KCNK16 (Potassium Two Pore Domain Channel Subfamily K Member 16)
A pH-sensitive potassium channel implicated in pancreatic function and potential cancer biology
Gene Information Card
| Symbol | KCNK16 |
|---|---|
| Full Name | Potassium Two Pore Domain Channel Subfamily K Member 16 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p21.2 |
| NCBI Gene ID | 83795 ncbi.nlm.nih.gov/gene/83795 |
| Ensembl ID | ENSG00000153885 |
| UniProt ID | Q96T54 |
| OMIM ID | 607370 |
| HGNC ID | 20317 |
| Aliases | TALK-1, TALK1, K2P16.1 |
Description
KCNK16 encodes a member of the two-pore-domain potassium channel family, specifically the TWIK-related alkaline pH-activated channel (TALK-1). This channel is characterized by its sensitivity to extracellular pH, being activated by alkaline conditions. KCNK16 is predominantly expressed in the pancreas, particularly in insulin-secreting beta cells, where it contributes to the regulation of resting membrane potential and insulin secretion. Its expression has also been detected in other tissues, and emerging evidence suggests a role in certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | Altered KCNK16 expression or function may affect insulin secretion, contributing to beta-cell dysfunction. | Association studies and functional experiments in beta-cell models (e.g., PMID: 25552656, 28953879) |
| Pancreatic Cancer | KCNK16 expression is upregulated in pancreatic ductal adenocarcinoma and may promote tumor growth and migration. | Expression analysis in tumor samples and in vitro studies (e.g., PMID: 31133751) |
| Maturity-Onset Diabetes of the Young (MODY) | Potential rare variants in KCNK16 could impair beta-cell function, though definitive clinical evidence is limited. | Case reports and functional characterization of variants (e.g., PMID: 28953879) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 82.3 | High |
| Stomach | 12.1 | Low |
| Small Intestine | 8.5 | Low |
| Kidney | 5.2 | Low |
| Liver | 3.1 | Low |
| Lung | 1.8 | Not detected |
| Brain | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| PANC-1 | 15.2 | Pancreatic cancer cell line |
| MIA PaCa-2 | 12.8 | Pancreatic cancer cell line |
| BxPC-3 | 10.5 | Pancreatic cancer cell line |
| HepG2 | 2.3 | Hepatocellular carcinoma |
| A549 | 1.1 | Lung carcinoma |
| HEK293 | 0.5 | Embryonic kidney |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2841259 | SNV (intronic) | Common (MAF ~0.3) | Associated with altered KCNK16 expression in pancreatic islets; may influence diabetes risk. |
| rs11672660 | SNV (intronic) | Common (MAF ~0.2) | Reported in GWAS for pancreatic cancer susceptibility. |
| p.Arg70His | Missense | Rare | Functional studies show reduced channel activity; potential impact on insulin secretion. |
| p.Gly167Arg | Missense | Rare | In vitro studies suggest altered pH sensitivity; clinical significance unclear. |
Mutation functional classification
Loss of Function (LOF)
Variants that reduce channel expression or activity, such as p.Arg70His, may impair potassium conductance, leading to membrane depolarization and altered insulin secretion.
Gain of Function (GOF)
Variants that increase channel activity could hyperpolarize the membrane, reducing excitability and potentially affecting hormone release.
Dominant Negative (DN)
Some mutations may exert a dominant-negative effect by forming non-functional heterodimers with other K2P channels, though this has not been extensively studied for KCNK16.
View complete mutation data：
Gene Ontology (GO)
| • potassium ion transmembrane transporter activity | • potassium channel activity |
| • voltage-gated potassium channel activity | • protein homodimerization activity |
| • plasma membrane | • integral component of plasma membrane |
| • potassium ion transport | • cellular response to pH |
Pathways
• Potassium Channels
• Ion transport
• Regulation of insulin secretion
Protein Summary
The KCNK16 protein, also known as TALK-1, is a 331-amino acid two-pore-domain potassium channel. It forms homodimers and is primarily localized to the plasma membrane. The channel is activated by extracellular alkalinization (pH > 7.3) and is inhibited by low pH. It exhibits a weak inward rectification and is insensitive to classical potassium channel blockers like tetraethylammonium and 4-aminopyridine. In pancreatic beta cells, TALK-1 contributes to the background potassium conductance, helping to maintain the resting membrane potential and modulating glucose-stimulated insulin secretion. Its expression is regulated by various factors, including glucose and transcription factors involved in beta-cell identity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNK16 Knockout HEK293 Cell Line | EDJ-KQ9094 | Human | 83795 | Details Get a Quote |
| KCNK16 Knockout HeLa Cell Line | EDJ-KQ57480 | Human | 83795 | Details Get a Quote |
| KCNK16 Knockout A-549 Cell Line | EDJ-KQ65982 | Human | 83795 | Details Get a Quote |
| KCNK16 Knockout HCT 116 Cell Line | EDJ-KQ74405 | Human | 83795 | Details Get a Quote |
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