Protein / target

Metabotropic glutamate receptor 5

Encoded byGRM5P41594Homo sapiensSwiss-Prot

UniProt: P41594 Ensembl: ENSG00000168959 HGNC: HGNC:4597 NCBI Gene: 2915

Clinical-stage

Therapeutic maturity

Clinical candidates

Small-molecule tractable

Druggability

Advanced Clinical

Research papers

Protein at a glance

Biological role

Protein tyrosine kinase activator

Strongest disease association

Major depressive disorder

Via encoding gene GRM5 · Genetic evidence · score 0.72

Therapeutic position

Clinically advancing target

Small molecules

Research activity

Emerging research

4 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

G protein-coupled receptor for glutamate.

View complete UniProt function annotation

G protein-coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity

Subcellular location

Cell membrane

Domains and Gene Ontology detail (51)

Gene Ontology

Castrocyte projection
Ccytoplasm
Cdendrite
Cdendritic shaft
Cdendritic spine
Cglutamatergic synapse
Cneuronal cell body
Cnuclear inner membrane
Cplasma membrane
Cpostsynaptic density membrane
CSchaffer collateral - CA1 synapse
FA2A adenosine receptor binding

1212 aa · 132 kDa · 3 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Excitatory neurotransmissionGOG protein-coupled signallingUniProt · GO

View supporting evidence

Excitatory neurotransmission

·glutamatergic synapse
·negative regulation of excitatory postsynaptic potential
·regulation of synaptic transmission, glutamatergic

G protein-coupled signalling

·G protein-coupled receptor for glutamate. Ligand binding causes a conformation change th…
·adenylate cyclase inhibiting G protein-coupled glutamate receptor activity
·G protein-coupled receptor activity
·G protein-coupled receptor activity involved in regulation of postsynaptic membrane pote…

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene GRM5

Gene-level evidence surfaced through the gene GRM5that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Major depressive disorder

0.79Well supported

Genetic evidence dominant · Open Targets 0.48

Skin Neoplasms

0.65Moderately supported

Genetic evidence dominant · Open Targets 0.40

Retinal Detachment

0.65Moderately supported

Genetic evidence dominant · Open Targets 0.40

Cutaneous melanoma

0.62Moderately supported

Genetic evidence dominant · Open Targets 0.38

Actinic keratosis

0.60Moderately supported

Genetic evidence dominant · Open Targets 0.37

View evidence synthesis (5)

Major depressive disorderWell supported

0.79

agreement 0.68–0.90

Genetic73%Literature14%Clinical13%

Open Targets aggregate 0.48 · 3 independent evidence families

Skin NeoplasmsModerately supported

0.65

agreement 0.51–0.79

Genetic99%Literature1%

Open Targets aggregate 0.40 · 2 independent evidence families

Retinal DetachmentModerately supported

0.65

agreement 0.53–0.77

Genetic100%

Open Targets aggregate 0.40 · 1 independent evidence family

Cutaneous melanomaModerately supported

0.62

agreement 0.50–0.74

Genetic100%

Open Targets aggregate 0.38 · 1 independent evidence family

Actinic keratosisModerately supported

0.60

agreement 0.48–0.72

Genetic100%

Open Targets aggregate 0.37 · 1 independent evidence family

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Major depressive disorder0.48

Skin Neoplasms0.40

Retinal Detachment0.40

Cutaneous melanoma0.38

Actinic keratosis0.37

Autism Spectrum Disorder0.35

Alcohol drinking0.33

Drug development

9 compounds recorded · 9 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (9)

BASIMGLURANTPhase 2 3

AZD2516Phase 2

AZD2066Phase 2

DASOLAMPANEL ETIBUTILPhase 2

MAVOGLURANTPhase 2 3

RG7342Phase 1

RASEGLURANTPhase 2

STX107Phase 2

DIPRAGLURANTPhase 2 3

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Advanced Clinical and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (11)

SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.