GRM1 glutamate metabotropic receptor 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRM1provided by HGNC
Official Full Name: glutamate metabotropic receptor 1provided by HGNC
Primary source: HGNC:HGNC:4593
See related: Ensembl:ENSG00000152822 MIM:604473; AllianceGenome:HGNC:4593
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: MGLU1; SCA44; GPRC1A; MGLUR1; SCAR13; PPP1R85
Summary: This gene encodes a metabotropic glutamate receptor that functions by activating phospholipase C. 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 canonical alpha isoform of the encoded protein is a disulfide-linked homodimer whose activity is mediated by a G-protein-coupled phosphatidylinositol-calcium second messenger system. This gene may be associated with many disease states, including schizophrenia, bipolar disorder, depression, and breast cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]
Expression: Biased expression in brain (RPKM 2.8), heart (RPKM 1.1) and 2 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6q24.3

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (146027707..146437601)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (147215189..147630683)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (146348843..146758737)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Genetic Variant in GRM1 Underlies Congenital Cerebellar Ataxia with No Obvious Intellectual Disability.
Title: Genetic Variant in GRM1 Underlies Congenital Cerebellar Ataxia with No Obvious Intellectual Disability.
A Novel Nonsense Variant in GRM1 Causes Autosomal Recessive Spinocerebellar Ataxia 13 in a Consanguineous Pakistani Family.
Title: A Novel Nonsense Variant in GRM1 Causes Autosomal Recessive Spinocerebellar Ataxia 13 in a Consanguineous Pakistani Family.
The Emerging Key Role of the mGluR1-PKCgamma Signaling Pathway in the Pathogenesis of Spinocerebellar Ataxias: A Neurodevelopmental Viewpoint.
Title: The Emerging Key Role of the mGluR1-PKCγ Signaling Pathway in the Pathogenesis of Spinocerebellar Ataxias: A Neurodevelopmental Viewpoint.
Structural insights into the activation initiation of full-length mGlu1.
Title: Structural insights into the activation initiation of full-length mGlu1.
Brain (11) C-ITMM PET to longitudinally assess type 1 metabotropic glutamate receptor availability in Alzheimer's disease.
Title: Brain (11) C-ITMM PET to longitudinally assess type 1 metabotropic glutamate receptor availability in Alzheimer's disease.
Mutations in Metabotropic Glutamate Receptor 1 Contribute to Natural Short Sleep Trait.
Title: Mutations in Metabotropic Glutamate Receptor 1 Contribute to Natural Short Sleep Trait.
Metabotropic glutamate receptor 1 is associated with unfavorable prognosis in ER-negative and triple-negative breast cancer.
Title: Metabotropic glutamate receptor 1 is associated with unfavorable prognosis in ER-negative and triple-negative breast cancer.
This study provided the evidence that glutamate causes a dose-dependent increase in [Ca2+]i by activating mGluR1 and, at a larger extent, mGluR5.
Title: Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular Ca(2+) signals and nitric oxide release in human brain microvascular endothelial cells.
we report the third pathogenic variant in GRM1 gene causing an autosomal-recessive form of cerebellar ataxia. Our observation not only emphasizes the central role of mGluR1-mediated signaling in cerebellar function but also provides valuable insights into the early clinical signs of recessive ataxia due to biallelic GRM1 pathogenic variants.
Title: A novel truncating variant p.(Arg297*) in the GRM1 gene causing autosomal-recessive cerebellar ataxia with juvenile-onset.
TRPC6 regulates actin stress fiber formation and focal adhesions via the RhoA pathway in response to group I metabotropic glutamate receptor activation.
Title: Group I metabotropic glutamate receptor activation induces TRPC6-dependent calcium influx and RhoA activation in cultured human kidney podocytes.

