KCNJ1
Chr 11ARpotassium inwardly rectifying channel subfamily J member 1
Also known as: KIR1.1, ROMK, ROMK1
This gene encodes an inward-rectifier potassium channel that is activated by internal ATP and plays a major role in renal potassium homeostasis by allowing potassium to flow preferentially into cells. Mutations cause Bartter syndrome type 2, an autosomal recessive disorder characterized by antenatal onset of salt wasting, hypokalemic alkalosis, hypercalciuria, and low blood pressure. The gene is not highly constrained against loss-of-function variants (pLI = 0.00004), consistent with its recessive inheritance pattern.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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
340 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 | 21 | 5 | 66 | 0 | 92 |
Likely Pathogenic | 17 | 20 | 3 | 0 | 40 |
VUS | 1 | 79 | 15 | 0 | 95 |
Likely Benign | 0 | 4 | 12 | 79 | 95 |
Benign | 0 | 0 | 5 | 0 | 5 |
Conflicting | — | 12 | |||
| Total | 39 | 108 | 101 | 79 | 339 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KCNJ1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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