AGPAT3

Chr 21

1-acylglycerol-3-phosphate O-acyltransferase 3

Also known as: 1-AGPAT 3, LPAAT-GAMMA1, LPAAT3, LPLAT3

NCBI Gene: 56894 ENSG00000160216 UniProt: Q9NRZ7 OMIM: 614794

The protein encoded by AGPAT3 is an acyltransferase that converts lysophosphatidic acid to phosphatidic acid in the de novo phospholipid biosynthetic pathway and also acts on other lysophospholipids including lysophosphatidylcholine and lysophosphatidylinositol. Mutations cause autosomal recessive congenital generalized lipodystrophy type 9, characterized by severe loss of subcutaneous and visceral adipose tissue from birth leading to metabolic complications including insulin resistance and hypertriglyceridemia. The gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is an acyltransferase that converts lysophosphatidic acid into phosphatidic acid, which is the second step in the de novo phospholipid biosynthetic pathway. The encoded protein may be an integral membrane protein. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.14

Clinical Summary— AGPAT3

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 29 VUS of 48 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.14LOEUF

pLI 0.999

Z-score 4.25

OE 0.00 (0.00–0.14)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.54Z-score

OE missense 0.54 (0.47–0.63)

131 obs / 242.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.14)

0≤0.351.4

Missense OE?0.54 (0.47–0.63)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 0 / 21.1Missense obs/exp: 131 / 242.1Syn Z: 0.82

ClinVar Variant Classifications

48 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS29

Likely Benign5

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	0	29	0	0	29
Likely Benign	0	0	1	4	5
Benign	0	0	0	1	1
Total	1	29	1	5	36

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

View in ClinVar →

90 pathogenic / likely-pathogenic (of 107) ClinVar copy-number / structural variants overlap AGPAT3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →