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Protein / target

Glutamate receptor ionotropic, kainate 2

Encoded byGRIK2Q13002Homo sapiensSwiss-Prot
UniProt: Q13002Ensembl: ENSG00000164418HGNC: HGNC:4580NCBI Gene: 2898
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

Glutamate-gated ion channel

Strongest disease association

Autosomal recessive non-syndromic intellectual disability

Via encoding gene GRIK2 · Genetic literature evidence · score 0.76

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 (PubMed:7536611, PubMed:8730589, PubMed:14511640). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system (By similarity). Binding of the excitatory neurotransmitter L-glutamate induces a conformational change leading to the opening of the cation channel, converting the chemical signal to an electrical impulse (By similarity). The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist (PubMed:14511640, PubMed:28180184, PubMed:34375587, PubMed:7536611, PubMed:8730589). Modulates cell surface expression of NETO2 (By similarity). In association with GRIK3, 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 (35)

Gene Ontology

  • Cdendrite cytoplasm
  • Cglutamatergic synapse
  • Chippocampal mossy fiber to CA3 synapse
  • Ckainate selective glutamate receptor complex
  • Cmossy fiber rosette
  • Cperikaryon
  • Cplasma membrane
  • Cpostsynaptic density membrane
  • Cpresynaptic membrane
  • Cterminal bouton
  • Fextracellularly glutamate-gated ion channel activity
  • Fglutamate-gated calcium ion channel activity

908 aa · 103 kDa · 7 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 gatingGOApoptosis & cell deathGO
View supporting evidence

Excitatory neurotransmission

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

Ligand-gated signalling

  • ·Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion chan…
  • ·extracellularly glutamate-gated 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…

Ion channel gating

  • ·extracellularly glutamate-gated ion channel activity
  • ·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…

Apoptosis & cell death

  • ·neuron apoptotic process
  • ·positive regulation of neuron apoptotic process

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
topiramate
Migraine Disorders1 medicine
topiramate
Seizures1 medicine
topiramate

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 GRIK2

Gene-level evidence surfaced through the gene GRIK2that 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
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Migraine Disorders
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.59

Lennox-Gastaut syndrome
0.72Moderately supported

Clinical evidence dominant · Open Targets 0.53

Alcoholism
0.70Moderately supported

Clinical evidence dominant · Open Targets 0.57

Autosomal recessive non-syndromic intellectual disability
0.61Moderately supported

Genetic literature evidence dominant · Open Targets 0.55

View evidence synthesis (5)
EpilepsyWell supported
0.76
agreement 0.60–0.91
Clinical95%Literature5%

Open Targets aggregate 0.61 · 2 independent evidence families

Migraine DisordersModerately supported
0.73
agreement 0.57–0.88
Clinical97%Literature3%

Open Targets aggregate 0.59 · 2 independent evidence families

Lennox-Gastaut syndromeModerately supported
0.72
agreement 0.59–0.86
Clinical70%Animal model30%

Open Targets aggregate 0.53 · 2 independent evidence families

AlcoholismModerately supported
0.70
agreement 0.55–0.86
Clinical99%Literature1%

Open Targets aggregate 0.57 · 2 independent evidence families

Autosomal recessive non-syndromic intellectual disabilityModerately supported
0.61
agreement 0.46–0.76
Genetic literature99%Literature1%Geneticdup

Open Targets aggregate 0.55 · 2 independent evidence families · 1 not counted as duplicate

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
Migraine Disorders0.59
Alcoholism0.57
Autosomal recessive non-syndromic intellectual disability0.55
Lennox-Gastaut syndrome0.53
Complex neurodevelopmental disorder0.51

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)
SELURAMPANELPhase 2
TOPIRAMATEApproval
TEZAMPANELPhase 2
TEZAMPANEL ANHYDROUSPhase 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 molecules — Strong

Approved Drug 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 (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (12)
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 · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

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.

Comparative Outcomes of Migraine Preventives and Anti-CGRP Therapies for Tinnitus in Patients With Migraine: A Randomized Active-Comparator Controlled Trial (COMPACT-PM)PHASE4

NOT_YET_RECRUITING · via topiramate · NCT07655440

Individualized Pharmacological Approach to Obesity in Patients With Bipolar Disorder - OBOE-MayoPHASE4

RECRUITING · via topiramate · NCT07213466

A Comparative Effectiveness Study of Oral Medications Used for Migraine Prevention: The APT Comparison StudyPHASE4

RECRUITING · via topiramate · NCT06972056

Management of Acute Tinnitus With Migraine Medications: A Randomized Clinical TrialPHASE4

ACTIVE_NOT_RECRUITING · via topiramate · NCT06799169

View all trials (26)
Pharmacotherapy in Conjunction With Lifestyle Counseling for Management of Weight Regain After Bariatric SurgeryPHASE4

RECRUITING · via topiramate · NCT05975580

Curing HIV: Proof of Concept Randomized Clinical Trial With Pyrimethamine, Lenalidomide, TOpiramatePHASE1/PHASE2

NOT_YET_RECRUITING · via topiramate · NCT07384624

Pharmacologic Weight Loss as Adjunct Therapy for Ulcerative Colitis in Obese Patients: A Phase 2A, Randomized, Placebo-Controlled TrialPHASE2

RECRUITING · via topiramate · NCT04721873

Leveraging Biomarkers for Personalized Treatment of Alcohol Use Disorder Comorbid With Post Traumatic Stress DisorderPHASE2

