KCNJ6 Gene

HGNC Family	Ion channels
Name	potassium channel, inwardly rectifying subfamily J, member 6
Description	This gene encodes a member of the G protein-coupled inwardly-rectifying potassium channel family of inward rectifier potassium channels. This type of potassium channel allows a greater flow of potassium into the cell than out of it. These proteins modulate many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells, through G-protein coupled receptor stimulation. Mutations in this gene are associated with Keppen-Lubinsky Syndrome, a rare condition characterized by severe developmental delay, facial dysmorphism, and intellectual disability. [provided by RefSeq, Apr 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KCNJ6 encodes the GIRK2 subunit of G‐protein–gated inwardly rectifying potassium channels that play a pivotal role in modulating neuronal excitability and synaptic transmission. Genetic studies have implicated variants in KCNJ6 as potential risk factors for nicotine dependence, suggesting that altered GIRK2 function may influence reward pathways and addiction susceptibility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, studies in models of Down syndrome demonstrate that overexpression of GIRK2 leads to enhanced GABA<sub>B</sub>–mediated potassium currents and increased inhibitory drive in hippocampal neurons, a change that can disturb the excitatory/inhibitory balance and contribute to cognitive deficits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functional analyses using GIRK2 knockout mice further reveal that GIRK2‐containing channels are critical mediators of analgesic responses: loss of GIRK2 markedly diminishes the antinociceptive effects of various neurotransmitter receptor agonists, emphasizing its role in postsynaptic inhibitory signaling and the regulation of pain sensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " At the molecular level, reconstitution studies show that GIRK2 channel activation requires coordinated input from Gβγ subunits and phosphatidylinositol 4,5‐bisphosphate, mechanisms that finely tune its gating and highlight its responsiveness to diverse neuromodulatory signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, immunolocalization studies confirm that GIRK2 is highly expressed in key midbrain regions, including the substantia nigra and ventral tegmental area, where it participates in the regulation of dopaminergic neuronal activity. This distribution underscores its importance in controlling neural circuits implicated in movement, motivation, and neuroprotection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings establish KCNJ6/GIRK2 as a central component in the regulation of neuronal excitability and inhibitory signaling. Its activity influences a range of physiological processes—from addictive behaviors and pain modulation to the maintenance of proper neuronal network balance—with dysregulation potentially contributing to neurodevelopmental disorders and altered neurophysiological states.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Scott F Saccone, Anthony L Hinrichs, Nancy L Saccone, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddl438"}], "href": "https://doi.org/10.1093/hmg/ddl438"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17135278"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17135278"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tyler K Best, Richard J Siarey, Zygmunt Galdzicki "}, {"type": "b", "children": [{"type": "t", "text": "Ts65Dn, a mouse model of Down syndrome, exhibits increased GABAB-induced potassium current."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurophysiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/jn.00626.2006"}], "href": "https://doi.org/10.1152/jn.00626.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17093127"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17093127"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Y A Blednov, M Stoffel, H Alva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A pervasive mechanism for analgesia: activation of GIRK2 channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.012682399"}], "href": "https://doi.org/10.1073/pnas.012682399"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12493843"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12493843"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Weiwei Wang, Matthew R Whorton, Roderick MacKinnon "}, {"type": "b", "children": [{"type": "t", "text": "Quantitative analysis of mammalian GIRK2 channel regulation by G proteins, the signaling lipid PIP2 and Na+ in a reconstituted system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.03671"}], "href": "https://doi.org/10.7554/eLife.03671"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25049222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25049222"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Stefanie Reyes, Yuhong Fu, Kay Double, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GIRK2 expression in dopamine neurons of the substantia nigra and ventral tegmental area."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Comp Neurol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cne.23051"}], "href": "https://doi.org/10.1002/cne.23051"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22252428"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22252428"}]}]}]}
Synonyms	KIR3.2, KPLBS, GIRK-2, KATP2, HIGIRK2, GIRK2, KATP-2, BIR1, KCNJ7
Proteins	KCNJ6_HUMAN
NCBI Gene ID	3763
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KCNJ6 has 5,321 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 122 datasets.

Click the + buttons to view associations for KCNJ6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KCNJ6 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by KCNJ6 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of KCNJ6 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 KCNJ6 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of KCNJ6 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of KCNJ6 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 KCNJ6 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 KCNJ6 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 KCNJ6 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 KCNJ6 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 KCNJ6 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of KCNJ6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of KCNJ6 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 KCNJ6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KCNJ6 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 KCNJ6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KCNJ6 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 KCNJ6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with KCNJ6 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KCNJ6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing KCNJ6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with KCNJ6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing KCNJ6 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of KCNJ6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KCNJ6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KCNJ6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KCNJ6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with KCNJ6 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by KCNJ6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving KCNJ6 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with KCNJ6 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 KCNJ6 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 KCNJ6 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 KCNJ6 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 KCNJ6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KCNJ6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for KCNJ6 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at KCNJ6 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 KCNJ6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KCNJ6 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 KCNJ6 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.