GRM5 Gene: Glutamate Metabotropic Receptor 5 - Function, Mutations & Disease

GRM5 encodes the metabotropic glutamate receptor 5 (mGluR5), a G protein-coupled receptor that binds glutamate as its primary ligand. It is predominantly expressed in the central nervous system, where it modulates synaptic plasticity, neuronal excitability, and long-term potentiation. mGluR5 couples to Gq/11 proteins, activating phospholipase C and intracellular calcium signaling. The gene is implicated in neurodevelopmental and psychiatric disorders, including Fragile X syndrome, autism spectrum disorder, and schizophrenia.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Glutamatergic synapse

• Neuroactive ligand-receptor interaction

• Long-term potentiation

• Alzheimer disease

• Huntington disease

The mGluR5 protein is a 1,212-amino acid transmembrane receptor with a large extracellular N-terminal domain containing the glutamate-binding Venus flytrap module, seven transmembrane helices, and a cytoplasmic C-terminal tail. It functions as a homodimer and is involved in modulating synaptic strength and plasticity. Post-translational modifications include N-glycosylation and phosphorylation, which regulate receptor trafficking and desensitization.