KCNJ5
Chr 11ADpotassium inwardly rectifying channel subfamily J member 5
Also known as: CIR, GIRK4, KATP1, KIR3.4, LQT13
This gene encodes an inward-rectifier potassium channel subunit that preferentially allows potassium influx and is regulated by G-proteins and extracellular potassium concentrations. Mutations cause autosomal dominant familial hyperaldosteronism type III and long QT syndrome 13, affecting adrenal hormone regulation and cardiac electrophysiology. The gene shows low constraint to loss-of-function variants (pLI 0.0003), suggesting that complete protein loss may be tolerated.
Primary Disease Associations & Inheritance
Disputed — evidence questions this relationship
2 total gene-disease associations curated
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 39 | 0 | 39 |
Likely Pathogenic | 0 | 1 | 2 | 0 | 3 |
VUS | 8 | 190 | 49 | 4 | 251 |
Likely Benign | 0 | 3 | 18 | 124 | 145 |
Benign | 0 | 2 | 29 | 2 | 33 |
Conflicting | — | 18 | |||
| Total | 8 | 196 | 137 | 130 | 489 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KCNJ5 · 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
External Resources
Links to major genomics databases and tools