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    GRM5 glutamate metabotropic receptor 5 [ Homo sapiens (human) ]

    Gene ID: 2915, updated on 11-Apr-2024

    Summary

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    Official Symbol
    GRM5provided by HGNC
    Official Full Name
    glutamate metabotropic receptor 5provided by HGNC
    Primary source
    HGNC:HGNC:4597
    See related
    Ensembl:ENSG00000168959 MIM:604102; AllianceGenome:HGNC:4597
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    mGlu5; GPRC1E; MGLUR5; PPP1R86
    Summary
    This gene encodes a member of the G-protein coupled receptor 3 protein family. The encoded protein is a metabatropic glutamate receptor, whose signaling activates a phosphatidylinositol-calcium second messenger system. This protein may be involved in the regulation of neural network activity and synaptic plasticity. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. A pseudogene of this gene has been defined on chromosome 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
    Expression
    Restricted expression toward brain (RPKM 10.2) See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    11q14.2-q14.3
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (88504642..89065982, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (88423789..88985122, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (88237810..88799150, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr11:88030550-88031243 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5380 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr11:88040649-88041604 Neighboring gene MPRA-validated peak1386 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5381 Neighboring gene Sharpr-MPRA regulatory region 1780 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5382 Neighboring gene uncharacterized LOC101929174 Neighboring gene CRISPRi-validated cis-regulatory element chr11.4755 Neighboring gene CRISPRi-validated cis-regulatory element chr11.4758 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5383 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5384 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5385 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5386 Neighboring gene cathepsin C Neighboring gene glyceraldehyde 3 phosphate dehydrogenase pseudogene 70 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3833 Neighboring gene Sharpr-MPRA regulatory region 7525 Neighboring gene GRM5 antisense RNA 1 Neighboring gene RNA, U6 small nuclear 16, pseudogene Neighboring gene NANOG hESC enhancer GRCh37_chr11:88521820-88522321 Neighboring gene tyrosinase 5' upstream regulatory sequence Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr11:88914222-88914816 Neighboring gene tyrosinase Neighboring gene CBX3 pseudogene 7 Neighboring gene Sharpr-MPRA regulatory region 6977 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:89189921-89190421 Neighboring gene NADPH oxidase 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:89224088-89224794 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:89224795-89225501 Neighboring gene H3 histone pseudogene 34

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Inhibition of mGluR5 ameliorates lipid accumulation and inflammation in HepG2 cells. Zeng S, et al. Biochem Biophys Res Commun, 2023 Apr 23. PMID 36842305
    2. [Association of glutamate receptor metabotropic 5 polymorphisms with schizophrenia susceptibility in a Chinese Han population]. Song M, et al. Zhonghua Yi Xue Za Zhi, 2022 Jul 19. PMID 35844113
    3. mGluR5 binding changes during a mismatch negativity task in a multimodal protocol with [(11)C]ABP688 PET/MR-EEG. Régio Brambilla C, et al. Transl Psychiatry, 2022 Jan 10. PMID 35013095, Free PMC Article
    4. Noncanonical Metabotropic Glutamate Receptor 5 Signaling in Alzheimer's Disease. Abd-Elrahman KS, et al. Annu Rev Pharmacol Toxicol, 2022 Jan 6. PMID 34516293
    5. Agonists and allosteric modulators promote signaling from different metabotropic glutamate receptor 5 conformations. Nasrallah C, et al. Cell Rep, 2021 Aug 31. PMID 34469715, Free PMC Article

