1, PPP1CC, RNGTT |
| Proteasome | 8.41E−02 | PSMC6, PSME1, PSMD11, PSMD4, PSME4, PSMD7, PSMB8 | Viral carcinogenesis | 7.71E−02 | YWHAZ, GRB2, LOC684797, CREBBP, HDAC10, GTF2H4, YWHAE, SRF, PXN, SRC, HIST2H4, RT1-A2, CDC42, MAPK1, RT1-A1, CCND1, YWHAH, CDKN1B, HIST1H4B, YWHAQ, RBPJ, CHD4, TRAF3, PIK3R2 |
| Endocrine and other factor-regulated calcium reabsorption | 8.41E−02 | DNM3, ATP1B1, AP2B1, GNAS, PLCB1, CLTC, PRKCB | Inositol phosphate metabolism | 8.07E−02 | INPP1, MTMR2, MTMR3, MTMR14, IMPAD1, CDIPT, PIK3C2A, PLCH2, PLCD4, SYNJ2 |
| Protein export | 8.63E−02 | MGC109340, HSPA5, SRPRB, SEC61G, SEC61A2 | Chemokine signaling pathway | 8.23E−02 | PARD3, GNAI2, GRB2, ADCY6, FOXO3, CX3CL1, PXN, SRC, STAT2, MAPK1, CDC42, GNB2, GNB1, SOS2, SHC1, RAP1B, GNG5, CHUK, PIK3R2 |
| Alzheimer's disease | 8.66E−02 | ATP5D, NDUFA4, ATP5E, NDUFA8, APH1A, CYC1, IDE, PPP3R1, ATP5G2, ATP5G1, NDUFV3, MAPK1, TNFRSF1A, ATP2A2, MAPT, PSEN2, CALM3, PLCB1 | Circadian entrainment | 8.56E−02 | RPS6KA5, MAPK1, GNAO1, GNB2, GNAI2, GNB1, ADCYAP1R1, ADCY6, GNAS, GRIA4, GNG5, PRKCB |
| Viral carcinogenesis | 8.90E−02 | YWHAZ, GRB2, IL6ST, LOC684797, CREBBP, GTF2H4, HDAC1L, MAPKAPK2, YWHAE, SRF, PXN, CDK2, SRC, RT1-A2, CDC42, MAPK1, RT1-A1, YWHAH, CDKN1B, YWHAQ, TRAF3, RT1-N2 | Metabolic pathways | 8.87E−02 | LDHB, CDIPT, IMPAD1, HMGCR, CNDP2, PGAM1, ACSS1, TRAK2, IDUA, PLD3, PLD1, CRLS1, C1GALT1C1, GATM, QDPR, CHPT1, KDSR, PRPS2, ME1, CHKA, EXTL3, MGAT5B, GCLC, AHCY, SRM, CHKB, GLUD1, ATP6V1B2, ACAT2, CERS2, PLCH2, IDH2, B4GALT6, DNMT3A, MGAT4A, GCDH, B4GALT3, ACER1, ACACA, AK2, NDUFV3, GLS, AHCYL1, IDI1, NAT8L, ATP5D, ATP5E, NDST2, CYC1, MAN1B1, QARS, CKB, ACOX3, ACOT8, P4HA2, P4HA1, MCCC1, MGLL, SYNJ2, ATP5L, AGPAT4, PTDSS1, AGPAT3, PFKL, ACADS, PIK3C2A, PIGU, COQ5, MAN2A1, COQ3, MTMR14, PANK3, DGAT1, CHSY1, PLA2G3, DEGS1, INPP1, BCAT1, CYP2U1, GALNT2, GALNT1, GALNT7, UGDH, ATP5G2, ATP5G1, MTMR2, MTMR3, MTHFR, STT3A, AKR1A1, DGKE, DGKG, PLCD4, TSTA3, ACSL3, HPGDS, HSD17B7, GALNT14, B4GALNT1, HSD17B8, NDUFA4, DLST, NDUFA8, ACLY, POLR3C |
| TNF signaling pathway | 9.93E−02 | RPS6KA5, VCAM1, MAPK1, TNFRSF1A, TNFRSF1B, DNM1L, MAP2K3, MAPK14, CX3CL1, TAB2, CHUK, TRAF3 | TNF signaling pathway | 8.90E−02 | RPS6KA5, VCAM1, TNFRSF1A, MAPK1, TNFRSF1B, DNM1L, MAPK14, MAP2K3, CX3CL1, TAB2, CHUK, TRAF3, PIK3R2 |
| Long-term potentiation | 9.12E−02 | MAPK1, PPP1CA, RPS6KA1, ARAF, CREBBP, PPP3R1, RAP1B, PPP1CC, PRKCB | |||
| Melanogenesis | 9.57E−02 | MAPK1, EDNRB, GNAO1, GNAI2, ADCY6, MITF, CREBBP, GNAS, TCF7L2, WNT7A, DVL1, PRKCB | |||