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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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KCNJ10
potassium inwardly rectifying channel subfamily J member 10
Chromosome 1 Β· 1q23.2
NCBI Gene: 3766Ensembl: ENSG00000177807.12HGNC: HGNC:6256UniProt: P78508
97PubMed Papers
21Diseases
0Drugs
30Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
potassium ion transmembrane transportprotein bindinginward rectifier potassium channel activitybasolateral plasma membraneEAST syndromeautosomal recessive nonsyndromic hearing loss 4Pendred syndromehearing loss, autosomal recessive
✦AI Summary

KCNJ10 encodes Kir4.1, an inwardly rectifying potassium channel critical for cellular potassium homeostasis in multiple tissues. The channel primarily functions in potassium buffering by glial cells in the brain and potassium recycling in renal distal tubules 1. In the kidney, KCNJ10 localizes to the basolateral membrane of distal convoluted tubules, connecting tubules, and cortical collecting ducts, where it mediates potassium recycling essential for sodium reabsorption 1. In the nervous system, KCNJ10 is expressed in satellite glial cells of dorsal root ganglia and astrocytes, where it regulates neuronal excitability through potassium homeostasis 2 3. Loss-of-function mutations cause EAST syndrome, characterized by epilepsy, ataxia, sensorineural deafness, and renal tubulopathy, demonstrating the channel's critical role in brain and kidney function 1. Recent studies have identified heterozygous KCNJ10 variants as a cause of paroxysmal kinesigenic dyskinesia through haploinsufficiency mechanisms, expanding the phenotypic spectrum beyond classical EAST syndrome 4 5. Additionally, variants show association with seizure susceptibility, with certain alleles conferring resistance to epilepsy 6. The channel represents a potential therapeutic target for depression and neurological disorders involving glial dysfunction 3.

Sources cited
1
KCNJ10 mutations cause EAST syndrome and the channel localizes to basolateral membrane of renal tubules
PMID: 20651251
2
KCNJ10 is expressed in satellite glial cells and regulates potassium channel signaling
PMID: 38530364
3
KCNJ10 in astrocytes affects depression-like phenotypes and represents a therapeutic target
PMID: 38355723
4
Heterozygous KCNJ10 variants cause paroxysmal kinesigenic dyskinesia
PMID: 39367724
5
KCNJ10 haploinsufficiency causes paroxysmal kinesigenic dyskinesia through glial involvement
PMID: 38979912
6
KCNJ10 variants are associated with seizure susceptibility and resistance
PMID: 15120748
Disease Associationsβ“˜21
EAST syndromeOpen Targets
0.84Strong
autosomal recessive nonsyndromic hearing loss 4Open Targets
0.63Moderate
Pendred syndromeOpen Targets
0.59Moderate
hearing loss, autosomal recessiveOpen Targets
0.51Moderate
episodic kinesigenic dyskinesia 1Open Targets
0.45Moderate
episodic kinesigenic dyskinesiaOpen Targets
0.44Moderate
nonsyndromic genetic hearing lossOpen Targets
0.42Moderate
hypercoagulability syndrome due to glycosylphosphatidylinositol deficiencyOpen Targets
0.41Moderate
genetic disorderOpen Targets
0.38Weak
cerebellar ataxiaOpen Targets
0.34Weak
Sensorineural hearing impairmentOpen Targets
0.33Weak
microcephalyOpen Targets
0.33Weak
renal tubule diseaseOpen Targets
0.33Weak
spastic diplegiaOpen Targets
0.33Weak
SeizureOpen Targets
0.30Weak
Abnormality of the nervous systemOpen Targets
0.27Weak
deafnessOpen Targets
0.12Weak
HypercholesterolemiaOpen Targets
0.12Weak
peripheral neuropathyOpen Targets
0.12Weak
liver diseaseOpen Targets
0.12Weak
Seizures, sensorineural deafness, ataxia, impaired intellectual development, and electrolyte imbalanceUniProt
Pathogenic Variants30
NM_002241.5(KCNJ10):c.889C>T (p.Arg297Cys)Pathogenic
EAST syndrome|not provided|Autosomal recessive nonsyndromic hearing loss 4;Pendred syndrome;EAST syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 297
NM_002241.5(KCNJ10):c.193C>T (p.Arg65Cys)Likely pathogenic
