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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.
KCNA1
potassium voltage-gated channel subfamily A member 1
Chromosome 12 Β· 12p13.32
NCBI Gene: 3736Ensembl: ENSG00000111262.6HGNC: HGNC:6218UniProt: Q09470
96PubMed Papers
22Diseases
7Drugs
43Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
juxtaparanode region of axonplasma membranedisordered domain specific bindingmagnesium ion homeostasisepisodic ataxia type 1multiple sclerosisMyasthenia gravisLambert-Eaton myasthenic syndrome
✦AI Summary

KCNA1 encodes Kv1.1, a voltage-gated potassium channel that mediates transmembrane potassium transport primarily in the brain and central nervous system 1. The channel regulates membrane potential and prevents neuronal hyperexcitability by forming tetrameric potassium-selective channels that open in response to membrane depolarization 23. KCNA1 can form homotetrameric delayed-rectifier channels or heterotetrameric channels with other KCNA family members, with properties modulated by cytoplasmic beta subunits 4. The channel is essential for regulating neuronal excitability in the hippocampus, neuromuscular responses, auditory processing, and magnesium ion homeostasis in the kidney 526. KCNA1 mutations cause channelopathies with diverse clinical manifestations. Episodic ataxia type 1 (EA1), the primary KCNA1-associated disorder, results from heterozygous mutations causing recurrent episodes of incoordination triggered by physical exertion or stress 78. Loss-of-function mutations predominantly cause EA1, while mutations clustering in the pore region correlate with epilepsy presentations 910. Emerging phenotypes include paroxysmal kinesigenic dyskinesia and hypomagnesemia, complicated by genetic modifiers influencing disease severity 1110. Understanding KCNA1 genotype-phenotype correlations enables personalized diagnosis and therapeutic strategies for affected patients.

Sources cited
1
KCNA1 mediates transmembrane potassium transport in brain, CNS, and kidney
PMID: 19903818
2
Homotetrameric KCNA1 forms delayed-rectifier potassium channel; role in magnesium ion homeostasis
PMID: 19307729
3
Channel opens in response to membrane depolarization with slow spontaneous closure
PMID: 19912772
4
KCNA1 forms homotetrameric and heterotetrameric channels; modulated by beta subunits
PMID: 12077175
5
KCNA1 required for normal neuromuscular responses
PMID: 11026449
6
KCNA1 plays role in magnesium ion homeostasis in kidney distal convoluted tubules
PMID: 23903368
7
EA1 caused by KCNA1 mutations; recurrent attacks triggered by physical exertion
PMID: 37008993
8
EA1 caused by KCNA1 mutations encoding neuronal voltage-gated potassium channel
PMID: 39174244
9
Epilepsy-linked KCNA1 variants cluster in S1/S2 domains and pore region; EA1 variants distributed throughout protein
PMID: 32316562
10
KCNA1 mutations cause EA1, epilepsy, and emerging phenotypes; gain-of-function variants discovered
PMID: 37240170
11
Both gain- and loss-of-function KCNA1 variants associated with paroxysmal kinesigenic dyskinesia and EA1
PMID: 38570113
Disease Associationsβ“˜22
episodic ataxia type 1Open Targets
0.86Strong
multiple sclerosisOpen Targets
0.59Moderate
Myasthenia gravisOpen Targets
0.56Moderate
Lambert-Eaton myasthenic syndromeOpen Targets
0.55Moderate
MyokymiaOpen Targets
0.51Moderate
Familial paroxysmal ataxiaOpen Targets
0.51Moderate
genetic disorderOpen Targets
0.49Moderate
Familial dyskinesia and facial myokymiaOpen Targets
0.47Moderate
Muscle weaknessOpen Targets
0.46Moderate
Congenital myasthenic syndromesOpen Targets
0.45Moderate
episodic kinesigenic dyskinesia 1Open Targets
0.44Moderate
episodic kinesigenic dyskinesiaOpen Targets
0.44Moderate
congenital myasthenic syndromeOpen Targets
0.43Moderate
neoplasmOpen Targets
0.39Weak
epilepsyOpen Targets
0.38Weak
hereditary continuous muscle fiber activityOpen Targets
0.38Weak
cancerOpen Targets
0.38Weak
nervous system diseaseOpen Targets
0.37Weak
cardiac arrhythmiaOpen Targets
