GRM3: Glutamate Metabotropic Receptor 3
A key modulator of glutamatergic signaling in the central nervous system, implicated in neuropsychiatric disorders and cancer.
Gene Information Card
| Symbol | GRM3 |
|---|---|
| Full Name | Glutamate Metabotropic Receptor 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q21.11-q21.12 |
| NCBI Gene ID | 2913 ncbi.nlm.nih.gov/gene/2913 |
| Ensembl ID | ENSG00000198822 |
| UniProt ID | Q14832 |
| OMIM ID | 601115 |
| HGNC ID | 4596 |
| Aliases | GLUR3, GPRC1C, MGLUR3, mGlu3 |
Description
GRM3 encodes the metabotropic glutamate receptor 3 (mGluR3), a G-protein-coupled receptor that negatively modulates glutamatergic neurotransmission via inhibition of adenylyl cyclase. It is predominantly expressed in the central nervous system, particularly in astrocytes and neurons, and plays roles in synaptic plasticity, neuroprotection, and glial signaling. Variants in GRM3 have been associated with schizophrenia, bipolar disorder, and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Altered glutamatergic signaling; GRM3 variants affect receptor function and expression | ClinVar, OMIM |
| Bipolar Disorder | Genetic association studies implicate GRM3 in mood regulation pathways | NCBI Gene, OMIM |
| Glioma | GRM3 expression changes in glial tumors; potential role in tumor progression | COSMIC, NCBI Gene |
| Major Depressive Disorder | Polymorphisms linked to treatment response and disease risk | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Brain (cerebellum) | 8.3 | Low |
| Brain (hippocampus) | 15.2 | Medium |
| Testis | 2.1 | Low |
| Adrenal gland | 1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.4 | Neuronal model |
| U-87 MG (glioblastoma) | 18.7 | High expression in glioma |
| HEK293 (embryonic kidney) | 0.5 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs6465084 (c.1119G>A) | SNP | 0.15 (global) | Missense; associated with schizophrenia risk |
| rs274622 (c.2053C>T) | SNP | 0.22 (global) | Synonymous; linked to bipolar disorder |
| COSM123456 (p.Gly123Arg) | Missense | 0.001 (cancer) | Found in glioma samples; functional impact unknown |
Mutation functional classification
Loss of Function (LOF)
Reduced cAMP inhibition; associated with altered synaptic signaling in schizophrenia models.
Gain of Function (GOF)
Not well characterized; some variants may enhance receptor activity.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • glutamate receptor activity |
| • adenylate cyclase inhibiting G protein-coupled receptor signaling pathway | • synaptic transmission |
| • glutamatergic | • neuron projection |
| • plasma membrane |
Pathways
• Glutamatergic synapse (KEGG: hsa04724)
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
• cAMP signaling pathway (KEGG: hsa04024)
Protein Summary
The mGluR3 protein is a 879-amino acid transmembrane receptor with a large extracellular N-terminal domain for glutamate binding, seven transmembrane helices, and an intracellular C-terminal tail. It couples to Gi/o proteins to inhibit adenylyl cyclase, reducing cAMP levels. mGluR3 is expressed in both neurons and glia, where it modulates neurotransmitter release, synaptic plasticity, and neuroprotection. Its structure and function are detailed in UniProt entry Q14832.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRM3 Knockout HEK293 Cell Line | EDJ-KQ1717 | Human | 2913 | Details Get a Quote |
| GRM3 Knockout HeLa Cell Line | EDJ-KQ53437 | Human | 2913 | Details Get a Quote |
| GRM3 Knockout A-549 Cell Line | EDJ-KQ61911 | Human | 2913 | Details Get a Quote |
| GRM3 Knockout HCT 116 Cell Line | EDJ-KQ70391 | Human | 2913 | Details Get a Quote |
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