Table 3. Pathways significantly enriched in mutated genes by ToppGene analysis.
| Pathway | Source | p-value | FDR q-value | No. Damaging/Total variants | Genes |
|---|---|---|---|---|---|
| Cadherin signaling pathway | PantherDB (ID P00012) | 1.26E-07 | 3.07E-04 | 24/48 | PCDH15*, FZD6, PCDH7*, PCDH20*, CDH20*, DCHS1*, CDH17*, CDH4*, CDH9*, CDH23*, CTNNA2, PCDHGB1*, PCDHGC5*, PCDHGC4*, PCDHGA2*, PCDHGA1*, PCDHA7*, PCDHA13*, PCDHAC1*, PCDHB2*, PCDHB3*, PCDHB7*, PCDHB8*, PCDHA2*, PCDHA1*, PCDHA3*, CELSR3*, FAT1*, FAT2*, FER, FZD10, CDHR2*, FAT3*, YES1, PCDH11X* |
| ECM-receptor interaction | BioSystems: KEGG (ID 83068) | 2.01E-06 | 2.45E-03 | 9/26 | CD36, SV2B, COL1A2†, COL1A1†, COL5A1†, COL6A3†, COL4A2†, DAG1†, COL6A6†, RELN†, TNN†, FN1†, THBS3, TNXB†, HMMR, HSPG2†, ITGA1, LAMB1†, LAMA4†, LAMA5†, LAMA2†, LAMA3† |
| Cell Cycle G2/M Checkpoint | MSigDB C2: BioCarta (ID M8560) | 1.25E-05 | 1.02E-02 | 13/20‡ | ATM, ATR, BRCA1, CDC25A, CDKN1A, PRKDC, EP300, CHEK2, RPS6KA1, TP53 |
| Wnt signaling pathway | PantherDB (ID P00057) | 2.17E-05 | 1.18E-02 | 36/66‡ | MYH13, PCDH15*, FZD6, PCDH7*, MYH7, PCDH20*, CDH20*, DCHS1*, CDH17*, CDH4*, CDH9*, CDH23*, PRKCZ, PPP2R5E, PPP3R2, CREBBP, CTNNA2, PLCB4, PCDHGB1*, PCDHGC5*, PCDHGC4*, PCDHGA2*, PCDHGA1*, DVL3, PCDHA7*, PCDHA13*, PCDHAC1*, PCDHB2*, PCDHB3*, PCDHB7*, PCDHB8*, PCDHA2*, PCDHA1*, PCDHA3*, EP300, CELSR3*, FAT1*, FAT2*, SRCAP, FZD10, INO80, TP53, CDHR2*, FAT3*, PCDH11X*, KREMEN1, ITPR2, MYH14, PLCB1 |
| Extracellular matrix organization | BioSystems: REACTOME (ID 576262) | 2.50E-05 | 1.18E-02 | 22/51 | ACTN1, ACAN†, COL6A5†, DDR2, LTBP4†, ADAMTS9†, COL1A2†, COL1A1†, COL15A1†, COL17A1†, COL9A3†, PDGFB, COL9A1†, COL5A1†, COL6A3†, COL4A2†, PLEC, VCAN†, DAG1†, ADAMTS16†, ADAMTS18†, COL6A6†, BCAN†, PSEN1, DSPP†, TNN†, PTPRS, FBN2†, FGA, FN1†, ADAMTS5†, TNXB†, ADAM18, LEPREL1†, HSPG2†, ICAM4, ITGA1, LOXL4, LAMB1†, LAMA4†, LAMA5†, LAMA2†, LAMA3†, FBN3† |
Note:
*
30 genes showing a cadherin domain according to significant enrichment by ToppGene analysis (InterPro IPR002126 domain, q-value 3.24E-08, FDR correction).
†
34 genes annotated as proteinaceous extracellular matrix (ECM) cellular components according to significant enrichment by ToppGene analysis (GO Cellular Component GO:0005578, q-value 4.62E-04, FDR correction).
‡
Significant enrichment for damaging variants (q-value < 0.05, Bonferroni correction).