AGPAT3

Chr 21

1-acylglycerol-3-phosphate O-acyltransferase 3

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

NCBI Gene: 56894ENSG00000160216UniProt: Q9NRZ7OMIM: 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.

OMIMResearchSummary from RefSeq, UniProt
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
91 unique Pathogenic / Likely Pathogenic· 44 VUS of 155 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 OE0.00 (0.00–0.14)
0≤0.351.4
Missense OE0.54 (0.47–0.63)
0≤0.61.4
Synonymous OE0.90
0≤1.21.6
LoF obs/exp: 0 / 21.1Missense obs/exp: 131 / 242.1Syn Z: 0.82

ClinVar Variant Classifications

155 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic87
Likely Pathogenic4
VUS44
Likely Benign5
Benign1
Conflicting2
87
Pathogenic
4
Likely Pathogenic
44
VUS
5
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
86
0
87
Likely Pathogenic
0
0
4
0
4
VUS
0
29
15
0
44
Likely Benign
0
0
1
4
5
Benign
0
0
0
1
1
Conflicting
—2
Total1291065143

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

View in ClinVar →

Protein Context — Lollipop Plot

AGPAT3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
A post-GWAS confirming the genetic effects and functional polymorphisms of AGPAT3 gene on milk fatty acids in dairy cattle
Shi L et al.·J Anim Sci Biotechnol
2021Functional
AGPAT3 Gene polymorphisms are associated with milk production traits in Chinese Holstein cows.
Sun X et al.·J Dairy Res
2021
Expression pattern of AGPATs isoforms indicate different functions during the triacylglyceride synthesis in Chinese mitten crab, Eriocheir sinensis.
Pan K et al.·Comp Biochem Physiol A Mol Integr Physiol
2023
Dietary omega-3 fatty acid does not improve male infertility caused by lysophospholipid acyltransferase 3 (LPLAT3/AGPAT3) deficiency.
Nagata K et al.·Biochem Biophys Res Commun
2023
Role of Different Members of the AGPAT Gene Family in Milk Fat Synthesis in Bubalus bubalis
Li Z et al.·Genes (Basel)
2023
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
A loss of function variant in AGPAT3 underlies intellectual disability and retinitis pigmentosa (IDRP) syndrome.
Malik MA et al.·Eur J Hum Genet
2023
Exogenous H(2) S promotes ubiquitin-mediated degradation of SREBP1 to alleviate diabetic cardiomyopathy via SYVN1 S-sulfhydration.
Zhang S et al.·J Cachexia Sarcopenia Muscle
2023
Meta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function.
Kintu C et al.·BMC Genomics
2023Meta-analysis
AGPAT3 Regulates Immune Microenvironment in Osteosarcoma via Lysophosphatidic Acid Metabolism.
Su S et al.·Oncol Res
2025
The association between lipid metabolism and coronary artery disease: A systematic Mendelian randomization study combined with transcriptome analysis.
Bure Q et al.·Medicine (Baltimore)
2026
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients