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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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KCNG1
potassium voltage-gated channel modifier subfamily G member 1
Chromosome 20 · 20q13.13
NCBI Gene: 3755Ensembl: ENSG00000026559.15HGNC: HGNC:6248UniProt: Q86Y85
24PubMed Papers
20Diseases
7Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
potassium channel regulator activityvoltage-gated potassium channel complexaction potentialregulation of potassium ion transmembrane transportmultiple sclerosisMyasthenia gravisLambert-Eaton myasthenic syndromeMuscle weakness
✦AI Summary

KCNG1 (Kv6.1) is a regulatory alpha-subunit of voltage-gated potassium channels that functions as a non-pore-forming subunit. When coassembled with KCNB1 or KCNB2, KCNG1 modulates channel expression and gating kinetics by affecting deactivation upon repolarization and inactivation during sustained depolarization 1. KCNG1 does not form functional channels independently but contributes to heteromeric Kv2/KvS channels that predominate in dorsal root ganglion neurons, where they can be pharmacologically distinguished from Kv2-only channels 23. Genetically, KCNG1 variants associate with multiple disease phenotypes. A common variant near KCNG1 was identified in a multi-ancestry Alzheimer's disease GWAS, suggesting involvement in neurodegeneration 4. A heterozygous KCNG1 missense variant (p.Trp416Cys) in a bovine model caused myotonia congenita with craniofacial dysmorphism and myelodysplasia, implicating KCNG1 in neurodegeneration 5. Elevated KCNG1 expression characterizes triple-negative breast cancer and correlates with sensitivity to platinum-based chemotherapy, with guanidine hydrochloride identified as a potential KCNG1 inhibitor 6. Additionally, a KCNG1-proximal variant modifies the protective association between physical activity and colorectal cancer risk 7, and KCNG1 expression predicts cervical cancer radiotherapy sensitivity 8.

Sources cited
1
KCNG1 modulates KCNB1/KCNB2 channel expression and gating kinetics; does not form functional channels independently
PMID: 19074135
2
KCNG1 (Kv6.1) is a KvS subunit forming Kv2/KvS heteromers; predominates in dorsal root ganglion neurons
PMID: 40423692
3
KCNG1 (Kv6.1) forms heteromeric channels with Kv2.1/Kv2.2; contributes to neuronal potassium conductances
PMID: 38352561
4
KCNG1/AL121785.1 locus identified as novel common variant associated with Alzheimer's disease
PMID: 39998322
5
Heterozygous KCNG1 missense variant (p.Trp416Cys) causes myotonia congenita, craniofacial dysmorphism, and myelodysplasia
PMID: 34828398
6
KCNG1 highly expressed in triple-negative breast cancer; associated with platinum chemotherapy sensitivity
PMID: 37311278
7
KCNG1-proximal variant modifies association between physical activity and colorectal cancer risk
PMID: 41645200
8
KCNG1 expression predicts cervical cancer radiotherapy sensitivity
PMID: 38327905
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
congenital myasthenic syndromeOpen Targets
0.43Moderate
Congenital myasthenic syndromesOpen Targets
0.43Moderate
cancerOpen Targets
0.38Weak
neoplasmOpen Targets
0.37Weak
nervous system diseaseOpen Targets
0.37Weak
autoimmune diseaseOpen Targets
0.37Weak
autoimmune disorder of the nervous systemOpen Targets
0.37Weak
cardiac arrhythmiaOpen Targets
0.37Weak
immune system diseaseOpen Targets
0.37Weak
Increased muscle fatiguabilityOpen 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
FXR1Protein interaction100%PCBP2Protein interaction100%HNRNPKProtein interaction96%FAUProtein interaction91%FMR1Protein interaction87%FXR2Protein interaction87%
Tissue Expression6 tissues
Brain
100%
Ovary
51%
Liver
40%
Heart
30%
Lung
26%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
KCNG1FXR1PCBP2HNRNPKFAUFMR1FXR2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q86Y85
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.93LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.61 [0.41–0.93]
RankingsWhere KCNG1 stands among ~20K protein-coding genes
  • #13,218of 20,598
    Most Researched24
  • #333of 1,025
    FDA-Approved Drug Targets5
  • #8,656of 17,882
    Most Constrained (LOEUF)0.93
Genes detectedKCNG1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Identification of 16 novel Alzheimer's disease loci using multi-ancestry meta-analyses.
PMID: 39998322
Alzheimers Dement · 2025
1.00
2
Therapeutic effects of guanidine hydrochloride on breast cancer through targeting KCNG1 gene.
PMID: 37311278
Biomed Pharmacother · 2023
0.90
3
A Kv2 inhibitor combination reveals native neuronal conductances consistent with Kv2/KvS heteromers.
PMID: 40423692
Elife · 2025
0.80
4
Genetic risk factors modulate the association between physical activity and colorectal cancer.
PMID: 41645200
BMC Med · 2026
0.70
5
Naturally occurring genetic diseases caused by de novo variants in domestic animals.
PMID: 38323510
Anim Genet · 2024
0.60