0.37Weak
small cell carcinomaOpen Targets
0.37Weak
Episodic ataxia 1UniProt
Myokymia isolated 1UniProt
Pathogenic Variants43
NM_000217.3(KCNA1):c.913C>T (p.Leu305Phe)Likely pathogenic
not provided|Episodic ataxia type 1
β˜…β˜…β˜†β˜†2025β†’ Residue 305
NM_000217.3(KCNA1):c.745TTC[1] (p.Phe250del)Pathogenic
Inborn genetic diseases|Episodic ataxia type 1|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 250
NM_000217.3(KCNA1):c.1249C>T (p.Arg417Ter)Pathogenic
Episodic ataxia type 1|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 417
NM_000217.3(KCNA1):c.941T>C (p.Ile314Thr)Likely pathogenic
not provided|Episodic ataxia type 1
β˜…β˜…β˜†β˜†2025β†’ Residue 314
NM_000217.3(KCNA1):c.677C>T (p.Thr226Met)Pathogenic
Episodic ataxia type 1|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 226
NM_000217.3(KCNA1):c.677C>G (p.Thr226Arg)Pathogenic
Episodic ataxia type 1|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 226
NM_000217.3(KCNA1):c.520G>T (p.Val174Phe)Pathogenic
Episodic ataxia type 1|Inborn genetic diseases
β˜…β˜…β˜†β˜†2024β†’ Residue 174
NM_000217.3(KCNA1):c.1210G>A (p.Val404Ile)Pathogenic
Episodic ataxia type 1|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 404
NM_000217.3(KCNA1):c.847G>A (p.Glu283Lys)Pathogenic
Episodic ataxia type 1
β˜…β˜…β˜†β˜†2023β†’ Residue 283
NM_000217.3(KCNA1):c.785T>C (p.Ile262Thr)Pathogenic
Episodic ataxia type 1|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 262
NM_000217.3(KCNA1):c.1213C>G (p.Pro405Ala)Likely pathogenic
Inborn genetic diseases|Episodic ataxia type 1
β˜…β˜…β˜†β˜†2022β†’ Residue 405
NM_000217.3(KCNA1):c.1214C>T (p.Pro405Leu)Pathogenic
not provided|Episodic ataxia type 1
β˜…β˜…β˜†β˜†2022β†’ Residue 405
NM_000217.3(KCNA1):c.1187G>T (p.Gly396Val)Pathogenic
Episodic kinesigenic dyskinesia|Episodic ataxia type 1
β˜…β˜…β˜†β˜†2021β†’ Residue 396
NM_000217.3(KCNA1):c.992T>C (p.Phe331Ser)Likely pathogenic
Episodic ataxia type 1
β˜…β˜†β˜†β˜†2026β†’ Residue 331
NM_000217.3(KCNA1):c.893G>C (p.Arg298Thr)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 298
NM_000217.3(KCNA1):c.677C>A (p.Thr226Lys)Pathogenic
Myokymia 1|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 226
NM_000217.3(KCNA1):c.974A>G (p.Glu325Gly)Likely pathogenic
Episodic ataxia type 1
β˜…β˜†β˜†β˜†2025β†’ Residue 325
NM_000217.3(KCNA1):c.1241T>C (p.Phe414Ser)Likely pathogenic
Episodic ataxia type 1
β˜…β˜†β˜†β˜†2025β†’ Residue 414
NM_000217.3(KCNA1):c.730C>T (p.Pro244Ser)Likely pathogenic
Episodic ataxia type 1
β˜…β˜†β˜†β˜†2024β†’ Residue 244
NM_000217.3(KCNA1):c.1126G>A (p.Gly376Ser)Pathogenic
Episodic ataxia type 1
β˜…β˜†β˜†β˜†2024β†’ Residue 376
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
LGI1Protein interaction100%KCNA4Protein interaction96%KCNAB2Protein interaction95%SCN2AProtein interaction95%ADAM22Protein interaction94%CNTN2Protein interaction94%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
0%
Ovary
0%
Liver
0%
Heart
0%
Lung
0%
Gene Interaction Network
Click a node to explore
KCNA1LGI1KCNA4KCNAB2SCN2AADAM22CNTN2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q09470
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.94LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.64 [0.44–0.94]
RankingsWhere KCNA1 stands among ~20K protein-coding genes
  • #4,988of 20,598
    Most Researched96 Β· top quartile
  • #300of 1,025
    FDA-Approved Drug Targets5
  • #1,465of 5,498
    Most Pathogenic Variants43
  • #8,669of 17,882
    Most Constrained (LOEUF)0.94
Genes detectedKCNA1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Episodic Ataxias: Primary and Secondary Etiologies, Treatment, and Classification Approaches.
PMID: 37008993
Tremor Other Hyperkinet Mov (N Y) Β· 2023
1.00
2
Potassium channels and epilepsy.
PMID: 36225112
Acta Neurol Scand Β· 2022
0.90
3
The episodic ataxias.
PMID: 39174244
Handb Clin Neurol Β· 2024
0.80
4
Episodic ataxias.
PMID: 29891059
Handb Clin Neurol Β· 2018
0.70
5
Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas.
PMID: 22358457
Acta Neuropathol Β· 2012
0.60