Relevance to Autism

Soldovieri et al., 2023 described 14 individuals carrying de novo missense variants in the KCNA3 gene, most of whom presented with a developmental and epileptic encephalopathy characterized by speech delay with or without motor delay, intellectual disability, epilepsy, and autism spectrum disorder; functional analysis of Kv1.3 channels carrying each missense variant revealed heterogeneous functional changes, ranging from loss-of-function effects with or without dominant negative effects to mixed loss- and gain-of-function effects. A de novo nonsense variant in the KCNA3 gene had previously been reported in an ASD proband from the SPARK cohort (Zhou et al., 2022).

Molecular Function

Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. It plays an essential role in T-cell proliferation and activation.

External Links

References