ANGPTL4 (Angiopoietin Like 4)
Key regulator of lipid metabolism, angiogenesis, and energy homeostasis
Gene Information Card
| Symbol | ANGPTL4 |
|---|---|
| Full Name | Angiopoietin Like 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.2 |
| NCBI Gene ID | 51129 ncbi.nlm.nih.gov/gene/51129 |
| Ensembl ID | ENSG00000139372 |
| UniProt ID | Q9BY76 |
| OMIM ID | 604774 |
| HGNC ID | 16039 |
| Aliases | ARP4, FIAF, HFARP, PGAR, pp1158, ANGPTL2 |
Description
ANGPTL4 encodes a glycosylated, secreted protein belonging to the angiopoietin-like family. It functions as a regulator of lipoprotein lipase (LPL) activity, thereby modulating plasma triglyceride levels. ANGPTL4 also plays roles in angiogenesis, wound healing, and energy metabolism. Expression is induced by fasting and hypoxia, and the protein is cleaved into N-terminal and C-terminal fragments with distinct biological activities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypertriglyceridemia, familial | Loss-of-function variants reduce LPL inhibition, leading to elevated triglycerides | ClinVar, OMIM |
| Coronary artery disease | ANGPTL4 variants associated with altered lipid profiles and cardiovascular risk | ClinVar, NCBI |
| Type 2 diabetes | Dysregulation of ANGPTL4 linked to insulin resistance and lipid metabolism | NCBI, OMIM |
| Cancer (various) | ANGPTL4 promotes tumor angiogenesis and metastasis via integrin signaling | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Adipose tissue | 8.3 | Low |
| Heart | 6.1 | Low |
| Skeletal muscle | 4.7 | Low |
| Placenta | 15.2 | Medium |
| Lung | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 18.4 | Hepatocellular carcinoma cell line |
| HUVEC | 22.1 | Endothelial cells |
| MCF7 | 5.6 | Breast cancer cell line |
| A549 | 7.3 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Glu40Lys | Missense | 0.02% | Reduced LPL inhibition, associated with hypertriglyceridemia |
| p.Arg371Ter | Nonsense | <0.01% | Loss of function, increased LPL activity |
| p.Ser167Pro | Missense | 0.01% | Altered protein stability, unclear effect |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift) reduce ANGPTL4's ability to inhibit LPL, leading to lower plasma triglycerides and potential protection against hypertriglyceridemia.
Gain of Function (GOF)
Gain-of-function mutations enhance LPL inhibition, increasing triglyceride levels and cardiovascular risk.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for ANGPTL4.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005615 (extracellular space) | • GO:0008201 (heparin binding) |
| • GO:0004857 (enzyme inhibitor activity) | • GO:0001525 (angiogenesis) |
| • GO:0010906 (regulation of triglyceride metabolic process) | • GO:0042802 (identical protein binding) |
Pathways
• Lipoprotein lipase regulation (Reactome: R-HSA-8963896)
• PPAR signaling pathway (KEGG: hsa03320)
• Angiogenesis (KEGG: hsa04370)
Protein Summary
ANGPTL4 is a 406-amino acid secreted glycoprotein that undergoes proteolytic cleavage into an N-terminal coiled-coil domain (responsible for LPL inhibition) and a C-terminal fibrinogen-like domain (involved in angiogenesis and cell adhesion). The protein is highly expressed in liver, adipose tissue, and placenta. It modulates lipid metabolism by inhibiting LPL, thereby reducing fatty acid uptake into tissues. ANGPTL4 also promotes angiogenesis via integrin-mediated signaling and is implicated in cancer progression and metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ANGPTL4 Knockout HEK293 Cell Line | EDJ-KQ10931 | Human | 51129 | Details Get a Quote |
| ANGPTL4 Knockout A-549 Cell Line | EDJ-KQ38711 | Human | 51129 | Details Get a Quote |
| ANGPTL4 Knockout HCT 116 Cell Line | EDJ-KQ38712 | Human | 51129 | Details Get a Quote |
| ANGPTL4 Knockout HeLa Cell Line | EDJ-KQ38713 | Human | 51129 | Details Get a Quote |
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