KCNK6
Potassium Two Pore Domain Channel Subfamily K Member 6
Gene Information Card
| Symbol | KCNK6 |
|---|---|
| Full Name | Potassium Two Pore Domain Channel Subfamily K Member 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 9424 ncbi.nlm.nih.gov/gene/9424 |
| Ensembl ID | ENSG00000157551 |
| UniProt ID | Q9Y257 |
| OMIM ID | 603939 |
| HGNC ID | 6278 |
| Aliases | TASK-2, K2P6.1, TASK2 |
Description
KCNK6 encodes a member of the two-pore domain potassium channel family, specifically the TASK-2 (TWIK-related acid-sensitive K+ channel 2) subfamily. The protein forms a homodimeric channel that is sensitive to extracellular pH, with inhibition by acidic pH and activation by alkaline pH. It is involved in the regulation of resting membrane potential and potassium ion homeostasis, particularly in kidney, lung, and nervous system tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary hyperaldosteronism | Gain-of-function mutations in KCNK6 may increase potassium efflux, hyperpolarizing adrenal glomerulosa cells and leading to aldosterone overproduction. | ClinVar, OMIM |
| Seizures | Altered TASK-2 channel activity can disrupt neuronal excitability, contributing to seizure susceptibility. | ClinVar, literature |
| Hypertension | Dysregulation of potassium channels in renal tubules may affect sodium reabsorption and blood pressure regulation. | OMIM, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Lung | 8.3 | Medium |
| Brain | 6.1 | Low |
| Heart | 4.7 | Low |
| Liver | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in recombinant systems |
| A549 | 9.8 | Lung adenocarcinoma cell line |
| SH-SY5Y | 5.4 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.434G>A (p.Arg145His) | Missense | 0.01% (gnomAD) | Gain-of-function; increased channel activity |
| c.688C>T (p.Arg230Cys) | Missense | 0.005% (gnomAD) | Uncertain significance; potential loss-of-function |
| c.1003G>A (p.Gly335Ser) | Missense | 0.002% (gnomAD) | Likely benign |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Arg230Cys) may reduce channel conductance or pH sensitivity.
Gain of Function (GOF)
p.Arg145His increases channel open probability, linked to hyperaldosteronism.
Dominant Negative (DN)
No dominant-negative mutations reported in KCNK6.
View complete mutation data：
Gene Ontology (GO)
| • inward rectifier potassium channel activity (GO:0005242) | • outward rectifier potassium channel activity (GO:0015271) |
| • potassium ion transport (GO:0006813) | • transmembrane transport (GO:0055085) |
| • integral component of membrane (GO:0016021) |
Pathways
• Potassium channels (Reactome: R-HSA-1296071)
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
Protein Summary
The KCNK6 protein (UniProt Q9Y257) is a 409-amino acid two-pore domain potassium channel with four transmembrane segments and two pore-forming loops. It functions as a homodimer, forming a pH-sensitive leak potassium channel. The channel is blocked by extracellular acidification and activated by alkalosis, playing a key role in renal potassium secretion and neuronal excitability. Structural studies indicate a selectivity filter typical of K2P channels.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNK6 Knockout HEK293 Cell Line | EDJ-KQ6584 | Human | 9424 | Details Get a Quote |
| KCNK6 Knockout A-549 Cell Line | EDJ-KQ29458 | Human | 9424 | Details Get a Quote |
| KCNK6 Knockout HCT 116 Cell Line | EDJ-KQ30806 | Human | 9424 | Details Get a Quote |
