KCNA4

Chr 11

potassium voltage-gated channel subfamily A member 4

Also known as: HBK4, HK1, HPCN2, HUKII, KCNA4L, KCNA8, KV1.4, MCIDDS

NCBI Gene: 3739 ENSG00000182255 UniProt: P22459

KCNA4 encodes a voltage-gated potassium channel that mediates potassium transport in excitable membranes and can form homotetrameric or heterotetrameric channels with other KCNA family members. Autosomal recessive mutations cause a neurodevelopmental disorder characterized by microcephaly, cataracts, intellectual disability, and dystonia with striatal abnormalities. The gene is highly constrained against loss-of-function variants (pLI = 0.98, LOEUF = 0.28), indicating intolerance to functional disruption.

ResearchSummary from RefSeq, OMIM, UniProt

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 A-type potassium current class, the members of which may be important in the regulation of the fast repolarizing phase of action potentials in heart and thus may influence the duration of cardiac action potential.[provided by RefSeq, Mar 2011]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMicrocephaly, cataracts, impaired intellectual development, and dystonia with abnormal striatum

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.28

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429