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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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KCNJ1
potassium inwardly rectifying channel subfamily J member 1
Chromosome 11 Β· 11q24.3
NCBI Gene: 3758Ensembl: ENSG00000151704.17HGNC: HGNC:6255UniProt: A8K432
63PubMed Papers
21Diseases
0Drugs
76Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
gene expressioninward rectifier potassium channel activitycell surfacepotassium channel activityBartter syndromeantenatal Bartter syndromepolyarteritis nodosagenetic disorder
✦AI Summary

KCNJ1 encodes ROMK, an ATP-activated inwardly rectifying potassium channel that plays a crucial role in renal potassium homeostasis 1. This channel is primarily expressed in the thick ascending limb of Henle's loop, where it facilitates potassium recycling essential for sodium-potassium-chloride cotransporter function 1. Loss-of-function mutations in KCNJ1 cause Bartter syndrome type II, typically presenting as severe antenatal disease with polyhydramnios, hypokalemic metabolic alkalosis, and hyperreninemic hyperaldosteronism 23. However, phenotypic variability exists, with rare late-onset cases reported despite identical mutations 2. Beyond its renal function, KCNJ1 appears to have tumor suppressor properties in clear cell renal cell carcinoma, where low expression correlates with poor prognosis and increased metastasis 4. Additionally, KCNJ1 polymorphisms are associated with thiazide-induced glucose changes and new-onset diabetes, likely through potassium-mediated effects on insulin secretion 5. The gene variants may also influence colorectal adenoma risk through interactions with dietary calcium intake 6. These findings highlight KCNJ1's importance in both normal physiology and disease pathogenesis across multiple organ systems.

Sources cited
1
KCNJ1 encodes ROMK potassium channel causing Bartter syndrome type II with renal salt wasting
PMID: 12920401
2
Loss-of-function mutations cause severe antenatal Bartter syndrome with phenotypic variability
PMID: 32997650
3
KCNJ1 mutations cause neonatal Bartter syndrome with hypokalemic metabolic alkalosis
PMID: 15518434
4
KCNJ1 acts as tumor suppressor in clear cell renal cell carcinoma with prognostic significance
PMID: 25344677
5
KCNJ1 variants associate with thiazide-induced glucose changes and new-onset diabetes
PMID: 22907731
6
KCNJ1 polymorphisms interact with dietary calcium to influence colorectal adenoma risk
PMID: 37074453
Disease Associationsβ“˜21
Bartter syndromeOpen Targets
0.75Strong
antenatal Bartter syndromeOpen Targets
0.41Moderate
polyarteritis nodosaOpen Targets
0.32Weak
genetic disorderOpen Targets
0.19Weak
gastric ulcerOpen Targets
0.12Weak
hemorrhageOpen Targets
0.12Weak
Familial prostate cancerOpen Targets
0.11Weak
prostate cancerOpen Targets
0.11Weak
clear cell renal carcinomaOpen Targets
0.08Suggestive
Sensorineural hearing impairmentOpen Targets
0.06Suggestive
papillary renal cell carcinomaOpen Targets
0.05Suggestive
atrial fibrillationOpen Targets
0.05Suggestive
familial renal glucosuriaOpen Targets
0.04Suggestive
Renal glucosuriaOpen Targets
0.04Suggestive
nephronophthisis 1Open Targets
0.04Suggestive
primary Fanconi syndromeOpen Targets
0.04Suggestive
Fanconi renotubular syndrome 1Open Targets
0.04Suggestive
renal hypoplasiaOpen Targets
0.04Suggestive
HyponatremiaOpen Targets
0.04Suggestive
nephrogenic diabetes insipidusOpen Targets
0.04Suggestive
Bartter syndrome 2, antenatalUniProt
Pathogenic Variants76
NM_153766.3(KCNJ1):c.577C>T (p.Arg193Ter)Pathogenic
Bartter disease type 2|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 193
NM_153766.3(KCNJ1):c.955C>T (p.Arg319Ter)Pathogenic
not provided|Bartter disease type 2
β˜…β˜…β˜†β˜†2026β†’ Residue 319
