LPAR5

Chr 12

lysophosphatidic acid receptor 5

Also known as: GPR92, GPR93, KPG_010, LPA5

The protein functions as a G protein-coupled receptor that transmits signals from lysophosphatidic acid to mediate diverse cellular processes. Mutations cause autosomal recessive hypotrichosis simplex, characterized by sparse hair growth typically present from birth. The gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance requiring biallelic mutations to cause disease.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
10
Pubs (1 yr)
44
P/LP submissions
0%
P/LP missense
1.07
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryLPAR5
Population Constraint (gnomAD)
Low constraint (pLI 0.05) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
44 unique Pathogenic / Likely Pathogenic· 70 VUS of 116 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.051
Z-score 1.46
OE 0.42 (0.191.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.18Z-score
OE missense 0.79 (0.700.89)
191 obs / 242.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.191.07)
00.351.4
Missense OE0.79 (0.700.89)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 3 / 7.2Missense obs/exp: 191 / 242.7Syn Z: 1.32
DN
0.75top 25%
GOF
0.86top 5%
LOF
0.2387th %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

116 submitted variants in ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic2
VUS70
42
Pathogenic
2
Likely Pathogenic
70
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
42
0
42
Likely Pathogenic
0
0
2
0
2
VUS
0
61
9
0
70
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total061530114

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

View in ClinVar →

Protein Context — Lollipop Plot

LPAR5 · 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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