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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GRIK3
glutamate ionotropic receptor kainate type subunit 3
Chromosome 1 · 1p34.3
NCBI Gene: 2899Ensembl: ENSG00000163873.10HGNC: HGNC:4581UniProt: Q13003
43PubMed Papers
20Diseases
4Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelReceptorTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
glutamate receptor signaling pathwayadenylate cyclase inhibiting G protein-coupled glutamate receptor activityglutamate-gated receptor activityplasma membraneepilepsymigraine disorderalcohol dependenceSeizure
✦AI Summary

GRIK3 encodes a kainate-selective ionotropic glutamate receptor that functions as a ligand-gated cation channel. Upon L-glutamate binding, GRIK3 undergoes conformational changes to open its ion channel, converting chemical signals to electrical impulses before rapidly desensitizing 1. In the central nervous system, GRIK3 plays critical roles in synaptic transmission and plasticity essential for learning and memory 2. Developmentally, GRIK3 shows transient expression on rod precursors within the retina, where it detects light-dependent glutamate released from intrinsically photosensitive retinal ganglion cells, controlling developmental rod apoptosis 3. GRIK3 haploinsufficiency causes severe developmental delay affecting language and fine motor skills 2, while genetic variants associate with recurrent major depressive disorder through preferential maternal transmission 4. Beyond neurodevelopmental functions, GRIK3 has pathological roles in cancer. Aberrant GRIK3 expression in pediatric pilocytic astrocytomas couples with glutamate signaling to activate Src-mediated PDGF receptor signaling and ERK-dependent proliferation 5. In gastric and colorectal cancers, elevated GRIK3 expression correlates with poor prognosis, lymph node metastasis, and TNM stage advancement, with GRIK3 serving as an independent prognostic biomarker 67. These findings establish GRIK3 as both a neurodevelopmental protein and emerging oncogenic target.

Sources cited
1
GRIK3 functions as a ligand-gated cation channel that opens upon L-glutamate binding and rapidly desensitizes
PMID: 7719709
2
GRIK3 haploinsufficiency causes severe developmental delay and is critical for synaptic potentiation in learning and memory
PMID: 24449200
3
GRIK3 is transiently expressed on rod precursors and detects glutamate from ipRGCs to control developmental rod apoptosis
PMID: 39142280
4
GRIK3 genetic variants show preferential maternal transmission associated with recurrent major depressive disorder susceptibility
PMID: 16958029
5
Aberrant GRIK3 expression in pilocytic astrocytomas activates Src-mediated PDGFRα/ERK signaling to promote tumor proliferation
PMID: 40897174
6
Elevated GRIK3 expression in gastric cancer correlates with poor prognosis, lymph node metastasis, and serves as independent prognostic biomarker
PMID: 28631555
7
GRIK3 is regulated by the hsa_circ_0038646/miR-331-3p axis and promotes colorectal cancer cell proliferation and migration
PMID: 32565953
Disease Associationsⓘ20
epilepsyOpen Targets
0.61Moderate
migraine disorderOpen Targets
0.59Moderate
alcohol dependenceOpen Targets
0.57Moderate
SeizureOpen Targets
0.56Moderate
Lennox-Gastaut syndromeOpen Targets
0.49Moderate
obesityOpen Targets
0.42Moderate
bipolar disorderOpen Targets
0.38Weak
partial epilepsyOpen Targets
0.38Weak
HeadacheOpen Targets
0.37Weak
cocaine dependenceOpen Targets
0.36Weak
neurodegenerative diseaseOpen Targets
0.35Weak
major depressive disorderOpen Targets
0.35Weak
Tourette syndromeOpen Targets
0.34Weak
PainOpen Targets
0.34Weak
nicotine dependenceOpen Targets
0.32Weak
Non-Neoplastic Bile Duct DisorderOpen Targets
0.31Weak
brain compressionOpen Targets
0.30Weak
edemaOpen Targets
0.30Weak
hypertrophic cardiomyopathyOpen Targets
0.29Weak
obsessive-compulsive disorderOpen Targets
0.29Weak
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
GRIN2AProtein interaction88%GRIK5Protein interaction85%GRIK1Protein interaction79%GRIA1Protein interaction69%GRIK4Protein interaction66%GRIN2BProtein interaction65%
Tissue Expression6 tissues
Brain
100%
Heart
72%
Ovary
10%
Bone Marrow
8%
Liver
3%
Lung
1%
Gene Interaction Network
Click a node to explore
GRIK3GRIN2AGRIK5GRIK1GRIA1GRIK4GRIN2B
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q13003
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.40Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.28 [0.19–0.40]
RankingsWhere GRIK3 stands among ~20K protein-coding genes
  • #9,737of 20,598
    Most Researched43
  • #1,008of 1,025
    FDA-Approved Drug Targets1
  • #1,973of 17,882
    Most Constrained (LOEUF)0.40 · top quartile
Genes detectedGRIK3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
1p34.3 deletion involving GRIK3: Further clinical implication of GRIK family glutamate receptors in the pathogenesis of developmental delay.
PMID: 24449200
Am J Med Genet A · 2014
1.00
2
Developmental control of rod number via a light-dependent retrograde pathway from intrinsically photosensitive retinal ganglion cells.
PMID: 39142280
Dev Cell · 2024
0.90
3
Aberrant coupling of glutamate and tyrosine kinase receptors enables neuronal control of brain-tumor growth.
PMID: 40897174
Neuron · 2025
0.80
4
Frequency and transmission of glutamate receptors GRIK2 and GRIK3 polymorphisms in patients with obsessive compulsive disorder.
PMID: 15094479
Neuroreport · 2004
0.70
5
Association of the human kainate receptor GluR7 gene (GRIK3) with recurrent major depressive disorder.
PMID: 16958029
Am J Med Genet B Neuropsychiatr Genet · 2007
0.60