RECRUITING · via topiramate · NCT03667846

Topiramate in Treatment Refractory Psychotic Illness: Effects on Weight Gain and PsychopathologyNA

ACTIVE_NOT_RECRUITING · via topiramate · NCT02808533

Zolmitriptane as Prophylactic Therapy Childhood MigrainePHASE4

UNKNOWN · via topiramate · NCT06089356

Efficacy and Safety of Add-on Topiramate vs Metformin on Cardio-Metabolic Profile in Patients With Schizophrenia on Atypical Antipsychotics With Metabolic Syndrome: a Randomized Controlled TrialPHASE4

COMPLETED · via topiramate · NCT05663749

Topiramate, Amitriptyline Monotherapy and Combination Therapy in Migraine Prophylaxis: An Open Label Randomized Clinical TrialPHASE4

UNKNOWN · via topiramate · NCT05759845

Efficacy and Tolerability of Low vs. Standard Daily Doses of Antiepileptic Drugs in Newly Diagnosed, Previously Untreated Epilepsy (STANDLOW). A Multicenter, Randomized, Single-blind, Parallel-group TrialPHASE4

COMPLETED · via topiramate · NCT03689114

Generating Evidence on NonEpileptic, Stereotypical and Intermittent Symptoms (NESIS) in Chronic Subdural HematomasPHASE4

UNKNOWN · via topiramate · NCT04759196

Head-to-head Study of Erenumab Against topiRamate-a Double-blind, Double Dummy Migraine Study to Assess Tolerability and Efficacy in a patiEnt -Centered SettingPHASE4

COMPLETED · via topiramate · NCT03828539

Topiramate Treatment of Alcohol Use Disorder in African AmericansPHASE4

TERMINATED · via topiramate · NCT03018704

A Multicenter, Prospective, Randomized, Open-label Study to Compare the Efficacy, Safety, and Tolerability of BOTOX® and Topiramate for Headache Prophylaxis in Adults With Chronic MigrainePHASE4

COMPLETED · via topiramate · NCT02191579

Treatment of Obesity With Topiramate in Patients With Polycystic Ovary Syndrome: a Double-blind Placebo-controlled Clinical TrialPHASE4

UNKNOWN · via topiramate · NCT04453306

Characterizing and Predicting Drug Effects on CognitionPHASE4

COMPLETED · via topiramate · NCT01889602

Topiramate Treatment of Hazardous and Harmful Alcohol Use in Veterans With TBIPHASE4

COMPLETED · via topiramate · NCT01750268

A Randomized, Pilot Study to Evaluate the Tolerability of OnabotulinumtoxinA Plus Topiramate vs. OnabotulinumtoxinA Plus Placebo and Long Term Effect of Treatment on Cognitive Efficiency and Continuation of CarePHASE4

COMPLETED · via topiramate · NCT01700387

Flunarizine Versus Topiramate for Chronic Migraine ProphylaxisPHASE4

COMPLETED · via topiramate · NCT02639598

A Randomized, Open-label, Parallel Group, Multi-center, Comparative, Phase IV Trial of Levetiracetam (LEV) Versus Topiramate (TPM) as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset SeizuresPHASE4

COMPLETED · via topiramate · NCT01229735

Topiramate for Hospitalized Patients With Alcoholism: a 12-Week Open-Label StudyPHASE4

UNKNOWN · via topiramate · NCT01135602

Topiramate Treatment of Alcohol Use Disorders in Veterans With Post Traumatic Stress Disorder (PTSD): A Pilot Controlled Trial of Augmentation TherapyPHASE4

COMPLETED · via topiramate · NCT01087736

Topiramate in the Treatment of Epilepsy: 1st Add-on vs. Mono-therapy Study in Neuro-Surgical PatientsPHASE4

COMPLETED · via topiramate · NCT01627860

Topiramate Augmentation in Bulimia Nervosa Partial RespondersPHASE4

WITHDRAWN · via topiramate · NCT00988481

A Randomized, Single-Blind Pilot Study to Compare the Efficacy and Cost-Effectiveness of Frovatriptan vs. Topiramate for the Prevention of MigrainePHASE4

COMPLETED · via topiramate · NCT00846495

Effect of Topiramate on Cerebrovascular Response to Photic Stimulation in MigraineursPHASE4

COMPLETED · via topiramate · NCT02424318

A Randomized Controlled Trial of Medical Therapies for Chronic Post-Traumatic HeadachesPHASE4

TERMINATED · via topiramate · NCT00862095

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 approval2026-07-22

    Approval: TOPIRAMATE (ANDA220943)

    fda · regulatory · fda · via topiramate

  2. Product recall2026-07-06

    Recall (Class III): TOPIRAMATE

    fda · safety · fda · via topiramate

  3. Supplemental approval2026-06-29

    Supplemental approval: PHENTERMINE AND TOPIRAMATE (NDA022580)

    fda · regulatory · fda · via topiramate

  4. Label change2026-06-15

    Label change: TOPIRAMATE (ANDA078499)

    fda · regulatory · fda · via topiramate

  5. Label change2026-03-06

    Label change: PHENTERMINE AND TOPIRAMATE (NDA022580)

    fda · regulatory · fda · via topiramate

  6. Supplemental approval2025-07-11

    Supplemental approval: PHENTERMINE AND TOPIRAMATE (NDA022580)

    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.