GRIK2 Gene

HGNC Family	Glutamate receptors, Ion channels
Name	glutamate receptor, ionotropic, kainate 2
Description	Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. The subunit encoded by this gene is subject to RNA editing at multiple sites within the first and second transmembrane domains, which is thought to alter the structure and function of the receptor complex. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. Mutations in this gene have been associated with autosomal recessive cognitive disability. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GRIK2, which encodes the kainate receptor subunit GluR6, plays multifaceted roles in brain function by modulating excitatory neurotransmission, synaptic integration, and neuronal network oscillations. A number of genetic studies have implicated GRIK2 in neuropsychiatric and neurodevelopmental disorders. For example, alterations in its expression or function have been associated with schizophrenia and bipolar disorder, where network analyses reveal that GRIK2 (often together with the related GRIK3) is up‐regulated in specific hippocampal layers (e.g. in the CA2/3 region) and may contribute to GABAergic dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Likewise, mutation or deregulation of GRIK2 is linked to autism spectrum disorders through genetic linkage and association signals on chromosome 6q21"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", and loss‐of‐function mutations in GRIK2 have been shown to cause moderate-to-severe nonsyndromic mental retardation in humans."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond these developmental and psychiatric associations, functional studies in animal models have underscored the importance of GRIK2 in the proper regulation of synaptic transmission. Knockout studies demonstrate that ablation of GluR6 prevents kainate-induced gamma oscillations and epileptiform burst activity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while other models have revealed that GRIK2-containing receptors are critical for presynaptic facilitation when co-assembling with other subunits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, mouse studies have indicated that deletion of GluR6 leads to a collection of behavioral changes—including hyperactivity, altered risk-taking and aggression—that are reminiscent of manic syndromes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and modulation of GRIK2 expression has been implicated in altered seizure susceptibility associated with neurotoxic insults."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to these roles in neural excitability and behavior, epigenetic studies have identified differentially methylated regions within the GRIK2 gene that correlate with altered gene expression in astrocytic dysfunction associated with depressive psychopathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " GRIK2 has also emerged in genome-wide association analyses as a potential locus related to longevity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "and has been implicated in the modulation of adverse treatment effects, such as sexual dysfunction and treatment-emergent suicidal ideation during antidepressant exposure."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, the current body of evidence indicates that GRIK2 is a crucial component in the modulation of excitatory synaptic transmission and network plasticity. Its diverse roles encompass the regulation of synaptic oscillatory behavior, determination of cell-fate in excitatory versus inhibitory circuits, and involvement in various neuropsychiatric and neurodevelopmental conditions. Alterations in GRIK2 function—whether by genetic mutation, dysregulated expression, or epigenetic modifications—can disrupt neuronal homeostasis, contributing to disorders ranging from autism and intellectual disability to mood dysregulation and seizure susceptibility.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Francine M Benes, Benjamin Lim, David Matzilevich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0703806104"}], "href": "https://doi.org/10.1073/pnas.0703806104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17553960"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17553960"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "S Jamain, C Betancur, H Quach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Linkage and association of the glutamate receptor 6 gene with autism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.mp.4000979"}], "href": "https://doi.org/10.1038/sj.mp.4000979"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11920157"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11920157"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mohammad Mahdi Motazacker, Benjamin Rainer Rost, Tim Hucho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/521275"}], "href": "https://doi.org/10.1086/521275"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17847003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17847003"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "André Fisahn, Anis Contractor, Roger D Traub, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct roles for the kainate receptor subunits GluR5 and GluR6 in kainate-induced hippocampal gamma oscillations."}]}, {"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.2973-04.2004"}], "href": "https://doi.org/10.1523/JNEUROSCI.2973-04.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15509753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15509753"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Paulo S Pinheiro, David Perrais, Françoise Coussen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GluR7 is an essential subunit of presynaptic kainate autoreceptors at hippocampal mossy fiber synapses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0608891104"}], "href": "https://doi.org/10.1073/pnas.0608891104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17620617"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17620617"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "G Shaltiel, S Maeng, O Malkesman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for the involvement of the kainate receptor subunit GluR6 (GRIK2) in mediating behavioral displays related to behavioral symptoms of mania."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mp.2008.20"}], "href": "https://doi.org/10.1038/mp.2008.20"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18332879"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18332879"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Alejandra Rangel, Ferran Burgaya, Rosalina Gavín, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enhanced susceptibility of Prnp-deficient mice to kainate-induced seizures, neuronal apoptosis, and death: Role of AMPA/kainate receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jnr.21215"}], "href": "https://doi.org/10.1002/jnr.21215"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17304577"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17304577"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "C Nagy, M Suderman, J Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Astrocytic abnormalities and global DNA methylation patterns in depression and suicide."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mp.2014.21"}], "href": "https://doi.org/10.1038/mp.2014.21"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24662927"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24662927"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Linda Broer, Aron S Buchman, Joris Deelen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gerontol A Biol Sci Med Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/gerona/glu166"}], "href": "https://doi.org/10.1093/gerona/glu166"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25199915"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25199915"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Roy H Perlis, Gonzalo Laje, Jordan W Smoller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic and clinical predictors of sexual dysfunction in citalopram-treated depressed patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropsychopharmacology (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/npp.2009.4"}], "href": "https://doi.org/10.1038/npp.2009.4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19295509"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19295509"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Gonzalo Laje, Andrew S Allen, Nirmala Akula, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study of suicidal ideation emerging during citalopram treatment of depressed outpatients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacogenet Genomics (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/FPC.0b013e32832e4bcd"}], "href": "https://doi.org/10.1097/FPC.0b013e32832e4bcd"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19724244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19724244"}]}]}]}
Synonyms	GLUK6, GLR6, GLUR6, GLUK2, MRT6, EAA4
Proteins	GRIK2_HUMAN
NCBI Gene ID	2898
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GRIK2 has 5,006 functional associations with biological entities spanning 8 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) extracted from 113 datasets.

Click the + buttons to view associations for GRIK2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GRIK2 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 GRIK2 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 GRIK2 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 GRIK2 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 GRIK2 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 GRIK2 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 GRIK2 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 GRIK2 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 GRIK2 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 GRIK2 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 GRIK2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with GRIK2 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 GRIK2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GRIK2 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 GRIK2 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 GRIK2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GRIK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with GRIK2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	CORUM Protein Complexes	protein complexs containing GRIK2 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of GRIK2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GRIK2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with GRIK2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with GRIK2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with GRIK2 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 GRIK2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving GRIK2 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving GRIK2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with GRIK2 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 GRIK2 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 GRIK2 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 GRIK2 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 GRIK2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with GRIK2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for GRIK2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at GRIK2 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 GRIK2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GRIK2 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 GRIK2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with GRIK2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with GRIK2 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 GRIK2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.