Relevance to Autism

De novo variants in the KCNC2 gene, including a missense variant that was predicted to be deleterious, have been identified in ASD probands (Yuen et al., 2017; Turner et al., 2017; Satterstrom et al., 2020), while an inherited loss-of-function variant in this gene was reported in an ASD proband from the iHART cohort (Ruzzo et al.,2019). De novo variants in this gene have also been implicated in several forms of epilepsy, including developmental and epileptic encephalopathy (Vetri et al., 2020; Rydzanicz et al., 2021) and West syndrome (Rademacher et al., 2020), and other developmental disorders (Kaplanis et al., 2020). More recently, Schwarz et al., 2022 identified.novel KCNC2 variants in 18 patients with various forms of epilepsy, and functional analysis of four of the variants reported in this paper demonstrated gain-of-function in three severely affected cases with developmental and epileptic encephalopathy and loss-of-function in one case with genetic generalized epilepsy; one of the gain-of-function variants was identified de novo in a patient who also presented with autism spectrum disorder. Mehniovic et al., 2022 reported a de novo likely germline mosaic missense variant in KCNC2 that was observed in two female siblings affected by autism, epileptic encephalopathy, developmental delay, and cognitive impairment; in the same report, a literature review identified additional individuals with neurodevelopmental disorders with a missense variant in this gene (de novo missense p-value 1.03E-05).

Molecular Function

The Shaker gene family of Drosophila encodes components of voltage-gated potassium channels and is comprised of four subfamilies. Based on sequence similarity, this gene is similar to one of these subfamilies, namely the Shaw subfamily. The protein encoded by this gene belongs to the delayed rectifier class of channel proteins and is an integral membrane protein that mediates the voltage-dependent potassium ion permeability of excitable membranes.

External Links

References