LPAR1

Chr 9

lysophosphatidic acid receptor 1

Also known as: EDG2, Gpcr26, LPA1, Mrec1.3, VZG1, edg-2, rec.1.3, vzg-1

The lysophosphatidic acid receptor 1 functions as a G protein-coupled receptor that binds lysophosphatidic acid and regulates actin cytoskeleton reorganization, cell migration, proliferation, and neuronal development including neurite retraction and formation of new neurons in the adult brain. Gain-of-function mutations in LPAR1 cause neurodevelopmental disorders, though the specific inheritance pattern requires further clinical characterization. The pathogenic mechanism involves excessive receptor activation leading to dysregulated cellular signaling that disrupts normal brain development and neuronal function.

Summary from RefSeq, UniProt, Mechanism
0
Active trials
55
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.71
LOEUF
GOF
Mechanism· predicted
Clinical SummaryLPAR1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.71LOEUF
pLI 0.186
Z-score 2.21
OE 0.28 (0.130.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.42Z-score
OE missense 0.55 (0.470.64)
126 obs / 228.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.28 (0.130.71)
00.351.4
Missense OE0.55 (0.470.64)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 3 / 10.9Missense obs/exp: 126 / 228.9Syn Z: -0.51
DN
0.7326th %ile
GOF
0.81top 10%
LOF
0.2775th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LPAR1 · 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

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