Overrepresentation of genetic variation in the AnkyrinG interactome is related to a range of neurodevelopmental disorders

Abstract

Upon the discovery of numerous genes involved in the pathogenesis of neurodevelopmental disorders, several studies showed that a significant proportion of these genes converge on common pathways and protein networks. Here, we used a reversed approach, by screening the AnkyrinG protein-protein interaction network for genetic variation in a large cohort of 1009 cases with neurodevelopmental disorders. We identified a significant enrichment of de novo potentially disease-causing variants in this network, confirming that this protein network plays an important role in the emergence of several neurodevelopmental disorders.

Fig. 1. Schematic overview of the ANK3 protein-protein interaction network members.

Light blue boxes indicate genes encoding proteins or protein complexes that directly interact with AnkyrinG. Dark blue box indicates genes encoding the components of casein kinase 2 (CK2), which regulates the binding affinity of voltage-gated sodium channels for AnkyrinG through phosphorylation.