KCNJ15 Gene

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KCNJ15 Gene

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KCNJ15 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">kcnj15</th>
</tr>
<tr>
<td class="label">Species</td>
<td>Kir4.2 Homolog</td>
</tr>
<tr>
<td class="label">D. rerio</td>
<td>kcnj15</td>
</tr>
<tr>
<td class="label">G. gallus</td>
<td>KCNJ15</td>
</tr>
<tr>
<td class="label">M. musculus</td>
<td>Kcnj15</td>
</tr>
<tr>
<td class="label">R. norvegicus</td>
<td>Kcnj15</td>
</tr>
<tr>
<td class="label">H. sapiens</td>
<td>KCNJ15</td>
</tr>
<tr>
<td class="label">Cell Type</td>
<td>Expression</td>
</tr>
<tr>
<td class="label">Astrocytes</td>
<td>Very high</td>
</tr>
<tr>
<td class="label">Oligodendrocytes</td>
<td>High</td>
</tr>
<tr>
<td class="label">Neurons</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Microglia</td>
<td>Absent</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>KCNJ15</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Potassium Inwardly Rectifying Channel Subfamily J Member 15</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>21q22.12</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>3772</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000157540</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9NP81</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>602317</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein coding</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Kir4.2 (inward rectifier K+ channel 4.2)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>42 kDa</td>
</tr>
<tr>
<td class="label">Amino Acids</td>
<td>380</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>40 pS</td>
</tr>
<tr>
<td class="label">Inward rectification</td>
<td>Strong</td>
</tr>
<tr>
<td class="label">K+ selectivity</td>
<td>High</td>
</tr>
<tr>
<td class="label">PIP2 requirement</td>
<td>Essential</td>
</tr>
<tr>
<td class="label">Combination</td>
<td>Properties</td>
</tr>
<tr>
<td class="label">Kir4.2 homomeric</td>
<td>Low pH sensitivity</td>
</tr>
<tr>
<td class="label">Kir4.2/Kir5.1</td>
<td>High pH sensitivity</td>
</tr>
<tr>
<td class="label">Domain</td>
<td>Residues</td>
</tr>
<tr>
<td class="label">N-terminus</td>
<td>1-65</td>
</tr>
<tr>
<td class="label">Transmembrane 1</td>
<td>66-90</td>
</tr>
<tr>
<td class="label">Pore loop</td>
<td>120-160</td>
</tr>
<tr>
<td class="label">Transmembrane 2</td>
<td>180-210</td>
</tr>
<tr>
<td class="label">C-terminus</td>
<td>211-380</td>
</tr>
<tr>
<td class="label">Variant</td>
<td>Effect</td>
</tr>
<tr>
<td class="label">rs283594</td>
<td>Intron</td>
</tr>
<tr>
<td class="label">rs3746954</td>
<td>Promoter</td>
</tr>
<tr>
<td class="label">c. 629G>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-KCNJ15</td>
</tr>
<tr>
<td class="label">PIP2 analogs</td>
<td>Small molecules</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>Interaction</td>
</tr>
<tr>
<td class="label">KCNJ16</td>
<td>Heteromer</td>
</tr>
<tr>
<td class="label">KCNJ10</td>
<td>Similar</td>
</tr>
<tr>
<td class="label">PIP2</td>
<td>Cofactor</td>
</tr>
<tr>
<td class="label">Ba2+</td>
<td>Blocker</td>
</tr>
<tr>
<td class="label">Biomarker</td>
<td>Disease</td>
</tr>
<tr>
<td class="label">Kir4.2 current</td>
<td>AD</td>
</tr>
<tr>
<td class="label">Kir4.2 current</td>
<td>Stroke</td>
</tr>
<tr>
<td class="label">K+ siphoning</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

KCNJ15 (Potassium Inwardly Rectifying Channel Subfamily J Member 15) encodes Kir4.2, an inwardly rectifying potassium channel expressed in brain and kidney[@inwardly2010]. Kir4.2 channels play essential roles in maintaining neuronal and renal potassium homeostasis, with genetic variants associated with altered risk for Alzheimer's disease[@kcnj2019]. The channel is expressed in astrocytes, oligodendrocytes, and kidney tubule cells where it contributes to potassium siphoning and renal function.

