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 n... See more...

Aliases for APOA4 Gene

Aliases for APOA4 Gene

  • Apolipoprotein A4 2 3 4 5
  • Apolipoprotein A-IV 2 3 4
  • Apo-AIV 3 4
  • ApoA-IV 3 4

External Ids for APOA4 Gene

Previous GeneCards Identifiers for APOA4 Gene

  • GC11M119044
  • GC11M118203
  • GC11M116725
  • GC11M116229
  • GC22P9A0027
  • GC11M116198
  • GC11M116692
  • GC11M112623

Summaries for APOA4 Gene

Entrez Gene Summary for APOA4 Gene

  • 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. [provided by RefSeq, Jul 2008]

GeneCards Summary for APOA4 Gene

APOA4 (Apolipoprotein A4) is a Protein Coding gene. Diseases associated with APOA4 include Carotenemia and Familial Hypercholesterolemia. Among its related pathways are Lipoprotein metabolism and Cholesterol and Sphingolipids transport / Recycling to plasma membrane in lung (normal and CF). 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 for APOA4 Gene

  • 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.

Gene Wiki entry for APOA4 Gene

Additional gene information for APOA4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for APOA4 Gene

Genomics for APOA4 Gene

GeneHancer (GH) Regulatory Elements for APOA4 Gene

Promoters and enhancers for APOA4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around APOA4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for APOA4

Top Transcription factor binding sites by QIAGEN in the APOA4 gene promoter:
  • COUP
  • COUP-TF
  • COUP-TF1
  • HNF-4alpha1
  • HNF-4alpha2
  • PPAR-gamma1
  • PPAR-gamma2

Genomic Locations for APOA4 Gene

Genomic Locations for APOA4 Gene
chr11:116,820,700-116,823,304
(GRCh38/hg38)
Size:
2,605 bases
Orientation:
Minus strand
chr11:116,691,418-116,694,022
(GRCh37/hg19)
Size:
2,605 bases
Orientation:
Minus strand

Genomic View for APOA4 Gene

Genes around APOA4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
APOA4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for APOA4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for APOA4 Gene

Proteins for APOA4 Gene

  • Protein details for APOA4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P06727-APOA4_HUMAN
    Recommended name:
    Apolipoprotein A-IV
    Protein Accession:
    P06727
    Secondary Accessions:
    • A8MSL6
    • Q14CW8
    • Q6Q787

    Protein attributes for APOA4 Gene

    Size:
    396 amino acids
    Molecular mass:
    45399 Da
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for APOA4 Gene

neXtProt entry for APOA4 Gene

Post-translational modifications for APOA4 Gene

  • Phosphorylation sites are present in the extracellular medium.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for APOA4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for APOA4
  • Santa Cruz Biotechnology (SCBT) Antibodies for APOA4

No data available for DME Specific Peptides for APOA4 Gene

Domains & Families for APOA4 Gene

Gene Families for APOA4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Candidate cardiovascular disease genes
  • Plasma proteins
  • Predicted secreted proteins

Protein Domains for APOA4 Gene

Blocks:
  • Apolipoprotein A1/A4/E
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for APOA4 Gene

GenScript: Design optimal peptide antigens:
  • Apolipoprotein A4 (APOA4_HUMAN)
  • APOA4 protein (Q13784_HUMAN)
  • Apolipoprotein A-IV (Q15969_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P06727

UniProtKB/Swiss-Prot:

APOA4_HUMAN :
  • Nine of the thirteen 22-amino acid tandem repeats (each 22-mer is actually a tandem array of two, A and B, related 11-mers) occurring in this sequence are predicted to be highly alpha-helical, and many of these helices are amphipathic. They may therefore serve as lipid-binding domains with lecithin:cholesterol acyltransferase (LCAT) activating abilities.
  • Belongs to the apolipoprotein A1/A4/E family.
Domain:
  • Nine of the thirteen 22-amino acid tandem repeats (each 22-mer is actually a tandem array of two, A and B, related 11-mers) occurring in this sequence are predicted to be highly alpha-helical, and many of these helices are amphipathic. They may therefore serve as lipid-binding domains with lecithin:cholesterol acyltransferase (LCAT) activating abilities.
Family:
  • Belongs to the apolipoprotein A1/A4/E family.
genes like me logo Genes that share domains with APOA4: view

