GRM5 (P41594) variants and mutations

GRM5 (also known as P41594) is a human protein-coding gene encoding a metabotropic glutamate receptor 5 protein. Its activation by glutamate engages Gq-dependent intracellular signaling and modulates synaptic plasticity, excitability, and learning-related circuits. Abnormal signaling has been implicated in several neuropsychiatric and neurodevelopmental disorders and remains a target of experimental therapeutics. This analysis covers 1,860 GRM5 variants and mutations. Of these, 73% have computational variant effect predictions. Disease context includes major depressive disorder, skin neoplasm, and retinal detachment. Example GRM5 variants include M1?, V2A, and V2F.

Variant analysis overview

Gene: GRM5
Protein: P41594
UniProt accession: P41594
Organism: Homo sapiens
Variants analyzed: 1860
Variant scope: all variants
Completed: 2026-08-21

Variant and mutation evidence

Variant composition: 1,329 unspecified-consequence records; 1 stop lost; 168 synonymous variants; 319 missense variants; 6 in-frame deletions; 19 stop-gained variants; 4 in-frame insertions; 15 frameshift variants
Prediction scores: 1,366 variants have prediction scores (73% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: major depressive disorder, skin neoplasm, retinal detachment, skin cancer, cutaneous melanoma, benign neoplasm of eye, actinic keratosis, autism spectrum disorder, alcohol drinking, neurotic disorder, smoking initiation, skin disorder.

Protein structure and variant hotspots

Protein features: 7 transmembrane segments; 6 binding sites; 11 post-translational modification sites.
Structural context: 121 variants have structural context.
PTM context: 18 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable GRM5 variants

Examples include M1?, V2A, V2F, L4M, S8*, S8P, V9A, V9I. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

GRM5 analysis run — GRM5 (1,860 variants) — completed 2026-08-21