KCNA2

Chr 1AD

potassium voltage-gated channel subfamily A member 2

Also known as: DEE32, EIEE32, HBK5, HK4, HUKIV, KV1.2, MK2, NGK1

NCBI Gene: 3737 ENSG00000177301 UniProt: P16389 OMIM: 176262

The protein forms voltage-gated potassium channels that allow neurons to repolarize following action potentials by functioning as delayed rectifiers. Mutations cause developmental and epileptic encephalopathy 32 through an autosomal dominant inheritance pattern, predominantly through gain-of-function mechanisms that disrupt normal neuronal excitability. The gene shows high constraint against loss-of-function variants, consistent with the importance of proper potassium channel dosage for neuronal function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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. The coding region of this gene is intronless, and the gene is clustered with genes KCNA3 and KCNA10 on chromosome 1. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 32MIM #616366

UniProtNizon-Isidor syndrome

Clinical highlights

Gene-disease validity (ClinGen)

genetic developmental and epileptic encephalopathy · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Both gain of function and loss of function mechanisms are described for this gene and which one applies is variant-dependent. Do not assume a null variant is — or isn't — the pathogenic class without checking the specific variant against curated evidence.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.38

LOEUF

GOF/LOF*

Mechanism· annotated

📖

GeneReview available — KCNA2