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Protein / target

Glutamate receptor ionotropic, kainate 3

Encoded byGRIK3Q13003Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Kainate selective glutamate receptor

Strongest disease association

Major depressive disorder

Via encoding gene GRIK3 · Genetic evidence · score 0.67

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

Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid.

View complete UniProt function annotation

Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist (PubMed:7719709). In association with GRIK2, involved in presynaptic facilitation of glutamate release at hippocampal mossy fiber synapses (By similarity)

Subcellular location

Cell membranePostsynaptic cell membrane
Domains and Gene Ontology detail (23)

Gene Ontology

  • Caxon
  • Cdendrite
  • Cdendrite cytoplasm
  • Cglutamatergic synapse
  • Ckainate selective glutamate receptor complex
  • Cperikaryon
  • Cplasma membrane
  • Cpostsynaptic density membrane
  • Cpresynaptic membrane
  • Cterminal bouton
  • Fadenylate cyclase inhibiting G protein-coupled glutamate receptor activity
  • Fglutamate receptor activity

919 aa · 104 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 gatingGOG protein-coupled signallingGO
View supporting evidence

Excitatory neurotransmission

  • ·Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion chan…
  • ·glutamatergic synapse
  • ·negative regulation of synaptic transmission, glutamatergic
  • ·synaptic transmission, glutamatergic

Ligand-gated signalling

  • ·Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion chan…
  • ·ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membr…
  • ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…

Ion channel gating

  • ·glutamate-gated calcium ion channel activity
  • ·ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membr…
  • ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…

G protein-coupled signalling

  • ·adenylate cyclase inhibiting G protein-coupled glutamate receptor activity
  • ·G protein-coupled glutamate receptor signaling pathway

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

Approved medicines with mapped indications

1 medicine · 3 areas

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.

Epilepsy1 medicine
Migraine Disorders1 medicine
Seizures1 medicine

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.

topiramate
ApprovedAntagonist

Glutamate receptor ionotropic kainate antagonist

Indicated for Epilepsy, Migraine Disorders, Seizures

Acts on a complex — shared with GRIK1, GRIK5, GRIK4 +1 more · 1 of 37 recorded protein targets — broad pharmacology

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 GRIK3

Gene-level evidence surfaced through the gene GRIK3 that 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.

Epilepsy
0.75Moderately supported

Clinical evidence dominant · Open Targets 0.61

Alcoholism
0.70Moderately supported

Clinical evidence dominant · Open Targets 0.57

Major depressive disorder
0.68Moderately supported

Genetic evidence dominant · Open Targets 0.41

Bipolar Disorder
0.61Moderately supported

Clinical evidence dominant · Open Targets 0.40

Obesity disorder
0.55Moderately supported

Clinical evidence dominant · Open Targets 0.42

View evidence synthesis (5)
EpilepsyModerately supported
0.75
agreement 0.590.90
Clinical98%Literature2%

Open Targets aggregate 0.61 · 2 independent evidence families

AlcoholismModerately supported
0.70
agreement 0.550.86
Clinical98%Literature2%

Open Targets aggregate 0.57 · 2 independent evidence families

Major depressive disorderModerately supported
0.68
agreement 0.540.81
Genetic97%Literature3%

Open Targets aggregate 0.41 · 2 independent evidence families

Bipolar DisorderModerately supported
0.61
agreement 0.500.72
Clinical59%Genetic41%Literature1%

Open Targets aggregate 0.40 · 3 independent evidence families

Obesity disorderModerately supported
0.55
agreement 0.450.65
Clinical83%Genetic17%

Open Targets aggregate 0.42 · 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
Epilepsy0.61
Alcoholism0.57
Obesity disorder0.42
Major depressive disorder0.41
Bipolar Disorder0.40
Diabetes Mellitus, Type 20.36

Drug development

4 compounds recorded · 1 approved · 3 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 (4)
TEZAMPANEL ANHYDROUSPhase 2
SELURAMPANELPhase 2
TOPIRAMATEApproval
TEZAMPANELPhase 2

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 Druggable Family support this modality.

AntibodiesEmerging

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

Protein degradersEmerging

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

View underlying tractability evidence (8)
SM · Approved DrugSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

extrapyramidal symptomsClinPGx

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)

UNKNOWN · via topiramate · NCT06089356

TERMINATED · via topiramate · NCT03018704

COMPLETED · via topiramate · NCT01889602

COMPLETED · via topiramate · NCT02639598

WITHDRAWN · via topiramate · NCT00988481

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Regulatory approval2026-09-04

    Approval: TOPIRAMATE (ANDA219183)

    fda · regulatory · fda · via topiramate

  2. Product recall2026-08-31

    Recall (Class III): TOPIRAMATE

    fda · safety · fda · via topiramate

  3. Regulatory approval2026-07-22

    Approval: TOPIRAMATE (ANDA220943)

    fda · regulatory · fda · via topiramate

  4. Product recall2026-07-06

    Recall (Class III): TOPIRAMATE

    fda · safety · fda · via topiramate

  5. Supplemental approval2026-06-29

    Supplemental approval: PHENTERMINE AND TOPIRAMATE (NDA022580)

    fda · regulatory · fda · via topiramate

  6. Label change2026-06-15

    Label change: TOPIRAMATE (ANDA078499)

    fda · regulatory · fda · via topiramate

  7. Safety communication2024-06-20

    Drug Safety Update: Topiramate (Topamax): introduction of new safety measures, including a Pregnancy Prevention Programme

    mhra · safety · mhra · via topiramate

  8. Safety communication2022-07-21

    Drug Safety Update: Topiramate (Topamax): start of safety review triggered by a study reporting an increased risk of neurodevelopmental disabilities in children with prenatal exposure

    mhra · safety · mhra · via topiramate

  9. New publication2020-07-02
    A randomized pilot trial of topiramate for alcohol use disorder in veterans with traumatic brain injury: Effects on alcohol use, cognition, and post-concussive symptoms.

    Drug and alcohol dependence · 2020 · 6 citations · Europe PMC · via topiramate

  10. New publication2005-06-01
    Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers.

    Neurology · 2005 · 95 citations · Europe PMC · via topiramate

  11. New publication1999-06-01
    A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group.

    Neurology · 1999 · 245 citations · Europe PMC · via topiramate

  12. New publication1999-04-01
    A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures. Topiramate YTC Study Group.

    Neurology · 1999 · 207 citations · Europe PMC · via topiramate

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.