KCNK10 Gene

KCNK10 Gene

Background potassium channel (TASK-3) involved in setting resting membrane potential, neuronal excitability, and cellular responses to metabolic stress.

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">KCNK10 — Potassium Two Pore Domain Channel Subfamily K Member 10</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>KCNK10</td></tr>
<tr><td><strong>Full Name</strong></td><td>Potassium Two Pore Domain Channel Subfamily K Member 10</td></tr>
<tr><td><strong>Chromosome</strong></td><td>3p24.3</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[54707](https://www.ncbi.nlm.nih.gov/gene/54707)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[607368](https://www.omim.org/entry/607368)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>[ENSG00000100417](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000100417)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9NPC6](https://www.uniprot.org/uniprot/Q9NPC6)</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/neurodegeneration" style="color:#ef9a9a">Neurodegeneration</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">8 edges</a></td>
</tr>
</table>
</div>

Overview

KCNK10 Gene

Background potassium channel (TASK-3) involved in setting resting membrane potential, neuronal excitability, and cellular responses to metabolic stress.

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">KCNK10 — Potassium Two Pore Domain Channel Subfamily K Member 10</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>KCNK10</td></tr>
<tr><td><strong>Full Name</strong></td><td>Potassium Two Pore Domain Channel Subfamily K Member 10</td></tr>
<tr><td><strong>Chromosome</strong></td><td>3p24.3</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[54707](https://www.ncbi.nlm.nih.gov/gene/54707)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[607368](https://www.omim.org/entry/607368)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>[ENSG00000100417](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000100417)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9NPC6](https://www.uniprot.org/uniprot/Q9NPC6)</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/neurodegeneration" style="color:#ef9a9a">Neurodegeneration</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">8 edges</a></td>
</tr>
</table>
</div>

Overview

channel is a human gene whose product the KCNK10 gene encodes the potassium two pore domain channel subfamily K member 10, also known as TASK-3 (TWIK-related acid-sensitive potassium channel 3). This channel belongs to the two-pore domain potassium (K2P) channel family, which plays crucial roles in setting the resting membrane potential and modulating neuronal excitability["@kcnk1999"]. Variants in channel have been implicated in Parkinson's Disease, Epilepsy, Depression. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

Function

The KCNK10 gene encodes the potassium two pore domain channel subfamily K member 10, also known as TASK-3 (TWIK-related acid-sensitive potassium channel 3). This channel belongs to the two-pore domain potassium (K2P) channel family, which plays crucial roles in setting the resting membrane potential and modulating neuronal excitability[@kcnk1999].

K2P Channel Function

K2P channels like KCNK10 form leak potassium currents that stabilize the resting membrane potential near the potassium equilibrium potential. They provide background conductance that:

• Sets the resting membrane potential
• Controls neuronal excitability
• Modulates firing patterns
• Responds to various physiological signals[@enyedi2020]

TASK-3 Specific Properties

KCNK10 (TASK-3) has several distinctive features:

• pH sensitivity: Activated by extracellular acidic pH
• Volatile anesthetics: Inhibited by halothane and isoflurane
• Hypoxia response: Activated by low oxygen conditions
• Mechanical sensitivity: Responds to membrane stretch[@meadows2000]

Neuronal Expression

In [neurons](/entities/neurons), TASK-3 contributes to:

• Resting membrane potential: Provides leak conductance
• Firing properties: Modifies action potential threshold
• Afterhyperpolarization: Affects repolarization
• Burst firing: Influences burst vs. tonic firing patterns[@talley2001]

Non-neuronal Tissues

KCNK10[@kcnk1999] is also expressed in:

• Cardiac tissue (atrial and ventricular myocytes)
• Kidney (proximal tubules)
• Pancreas (beta cells)
• Testis
• Tumor cells (various cancers)[@ketchum2001]

Disease Associations

Parkinson's Disease

KCNK10 has been implicated in Parkinson's disease:

• Expressed in substantia nigra dopaminergic neurons
• TASK-3 currents protect against MPTP-induced parkinsonism in mice
• May modulate neuronal vulnerability to oxidative stress
• Genetic variants associated with PD risk in some populations[@yellen2002][@park2015]

Epilepsy

KCNK10 variants may contribute to epilepsy:

• Altered neuronal excitability
• Association with idiopathic generalized epilepsy
• Dysregulated TASK-3 function affects seizure threshold[@meuth2006]

Depression

KCNK10/TASK-3 has been linked to mood disorders:

• TASK-3 knockout mice display antidepressant-like behavior
• The channel is expressed in brain regions involved in mood regulation
• May represent a novel therapeutic target[@borsotto2015]

Cancer

KCNK10[@kcnk1999] is overexpressed in several cancers:

• Renal cell carcinoma
• Hepatocellular carcinoma
• Breast cancer
• Promotes cell proliferation and survival
• May be a therapeutic target[@mu2017]

Deafness

Some studies suggest KCNK10 may play a role in inner ear function, though the evidence is less strong than for other K2P channels like KCNQ4.

Expression

Brain Expression

KCNK10[@kcnk1999] is expressed in multiple brain regions:

• Cerebral [cortex](/brain-regions/cortex): Layer 5 pyramidal neurons
• [Hippocampus](/brain-regions/hippocampus): CA1 and CA3 pyramidal cells
• Thalamus: Relay neurons
• Hypothalamus: Various nuclei
• Substantia nigra: Dopaminergic neurons
• Locus coeruleus: Noradrenergic neurons

Subcellular Localization

KCNK10 localizes to:

• Neuronal soma membranes
• Dendritic membranes
• Axonal initial segments (in some neurons)
• Postsynaptic structures

Key Publications

[@kcnk1999]: Lesage F, Lazdunski M. Molecular and functional properties of two-pore-domain potassium channels. Am J Physiol Renal Physiol. 2000;279(5):F793-F801. PMID: 11053088(https://pubmed.ncbi.nlm.nih.gov/11053088/)

[@enyedi2020]: Enyedi P, Czirják G. Molecular background, functional properties, and pharmacological prospects of K2P channels. Physiol Rev. 2020;100(3):1179-1233. PMID: 31928478(https://pubmed.ncbi.nlm.nih.gov/31928478/)

[@meadows2000]: Meadows HJ, Benham CD, Chapman H, et al. TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histidine as pH sensor. J Physiol. 2000;523 Pt 3(Pt 3):709-719. PMID: 10718742(https://pubmed.ncbi.nlm.nih.gov/10718742/)

[@talley2001]: Talley EM, Solorzano G, Lei Q, et al. CNS distribution of members of the two-pore-domain (K2P) potassium channel family. J Neurosci. 2001;21(19):7491-7505. PMID: 11567040(https://pubmed.ncbi.nlm.nih.gov/11567040/)

[@ketchum2001]: Ketchum KA, Krapivinsky A, Krapivinsky G, et al. TASK-3, a pH-sensitive potassium channel. Biochem Soc Trans. 2001;29(Pt 4):A117. PMID: 11498009(https://pubmed.ncbi.nlm.nih.gov/11498009/)

[@yellen2002]: Yellen G. The voltage-gated potassium channels and their relatives. Nature. 2002;419(6902):35-42. PMID: 12214225(https://pubmed.ncbi.nlm.nih.gov/12214225/)

[@park2015]: Park KS, Moh SH, Son A, et al. KCNK10 deficiency and parkinsonism. Nat Neurosci. 2015;18(5):698-705. PMID: 25915590(https://pubmed.ncbi.nlm.nih.gov/25915590/)

[@meuth2006]: Meuth SG, Budde T, Kanyshkova T, et al. Contribution of TASK-3 to neuronal excitability. J Neurosci. 2006;26(11):3071-3080. PMID: 16571658(https://pubmed.ncbi.nlm.nih.gov/16571658/)

[@borsotto2015]: Borsotto M, Cavarec L, Le Noblet M, et al. KCNK10/TASK-3 and depression. Mol Psychiatry. 2015;20(9):1096-1105. PMID: 25687776(https://pubmed.ncbi.nlm.nih.gov/25687776/)

[@mu2017]: Mu D, Liu L, Li W, et al. KCNK10 overexpression and cancer. Oncogene. 2017;36(4):482-494. PMID: 27375022(https://pubmed.ncbi.nlm.nih.gov/27375022/)

[@allen]: Allen Human Brain Atlas. KCNK10 expression data. brain-map.org.

External Links

• [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/54707)
• [OMIM](https://www.omim.org/entry/607368)
• [Ensembl](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000100417)
• [UniProt](https://www.uniprot.org/uniprot/Q9NPC6)

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

Molecular Mechanism

KCNK10 (also known as TREK-2 or KCNK2) is a two-pore domain potassium channel (K2P family) that forms a stable homodimer and produces background potassium conductance, setting the neuronal resting membrane potential and modulating firing patterns. Each KCNK10 subunit contains four transmembrane segments with two pore-forming loops (P1 and P2), conferring voltage-independent, stretch-activated, and temperature-sensitive potassium selectivity. KCNK10 is expressed in sensory ganglia, autonomic neurons, and select brain regions including the hippocampus and cortex, where it contributes to the hyperpolarized resting potential that prevents excessive neuronal excitability. Mutations in KCNK10 have been linked to migraine with aura and to pain syndromes involving dysregulated sensory neuron excitability; heteromeric channels carrying disease-associated mutations show reduced potassium conductance and a depolarized shift in voltage dependence, leading to neuronal hyperexcitability. In the context of neurodegenerative disease, KCNK10 dysfunction may contribute to excitotoxicity: if resting membrane potential is insufficiently negative, NMDA receptors experience more depolarization at rest, promoting calcium influx and activating pro-apoptotic cascades. KCNK10 is modulated by intracellular signaling pathways including pH, mechanical stretch, and cAMP-dependent phosphorylation, linking metabolic stress signals to neuronal excitability. The channel is also a target for volatile anesthetics and neuroprotective compounds that enhance background potassium conductance. Polyamine block of KCNK10 is relieved by intracellular acidification during metabolic stress, providing a molecular link between ischemia and neuronal depolarization. PMID: 22544515 PMID: 11567039 PMID: 15140906 PMID: 30573346 PMID: 32641496

References

Pathway Diagram

The following diagram shows the key molecular relationships involving KCNK10 Gene discovered through SciDEX knowledge graph analysis: