A de novo missense variant (p.Val404Met) was identified in the KCND2 gene in monozygotic twins affected with autism and severe, intractable seizures; functional analysis revealed the likely pathogenicity of this variant in that the p.Val404Met construct showed significantly slowed inactivation, consistent with a gain-of-function effect (PMID 24501278). In a genome-wide association study of 2165 participants from the Autism Genetic Resource Exchange (AGRE) performed to examine associations between genomic loci and endophenotypes associated with ASDs, it was shown that item 46 ("has overly serious facial expressions") on the Social Responsiveness Scale (SRS) significantly associates with the gene KCND2 (Connolly et al., 2012).
Molecular Function
Voltage-gated potassium (Kv) 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, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member mediates a rapidly inactivating, A-type outward potassium current which is not under the control of the N terminus as it is in Shaker channels.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
A genome-wide association study of autism incorporating autism diagnostic interview-revised, autism diagnostic observation schedule, and social res...
243 ASD probands of Han Chinese descent recruited from the Child Development and Behavior Research Center of Harbin Medical University (Harbin, China) and 243 ethnically-matched controls.
243 ASD probands of Han Chinese descent recruited from the Child Development and Behavior Research Center of Harbin Medical University (Harbin, China) and 243 ethnically-matched controls.
243 ASD probands of Han Chinese descent recruited from the Child Development and Behavior Research Center of Harbin Medical University (Harbin, China) and 243 ethnically-matched controls.