Function for APOA4 Gene

Molecular function for APOA4 Gene

UniProtKB/Swiss-Prot Function:
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.
GENATLAS Biochemistry:
apolipoprotein A-IV,major component of HDL and chylomicrons,involved in the catabolism of chylomicrons and VLDL

Phenotypes From GWAS Catalog for APOA4 Gene

Gene Ontology (GO) - Molecular Function for APOA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005319 lipid transporter activity TAS 3080432
GO:0005507 copper ion binding IDA 16945374
GO:0005515 protein binding IPI 24311788
GO:0005543 phospholipid binding IBA 21873635
GO:0008289 lipid binding IMP 16159879
genes like me logo Genes that share ontologies with APOA4: view
genes like me logo Genes that share phenotypes with APOA4: view

Animal Models for APOA4 Gene

MGI Knock Outs for APOA4:

Animal Model Products

  • Taconic Biosciences Mouse Models for APOA4

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for APOA4

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for APOA4 Gene

Localization for APOA4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for APOA4 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for APOA4 gene
Compartment Confidence
extracellular 5
cytosol 5
endoplasmic reticulum 4
endosome 4
cytoskeleton 3
plasma membrane 2
mitochondrion 2
peroxisome 2
nucleus 2
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for APOA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region HDA,TAS --
GO:0005615 extracellular space IDA,IEA 1935934
GO:0005769 early endosome TAS --
GO:0005788 endoplasmic reticulum lumen TAS --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with APOA4: view

Pathways & Interactions for APOA4 Gene

genes like me logo Genes that share pathways with APOA4: view

Pathways by source for APOA4 Gene

1 GeneGo (Thomson Reuters) pathway for APOA4 Gene
  • Cholesterol and Sphingolipids transport / Recycling to plasma membrane in lung (normal and CF)
1 Cell Signaling Technology pathway for APOA4 Gene

Gene Ontology (GO) - Biological Process for APOA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001523 retinoid metabolic process TAS --
GO:0002227 innate immune response in mucosa IDA 15254593
GO:0006695 cholesterol biosynthetic process IBA 21873635
GO:0006869 lipid transport IDA 1935934
GO:0006982 response to lipid hydroperoxide IDA 16945374
genes like me logo Genes that share ontologies with APOA4: view

No data available for SIGNOR curated interactions for APOA4 Gene

Drugs & Compounds for APOA4 Gene

(16) Drugs for APOA4 Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Copper Approved, Investigational Pharma Target 236
Zinc Approved, Investigational Pharma Target 2822
zinc acetate Approved, Investigational Pharma Target 0
Zinc chloride Approved, Investigational Pharma Target 0

(17) Additional Compounds for APOA4 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Triglycerides Group B
  • 1-Myristoyl-2-pentadecanoyl-3-g-linolenoyl-glycerol
  • 1-Tetradecanoyl-2-pentadecanoyl-3-(6Z,9Z,12Z-octadecatrienoyl)-glycerol
  • TAG(14:0/15:0/18:3)
  • TAG(47:3)
  • TG(14:0/15:0/18:3)
555-45-3, 30719-27-8, 2190-24-1, 18641-57-1, 56933-26-7
Triglycerides Group C
  • 2,3-Di(octadecanoyloxy)propyl octadecanoate
  • Glyceryl tristearate
  • Stearic acid triglycerin ester
  • Stearin
  • Trioctadecanoin
620-64-4
genes like me logo Genes that share compounds with APOA4: view

Transcripts for APOA4 Gene

mRNA/cDNA for APOA4 Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for APOA4

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for APOA4 Gene

No ASD Table

Relevant External Links for APOA4 Gene

GeneLoc Exon Structure for
APOA4

Expression for APOA4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for APOA4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for APOA4 Gene

This gene is overexpressed in Small Intestine - Terminal Ileum (x37.5) and Liver (x15.0).

