PLAAT2

Chr 11

phospholipase A and acyltransferase 2

NCBI Gene: 54979 ENSG00000133328 UniProt: Q9NWW9

This protein functions as a phospholipase and acyltransferase that hydrolyzes phospholipids and catalyzes fatty acid transfers in cellular membranes. Mutations cause neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed puberty, inherited in an autosomal recessive pattern. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern.

ResearchSummary from RefSeq, UniProt

Exhibits both phospholipase A1/2 and acyltransferase activities (PubMed:19615464, PubMed:22605381, PubMed:22825852, PubMed:26503625). Shows phospholipase A1 (PLA1) and A2 (PLA2) activity, catalyzing the calcium-independent release of fatty acids from the sn-1 or sn-2 position of glycerophospholipids (PubMed:19615464, PubMed:22605381, PubMed:22825852). For most substrates, PLA1 activity is much higher than PLA2 activity (PubMed:19615464). Shows O-acyltransferase activity, catalyzing the transfer of a fatty acyl group from glycerophospholipid to the hydroxyl group of lysophospholipid (PubMed:19615464). Shows N-acyltransferase activity, catalyzing the calcium-independent transfer of a fatty acyl group at the sn-1 position of phosphatidylcholine (PC) and other glycerophospholipids to the primary amine of phosphatidylethanolamine (PE), forming N-acylphosphatidylethanolamine (NAPE), which serves as precursor for N-acylethanolamines (NAEs) (PubMed:19615464, PubMed:22605381, PubMed:22825852). Catalyzes N-acylation of PE using both sn-1 and sn-2 palmitoyl groups of PC as acyl donor (PubMed:22605381). Exhibits high phospholipase A1/2 activity and low N-acyltransferase activity (PubMed:22825852)

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.83

LOEUF

Multiple*

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.83LOEUF

pLI 0.000

Z-score -0.19

OE 1.09 (0.58–1.83)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.87Z-score

OE missense 0.76 (0.63–0.92)

76 obs / 100.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.09 (0.58–1.83)

0≤0.351.4

Missense OE?0.76 (0.63–0.92)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 6 / 5.5Missense obs/exp: 76 / 100.5Syn Z: 0.37

Background carrier burden — how many people carry a rare variant somewhere in PLAAT2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

177 rare PASS variants

Rare truncating (LoF)

1 in 2,400

26 rare PASS variants

Rare synonymous (reference)

1 in 470

84 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PLAAT2. 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 340	1 in 2,100
South Asian	~43k	1 in 450	≈ 1 in 21,000
Remaining (unassigned)	~30k	1 in 240	≈ 1 in 7,500
European (Finnish)	~27k	1 in 740	≈ 1 in 27,000
Admixed American	~22k	1 in 170	none seen
African / African American	~21k	1 in 200	1 in 3,600
East Asian	~20k	1 in 470	none seen
Ashkenazi Jewish	~13k	≈ 1 in 4,400	1 in 1,700
Middle Eastern	~2,884	1 in 320	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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