HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
KCNS3
potassium voltage-gated channel modifier subfamily S member 3
Chromosome 2 · 2p24.2
NCBI Gene: 3790Ensembl: ENSG00000170745.13HGNC: HGNC:6302UniProt: Q9BQ31
21PubMed Papers
20Diseases
7Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membranecytosolpotassium ion transmembrane transportmembraneMyasthenia gravismultiple sclerosisLambert-Eaton myasthenic syndromeMuscle weakness
✦AI Summary

KCNS3 encodes Kv9.3, a regulatory subunit of voltage-gated potassium channels that does not form functional channels independently but modulates delayed rectifier potassium channel activity when assembled into heteromeric complexes with KCNB1 (Kv2.1) 1. KCNS3-containing channels slow deactivation and inactivation kinetics, amplifying Kv2.1-mediated currents 1. In neurons, Kv2/KCNS3 heteromers comprise a distinct pharmacologically-separable conductance, particularly abundant in dorsal root ganglion neurons 2. KCNS3 is selectively expressed in parvalbumin-positive fast-spiking inhibitory neurons, where it is critical for their characteristic firing properties and participation in gamma-frequency oscillations 3. KCNS3 deficiency disrupts the precise timing of action potentials in these neurons, causing irregular spike trains and impairing gamma oscillation generation 3. Clinically, KCNS3 expression is significantly reduced (~23-40% lower) in prefrontal cortical parvalbumin neurons in schizophrenia patients, potentially contributing to impaired cognitive function and altered neural synchronization characteristic of the disease 43. Additionally, KCNS3 polymorphisms are associated with airway hyperresponsiveness in asthma 5, and specific variants show association with Parkinson's disease risk in Asian populations 6.

Sources cited
1
KCNS3 is a regulatory subunit that modulates KCNB1 delayed rectifier channels by slowing deactivation and inactivation kinetics; forms functional heteromeric channels with KCNB1
PMID: 10484328
2
KCNS3 (Kv9.3) forms heteromeric channels with Kv2 subunits; these heteromers are pharmacologically distinct and predominate in dorsal root ganglion neurons
PMID: 40423692
3
KCNS3 deficiency in parvalbumin neurons causes irregular spike trains, impaired firing at gamma frequencies, and altered action potential timing; is critical for fast-spiking phenotype
PMID: 33940180
4
KCNS3 mRNA expression is 23-40% lower in prefrontal cortical parvalbumin neurons in schizophrenia subjects; involved in precise detection of coincident synaptic inputs and gamma oscillations
PMID: 24170294
5
KCNS3 SNPs (rs1031771, rs1031772) are significantly associated with airway hyperresponsiveness in asthma
PMID: 15714333
6
KCNS3 variant rs76116224 is significantly associated with Parkinson's disease risk in Chinese population
PMID: 34352340
7
KCNB1 and KCNS3 form known heteromeric channel complexes that can interact on liposomes
PMID: 36676855
Disease Associationsⓘ20
Myasthenia gravisOpen Targets
0.62Moderate
multiple sclerosisOpen Targets
0.59Moderate
Lambert-Eaton myasthenic syndromeOpen Targets
0.55Moderate
Muscle weaknessOpen Targets
0.46Moderate
congenital myasthenic syndromeOpen Targets
0.43Moderate
Congenital myasthenic syndromesOpen Targets
0.43Moderate
neoplasmOpen Targets
0.37Weak
cancerOpen 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 diseaseOpen 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
KCNS1Shared pathway100%KCNS2Shared pathway100%FAUProtein interaction91%KCNG1Shared pathway86%KCNG4Shared pathway86%KCNG3Shared pathway86%
Tissue Expression6 tissues
Lung
100%
Heart
45%
Liver
18%
Brain
12%
Ovary
4%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
KCNS3KCNS1KCNS2FAUKCNG1KCNG4KCNG3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9BQ31
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.65LoF Tolerant
pLIⓘ
0.28Tolerant
Observed/Expected LoF0.41 [0.27–0.65]
RankingsWhere KCNS3 stands among ~20K protein-coding genes
  • #13,940of 20,598
    Most Researched21
  • #335of 1,025
    FDA-Approved Drug Targets5
  • #4,644of 17,882
    Most Constrained (LOEUF)0.65
Genes detectedKCNS3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
A Kv2 inhibitor combination reveals native neuronal conductances consistent with Kv2/KvS heteromers.
PMID: 40423692
Elife · 2025
1.00
2
Identification of m
PMID: 37670341
BMC Med Genomics · 2023
0.90
3
Kcns3 deficiency disrupts Parvalbumin neuron physiology in mouse prefrontal cortex: Implications for the pathophysiology of schizophrenia.
PMID: 33940180
Neurobiol Dis · 2021
0.80
4
Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex in schizophrenia.
PMID: 24170294
Am J Psychiatry · 2014
0.70
5
Single-nucleotide polymorphisms of the KCNS3 gene are significantly associated with airway hyperresponsiveness.
PMID: 15714333
Hum Genet · 2005
0.60