Submit: New GeneRIF Correction See all GeneRIFs (86)

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

Associated conditions

Description	Tests
Autosomal recessive spinocerebellar ataxia 13 MedGen: C3553816 OMIM: 614831 GeneReviews: Not available	Compare labs
Spinocerebellar ataxia 44 MedGen: C4521563 OMIM: 617691 GeneReviews: Not available	Compare labs

Variation

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See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat upregulates N-methyl-D-aspartate receptor function by activating metabotropic glutamate receptor 1 in human brain noradrenergic neurons	PubMed
	tat	HIV-1 Tat potentiates the depolarization-evoked exocytosis of aspartate from human neocortical terminals, which involves the metabotropic glutamate (mGlu) 1 receptor	PubMed

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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

SHGC-68263 (e-PCR)
- UniSTS:100615

RH79141 (e-PCR)
- UniSTS:3355

SHGC-35565 (e-PCR)
- UniSTS:29736

RH123919 (e-PCR)
- UniSTS:136294

D6S971 (e-PCR), detects polymorphism
- UniSTS:149358

RH37583 (e-PCR)
- UniSTS:24942

D6S1342 (e-PCR)
- UniSTS:46202

RH120949 (e-PCR)
- UniSTS:133808

D6S1042 (e-PCR), detects polymorphism
- UniSTS:27316

RH121456 (e-PCR)
- UniSTS:134585

G48324 (e-PCR)
- UniSTS:95419

G29866 (e-PCR)
- UniSTS:53697

G10437 (e-PCR)
- UniSTS:59078

D6S1480 (e-PCR)
- UniSTS:33769

AL021851 (e-PCR)
- UniSTS:28402

D6S1649 (e-PCR), detects polymorphism
- UniSTS:15607

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration	IEA Inferred from Electronic Annotation more info
enables G protein-coupled receptor activity	TAS Traceable Author Statement 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 G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential	IDA Inferred from Direct Assay more info	PubMed
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 glutamate receptor activity	TAS Traceable Author Statement 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

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 receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in L-glutamate import across plasma membrane	IEA Inferred from Electronic Annotation more info
involved_in adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in cellular response to electrical stimulus	IEA Inferred from Electronic Annotation more info
involved_in chemical synaptic transmission	IEA Inferred from Electronic Annotation 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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phospholipase C-activating G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MAPK cascade	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 sensory perception of pain	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic transmission, glutamatergic	IBA Inferred from Biological aspect of Ancestor more info
involved_in sensory perception of pain	IEA Inferred from Electronic Annotation more info
involved_in synaptic signaling via neuropeptide	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of G protein-coupled receptor dimeric complex	IDA Inferred from Direct Assay more info	PubMed
part_of G protein-coupled receptor homodimeric complex	IPI Inferred from Physical Interaction more info	PubMed
located_in Schaffer collateral - CA1 synapse	IEA Inferred from Electronic Annotation more info
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in nucleus	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 1

Names: glutamate receptor, metabotropic 1; protein phosphatase 1, regulatory subunit 85

NCBI Reference Sequences (RefSeq)

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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

NG_012839.2 RefSeqGene

Range

6417..414956

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001278064.2 → NP_001264993.1 metabotropic glutamate receptor 1 isoform alpha precursor

See identical proteins and their annotated locations for NP_001264993.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) encodes the longest isoform (alpha).

Source sequence(s)

AB208837, AL035698, AL096867, BC136280, L76627, L76631

Consensus CDS

CCDS5209.1

UniProtKB/Swiss-Prot

B9EG79, F8W805, Q13255, Q13256, Q14757, Q14758, Q5VTF7, Q5VTF8, Q9NU10, Q9UGS9, Q9UGT0

Related

ENSP00000282753.1, ENST00000282753.6

Conserved Domains (4) summary

cd15449
Location:591 → 840

7tmC_mGluR1; metabotropic glutamate receptor 1 in group 1, member of the class C family of seven-transmembrane G protein-coupled receptors

cd06374
Location:36 → 510

PBP1_mGluR_groupI; ligand binding domain of the group I metabotropic glutamate receptor

pfam07562
Location:521 → 571

NCD3G; Nine Cysteines Domain of family 3 GPCR

pfam10606
Location:1145 → 1194

GluR_Homer-bdg; Homer-binding domain of metabotropic glutamate receptor
NM_001278065.2 → NP_001264994.1 metabotropic glutamate receptor 1 isoform beta precursor

