GPR34

Chr X

G protein-coupled receptor 34

Also known as: LPS1, LYPSR1

NCBI Gene: 2857ENSG00000171659UniProt: Q9UPC5

G protein-coupled receptors (GPCRs), such as GPR34, are integral membrane proteins containing 7 putative transmembrane domains (TMs). These proteins mediate signals to the interior of the cell via activation of heterotrimeric G proteins that in turn activate various effector proteins, ultimately resulting in a physiologic response.[supplied by OMIM, Apr 2006]

12
ClinVar variants
12
Pathogenic / LP
0.26
pLI score
0
Active trials
Clinical Summary— GPR34
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic of 12 total submissions

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.
0.82LOEUF
pLI 0.264
Z-score 1.91
OE 0.26 (0.10–0.82)
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.
1.71Z-score
OE missense 0.60 (0.50–0.72)
86 obs / 143.7 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.0.26 (0.10–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.60 (0.50–0.72)
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.0.79
0≤1.21.6
LoF obs/exp: 2 / 7.7Missense obs/exp: 86 / 143.7Syn Z: 1.15

ClinVar Variant Classifications

12 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
12
Pathogenic

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————12
Likely Pathogenic
————0
VUS
————0
Likely Benign
————0
Benign
————0
Total—12

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Cryo-EM structures of human GPR34 enable the identification of selective antagonists.
Xia A et al.·Proc Natl Acad Sci U S A
2023
Demyelination-derived lysophosphatidylserine promotes microglial dysfunction and neuropathology in a mouse model of Alzheimer's disease.
Zhou Y et al.·Cell Mol Immunol
2025Functional
The G protein-coupled receptor GPR34 - The past 20 years of a grownup.
Schöneberg T et al.·Pharmacol Ther
2018Review
Druggable Lysophospholipid Signaling Pathways.
Yanagida K et al.·Adv Exp Med Biol
2020Review
G-protein Coupled Receptor 34 Promotes Gliomagenesis by Inducing Proliferation and Malignant Phenotype via TGF-Beta/Smad Signaling Pathway.
Cheng Y et al.·Technol Cancer Res Treat
2022
G-protein coupled receptor 34 activates Erk and phosphatidylinositol 3-kinase/Akt pathways and functions as alternative pathway to mediate p185Bcr-Abl-induced transformation and leukemogenesis.
Zuo B et al.·Leuk Lymphoma
2015
Lysophosphatidylserine receptor P2Y10: A G protein-coupled receptor that mediates eosinophil degranulation.
Hwang SM et al.·Clin Exp Allergy
2018
Physical mapping and exclusion of GPR34 as the causative gene for congenital stationary night blindness type 1.
Jacobi FK et al.·Hum Genet
2000
Clinical, histopathological, and molecular features of mucosa-associated lymphoid tissue (MALT) lymphoma carrying the t(X;14) (p11;q32)/GPR34-immunoglobulin heavy chain gene.
Akasaka T et al.·Leuk Lymphoma
2017Case report
Mirtronic miR-4646-5p promotes gastric cancer metastasis by regulating ABHD16A and metabolite lysophosphatidylserines.
Yang L et al.·Cell Death Differ
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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