GRM8 Gene

HGNC Family	Glutamate receptors, G protein-coupled receptors
Name	glutamate receptor, metabotropic 8
Description	L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GRM8 encodes the metabotropic glutamate receptor 8 (mGluR8), a G protein–coupled receptor predominantly located at presynaptic sites that modulates glutamatergic neurotransmission. Genetic association studies have implicated variation in GRM8 in influencing behavioral and psychiatric phenotypes; for instance, GRM8 variants have been linked to differences in personality traits related to depressive affect and alcohol dependence"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", as well as smoking behavior"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", and have been nominated as candidate loci in studies of hearing function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In animal models, targeted deletion of mGluR8 has revealed subtle but significant alterations in exploratory and anxiety‐related behaviors, suggesting that mGluR8 plays a role in modulating responses to novel and aversive environments."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, human genetic studies have identified GRM8 as a susceptibility locus for schizophrenia and major depressive disorder, with haplotype analyses supporting its role in neuropsychiatric risk."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its neurological functions, aberrant GRM8 signaling has also been implicated in cancer biology. Functional analyses in lung squamous cell carcinoma have uncovered activating GRM8 variants that promote tumor cell survival through inhibition of the cyclic AMP pathway and activation of the MAPK cascade, suggesting that dysregulated GRM8 signaling may serve as a growth‐promoting mechanism and a potential therapeutic target in this cancer type."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that GRM8 is a multifunctional receptor whose normal role in modulating synaptic transmission has broad effects on behavior and psychiatric vulnerability, while its aberrant activation may also contribute to oncogenic processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Antonio Terracciano, Toshiko Tanaka, Angelina R Sutin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association scan of trait depression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Psychiatry (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopsych.2010.06.030"}], "href": "https://doi.org/10.1016/j.biopsych.2010.06.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20800221"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20800221"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jacqueline M Vink, August B Smit, Eco J C de Geus, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study of smoking initiation and current smoking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2009.02.001"}], "href": "https://doi.org/10.1016/j.ajhg.2009.02.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19268276"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19268276"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Giorgia Girotto, Nicola Pirastu, Rossella Sorice, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2010.088310"}], "href": "https://doi.org/10.1136/jmg.2010.088310"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21493956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21493956"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "A-M Linden, B G Johnson, S C Peters, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased anxiety-related behavior in mice deficient for metabotropic glutamate 8 (mGlu8) receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropharmacology (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0028-3908(02)00079-5"}], "href": "https://doi.org/10.1016/s0028-3908(02"}, {"type": "t", "text": "00079-5) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12213279"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12213279"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hiromi Takaki, Rumiko Kikuta, Hiroki Shibata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene (GRM8) with schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.20108"}], "href": "https://doi.org/10.1002/ajmg.b.20108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15211621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15211621"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Wenjin Li, Kang Ju, Zhiqiang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Significant association of GRM7 and GRM8 genes with schizophrenia and major depressive disorder in the Han Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Neuropsychopharmacol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.euroneuro.2015.05.004"}], "href": "https://doi.org/10.1016/j.euroneuro.2015.05.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26655190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26655190"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Henry A Dunn, Dipak N Patil, Yan Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Synaptic adhesion protein ELFN1 is a selective allosteric modulator of group III metabotropic glutamate receptors "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "in trans"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1722498115"}], "href": "https://doi.org/10.1073/pnas.1722498115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29686062"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29686062"}]}]}]}
Synonyms	MGLU8, GPRC1H, GLUR8, MGLUR8
Proteins	GRM8_HUMAN
NCBI Gene ID	2918
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GRM8 has 5,395 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 120 datasets.

Click the + buttons to view associations for GRM8 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GRM8 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 GRM8 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 GRM8 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 GRM8 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 GRM8 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 GRM8 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 GRM8 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 GRM8 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 GRM8 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 GRM8 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 GRM8 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 GRM8 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of GRM8 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 GRM8 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with GRM8 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 GRM8 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GRM8 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 GRM8 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 GRM8 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GRM8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with GRM8 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 GRM8 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of GRM8 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GRM8 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with GRM8 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with GRM8 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with GRM8 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 GRM8 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with GRM8 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 GRM8 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 GRM8 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 GRM8 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 GRM8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with GRM8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for GRM8 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at GRM8 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 GRM8 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GRM8 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 GRM8 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with GRM8 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with GRM8 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.