GPR75

Chr 2

G protein-coupled receptor 75

Also known as: GPRchr2, WI31133

NCBI Gene: 10936ENSG00000119737UniProt: O95800

GPR75 encodes a G protein-coupled receptor that is activated by the chemokine CCL5/RANTES and stimulates calcium mobilization, with roles in neuron survival and pancreatic insulin secretion. The gene shows low constraint to loss-of-function variants (pLI 0.00002, LOEUF 1.23), and no definitive disease associations have been established in OMIM or major clinical databases. Currently, GPR75 variants are not considered a cause of pediatric neurological disease.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
22
Pubs (1 yr)
10
P/LP submissions
0%
P/LP missense
1.23
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— GPR75
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 90 VUS of 113 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.23LOEUF
pLI 0.000
Z-score 0.97
OE 0.71 (0.42–1.23)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.04Z-score
OE missense 1.01 (0.91–1.11)
292 obs / 290.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.71 (0.42–1.23)
0≤0.351.4
Missense OE1.01 (0.91–1.11)
0≤0.61.4
Synonymous OE1.19
0≤1.21.6
LoF obs/exp: 9 / 12.7Missense obs/exp: 292 / 290.3Syn Z: -1.62
DN
0.7130th %ile
GOF
0.82top 10%
LOF
0.2970th %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

113 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS90
Likely Benign7
Benign6
9
Pathogenic
1
Likely Pathogenic
90
VUS
7
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
1
0
1
VUS
0
90
0
0
90
Likely Benign
0
1
2
4
7
Benign
0
4
1
1
6
Total095135113

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

View in ClinVar →

Protein Context — Lollipop Plot

GPR75 · 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.

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Clinical Literature
Open Research Assistant →
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