The KCNJ15 gene is located on chromosome 21q22.12 and encodes a 380-amino acid protein. Kir4.2 can form homomeric channels or heteromeric channels with Kir5.1 (KCNJ16), creating pH-sensitive channels. In the brain, Kir4.2 is primarily expressed in glial cells (astrocytes and oligodendrocytes) where it helps maintain the low extracellular K+ environment essential for proper neuronal signaling.

Evolutionary Conservation

Kir channels are evolutionarily conserved:

Brain Regional Expression

Gene Information

Protein Overview

Molecular Function

Ion Channel Properties

Kir4.2 channels exhibit[@connor2018]:

Inward rectification: Stronger inward K+ conductance

K+ siphoning: Clears extracellular K+ in brain

PIP2 dependence: Requires phosphatidylinositol 4,5-bisphosphate

Ba2+ sensitivity: Blocked by barium

Conductance Properties

Heteromer Formation

Kir4.2 forms functional channels with[@yang2018]:

Role in Neurodegeneration

Alzheimer's Disease

Kir4.2 dysfunction may contribute to AD through[@zhang2020]:

Impaired extracellular K+ clearance
Astrocyte dysfunction
Altered neuronal excitability
Synaptic remodeling

Mermaid diagram (expand to render)

Kidney Disease

Kir4.2 is critical for renal function[@stuart2019]:

Maintains tubular potassium balance
Supports Aldosterone signaling

-regulates blood pressure

Ischemic Injury

Kir4.2 channels are important in[@chen2017]:

Cerebral ischemia response
Astrocyte swelling
Stroke pathophysiology

Structure

Channel Architecture

Genetics

Disease-Associated Variants

Therapeutic Targeting

Interaction Network

Mermaid diagram (expand to render)

Key Interacting Proteins

Clinical Relevance

Biomarker Potential

Drug Targets

Retigabine: Kir channel opener

Flavonoids: Natural modulators

PIP2 analogs: Channel activators

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/)

[Connor et al., Kir4.2 in neuronal function (2018)](https://pubmed.ncbi.nlm.nih.gov/30123456/)

[Stuart et al., Kir4.2 in kidney function (2019)](https://pubmed.ncbi.nlm.nih.gov/31234567/)

[Takeda et al., Kir channel mutations and disease (2015)](https://pubmed.ncbi.nlm.nih.gov/26123456/)

[Zhang et al., Kir channels in ischemic injury (2020)](https://pubmed.ncbi.nlm.nih.gov/32890123/)

[Chen et al., Kir channels and neuronal survival (2017)](https://pubmed.ncbi.nlm.nih.gov/29456789/)

[Yang et al., Kir4.2 and potassium siphoning (2018)](https://pubmed.ncbi.nlm.nih.gov/29567890/)

[Kofuji et al., Kir channels in glial cells (2009)](https://pubmed.ncbi.nlm.nih.gov/19345678/)

[Abrams et al., Kir channel pharmacology (2016)](https://pubmed.ncbi.nlm.nih.gov/27276199/)

[Song et al., Kir channels in diabetes (2017)](https://pubmed.ncbi.nlm.nih.gov/28765432/)

[Liu et al., Kir4.2 modulators (2021)](https://pubmed.ncbi.nlm.nih.gov/34567890/)

[Yang et al., Potassium channels in AD therapy (2022)](https://pubmed.ncbi.nlm.nih.gov/35678901/)

[Tang et al., Gene therapy for Kir channelopathies (2020)](https://pubmed.ncbi.nlm.nih.gov/32345678/)

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KCNJ15 Gene

KCNJ15 Gene

KCNJ15 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

Kidney Disease

Ischemic Injury

Structure

Channel Architecture

Genetics

Disease-Associated Variants

Therapeutic Targeting

Interaction Network

Key Interacting Proteins

Clinical Relevance

Biomarker Potential

Drug Targets

See Also

References