HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
KCNK6
potassium two pore domain channel subfamily K member 6
Chromosome 19 · 19q13.2
NCBI Gene: 9424Ensembl: ENSG00000099337.6HGNC: HGNC:6281UniProt: B2RDS2
19PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
lysosomal membranepotassium channel activityoutward rectifier potassium channel activitypotassium ion leak channel activityneuroinflammatory disorderdiabetic ketoacidosisbreast cancerhypertension
✦AI Summary

KCNK6 (TWIK-2) encodes a two-pore domain potassium channel that regulates K+ efflux and plays critical roles in inflammation and ion homeostasis 1. The channel demonstrates voltage-dependent gating and is insensitive to extracellular pH changes 2. KCNK6 promotes NLRP3 inflammasome activation through accelerated potassium channel activity, contributing to inflammation-associated carcinogenesis and colitis progression 1. Loss of Kcnk6 prevented spontaneous colitis and reduced AOM/DSS-induced carcinogenesis severity in mouse models 1. In the inner ear, TWIK-2 is expressed predominantly in the stria vascularis, suggesting involvement in potassium ion recycling pathways that maintain endolymph composition 3. The channel also participates in electrogenic transport in human endolymphatic sac epithelium, contributing to inner ear fluid homeostasis 4. KCNK6 stability is regulated by METTL3-mediated m6A modification through YTHDF2-dependent mechanisms 1. The gene has been identified as a potential biomarker in bladder cancer prognosis models and shows upregulation in epilepsy models 56. Clinical significance includes potential therapeutic targeting for inflammatory diseases and cancer treatment.

Sources cited
1
KCNK6 regulates K+ efflux, promotes NLRP3 inflammasome activation, and contributes to inflammation-associated carcinogenesis
PMID: 39269733
2
TWIK-2 demonstrates voltage-dependent gating and pH insensitivity
PMID: 40161613
3
TWIK-2 is expressed in cochlear stria vascularis and involved in potassium ion recycling
PMID: 14689445
4
KCNK6 participates in electrogenic transport in human endolymphatic sac epithelium
PMID: 26655723
5
KCNK6 identified as biomarker in bladder cancer prognosis models
PMID: 41139554
6
Kcnk6 shows upregulation in pilocarpine-induced status epilepticus
PMID: 40580058
Disease Associationsⓘ20
neuroinflammatory disorderOpen Targets
0.32Weak
diabetic ketoacidosisOpen Targets
0.30Weak
breast cancerOpen Targets
0.08Suggestive
hypertensionOpen Targets
0.06Suggestive
essential hypertensionOpen Targets
0.05Suggestive
essential hypertension, geneticOpen Targets
0.05Suggestive
pulmonary arterial hypertensionOpen Targets
0.05Suggestive
pseudotumor cerebriOpen Targets
0.05Suggestive
supravalvular aortic stenosisOpen Targets
0.05Suggestive
metabolic syndromeOpen Targets
0.05Suggestive
metabolic syndrome XOpen Targets
0.05Suggestive
focal segmental glomerulosclerosisOpen Targets
0.05Suggestive
hyperaldosteronism, familial, type IVOpen Targets
0.04Suggestive
Brachydactyly - arterial hypertensionOpen Targets
0.04Suggestive
brachydactyly-arterial hypertension syndromeOpen Targets
0.04Suggestive
pseudohyperaldosteronism type 2Open Targets
0.04Suggestive
ParagangliomaOpen Targets
0.04Suggestive
pheochromocytoma/paraganglioma syndrome 6Open Targets
0.04Suggestive
familial idiopathic steroid-resistant nephrotic syndromeOpen Targets
0.04Suggestive
cardiomyopathy, familial hypertrophic, 30, atrialOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KRT76Protein interaction98%KCNK13Protein interaction76%KCNK17Shared pathway50%KCNK7Shared pathway50%KCNN3Shared pathway50%KCNT2Shared pathway40%
Tissue Expression6 tissues
Lung
100%
Ovary
90%
Heart
56%
Bone Marrow
39%
Liver
30%
Brain
7%
Gene Interaction Network
Click a node to explore
KCNK6KRT76KCNK13KCNK17KCNK7KCNN3KCNT2
PROTEIN STRUCTURE
Preparing viewer…
PDB9MEK · 2.85 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.54LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.06 [0.74–1.54]
RankingsWhere KCNK6 stands among ~20K protein-coding genes
  • #14,450of 20,598
    Most Researched19
  • #15,386of 17,882
    Most Constrained (LOEUF)1.54
Genes detectedKCNK6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The m6A methyltransferase METTL3 modifies Kcnk6 promoting on inflammation associated carcinogenesis is essential for colon homeostasis and defense system through histone lactylation dependent YTHDF2 binding.
PMID: 39269733
Int Rev Immunol · 2025
1.00
2
Genomic structure, cochlear expression, and mutation screening of KCNK6, a candidate gene for DFNA4.
PMID: 14689445
J Neurosci Res · 2004
0.90
3
Genomic sequencing reveals the structure of the Kcnk6 and map3k11 genes and their close vicinity to the sipa1 gene on mouse chromosome 19.
PMID: 10894943
Cytogenet Cell Genet · 2000
0.80
4
Insights into the structure and modulation of human TWIK-2.
PMID: 40161613
bioRxiv · 2025
0.70
5
Identification of Novel Genetic Risk Factors for Focal Segmental Glomerulosclerosis in Children: Results From the Chronic Kidney Disease in Children (CKiD) Cohort.
PMID: 36623684
Am J Kidney Dis · 2023
0.60