LPCAT3

Chr 12

lysophosphatidylcholine acyltransferase 3

Also known as: C3F, LPCAT, LPLAT 5, LPLAT12, LPSAT, MBOAT5, OACT5, nessy

NCBI Gene: 10162 ENSG00000111684 UniProt: Q6P1A2 OMIM: 611950

This enzyme catalyzes the reacylation of lysophospholipids to form phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine as part of the Lands cycle phospholipid remodeling pathway, with particular importance in liver and intestinal lipid metabolism. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and seizures. The gene is highly constrained against loss-of-function variants (pLI 0.995), indicating that complete loss of function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables 1-acylglycerophosphocholine O-acyltransferase activity; 1-acylglycerophosphoethanolamine O-acyltransferase activity; and 1-acylglycerophosphoserine O-acyltransferase activity. Involved in phosphatidylcholine acyl-chain remodeling; phosphatidylethanolamine acyl-chain remodeling; and phosphatidylserine acyl-chain remodeling. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jul 2025]

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

133

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.27

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.27LOEUF

pLI 0.995

Z-score 4.47

OE 0.10 (0.05–0.27)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.45Z-score

OE missense 0.58 (0.50–0.66)

153 obs / 265.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.10 (0.05–0.27)

0≤0.351.4

Missense OE?0.58 (0.50–0.66)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 3 / 29.0Missense obs/exp: 153 / 265.5Syn Z: -0.12

Background carrier burden — how many people carry a rare variant somewhere in LPCAT3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

478 rare PASS variants

Rare truncating (LoF)

1 in 8,200

44 rare PASS variants

Rare synonymous (reference)

1 in 210

259 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LPCAT3. 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 210	1 in 2,300
South Asian	~43k	1 in 200	1 in 2,700
Remaining (unassigned)	~30k	1 in 140	≈ 1 in 15,000
European (Finnish)	~27k	1 in 560	1 in 1,400
Admixed American	~22k	1 in 200	none seen
African / African American	~21k	1 in 130	≈ 1 in 6,000
East Asian	~20k	1 in 180	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 790	none seen
Middle Eastern	~2,884	1 in 190	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): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