KCNJ10

Chr 1AR

potassium inwardly rectifying channel subfamily J member 10

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

NCBI Gene: 3766ENSG00000177807UniProt: P78508

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]

Primary Disease Associations & Inheritance

Enlarged vestibular aqueduct, digenicMIM #600791
AR
SESAME syndromeMIM #612780
AR
UniProtSeizures, sensorineural deafness, ataxia, impaired intellectual development, and electrolyte imbalance
467
ClinVar variants
16
Pathogenic / LP
0.15
pLI score
1
Active trials
Clinical Summary— KCNJ10
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 186 VUS of 467 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.76LOEUF
pLI 0.150
Z-score 2.09
OE 0.29 (0.13–0.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.48Z-score
OE missense 0.72 (0.63–0.82)
161 obs / 223.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.29 (0.13–0.76)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.63–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 3 / 10.2Missense obs/exp: 161 / 223.0Syn Z: -0.15

ClinVar Variant Classifications

467 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic6
VUS186
Likely Benign81
Benign7
Conflicting10
10
Pathogenic
6
Likely Pathogenic
186
VUS
81
Likely Benign
7
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
5
0
10
Likely Pathogenic
1
4
1
0
6
VUS
5
157
24
0
186
Likely Benign
0
0
12
69
81
Benign
0
0
7
0
7
Conflicting
—10
Total111614969300

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

View 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.

Gene2Phenotype Curations

KCNJ10-related seizures-sensorineural deafness-ataxia-intellectual developmental disorder-electrolyte imbalance

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEar
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Enlarged vestibular aqueduct, digenic

MIM #600791

Molecular basis of disorder known

Autosomal recessive

SESAME syndrome

MIM #612780

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
KCNJ10 may not be a contributor to nonsyndromic enlargement of vestibular aqueduct (NSEVA) in Chinese subjects.
Zhao J et al.·PLoS One
2014
Satellite glial GPR37L1 and its ligand maresin 1 regulate potassium channel signaling and pain homeostasis.
Bang S et al.·J Clin Invest
2024
Heterozygous KCNJ10 Variants Affecting Kir4.1 Channel Cause Paroxysmal Kinesigenic Dyskinesia.
Huang X et al.·Mov Disord
2024
Rare Missense Variants in KCNJ10 Are Associated with Paroxysmal Kinesigenic Dyskinesia.
Wirth T et al.·Mov Disord
2024
The genetic spectrum of Gitelman(-like) syndromes.
Schlingmann KP et al.·Curr Opin Nephrol Hypertens
2022Review
Generalized myokymia, or neuromyotonia, or both in dogs with or without spinocerebellar ataxia.
Vanhaesebrouck A et al.·J Vet Intern Med
2023
Association of KCNJ10 variants and the susceptibility to clinical epilepsy.
Jiang C et al.·Clin Neurol Neurosurg
2021
Biochemical and neurophysiological effects of deficiency of the mitochondrial import protein TIMM50.
Paz E et al.·Elife
2024
Novel mutations in the KCNJ10 gene associated to a distinctive ataxia, sensorineural hearing loss and spasticity clinical phenotype.
Morin M et al.·Neurogenetics
2020
Analysis of SLC26A4, FOXI1, and KCNJ10 Gene Variants in Patients with Incomplete Partition of the Cochlea and Enlarged Vestibular Aqueduct (EVA) Anomalies.
Klarov LA et al.·Int J Mol Sci
2022Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Epilepsy

Precision Medicine in the Treatment of Epilepsy

RECRUITING
NCT05450822Gitte Moos KnudsenStarted 2022-02-18
LevetiracetamLevetiracetam TabletsLamotrigine tablet

External Resources

Links to major genomics databases and tools