1. Gene Aliases

Apoa4, Apolipoprotein A4, Apolipoprotein A-IV, ApoA-IV

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=APOA4].

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

cholesterol efflux [The directed movement of cholesterol, cholest-5-en-3-beta-ol, out of a cell or organelle. GO:0033344]

cholesterol homeostasis [Any process involved in the maintenance of an internal steady state of cholesterol within an organism or cell. GO:0042632]

cholesterol metabolic process [The chemical reactions and pathways involving cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones. It is a component of the plasma membrane lipid bilayer and of plasma lipoproteins and can be found in all animal tissues. GO:0008203]

high-density lipoprotein particle remodeling [The acquisition, loss or modification of a protein or lipid within a high-density lipoprotein particle, including the hydrolysis of triglyceride by hepatic lipase, with the subsequent loss of free fatty acid, and the transfer of cholesterol esters from LDL to a triglyceride-rich lipoprotein particle by cholesteryl ester transfer protein (CETP), with the simultaneous transfer of triglyceride to LDL. GO:0034375]

hydrogen peroxide catabolic process [The chemical reactions and pathways resulting in the breakdown of hydrogen peroxide (H2O2). GO:0042744]

innate immune response in mucosa [Any process of the innate immune response that takes place in the mucosal tissues. GO:0002227]

intermembrane lipid transfer [The transport of lipids between membranes in which a lipid molecule is transported through an aqueous phase from the outer leaflet of a donor membrane to the outer leaflet of an acceptor membrane. This process does not require metabolic energy and can be either spontaneous or mediated by lipid transfer proteins (LTPs). GO:0120009]

leukocyte cell-cell adhesion [The attachment of a leukocyte to another cell via adhesion molecules. GO:0007159]

lipid catabolic process [The chemical reactions and pathways resulting in the breakdown of lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent. GO:0016042]

lipid homeostasis [Any process involved in the maintenance of an internal steady state of lipid within an organism or cell. GO:0055088]

lipid transport [The directed movement of lipids into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Lipids are compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent. GO:0006869]

lipoprotein metabolic process [The chemical reactions and pathways involving any conjugated, water-soluble protein in which the covalently attached nonprotein group consists of a lipid or lipids. GO:0042157]

negative regulation of plasma lipoprotein oxidation [Any process that stops, prevents, or reduces the frequency, rate or extent of lipoprotein particle oxidation, occurring in the blood plasma. GO:0034445]

peripheral nervous system axon regeneration [The regrowth of axons outside the central nervous system (outside the brain and spinal cord) following an axonal injury. GO:0014012]

phosphatidylcholine metabolic process [The chemical reactions and pathways involving phosphatidylcholines, any of a class of glycerophospholipids in which the phosphatidyl group is esterified to the hydroxyl group of choline. They are important constituents of cell membranes. GO:0046470]

phospholipid efflux [The directed movement of a phospholipid out of a cell or organelle. GO:0033700]

positive regulation of fatty acid biosynthetic process [Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of fatty acids. GO:0045723]

positive regulation of triglyceride catabolic process [Any process that increases the frequency, rate, or extent of the chemical reactions and pathways resulting in the breakdown of triglyceride. GO:0010898]

protein-lipid complex assembly [The aggregation, arrangement and bonding together of proteins and lipids to form a protein-lipid complex. GO:0065005]

regulation of cholesterol transport [Any process that modulates the frequency, rate or extent of the directed movement of cholesterol into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. GO:0032374]

regulation of intestinal cholesterol absorption [Any process that modulates the frequency, rate or extent of absorption of cholesterol into the blood, and the exclusion of other sterols from absorption. GO:0030300]

removal of superoxide radicals [Any process, acting at the cellular level, involved in removing superoxide radicals (O2-) from a cell or organism, e.g. by conversion to dioxygen (O2) and hydrogen peroxide (H2O2). GO:0019430]

response to food [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a food stimulus; food is anything which, when taken into the body, serves to nourish or build up the tissues or to supply body heat. GO:0032094]

