KCNJ3 Gene

HGNC Family	Ion channels
Name	potassium channel, inwardly rectifying subfamily J, member 3
Description	Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and plays an important role in regulating heartbeat. It associates with three other G-protein-activated potassium channels to form a heteromultimeric pore-forming complex that also couples to neurotransmitter receptors in the brain and whereby channel activation can inhibit action potential firing by hyperpolarizing the plasma membrane. These multimeric G-protein-gated inwardly-rectifying potassium (GIRK) channels may play a role in the pathophysiology of epilepsy, addiction, Down's syndrome, ataxia, and Parkinson's disease. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, May 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KCNJ3 encodes the GIRK1 subunit of G protein–gated inwardly rectifying potassium (GIRK) channels, which play a central role in translating G protein–coupled receptor (GPCR) activation into membrane hyperpolarization and reduced cellular excitability. Structural investigations have revealed that GIRK1 forms a critical component of multimeric channel complexes—with other GIRK subunits—that possess extended intracellular domains and a specialized cytoplasmic pore environment enabling inward rectification through polyamine and Mg²⁺ block."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the cardiac system, GIRK1-containing channels are essential mediators of the parasympathetic regulation of heart rate. By coupling to muscarinic M2 receptors, these channels contribute to the acetylcholine-activated potassium current (I<sub>KACh</sub>), thereby promoting bradycardia and ensuring appropriate cardiac automaticity; loss or dysfunction of GIRK1 has been associated with impaired current kinetics and altered heart rate responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Within the central nervous system, GIRK1 is a key effector downstream of diverse GPCRs—including opioid, cannabinoid, and GABA<sub>B</sub> receptors—that mediate inhibitory postsynaptic responses. Activation of GIRK1‐containing channels in various neuronal populations, such as cortical pyramidal, hippocampal, cerebellar, and platelet cells, diminishes neuronal excitability and modulates synaptic transmission and plasticity. This mechanism has been implicated in processes ranging from analgesia and the regulation of mood to the shaping of dendritic input integration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its classical roles in excitable tissues, aberrant GIRK1 expression has been observed in other contexts—for instance, altered GIRK1 levels in pancreatic adenocarcinoma suggest that GIRK channels may also influence cell proliferation and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " In addition, modulation of GIRK channel activity by regulatory proteins and signaling cascades further underscores its versatility as a modulator of both neuronal and non‐neuronal physiology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, KCNJ3/GIRK1 is an essential component of GIRK channel complexes that bridges GPCR activation to hyperpolarizing potassium currents. This coupling mechanism is critical for regulating cardiac rhythm, controlling neuronal excitability and synaptic integration, and may even extend to modulating cellular growth processes. Collectively, these findings underscore the broad physiological relevance of GIRK1 across multiple tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_fs", "start_ref": "7", "end_ref": "11"}, {"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Motohiko Nishida, Roderick MacKinnon "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(02)01227-8"}], "href": "https://doi.org/10.1016/s0092-8674(02"}, {"type": "t", "text": "01227-8) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12507423"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12507423"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sean D McAllister, Dow P Hurst, Judy Barnett-Norris, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural mimicry in class A G protein-coupled receptor rotamer toggle switches: the importance of the F3.36(201)/W6.48(357) interaction in cannabinoid CB1 receptor activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M406648200"}], "href": "https://doi.org/10.1074/jbc.M406648200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15326174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15326174"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Cheryl L Marker, Markus Stoffel, Kevin Wickman "}, {"type": "b", "children": [{"type": "t", "text": "Spinal G-protein-gated K+ channels formed by GIRK1 and GIRK2 subunits modulate thermal nociception and contribute to morphine analgesia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.5251-03.2004"}], "href": "https://doi.org/10.1523/JNEUROSCI.5251-03.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15028774"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15028774"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ilham Bettahi, Cheryl L Marker, Maria I Roman, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "RGS6, a modulator of parasympathetic activation in heart."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.110.224220"}], "href": "https://doi.org/10.1161/CIRCRESAHA.110.224220"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20864673"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20864673"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jonathan M Ehrich, Daniel I Messinger, Cerise R Knakal, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Reelin signaling specifies the molecular identity of the pyramidal neuron distal dendritic compartment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2014.07.035"}], "href": "https://doi.org/10.1016/j.cell.2014.07.035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25201528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25201528"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Haripriya Shankar, Swaminathan Murugappan, Soochong Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of G protein-gated inwardly rectifying potassium channels in P2Y12 receptor-mediated platelet functional responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-01-0069"}], "href": "https://doi.org/10.1182/blood-2004-01-0069"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15142872"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15142872"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Laura Fernández-Alacid, Carolina Aguado, Francisco Ciruela, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Subcellular compartment-specific molecular diversity of pre- and post-synaptic GABA-activated GIRK channels in Purkinje cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2009.06229.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2009.06229.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19558451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19558451"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Laura Fernández-Alacid, Masahiko Watanabe, Elek Molnár, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Developmental regulation of G protein-gated inwardly-rectifying K+ (GIRK/Kir3) channel subunits in the brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Neurosci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1460-9568.2011.07886.x"}], "href": "https://doi.org/10.1111/j.1460-9568.2011.07886.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22098295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22098295"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Melissa Richard-Lalonde, Karim Nagi, Nicolas Audet, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Repeated stress dysregulates κ-opioid receptor signaling in the dorsal raphe through a p38α MAPK-dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.2053-12.2012"}], "href": "https://doi.org/10.1523/JNEUROSCI.2053-12.2012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22956823"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22956823"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Marie Brevet, David Fucks, Denis Chatelain, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deregulation of 2 potassium channels in pancreas adenocarcinomas: implication of KV1.3 gene promoter methylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pancreas (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MPA.0b013e3181a56ebf"}], "href": "https://doi.org/10.1097/MPA.0b013e3181a56ebf"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19465885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19465885"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Borzoo Farhang, Lindsay Pietruszewski, Kabirullah Lutfy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of the NOP receptor in regulating food intake, meal pattern, and the excitability of proopiomelanocortin neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropharmacology (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuropharm.2010.05.007"}], "href": "https://doi.org/10.1016/j.neuropharm.2010.05.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20510254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20510254"}]}]}]}
Synonyms	GIRK1, KIR3.1
Proteins	KCNJ3_HUMAN
NCBI Gene ID	3760
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KCNJ3 has 5,906 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 115 datasets.

Click the + buttons to view associations for KCNJ3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KCNJ3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of KCNJ3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of KCNJ3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of KCNJ3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of KCNJ3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of KCNJ3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of KCNJ3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of KCNJ3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of KCNJ3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of KCNJ3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of KCNJ3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KCNJ3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of KCNJ3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KCNJ3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of KCNJ3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of KCNJ3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KCNJ3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing KCNJ3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with KCNJ3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with KCNJ3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing KCNJ3 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of KCNJ3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KCNJ3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KCNJ3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KCNJ3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by KCNJ3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with KCNJ3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with KCNJ3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with KCNJ3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with KCNJ3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with KCNJ3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KCNJ3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for KCNJ3 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at KCNJ3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of KCNJ3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KCNJ3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing KCNJ3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with KCNJ3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with KCNJ3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of KCNJ3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with KCNJ3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.