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…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.48

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in LPCAT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 73

671 rare PASS variants

Rare truncating (LoF)

1 in 2,600

70 rare PASS variants

Rare synonymous (reference)

1 in 110

371 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LPCAT1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 100	1 in 3,400
South Asian	~43k	1 in 82	1 in 880
Remaining (unassigned)	~30k	1 in 93	1 in 2,300
European (Finnish)	~27k	1 in 170	1 in 2,600
Admixed American	~22k	1 in 130	1 in 870
African / African American	~21k	1 in 74	1 in 1,500
East Asian	~20k	1 in 120	1 in 2,300
Ashkenazi Jewish	~13k	1 in 570	1 in 2,600
Middle Eastern	~2,884	1 in 110	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 14 coding exons well covered in gnomAD exomes; exons 1, 5 marginal. Genomes: all 14.? see exons ↓