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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GPAT3
glycerol-3-phosphate acyltransferase 3
Chromosome 4 · 4q21.23
NCBI Gene: 84803Ensembl: ENSG00000138678.12HGNC: HGNC:28157UniProt: A0A024RDG5
61PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
glycerol-3-phosphate O-acyltransferase activity1-acylglycerol-3-phosphate O-acyltransferase activitytriglyceride biosynthetic processregulation of TOR signalingAlzheimer diseasePeyronie diseaseglomerulonephritisrhabdomyolysis
✦AI Summary

GPAT3 (glycerol-3-phosphate acyltransferase 3) is an endoplasmic reticulum-localized enzyme catalyzing the first and rate-limiting steps of glycerolipid biosynthesis 1. It converts glycerol-3-phosphate to lysophosphatidic acid (LPA) and subsequently to phosphatidic acid (PA), both critical intermediates in triglyceride and phospholipid synthesis 23. GPAT3 is predominantly expressed in adipose tissue and is dramatically upregulated (~60-fold) during adipocyte differentiation, where it represents the major GPAT isoform driving lipid accumulation 4. Its expression is regulated by insulin signaling and endoplasmic reticulum stress through ATF4-mediated AP-1 elements 5. GPAT3 activity is stabilized and enhanced by the cofactor CHP1, which facilitates recruitment of GPAT3 to lipid droplets 6. Clinically, GPAT3 upregulation contributes to sorafenib resistance in hepatocellular carcinoma by promoting triglyceride synthesis and activating anti-apoptotic NF-κB/Bcl2 signaling 7. In Kupffer cells, GPAT3-mediated LPA synthesis exacerbates inflammation through ERK pathway activation 8. Conversely, GPAT3 deletion ameliorates metabolic dysfunction in lipodystrophy models, suggesting GPAT inhibitors may have therapeutic potential for metabolic and malignant diseases 9.

Sources cited
1
GPAT3 converts glycerol-3-phosphate to LPA
PMID: 17170135
2
GPAT3 converts LPA to phosphatidic acid
PMID: 19318427
3
GPAT3 is ER-localized and catalyzes rate-limiting step in glycerolipid biosynthesis
PMID: 30813330
4
GPAT3 is highly induced during adipocyte differentiation and represents major GPAT isoform in adipocytes
PMID: 20181984
5
GPAT3 expression is regulated by ER stress through ATF4 and AP-1 elements
PMID: 41392190
6
CHP1 stabilizes GPAT3 activity and facilitates its localization to lipid droplets
PMID: 40875810
7
GPAT3 upregulation promotes sorafenib resistance in hepatocellular carcinoma via triglyceride synthesis and NF-κB/Bcl2 signaling
PMID: 38948063
8
GPAT3-mediated LPA synthesis exacerbates Kupffer cell inflammation through ERK pathway
PMID: 36964139
9
GPAT3 deletion ameliorates metabolic dysfunction in lipodystrophy models
PMID: 31873720
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.28Weak
Peyronie diseaseOpen Targets
0.28Weak
glomerulonephritisOpen Targets
0.26Weak
rhabdomyolysisOpen Targets
0.17Weak
cardiac arrestOpen Targets
0.13Weak
ovarian neoplasmOpen Targets
0.13Weak
Respiratory insufficiencyOpen Targets
0.13Weak
parasitic infectionOpen Targets
0.12Weak
knee fractureOpen Targets
0.12Weak
chronic pancreatitisOpen Targets
0.11Weak
thyroid cancerOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
cystOpen Targets
0.10Suggestive
benign chondrogenic neoplasmOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.08Suggestive
frozen shoulderOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
small cell lung carcinomaOpen Targets
0.08Suggestive
lung cancerOpen Targets
0.07Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GPD1LProtein interaction94%GPD1Protein interaction94%GK2Protein interaction94%AGKProtein interaction91%ADPRMProtein interaction90%MBOAT2Protein interaction84%
Tissue Expression6 tissues
Heart
100%
Ovary
49%
Bone Marrow
25%
Liver
18%
Lung
17%
Brain
6%
Gene Interaction Network
Click a node to explore
GPAT3GPD1LGPD1GK2AGKADPRMMBOAT2
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q53EU6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.15LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.91 [0.72–1.15]
RankingsWhere GPAT3 stands among ~20K protein-coding genes
  • #7,557of 20,598
    Most Researched61
  • #12,020of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedGPAT3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
GPAT3 is a potential therapeutic target to overcome sorafenib resistance in hepatocellular carcinoma.
PMID: 38948063
Theranostics · 2024
1.00
2
GPAT3 regulates the synthesis of lipid intermediate LPA and exacerbates Kupffer cell inflammation mediated by the ERK signaling pathway.
PMID: 36964139
Cell Death Dis · 2023
0.90
3
Isolation and Characterization of GPAT3 Gene from Jojoba Plant and its Inferior Early Diagnosis of Sex.
PMID: 39820567
Pak J Biol Sci · 2025
0.80
4
AP-1 elements in the promoter and second intron mediate endoplasmic reticulum stress-induced expression of the GPAT3 gene.
PMID: 41392190
Sci Rep · 2025
0.70
5
Transcriptional Regulation of Acyl-CoA:Glycerol-
PMID: 30813330
Int J Mol Sci · 2019
0.60