Relevance to Autism

De novo variants in the KCNH1 gene, including a de novo loss-of-function variant and several de novo missense variants, have been identified in ASD probands from multiple cohorts, including the Simons Simplex Collection, the SPARK cohort, the Autism Sequencing Consortium, and a Chinese ASD cohort (Zhou et al., 2022; Fu et al., 2022; Trost et al., 2022; Wu et al., 2024). A missense variant in this gene was recently reported in a male patient from Pakistan presenting with pharmacoresistant seizures and autistic behavior (Chand et al., 2023).

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. This gene encodes a member of the potassium channel, voltage-gated, subfamily H. This member is a pore-forming (alpha) subunit of a voltage-gated non-inactivating delayed rectifier potassium channel. It is activated at the onset of myoblast differentiation. The gene is highly expressed in brain and in myoblasts. Overexpression of the gene may confer a growth advantage to cancer cells and favor tumor cell proliferation. Heterozygous mutations in this gene are responsible for both Temple-Baraitser syndrome (OMIM 611816) and Zimmermann-Laband syndrome 1 (OMIM 135500).

External Links

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