    See all (129) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Metabotropic glutamate receptor 5 (mGluR5) is associated with neurodegeneration and amyloid deposition in Alzheimer's disease: A [[18]F]PSS232 PET/MRI study.
      Title: Metabotropic glutamate receptor 5 (mGluR5) is associated with neurodegeneration and amyloid deposition in Alzheimer's disease: A [(18)F]PSS232 PET/MRI study.
    2. Blockade of mGluR5 in astrocytes derived from human iPSCs modulates astrocytic function and increases phagocytosis.
      Title: Blockade of mGluR5 in astrocytes derived from human iPSCs modulates astrocytic function and increases phagocytosis.
    3. Upregulation of Parkinson's disease-associated protein alpha-synuclein suppresses tumorigenesis via interaction with mGluR5 and gamma-synuclein in liver cancer.
      Title: Upregulation of Parkinson's disease-associated protein alpha-synuclein suppresses tumorigenesis via interaction with mGluR5 and gamma-synuclein in liver cancer.
    4. Inhibition of mGluR5 ameliorates lipid accumulation and inflammation in HepG2 cells.
      Title: Inhibition of mGluR5 ameliorates lipid accumulation and inflammation in HepG2 cells.
    5. From bench to bedside: The mGluR5 system in people with and without Autism Spectrum Disorder and animal model systems.
      Title: From bench to bedside: The mGluR5 system in people with and without Autism Spectrum Disorder and animal model systems.
    6. [Association of glutamate receptor metabotropic 5 polymorphisms with schizophrenia susceptibility in a Chinese Han population].
      Title: [Association of glutamate receptor metabotropic 5 polymorphisms with schizophrenia susceptibility in a Chinese Han population].
    7. Noncanonical Metabotropic Glutamate Receptor 5 Signaling in Alzheimer's Disease.
      Title: Noncanonical Metabotropic Glutamate Receptor 5 Signaling in Alzheimer's Disease.
    8. Agonists and allosteric modulators promote signaling from different metabotropic glutamate receptor 5 conformations.
      Title: Agonists and allosteric modulators promote signaling from different metabotropic glutamate receptor 5 conformations.
    9. mGluR5 binding changes during a mismatch negativity task in a multimodal protocol with [(11)C]ABP688 PET/MR-EEG.
      Title: mGluR5 binding changes during a mismatch negativity task in a multimodal protocol with [(11)C]ABP688 PET/MR-EEG.
    10. Specific changes in sleep oscillations after blocking human metabotropic glutamate receptor 5 in the absence of altered memory function.
      Title: Specific changes in sleep oscillations after blocking human metabotropic glutamate receptor 5 in the absence of altered memory function.
    Submit: New GeneRIF Correction See all GeneRIFs (94)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides.
    EBI GWAS Catalog
    Common genetic variation and the control of HIV-1 in humans.
    EBI GWAS Catalog
    Genome-wide association study in German patients with attention deficit/hyperactivity disorder.
    EBI GWAS Catalog
    Genome-wide association study of tanning phenotype in a population of European ancestry.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat The gene expression of GRM5 is significantly upregulated in both clade B and clade C Tat treated SK-N-MC neuroblastoma cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables A2A adenosine receptor binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables G protein-coupled receptor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables adenylate cyclase inhibiting G protein-coupled glutamate receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables glutamate receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein tyrosine kinase activator activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein tyrosine kinase binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in G protein-coupled glutamate receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in G protein-coupled glutamate receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in calcium-mediated signaling using intracellular calcium source IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in cellular response to amyloid-beta IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in cellular response to amyloid-beta ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in chemical synaptic transmission IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cognition IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in desensitization of G protein-coupled receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in learning IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in learning or memory ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in locomotory behavior IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in phospholipase C-activating G protein-coupled glutamate receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of long-term neuronal synaptic plasticity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of protein tyrosine kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein kinase C-activating G protein-coupled receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of DNA-templated transcription IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of postsynaptic cytosolic calcium ion concentration IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of postsynaptic membrane potential IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of protein phosphorylation IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in regulation of synaptic transmission, glutamatergic IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of translation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of translational elongation IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in synapse organization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in trans-synaptic signaling by endocannabinoid, modulating synaptic transmission IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in Schaffer collateral - CA1 synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in astrocyte projection IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in dendritic shaft IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in dendritic spine IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    is_active_in postsynaptic density membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    metabotropic glutamate receptor 5
    Names
    glutamate receptor, metabotropic 5
    protein phosphatase 1, regulatory subunit 86

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_052831.1 RefSeqGene

      Range
      4990..566330
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000842.5 → NP_000833.1  metabotropic glutamate receptor 5 isoform b precursor

      See identical proteins and their annotated locations for NP_000833.1

      Status: REVIEWED

      Source sequence(s)
      AP000626, AP001482, AP001828, AP003120, AP006215
      Consensus CDS
      CCDS8283.1
      UniProtKB/TrEMBL
      K9J9K9
      Related
      ENSP00000405690.2, ENST00000455756.6
      Conserved Domains (4) summary
      cd15450
      Location:578 → 827
      7tmC_mGluR5; metabotropic glutamate receptor 5 in group 1, member of the class C family of seven-transmembrane G protein-coupled receptors
      cd06374
      Location:26 → 497
      PBP1_mGluR_groupI; ligand binding domain of the group I metabotropic glutamate receptor
      pfam07562
      Location:508 → 558
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      pfam10606
      Location:1131 → 1180
      GluR_Homer-bdg; Homer-binding domain of metabotropic glutamate receptor

    2. NM_001143831.3 → NP_001137303.1  metabotropic glutamate receptor 5 isoform a precursor

      See identical proteins and their annotated locations for NP_001137303.1

      Status: REVIEWED

      Source sequence(s)
      AP000626, AP001482, AP001828, AP003120, AP006215
      Consensus CDS
      CCDS44694.1
      UniProtKB/Swiss-Prot
      P41594, Q6J164
      UniProtKB/TrEMBL
      K9J9K9
      Related
      ENSP00000306138.4, ENST00000305447.5
      Conserved Domains (5) summary
      cd06374
      Location:26 → 497
      PBP1_mGluR_groupI; Ligand binding domain of the group I metabotropic glutamate receptor
      pfam00003
      Location:591 → 824
      7tm_3; 7 transmembrane sweet-taste receptor of 3 GCPR
      pfam01094
      Location:67 → 472
      ANF_receptor; Receptor family ligand binding region
      pfam07562
      Location:508 → 557
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      pfam10606
      Location:1162 → 1212
      GluR_Homer-bdg; Homer-binding domain of metabotropic glutamate receptor

    3. NM_001384268.1 → NP_001371197.1  metabotropic glutamate receptor 5 isoform b precursor

      Status: REVIEWED

      Source sequence(s)
      AP000626, AP001482, AP001828, AP003120, AP006215
      Consensus CDS
      CCDS8283.1
      UniProtKB/TrEMBL
      K9J9K9
      Conserved Domains (4) summary
      cd15450
      Location:578 → 827
      7tmC_mGluR5; metabotropic glutamate receptor 5 in group 1, member of the class C family of seven-transmembrane G protein-coupled receptors
      cd06374
      Location:26 → 497
      PBP1_mGluR_groupI; ligand binding domain of the group I metabotropic glutamate receptor
      pfam07562
      Location:508 → 558
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      pfam10606
      Location:1131 → 1180
      GluR_Homer-bdg; Homer-binding domain of metabotropic glutamate receptor

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      88504642..89065982 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011542792.2 → XP_011541094.1  metabotropic glutamate receptor 5 isoform X1

      See identical proteins and their annotated locations for XP_011541094.1

      UniProtKB/Swiss-Prot
      P41594, Q6J164
      UniProtKB/TrEMBL
      K9J9K9
      Conserved Domains (5) summary
      cd06374
      Location:26 → 497
      PBP1_mGluR_groupI; Ligand binding domain of the group I metabotropic glutamate receptor
      pfam00003
      Location:591 → 824
      7tm_3; 7 transmembrane sweet-taste receptor of 3 GCPR
      pfam01094
      Location:67 → 472
      ANF_receptor; Receptor family ligand binding region
      pfam07562
      Location:508 → 557
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      pfam10606
      Location:1162 → 1212
      GluR_Homer-bdg; Homer-binding domain of metabotropic glutamate receptor

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      88423789..88985122 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054368585.1 → XP_054224560.1  metabotropic glutamate receptor 5 isoform X1

      UniProtKB/Swiss-Prot
      P41594, Q6J164
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P41594.2 GenPept UniProtKB/Swiss-Prot:P41594

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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