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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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KCNK13
potassium two pore domain channel subfamily K member 13
Chromosome 14 · 14q32.11
NCBI Gene: 56659Ensembl: ENSG00000152315.6HGNC: HGNC:6275UniProt: Q9HB14
18PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
potassium channel activityprotein bindingidentical protein bindingprotein heterodimerization activityvein disorderVaricose veinsrestless legs syndromelymphatic system disease
✦AI Summary

KCNK13 encodes THIK-1, a two-pore domain potassium channel that conducts outward rectifying tonic currents and plays a critical role in microglial function and neuroinflammation 1. The channel is specifically expressed in human microglia compared to other brain cell types and shows elevated expression in Alzheimer's disease and Parkinson's disease brains 23. KCNK13 maintains the resting membrane potential required for proper microglial morphology and phagocytosis, and contributes to ATP-triggered potassium efflux that underlies microglial NLRP3 inflammasome assembly and IL-1β release 3. The channel can be activated by arachidonic acid and linoleic acid, while being inhibited by halothane through binding sites within the inner cavity 14. Structurally, THIK-1 contains a distinctive tyrosine gate in the M4 transmembrane domain and a modulatory lipid-binding pocket that influences channel activity 1. Beyond the brain, KCNK13 is also expressed in kidney proximal tubules, thick ascending limbs, and collecting ducts, suggesting additional physiological roles 5. The channel's role in neuroinflammation makes it an attractive therapeutic target, with selective inhibitors like CVN293 and C101248 showing promise for treating neurodegenerative diseases by blocking microglial inflammasome activation 63.

Sources cited
1
THIK-1 structure reveals tyrosine gate in M4 domain and lipid-binding modulatory pocket
PMID: 40011745
2
KCNK13 expression elevated in Alzheimer's and Parkinson's disease brains
PMID: 37718820
3
THIK-1 specifically expressed in microglia and involved in NLRP3 inflammasome activation
PMID: 36375694
4
Channel activated by arachidonic acid and exhibits outward rectifying currents
PMID: 30472253
5
THIK-1 expressed in kidney proximal tubules, thick ascending limbs, and collecting ducts
PMID: 18209473
6
CVN293 is a brain-permeable THIK-1 inhibitor for clinical development
PMID: 38746889
7
C101248 selectively inhibits THIK-1 and prevents microglial IL-1β release
PMID: 36375694
Disease Associationsⓘ20
vein disorderOpen Targets
0.42Moderate
Varicose veinsOpen Targets
0.42Moderate
restless legs syndromeOpen Targets
0.38Weak
lymphatic system diseaseOpen Targets
0.38Weak
complicationOpen Targets
0.28Weak
hemorrhageOpen Targets
0.28Weak
oral mucosa leukoplakiaOpen Targets
0.26Weak
placenta praeviaOpen Targets
0.23Weak
brain aneurysmOpen Targets
0.23Weak
diabetes mellitusOpen Targets
0.22Weak
Blackfan-Diamond anemiaOpen Targets
0.08Suggestive
inosine triphosphatase deficiencyOpen Targets
0.06Suggestive
alpha thalassemia-intellectual disability syndrome type 1Open Targets
0.06Suggestive
Alpha-thalassemia - intellectual disability syndrome linked to chromosome 16Open Targets
0.06Suggestive
Neutropenia - monocytopenia - deafnessOpen Targets
0.05Suggestive
neutropenia-monocytopenia-deafness syndromeOpen Targets
0.05Suggestive
Adult-onset autosomal recessive sideroblastic anemiaOpen Targets
0.05Suggestive
autosomal dominant sideroblastic anemiaOpen Targets
0.05Suggestive
Constitutional sideroblastic anemiaOpen Targets
0.05Suggestive
X-linked severe congenital neutropeniaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KCNK18Protein interaction88%KCNK6Protein interaction76%KRT76Protein interaction76%KCNK4Protein interaction73%KCNK12Protein interaction72%KCNK7Protein interaction72%
Tissue Expression6 tissues
Brain
100%
Heart
95%
Bone Marrow
61%
Lung
42%
Liver
25%
Ovary
11%
Gene Interaction Network
Click a node to explore
KCNK13KCNK18KCNK6KRT76KCNK4KCNK12KCNK7
PROTEIN STRUCTURE
Preparing viewer…
PDB9C09 · 2.36 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.94LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.58 [0.37–0.94]
RankingsWhere KCNK13 stands among ~20K protein-coding genes
  • #14,723of 20,598
    Most Researched18
  • #8,724of 17,882
    Most Constrained (LOEUF)0.94
Genes detectedKCNK13
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Role of Microglia in Ataxias.
PMID: 30660620
J Mol Biol · 2019
1.00
2
Elevated Expression of Two Pore Potassium Channel THIK-1 in Alzheimer's Disease: An Inflammatory Mechanism.
PMID: 37718820
J Alzheimers Dis · 2023
0.90
3
Cryo-EM structure of the human THIK-1 K2P K
PMID: 40011745
Nat Struct Mol Biol · 2025
0.80
4
Cloning and characterization of zebrafish K
PMID: 30472253
J Mol Cell Cardiol · 2019
0.70
5
Discovery of CVN293, a Brain Permeable KCNK13 (THIK-1) Inhibitor Suitable for Clinical Assessment.
PMID: 38746889
ACS Med Chem Lett · 2024
0.60