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Protein / target

Glutamate receptor ionotropic, NMDA 3A

Encoded byGRIN3AQ8TCU5Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
13
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Glycine-gated cation channel

Strongest disease association

Alzheimer's Disease

Via encoding gene GRIN3A · Clinical evidence · score 0.61

Therapeutic position

Established drug target

Small molecules

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

Component of a non-conventional N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with low calcium permeability and low voltage-dependent block by Mg(2+).

View complete UniProt function annotation

Component of a non-conventional N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with low calcium permeability and low voltage-dependent block by Mg(2+) (By similarity). During the development of neural circuits, participates in the synaptic refinement period, restricting spine maturation and growth (By similarity). Forms glutamatergic receptor complexes with GluN1 and GluN2 subunits which are activated by glycine binding to the GluN1 and GluN3 subunits and L-glutamate binding to GluN2 subunits (By similarity). Forms excitatory glycinergic receptor complexes with GluN1 alone which are activated by glycine binding to the GluN1 and GluN3 subunits (PubMed:38598639). GluN3A subunit also binds D-serine (By similarity). Each GluN3 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (By similarity). By competing with GIT1 interaction with ARHGEF7/beta-PIX, may reduce GIT1/ARHGEF7-regulated local activation of RAC1, hence affecting signaling and limiting the maturation and growth of inactive synapses (By similarity)

Subcellular location

Cell membranePostsynaptic cell membranePostsynaptic density
Domains and Gene Ontology detail (32)

Gene Ontology

  • Cendoplasmic reticulum membrane
  • Cglutamatergic synapse
  • Cmembrane
  • Cneuron projection
  • Cneuronal cell body
  • Cneurotransmitter receptor complex
  • CNMDA selective glutamate receptor complex
  • Cplasma membrane
  • Cpostsynaptic density membrane
  • Cpostsynaptic membrane
  • Cpresynapse
  • Csynapse

1115 aa · 125 kDa

Biological roles

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

Excitatory neurotransmissionUniProt · GOLigand-gated signallingUniProt · GOIon channel gatingGOInhibitory neurotransmissionUniProt
View supporting evidence

Excitatory neurotransmission

  • ·Component of a non-conventional N-methyl-D-aspartate (NMDA) receptors (NMDARs) that func…
  • ·glutamatergic synapse
  • ·synaptic transmission, glutamatergic

Ligand-gated signalling

  • ·Component of a non-conventional N-methyl-D-aspartate (NMDA) receptors (NMDARs) that func…
  • ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…

Ion channel gating

  • ·glycine-gated cation channel activity
  • ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…
  • ·monoatomic cation transmembrane transport

Inhibitory neurotransmission

  • ·Component of a non-conventional N-methyl-D-aspartate (NMDA) receptors (NMDARs) that func…

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

Approved medicines with mapped indications

1 medicine · 1 area

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Depressive Disorder1 medicine

13 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

esketamine
ApprovedNegative allosteric modulator

Glutamate [NMDA] receptor negative allosteric modulator

Indicated for Depressive Disorder

Acts on a complex — shared with GRIN1, GRIN2A, GRIN2B +3 more · 1 of 7 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

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 GRIN3A

Gene-level evidence surfaced through the gene GRIN3Athat 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.

Alzheimer's Disease
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Parkinson's Disease
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Depressive Disorder
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Infections
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.60

Major depressive disorder
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.59

View evidence synthesis (5)
Alzheimer's DiseaseWell supported
0.75
agreement 0.600.91
Clinical93%Literature7%

Open Targets aggregate 0.61 · 2 independent evidence families

Parkinson's DiseaseModerately supported
0.74
agreement 0.610.88
Clinical99%Literature1%RNA expression1%

Open Targets aggregate 0.60 · 3 independent evidence families

Depressive DisorderModerately supported
0.74
agreement 0.580.89
Clinical93%Literature7%

Open Targets aggregate 0.60 · 2 independent evidence families

InfectionsModerately supported
0.73
agreement 0.580.89
Clinical99%Literature1%

Open Targets aggregate 0.60 · 2 independent evidence families

Major depressive disorderModerately supported
0.73
agreement 0.580.89
Clinical93%Literature7%

Open Targets aggregate 0.59 · 2 independent evidence families

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
Alzheimer's Disease0.61
Parkinson's Disease0.60
Depressive Disorder0.60
Infections0.60
Major depressive disorder0.59
Alcoholism0.58
Dementia0.57

Drug development

27 compounds recorded · 13 approved · 14 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
ACAMPROSATE CALCIUMApproval
GW468816Phase 2
ACAMPROSATEApproval
DELUCEMINEPhase 1
AV-101Phase 3
ESKETAMINE HYDROCHLORIDEApproval
AMANTADINEApproval
NERAMEXANE MESYLATEPhase 3
PERZINFOTELPhase 2
MEMANTINE HYDROCHLORIDEApproval

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 moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc med conf and uniprot sigp or tmhmm) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (9)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · GO CC med confPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

convulsionsLynch et al. (2017)dizzinessLynch et al. (2017)painLynch et al. (2017)stereotypyLynch et al. (2017)increased locomotor activityLynch et al. (2017)increased heart rateLynch et al. (2017)neurodegenerationLynch et al. (2017)decreased convulsionsLynch et al. (2017)decreased painLynch et al. (2017)psychosisLynch et al. (2017)impaired social interactionsLynch et al. (2017)increased blood pressureLynch et al. (2017)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

RECRUITING · via esketamine · NCT06051227

NOT_YET_RECRUITING · via esketamine · NCT07315074

ClinicalTrials.gov via the drug-target graph.