GRM8

Chr 7

glutamate metabotropic receptor 8

Also known as: GLUR8, GPRC1H, MGLUR8, mGlu8

NCBI Gene: 2918ENSG00000179603UniProt: O00222

L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GRM8
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.64LOEUF
pLI 0.000
Z-score 3.42
OE 0.43 (0.30–0.64)
Tolerant

Typical tolerance to LoF variation

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.
0.91Z-score
OE missense 0.89 (0.82–0.96)
464 obs / 522.8 exp
Tolerant

Mild missense constraint

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.0.43 (0.30–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.82–0.96)
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.1.05
0≤1.21.6
LoF obs/exp: 18 / 41.9Missense obs/exp: 464 / 522.8Syn Z: -0.55

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GRM8 · 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
Escape from TGF-β-induced senescence promotes aggressive hallmarks in epithelial hepatocellular carcinoma cells.
Kalyoncu M et al.·Mol Oncol
2025
A genome wide association study links glutamate receptor pathway to sporadic Creutzfeldt-Jakob disease risk.
Sanchez-Juan P et al.·PLoS One
2015Meta-analysis
Personality traits associated with tinnitus: A systematic review and contributing genetic variants.
Bernal-Robledano A et al.·Neurosci Biobehav Rev
2025Review
Neuronal metabotropic glutamate receptor 8 protects against neurodegeneration in CNS inflammation.
Woo MS et al.·J Exp Med
2021
The Role of Glutamatergic Gene Polymorphisms in the Clinical Phenotypes of Schizophrenia.
Poltavskaya EG et al.·Genes (Basel)
2023
A pilot study on glutamate receptor and carrier gene variants and risk of childhood autism spectrum.
Liu J et al.·Metab Brain Dis
2023
Glutamatergic copy number variants and their role in attention-deficit/hyperactivity disorder.
Akutagava-Martins GC et al.·Am J Med Genet B Neuropsychiatr Genet
2014
The underlying molecular mechanism and drugs for treatment in adrenal cortical carcinoma.
Ma C et al.·Int J Med Sci
2021Functional
Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence.
Chen AC et al.·Am J Med Genet B Neuropsychiatr Genet
2009
Disease patterns of coronary heart disease and type 2 diabetes harbored distinct and shared genetic architecture.
Xiao H et al.·Cardiovasc Diabetol
2022
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
Developmental differentiation of mouse inner ear neuron subpopulations resolved with a peripherin-promoter reporter within the Grm8 locus.
Pearson LJ et al.·Sci Rep
2025🔓 Open AccessFunctional
Rare CRHR2 and GRM8 variants identified as candidate factors associated with eating disorders in Japanese patients by whole exome sequencing.
Oka A et al.·Heliyon
2024🔓 Open AccessCohort
GRM8 genotype is associated with externalizing disorders and greater inter-trial variability in brain activation during a response inhibition task.
Bauer LO et al.·Clin Neurophysiol
2020
Genomic sequencing and editing revealed the GRM8 signaling pathway as potential therapeutic targets of squamous cell lung cancer.
Zhang P et al.·Cancer Lett
2019
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