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Protein / target

Glutamate receptor ionotropic, NMDA 2A

Encoded byGRIN2AQ12879Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
16
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Glutamate-gated calcium ion channel

Strongest disease association

Major depressive disorder

Via encoding gene GRIN2A · Genetic evidence · score 0.43

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

View complete UniProt function annotation

Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed:20890276, PubMed:23933818, PubMed:23933819, PubMed:23933820, PubMed:24504326, PubMed:26875626, PubMed:26919761, PubMed:28242877, PubMed:36117210, PubMed:38538865, PubMed:8768735). NMDARs participate in synaptic plasticity for learning and memory formation by contributing to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity). Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:23933818, PubMed:23933819, PubMed:23933820, PubMed:24504326, PubMed:26875626, PubMed:26919761, PubMed:27288002, PubMed:28095420, PubMed:28105280, PubMed:28126851, PubMed:28182669, PubMed:29644724, PubMed:38307912, PubMed:8768735). NMDARs mediate simultaneously the potassium efflux and the influx of calcium and sodium (By similarity). Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (PubMed:26875626, PubMed:26919761). Participates in the synaptic plasticity regulation through activation by the L-glutamate releaseed by BEST1, into the synaptic cleft, upon F2R/PAR-1 activation in astrocyte (By similarity)

Subcellular location

Cell projection, dendritic spineCell membraneSynapsePostsynaptic cell membraneCytoplasmic vesicle membrane
Domains and Gene Ontology detail (37)

Gene Ontology

  • Ccell surface
  • Ccytoplasmic vesicle membrane
  • Cdendritic spine
  • Cendoplasmic reticulum membrane
  • Cglutamatergic synapse
  • CNMDA selective glutamate receptor complex
  • Cplasma membrane
  • Cpostsynaptic density
  • Cpostsynaptic density membrane
  • Cpostsynaptic membrane
  • Cpresynaptic membrane
  • Csynaptic membrane

1464 aa · 165 kDa · 2 isoforms

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 gatingGO
View supporting evidence

Excitatory neurotransmission

  • ·Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetra…
  • ·glutamatergic synapse
  • ·excitatory postsynaptic potential
  • ·positive regulation of excitatory postsynaptic potential

Ligand-gated signalling

  • ·Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetra…
  • ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…

Ion channel gating

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

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

16 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, GRIN2B, GRIN2D +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 GRIN2A

Gene-level evidence surfaced through the gene GRIN2Athat 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
0.86Well supported

Clinical evidence dominant · Open Targets 0.66

Parkinson's Disease
0.77Well supported

Clinical evidence dominant · Open Targets 0.62

Alzheimer's Disease
0.76Well supported

Clinical evidence dominant · Open Targets 0.62

Depressive Disorder
0.75Moderately supported

Clinical evidence dominant · Open Targets 0.61

View evidence synthesis (4)
Major depressive disorderWell supported
0.86
agreement 0.750.96
Clinical57%Genetic35%Literature8%

Open Targets aggregate 0.66 · 3 independent evidence families

Parkinson's DiseaseWell supported
0.77
agreement 0.620.93
Clinical86%Literature14%

Open Targets aggregate 0.62 · 2 independent evidence families

Alzheimer's DiseaseWell supported
0.76
agreement 0.630.90
Clinical90%Literature10%RNA expression1%

Open Targets aggregate 0.62 · 3 independent evidence families

Depressive DisorderModerately supported
0.75
agreement 0.590.90
Clinical88%Literature12%

Open Targets aggregate 0.61 · 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
Major depressive disorder0.66
Parkinson's Disease0.62
Alzheimer's Disease0.62
Depressive Disorder0.61

Drug development

30 compounds recorded · 16 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)
INDANTADOLPhase 2
DEXTROMETHORPHANApproval
CNS-5161Phase 2
GW468816Phase 2
DEXTROMETHORPHAN POLISTIREXApproval
ESKETAMINE HYDROCHLORIDEApproval
AV-101Phase 3
PERZINFOTELPhase 2
MEMANTINE HYDROCHLORIDEApproval
ACAMPROSATE CALCIUMApproval

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 high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

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

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (11)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · 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.