KCNK6 (Potassium Two Pore Domain Channel Subfamily K Member 6), also known as TASK-3 (TWIK-related acid-sensing potassium channel 3), is a gene located on chromosome 19q13.2 that encodes a pH-sensitive two-pore domain potassium channel highly expressed in the brain [1]. The KCNK6 protein forms homodimers or heterodimers with other two-pore domain channels (like KCNK3/TASK-1) to create background potassium channels that regulate neuronal excitability. While primarily studied in the context of depression, epilepsy, and cancer, emerging research suggests potential roles in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease through its effects on neuronal survival, pH regulation, and excitotoxicity [2].
The gene is catalogued as NCBI Gene ID 9479, Ensembl ID ENSG00000171303, and UniProt Q9Y5U5.
| Property | Value |
|---|---|
| Gene Symbol | KCNK6 |
| Full Name | Potassium Two Pore Domain Channel Subfamily K Member 6 |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 9479 |
| Ensembl ID | ENSG00000171303 |
| UniProt ID | Q9Y5U5 |
| Aliases | TASK-3, K2P3.1, TWIK-3 |
KCNK6/TASK-3 is a member of the two-pore domain potassium channel (K2P) family, which produces background leak currents that set the resting membrane potential [1:1]. Key properties include:
KCNK6 is highly expressed in:
TASK-3 channels have been implicated in depression pathophysiology [2:1]:
TASK channels play complex roles in seizure disorders [3]:
Emerging evidence links KCNK6 to Alzheimer's disease pathogenesis:
Potential roles in Parkinson's disease include:
KCNK6/TASK-3 is overexpressed in several cancers [4]:
TASK-3 channels represent therapeutic targets:
| Compound | Effect | Potential Use |
|---|---|---|
| Fluoxetine | Inhibitor | Depression (off-target) |
| Rottlerin | Inhibitor | Cancer |
| A1899 | Inhibitor | Analgesia |
| PD-118881 | Activator | Antidepressant |
Shieh, C.C. et al. (2000). Potassium channels: molecular defects, diseases, and therapeutic opportunities. Pharmacological Reviews, 52(4), 557-594. 2000. ↩︎ ↩︎
Weil, D. et al. (2006). TASK-3: a novel tandem pore domain background potassium channel. Biochemical Society Transactions, 34(Pt 5), 807-810. 2006. ↩︎ ↩︎
Meuth, S.G. et al. (2009). Function of two-pore domain potassium channels in neuronal excitability. Current Neuropharmacology, 7(3), 178-182. 2009. ↩︎
Patel, F. & Lazdunski, M. (2004). The two-pore domain (K2P) potassium channel family: anatomy, physiology, and pharmacology. Acute Pain, 7(1), 33-42. 2004. ↩︎