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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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KCNJ3
potassium inwardly rectifying channel subfamily J member 3
Chromosome 2 · 2q24.1
NCBI Gene: 3760Ensembl: ENSG00000162989.5HGNC: HGNC:6264UniProt: D2X9V0
57PubMed Papers
20Diseases
2Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedIon ChannelTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
inward rectifier potassium channel activityG-protein activated inward rectifier potassium channel activityprotein bindingpotassium ion import across plasma membraneatrial fibrillationintelligencesmoking initiationmathematical ability
✦AI Summary

KCNJ3 encodes Kir3.1, a G-protein-coupled inwardly rectifying potassium channel that permits preferential potassium influx into cells 12. The channel is characterized by voltage dependence regulated by extracellular potassium concentration, with inward rectification primarily mediated by internal magnesium blockade of outward current. KCNJ3 combines with KCNJ5-encoded Kir3.4 to form the acetylcholine-activated IKACh channel, which plays a critical role in cardiac electrophysiology 3. In disease pathophysiology, gain-of-function KCNJ3 mutations (p.N83H) cause hereditary bradyarrhythmias, sinus node dysfunction, and atrial fibrillation through increased basal IKACh channel current 3. Conversely, loss-of-function de novo variants (p.Leu333Ser, p.Arg313Gln) in the C-terminal domain are associated with early-onset epilepsy, suggesting KCNJ3's role in neuronal excitability 4. In pain homeostasis, the GPR37L1 ligand maresin 1 enhances KCNJ3-mediated potassium influx in satellite glial cells, promoting resolution of chemotherapy-induced neuropathic pain 5. Additionally, elevated KCNJ3 expression correlates with lymph node metastases and poor prognosis in breast cancer 6, with alternative splicing producing dominant-negative isoforms in cancer cells 7. These findings establish KCNJ3 as a multifunctional ion channel with implications for cardiac arrhythmias, neurological disorders, pain syndromes, and oncology.

Sources cited
1
KCNJ3 is a G-protein-controlled inwardly rectifying potassium channel
PMID: 8804710
2
KCNJ3 channel activity is regulated by G proteins
PMID: 8868049
3
KCNJ3 mutations cause bradyarrhythmias and atrial fibrillation; forms IKACh channel with KCNJ5; gain-of-function p.N83H mutation increases basal current; selective blocker NIP-151 improves phenotypes
PMID: 30764634
4
De novo loss-of-function KCNJ3 variants (p.Leu333Ser, p.Arg313Gln) cause early-onset epilepsy; variants located in C-terminal domain reduce current activities
PMID: 37963718
5
GPR37L1 ligand maresin 1 enhances KCNJ3-mediated potassium influx in satellite glial cells; involved in neuropathic pain resolution
PMID: 38530364
6
Increased KCNJ3 expression correlates with lymph node metastases and poor prognosis in breast cancer
PMID: 27698251
7
Alternative splicing of KCNJ3 produces truncated GIRK1 variants with dominant-negative effects in breast cancer cells
PMID: 20512921
Disease Associationsⓘ20
atrial fibrillationOpen Targets
0.53Moderate
intelligenceOpen Targets
0.46Moderate
smoking initiationOpen Targets
0.41Moderate
mathematical abilityOpen Targets
0.41Moderate
denturesOpen Targets
0.39Weak
familial atrial fibrillationOpen Targets
0.39Weak
cardiac arrhythmiaOpen Targets
0.37Weak
atrial flutterOpen Targets
0.34Weak
risk-taking behaviourOpen Targets
0.33Weak
response to xenobiotic stimulusOpen Targets
0.31Weak
sialolithiasisOpen Targets
0.31Weak
Alzheimer diseaseOpen Targets
0.30Weak
poisoningOpen Targets
0.29Weak
dental cariesOpen Targets
0.28Weak
attention deficit hyperactivity disorderOpen Targets
0.28Weak
substance abuseOpen Targets
0.28Weak
nerve plexus diseaseOpen Targets
0.27Weak
malunion fractureOpen Targets
0.27Weak
response to stimulusOpen Targets
0.24Weak
diabetes mellitusOpen Targets
0.23Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets2
VERNAKALANTApproved
Sodium channel protein type V alpha subunit blocker
cardiac arrhythmia
VERNAKALANT HYDROCHLORIDEApproved
Sodium channel protein type V alpha subunit blocker
atrial fibrillation
Related Genes
GNG13Protein interaction100%GNG2Protein interaction100%GNG12Protein interaction100%GABBR1Protein interaction96%GNAI2Protein interaction95%GNB1Protein interaction90%
Tissue Expression6 tissues
Brain
100%
Liver
10%
Heart
10%
Ovary
1%
Lung
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
KCNJ3GNG13GNG2GNG12GABBR1GNAI2GNB1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P48549
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.22Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.10 [0.05–0.22]
RankingsWhere KCNJ3 stands among ~20K protein-coding genes
  • #7,976of 20,598
    Most Researched57
  • #654of 1,025
    FDA-Approved Drug Targets2
  • #588of 17,882
    Most Constrained (LOEUF)0.22 · top 5%
Genes detectedKCNJ3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Satellite glial GPR37L1 and its ligand maresin 1 regulate potassium channel signaling and pain homeostasis.
PMID: 38530364
J Clin Invest · 2024
1.00
2
Critical evaluation of KCNJ3 gene product detection in human breast cancer: mRNA in situ hybridisation is superior to immunohistochemistry.
PMID: 27698251
J Clin Pathol · 2016
0.90
3
Mutant KCNJ3 and KCNJ5 Potassium Channels as Novel Molecular Targets in Bradyarrhythmias and Atrial Fibrillation.
PMID: 30764634
Circulation · 2019
0.80
4
Cloning and characterisation of GIRK1 variants resulting from alternative RNA editing of the KCNJ3 gene transcript in a human breast cancer cell line.
PMID: 20512921
J Cell Biochem · 2010
0.70
5
Genomic organization and promoter analysis of the human G-protein-coupled K+ channel Kir3.1 (KCNJ3/HGIRK1).
PMID: 9119365
Genomics · 1997
0.60