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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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KCNG3
potassium voltage-gated channel modifier subfamily G member 3
Chromosome 2 · 2p21
NCBI Gene: 170850Ensembl: ENSG00000171126.8HGNC: HGNC:18306UniProt: Q8TAE7
18PubMed Papers
20Diseases
7Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of potassium ion transportregulation of potassium ion transmembrane transportplasma membranevoltage-gated potassium channel complexmultiple sclerosisMyasthenia gravisLambert-Eaton myasthenic syndromeMuscle weakness
✦AI Summary

KCNG3 is a regulatory subunit of voltage-gated potassium channels that functions as a modifier of channel kinetics rather than forming functional channels independently. KCNG3 assembles with Kv2.1 (KCNB1) or Kv2.2 (KCNB2) to form heteromeric Kv2/KvS channels, which can be pharmacologically distinguished from Kv2-only channels by their resistance to RY785 pore-blocker while remaining sensitive to guangxitoxin-1E 12. The protein modulates potassium ion efflux and appears to regulate macrophage polarization through ASK1 activation, with KCNG3 knockdown promoting M1 polarization and enhancing inflammatory responses 3. KCNG3 is expressed in various tissues including neurons, interstitial cells of Cajal, and smooth muscle, with significant downregulation observed in Hirschsprung's disease suggesting a role in gastrointestinal motility 4. The gene shows altered methylation patterns in various cancers including lung adenocarcinomas and gastric cancer, where it functions as an oncogenic target of tumor suppressor miR-148a-5p 56. Additionally, KCNG3 is overexpressed in prostate cancer and shows potential gender-specific methylation differences in schizophrenia 78.

Sources cited
1
KCNG3 forms heteromeric channels with Kv2 subunits that are pharmacologically distinguishable from Kv2-only channels
PMID: 40423692
2
Kv2/KvS heteromeric channels containing KCNG3 are resistant to RY785 but sensitive to guangxitoxin-1E
PMID: 38352561
3
KCNG3 regulates macrophage polarization via potassium ion efflux and ASK1 activation
PMID: 40255142
4
KCNG3 expression is downregulated in Hirschsprung's disease and is found in neurons, ICC, and smooth muscle
PMID: 30386900
5
KCNG3 shows hypermethylation in lung adenocarcinomas
PMID: 22143938
6
KCNG3 is an oncogenic target of miR-148a-5p in gastric cancer
PMID: 32235846
7
KCNG3 is overexpressed in prostate cancer
PMID: 28380430
8
KCNG3 shows gender-specific methylation differences in schizophrenia patients
PMID: 25840049
Disease Associationsⓘ20
multiple sclerosisOpen Targets
0.59Moderate
Myasthenia gravisOpen Targets
0.56Moderate
Lambert-Eaton myasthenic syndromeOpen Targets
0.55Moderate
Muscle weaknessOpen Targets
0.46Moderate
Abnormality of the skeletal systemOpen Targets
0.44Moderate
congenital myasthenic syndromeOpen Targets
0.43Moderate
Congenital myasthenic syndromesOpen Targets
0.43Moderate
neoplasmOpen Targets
0.39Weak
cancerOpen Targets
0.38Weak
autoimmune diseaseOpen Targets
0.37Weak
cardiac arrhythmiaOpen Targets
0.37Weak
immune system diseaseOpen Targets
0.37Weak
Increased muscle fatiguabilityOpen Targets
0.37Weak
nervous system diseaseOpen Targets
0.37Weak
nervous system neoplasmOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.37Weak
neuromuscular diseaseOpen Targets
0.37Weak
neuromuscular junction diseaseOpen Targets
0.37Weak
paraneoplastic neurologic syndromeOpen Targets
0.37Weak
small cell carcinomaOpen Targets
0.37Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets7
AMIFAMPRIDINEApproved
Voltage-gated potassium channel blocker
Myasthenia gravis
AMIFAMPRIDINE PHOSPHATEApproved
Voltage-gated potassium channel blocker
Lambert-Eaton myasthenic syndrome
DALFAMPRIDINEApproved
Voltage-gated potassium channel blocker
multiple sclerosis
GUANIDINEPhase III
Voltage-gated potassium channel blocker
neuroendocrine neoplasm
GUANIDINE HYDROCHLORIDEApproved
Voltage-gated potassium channel blocker
Myasthenia gravis
NERISPIRDINEPhase II
Voltage-gated potassium channel blocker
multiple sclerosis
TEDISAMILApproved
Voltage-gated potassium channel blocker
cardiac arrhythmia
Related Genes
FAUProtein interaction91%KCNS3Shared pathway86%KCNS1Shared pathway86%KCNG4Shared pathway72%KCNV2Shared pathway71%KCNV1Shared pathway71%
Tissue Expression6 tissues
Brain
100%
Ovary
42%
Bone Marrow
8%
Lung
6%
Heart
0%
Liver
0%
Gene Interaction Network
Click a node to explore
KCNG3FAUKCNS3KCNS1KCNG4KCNV2KCNV1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8TAE7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.95LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.62 [0.41–0.95]
RankingsWhere KCNG3 stands among ~20K protein-coding genes
  • #14,722of 20,598
    Most Researched18
  • #340of 1,025
    FDA-Approved Drug Targets5
  • #8,896of 17,882
    Most Constrained (LOEUF)0.95
Genes detectedKCNG3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
A Kv2 inhibitor combination reveals native neuronal conductances consistent with Kv2/KvS heteromers.
PMID: 40423692
Elife · 2025
1.00
2
Altered expression of KCNG3 and KCNG4 in Hirschsprung's disease.
PMID: 30386900
Pediatr Surg Int · 2019
0.90
3
Early onset schizophrenia: Gender analysis of genome-wide potential methylation.
PMID: 25840049
Clin Chim Acta · 2015
0.80
4
The Polarization of Macrophages Regulated by KCNG3 via the Activation of ASK1 Mediated by Potassium Ion Efflux.
PMID: 40255142
Cell Biol Int · 2025
0.70
5
DNA methylation biomarkers for lung cancer.
PMID: 22143938
Tumour Biol · 2012
0.60