See identical proteins and their annotated locations for NP_001264994.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate exon in the 3' coding region, compared to variant 3. The encoded isoform (beta) is shorter and contains a distinct C-terminus, compared to isoform alpha. Isoform beta has a different subcellular distribution than isoform alpha and may be functionally distinct due to differential G-protein coupling of its novel C-terminal sequence (PMID: 9076744). Variants 4 and 5 encode the same isoform.

Source sequence(s)

AB208837, AL035698, AL096867, L76627, L76631

Consensus CDS

CCDS47497.1

UniProtKB/TrEMBL

Q59HC2

Related

ENSP00000424095.1, ENST00000492807.6

Conserved Domains (3) summary

cd15449
Location:591 → 840

7tmC_mGluR1; metabotropic glutamate receptor 1 in group 1, member of the class C family of seven-transmembrane G protein-coupled receptors

cd06374
Location:36 → 510

PBP1_mGluR_groupI; ligand binding domain of the group I metabotropic glutamate receptor

pfam07562
Location:521 → 571

NCD3G; Nine Cysteines Domain of family 3 GPCR
NM_001278066.1 → NP_001264995.1 metabotropic glutamate receptor 1 isoform beta precursor

See identical proteins and their annotated locations for NP_001264995.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) contains an alternate internal exon in the 3' coding region and uses an alternate splice site in the 3'-terminal exon, compared to variant 3. The encoded isoform (beta) is shorter and contains a distinct C-terminus, compared to isoform alpha. Isoform beta has a different subcellular distribution than isoform alpha and may be functionally distinct due to differential G-protein coupling of its novel C-terminal sequence (PMID: 9076744). Variants 4 and 5 encode the same isoform.

Source sequence(s)

AB208837, BC143777, L76627, L76631

Consensus CDS

CCDS47497.1

UniProtKB/TrEMBL

Q59HC2

Related

ENSP00000425599.1, ENST00000507907.1

Conserved Domains (3) summary

cd15449
Location:591 → 840

7tmC_mGluR1; metabotropic glutamate receptor 1 in group 1, member of the class C family of seven-transmembrane G protein-coupled receptors

cd06374
Location:36 → 510

PBP1_mGluR_groupI; ligand binding domain of the group I metabotropic glutamate receptor

pfam07562
Location:521 → 571

NCD3G; Nine Cysteines Domain of family 3 GPCR
NM_001278067.1 → NP_001264996.1 metabotropic glutamate receptor 1 isoform d precursor

See identical proteins and their annotated locations for NP_001264996.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 3. The encoded isoform (d) is shorter and contains a distinct C-terminus, compared to isoform alpha. Isoform d may have a distinct function compared to isoform alpha (PMID: 9776379).

Source sequence(s)

AB208837, BC143779, L76627, L76631

Consensus CDS

CCDS64548.1

UniProtKB/TrEMBL

Q59HC2

Related

ENSP00000347437.4, ENST00000355289.8

Conserved Domains (3) summary

cd15449
Location:591 → 840

7tmC_mGluR1; metabotropic glutamate receptor 1 in group 1, member of the class C family of seven-transmembrane G protein-coupled receptors

cd06374
Location:36 → 510

PBP1_mGluR_groupI; ligand binding domain of the group I metabotropic glutamate receptor

pfam07562
Location:521 → 571

NCD3G; Nine Cysteines Domain of family 3 GPCR

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

146027707..146437601

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017010784.2 → XP_016866273.1 metabotropic glutamate receptor 1 isoform X1