NM_153766.3(KCNJ1):c.875G>A (p.Arg292Gln)Pathogenic
not provided|Bartter disease type 2
β˜…β˜…β˜†β˜†2026β†’ Residue 292
NM_153766.3(KCNJ1):c.874C>T (p.Arg292Trp)Pathogenic
Bartter syndrome|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 292
NM_153766.3(KCNJ1):c.939_942del (p.Glu315fs)Pathogenic
not provided|Bartter disease type 2
β˜…β˜…β˜†β˜†2025β†’ Residue 315
NM_153766.3(KCNJ1):c.867C>A (p.Cys289Ter)Pathogenic
not provided|Bartter disease type 2
β˜…β˜…β˜†β˜†2025β†’ Residue 289
NM_153766.3(KCNJ1):c.89G>A (p.Cys30Tyr)Pathogenic
not provided|Bartter disease type 2|Bartter syndrome|Renal tubulopathies
β˜…β˜…β˜†β˜†2025β†’ Residue 30
NM_153766.3(KCNJ1):c.1001dup (p.His335fs)Pathogenic
not provided|Bartter disease type 2
β˜…β˜…β˜†β˜†2025β†’ Residue 335
NM_153766.3(KCNJ1):c.550C>T (p.Arg184Trp)Likely pathogenic
Bartter disease type 2
β˜…β˜…β˜†β˜†2025β†’ Residue 184
NM_153766.3(KCNJ1):c.308T>A (p.Val103Glu)Likely pathogenic
Bartter disease type 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 103
NM_153766.3(KCNJ1):c.155C>T (p.Thr52Met)Pathogenic
Bartter disease type 2|not provided|Bartter syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 52
NM_153766.3(KCNJ1):c.443G>A (p.Gly148Glu)Likely pathogenic
Bartter disease type 2|Bartter syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 148
NM_153766.3(KCNJ1):c.731T>G (p.Ile244Ser)Likely pathogenic
Bartter disease type 2
β˜…β˜…β˜†β˜†2025β†’ Residue 244
NM_153766.3(KCNJ1):c.551G>A (p.Arg184Gln)Likely pathogenic
Bartter disease type 2
β˜…β˜…β˜†β˜†2025β†’ Residue 184
NM_153766.3(KCNJ1):c.983del (p.Thr328fs)Pathogenic
Bartter disease type 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 328
NM_153766.3(KCNJ1):c.887T>G (p.Val296Gly)Pathogenic
Bartter syndrome|not provided|Bartter disease type 2
β˜…β˜…β˜†β˜†2024β†’ Residue 296
NM_153766.3(KCNJ1):c.251C>T (p.Ala84Val)Pathogenic
Bartter disease type 2|not provided|Bartter syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 84
NM_153766.3(KCNJ1):c.272C>T (p.Pro91Leu)Pathogenic
Bartter disease type 2|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 91
NM_153766.3(KCNJ1):c.76A>G (p.Lys26Glu)Likely pathogenic
not provided|Bartter disease type 2
β˜…β˜…β˜†β˜†2024β†’ Residue 26
NM_153766.3(KCNJ1):c.416_417del (p.Phe139fs)Pathogenic
not provided|Bartter disease type 2
β˜…β˜…β˜†β˜†2024β†’ Residue 139
View on ClinVar β†—
Related Genes
BSNDProtein interaction100%WNK4Protein interaction97%CASRProtein interaction94%CLCNKBProtein interaction94%CFTRProtein interaction93%UMODProtein interaction92%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
26%
Brain
22%
Heart
14%
Liver
6%
Ovary
3%
Gene Interaction Network
Click a node to explore
KCNJ1BSNDWNK4CASRCLCNKBCFTRUMOD
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P48048
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.47LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.05 [0.76–1.47]
RankingsWhere KCNJ1 stands among ~20K protein-coding genes
  • #7,379of 20,598
    Most Researched63
  • #972of 5,498
    Most Pathogenic Variants76 Β· top quartile
  • #15,003of 17,882
    Most Constrained (LOEUF)1.47
Genes detectedKCNJ1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Bartter syndrome.
PMID: 12920401
Curr Opin Nephrol Hypertens Β· 2003
1.00
2
[Bartter's syndrome].
PMID: 15518434
Pol Merkur Lekarski Β· 2004
0.90
3
Late-Onset Bartter Syndrome Type II Due to a Homozygous Mutation in KCNJ1 Gene: A Case Report and Literature Review.
PMID: 32997650
Am J Case Rep Β· 2020
0.80
4
KCNJ1 inhibits tumor proliferation and metastasis and is a prognostic factor in clear cell renal cell carcinoma.
PMID: 25344677
Tumour Biol Β· 2015
0.70
5
Association of KCNJ1 variation with change in fasting glucose and new onset diabetes during HCTZ treatment.
PMID: 22907731
Pharmacogenomics J Β· 2013
0.60