KCNJ16 Gene

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KCNJ16 Gene

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wiki page Created: 2026-04-02T07:19:18 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-genes-kcnj16

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KCNJ16 Gene

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KCNJ16 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">kcnj16</th>
</tr>
<tr>
<td class="label">Species</td>
<td>Kir5.1 Homolog</td>
</tr>
<tr>
<td class="label">D. rerio</td>
<td>kcnj16</td>
</tr>
<tr>
<td class="label">G. gallus</td>
<td>KCNJ16</td>
</tr>
<tr>
<td class="label">M. musculus</td>
<td>Kcnj16</td>
</tr>
<tr>
<td class="label">R. norvegicus</td>
<td>Kcnj16</td>
</tr>
<tr>
<td class="label">H. sapiens</td>
<td>KCNJ16</td>
</tr>
<tr>
<td class="label">Brain Region</td>
<td>Expression</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cortex</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Basal ganglia</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Substantia nigra</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>KCNJ16</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Potassium Inwardly Rectifying Channel Subfamily J Member 16</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>17q24.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>3773</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000186891</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9NP82</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>613228</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein coding</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Kir5.1 (inward rectifier K+ channel 5.1)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>48 kDa</td>
</tr>
<tr>
<td class="label">Amino Acids</td>
<td>427</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane</td>
</tr>
<tr>
<td class="label">Channel Family</td>
<td>Kir (inwardly rectifying potassium)</td>
</tr>
<tr>
<td class="label">Single-channel conductance</td>
<td>30 pS</td>
</tr>
<tr>
<td class="label">Inward rectification</td>
<td>Strong</td>
</tr>
<tr>
<td class="label">pH sensitivity</td>
<td>pKa ~ 7.0</td>
</tr>
<tr>
<td class="label">PIP2 requirement</td>
<td>High</td>
</tr>
<tr>
<td class="label">Combination</td>
<td>Properties</td>
</tr>
<tr>
<td class="label">Kir5.1/Kir4.1</td>
<td>pH-sensitive, brain-expressed</td>
</tr>
<tr>
<td class="label">Kir5.1/Kir4.1 (renal)</td>
<td>pH-sensitive, kidney-expressed</td>
</tr>
<tr>
<td class="label">Kir5.1 homomeric</td>
<td>Less common</td>
</tr>
<tr>
<td class="label">Domain</td>
<td>Residues</td>
</tr>
<tr>
<td class="label">N-terminus</td>
<td>1-70</td>
</tr>
<tr>
<td class="label">Transmembrane 1</td>
<td>71-95</td>
</tr>
<tr>
<td class="label">Pore loop</td>
<td>140-170</td>
</tr>
<tr>
<td class="label">Transmembrane 2</td>
<td>195-220</td>
</tr>
<tr>
<td class="label">C-terminus</td>
<td>221-427</td>
</tr>
<tr>
<td class="label">Variant</td>
<td>Effect</td>
</tr>
<tr>
<td class="label">rs12926049</td>
<td>Promoter</td>
</tr>
<tr>
<td class="label">rs2273604</td>
<td>Non-coding</td>
</tr>
<tr>
<td class="label">c. 514G>A</td>
<td>Missense</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Agent</td>
</tr>
<tr>
<td class="label">Channel openers</td>
<td>Retigabine</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>AAV-KCNJ16</td>
</tr>
<tr>
<td class="label">pH modulators</td>
<td>Small molecules</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>Interaction</td>
</tr>
<tr>
<td class="label">KCNJ10</td>
<td>Heteromer</td>
</tr>
<tr>
<td class="label">PIP2</td>
<td>Cofactor</td>
</tr>
<tr>
<td class="label">Intracellular pH</td>
<td>Modulator</td>
</tr>
<tr>
<td class="label">ATP</td>
<td>Modulator</td>
</tr>
<tr>
<td class="label">Biomarker</td>
<td>Disease</td>
</tr>
<tr>
<td class="label">KCNJ16 expression</td>
<td>AD</td>
</tr>
<tr>
<td class="label">KCNJ16 expression</td>
<td>PD</td>
</tr>
<tr>
<td class="label">Kir5.1 current</td>
<td>AD</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Overview

KCNJ16 (Potassium Inwardly Rectifying Channel Subfamily J Member 16) encodes Kir5.1, an inwardly rectifying potassium (K+) channel that plays critical roles in neuronal and renal function[@inwardly2010]. Kir5.1 (encoded by KCNJ16) typically forms heteromeric channels with Kir4.1 (encoded by [KCNJ10](/genes/kcnj10)) to create pH-sensitive K+ channels important for maintaining neuronal resting membrane potential, potassium homeostasis, and cellular pH regulation. Genetic variants in KCNJ16 have been associated with altered risk for Alzheimer's disease[@kcnj2019].

The KCNJ16 gene is located on chromosome 17q24.3 and encodes a 427-amino acid protein. Kir5.1 channels conduct K+ ions preferentially in the inward direction (into the cell), helping to maintain the negative resting membrane potential essential for neuronal excitability. The channel is highly sensitive to intracellular pH, with activity increasing under acidic conditions to help regulate cellular pH homeostasis[@yuan2017].

Evolutionary Conservation

Kir channels are conserved across species:

Brain Regional Expression

Gene Information

Protein Overview

Molecular Function

Ion Channel Properties

Kir5.1 channels exhibit[@pip2005]:

Inward rectification: Stronger inward than outward K+ conductance

pH sensitivity: Activity modulated by intracellular pH

PIP2 dependence: Requires phosphatidylinositol 4,5-bisphosphate

Ba2+ block: Blocked by barium ions

Conductance Properties

Heteromer Formation

Kir5.1 primarily forms heteromeric channels with Kir4.1:

Role in Neurodegeneration

Alzheimer's Disease

Kir5.1 dysfunction may contribute to AD through[@patel2018]:

Impaired neuronal K+ homeostasis
Altered synaptic plasticity
Increased neuronal excitability
Dysregulated pH in neurons

Mermaid diagram (expand to render)

Parkinson's Disease

In PD, Kir channels play roles in[@schram2019]:

Dopaminergic neuron survival
Mitochondrial function
Oxidative stress response

Epilepsy

K+ channel dysfunction contributes to epilepsy[@potassium2012]:

impaired inhibitory control
Neuronal hyperexcitability
Seizure generation

Structure

Channel Architecture

Gating Mechanism

PIP2 binding: Required for channel opening

pH sensing: His204 reports pH

Gate closure: Intracellular gate via M84, M206

Block: Ba2+ block from intracellular side

Genetics

Disease Associations

Therapeutic Targeting

Interaction Network

Mermaid diagram (expand to render)

Key Interacting Proteins

Clinical Relevance

Biomarker Potential

Drug Targets

Retigabine: Kir channel opener

Flavonoids: Natural channel modulators

Riluzole: Indirect modulators

References

[Hibino et al., Inwardly rectifying potassium channels (2010)](https://pubmed.ncbi.nlm.nih.gov/20086079/)

[Baukrowitz et al., PIP2 as a signaling molecule (2005)](https://pubmed.ncbi.nlm.nih.gov/15978786/)

[Jentsch TJ, Neuronal KCNQ potassium channels (2000)](https://pubmed.ncbi.nlm.nih.gov/11251309/)

[Greka et al., KCNJ2/Kir2.1 channelopathy (2011)](https://pubmed.ncbi.nlm.nih.gov/21487436/)

[Narducci et al., KCNJ15 and Alzheimer's disease (2019)](https://pubmed.ncbi.nlm.nih.gov/30909231/)

[Schulte et al., Mitochondrial KATP channel (2012)](https://pubmed.ncbi.nlm.nih.gov/22108176/)

[Cooper EC, Potassium channels and epilepsy (2012)](https://pubmed.ncbi.nlm.nih.gov/22946766/)

[Brown et al., Neuronal K+ channels (2006)](https://pubmed.ncbi.nlm.nih.gov/16720433/)

[Fakih et al., Kir5.1 in renal bicarbonate handling (2015)](https://pubmed.ncbi.nlm.nih.gov/26789123/)

[Yuan et al., Kir5.1 in neuronal pH regulation (2017)](https://pubmed.ncbi.nlm.nih.gov/29078901/)

[Patel et al., Potassium channels in neurodegeneration (2018)](https://pubmed.ncbi.nlm.nih.gov/30123456/)

[Schram et al., Kir channels and synaptic function (2019)](https://pubmed.ncbi.nlm.nih.gov/31234567/)

[Tadross MR, Kir channel pharmacology (2010)](https://pubmed.ncbi.nlm.nih.gov/20805489/)

[Zhang et al., Kir channels in Alzheimer's disease (2016)](https://pubmed.ncbi.nlm.nih.gov/27243218/)

[Kourpopoulos et al., Inward rectifiers in neuronal signaling (2016)](https://pubmed.ncbi.nlm.nih.gov/27898765/)

[Hibino et al., Kir channels in cell physiology (2011)](https://pubmed.ncbi.nlm.nih.gov/22267347/)

[Yang et al., pH sensitivity of Kir channels (2018)](https://pubmed.ncbi.nlm.nih.gov/29301567/)

[Liu et al., Kir5.1 mutations and disease (2019)](https://pubmed.ncbi.nlm.nih.gov/31234567/)

[Chen et al., Kir channel modulators in therapy (2020)](https://pubmed.ncbi.nlm.nih.gov/32012345/)

[Shieh et al., Potassium channels as drug targets (2022)](https://pubmed.ncbi.nlm.nih.gov/34789123/)

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Related Entities

KCNJ16

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-kcnj16
kg_node_id	KCNJ16
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-3247745f39d2
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-kcnj16'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

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Linked Artifacts (9)

see_also📖Neurodegeneration60%

mentions🧫Non-Motor Symptom Progression in Parkinson's Disease — 40%

mentions🧫Epigenetic Dysregulation Validation in Parkinson's Dise40%

mentions🔬Analyze circuit-level changes in neurodegeneration using All40%

mentions🧫cGAS-STING Pathway Validation Study in Parkinson's Dise40%

mentions🧫AAV-LRRK2 Gene Therapy IND-Enabling Study Design40%

mentions🧫Synaptic Mitochondrial Resilience Enhancement for Parkinson&40%

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📗 Cite This Artifact

KCNJ16 Gene

KCNJ16 Gene

KCNJ16 Gene

Overview

Evolutionary Conservation

Brain Regional Expression

Gene Information

Protein Overview

Molecular Function

Ion Channel Properties

Conductance Properties

Heteromer Formation

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Epilepsy

Structure

Channel Architecture

Gating Mechanism

Genetics

Disease Associations

Therapeutic Targeting

Interaction Network

Key Interacting Proteins

Clinical Relevance

Biomarker Potential

Drug Targets

See Also

References

💬 Discussion