Relevance to Autism

A de novo missense variant in the KCNH5 gene (p.Arg327His) was identified in a 13-year-old male presenting with epilepsy, epileptic encephalopathy, developmental delay and regression, and autism in Veeramah et al., 2013; functional assessment of the p.Arg327His variant by voltage-clamp recordings in Yang et al., 2013 demonstrated that this variant caused a hyperpolarizing shift in the voltage dependence of activation and an acceleration of activation, findings consistent with a gain-of-function effect. Galan-Vidal et al., 2022 reported an 11-year-old male presenting with developmental delay and regression, autism and epilepsy who inherited a KCNH5 missense variant (p.Asn856His) from his healthy mother; functional assessment of the p.Asn856His variant in the same report demonstrated that this variant resulted in slower activating outward currents and slower activation kinetics, consistent with a loss-of-function effect. A rare and potentially damaging de novo missense variant in this gene has also been identified in an ASD proband from the SPARK cohort (Zhou et al., 2022).

Molecular Function

This gene encodes a member of voltage-gated potassium channels. Members of this family have diverse functions, including regulating neurotransmitter and hormone release, cardiac function, and cell volume. This protein is an outward-rectifying, noninactivating channel.

External Links

References