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.
KCNK12
potassium two pore domain channel subfamily K member 12
Chromosome 2 · 2p16.3
NCBI Gene: 56660Ensembl: ENSG00000184261.5HGNC: HGNC:6274UniProt: Q9HB15
15PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
potassium channel activityprotein bindingidentical protein bindingprotein heterodimerization activityneurodegenerative diseasebenign neoplasmpremature birthbiliary tract disease
✦AI Summary

KCNK12 (potassium two pore domain channel subfamily K member 12) encodes a leak potassium channel that functions as a K(+) channel subunit capable of homo- and heterodimerization to form functional channels with distinct regulatory properties [UniProt]. The channel can heterodimerize with KCNK13 to conduct K(+) outward rectifying currents at the plasma membrane, while homodimers are primarily retained in the endoplasmic reticulum and may traffic to the cell surface upon activation signals. KCNK12 is abundantly expressed in mammalian kidney nephron segments including the proximal tubule, thick ascending limb, connecting tubule, and cortical collecting duct, where it fulfills important functions in volume regulation and ion homeostasis 1. The channel is also expressed in mammalian central neurons, suggesting roles in maintaining neuronal phenotype 2. KCNK12 has clinical significance as a methylation biomarker for pancreatic cancer detection; methylated KCNK12 DNA in pancreatic juice achieved an AUC of 0.88 for pancreatic cancer discrimination and was among the most important genes distinguishing COVID-19 infected from recovered patients in respiratory immune profiling 34. A KCNK12 SNP variant (rs748780) shows population-specific associations with MSH2 gene variants across diverse ethnic groups 5. KCNK12 genetic gains have been detected in malignant peripheral nerve sheath tumors and synovial sarcomas 67.

Sources cited
1
KCNK12 (THIK-2) is expressed in proximal tubule, thick ascending limb, connecting tubule, and cortical collecting duct of mammalian kidney
PMID: 18209473
2
KCNK12 (THIK-2) is orthologous to molluscan K2p channel AcK2p1 and is expressed in restricted neuronal populations
PMID: 15306118
3
KCNK12 DNA methylation in pancreatic juice achieves AUC of 0.88 for pancreatic cancer detection
PMID: 26023084
4
KCNK12 SNP variant rs748780 is associated with MSH2 gene and shows population-specific patterns of genetic association
PMID: 24562863
5
KCNK12 was identified as one of the most important genes distinguishing COVID-19 infected from recovered patients
PMID: 36483456
6
KCNK12 is involved in significant gain aberrations in malignant peripheral nerve sheath tumors
PMID: 23830351
7
KCNK12 gains were detected by microarray CGH in synovial sarcoma analysis
PMID: 16557383
8
KCNK12 methylation is used as a marker in pancreatic cancer surgical margin analysis
PMID: 34530906
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.33Weak
benign neoplasmOpen Targets
0.32Weak
premature birthOpen Targets
0.32Weak
biliary tract diseaseOpen Targets
0.29Weak
bronchopneumoniaOpen Targets
0.26Weak
Lung AbscessOpen Targets
0.26Weak
autoimmune thyroid diseaseOpen Targets
0.25Weak
ulcerative colitisOpen Targets
0.22Weak
ovarian neoplasmOpen Targets
0.19Weak
hereditary neoplastic syndromeOpen Targets
0.12Weak
Inherited cancer-predisposing syndromeOpen Targets
0.12Weak
Lynch syndromeOpen Targets
0.12Weak
familial isolated hyperparathyroidismOpen Targets
0.05Suggestive
hyperparathyroidismOpen Targets
0.05Suggestive
hypoparathyroidism, familial isolated, 2Open Targets
0.05Suggestive
intestinal hypomagnesemia 1Open Targets
0.05Suggestive
Primary hypomagnesemia with secondary hypocalcemiaOpen Targets
0.05Suggestive
adamantinomaOpen Targets
0.04Suggestive
ulna metaphyseal dysplasia syndromeOpen Targets
0.04Suggestive
blue diaper syndromeOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KCNK10Shared pathway100%LRRC52Shared pathway100%LRRC26Shared pathway100%LRRC55Shared pathway100%LRRC38Shared pathway100%KCNK18Protein interaction88%
Tissue Expression6 tissues
Brain
100%
Ovary
4%
Bone Marrow
1%
Liver
1%
Lung
1%
Heart
0%
Gene Interaction Network
Click a node to explore
KCNK12KCNK10LRRC52LRRC26LRRC55LRRC38KCNK18
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9HB15
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.92LoF Tolerant
pLIⓘ
0.16Tolerant
Observed/Expected LoF0.47 [0.25–0.92]
RankingsWhere KCNK12 stands among ~20K protein-coding genes
  • #15,598of 20,598
    Most Researched15
  • #8,419of 17,882
    Most Constrained (LOEUF)0.92
Genes detectedKCNK12
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
DNA mismatch repair MSH2 gene-based SNP associated with different populations.
PMID: 24562863
Mol Genet Genomics · 2014
1.00
2
Impact of molecular surgical margin analysis on the prediction of pancreatic cancer recurrences after pancreaticoduodenectomy.
PMID: 34530906
Clin Epigenetics · 2021
0.90
3
Genomic and molecular aberrations in malignant peripheral nerve sheath tumor and their roles in personalized target therapy.
PMID: 23830351
Surg Oncol · 2013
0.80
4
Cellular localization of THIK-1 (K(2P)13.1) and THIK-2 (K(2P)12.1) K channels in the mammalian kidney.
PMID: 18209473
Cell Physiol Biochem · 2008
0.70
5
Respiratory immune status and microbiome in recovered COVID-19 patients revealed by metatranscriptomic analyses.
PMID: 36483456
Front Cell Infect Microbiol · 2022
0.60