ANGPTL3: Angiopoietin-Like 3 – Lipid Metabolism Regulator and Therapeutic Target
A key regulator of lipoprotein metabolism, ANGPTL3 inhibits LPL and endothelial lipase, influencing plasma lipid levels and cardiovascular risk.
Gene Information Card
| Symbol | ANGPTL3 |
|---|---|
| Full Name | Angiopoietin-like 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p31.3 |
| NCBI Gene ID | 27329 ncbi.nlm.nih.gov/gene/27329 |
| Ensembl ID | ENSG00000132825 |
| UniProt ID | Q9Y5C1 |
| OMIM ID | 604774 |
| HGNC ID | 491 |
| Aliases | ANG-5, ANGPT5, FHBL2 |
Description
The ANGPTL3 gene encodes angiopoietin-like 3, a secreted protein primarily expressed in the liver. It plays a critical role in lipid metabolism by inhibiting lipoprotein lipase (LPL) and endothelial lipase, thereby regulating plasma triglyceride and HDL cholesterol levels. Loss-of-function mutations lead to familial combined hypolipidemia, characterized by low levels of LDL, HDL, and triglycerides. ANGPTL3 is also a therapeutic target for hyperlipidemia and cardiovascular disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial combined hypolipidemia (FHBL2) | Loss-of-function mutations in ANGPTL3 lead to reduced inhibition of LPL and endothelial lipase, resulting in increased lipolysis and decreased plasma lipid levels. | OMIM 605019; ClinVar |
| Coronary artery disease (protective) | Loss-of-function variants are associated with lower risk of coronary artery disease due to reduced plasma lipid levels. | Stitziel et al., NEJM 2017; ClinVar |
| Hyperlipidemia (therapeutic target) | Inhibition of ANGPTL3 (e.g., evinacumab) lowers LDL, HDL, and triglycerides, used in homozygous familial hypercholesterolemia. | Clinical trials; FDA approval 2021 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High | Primary expression site |
| Kidney | Low | Detected |
| Adipose tissue | Low | Detected |
| Skeletal muscle | Not detected | Below threshold |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | High | Hepatocellular carcinoma cell line |
| Huh7 | High | Hepatoma cell line |
| Caco-2 | Low | Colorectal adenocarcinoma |
| A549 | Not detected | Lung carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.S17X | Nonsense | Rare | Loss of function; associated with hypolipidemia |
| p.R121X | Nonsense | Rare | Loss of function; associated with hypolipidemia |
| p.E129K | Missense | Rare | Loss of function; reduced secretion |
| p.N147K | Missense | Rare | Loss of function; reduced LPL inhibition |
| p.R300C | Missense | Rare | Loss of function; reduced secretion |
Mutation functional classification
Loss of Function (LOF)
Most ANGPTL3 mutations are loss-of-function, leading to reduced inhibition of LPL and endothelial lipase, resulting in lower plasma lipids and protection against cardiovascular disease.
Gain of Function (GOF)
No gain-of-function mutations have been reported; such mutations would theoretically increase LPL inhibition and elevate lipid levels, but are not observed.
Dominant Negative (DN)
No dominant-negative effects have been described; ANGPTL3 haploinsufficiency is sufficient to cause hypolipidemia.
View complete mutation data：
Gene Ontology (GO)
| • heparin binding | • lipoprotein lipase inhibitor activity |
| • extracellular space | • lipid metabolic process |
| • triglyceride homeostasis | • cholesterol homeostasis |
Pathways
• Lipoprotein metabolism
• PPAR signaling pathway
• LPL inhibition pathway
Protein Summary
ANGPTL3 is a 460-amino-acid secreted glycoprotein with an N-terminal coiled-coil domain and a C-terminal fibrinogen-like domain. The N-terminal domain is responsible for LPL inhibition. It is cleaved by proprotein convertases, generating active fragments. ANGPTL3 also inhibits endothelial lipase, affecting HDL metabolism. It is primarily expressed in the liver and regulates plasma lipid levels.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ANGPTL3 Knockout HEK293 Cell Line | EDJ-KQ8764 | Human | 27329 | Details Get a Quote |
| ANGPTL3 Knockout HeLa Cell Line | EDJ-KQ56059 | Human | 27329 | Details Get a Quote |
| ANGPTL3 Knockout A-549 Cell Line | EDJ-KQ64543 | Human | 27329 | Details Get a Quote |
| ANGPTL3 Knockout HCT 116 Cell Line | EDJ-KQ73002 | Human | 27329 | Details Get a Quote |
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