response to lipid hydroperoxide [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipid hydroperoxide stimulus. Lipid hydroperoxide is the highly reactive primary oxygenated products of polyunsaturated fatty acids. GO:0006982]

response to stilbenoid [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of exposure to a stilbenoid. Stilbenoids are secondary products of heartwood formation in trees that can act as phytoalexins. Stilbenoids are hydroxylated derivatives of stilbene. They belong to the family of phenylpropanoids and share most of their biosynthesis pathway with chalcones. GO:0035634]

response to triglyceride [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a triglyceride stimulus. GO:0034014]

reverse cholesterol transport [The directed movement of peripheral cell cholesterol, cholest-5-en-3-beta-ol, towards the liver for catabolism. GO:0043691]

triglyceride homeostasis [Any process involved in the maintenance of an internal steady state of triglyceride within an organism or cell. GO:0070328]

very-low-density lipoprotein particle remodeling [The acquisition, loss or modification of a protein or lipid within a very-low-density lipoprotein particle, including the hydrolysis of triglyceride by hepatic lipase or lipoprotein lipase and the subsequent loss of free fatty acid. GO:0034372]

MSigDB Signatures:

WP_FATTY_ACIDS_AND_LIPOPROTEINS_TRANSPORT_IN_HEPATOCYTES: Fatty Acids and Lipoproteins Transport in Hepatocytes [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_FATTY_ACIDS_AND_LIPOPROTEINS_TRANSPORT_IN_HEPATOCYTES.html]

WP_CHOLESTEROL_METABOLISM: Cholesterol metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_CHOLESTEROL_METABOLISM.html]

REACTOME_CHYLOMICRON_ASSEMBLY: Chylomicron assembly [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CHYLOMICRON_ASSEMBLY.html]

REACTOME_METABOLISM_OF_FAT_SOLUBLE_VITAMINS: Metabolism of fat-soluble vitamins [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_METABOLISM_OF_FAT_SOLUBLE_VITAMINS.html]

REACTOME_CHYLOMICRON_REMODELING: Chylomicron remodeling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CHYLOMICRON_REMODELING.html]

REACTOME_METABOLISM_OF_VITAMINS_AND_COFACTORS: Metabolism of vitamins and cofactors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_METABOLISM_OF_VITAMINS_AND_COFACTORS.html]

REACTOME_PLASMA_LIPOPROTEIN_ASSEMBLY: Plasma lipoprotein assembly [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_PLASMA_LIPOPROTEIN_ASSEMBLY.html]

REACTOME_PLASMA_LIPOPROTEIN_ASSEMBLY_REMODELING_AND_CLEARANCE: Plasma lipoprotein assembly, remodeling, and clearance [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_PLASMA_LIPOPROTEIN_ASSEMBLY_REMODELING_AND_CLEARANCE.html]

WP_ENTEROCYTE_CHOLESTEROL_METABOLISM: Enterocyte cholesterol metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_ENTEROCYTE_CHOLESTEROL_METABOLISM.html]

WP_FAMILIAL_HYPERLIPIDEMIA_TYPE_1: Familial hyperlipidemia type 1 [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_FAMILIAL_HYPERLIPIDEMIA_TYPE_1.html]

WP_FAMILIAL_HYPERLIPIDEMIA_TYPE_2: Familial hyperlipidemia type 2 [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_FAMILIAL_HYPERLIPIDEMIA_TYPE_2.html]

WP_FAMILIAL_HYPERLIPIDEMIA_TYPE_5: Familial hyperlipidemia type 5 [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_FAMILIAL_HYPERLIPIDEMIA_TYPE_5.html]

REACTOME_TRANSPORT_OF_SMALL_MOLECULES: Transport of small molecules [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_TRANSPORT_OF_SMALL_MOLECULES.html]

WP_FAMILIAL_HYPERLIPIDEMIA_TYPE_3: Familial hyperlipidemia type 3 [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_FAMILIAL_HYPERLIPIDEMIA_TYPE_3.html]

REACTOME_PLASMA_LIPOPROTEIN_REMODELING: Plasma lipoprotein remodeling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_PLASMA_LIPOPROTEIN_REMODELING.html]

REACTOME_AMYLOID_FIBER_FORMATION: Amyloid fiber formation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_AMYLOID_FIBER_FORMATION.html]

WP_STATIN_INHIBITION_OF_CHOLESTEROL_PRODUCTION: Statin inhibition of cholesterol production [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_STATIN_INHIBITION_OF_CHOLESTEROL_PRODUCTION.html]

WP_FAMILIAL_HYPERLIPIDEMIA_TYPE_4: Familial hyperlipidemia type 4 [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_FAMILIAL_HYPERLIPIDEMIA_TYPE_4.html]

REACTOME_SENSORY_PERCEPTION: Sensory Perception [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SENSORY_PERCEPTION.html]

REACTOME_ASSEMBLY_OF_ACTIVE_LPL_AND_LIPC_LIPASE_COMPLEXES: Assembly of active LPL and LIPC lipase complexes [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ASSEMBLY_OF_ACTIVE_LPL_AND_LIPC_LIPASE_COMPLEXES.html]

REACTOME_VISUAL_PHOTOTRANSDUCTION: Visual phototransduction [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_VISUAL_PHOTOTRANSDUCTION.html]

7. Gene Descriptions

NCBI Gene Summary: Apoliprotein (apo) A-IV gene contains 3 exons separated by two introns. A sequence polymorphism has been identified in the 3'UTR of the third exon. The primary translation product is a 396-residue preprotein which after proteolytic processing is secreted its primary site of synthesis, the intestine, in association with chylomicron particles. Although its precise function is not known, apo A-IV is a potent activator of lecithin-cholesterol acyltransferase in vitro.

GeneCards Summary: APOA4 (Apolipoprotein A4) is a Protein Coding gene. Diseases associated with APOA4 include Familial Hyperlipidemia and Familial Hypercholesterolemia. Among its related pathways are Plasma lipoprotein assembly, remodeling, and clearance and Familial hyperlipidemia type 1. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and copper ion binding. An important paralog of this gene is APOA5

UniProtKB/Swiss-Prot Summary: May have a role in chylomicrons and VLDL secretion and catabolism. Required for efficient activation of lipoprotein lipase by ApoC-II; potent activator of LCAT. Apoa-IV is a major component of HDL and chylomicrons.

8. Cellular Location of Gene Product

High expression in small intestine and distinct positivity in plasma. Localized to vesicles. Predicted location: Secreted [https://www.proteinatlas.org/ENSG00000110244/subcellular]

9. Mechanistic Information

Summary

In liver diseases and toxicities, ApoA4 is upregulated as a response to disturbances in lipid metabolism and inflammatory stress [CS: 7]. Specifically, in conditions like hepatic steatosis where there's excess fat in the liver, ApoA4 helps by activating key enzymes like lipoprotein lipase [CS: 6] and lecithin-cholesterol acyltransferase [CS: 6], aiding in lipid breakdown and HDL formation [CS: 7]. This suggests its role in managing the lipid overload [CS: 8].

Moreover, in liver toxicity scenarios, such as with Bisphenol S exposure, ApoA4's increase is linked to its function in lipid metabolism, counteracting the buildup of hepatic triglycerides [CS: 5]. In inflammatory responses, like those triggered by bacterial endotoxins, ApoA4 interacts with nuclear receptors NR4A1 [CS: 6] and NR1D1 [CS: 6], influencing inflammatory gene expression [CS: 7]. This interaction indicates its role in moderating inflammation, aiming to protect the liver from further damage [CS: 8].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: intestine (tissue enriched) [https://www.proteinatlas.org/ENSG00000110244/tissue]

Cell type enchanced: proximal enterocytes (cell type enriched) [https://www.proteinatlas.org/ENSG00000110244/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: