KCNE5
Chr Xpotassium voltage-gated channel subfamily E regulatory subunit 5
Also known as: KCNE1L
The protein functions as an ancillary subunit that regulates voltage-gated potassium channels, particularly serving as an inhibitory beta-subunit of the cardiac potassium channel KCNQ1. Mutations cause AMME complex (a neurodevelopmental disorder with autism, microcephaly, mild intellectual disability, and epilepsy) and are associated with Brugada syndrome 6, a cardiac arrhythmia disorder. The gene shows tolerance to loss-of-function variants (LOEUF 1.83), suggesting variable penetrance or that some variants may act through other mechanisms.
Primary Disease Associations & Inheritance
Disputed — evidence questions this relationship
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
KCNE5 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools