LPCAT4

Chr 15

lysophosphatidylcholine acyltransferase 4

Also known as: AGPAT7, AYTL3, LPAAT-eta, LPEAT2, LPLAT10

NCBI Gene: 254531 ENSG00000176454 UniProt: Q6ZWT7

Members of the 1-acylglycerol-3-phosphate O-acyltransferase (EC 2.3.1.51) family, such as AGPAT7, catalyze the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA), a precursor in the biosynthesis of all glycerolipids. Both LPA and PA are involved in signal transduction (Ye et al., 2005 [PubMed 16243729]).[supplied by OMIM, May 2008]

Research

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

0.41

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.482

Z-score 4.12

OE 0.22 (0.12–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.55Z-score

OE missense 0.75 (0.67–0.84)

224 obs / 299.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.12–0.41)

0≤0.351.4

Missense OE?0.75 (0.67–0.84)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 7 / 32.2Missense obs/exp: 224 / 299.3Syn Z: 0.71

Background carrier burden — how many people carry a rare variant somewhere in LPCAT4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

589 rare PASS variants

Rare truncating (LoF)

1 in 3,300

71 rare PASS variants

Rare synonymous (reference)

1 in 140

275 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LPCAT4. 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 120	1 in 3,300
South Asian	~43k	1 in 88	1 in 5,600
Remaining (unassigned)	~30k	1 in 88	1 in 5,700
European (Finnish)	~27k	1 in 910	≈ 1 in 27,000
Admixed American	~22k	1 in 99	1 in 2,700
African / African American	~21k	1 in 100	1 in 1,900
East Asian	~20k	1 in 140	1 in 1,900
Ashkenazi Jewish	~13k	1 in 240	1 in 2,500
Middle Eastern	~2,884	1 in 120	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): 13 of 14 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 14.? see exons ↓