PLAAT1

Chr 3

phospholipase A and acyltransferase 1

Also known as: A-C1, H-REV107, HRASLS, HRASLS1, HRSL1, HSD28, PLA/AT1, PLAAT-1

NCBI Gene: 57110 ENSG00000127252 UniProt: Q9HDD0 OMIM: 606487

Enables acyltransferase activity, transferring groups other than amino-acyl groups and phospholipase activity. Involved in N-acylphosphatidylethanolamine metabolic process and phosphatidylcholine metabolic process. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.56

Clinical Summary— PLAAT1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

45 VUS of 54 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.56LOEUF

pLI 0.000

Z-score 0.49

OE 0.81 (0.44–1.56)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.08Z-score

OE missense 0.98 (0.83–1.16)

95 obs / 97.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.81 (0.44–1.56)

0≤0.351.4

Missense OE?0.98 (0.83–1.16)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 6 / 7.4Missense obs/exp: 95 / 97.2Syn Z: 0.46

This gene — mechanism propensity

0.78top 25%

GOF

0.80top 10%

LOF

0.2092th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

54 submitted variants in ClinVar

ClinVar

Classification Summary

VUS45

Likely Benign3

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	0	45	0	45
Likely Benign	0	3	0	3
Benign	1	0	1	2
Total	1	48	1	50

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

36 pathogenic / likely-pathogenic (of 39) ClinVar copy-number / structural variants overlap PLAAT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →