KCNK9 (KCNK9) - Potassium Channel, Two Pore Domain Subfamily K, Member 9
KCNK9 encodes a pH-sensitive potassium channel implicated in Birk Barel syndrome and cancer progression.
Gene Information Card
| Symbol | KCNK9 |
|---|---|
| Full Name | Potassium Two Pore Domain Channel Subfamily K Member 9 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.3 |
| NCBI Gene ID | 51305 ncbi.nlm.nih.gov/gene/51305 |
| Ensembl ID | ENSG00000169427 |
| UniProt ID | Q9NPC2 |
| OMIM ID | 605874 |
| HGNC ID | 6283 |
| Aliases | TASK3, K2P9.1, TASK-3 |
Description
KCNK9 encodes a member of the two-pore domain potassium channel family, specifically the TWIK-related acid-sensitive K+ channel 3 (TASK3). This channel is characterized by four transmembrane segments and two pore-forming domains. TASK3 is a pH-sensitive, background potassium channel that is highly expressed in the brain and plays roles in neuronal excitability, apoptosis, and cell proliferation. Mutations in KCNK9 are associated with Birk Barel syndrome, a rare genetic disorder, and altered expression is linked to various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Birk Barel syndrome | Loss-of-function mutations in KCNK9 lead to reduced potassium current, affecting neuronal development and function. | OMIM #612292; ClinVar |
| Cancer (various) | Overexpression of KCNK9 in tumors promotes cell survival and proliferation, possibly by hyperpolarizing the membrane and modulating apoptosis. | COSMIC; multiple studies |
| Epilepsy | Rare variants in KCNK9 may contribute to epilepsy susceptibility, though evidence is limited. | ClinVar; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | Highest expression in cerebellum, cerebral cortex, and hippocampus |
| Adrenal gland | Moderate | Expression in adrenal cortex |
| Lung | Low | Low expression in lung tissue |
| Heart | Low | Minimal expression in heart |
| Kidney | Low | Low expression in kidney |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal cell line with high KCNK9 expression |
| U87 (glioblastoma) | Moderate | Glioblastoma cell line expressing KCNK9 |
| MCF7 (breast cancer) | Low | Breast cancer cell line with low expression |
| HEK293 (embryonic kidney) | Low | Commonly used for heterologous expression studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| G236R | Missense | Rare | Loss-of-function; associated with Birk Barel syndrome |
| G236E | Missense | Rare | Loss-of-function; associated with Birk Barel syndrome |
| Y256C | Missense | Rare | Loss-of-function; associated with Birk Barel syndrome |
| T108P | Missense | Rare | Potential gain-of-function; reported in cancer |
| R224Q | Missense | Rare | Uncertain significance; reported in epilepsy |
Mutation functional classification
Loss of Function (LOF)
Mutations such as G236R, G236E, and Y256C reduce or abolish potassium channel activity, leading to Birk Barel syndrome.
Gain of Function (GOF)
Some variants, like T108P, may increase channel activity, potentially contributing to cancer cell survival.
Dominant Negative (DN)
Not clearly established; however, some loss-of-function mutations may exert dominant-negative effects when co-expressed with wild-type subunits.
View complete mutation data：
Gene Ontology (GO)
| • Potassium ion transmembrane transport | • Potassium channel activity |
| • Voltage-gated potassium channel complex | • Plasma membrane |
| • Response to pH |
Pathways
• Potassium channel activity
• Ion transport
• Apoptosis regulation
• Cell proliferation
Protein Summary
The KCNK9 protein, also known as TASK3, is a 374-amino acid potassium channel with two pore domains. It forms homodimers and functions as a background potassium channel, setting the resting membrane potential. TASK3 is sensitive to extracellular pH, being inhibited by acidic pH and activated by alkaline pH. It is also modulated by volatile anesthetics and G-protein coupled receptors. In the brain, TASK3 contributes to neuronal excitability and is involved in neuroprotection. In cancer, overexpression of TASK3 has been shown to promote tumor growth and resistance to apoptosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNK9 Knockout HEK293 Cell Line | EDJ-KQ11030 | Human | 51305 | Details Get a Quote |
| KCNK9 Knockout HCT 116 Cell Line | EDJ-KQ38926 | Human | 51305 | Details Get a Quote |
| KCNK9 Knockout HeLa Cell Line | EDJ-KQ56279 | Human | 51305 | Details Get a Quote |
| KCNK9 Knockout A-549 Cell Line | EDJ-KQ64768 | Human | 51305 | Details Get a Quote |
