KCNJ8
Chr 12potassium inwardly rectifying channel subfamily J member 8
Also known as: KIR6.1, uKATP-1
The protein functions as an inward-rectifier potassium channel that allows potassium to flow preferentially into cells and is regulated by G-proteins and internal ATP. Mutations cause J-wave syndromes and have been associated with sudden infant death syndrome (SIDS), with inheritance patterns not clearly established from available data. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.575) and has a dedicated GeneReviews entry reflecting its clinical importance.
Primary Disease Associations & Inheritance
Disputed — evidence questions this relationship
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
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
337 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 | 38 | 0 | 38 |
Likely Pathogenic | 0 | 2 | 2 | 0 | 4 |
VUS | 3 | 124 | 30 | 0 | 157 |
Likely Benign | 0 | 3 | 9 | 106 | 118 |
Benign | 0 | 0 | 8 | 4 | 12 |
Conflicting | — | 6 | |||
| Total | 3 | 129 | 87 | 110 | 335 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KCNJ8 · 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