GRIK3

Chr 1

glutamate ionotropic receptor kainate type subunit 3

Also known as: EAA5, GLR7, GLUR7, GluK3, GluR7a

NCBI Gene: 2899ENSG00000163873UniProt: Q13003

Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. It is not certain if the subunit encoded by this gene is subject to RNA editing as the other 2 family members (GRIK1 and GRIK2). A Ser310Ala polymorphism has been associated with schizophrenia, and there are conflicting reports of its association with the pathogenesis of delirium tremens in alcoholics. [provided by RefSeq, Jul 2008]

130
ClinVar variants
7
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— GRIK3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 107 VUS of 130 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.19LOEUF
pLI 1.000
Z-score 5.86
OE 0.08 (0.04–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.01Z-score
OE missense 0.65 (0.60–0.71)
386 obs / 591.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.04–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.60–0.71)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 4 / 47.6Missense obs/exp: 386 / 591.7Syn Z: -0.40

ClinVar Variant Classifications

130 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS107
Likely Benign7
Benign8
Conflicting1
5
Pathogenic
2
Likely Pathogenic
107
VUS
7
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
2
0
2
VUS
0
103
4
0
107
Likely Benign
0
1
2
4
7
Benign
0
0
1
7
8
Conflicting
—1
Total01041411130

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GRIK3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
1p34.3 deletion involving GRIK3: Further clinical implication of GRIK family glutamate receptors in the pathogenesis of developmental delay.
Takenouchi T et al.·Am J Med Genet A
2014Review
Frequency and transmission of glutamate receptors GRIK2 and GRIK3 polymorphisms in patients with obsessive compulsive disorder.
Delorme R et al.·Neuroreport
2004Cohort
GRIK3: A novel oncogenic protein related to tumor TNM stage, lymph node metastasis, and poor prognosis of GC.
Gong B et al.·Tumour Biol
2017
A possible association between schizophrenia and GRIK3 polymorphisms in a multicenter sample of Scandinavian origin (SCOPE).
Djurovic S et al.·Schizophr Res
2009
Ionotropic glutamate receptor gene GRIK3 SER310ALA functional polymorphism is related to delirium tremens in alcoholics.
Preuss UW et al.·Pharmacogenomics J
2006Functional
Meta-analysis on the association between genetic polymorphisms and prepulse inhibition of the acoustic startle response.
Quednow BB et al.·Schizophr Res
2018Review
Genetic association studies of glutamate, GABA and related genes in schizophrenia and bipolar disorder: a decade of advance.
Cherlyn SY et al.·Neurosci Biobehav Rev
2010Review
Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol.
Giegling I et al.·Pharmacogenet Genomics
2011
Sex differences in glutamate receptor gene expression in major depression and suicide.
Gray AL et al.·Mol Psychiatry
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Isoliquiritigenin as a Neuronal Radiation Mitigant: Mitigating Radiation-Induced Anhedonia Tendency Targeting Grik3/Grm8/Grin3a via Integrated Proteomics and AI-Driven Discovery.
Li B et al.·Pharmaceuticals (Basel)
2025🔓 Open Access
GRIK3 deficiency promotes non-small cell lung cancer progression by the regulation of the UBE2C/CDK1/Wnt signaling pathway.
Liu J et al.·Am J Cancer Res
2023
CircASXL1 knockdown represses the progression of colorectal cancer by downregulating GRIK3 expression by sponging miR-1205.
Fang G et al.·World J Surg Oncol
2021🔓 Open Access
Hsa_circ_0038646 promotes cell proliferation and migration in colorectal cancer via miR-331-3p/GRIK3.
Du H et al.·Oncol Lett
2020🔓 Open Access
The association between eating behavior and polymorphisms in GRIN2B, GRIK3, GRIA1 and GRIN1 genes in people with type 2 diabetes mellitus.
Kochetova OV et al.·Mol Biol Rep
2020
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools