LPCAT1

Chr 5

lysophosphatidylcholine acyltransferase 1

Also known as: AGPAT10, AGPAT9, AYTL2, LPCAT-1, LPLAT8, PFAAP3, lpcat, lysoPAFAT

NCBI Gene: 79888 ENSG00000153395 UniProt: Q8NF37 OMIM: 610472

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the 1-acyl-sn-glycerol-3-phosphate acyltransferase family of proteins. The encoded enzyme plays a role in phospholipid metabolism, specifically in the conversion of lysophosphatidylcholine to phosphatidylcholine in the presence of acyl-CoA. This process is important in the synthesis of lung surfactant and platelet-activating factor (PAF). Elevated expression of this gene may contribute to the progression of oral squamous cell, prostate, breast, and other human cancers. [provided by RefSeq, Sep 2016]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.48

Clinical Summary— LPCAT1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.48LOEUF

pLI 0.137

Z-score 3.62

OE 0.25 (0.14–0.48)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.61Z-score

OE missense 0.75 (0.68–0.84)

254 obs / 337.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.25 (0.14–0.48)

0≤0.351.4

Missense OE?0.75 (0.68–0.84)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 7 / 27.5Missense obs/exp: 254 / 337.3Syn Z: -1.07

This gene — mechanism propensity

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.