GPR50

Chr X

G protein-coupled receptor 50

Also known as: H9, Mel1c

NCBI Gene: 9248ENSG00000102195UniProt: Q13585

This gene product belongs to the G-protein coupled receptor 1 family. Even though this protein shares similarity with the melatonin receptors, it does not bind melatonin, however, it inhibits melatonin receptor 1A function through heterodimerization. Polymorphic variants of this gene have been associated with bipolar affective disorder in women. [provided by RefSeq, Jan 2010]

0
Active trials
99
Pathogenic / LP
196
ClinVar variants
3
Pubs (1 yr)
0.1
Missense Z
0.62
LOEUF
Clinical Summary— GPR50
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.65) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
99 Pathogenic / Likely Pathogenic· 84 VUS of 196 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.62LOEUF
pLI 0.646
Z-score 2.22
OE 0.13 (0.05–0.62)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
0.07Z-score
OE missense 0.99 (0.89–1.09)
265 obs / 268.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.13 (0.05–0.62)
0≤0.351.4
Missense OE0.99 (0.89–1.09)
0≤0.61.4
Synonymous OE1.10
0≤1.21.6
LoF obs/exp: 1 / 7.6Missense obs/exp: 265 / 268.3Syn Z: -0.82
GOFDN
DN
0.6259th %ile
GOF
0.79top 25%
LOF
0.4529th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction 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.

ClinVar Variant Classifications

196 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic97
Likely Pathogenic2
VUS84
Likely Benign8
Benign3
Conflicting2
97
Pathogenic
2
Likely Pathogenic
84
VUS
8
Likely Benign
3
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
97
0
97
Likely Pathogenic
0
0
2
0
2
VUS
0
78
6
0
84
Likely Benign
0
5
0
3
8
Benign
0
0
0
3
3
Conflicting
—2
Total0831056196

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

View in ClinVar →

GPR50 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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