KCNJ10

Chr 1AR

potassium inwardly rectifying channel subfamily J member 10

Also known as: BIRK-10, KCNJ13-PEN, KIR1.2, KIR4.1, SESAME

The protein functions as an inwardly rectifying potassium channel that contributes to potassium buffering by glial cells in the brain. Biallelic mutations cause SESAME syndrome (seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance) and can contribute to enlarged vestibular aqueduct in a digenic pattern, both inherited in an autosomal recessive manner. The pathogenic mechanism appears to involve loss of normal channel function, disrupting potassium homeostasis in neural and other tissues.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.762 OMIM phenotypes
Clinical SummaryKCNJ10
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Gene-Disease Validity (ClinGen)
enlarged vestibular aqueduct syndrome · ADDisputed

Disputed — evidence questions this relationship

2 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.76LOEUF
pLI 0.150
Z-score 2.09
OE 0.29 (0.130.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.48Z-score
OE missense 0.72 (0.630.82)
161 obs / 223.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.130.76)
00.351.4
Missense OE0.72 (0.630.82)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 3 / 10.2Missense obs/exp: 161 / 223.0Syn Z: -0.15
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveKCNJ10-related seizures-sensorineural deafness-ataxia-intellectual developmental disorder-electrolyte imbalanceLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.78top 25%
GOF
0.85top 5%
LOF
0.2484th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KCNJ10 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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