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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
KCNC3
potassium voltage-gated channel subfamily C member 3
Chromosome 19 Β· 19q13.33
NCBI Gene: 3748Ensembl: ENSG00000131398.15HGNC: HGNC:6235UniProt: Q14003
32PubMed Papers
21Diseases
7Drugs
11Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein tetramerizationvoltage-gated potassium channel activitypotassium ion transmembrane transportcell cortexspinocerebellar ataxia type 13multiple sclerosisMyasthenia gravisLambert-Eaton myasthenic syndrome
✦AI Summary

KCNC3 encodes Kv3.3, a voltage-gated potassium channel critical for neuronal excitability. The channel exhibits rapid activation and inactivation kinetics 12, enabling fast-firing neurons to repolarize quickly. In cerebellar Purkinje cells, KCNC3 regulates action potential frequency, shape, and duration, thereby controlling calcium homeostasis and neuronal survival 3. The channel also organizes cortical actin cytoskeleton structures in neuronal growth cones through interactions with HAX1 and the Arp2/3 complex 4. KCNC3 is required for normal motor function 25. Mutations in KCNC3 cause spinocerebellar ataxia type 13 (SCA13), a neurodegenerative disorder presenting with variable onset and severity 6. Disease-causing mutations alter channel function through distinct mechanisms: some eliminate channel activity with dominant-negative effects (e.g., R420H) 7, others shift activation voltage curves, affecting neuronal firing patterns 8. The R420H mutation exhibits aberrant intracellular trafficking, with reduced surface expression and Golgi retention 9. SCA13 manifests as early-onset developmental delay or late-onset cerebellar ataxia, often accompanied by epilepsy, cognitive impairment, and progressive myoclonus 1011. Estimated KCNC3-related SCA13 prevalence in the Netherlands is 0.6-1.3% 8.

Sources cited
1
In cerebellar Purkinje cells, KCNC3 regulates action potential frequency, shape, and duration, thereby controlling calcium homeostasis and neuronal survival .
PMID: 26442672
2
The channel also organizes cortical actin cytoskeleton structures in neuronal growth cones through interactions with HAX1 and the Arp2/3 complex .
PMID: 26997484
3
Mutations in KCNC3 cause spinocerebellar ataxia type 13 (SCA13), a neurodegenerative disorder presenting with variable onset and severity .
PMID: 37301203
4
Disease-causing mutations alter channel function through distinct mechanisms: some eliminate channel activity with dominant-negative effects (e.g., R420H) , others shift activation voltage curves, affecting neuronal firing patterns .
PMID: 18592334
5
Disease-causing mutations alter channel function through distinct mechanisms: some eliminate channel activity with dominant-negative effects (e.g., R420H) , others shift activation voltage curves, affecting neuronal firing patterns .
PMID: 25756792
6
The R420H mutation exhibits aberrant intracellular trafficking, with reduced surface expression and Golgi retention .
PMID: 25152487
Disease Associationsβ“˜21
spinocerebellar ataxia type 13Open Targets
0.84Strong
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
neurodegenerative diseaseOpen Targets
0.42Moderate
genetic disorderOpen Targets
0.41Moderate
neoplasmOpen Targets
0.39Weak
cancerOpen Targets
0.39Weak
cerebellar ataxiaOpen 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
Increased muscle fatiguabilityOpen Targets
0.37Weak
nervous system neoplasmOpen Targets
0.37Weak
neuromuscular junction diseaseOpen Targets
0.37Weak
paraneoplastic neurologic syndromeOpen Targets
0.37Weak
Spinocerebellar ataxia 13UniProt
Pathogenic Variants11
NM_004977.3(KCNC3):c.1259G>A (p.Arg420His)Pathogenic
Spinocerebellar ataxia type 13|not provided|Hereditary ataxia
β˜…β˜…β˜†β˜†2025β†’ Residue 420
NM_004977.3(KCNC3):c.1268G>A (p.Arg423His)Pathogenic
Inborn genetic diseases|not provided|Spinocerebellar ataxia type 13
β˜…β˜…β˜†β˜†2025β†’ Residue 423
NM_004977.3(KCNC3):c.1267C>T (p.Arg423Cys)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 423
NM_004977.3(KCNC3):c.1223A>G (p.Asp408Gly)Likely pathogenic
Spinocerebellar ataxia type 13
β˜…β˜†β˜†β˜†2019β†’ Residue 408
NM_004977.3(KCNC3):c.11_12del (p.Ser4fs)Pathogenic
Spinocerebellar ataxia type 13
β˜…β˜†β˜†β˜†2017β†’ Residue 4
NM_004977.3(KCNC3):c.2079C>G (p.Ile693Met)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2016β†’ Residue 693
NM_004977.3(KCNC3):c.2113C>T (p.Arg705Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2016β†’ Residue 705
NM_004977.3(KCNC3):c.1344C>G (p.Phe448Leu)Pathogenic
not provided
β˜†β˜†β˜†β˜†2016β†’ Residue 448
NM_004977.3(KCNC3):c.1283C>T (p.Thr428Ile)Pathogenic
Spinocerebellar ataxia type 13
β˜†β˜†β˜†β˜†2016β†’ Residue 428
NM_004977.3(KCNC3):c.1344C>A (p.Phe448Leu)Pathogenic
Spinocerebellar ataxia type 13
β˜†β˜†β˜†β˜†2006β†’ Residue 448
NM_004977.3(KCNC3):c.2077A>C (p.Ile693Leu)Likely pathogenic
Tip-toe gait
β˜†β˜†β˜†β˜†β†’ Residue 693
View on ClinVar β†—
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%KCNC4Protein interaction91%KCNAB1Protein interaction91%KCNAB2Protein interaction89%CACNA1AProtein interaction82%SLC17A7Protein interaction81%
Tissue Expression6 tissues
Brain
100%
Liver
55%
Lung
39%
Bone Marrow
35%
Heart
22%
Ovary
3%
Gene Interaction Network
Click a node to explore
KCNC3FAUKCNC4KCNAB1KCNAB2CACNA1ASLC17A7
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q14003
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.65LoF Tolerant
pLIβ“˜
0.30Tolerant
Observed/Expected LoF0.41 [0.27–0.65]
RankingsWhere KCNC3 stands among ~20K protein-coding genes
  • #11,532of 20,598
    Most Researched32
  • #329of 1,025
    FDA-Approved Drug Targets5
  • #2,798of 5,498
    Most Pathogenic Variants11
  • #4,764of 17,882
    Most Constrained (LOEUF)0.65
Genes detectedKCNC3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Sca13.
PMID: 18592334
Cerebellum Β· 2008
1.00
2
Extreme phenotypic heterogeneity in non-expansion spinocerebellar ataxias.
PMID: 37301203
Am J Hum Genet Β· 2023
0.90
3
Diagnosis of hereditary ataxias: a real-world single center experience.
PMID: 39812846
J Neurol Β· 2025
0.80
4
The natural history of progressive myoclonus ataxia.
PMID: 38844245
Neurobiol Dis Β· 2024
0.70
5
KCNC3(R420H), a K(+) channel mutation causative in spinocerebellar ataxia 13 displays aberrant intracellular trafficking.
PMID: 25152487
Neurobiol Dis Β· 2014
0.60