UniProtKB/Swiss-Prot

B9EG79, F8W805, Q13255, Q13256, Q14757, Q14758, Q5VTF7, Q5VTF8, Q9NU10, Q9UGS9, Q9UGT0

Related

ENSP00000354896.2, ENST00000361719.6

Conserved Domains (4) summary

cd15449
Location:591 → 840

7tmC_mGluR1; metabotropic glutamate receptor 1 in group 1, member of the class C family of seven-transmembrane G protein-coupled receptors

cd06374
Location:36 → 510

PBP1_mGluR_groupI; ligand binding domain of the group I metabotropic glutamate receptor

pfam07562
Location:521 → 571

NCD3G; Nine Cysteines Domain of family 3 GPCR

pfam10606
Location:1145 → 1194

GluR_Homer-bdg; Homer-binding domain of metabotropic glutamate receptor
XM_011535782.2 → XP_011534084.1 metabotropic glutamate receptor 1 isoform X1

See identical proteins and their annotated locations for XP_011534084.1

UniProtKB/Swiss-Prot

B9EG79, F8W805, Q13255, Q13256, Q14757, Q14758, Q5VTF7, Q5VTF8, Q9NU10, Q9UGS9, Q9UGT0

Related

ENSP00000516579.1, ENST00000706833.1

Conserved Domains (4) summary

cd15449
Location:591 → 840

7tmC_mGluR1; metabotropic glutamate receptor 1 in group 1, member of the class C family of seven-transmembrane G protein-coupled receptors

cd06374
Location:36 → 510

PBP1_mGluR_groupI; ligand binding domain of the group I metabotropic glutamate receptor

pfam07562
Location:521 → 571

NCD3G; Nine Cysteines Domain of family 3 GPCR

pfam10606
Location:1145 → 1194

GluR_Homer-bdg; Homer-binding domain of metabotropic glutamate receptor
XM_017010783.2 → XP_016866272.1 metabotropic glutamate receptor 1 isoform X1

UniProtKB/Swiss-Prot

B9EG79, F8W805, Q13255, Q13256, Q14757, Q14758, Q5VTF7, Q5VTF8, Q9NU10, Q9UGS9, Q9UGT0

Related

ENSP00000516581.1, ENST00000706835.1

Conserved Domains (4) summary

cd15449
Location:591 → 840

7tmC_mGluR1; metabotropic glutamate receptor 1 in group 1, member of the class C family of seven-transmembrane G protein-coupled receptors

cd06374
Location:36 → 510

PBP1_mGluR_groupI; ligand binding domain of the group I metabotropic glutamate receptor

pfam07562
Location:521 → 571

NCD3G; Nine Cysteines Domain of family 3 GPCR

pfam10606
Location:1145 → 1194

GluR_Homer-bdg; Homer-binding domain of metabotropic glutamate receptor
XM_017010788.2 → XP_016866277.1 metabotropic glutamate receptor 1 isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

147215189..147630683

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054355250.1 → XP_054211225.1 metabotropic glutamate receptor 1 isoform X1
XM_054355248.1 → XP_054211223.1 metabotropic glutamate receptor 1 isoform X1
XM_054355249.1 → XP_054211224.1 metabotropic glutamate receptor 1 isoform X1
XM_054355251.1 → XP_054211226.1 metabotropic glutamate receptor 1 isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_000838.3: Suppressed sequence

Description

NM_000838.3: This RefSeq was based on transcripts that have no full-length support, compared to the NM_001278064.1, which is also valid for CCDS5209.1. Therefore, NM_001114329.1 is suppressed, but the CCDS ID is retained for the other variant.
NM_001114329.1: Suppressed sequence

Description

NM_001114329.1: This RefSeq was based on transcripts that have no full-length support, compared to NM_001278065.1, which is also valid for CCDS47497.1. Therefore, NM_001114329.1 is suppressed, but the CCDS ID is retained for the other variant.