LPAR3

Chr 1

lysophosphatidic acid receptor 3

Also known as: EDG7, Edg-7, GPCR, HOFNH30, LP-A3, LPA3, RP4-678I3

NCBI Gene: 23566ENSG00000171517UniProt: Q9UBY5

The encoded protein is a G protein-coupled receptor that binds lysophosphatidic acid and mediates calcium mobilization through G(q/11) signaling pathways. Mutations cause autosomal recessive hypotrichosis simplex, characterized by sparse hair growth from birth. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.593), suggesting intolerance to complete protein loss.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
15
Pubs (1 yr)
16
P/LP submissions
0%
P/LP missense
0.59
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— LPAR3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.68) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 62 VUS of 87 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.679
Z-score 2.29
OE 0.12 (0.04–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.26Z-score
OE missense 0.95 (0.84–1.07)
195 obs / 205.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.04–0.59)
0≤0.351.4
Missense OE0.95 (0.84–1.07)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 1 / 8.0Missense obs/exp: 195 / 205.3Syn Z: 0.51
DN
0.6162th %ile
GOF
0.72top 25%
LOF
0.4331th %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

87 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic2
VUS62
Benign3
14
Pathogenic
2
Likely Pathogenic
62
VUS
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
2
0
2
VUS
0
61
1
0
62
Likely Benign
0
0
0
0
0
Benign
0
1
0
2
3
Total06217281

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

View in ClinVar →

Protein Context — Lollipop Plot

LPAR3 · 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
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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