Table 1.
GeneGo (Metacore) Pathway Maps | p-value | Ratio | RefSeq Genes | # TS subjects |
---|---|---|---|---|
Proteolysis_Role of Parkin in the Ubiquitin-Proteasomal Pathway | 9.6 × 10-5 | 6/24 | CUL1, PSMD13, PARK2, SEPT5, SIAH1, TUBB4Q, TUBB8, UBE2J1 | 10 |
Neurophysiological process_GABA-A receptor life cycle | 1.9 × 10-4 | 6/27 | CLTB, GABRA1, GABRA6, GABRB1, GABRB2, GABRD, GABRG1, GABRG2, TUBB4Q, TUBB8 | 9 |
Cell adhesion_Histamine H1 receptor signaling in the interruption of cell barrier | 5.8 × 10-4 | 7/45 | CTNNA3, GNB4, GNG7, ITPR1, MYH11, MYLK3, OCLN, PPP1R12A, TLN1 | 17 |
Transport_Alpha-2 adrenergic receptor regulation of ion channels | 7.7 × 10-4 | 7/47 | CACNA1C, GNB4, GNG7, ITPR1, PRKACB, PRKCZ | 11 |
Regulation of metabolism_Bile acids regulation of glucose and lipid metabolism via FXR | 0.0012 | 6/37 | ACACA, ACACB, APOC4, FOXO1, ADD1 | 5 |
Muscle contraction_ GPCRs in the regulation of smooth muscle tone | 0.0015 | 9/83 | ADRB2, CACNA1C, CAMK1, ITPR1, MYH11, MYLK3, OXT, OXTR, PPP1R12A, PRKACB | 10 |
Cytoskeleton remodeling_Role of PKA in cytoskeleton reorganization | 0.0018 | 6/40 | ADD1, GNB4, GNG7, ITPR1, MYLK3, PPP1R12A, PRKACB | 12 |
Regulation of lipid metabolism_Regulation of acetyl-CoA carboxylase 1 activity in lipogenic tissue | 0.0019 | 4/17 | ACACA, ACACB, PRKAB2, ADD1 | 4 |
Muscle contraction_S1P2 receptor-mediated smooth muscle contraction | 0.0026 | 5/30 | GNB4, GNG7, ITPR1, MYLK3, PPP1R12A, PRKCZ | 10 |
Cell adhesion_Gap junctions | 0.0026 | 5/30 | GJA5, GJA8, OCLN, PRKCZ, TUBB4Q, TUBB8 | 8 |
PANTHER Pathways | p-value | Ratio | RefSeq Genes | # TS |
Beta2 adrenergic receptor signaling | 0.0047 | 8/44 | PRKX, CACNA1C, GNB4, SNAP29, PRKACB, ADRB2, GNB1L, GNG7 | 12 |
Coenzyme A biosynthesis | 0.0054 | 3/6 | PANK2, PANK3, PANK4 | 3 |
5HT4 type receptor mediated signaling | 0.010 | 6/31 | HTT, HTR4, GNB4, SNAP29, GNB1L, GNG7 | 9 |
Muscarinic acetylcholine receptor 2 and 4 signaling | 0.011 | 9/62 | PRKX, SLC18A3, CACNA2D1, GNB4, SNAP29, PRKACB, CHAT, GNB1L, GNG7 | 12 |
Beta1 adrenergic receptor signaling | 0.016 | 7/44 | PRKX, CACNA1C, GNB4, SNAP29, PRKACB, GNB1L, GNG7 | 11 |
5HT1 type receptor mediated signaling | 0.016 | 7/44 | PRKX, HTT, GNB4, SNAP29, PRKACB, GNB1L, GNG7 | 11 |
Histamine H2 receptor mediated signaling | 0.016 | 5/25 | PRKX, GNB4, PRKACB, GNB1L, GNG7 | 10 |
Heterotrimeric G-protein signaling pathway-rod outer segment phototransduction | 0.017 | 7/45 | PRKX, GRK4, GRK6, GNB4, PRKACB, GNB1L, GNG7 | 13 |
Oxytocin receptor mediated signaling | 0.026 | 8/60 | PRKCZ, CACNA1C, OXTR, GNB4, SNAP29, PLCH2, GNB1L, GNG7 | 11 |
Muscarinic acetylcholine receptor 1 and 3 signaling pathway | 0.028 | 8/61 | ITPR1, PRKCZ, SLC18A3, GNB4, SNAP29, CHAT, GNB1L, GNG7 | 10 |
Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | 0.036 | 16/166 | PRKX, GRM7, ADRA18, CLTCL1, RGS14, GRK4, GRK6, HTR4, GNB4, CLTB, CKB, PRKACB, ADRB2, HTR7, GNB1L, GNG7 | 17 |
5HT2 type receptor mediated signaling | 0.051 | 8/69 | PRKCZ, CACNA1C, HTT, GNB4, SNAP29, PLCH2, GNB1L, GNG7 | 11 |
Histamine H1 receptor mediated signaling | 0.058 | 6/47 | ITPR1, PRKCA, GNB4, PLCH2, GNB1L, GNG7 | 10 |
IPA Pathways | p-value | Ratio | RefSeq Genes | # TS |
Sphingolipid Metabolism | 3.1 × 10-4 | 14/82 | ARSB, ARSD, ARSE, ARSF, ARSH, ASAH2, GBA3, GLB1L2, GLB1L3, PPAP2A, SGMS1, SGPP1, SPHK1, SULF1 | 14 |
Glycosaminoglycan Degradation | 0.0010 | 8/36 | ARSB, FGFRL1, GBA3, GLB1L2, GLB1L3, HEXB, IDUA, SULF1 | 11 |
GABA Receptor Signaling | 0.0060 | 8/47 | AP1B1, GABRA1, GABRA6, GABRB1, GABRB2, GABRD, GABRG1, GABRG2 | 6 |
N-Glycan Degradation | 0.027 | 5/29 | EDEM1, GBA3, GLB1L2, GLB1L3, HEXB | 5 |
Neuropathic Pain Signaling in Dorsal Horn Nucleus | 0.033 | 11/102 | CAMK1, GRIA1, GRINA, GRM7, ITPR1, PIK3C3, PLCH2, PRKACB, PRKCZ, TAC1, TACR1 | 14 |
The assessment of relative representation is compared to the entire genome, using the programs MetaCore (GeneGo, Inc), PANTHER, and Ingenuity Pathway Analysis (IPA). Ratios indicate the proportion of genes (PANTHER and IPA) or network objects (GeneGo Metacore) in known biological pathways that coincide with rare TS gene CNVs. The top five pathways with lowest p-values are shaded grey. Pathways with overlap between algorithms are highlighted in bold. “#TS” is number of unique TS subjects contributing at least one gene to the pathway result.