KCNJ11
Chr 11ADARpotassium inwardly rectifying channel subfamily J member 11
Also known as: BIR, HHF2, IKATP, KIR6.2, MODY13, PHHI, PNDM2, TNDM3
This protein forms an inward-rectifying potassium channel that associates with the sulfonylurea receptor to regulate insulin secretion in pancreatic beta cells. Mutations cause a spectrum of glucose homeostasis disorders including familial hyperinsulinemic hypoglycemia (autosomal recessive), transient and permanent neonatal diabetes mellitus, and maturity-onset diabetes of the young type 13 (autosomal dominant), with some forms of permanent neonatal diabetes presenting with neurologic features. Disease predominantly results from gain-of-function effects that disrupt normal channel regulation and insulin secretion control.
Definitive — sufficient evidence for diagnostic panels
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
477 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 | 9 | 12 | 9 | 0 | 30 |
Likely Pathogenic | 19 | 26 | 1 | 0 | 46 |
VUS | 0 | 176 | 23 | 9 | 208 |
Likely Benign | 0 | 6 | 1 | 97 | 104 |
Benign | 0 | 7 | 1 | 1 | 9 |
Conflicting | — | 74 | |||
| Total | 28 | 227 | 35 | 107 | 471 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KCNJ11 · 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
A Study of Endocrine, Metabolic, and Genetic Risk Factors of Pediatric Persistent Hypoglycemia at Sohag University Hospital
NOT YET RECRUITINGImpact of Sulphonylureas on Neurodevelopmental Outcomes in KCNJ11-related Intermediate Developmental Delay, Epilepsy and Neonatal Diabetes (iDEND) Syndrome
RECRUITINGExercise to Fight Obesity
RECRUITINGExternal Resources
Links to major genomics databases and tools