GPR63

Chr 6

G protein-coupled receptor 63

Also known as: PSP24(beta), PSP24B

NCBI Gene: 81491ENSG00000112218UniProt: Q9BZJ6

Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cytosol; nucleoplasm; and plasma membrane. Part of receptor complex. [provided by Alliance of Genome Resources, Jul 2025]

61
ClinVar variants
16
Pathogenic / LP
0.20
pLI score
0
Active trials
Clinical Summary— GPR63
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 45 VUS of 61 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.
0.70LOEUF
pLI 0.197
Z-score 2.25
OE 0.27 (0.12–0.70)
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.
0.51Z-score
OE missense 0.90 (0.81–1.01)
206 obs / 227.8 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.0.27 (0.12–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.81–1.01)
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.0.94
0≤1.21.6
LoF obs/exp: 3 / 11.1Missense obs/exp: 206 / 227.8Syn Z: 0.44

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS45
15
Pathogenic
1
Likely Pathogenic
45
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
39
6
0
45
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total03922061

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

View in ClinVar →

Protein Context — Lollipop Plot

GPR63 · 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
Endothelial cell-derived S1P promotes migration and stemness by binding with GPR63 in colorectal cancer.
Zeng S et al.·Pathol Res Pract
2022
Gpr63 is a modifier of microcephaly in Ttc21b mouse mutants.
Snedeker J et al.·PLoS Genet
2019Functional
Neuro-psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein-coupled receptors.
Khan MZ et al.·Psychopharmacology (Berl)
2017Review
Novel clusters of receptors for sphingosine-1-phosphate, sphingosylphosphorylcholine, and (lyso)-phosphatidic acid: new receptors for "old" ligands.
Kostenis E·J Cell Biochem
2004Review
Identification of four novel human G protein-coupled receptors expressed in the brain.
Lee DK et al.·Brain Res Mol Brain Res
2001
Genetic study of intracranial aneurysms.
Yan J et al.·Stroke
2015
Investigating Motor Coordination Using BXD Recombinant Inbred Mice to Model the Genetic Underpinnings of Developmental Coordination Disorder.
Rajan JRS et al.·Genes Brain Behav
2025Functional
Sphingosine 1-phosphate and dioleoylphosphatidic acid are low affinity agonists for the orphan receptor GPR63.
Niedernberg A et al.·Cell Signal
2003
Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay.
Yin H et al.·J Biol Chem
2009
Genome-wide sequencing for the identification of rearrangements associated with Tourette syndrome and obsessive-compulsive disorder.
Hooper SD et al.·BMC Med Genet
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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