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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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KCNH8
potassium voltage-gated channel subfamily H member 8
Chromosome 3 · 3p24.3
NCBI Gene: 131096Ensembl: ENSG00000183960.10HGNC: HGNC:18864UniProt: Q96L42
14PubMed Papers
20Diseases
7Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
delayed rectifier potassium channel activityplasma membranepotassium ion transportpotassium ion transmembrane transportmultiple sclerosisMyasthenia gravisLambert-Eaton myasthenic syndromeneurodegenerative disease
✦AI Summary

KCNH8 encodes the pore-forming subunit of a voltage-gated delayed rectifier potassium channel that mediates outward-rectifying potassium currents 1. The channel exhibits slowly activating, non-inactivating kinetics with slow deactivation, opening at hyperpolarized potentials (half-maximal activation at -62 mV) 2. KCNH8 is primarily expressed in the human nervous system with substantial overlap with related Elk family channels KCNH3 and KCNH4 2. The channel can form heteromultimers with other Elk family members but not with Eag, Erg, or Kv family channels 2. Genetically, KCNH8 variants associate with multiple common disorders. Genome-wide association studies identified KCNH8 as a susceptibility locus for chr3 venous disease 3 and eczema 4. The KCNH8 rs4973706 polymorphism associates with elite rugby union athletic status, with TT genotype carriers showing 1.57-fold greater odds of elite athlete status 5. KCNH8 variants also predict maximal oxygen uptake (VO₂max) trainability response 6. In disease contexts, KCNH8 mutations appear in peripheral T cell lymphoma 7 and associate with rectal cancer radiotherapy resistance 8. These findings suggest KCNH8's broader physiological roles beyond neuronal potassium homeostasis, potentially involving vascular function, immune regulation, and metabolic adaptation.

Sources cited
1
KCNH8 is the pore-forming subunit of a voltage-gated delayed rectifier potassium channel mediating outward-rectifying currents with slowly activating, non-inactivating, and slowly deactivating kinetics
PMID: 11897058
2
KCNH8 is primarily expressed in the human nervous system, opens at hyperpolarized potentials (-62 mV half-maximal activation), and forms heteromultimers with other Elk family channels but not with Eag, Erg, or Kv channels
PMID: 12890647
3
KCNH8 is a genome-wide significant susceptibility locus for chronic venous disease
PMID: 28374850
4
KCNH8 rs4973706 TT genotype associates with elite rugby union athletic status
PMID: 34088882
5
KCNH8 variants predict VO₂max trainability response to standardized exercise training
PMID: 21183627
6
KCNH8 harbors somatic mutations in peripheral T cell lymphoma
PMID: 26536348
7
KCNH8 is an unfavorable epithelial-associated marker associated with rectal cancer radiotherapy resistance
PMID: 39520737
8
KCNH8 common variants at SATB1-AS1/KCNH8 associate with eczema susceptibility
PMID: 34785669
Disease Associationsⓘ20
multiple sclerosisOpen Targets
0.60Moderate
Myasthenia gravisOpen Targets
0.56Moderate
Lambert-Eaton myasthenic syndromeOpen Targets
0.55Moderate
neurodegenerative diseaseOpen Targets
0.54Moderate
Muscle weaknessOpen Targets
0.46Moderate
congenital myasthenic syndromeOpen Targets
0.43Moderate
Congenital myasthenic syndromesOpen Targets
0.43Moderate
autoimmune diseaseOpen Targets
0.39Weak
neoplasmOpen Targets
0.37Weak
cancerOpen Targets
0.37Weak
nervous system 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 neoplasmOpen 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 Variants1
NM_144633.3(KCNH8):c.298T>C (p.Tyr100His)Likely pathogenic
Action myoclonus-renal failure syndrome
★☆☆☆→ Residue 100
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
KCNH4Shared pathway100%KCNH3Shared pathway100%KCNH7Shared pathway100%ELK4Protein interaction97%ELK3Protein interaction87%KCNH5Shared pathway80%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
32%
Heart
3%
Liver
2%
Ovary
1%
Lung
0%
Gene Interaction Network
Click a node to explore
KCNH8KCNH4KCNH3KCNH7ELK4ELK3KCNH5
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96L42
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.81LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.66 [0.54–0.81]
RankingsWhere KCNH8 stands among ~20K protein-coding genes
  • #15,898of 20,598
    Most Researched14
  • #343of 1,025
    FDA-Approved Drug Targets5
  • #5,443of 5,498
    Most Pathogenic Variants1
  • #6,807of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedKCNH8
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Distribution and functional properties of human KCNH8 (Elk1) potassium channels.
PMID: 12890647
Am J Physiol Cell Physiol · 2003
1.00
2
Deconvolution of cell-type-associated markers predictive of response to neoadjuvant radiotherapy.
PMID: 39520737
Comput Biol Chem · 2024
0.90
3
Genome-wide association analysis for chronic venous disease identifies EFEMP1 and KCNH8 as susceptibility loci.
PMID: 28374850
Sci Rep · 2017
0.80
4
Genetic Polymorphisms Related to VO2max Adaptation Are Associated With Elite Rugby Union Status and Competitive Marathon Performance.
PMID: 34088882
Int J Sports Physiol Perform · 2021
0.70
5
Concurrent Mutations in ATM and Genes Associated with Common γ Chain Signaling in Peripheral T Cell Lymphoma.
PMID: 26536348
PLoS One · 2015
0.60