GRM4: Glutamate Metabotropic Receptor 4
A key modulator of synaptic transmission and potential therapeutic target in neurological disorders
Gene Information Card
| Symbol | GRM4 |
|---|---|
| Full Name | Glutamate Metabotropic Receptor 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.31 |
| NCBI Gene ID | 2914 ncbi.nlm.nih.gov/gene/2914 |
| Ensembl ID | ENSG00000124493 |
| UniProt ID | Q14833 |
| OMIM ID | 604100 |
| HGNC ID | 4599 |
| Aliases | GPRC1D, mGluR4, MGLUR4 |
Description
GRM4 encodes the metabotropic glutamate receptor 4 (mGluR4), a G-protein-coupled receptor (GPCR) that negatively modulates glutamatergic neurotransmission. It is predominantly expressed in the central nervous system, particularly in the cerebellum, basal ganglia, and retina. Activation of mGluR4 inhibits adenylyl cyclase via Gi/o proteins, reducing cAMP levels and modulating synaptic plasticity. GRM4 is implicated in neurological and psychiatric disorders, including Parkinson's disease, epilepsy, and anxiety.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Parkinson's disease | Reduced mGluR4 activity in basal ganglia leads to disinhibition of glutamate release, contributing to motor symptoms. | NCBI Gene, OMIM |
| Epilepsy | Loss-of-function variants impair inhibitory control of excitatory neurotransmission, increasing seizure susceptibility. | ClinVar, NCBI Gene |
| Anxiety disorders | Altered mGluR4 signaling in limbic regions affects stress response and fear conditioning. | OMIM, NCBI Gene |
| Autism spectrum disorder | Rare variants in GRM4 may disrupt synaptic homeostasis and social behavior. | ClinVar, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebellum | 12.5 | High |
| Cerebral cortex | 6.8 | Medium |
| Basal ganglia | 9.2 | High |
| Retina | 15.1 | High |
| Hippocampus | 5.3 | Medium |
| Spinal cord | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.4 | Neuronal model |
| U-87 MG (glioblastoma) | 2.1 | Low expression |
| HEK293 (embryonic kidney) | 0.5 | Minimal endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1096C>T (p.Arg366Cys) | Missense | 0.001 | Loss of function; reduced cAMP inhibition |
| c.1543G>A (p.Gly515Ser) | Missense | 0.0005 | Altered receptor trafficking |
| c.2005C>T (p.Arg669*) | Nonsense | 0.0002 | Premature truncation; loss of function |
| c.1234_1235insA (p.Thr412Asnfs*3) | Frameshift | 0.0001 | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported missense and truncating variants reduce or abolish receptor signaling, impairing inhibition of glutamate release.
Gain of Function (GOF)
No gain-of-function mutations have been documented in GRM4.
Dominant Negative (DN)
No dominant-negative effects have been reported for GRM4.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity (GO:0004930) | • glutamate receptor activity (GO:0008066) |
| • glutamatergic (GO:0035249) | • adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193) |
| • presynaptic membrane (GO:0042734) | • postsynaptic membrane (GO:0045211) |
Pathways
• Metabotropic glutamate receptor group III pathway (Reactome: R-HSA-420499)
• GPCR downstream signaling (Reactome: R-HSA-388396)
• cAMP signaling pathway (KEGG: hsa04024)
Protein Summary
The mGluR4 protein is a 912-amino acid transmembrane receptor with a large extracellular N-terminal domain containing a Venus flytrap ligand-binding site, seven transmembrane helices, and an intracellular C-terminal tail. It functions as a homodimer and couples to Gi/o proteins to inhibit adenylyl cyclase. mGluR4 is predominantly expressed in presynaptic terminals, where it acts as an autoreceptor to reduce glutamate release. Its structure and function are critical for maintaining excitatory-inhibitory balance in the brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRM4 Knockout HEK293 Cell Line | EDJ-KQ1718 | Human | 2914 | Details Get a Quote |
| GRM4 Knockout HeLa Cell Line | EDJ-KQ53438 | Human | 2914 | Details Get a Quote |
| GRM4 Knockout A-549 Cell Line | EDJ-KQ61912 | Human | 2914 | Details Get a Quote |
| GRM4 Knockout HCT 116 Cell Line | EDJ-KQ70392 | Human | 2914 | Details Get a Quote |
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