Fig. 3: VOGM-associated variants in ACVRL1 and other Mendelian vascular disease genes.
From: Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
a Top 10 GO molecular function, GO biological process, and Reactome pathway enrichment terms. The y-axis depicts GO term and Reactome pathway ID numbers. The x-axis depicts -log (p-value) and the dotted line represents the α = 0.05 significance threshold (one-sided Fisher’s exact test, Bonferroni multiple-testing adjusted). The GO term and Reactome pathway term name overline their respective bars. b Interactome of mutated Ras signaling genes in VOGM. Genes with damaging Ras signaling variants (WP4223 in Wiki pathway analysis) and EPHB4, NOTCH1, ACVRL1, and ITGB1 (27 genes in total) were inputted into String (https://string-db.org/cgi/about.pl) and mapped onto a single STRING interactome that includes a higher than expected number of interactions (PPI enrichment p-value < 1.0 x 10-16, one-sided hypergeometric test, Bonferroni multiple-testing adjusted). All 6 VOGM risk genes (highlighted by red box) contribute significantly to the PPI enrichment of this network. c Multi-generational VOGM family in KVOGM-91. Two transmitted D-mis variants (p. Cys344Tyr and p. Arg484Gln) are located in the kinase domain of ALK1 (ACVRL1) shown in ribbon structure (PDB ID: 3MY0)157. Cys344 and Arg484 are indicated with yellow spheres. A small molecule inhibitor (purple) is bound in the catalytic cleft. HHT, hereditary hemorrhagic telangiectasia.
