KCNJ12
Chr 17potassium inwardly rectifying channel subfamily J member 12
Also known as: IRK-2, IRK2, KCNJN1, Kir2.2, hIRK, hIRK1, hkir2.2x, kcnj12x
The protein functions as an inwardly rectifying potassium channel that controls resting membrane potential and contributes to action potential waveform in neurons and muscle, including participation in the cardiac inward rectifier current. Mutations cause autosomal recessive SeSAME syndrome (seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance), a multisystem disorder affecting the nervous system, hearing, and electrolyte balance with onset in infancy or early childhood.
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
KCNJ12 · 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