Details for: KCNJ15

Gene ID: 3772

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: KCNJ15

Ensembl ID: ENSG00000157551

Description: potassium inwardly rectifying channel subfamily J member 15

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • epithelial cell of proximal tubule CL0002306
    CSI 10.32
    rCSI 25.21%
    PRS 92.47
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 7.98
    rCSI 11.31%
    PRS 95.56
  • mononuclear phagocyte CL0000113
    CSI 7.16
    rCSI 15.77%
    PRS 97.85
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 6.86
    rCSI 17.73%
    PRS 95.27
  • secretory cell CL0000151
    CSI 6.78
    rCSI 7.07%
    PRS 96.05
  • kidney connecting tubule epithelial cell CL1000768
    CSI 6.57
    rCSI 16.67%
    PRS 93.72
  • renal principal cell CL0005009
    CSI 5.7
    rCSI 14.82%
    PRS 95.99
  • epithelial cell of lung CL0000082
    CSI 5.69
    rCSI 4.71%
    PRS 97.47
  • epithelial cell of lower respiratory tract CL0002632
    CSI 4.74
    rCSI 3.67%
    PRS 97.91
  • kidney collecting duct principal cell CL1001431
    CSI 4.66
    rCSI 23.46%
    PRS 93.66
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 4.62
    rCSI 12.04%
    PRS 97.59
  • pulmonary alveolar type 2 cell CL0002063
    CSI 4.19
    rCSI 6.5%
    PRS 96.56
  • glutamatergic neuron CL0000679
    CSI 4.13
    rCSI 8.49%
    PRS 88.81
  • podocyte CL0000653
    CSI 3.84
    rCSI 17.07%
    PRS 96.49
  • renal alpha-intercalated cell CL0005011
    CSI 3.65
    rCSI 4.88%
    PRS 97.67
  • renal interstitial pericyte CL1001318
    CSI 3.57
    rCSI 9.83%
    PRS 95.75
  • neutrophil CL0000775
    CSI 3.03
    rCSI 16.98%
    PRS 93.99
  • respiratory basal cell CL0002633
    CSI 3.03
    rCSI 3.14%
    PRS 97.31
  • kidney proximal convoluted tubule epithelial cell CL1000838
    CSI 2.8
    rCSI 29.65%
    PRS 92.34
  • intrahepatic cholangiocyte CL0002538
    CSI 2.65
    rCSI 6.36%
    PRS 96.01
  • lung secretory cell CL1000272
    CSI 2.52
    rCSI 6.23%
    PRS 97.53
  • renal beta-intercalated cell CL0002201
    CSI 2.48
    rCSI 5.91%
    PRS 96.37
  • parietal epithelial cell CL1000452
    CSI 2.19
    rCSI 5.86%
    PRS 94.13
  • pancreatic ductal cell CL0002079
    CSI 1.33
    rCSI 2.58%
    PRS 96.7
  • cholangiocyte CL1000488
    CSI 1.18
    rCSI 7.1%
    PRS 94.76
  • kidney connecting tubule principal cell CL4030018
    CSI 1.12
    rCSI 8.13%
    PRS 96.39
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.57
    rCSI 6.04%
    PRS 93.97

