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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
KCND3
potassium voltage-gated channel subfamily D member 3
Chromosome 1 Β· 1p13.2
NCBI Gene: 3752Ensembl: ENSG00000171385.12HGNC: HGNC:6239UniProt: Q9UK17
77PubMed Papers
22Diseases
9Drugs
28Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedIon ChannelTransporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
A-type (transient outward) potassium channel activityvoltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarizationprotein bindingpotassium ion transportspinocerebellar ataxia type 19/22atrial fibrillationMyasthenia gravisBrugada syndrome 9
✦AI Summary

KCND3 encodes Kv4.3, a voltage-gated potassium channel subunit that forms A-type potassium channels mediating transient outward potassium currents in excitable tissues 1. The channel exhibits characteristic fast activation at subthreshold membrane potentials, rapid inactivation, and quick recovery from inactivation 1. In cardiac muscle, KCND3 contributes to ventricular repolarization and may generate the transient outward potassium current I(To), with genetic variants associated with early repolarization patterns on ECG and Brugada syndrome 23. In the nervous system, the channel conducts transient subthreshold somatodendritic A-type potassium currents involved in neuronal excitability regulation 4. KCND3 mutations cause spinocerebellar ataxia types 19/22 (SCA19/22) through dominant-negative effects, where mutant channels exhibit loss-of-function phenotypes, enhanced protein degradation, and defective membrane trafficking that disrupts wild-type channel function 1. The clinical spectrum includes both early-onset neurodevelopmental disorders with epilepsy and late-onset ataxic syndromes 45. Recent studies have identified KCND3 variants in childhood epileptic encephalopathies, expanding the recognized phenotypic spectrum beyond traditional cardiac and cerebellar presentations 5.

Sources cited
1
KCND3 encodes Kv4.3 channel with fast activation/inactivation kinetics and causes SCA19/22 through dominant-negative effects
PMID: 31293010
2
KCND3 genetic variants are associated with early repolarization patterns on ECG
PMID: 31600170
3
KCND3 is involved in Brugada syndrome and cardiac repolarization
PMID: 35675436
4
KCND3 mutations cause SCA19/22 with early-onset neurodevelopmental and late-onset ataxic phenotypes
PMID: 32823520
5
KCND3 variants identified in childhood epileptic encephalopathies, expanding the phenotypic spectrum
PMID: 30776697
Disease Associationsβ“˜22
spinocerebellar ataxia type 19/22Open Targets
0.80Strong
atrial fibrillationOpen Targets
0.64Moderate
Myasthenia gravisOpen Targets
0.63Moderate
Brugada syndrome 9Open Targets
0.60Moderate
multiple sclerosisOpen Targets
0.59Moderate
cardiac arrhythmiaOpen Targets
0.56Moderate
Lambert-Eaton myasthenic syndromeOpen Targets
0.55Moderate
neurodegenerative diseaseOpen Targets
0.53Moderate
atrial flutterOpen Targets
0.49Moderate
Muscle weaknessOpen Targets
0.46Moderate
congenital myasthenic syndromeOpen Targets
0.43Moderate
Congenital myasthenic syndromesOpen Targets
0.43Moderate
Abnormality of the cardiovascular systemOpen Targets
0.38Weak
cancerOpen Targets
0.37Weak
nervous system diseaseOpen Targets
0.37Weak
Neurodevelopmental disorderOpen Targets
0.37Weak
neoplasmOpen Targets
0.37Weak
autoimmune diseaseOpen Targets
0.37Weak
autoimmune disorder of the nervous systemOpen Targets
0.37Weak
neuromuscular diseaseOpen Targets
0.37Weak
Brugada syndrome 9UniProt
Spinocerebellar ataxia 19UniProt
Pathogenic Variants28
NM_001378969.1(KCND3):c.1174G>A (p.Val392Ile)Pathogenic
Brugada syndrome 9|not provided|Spinocerebellar ataxia type 19/22
β˜…β˜…β˜†β˜†2024β†’ Residue 392
NM_001378969.1(KCND3):c.1150G>A (p.Gly384Ser)Pathogenic
not provided|Spinocerebellar ataxia type 19/22|Cardiovascular phenotype|Hereditary ataxia
β˜…β˜…β˜†β˜†2024β†’ Residue 384
NM_001378969.1(KCND3):c.677TCT[1] (p.Phe227del)Pathogenic
Spinocerebellar ataxia type 19/22|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 227
NM_001378969.1(KCND3):c.1130C>T (p.Thr377Met)Pathogenic
Spinocerebellar ataxia type 19/22|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 377
NM_001378969.1(KCND3):c.869G>A (p.Arg290Gln)Likely pathogenic
Spinocerebellar ataxia type 19/22|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 290
NM_001378969.1(KCND3):c.1061T>A (p.Ile354Asn)Likely pathogenic
Cardiovascular phenotype
β˜…β˜†β˜†β˜†2025β†’ Residue 354
NM_001378969.1(KCND3):c.905G>A (p.Arg302His)Likely pathogenic
Spinocerebellar ataxia type 19/22
β˜…β˜†β˜†β˜†2025β†’ Residue 302
NM_001378969.1(KCND3):c.1169G>A (p.Ser390Asn)Likely pathogenic
Variant of unknown significance|Spinocerebellar ataxia type 19/22
β˜…β˜†β˜†β˜†2024β†’ Residue 390
NM_001378969.1(KCND3):c.916G>A (p.Gly306Ser)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 306
NM_001378969.1(KCND3):c.1094T>C (p.Met365Thr)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 365
NM_001378969.1(KCND3):c.877_885dup (p.Arg296_Ile297insValPheArg)Likely pathogenic
Spinocerebellar ataxia type 19/22|not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 296
NM_001378969.1(KCND3):c.1129A>G (p.Thr377Ala)Likely pathogenic
Spinocerebellar ataxia type 19/22
β˜…β˜†β˜†β˜†2023β†’ Residue 377
NM_001378969.1(KCND3):c.1201G>A (p.Val401Met)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 401
NM_001378969.1(KCND3):c.848C>G (p.Ser283Cys)Likely pathogenic
Spinocerebellar ataxia type 19/22
β˜…β˜†β˜†β˜†2023β†’ Residue 283
NM_001378969.1(KCND3):c.1153T>C (p.Ser385Pro)Pathogenic
Spinocerebellar ataxia type 19/22|not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 385
NM_001378969.1(KCND3):c.1154C>G (p.Ser385Cys)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 385
NM_001378969.1(KCND3):c.1201G>C (p.Val401Leu)Pathogenic
Epilepsy
β˜…β˜†β˜†β˜†2023β†’ Residue 401
NM_001378969.1(KCND3):c.911C>T (p.Ser304Phe)Likely pathogenic
Spinocerebellar ataxia type 19/22
β˜…β˜†β˜†β˜†2022β†’ Residue 304
NM_001378969.1(KCND3):c.1138G>T (p.Gly380Trp)Likely pathogenic
Spinocerebellar ataxia type 19/22
β˜…β˜†β˜†β˜†2022β†’ Residue 380
NM_001378969.1(KCND3):c.1054A>C (p.Thr352Pro)Pathogenic
Spinocerebellar ataxia type 19/22|not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 352
View on ClinVar β†—
Drug Targets9
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
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
KCNIP4Protein interaction97%DPP6Protein interaction93%FAUProtein interaction91%SCN5AProtein interaction90%KCNIP3Protein interaction87%KCNA4Protein interaction86%
Tissue Expression6 tissues
Brain
100%
Heart
71%
Liver
51%
Lung
7%
Bone Marrow
2%
Ovary
1%
Gene Interaction Network
Click a node to explore
KCND3KCNIP4DPP6FAUSCN5AKCNIP3KCNA4
PROTEIN STRUCTURE
Preparing viewer…
PDB1S1G Β· 2.60 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.30Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.17 [0.10–0.30]
RankingsWhere KCND3 stands among ~20K protein-coding genes
  • #6,175of 20,598
    Most Researched77
  • #233of 1,025
    FDA-Approved Drug Targets7 Β· top quartile
  • #1,872of 5,498
    Most Pathogenic Variants28
  • #1,176of 17,882
    Most Constrained (LOEUF)0.30 Β· top 10%
Genes detectedKCND3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Involvement of muscle satellite cell dysfunction in neuromuscular disorders: Expanding the portfolio of satellite cell-opathies.
PMID: 35302338
Eur J Transl Myol Β· 2022
1.00
2
Efficacy of Exome-Targeted Capture Sequencing to Detect Mutations in Known Cerebellar Ataxia Genes.
PMID: 29482223
JAMA Neurol Β· 2018
0.90
3
KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.
PMID: 31600170
JCI Insight Β· 2019
0.80
4
Novel SCA19/22-associated KCND3 mutations disrupt human K
PMID: 31293010
Hum Mutat Β· 2019
0.70
5
Gene therapy targeting protein trafficking regulator MOG1 in mouse models of Brugada syndrome, arrhythmias, and mild cardiomyopathy.
PMID: 35675436
Sci Transl Med Β· 2022
0.60