EAST syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 65
NM_002241.5(KCNJ10):c.-1+1G>TLikely pathogenic
not provided|EAST syndrome
β˜…β˜…β˜†β˜†2025
NM_002241.5(KCNJ10):c.595C>T (p.Arg199Ter)Pathogenic
EAST syndrome|not provided|Autosomal recessive nonsyndromic hearing loss 4;Pendred syndrome;EAST syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 199
NM_002241.5(KCNJ10):c.500C>T (p.Ala167Val)Pathogenic
EAST syndrome|Autosomal recessive nonsyndromic hearing loss 4;Pendred syndrome;EAST syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 167
NM_002241.5(KCNJ10):c.890G>T (p.Arg297Leu)Likely pathogenic
EAST syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 297
NM_002241.5(KCNJ10):c.68del (p.Pro23fs)Pathogenic
EAST syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 23
NM_002241.5(KCNJ10):c.305del (p.Pro102fs)Pathogenic
EAST syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 102
NM_002241.5(KCNJ10):c.198C>G (p.Tyr66Ter)Pathogenic
EAST syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 66
NM_002241.5(KCNJ10):c.581C>A (p.Pro194His)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 4|Autosomal recessive nonsyndromic hearing loss 4;EAST syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 194
NM_002241.5(KCNJ10):c.331C>T (p.Gln111Ter)Pathogenic
EAST syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 111
NM_002241.5(KCNJ10):c.229G>C (p.Gly77Arg)Pathogenic
EAST syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 77
NM_002241.5(KCNJ10):c.170C>T (p.Thr57Ile)Likely pathogenic
EAST syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 57
NM_002241.5(KCNJ10):c.487G>T (p.Gly163Cys)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 163
NM_002241.5(KCNJ10):c.236G>A (p.Trp79Ter)Pathogenic
EAST syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 79
NM_002241.5(KCNJ10):c.321_322del (p.Val109fs)Pathogenic
EAST syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 109
NM_002241.5(KCNJ10):c.305dup (p.Ala103fs)Likely pathogenic
EAST syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 103
NM_002241.5(KCNJ10):c.211_212del (p.Phe71fs)Pathogenic
EAST syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 71
NM_002241.5(KCNJ10):c.19_20insC (p.Val7fs)Pathogenic
EAST syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 7
NM_002241.5(KCNJ10):c.798dup (p.Asp267fs)Pathogenic
EAST syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 267
View on ClinVar β†—
Related Genes
SLC26A4Protein interaction95%DMDProtein interaction91%FOXI1Protein interaction85%GJB2Protein interaction85%KCNJ16Protein interaction81%SLC1A2Protein interaction76%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
1%
Liver
1%
Ovary
0%
Lung
0%
Heart
0%
Gene Interaction Network
Click a node to explore
KCNJ10SLC26A4DMDFOXI1GJB2KCNJ16SLC1A2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P78508
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.68LoF Tolerant
pLIβ“˜
0.46Tolerant
Observed/Expected LoF0.39 [0.23–0.68]
RankingsWhere KCNJ10 stands among ~20K protein-coding genes
  • #4,945of 20,598
    Most Researched97 Β· top quartile
  • #1,806of 5,498
    Most Pathogenic Variants30
  • #5,002of 17,882
    Most Constrained (LOEUF)0.68
Genes detectedKCNJ10
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
KCNJ10 may not be a contributor to nonsyndromic enlargement of vestibular aqueduct (NSEVA) in Chinese subjects.
PMID: 25372295
PLoS One Β· 2014
1.00
2
Satellite glial GPR37L1 and its ligand maresin 1 regulate potassium channel signaling and pain homeostasis.
PMID: 38530364
J Clin Invest Β· 2024
0.90
3
Pharmacological inhibition of Kir4.1 evokes rapid-onset antidepressant responses.
PMID: 38355723
Nat Chem Biol Β· 2024
0.80
4
Heterozygous KCNJ10 Variants Affecting Kir4.1 Channel Cause Paroxysmal Kinesigenic Dyskinesia.
PMID: 39367724
Mov Disord Β· 2024
0.70
5
KCNJ10 gene mutations causing EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) disrupt channel function.
PMID: 20651251
Proc Natl Acad Sci U S A Β· 2010
0.60