PLAAT4

Chr 11

phospholipase A and acyltransferase 4

Also known as: HRASLS4, HRSL4, PLA1/2-3, PLAAT-4, RARRES3, RIG1, TIG3

NCBI Gene: 5920 ENSG00000133321 UniProt: Q9UL19

The protein functions as a phospholipase A1/A2 and acyltransferase, catalyzing calcium-independent release of fatty acids from glycerophospholipids and transfer of fatty acyl groups to form N-acylphosphatidylethanolamine precursors. Mutations cause neurodevelopmental disorder with hypotonia, seizures, and brain abnormalities, inherited in an autosomal recessive pattern. The gene shows very low constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, UniProt

Retinoids exert biologic effects such as potent growth inhibitory and cell differentiation activities and are used in the treatment of hyperproliferative dermatological diseases. These effects are mediated by specific nuclear receptor proteins that are members of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. RARRES1, RARRES2, and RARRES3 are genes whose expression is upregulated by the synthetic retinoid tazarotene. RARRES3 is thought act as a tumor suppressor or growth regulator. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.92

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?

1.92LOEUF

pLI 0.000

Z-score -1.03

OE 1.45 (0.83–1.92)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.36Z-score

OE missense 0.90 (0.75–1.07)

88 obs / 98.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.45 (0.83–1.92)

0≤0.351.4

Missense OE?0.90 (0.75–1.07)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 9 / 6.2Missense obs/exp: 88 / 98.1Syn Z: -0.15

Background carrier burden — how many people carry a rare variant somewhere in PLAAT4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

204 rare PASS variants

Rare truncating (LoF)

1 in 950

42 rare PASS variants

Rare synonymous (reference)

1 in 720

100 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PLAAT4. 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 170	1 in 1,100
South Asian	~43k	1 in 190	1 in 560
Remaining (unassigned)	~30k	1 in 160	1 in 690
European (Finnish)	~27k	1 in 420	1 in 2,100
Admixed American	~22k	1 in 190	1 in 3,700
African / African American	~21k	1 in 190	1 in 1,100
East Asian	~20k	1 in 180	1 in 1,800
Ashkenazi Jewish	~13k	1 in 2,200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 240	1 in 350

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 ↓