GPR85

Chr 7

G protein-coupled receptor 85

Also known as: SREB, SREB2

NCBI Gene: 54329ENSG00000164604UniProt: P60893

Members of the G protein-coupled receptor (GPCR) family, such as GPR85, have a similar structure characterized by 7 transmembrane domains. Activation of GPCRs by extracellular stimuli, such as neurotransmitters, hormones, or light, induces an intracellular signaling cascade mediated by heterotrimeric GTP-binding proteins, or G proteins (Matsumoto et al., 2000 [PubMed 10833454]).[supplied by OMIM, Aug 2008]

73
ClinVar variants
20
Pathogenic / LP
0.77
pLI score
0
Active trials
Clinical Summary— GPR85
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 51 VUS of 73 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.51LOEUF
pLI 0.773
Z-score 2.51
OE 0.11 (0.04–0.51)
Moderately constrained

More LoF-intolerant than ~75% 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.
2.05Z-score
OE missense 0.59 (0.51–0.69)
117 obs / 198.1 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.0.11 (0.04–0.51)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.59 (0.51–0.69)
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.0.99
0≤1.21.6
LoF obs/exp: 1 / 9.3Missense obs/exp: 117 / 198.1Syn Z: 0.09

ClinVar Variant Classifications

73 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic1
VUS51
Likely Benign1
Benign1
19
Pathogenic
1
Likely Pathogenic
51
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
1
0
1
VUS
0
39
12
0
51
Likely Benign
0
0
1
0
1
Benign
0
0
0
1
1
Total03933173

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

View in ClinVar →

Protein Context — Lollipop Plot

GPR85 · 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
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Synaptic Gpr85 Influences Cerebellar-Granule-Cell Electrical Properties and Light-Induced Behavior in Zebrafish.
Darche-Gabinaud R et al.·J Neurosci
2025Functional
Development of novel potent ligands for GPR85, an orphan G protein-coupled receptor expressed in the brain.
Sakai A et al.·Genes Cells
2022
The association of GPR85 with PSD-95-neuroligin complex and autism spectrum disorder: a molecular analysis.
Fujita-Jimbo E et al.·Mol Autism
2015🔓 Open Access
Effect of schizophrenia risk-associated alleles in SREB2 (GPR85) on functional MRI phenotypes in healthy volunteers.
Radulescu E et al.·Neuropsychopharmacology
2013Functional
SREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent learning and memory.
Chen Q et al.·Eur J Neurosci
2012🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools