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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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GRIK1
glutamate ionotropic receptor kainate type subunit 1
Chromosome 21 · 21q21.3
NCBI Gene: 2897Ensembl: ENSG00000171189.18HGNC: HGNC:4579UniProt: B7Z256
73PubMed Papers
20Diseases
4Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelReceptorTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
glutamate-gated receptor activityplasma membranekainate selective glutamate receptor activitypostsynaptic density membraneepilepsymigraine disorderalcohol dependenceSeizure
✦AI Summary

GRIK1 encodes glutamate ionotropic receptor kainate type subunit 1, a cation-permeable ligand-gated ion channel activated by L-glutamate and kainic acid that modulates glutamatergic synaptic transmission and postsynaptic membrane potential regulation. The gene is highly expressed in brain regions governing learning and memory, making it functionally important for cognitive processes. GRIK1 polymorphisms have been associated with multiple neuropsychiatric disorders: rs363504 and rs363538 variants show association with ADHD etiology and treatment response to methylphenidate 1, rs469472 demonstrated nominal association with schizophrenia in both case-control and family-based analyses 2, and the intergenic rs360932 variant correlated with autism spectrum disorder susceptibility in Egyptian children 3. Regarding pharmacogenetics, the rs2832407 polymorphism has been examined in topiramate efficacy for alcohol use disorder, though in a recent controlled trial it showed no significant effect on treatment response 4. Mechanistically, rs2832407 genotype differentially modulates GRIK1 antisense-2 expression and topiramate's effects on neural excitatory activity in iPSC-derived neurons 5. Beyond psychiatric contexts, elevated GRIK1 expression promotes glioblastoma malignancy and correlates with poor prognosis 6, while the GRIK1-AS1 antisense transcript shows tumor-suppressive functions in gastric cancer 7 and endometriosis 8. These findings establish GRIK1 as a multifunctional gene with disease relevance across neuropsychiatric, oncological, and gynecological conditions.

Sources cited
1
GRIK1 variants rs363504 and rs363538 associate with ADHD; probands had higher risk genotype frequencies; quantitative trait analysis linked specific genotypes to hyperactivity scores; GRIK1 expression was downregulated in ADHD probands
PMID: 36323684
2
GRIK1 SNP rs469472 showed nominal significant association with schizophrenia in both case-control and family-based studies; similar findings across independent samples warrant further investigation
PMID: 22730074
3
GRIK1 rs360932 intergenic variant showed significant association with ASD susceptibility in Egyptian children; AG genotype was substantially associated with ASD
PMID: 41327126
4
GRIK1 rs2832407 polymorphism showed no effect on topiramate or naltrexone treatment response in alcohol use disorder despite mixed literature on its predictive role
PMID: 38706338
5
GRIK1 rs2832407 genotype differentially affects GRIK1 antisense-2 expression and modulates topiramate's effects on excitatory synaptic activity in iPSC-derived neural cultures
PMID: 32574382
6
GRIK1 expression is elevated in recurrent glioblastoma; high GRIK1 levels correlate with poor prognosis; GRIK1 knockdown retards glioblastoma cell growth, migration, and invasion
PMID: 38560566
7
GRIK1-AS1 long non-coding RNA is downregulated in gastric cancer and inhibits cancer cell proliferation and invasion by functioning as a miR-375 sponge
PMID: 34660323
8
GRIK1-AS1 is downregulated in endometriosis; overexpression of GRIK1-AS1 inhibits endometrial stromal cell proliferation through epigenetic regulation of SFRP1
PMID: 37392032
Disease Associationsⓘ20
epilepsyOpen Targets
0.61Moderate
migraine disorderOpen Targets
0.60Moderate
alcohol dependenceOpen Targets
0.57Moderate
SeizureOpen Targets
0.56Moderate
Lennox-Gastaut syndromeOpen Targets
0.49Moderate
obesityOpen Targets
0.41Moderate
partial epilepsyOpen Targets
0.38Weak
HeadacheOpen Targets
0.37Weak
bipolar disorderOpen Targets
0.36Weak
cocaine dependenceOpen Targets
0.36Weak
Tourette syndromeOpen Targets
0.34Weak
PainOpen Targets
0.34Weak
ocular hypertensionOpen Targets
0.32Weak
nicotine dependenceOpen Targets
0.32Weak
Alzheimer diseaseOpen Targets
0.31Weak
hepatocellular carcinomaOpen Targets
0.31Weak
complicationOpen Targets
0.30Weak
frozen shoulderOpen Targets
0.30Weak
Herpes ZosterOpen Targets
0.30Weak
placenta praeviaOpen Targets
0.30Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets4
SELURAMPANELPhase II
Glutamate receptor ionotropic AMPA antagonist
epilepsy
TEZAMPANELPhase II
Glutamate receptor ionotropic kainate antagonist
Pain
TEZAMPANEL ANHYDROUSPhase II
Glutamate receptor ionotropic kainate antagonist
Pain
TOPIRAMATEApproved
Glutamate receptor ionotropic AMPA antagonist
epilepsy
Related Genes
GRM5Protein interaction98%GRM4Protein interaction92%DLG4Protein interaction86%GRIK4Protein interaction85%NETO1Protein interaction84%GRIK5Protein interaction82%
Tissue Expression6 tissues
Brain
100%
Liver
9%
Bone Marrow
9%
Ovary
8%
Lung
7%
Heart
0%
Gene Interaction Network
Click a node to explore
GRIK1GRM5GRM4DLG4GRIK4NETO1GRIK5
PROTEIN STRUCTURE
Preparing viewer…
PDB3FV1 · 1.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.81LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.55 [0.38–0.81]
RankingsWhere GRIK1 stands among ~20K protein-coding genes
  • #6,467of 20,598
    Most Researched73
  • #974of 1,025
    FDA-Approved Drug Targets1
  • #6,738of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedGRIK1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial.
PMID: 38706338
Am J Psychiatry · 2024
1.00
2
Association study of GRIK1 gene polymorphisms in schizophrenia: case-control and family-based studies.
PMID: 22730074
Hum Psychopharmacol · 2012
0.90
3
Kainate receptor subunit 1 (GRIK1) risk variants and GRIK1 deficiency were detected in the Indian ADHD probands.
PMID: 36323684
Sci Rep · 2022
0.80
4
Association between GRIK1 rs363598 and intergenic rs360932 variants and susceptibility to autism spectrum disorders in Egyptian children.
PMID: 41327126
BMC Pediatr · 2025
0.70
5
GRIK1-AS1 deficiency accelerates endometriosis progression by boosting DNMT1-dependent SFRP1 promoter methylation in endometrial stromal cells.
PMID: 37392032
J Gene Med · 2023
0.60