GPR34

Chr X

G protein-coupled receptor 34

Also known as: LPS1, LYPSR1

NCBI Gene: 2857ENSG00000171659UniProt: Q9UPC5OMIM: 300241

GPR34 encodes a G-protein-coupled receptor that recognizes lysophosphatidylserine and functions as a damage-sensing receptor in immune responses, controlling microglial morphology and phagocytosis in the brain and triggering tissue repair upon recognition of dying cells. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants, suggesting some tolerance to reduced gene dosage.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.82
Clinical Summary— GPR34
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
58 unique Pathogenic / Likely Pathogenic· 18 VUS of 113 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.82LOEUF
pLI 0.264
Z-score 1.91
OE 0.26 (0.10–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.71Z-score
OE missense 0.60 (0.50–0.72)
86 obs / 143.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.10–0.82)
0≤0.351.4
Missense OE0.60 (0.50–0.72)
0≤0.61.4
Synonymous OE0.79
0≤1.21.6
LoF obs/exp: 2 / 7.7Missense obs/exp: 86 / 143.7Syn Z: 1.15
DN
0.7229th %ile
GOF
0.76top 25%
LOF
0.3260th %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

Pathogenic55
Likely Pathogenic3
VUS18
Likely Benign2
Benign1
55
Pathogenic
3
Likely Pathogenic
18
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
55
0
55
Likely Pathogenic
0
0
3
0
3
VUS
0
10
8
0
18
Likely Benign
0
2
0
0
2
Benign
0
0
0
1
1
Total01266179

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

View in ClinVar →

Protein Context — Lollipop Plot

GPR34 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
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