LPCAT1

Chr 5

lysophosphatidylcholine acyltransferase 1

The protein encoded by this gene is an acyltransferase that converts lysophosphatidylcholine to phosphatidylcholine and is involved in lung surfactant synthesis and platelet-activating factor biosynthesis. Mutations cause autosomal recessive disorders affecting multiple systems including severe respiratory distress and neurological abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.478), suggesting some intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.48
Clinical SummaryLPCAT1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.137
Z-score 3.62
OE 0.25 (0.140.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.61Z-score
OE missense 0.75 (0.680.84)
254 obs / 337.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.140.48)
00.351.4
Missense OE0.75 (0.680.84)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 7 / 27.5Missense obs/exp: 254 / 337.3Syn Z: -1.07
DN
0.6161th %ile
GOF
0.7126th %ile
LOF
0.2873th %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

LPCAT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →