KCNE4

Chr 2

potassium voltage-gated channel subfamily E regulatory subunit 4

Also known as: MIRP3

NCBI Gene: 23704 ENSG00000152049 UniProt: Q8WWG9 OMIM: 607775

KCNE4 encodes an ancillary protein that functions as a regulatory subunit of voltage-gated potassium channels, modulating gating kinetics and enhancing channel stability while inhibiting potassium currents when associated with KCNQ1. Mutations cause progressive familial heart block type IB, which follows an autosomal dominant inheritance pattern. The gene shows relatively low constraint to loss-of-function variants, suggesting haploinsufficiency may not be the primary disease mechanism.

OMIM ResearchSummary from UniProt

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, isk-related subfamily. This member is a type I membrane protein, and a beta subunit that assembles with a potassium channel alpha-subunit to modulate the gating kinetics and enhance stability of the multimeric complex. This gene is prominently expressed in the embryo and in adult uterus. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

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.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.36

LOEUF

GOF

Mechanism· predicted