GRIK5

Chr 19

glutamate ionotropic receptor kainate type subunit 5

Also known as: EAA2, GRIK2, GluK5, KA2

NCBI Gene: 2901ENSG00000105737UniProt: Q16478OMIM: 600283

This gene encodes an ionotropic glutamate receptor subunit (GluK5) that forms heteromeric kainate-preferring ion channels with other glutamate receptor subunits, functioning as cation-permeable channels gated by glutamate and kainic acid in the central nervous system. The gene is highly constrained against loss-of-function variants (pLI=0.99, LOEUF=0.29), but definitive disease associations have not been established in the current genetic literature. Inheritance pattern and specific clinical phenotypes remain to be characterized through additional research.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.28
Clinical Summary— GRIK5
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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.28LOEUF
pLI 0.994
Z-score 5.34
OE 0.15 (0.09–0.28)
Highly constrained

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

Missense Constraint
3.36Z-score
OE missense 0.61 (0.56–0.67)
358 obs / 587.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.15 (0.09–0.28)
0≤0.351.4
Missense OE0.61 (0.56–0.67)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 7 / 46.2Missense obs/exp: 358 / 587.4Syn Z: 0.06
DN
0.5673th %ile
GOF
0.6833th %ile
LOF
0.53top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.28
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GRIK5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Ursolic acid derivative UA312 ameliorates ionizing radiation-induced cardiotoxicity and neurodevelopmental toxicity in zebrafish via targeting chrna3 and grik5.
Xu FF et al.·Acta Pharmacol Sin
2025Functional
GRIK5 stimulates colon cancer growth and metastasis through cAMP/PKA/CADM3 signaling.
Xie Z et al.·Cell Biol Int
2023
Music alleviates pain perception in depression mouse models by promoting the release of glutamate in the hippocampus of mice to act on GRIK5.
Mao X et al.·Nucleosides Nucleotides Nucleic Acids
2022Functional
GRIK5 Genetically Regulated Expression Associated with Eye and Vascular Phenomes: Discovery through Iteration among Biobanks, Electronic Health Records, and Zebrafish.
Unlu G et al.·Am J Hum Genet
2019Functional
[Polymorphic Variants of Glutamate Receptor (GRIK5, GRIN2B) and Serotonin Receptor (HTR2A) Genes Are Associated with Chronic Obstructive Pulmonary Disease].
Korytina GF et al.·Mol Biol (Mosk)
2017
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients