APOA4: Apolipoprotein A4
A key regulator of lipid metabolism, satiety, and antioxidant defense
Gene Information Card
| Symbol | APOA4 |
|---|---|
| Full Name | Apolipoprotein A4 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q23.3 |
| NCBI Gene ID | 337 ncbi.nlm.nih.gov/gene/337 |
| Ensembl ID | ENSG00000110244 |
| UniProt ID | P06727 |
| OMIM ID | 107690 |
| HGNC ID | 602 |
| Aliases | apoA-IV, APOA-IV, Apo-AIV |
Description
APOA4 (Apolipoprotein A4) encodes a plasma apolipoprotein primarily synthesized in the small intestine during fat absorption. The protein is a component of chylomicrons and high-density lipoproteins (HDL), playing roles in lipid transport, satiety signaling, and antioxidant activity. It is also involved in glucose homeostasis and inflammation modulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiovascular disease | APOA4 modulates HDL metabolism and reverse cholesterol transport; variants may alter lipid profiles and atherosclerosis risk. | ClinVar, NCBI |
| Obesity | APOA4 acts as a satiety factor; reduced expression or function may impair appetite regulation. | OMIM, NCBI |
| Type 2 diabetes | APOA4 influences insulin sensitivity and glucose metabolism; polymorphisms associated with diabetes risk. | NCBI, ClinVar |
| Hypertriglyceridemia | APOA4 is a component of triglyceride-rich lipoproteins; mutations may affect lipid clearance. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small intestine | 128.2 | High |
| Liver | 3.5 | Low |
| Colon | 2.1 | Low |
| Stomach | 1.8 | Low |
| Pancreas | 0.6 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 | 15.2 | Intestinal epithelial cell line |
| HepG2 | 0.8 | Hepatocellular carcinoma cell line |
| HT-29 | 2.1 | Colorectal adenocarcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.127G>A (p.Glu43Lys) | Missense | 0.01% | Alters protein stability; associated with altered lipid levels |
| c.374C>T (p.Thr125Met) | Missense | 0.02% | May affect HDL binding; reported in hypertriglyceridemia |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of translation initiation; likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Start loss mutations (e.g., p.Met1Val) abolish protein production, impairing lipid transport and satiety signaling.
Gain of Function (GOF)
Not well documented; some missense variants may enhance antioxidant activity but evidence is limited.
Dominant Negative (DN)
No dominant-negative mutations reported for APOA4.
View complete mutation data：
Gene Ontology (GO)
| • lipid transporter activity (GO:0005319) | • cholesterol metabolic process (GO:0008203) |
| • cholesterol efflux (GO:0033344) | • lipoprotein metabolic process (GO:0042157) |
| • oxidation-reduction process (GO:0055114) | • extracellular space (GO:0005615) |
Pathways
• HDL-mediated lipid transport (Reactome: R-HSA-8963901)
• Chylomicron assembly and remodeling (Reactome: R-HSA-174800)
• Lipoprotein metabolism (KEGG: hsa04979)
Protein Summary
Apolipoprotein A4 (APOA4) is a 46 kDa protein (376 amino acids) secreted mainly by the small intestine. It circulates as a component of chylomicrons and HDL, facilitating lipid transport and reverse cholesterol transport. APOA4 also acts as a satiety factor in the brain, modulates glucose metabolism, and exhibits antioxidant properties by protecting against lipid peroxidation. Its expression is induced by fat ingestion and regulated by PPARα.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| APOA4 Knockout HEK293 Cell Line | EDJ-KQ4067 | Human | 337 | Details Get a Quote |
| APOA4 Knockout HeLa Cell Line | EDJ-KQ52631 | Human | 337 | Details Get a Quote |
| APOA4 Knockout A-549 Cell Line | EDJ-KQ61106 | Human | 337 | Details Get a Quote |
| APOA4 Knockout HCT 116 Cell Line | EDJ-KQ69592 | Human | 337 | Details Get a Quote |
