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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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LPCAT3
lysophosphatidylcholine acyltransferase 3
Chromosome 12 · 12p13.31
NCBI Gene: 10162Ensembl: ENSG00000111684.12HGNC: HGNC:30244UniProt: Q6P1A2
60PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
phosphatidylcholine acyl-chain remodelingphosphatidylethanolamine acyl-chain remodelingendoplasmic reticulum membrane1-acylglycerophosphocholine O-acyltransferase activityAlzheimer diseasecancernonpapillary renal cell carcinomatype 2 diabetes mellitus
✦AI Summary

LPCAT3 (lysophosphatidylcholine acyltransferase 3) is a phospholipid remodeling enzyme that catalyzes the reacylation step of the Lands cycle, converting lysophospholipids into mature phospholipids 1. Specifically, LPCAT3 transfers polyunsaturated fatty acyl chains from acyl-CoA donors to lysophosphatidylcholine, lysophosphatidylserine, and lysophosphatidylethanolamine, generating phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine respectively 1. In liver, LPCAT3 maintains systemic lipid homeostasis by regulating membrane phospholipid composition, particularly incorporating arachidonate into phospholipids that facilitate VLDL secretion and modulate ER stress responses 1. In intestine, LPCAT3 enables efficient lipid absorption and chylomicron assembly by regulating polyunsaturated phosphatidylcholine levels 1. Clinically, LPCAT3 dysfunction is implicated in nonalcoholic fatty liver disease (NAFLD) progression; decreased LPCAT3 expression correlates with NASH severity and impaired mitochondrial homeostasis 2. LPCAT3 also participates in ferroptosis regulation, with its upregulation promoting lipid peroxidation and enhancing anti-PD-1 immunotherapy efficacy in melanoma and lung cancer 3. Conversely, cancer cells evade immune-mediated ferroptosis by suppressing LPCAT3 expression through FABP7-driven epigenetic reprogramming 4. These findings suggest LPCAT3 modulation represents a therapeutic target for metabolic and immune-oncology diseases.

Sources cited
1
LPCAT3 catalyzes incorporation of fatty acyl chains into phosphatidylcholine and maintains systemic lipid homeostasis by regulating lipid absorption, lipoprotein secretion, and de novo lipogenesis
PMID: 30379616
2
LPCAT3 expression is suppressed in NASH livers, inversely correlates with disease severity, and its loss promotes NASH progression by impairing mitochondrial homeostasis
PMID: 36999536
3
LPCAT3 is a key gene involved in lipid peroxidation and ferroptosis; upregulation enhances anti-PD-1 immunotherapy efficacy in melanoma and lung cancer
PMID: 38471712
4
Cancer cells upregulate FABP7 which decreases LPCAT3 transcription, reducing ferroptosis susceptibility and promoting resistance to immunotherapy
PMID: 39901247
5
LPCAT3 is involved in ferroptosis promotion through membrane lipid repair during spinal cord injury pathology
PMID: 38907771
6
LPCAT3 participates in lipid peroxide production during ferroptosis and is involved in type 2 diabetes mellitus pathogenesis
PMID: 34258295
7
LPCAT3 is regulated by the SCAP/SREBP pathway and critical for proper phospholipid composition; its downregulation leads to ER stress and hepatocyte injury in NASH
PMID: 35380992
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.11Weak
cancerOpen Targets
0.09Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.08Suggestive
type 2 diabetes mellitusOpen Targets
0.08Suggestive
Schnyder corneal dystrophyOpen Targets
0.07Suggestive
acute myeloid leukemiaOpen Targets
0.06Suggestive
endocrine system diseaseOpen Targets
0.05Suggestive
microphthalmia with limb anomaliesOpen Targets
0.05Suggestive
Insulin resistanceOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.04Suggestive
Hyperlipoproteinemia type 5Open Targets
0.04Suggestive
hyperlipoproteinemia type VOpen Targets
0.04Suggestive
apolipoprotein c-III deficiencyOpen Targets
0.04Suggestive
familial hypobetalipoproteinemia 2Open Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
myeloid sarcomaOpen Targets
0.04Suggestive
glycogen storage disease VIOpen Targets
0.04Suggestive
Crigler-Najjar syndrome type 2Open Targets
0.04Suggestive
Gilbert syndromeOpen Targets
0.04Suggestive
glycine N-methyltransferase deficiencyOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PISDProtein interaction98%PEMTProtein interaction97%PLD1Protein interaction96%PLD2Protein interaction96%PTDSS1Protein interaction96%CHPT1Protein interaction96%
Tissue Expression6 tissues
Liver
100%
Lung
87%
Brain
50%
Bone Marrow
39%
Heart
37%
Ovary
32%
Gene Interaction Network
Click a node to explore
LPCAT3PISDPEMTPLD1PLD2PTDSS1CHPT1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q6P1A2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.48Moderately Constrained
pLIⓘ
0.99Intolerant
Observed/Expected LoF0.32 [0.22–0.48]
RankingsWhere LPCAT3 stands among ~20K protein-coding genes
  • #7,682of 20,598
    Most Researched60
  • #2,853of 17,882
    Most Constrained (LOEUF)0.48 · top quartile
Genes detectedLPCAT3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Phospholipid Remodeling in Physiology and Disease.
PMID: 30379616
Annu Rev Physiol · 2019
1.00
2
Copper metabolism in cell death and autophagy.
PMID: 37055935
Autophagy · 2023
0.90
3
Mefloquine enhances the efficacy of anti-PD-1 immunotherapy via IFN-γ-STAT1-IRF1-LPCAT3-induced ferroptosis in tumors.
PMID: 38471712
J Immunother Cancer · 2024
0.80
4
Mechanism of Ferroptosis and Its Role in Type 2 Diabetes Mellitus.
PMID: 34258295
J Diabetes Res · 2021
0.70
5
Membrane phospholipid remodeling modulates nonalcoholic steatohepatitis progression by regulating mitochondrial homeostasis.
PMID: 36999536
Hepatology · 2024
0.60