KCNK9 Protein

Migration, Crosslink

📖

KCNK9 Protein

active

wiki page Created: 2026-04-02T07:19:14 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-proteins-kcnk9-protein

📖 Wiki Page

protein772 wordssynced 2026-04-02

KCNK9 Protein

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">KCNK9 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>TASK-3 (Two-pore domain acid-sensitive potassium channel 3)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>KCNK9</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9NPC2</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~37 kDa</td>
</tr>
<tr>
<td class="label">Structure</td>
<td>4 transmembrane segments, 2 pore domains</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cell membrane</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>K2P (two-pore domain) channel family</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">6 edges</a></td>
</tr>
</table>

KCNK9 Protein — Potassium Two Pore Domain Channel Subfamily K Member 9 is a protein that kcnk9/task-3 channels serve several essential functions in [neurons](/entities/neurons)[@channels2007][@task2010]:. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

...

KCNK9 Protein

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">KCNK9 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>TASK-3 (Two-pore domain acid-sensitive potassium channel 3)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>KCNK9</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9NPC2</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~37 kDa</td>
</tr>
<tr>
<td class="label">Structure</td>
<td>4 transmembrane segments, 2 pore domains</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cell membrane</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>K2P (two-pore domain) channel family</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">6 edges</a></td>
</tr>
</table>

KCNK9 Protein — Potassium Two Pore Domain Channel Subfamily K Member 9 is a protein that kcnk9/task-3 channels serve several essential functions in [neurons](/entities/neurons)[@channels2007][@task2010]:. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

KCNK9 (Potassium Two Pore Domain Channel Subfamily K Member 9), also known as TASK-3, is a member of the two-pore domain (K2P) potassium channel family. KCNK9 is highly expressed in the brain, particularly in regions involved in respiratory control, arousal, and mood regulation. The channel contributes to the background potassium conductance that sets the resting membrane potential and modulates neuronal firing properties[@task2001][@task2005].

Protein Overview

KCNK9 forms leak potassium channels that provide background conductance in neurons. These channels are critical for maintaining neuronal resting membrane potential and regulating excitability.

Normal Function

KCNK9/TASK-3 channels serve several essential functions in neurons[@channels2007][@task2010]:

Background Potassium Conductance

Provides steady-state potassium leak current
Sets resting membrane potential near K+ equilibrium potential
Stabilizes neuronal membrane at ~-70mV
Prevents excessive neuronal excitation

Neuronal Excitability Regulation

TASK-3 modulates neuronal firing properties by:

Controlling action potential threshold
Regulating firing frequency
Modulating after-hyperpolarization
Affecting firing patterns

Brain Region-Specific Roles

KCNK9 is enriched in:

Thalamus: Sensory processing, arousal
[Cortex](/brain-regions/cortex): Cortical excitability, pyramidal neuron function
Hypothalamus: Respiratory control, homeostatic functions
Locus coeruleus: Noradrenergic neuron function, stress response
Raphe nuclei: Serotonergic neuron regulation

Regulation

TASK-3 activity is modulated by:

pH (acid-sensitive)
Volatile anesthetics (activated)
Neurotransmitters (GPCR modulation)
Oxygen levels (hypoxia-sensitive)

Role in Neurodegenerative Diseases

Alzheimer's Disease

KCNK9/TASK-3 is implicated in AD pathogenesis[@channels2012][@neuronal2014]:

Neuronal excitability:

Altered TASK-3 expression in AD brains
Contributes to hyperexcitability
May affect network oscillations

Amyloid interactions:

[Aβ](/proteins/amyloid-beta) alters potassium channel function
May potentiate excitotoxicity

Therapeutic potential:

TASK-3 modulators as cognitive enhancers
Targeting network dysfunction

Parkinson's Disease

In PD, KCNK9 plays complex roles[@channels2013]:

Dopaminergic neuron function:

TASK-3 in substantia nigra pars compacta
Modulates dopaminergic neuron excitability
May affect vulnerability to toxins

Levodopa-induced dyskinesia:

Altered K+ channel function in dyskinesia
Potential therapeutic target

Mood Disorders

KCNK9 is strongly associated with depression and anxiety[@task2011][@kcnk2008]:

Depression:

TASK-3-deficient mice show antidepressant-like behavior
Altered K+ conductance in depression models
Potential target for novel antidepressants

Anxiety:

KCNK9 mutations cause Birk-Barel syndrome
Anxiety-related phenotypes
Anxiolytic drug targets

Other Neurological Conditions

Epilepsy: Altered neuronal excitability
Migraine: Cortical spreading depression
Schizophrenia: Auditory gating deficits

Structure

KCNK9 is a K2P channel with distinctive features[@channel2012]:

Pore Architecture

Two pore domains (P1 and P2)
Four transmembrane segments (M1-M4)
Selectivity filter: GYG motif
Forms functional homodimers

Regulatory Domains

pH sensor: Histidine residues
Anesthetic binding sites
G protein coupling domains

Therapeutic Potential

KCNK9 is a promising drug target[@task2015][@modulators2018]:

Anesthetic Mechanisms

TASK-3 activated by volatile anesthetics
Contributes to anesthetic-induced unconsciousness
Target for novel anesthetic development

Mood Disorders

TASK-3 blockers as antidepressants
Rapid-acting antidepressant potential
Anxiolytic drug development

Neuroprotection

Modulating neuronal excitability
Preventing excitotoxicity
Anti-epileptic strategies

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/)
[KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References

[Unknown, TASK-3 potassium channel identification (2001) (2001)](https://pubmed.ncbi.nlm.nih.gov/11301061/)

[Unknown, TASK-3 structure and function (2005) (2005)](https://pubmed.ncbi.nlm.nih.gov/15949440/)

[Unknown, K2P channels in neuronal excitability (2007) (2007)](https://pubmed.ncbi.nlm.nih.gov/17693408/)

[Unknown, TASK channels in brain function (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/20399126/)

[Unknown, K+ channels in Alzheimer's disease (2012) (2012)](https://pubmed.ncbi.nlm.nih.gov/22572914/)

[Unknown, Neuronal excitability in AD (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/25022567/)

[Unknown, K+ channels in Parkinson's disease (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/23952945/)

[Unknown, TASK-3 and depression (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/21855138/)

[Unknown, KCNK9 and Birk-Barel syndrome (2008) (2008)](https://pubmed.ncbi.nlm.nih.gov/18672018/)

[Unknown, K2P channel structure (2012) (2012)](https://pubmed.ncbi.nlm.nih.gov/22427010/)

[Unknown, TASK channels as drug targets (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/26350462/)

[Unknown, K2P modulators in neurology (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29687128/)

📖 View canonical wiki page →

Related Entities

KCNK9PROTEIN

▸Metadataorigin_type: v1_polymorphic_backfill

slug	proteins-kcnk9-protein
kg_node_id	KCNK9PROTEIN
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-6d547fef5c5e
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-kcnk9-protein'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

45%

Debates

0

Incoming

9

Outgoing

11

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

No public annotations yet.

📗 Cite This Artifact

KCNK9 Protein

KCNK9 Protein

Overview

KCNK9 Protein

Overview

Protein Overview

Normal Function

Background Potassium Conductance

Neuronal Excitability Regulation

Brain Region-Specific Roles

Regulation

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Mood Disorders

Other Neurological Conditions

Structure

Pore Architecture

Regulatory Domains

Therapeutic Potential

Anesthetic Mechanisms

Mood Disorders

Neuroprotection

Cross-Links

See Also

External Links

References

💬 Discussion