HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
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.
KCND2
potassium voltage-gated channel subfamily D member 2
Chromosome 7 Β· 7q31.31
NCBI Gene: 3751Ensembl: ENSG00000184408.10HGNC: HGNC:6238UniProt: A4D0V9
80PubMed Papers
20Diseases
7Drugs
8Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
membrane repolarizationaction potentialpotassium ion transmembrane transportvoltage-gated potassium channel activitymultiple sclerosisMyasthenia gravisLambert-Eaton myasthenic syndromeearly-infantile DEE
✦AI Summary

KCND2 encodes Kv4.2, a voltage-gated potassium channel that mediates A-type potassium currents in neurons and cardiac cells 1. In the brain, KCND2 conducts the dendritic A-type current (I_SA), regulating neuronal excitability, action potential firing frequency, and back-propagation [UniProt]. The channel functions as a tetrameric complex, with surface expression and kinetics modulated by regulatory subunits including KCNIP family members [UniProt]. KCND2 plays roles in circadian rhythm regulation and pain signaling via metabotropic glutamate receptor pathways [UniProt]. Mutations in KCND2 are associated with genetic epilepsy, representing a significant research focus for precision therapy 2. KCND2 expression at the cancer-neuron interface in glioblastoma enhances neuronal excitability through extracellular potassium accumulation, linking the channel to seizure development in brain tumors 3. In breast cancer, elevated KCND2 expression correlates with reduced survival and promotes cell proliferation, migration, and G1/S phase transition 45. Conversely, KCND2 mutations do not frequently cause long QT syndrome, despite theoretical cardiac involvement 6. These findings establish KCND2 as both a critical regulator of neuronal excitability and an emerging oncogenic factor in multiple cancer types.

Sources cited
1
KCND2 mutations cause genetic epilepsy and are targets for precision therapy
PMID: 36225112
2
KCND2 at cancer-neuron interface enhances neuronal excitability via extracellular K+ accumulation in epileptogenic glioblastoma
PMID: 39532103
3
KCND2 overexpression promotes breast cancer proliferation, invasion, migration, and predicts poor prognosis
PMID: 37522982
4
KCND2 is a vasculogenic mimicry-related biomarker in triple-negative breast cancer affecting cell proliferation and migration
PMID: 38728245
5
KCND2 mutations are not a frequent cause of long QT syndrome
PMID: 15563876
6
KCND2/Kv4.2 mediates A-type currents (I_TO and I_SA) in heart and neurons with tissue-specific expression
PMID: 10729221
7
KCND2 is located on chromosome 7q31 with six exons in its genomic structure
PMID: 10942109
Disease Associationsβ“˜20
multiple sclerosisOpen Targets
0.59Moderate
Myasthenia gravisOpen Targets
0.56Moderate
Lambert-Eaton myasthenic syndromeOpen Targets
0.55Moderate
early-infantile DEEOpen Targets
0.52Moderate
Muscle weaknessOpen Targets
0.46Moderate
genetic disorderOpen Targets
0.45Moderate
congenital myasthenic syndromeOpen Targets
0.43Moderate
Congenital myasthenic syndromesOpen Targets
0.43Moderate
KCND2-related neurodevelopmental disorder with or without seizuresOpen Targets
0.42Moderate
smoking initiationOpen Targets
0.40Weak
neoplasmOpen Targets
0.38Weak
cancerOpen Targets
0.37Weak
Global developmental delayOpen Targets
0.37Weak
SeizureOpen Targets
0.37Weak
cardiac arrhythmiaOpen Targets
0.37Weak
nervous system diseaseOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.37Weak
immune system diseaseOpen Targets
0.37Weak
Increased muscle fatiguabilityOpen Targets
0.37Weak
paraneoplastic neurologic syndromeOpen Targets
0.37Weak
Pathogenic Variants8
NM_012281.3(KCND2):c.1210G>A (p.Val404Met)Pathogenic
not provided|Early myoclonic encephalopathy|Inborn genetic diseases|KCND2-related neurodevelopmental disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 404
NM_012281.3(KCND2):c.1207C>G (p.Pro403Ala)Pathogenic
Early myoclonic encephalopathy|Neurodevelopmental disorder|KCND2-related neurodevelopmental disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 403
NM_012281.3(KCND2):c.1208C>T (p.Pro403Leu)Pathogenic
Early myoclonic encephalopathy|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2023β†’ Residue 403
NM_012281.3(KCND2):c.1184T>C (p.Val395Ala)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 395
NM_012281.3(KCND2):c.1215T>G (p.Ile405Met)Likely pathogenic
Early myoclonic encephalopathy
β˜…β˜†β˜†β˜†2022β†’ Residue 405
NM_012281.3(KCND2):c.1096G>T (p.Val366Phe)Pathogenic
Early myoclonic encephalopathy
β˜…β˜†β˜†β˜†2022β†’ Residue 366
NM_012281.3(KCND2):c.1204G>C (p.Val402Leu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 402
NM_012281.3(KCND2):c.913C>T (p.Arg305Cys)Pathogenic
Early myoclonic encephalopathy
β˜…β˜†β˜†β˜†2021β†’ Residue 305
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
KCNE2Protein interaction100%KCNE1Protein interaction99%KCNIP3Protein interaction99%SCN5AProtein interaction98%KCNIP4Protein interaction97%KCNN2Protein interaction94%
Tissue Expression6 tissues
Brain
100%
Ovary
55%
Heart
2%
Lung
2%
Liver
2%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
KCND2KCNE2KCNE1KCNIP3SCN5AKCNIP4KCNN2
PROTEIN STRUCTURE
Preparing viewer…
PDB7UKG Β· 2.24 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.43Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.27 [0.18–0.43]
RankingsWhere KCND2 stands among ~20K protein-coding genes
  • #5,935of 20,598
    Most Researched80
  • #308of 1,025
    FDA-Approved Drug Targets5
  • #3,064of 5,498
    Most Pathogenic Variants8
  • #2,292of 17,882
    Most Constrained (LOEUF)0.43 Β· top quartile
Genes detectedKCND2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Potassium channels and epilepsy.
PMID: 36225112
Acta Neurol Scand Β· 2022
1.00
2
Potassium ion channel modulation at cancer-neural interface enhances neuronal excitability in epileptogenic glioblastoma multiforme.
PMID: 39532103
Neuron Β· 2025
0.90
3
Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors.
PMID: 35685361
Comput Struct Biotechnol J Β· 2022
0.80
4
Promoting proliferation and tumorigenesis of breast cancer: KCND2's significance as a prognostic factor.
PMID: 37522982
Funct Integr Genomics Β· 2023
0.70
5
Mutations in the genes KCND2 and KCND3 encoding the ion channels Kv4.2 and Kv4.3, conducting the cardiac fast transient outward current (ITO,f), are not a frequent cause of long QT syndrome.
PMID: 15563876
Clin Chim Acta Β· 2005
0.60