KCNJ10

Chr 1

potassium inwardly rectifying channel subfamily J member 10

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

NCBI Gene: 3766 ENSG00000177807 UniProt: P78508

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.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the inward rectifier-type potassium channel family, characterized by having a greater tendency to allow potassium to flow into, rather than out of, a cell. The encoded protein may form a heterodimer with another potassium channel protein and may be responsible for the potassium buffering action of glial cells in the brain. Mutations in this gene have been associated with seizure susceptibility of common idiopathic generalized epilepsy syndromes. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.76

Clinical Summary— KCNJ10

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Gene-Disease Validity (ClinGen)

enlarged vestibular aqueduct syndrome · ADDisputed

Disputed — evidence questions this relationship

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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ClinVar Variants

32 unique Pathogenic / Likely Pathogenic· 253 VUS of 454 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.150

Z-score 2.09

OE 0.29 (0.13–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.48Z-score

OE missense 0.72 (0.63–0.82)

161 obs / 223.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.13–0.76)

0≤0.351.4

Missense OE?0.72 (0.63–0.82)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

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

This gene — mechanism propensity

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

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

454 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18

Likely Pathogenic14

VUS253

Likely Benign108

Benign15

Conflicting46

Pathogenic

Likely Pathogenic

253

VUS

108

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	7	0	0	18
Likely Pathogenic	4	10	0	0	14
VUS	8	195	50	0	253
Likely Benign	0	1	16	91	108
Benign	0	0	15	0	15
Conflicting	—				46
Total	23	213	81	91	454

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap KCNJ10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →