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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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KCNK1
potassium two pore domain channel subfamily K member 1
Chromosome 1 · 1q42.2
NCBI Gene: 3775Ensembl: ENSG00000135750.16HGNC: HGNC:6272UniProt: O00180
45PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
sodium ion transmembrane transportregulation of resting membrane potentialsodium channel activityprotein bindingfunctional neutrophil defectscoliosishyperpigmentation of the skinsinusitis
✦AI Summary

KCNK1 is a potassium two pore domain channel that contributes to membrane potential regulation and ion transport across multiple tissues. The channel forms dimers with low intrinsic activity as homodimers but exhibits enhanced function when heterodimerizing with other KCNK family members 1. In the nervous system, KCNK1 plays a critical role in neuropathic pain regulation, where its downregulation in dorsal spinal horn neurons contributes to pain hypersensitivity through a ciRNA-Kat6b/miRNA-26a/Kcnk1 pathway 2. KCNK1 has also been implicated in trigeminal neuralgia, with genetic variants potentially contributing to disease susceptibility 3. In cardiac tissue, KCNK1 expression differs between atrium and ventricle, and its downregulation is associated with arrhythmic sudden cardiac death, suggesting involvement in lethal arrhythmia susceptibility 4. Emerging evidence indicates KCNK1 has significant oncological relevance, being overexpressed in both breast and bladder cancers where it promotes tumor proliferation, invasion, and metastasis 567. In breast cancer, KCNK1 activates lactate dehydrogenase A and increases glycolysis, while its knockdown enhances chemotherapy sensitivity 7. These diverse functions position KCNK1 as both a potential therapeutic target and prognostic biomarker across multiple disease contexts.

Sources cited
1
KCNK1 expression differs between cardiac atrium and ventricle
PMID: 16257073
2
KCNK1 downregulation in dorsal spinal horn contributes to neuropathic pain through ciRNA-Kat6b/miRNA-26a pathway
PMID: 37144575
3
KCNK1 genetic variants are associated with trigeminal neuralgia susceptibility
PMID: 34000891
4
KCNK1 downregulation is associated with arrhythmic sudden cardiac death
PMID: 39545913
5
KCNK1 promotes breast cancer proliferation and metastasis by activating LDHA and glycolysis
PMID: 38905316
6
KCNK1 is overexpressed in bladder cancer and regulates potassium channels affecting tumor progression
PMID: 38689322
7
KCNK1 overexpression predicts poor prognosis in breast cancer and its knockdown increases paclitaxel sensitivity
PMID: 36566598
Disease Associationsⓘ20
functional neutrophil defectOpen Targets
0.32Weak
scoliosisOpen Targets
0.27Weak
hyperpigmentation of the skinOpen Targets
0.27Weak
sinusitisOpen Targets
0.25Weak
neurodegenerative diseaseOpen Targets
0.20Weak
osteoarthritisOpen Targets
0.19Weak
thyroid cancerOpen Targets
0.19Weak
gastric cancerOpen Targets
0.16Weak
ovarian dysfunctionOpen Targets
0.12Weak
femoral neck fractureOpen Targets
0.11Weak
breast cancerOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.07Suggestive
Pallister-Hall syndromeOpen Targets
0.07Suggestive
head and neck malignant neoplasiaOpen Targets
0.07Suggestive
Dent diseaseOpen Targets
0.05Suggestive
primary Fanconi syndromeOpen Targets
0.05Suggestive
Idiopathic hypercalciuriaOpen Targets
0.05Suggestive
Fanconi renotubular syndrome 1Open Targets
0.05Suggestive
Autosomal recessive infantile hypercalcemiaOpen Targets
0.05Suggestive
hypercalcemia, infantile, 2Open Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KRT76Protein interaction88%KCNK18Protein interaction81%KCNK9Protein interaction79%SENP1Protein interaction73%KCNK2Protein interaction63%KCNK3Protein interaction62%
Tissue Expression6 tissues
Heart
100%
Brain
69%
Liver
29%
Ovary
17%
Lung
7%
Bone Marrow
6%
Gene Interaction Network
Click a node to explore
KCNK1KRT76KCNK18KCNK9SENP1KCNK2KCNK3
PROTEIN STRUCTURE
Preparing viewer…
PDB3UKM · 3.40 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.72LoF Tolerant
pLIⓘ
0.23Tolerant
Observed/Expected LoF0.42 [0.26–0.72]
RankingsWhere KCNK1 stands among ~20K protein-coding genes
  • #9,468of 20,598
    Most Researched45
  • #5,557of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedKCNK1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
KCNK1 promotes proliferation and metastasis of breast cancer cells by activating lactate dehydrogenase A (LDHA) and up-regulating H3K18 lactylation.
PMID: 38905316
PLoS Biol · 2024
1.00
2
Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer.
PMID: 38689322
Eur J Med Res · 2024
0.90
3
Identification of KCNK1 as a potential prognostic biomarker and therapeutic target of breast cancer.
PMID: 36566598
Pathol Res Pract · 2023
0.80
4
Trigeminal neuralgia and genetics: A systematic review.
PMID: 34000891
Mol Pain · 2021
0.70
5
Gene expression profiling of human cardiac potassium and sodium channels.
PMID: 16257073
Int J Cardiol · 2006
0.60