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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GRM2
glutamate metabotropic receptor 2
Chromosome 3 · 3p21.2
NCBI Gene: 2912Ensembl: ENSG00000164082.15HGNC: HGNC:4594UniProt: H7BXL3
71PubMed Papers
20Diseases
6Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingglutamate receptor activityG protein-coupled glutamate receptor signaling pathwayplasma membraneschizophreniacrystal arthropathyAbnormality of the skeletal systemneurodegenerative disease
✦AI Summary

GRM2 encodes the glutamate metabotropic receptor 2, a G-protein coupled receptor that mediates glutamatergic neurotransmission through group II metabotropic glutamate receptor activity 1. The gene is located on chromosome 3.1-p21.2 and consists of 5-6 exons spanning approximately 13 kb 21. GRM2 functions in synaptic transmission by negatively regulating adenylate cyclase activity and positively regulating PI3K/AKT signaling pathways, playing a crucial role in neuroplasticity and synaptic modulation. The receptor has been implicated in several psychiatric disorders, with genetic variants showing association with methamphetamine-induced psychosis in Japanese populations 3 and major depressive disorder 4. Expression studies reveal that GRM2 levels are decreased in alcohol use disorder patients and show significant recovery following treatment 5. Additionally, GRM2 expression is modulated by ketamine treatment, suggesting involvement in antidepressant mechanisms 6. Genetic variants in GRM2 also influence outcomes of antipsychotic treatments, affecting both efficacy and side effect profiles 7. These findings collectively demonstrate GRM2's critical role in glutamatergic neurotransmission and its potential as a therapeutic target for various neuropsychiatric conditions.

Sources cited
1
GRM2 encodes a G-protein coupled glutamate receptor with group II metabotropic glutamate receptor activity
PMID: 11317221
2
Gene localization to chromosome 3p21.1-p21.2 and consists of 5 exons
PMID: 11840499
3
Gene structure spans 13 kb with six exons including one non-coding exon
PMID: 11317221
4
Association with methamphetamine-induced psychosis in Japanese population
PMID: 20211215
5
Involvement in major depressive disorder pathophysiology
PMID: 19386277
6
Decreased expression in alcohol use disorder patients with recovery following treatment
PMID: 39518903
7
Expression modulated by ketamine treatment in depression
PMID: 40752781
8
Genetic variants influence antipsychotic treatment outcomes
PMID: 40527340
Disease Associationsⓘ20
schizophreniaOpen Targets
0.37Weak
crystal arthropathyOpen Targets
0.29Weak
Abnormality of the skeletal systemOpen Targets
0.28Weak
neurodegenerative diseaseOpen Targets
0.27Weak
major depressive disorderOpen Targets
0.13Weak
epilepsyOpen Targets
0.09Suggestive
depressive disorderOpen Targets
0.08Suggestive
psychiatric disorderOpen Targets
0.08Suggestive
SeizureOpen Targets
0.08Suggestive
anxiety disorderOpen Targets
0.07Suggestive
attention deficit hyperactivity disorderOpen Targets
0.06Suggestive
obsessive-compulsive disorderOpen Targets
0.06Suggestive
bipolar disorderOpen Targets
0.05Suggestive
infectionOpen Targets
0.05Suggestive
Abnormality of refractionOpen Targets
0.05Suggestive
psychosisOpen Targets
0.04Suggestive
AnxietyOpen Targets
0.04Suggestive
Alzheimer diseaseOpen Targets
0.04Suggestive
post-traumatic stress disorderOpen Targets
0.04Suggestive
Hepatic failureOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets6
DECOGLURANTPhase II
Metabotropic glutamate receptor 2 modulator
major depressive disorder
JNJ-40411813Phase II
Metabotropic glutamate receptor 2 positive allosteric modulator
anxiety disorder
LY2969822Phase I
Metabotropic glutamate receptor 2 agonist
LY2979165Phase I
Metabotropic glutamate receptor 2 agonist
bipolar disorder
LY404039Phase III
Metabotropic glutamate receptor 3 agonist
schizophrenia
POMAGLUMETAD METHIONIL ANHYDROUSPhase III
Metabotropic glutamate receptor 2 agonist
schizophrenia
Related Genes
GNAI3Protein interaction99%GNAI1Protein interaction91%GRIN2BProtein interaction85%GRIA1Protein interaction84%GRIA4Protein interaction84%GNB1Protein interaction84%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
46%
Heart
7%
Lung
4%
Ovary
4%
Liver
2%
Gene Interaction Network
Click a node to explore
GRM2GNAI3GNAI1GRIN2BGRIA1GRIA4GNB1
PROTEIN STRUCTURE
Preparing viewer…
PDB4XAQ · 2.21 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.75LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.56 [0.42–0.75]
RankingsWhere GRM2 stands among ~20K protein-coding genes
  • #6,634of 20,598
    Most Researched71
  • #5,934of 17,882
    Most Constrained (LOEUF)0.75
Genes detectedGRM2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Human metabotropic glutamate receptor 2 gene (GRM2): chromosomal sublocalization (3p21.1-p21.2) and genomic organization.
PMID: 11840499
Am J Med Genet · 2002
1.00
2
Structure and polymorphisms of the human metabotropic glutamate receptor type 2 gene (GRM2): analysis of association with schizophrenia.
PMID: 11317221
Mol Psychiatry · 2001
0.90
3
AP3B1 facilitates PDIA3/ERP57 function to regulate rabies virus glycoprotein selective degradation and viral entry.
PMID: 39128851
Autophagy · 2024
0.80
4
Association analysis of GRM2 and HTR2A with methamphetamine-induced psychosis and schizophrenia in the Japanese population.
PMID: 20211215
Prog Neuropsychopharmacol Biol Psychiatry · 2010
0.70
5
Altered Expression of Neuroplasticity-Related Genes in Alcohol Addiction and Treatment.
PMID: 39518903
Int J Mol Sci · 2024
0.60