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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LAP3
leucine aminopeptidase 3
Chromosome 4 · 4p15.32
NCBI Gene: 51056Ensembl: ENSG00000002549.14HGNC: HGNC:18449UniProt: P28838
93PubMed Papers
20Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Protease
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleusextracellular exosomefocal adhesionmitochondrionupper respiratory tract disorderpreeclampsiaAlzheimer diseasemultinodular goiter
✦AI Summary

LAP3 is a cytosolic metallopeptidase that catalyzes removal of N-terminal hydrophobic amino acids from peptides, with zinc ions essential for its catalytic activity 1. The enzyme is involved in glutathione metabolism and redox homeostasis through glutathione S-conjugate degradation. LAP3 demonstrates significant pathological relevance across multiple disease contexts. In hepatocellular carcinoma, LAP3 is upregulated and correlates with poor prognosis, promoting cell proliferation through G1/S checkpoint regulation and enhancing cell migration and invasion 1. In non-alcoholic fatty liver disease (NAFLD), cholesterol-dependent LAP3 upregulation inhibits hepatocyte autophagy, with serum LAP3 levels correlating positively with triglycerides and gamma-glutamyltransferase while negatively correlating with HDL levels 2. LAP3 also promotes glioma progression by enhancing cell viability, proliferation, migration, and invasion 3. In breast cancer pathogenesis, LAP3 mediates IFN-γ-induced arginine depletion through interference with argininosuccinate synthetase (ASS1), driving malignant transformation via HDAC2 upregulation and cell cycle protein expression 4. Additionally, LAP3 has been identified as a potential druggable inflammatory target in COVID-19 hyperinflammation 5 and is associated with viral immunosuppression in rhinovirus-induced asthma 6. Clinically, LAP3 represents a promising biomarker and therapeutic target for liver disease, hepatocellular carcinoma, glioma, and breast cancer.

Sources cited
1
LAP3 is upregulated in HCC, correlates with poor prognosis, promotes proliferation via G1/S checkpoint regulation, and enhances cell migration
PMID: 25120751
2
Cholesterol upregulates LAP3 in hepatocytes to inhibit autophagy in NAFLD pathogenesis; serum LAP3 correlates with metabolic markers
PMID: 35404840
3
LAP3 promotes glioma progression by regulating cell viability, proliferation, migration, and invasion; correlates with malignancy grade
PMID: 25453285
4
LAP3 mediates IFN-γ-induced arginine depletion and malignant transformation via ASS1 interference and HDAC2 upregulation
PMID: 35941558
5
LAP3 is an aminopeptidase upregulated in human and mouse NAFLD and cirrhosis data; identified via plasma proteome profiling
PMID: 30824564
6
LAP3 identified as potentially druggable target in COVID-19 hyperinflammation and neutrophil-driven inflammation
PMID: 32581077
7
LAP3 is an immunosuppression signature marker induced by rhinovirus through TGF-β pathway in asthma
PMID: 34691038
Disease Associationsⓘ20
upper respiratory tract disorderOpen Targets
0.32Weak
preeclampsiaOpen Targets
0.29Weak
Alzheimer diseaseOpen Targets
0.25Weak
multinodular goiterOpen Targets
0.23Weak
neoplasmOpen Targets
0.12Weak
acute myeloid leukemiaOpen Targets
0.12Weak
myelodysplastic syndromeOpen Targets
0.10Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.09Suggestive
acute myeloid leukemia by FAB classificationOpen Targets
0.07Suggestive
cryopyrin-associated periodic syndromeOpen Targets
0.07Suggestive
non-alcoholic steatohepatitisOpen Targets
0.06Suggestive
hearing lossOpen Targets
0.06Suggestive
systemic lupus erythematosusOpen Targets
0.06Suggestive
Hepatic fibrosisOpen Targets
0.06Suggestive
gallstonesOpen Targets
0.06Suggestive
acute lymphoblastic leukemiaOpen Targets
0.05Suggestive
ulcerative colitisOpen Targets
0.05Suggestive
Neoplasm of the lungOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
TOSEDOSTATPhase II
Aminopeptidase inhibitor
acute myeloid leukemia by FAB classification
Related Genes
PGA4Shared pathway100%PGA3Shared pathway100%CAPN14Shared pathway100%CTRB2Shared pathway100%CAPN8Shared pathway100%PRSS48Shared pathway100%
Tissue Expression6 tissues
Liver
100%
Lung
95%
Heart
84%
Brain
70%
Bone Marrow
51%
Ovary
24%
Gene Interaction Network
Click a node to explore
LAP3PGA4PGA3CAPN14CTRB2CAPN8PRSS48
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P28838
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.97LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.71 [0.53–0.97]
RankingsWhere LAP3 stands among ~20K protein-coding genes
  • #5,151of 20,598
    Most Researched93
  • #9,250of 17,882
    Most Constrained (LOEUF)0.97
Genes detectedLAP3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Emerging contaminants: A One Health perspective.
PMID: 38756954
Innovation (Camb) · 2024
1.00
2
Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease.
PMID: 30824564
Mol Syst Biol · 2019
0.90
3
Expression of leucine aminopeptidase 3 (LAP3) correlates with prognosis and malignant development of human hepatocellular carcinoma (HCC).
PMID: 25120751
Int J Clin Exp Pathol · 2014
0.80
4
Cholesterol-induced leucine aminopeptidase 3 (LAP3) upregulation inhibits cell autophagy in pathogenesis of NAFLD.
PMID: 35404840
Aging (Albany NY) · 2022
0.70
5
LAP3 contributes to IFN-γ-induced arginine depletion and malignant transformation of bovine mammary epithelial cells.
PMID: 35941558
BMC Cancer · 2022
0.60