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [KCNJ15](/details-gene/3772) encodes the potassium inwardly rectifying channel subfamily J member 15, an ATP-sensitive channel integral to potassium ion transport across the plasma membrane. Its expression profile indicates a highly specialized role in epithelial tissues, particularly within the kidney. **Overall**, it is most significantly expressed in the [epithelial cell of proximal tubule](/details-cell/CL0002306) and other segments of the renal tubules, suggesting a primary function in renal electrolyte homeostasis. Its involvement in neuronal signaling pathways is also supported by functional annotations and expression in neuronal cell types. The gene is located on chromosome 21 in a region associated with Down syndrome, as noted in early characterization studies [Link](https://doi.org/10.1006/geno.1997.4865). ## Cellular Roles and Expression Landscape The expression pattern of [KCNJ15](/details-gene/3772) strongly points to a critical role in specialized epithelial cell function, with a predominant signature in the kidney. The gene shows its highest significance in the [epithelial cell of proximal tubule](/details-cell/CL0002306) (CSI: 10.32), followed by various other epithelial cells of the nephron, including the [kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111) and [kidney connecting tubule epithelial cell](/details-cell/CL1000768). This concentrated expression across different parts of the renal tubule system establishes [KCNJ15](/details-gene/3772) as a key component of renal ion handling and fluid balance. Beyond the kidney, [KCNJ15](/details-gene/3772) also exhibits significant expression in other epithelial contexts, such as the [epithelial cell of lung](/details-cell/CL0000082) and [pulmonary alveolar type 2 cell](/details-cell/CL0002063), implying a broader role in maintaining epithelial membrane potential and transport functions in other organs. Interestingly, significant expression is also noted in [mononuclear phagocyte](/details-cell/CL0000113)s and [kidney interstitial alternatively activated macrophage](/details-cell/CL1000695)s, suggesting a potential, though less defined, role in modulating immune cell function. Furthermore, its expression in [glutamatergic neuron](/details-cell/CL0000679)s is consistent with its annotated involvement in neuronal signaling pathways. ## Pathways and Molecular Function Functionally, [KCNJ15](/details-gene/3772) is characterized by its [inward rectifier potassium channel activity](/details-term/GO:0005242) and its localization to the [plasma membrane](/details-term/GO:0005886) as part of a [monoatomic ion channel complex](/details-term/GO:0034702). This molecular function directly enables its primary biological process: [potassium ion import across plasma membrane](/details-term/GO:1990573) and the broader regulation of [potassium ion transport](/details-term/GO:0006813). Reactome pathway analysis further contextualizes its role, placing it within the [Potassium channels](/details-term/R-HSA-1296071) and specifically [Inwardly rectifying k+ channels](/details-term/R-HSA-1296065) superpathways. Its annotation in pathways such as [Activation of g protein gated potassium channels](/details-term/R-HSA-1296041) and [Neuronal system](/details-term/R-HSA-112316) aligns with its expression in neurons and its known interactions with G-protein coupled receptor signaling cascades. This is supported by evidence that related Kir channels interact with scaffolding proteins that also bind to NMDA receptors, implicating it in synaptic transmission [Link](https://doi.org/10.1006/mcne.1998.0679). ## Research Directions The highly specific expression of [KCNJ15](/details-gene/3772) in renal tubules, coupled with its fundamental role as a potassium channel, provides a clear basis for further investigation into renal physiology and pathology. ### Testable Hypotheses 1. **Hypothesis 1:** Given its dominant expression in the [epithelial cell of proximal tubule](/details-cell/CL0002306), dysregulation or genetic variation in [KCNJ15](/details-gene/3772) directly contributes to inherited or acquired renal tubulopathies characterized by impaired potassium reabsorption and electrolyte imbalance. 2. **Hypothesis 2:** In [mononuclear phagocyte](/details-cell/CL0000113)s, [KCNJ15](/details-gene/3772)-mediated potassium efflux is a key step in inflammasome activation, and its activity level dictates the magnitude of the inflammatory response to pathogens or sterile insults. ### Proposed Experiment To test the role of [KCNJ15](/details-gene/3772) in renal potassium handling (Hypothesis 1), a conditional knockout mouse model could be generated. A mouse line with loxP sites flanking the *Kcnj15* gene could be crossed with a line expressing Cre recombinase under the control of a kidney-specific promoter (e.g., Ksp-cadherin) to achieve tubule-specific deletion. These knockout mice and wild-type littermates would be subjected to metabolic cage studies under normal, low-, and high-potassium diets. Urine and serum electrolytes, creatinine clearance, and blood pressure would be monitored. A failure of the knockout mice to properly conserve potassium on a low-potassium diet or manage a potassium load, as evidenced by altered urine and serum potassium levels, would confirm the gene's critical role in renal potassium homeostasis. ### Therapeutic Potential As an ion channel, [KCNJ15](/details-gene/3772) is a potentially druggable target. Its high expression specificity in the kidney tubules makes it an attractive candidate for developing modulators to treat diseases of electrolyte imbalance, such as certain forms of hypertension or renal tubular acidosis. A therapeutic strategy would likely involve the development of small molecule agonists or antagonists to fine-tune channel activity rather than simple blockade. The specificity of such a compound for [KCNJ15](/details-gene/3772) over other potassium channels would be critical, but its distinct tissue distribution suggests that a targeted therapy could have a favorable safety profile with minimal off-target effects in the cardiovascular or central nervous systems.

Genular Protein ID: 171740982

Symbol: KCJ15_HUMAN

Name: ATP-sensitive inward rectifier potassium channel 15

UniProtKB Accession Codes:

Q99712 D3DSH5 O00564 Q96L28 Q99446

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 EMBL 7 Ensembl 7 ExpressionAtlas 1 GO 6 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIRSF 1 PRINTS 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 15 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9299242

Title: A new inward rectifier potassium channel gene (KCNJ15) localized on chromosome 21 in the Down syndrome chromosome region 1 (DCR1).

PubMed ID: 9299242

DOI: 10.1006/geno.1997.4865

PubMed ID: 8995301

Title: Cloning and characterization of two K+ inward rectifier (Kir) 1.1 potassium channel homologs from human kidney (Kir1.2 and Kir1.3).

PubMed ID: 8995301

DOI: 10.1074/jbc.272.1.586

PubMed ID: 10830953

Title: The DNA sequence of human chromosome 21.

PubMed ID: 10830953

DOI: 10.1038/35012518

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9647694

Title: CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0 family members, NMDA receptor subunits, neurexins, and neuroligins.

PubMed ID: 9647694

DOI: 10.1006/mcne.1998.0679

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 375
  • Mass: 42577
  • Checksum: CECCB4EDF827B24D
  • Sequence:
    • MDAIHIGMSS TPLVKHTAGA GLKANRPRVM SKSGHSNVRI DKVDGIYLLY LQDLWTTVID 
MKWRYKLTLF AATFVMTWFL FGVIYYAIAF IHGDLEPGEP ISNHTPCIMK VDSLTGAFLF 
SLESQTTIGY GVRSITEECP HAIFLLVAQL VITTLIEIFI TGTFLAKIAR PKKRAETIKF 
SHCAVITKQN GKLCLVIQVA NMRKSLLIQC QLSGKLLQTH VTKEGERILL NQATVKFHVD 
SSSESPFLIL PMTFYHVLDE TSPLRDLTPQ NLKEKEFELV VLLNATVEST SAVCQSRTSY 
IPEEIYWGFE FVPVVSLSKN GKYVADFSQF EQIRKSPDCT FYCADSEKQQ LEEKYRQEDQ 
RERELRTLLL QQSNV