KCNK6 Gene
Overview
Mermaid diagram (expand to render)
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">KCNK6 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>KCNK6</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Potassium Two Pore Domain Channel Subfamily K Member 6</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19q13.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>9479</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000171303</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y5U5</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>TASK-3, K2P3.1, TWIK-3</td>
</tr>
<tr>
<td class="label">Compound</td>
<td>Effect</td>
</tr>
<tr>
<td class="label">Fluoxetine</td>
<td>Inhibitor</td>
</tr>
<tr>
<td class="label">Rottlerin</td>
<td>Inhibitor</td>
</tr>
<tr>
<td class="label">A1899</td>
<td>Inhibitor</td>
</tr>
<tr>
<td class="label">PD-118881</td>
<td>Activator</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/fibrosis" style="color:#ef9a9a">Fibrosis</a>, <a href="/wiki/heart-failure" style="color:#ef9a9a">Heart Failure</a>, <a href="/wiki/hypertension" style="color:#ef9a9a">Hypertension</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">18 edges</a></td>
</tr>
</table>
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 [@shieh2000]. 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](/diseases/alzheimers-disease) and [Parkinson's disease](/diseases/parkinsons-disease) through its effects on neuronal survival, pH regulation, and excitotoxicity [@weil2006].
The gene is catalogued as NCBI Gene ID [9479](https://www.ncbi.nlm.nih.gov/gene/9479), Ensembl ID ENSG00000171303, and UniProt [Q9Y5U5](https://www.uniprot.org/uniprot/Q9Y5U5).
Function
Channel Properties
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 [@shieh2000]. Key properties include:
- pH sensitivity: TASK-3 channels are highly sensitive to extracellular pH, with activity inhibited by acidic pH (IC50 ~6.3)
- Volatile anesthetics: Activated by halogenated anesthetics like halothane and isoflurane
- Stretch sensitivity: Mechanical stretch can modulate channel activity
- Protein kinase modulation: Phosphorylation by PKC modulates channel function
Neuronal Expression
KCNK6 is highly expressed in:
- Hypothalamus: Particularly in the supraoptic and paraventricular nuclei
- [Cortex](/brain-regions/cortex): Layer 5 pyramidal [neurons](/entities/neurons)
- Thalamus: Thalamic relay neurons
- Substantia Nigra: Dopaminergic neurons express TASK-3 channels
- [Hippocampus](/brain-regions/hippocampus): CA1 pyramidal neurons
Physiological Roles
- Resting membrane potential: Contributes to the leak conductance that sets neuronal resting potential
- pH homeostasis: Acts as a pH sensor in brain regions with variable pH
- Hormone release: Modulates hypothalamic hormone secretion (vasopressin, oxytocin)
- Sleep-wake regulation: Hypothalamic TASK channels influence arousal states
Disease Associations
Depression
TASK-3 channels have been implicated in depression pathophysiology [@weil2006]:
- Expression changes: Reduced TASK-1/TASK-3 expression in prefrontal cortex of depressed patients
- Antidepressant effects: Some antidepressants (fluoxetine) block TASK-3 channels
- Stress response: Chronic stress alters TASK channel expression
- Therapeutic targeting: TASK-3 selective modulators are being investigated
Epilepsy
TASK channels play complex roles in seizure disorders [@meuth2009]:
- pH sensitivity: Acidic pH during seizures inhibits TASK currents
- Seizure termination: TASK activation may contribute to seizure termination
- Anti-epileptic drugs: Levetiracetam may modulate TASK-3 activity
- Absence seizures: Thalamic TASK channels implicated in spike-wave discharges
Neurodegenerative Diseases
Alzheimer's Disease
Emerging evidence links KCNK6 to [Alzheimer's disease](/diseases/alzheimers-disease) pathogenesis:
- Neuronal excitability: [Aβ](/proteins/amyloid-beta) peptides alter TASK channel function, affecting excitability
- pH dysregulation: Brain pH changes in AD may affect TASK-3 activity
- Calcium dysregulation: TASK channels indirectly influence calcium influx
- Synaptic dysfunction: Altered background currents may contribute to synaptic deficits
Parkinson's Disease
Potential roles in [Parkinson's disease](/diseases/parkinsons-disease) include:
- Dopaminergic neuron survival: TASK channels may protect dopaminergic neurons
- Oxidative stress: TASK-3 expression may be modulated by oxidative stress
- Mitochondrial dysfunction: Interactions with mitochondrial function
- Motor control: Basal ganglia excitability involves TASK channels
Cancer
KCNK6/TASK-3 is overexpressed in several cancers [@patel2004]:
- Breast cancer
- Glioma
- Lung cancer
- Ovarian cancer
- Prostate cancer
Therapeutic Implications
Drug Development
TASK-3 channels represent therapeutic targets:
- Depression: Selective TASK-3 activators as novel antidepressants
- Epilepsy: TASK modulators as anticonvulsants
- Cancer: TASK-3 blockers as anticancer agents
- Pain: TASK-1/3 modulators for analgesia
Channel Modulators
Interactions
Protein Interactions
- KCNK3 (TASK-1): Forms heterodimers
- KCNK9 (TASK-3): Brain-specific partner
- 14-3-3 proteins: Channel trafficking
- PICK1: PDZ domain interactions
Signaling Pathways
- p38 MAPK: Stress-induced modulation
- PKC: Phosphorylation
- cAMP/PKA: Modulation
- PI3K/Akt: Survival signaling
See Also
- [Genes Index](/genes)
- [Potassium Channels](/proteins)
- [Two-Pore Domain Channels](/mechanisms)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Epilepsy](/diseases/epilepsy)
- [Depression](/diseases/depression)
- [Mechanisms Index](/mechanisms)
External Links
- [NCBI Gene: KCNK6](https://www.ncbi.nlm.nih.gov/gene/9479)
- [UniProt: KCNK6](https://www.uniprot.org/uniprot/Q9Y5U5)
- [Ensembl: KCNK6](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000171303)
- [IUPHAR/BPS Guide: K2P channels](https://guidetopharmacology.org/GRAC/LectureF540)
References
[Shieh, C.C. et al., (2000). Potassium channels: molecular defects, diseases, and therapeutic opportunities. Pharmacological Reviews, 52(4), 557-594 (2000)](https://pubmed.ncbi.nlm.nih.gov/10893102/)
[Weil, D. et al., (2006). TASK-3: a novel tandem pore domain background potassium channel. Biochemical Society Transactions, 34(Pt 5), 807-810 (2006)](https://pubmed.ncbi.nlm.nih.gov/17052208/)
[Meuth, S.G. et al., (2009). Function of two-pore domain potassium channels in neuronal excitability. Current Neuropharmacology, 7(3), 178-182 (2009)](https://pubmed.ncbi.nlm.nih.gov/20190960/)
[Unknown, Patel, F. & Lazdunski, M. (2004). The two-pore domain (K2P) potassium channel family: anatomy, physiology, and pharmacology. Acute Pain, 7(1), 33-42 (2004)](https://pubmed.ncbi.nlm.nih.gov/15552194/)Pathway Diagram
The following diagram shows the key molecular relationships involving KCNK6 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)