Protein differential expression in normal tissues from HIPED for APOA4 Gene

This gene is overexpressed in Serum (28.2), Synovial fluid (13.5), and Plasma (12.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for APOA4 Gene



Protein tissue co-expression partners for APOA4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for APOA4

SOURCE GeneReport for Unigene cluster for APOA4 Gene:

Hs.1247

mRNA Expression by UniProt/SwissProt for APOA4 Gene:

P06727-APOA4_HUMAN
Tissue specificity: Synthesized primarily in the intestine and secreted in plasma.

Evidence on tissue expression from TISSUES for APOA4 Gene

  • Liver(4.7)
  • Intestine(4.6)
  • Nervous system(4.4)
  • Blood(2.5)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with APOA4: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for APOA4 Gene

Orthologs for APOA4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for APOA4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia APOA4 31 30
  • 99.07 (n)
OneToOne
dog
(Canis familiaris)
Mammalia APOA4 31 30
  • 86.12 (n)
OneToOne
cow
(Bos Taurus)
Mammalia APOA4 31 30
  • 84.51 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Apoa4 17 31 30
  • 75.2 (n)
rat
(Rattus norvegicus)
Mammalia Apoa4 30
  • 74.84 (n)
oppossum
(Monodelphis domestica)
Mammalia APOA4 31
  • 50 (a)
OneToOne
chicken
(Gallus gallus)
Aves APOA4 30
  • 65.75 (n)
APOAIV 31
  • 50 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia APOA4 31
  • 49 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia apoa4 30
  • 54.21 (n)
zebrafish
(Danio rerio)
Actinopterygii si:dkey-7f3.15 30
  • 51.29 (n)
apoa4 31
  • 31 (a)
OneToMany
APOA4 (4 of 4) 31
  • 31 (a)
OneToMany
APOA4 (1 of 4) 31
  • 30 (a)
OneToMany
APOA4 (3 of 4) 31
  • 29 (a)
OneToMany
Species where no ortholog for APOA4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for APOA4 Gene

ENSEMBL:
Gene Tree for APOA4 (if available)
TreeFam:
Gene Tree for APOA4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for APOA4: view image

Paralogs for APOA4 Gene

Paralogs for APOA4 Gene

genes like me logo Genes that share paralogs with APOA4: view

Variants for APOA4 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for APOA4 Gene

APOA4_HUMAN-P06727
Eight alleles have been characterized (APOA-IV*0 to APOA-IV*7). APOA-IV*1 is the major allele (90%), APOA-IV*2 is also common (8%), the others are rare alleles. The sequence shown represents allele APOA-IV*1.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for APOA4 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
rs121909576 Other: APOLIPOPROTEIN A-IV RARE VARIANT, APOA4*3. - 116,821,310(-) C/Tp.Glu250Lys MISSENSE_VARIANT
rs5110 Pathogenic: APOLIPOPROTEIN A-IV POLYMORPHISM, APOA4*1/APOA4*2. - 116,820,918(-) C/Ap.Gln380His MISSENSE_VARIANT
rs1042372 - p.Arg279Lys
rs1181852696 - p.Ser178Leu
rs12721041 - p.Val13Met

Additional dbSNP identifiers (rs#s) for APOA4 Gene

Variation tolerance for APOA4 Gene

Residual Variation Intolerance Score: 85.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.39; 54.15% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for APOA4 Gene

Human Gene Mutation Database (HGMD)
APOA4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
APOA4

SNP Genotyping and Copy Number Assay Products

No data available for Structural Variations from Database of Genomic Variants (DGV) for APOA4 Gene

Disorders for APOA4 Gene

MalaCards: The human disease database

(15) MalaCards diseases for APOA4 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
carotenemia
  • hypercarotinemia
familial hypercholesterolemia
  • hyperlipoproteinemia, type ii
amyloidosis, familial visceral
  • amyloidosis viii
demyelinating polyneuropathy
  • peripheral demyelinating neuropathy
hyperlipidemia, familial combined, 3
  • fchl3
- elite association - COSMIC cancer census association via MalaCards
Search APOA4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for APOA4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with APOA4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for APOA4 Gene

Publications for APOA4 Gene

  1. Nonsynonymous polymorphic sites in the apolipoprotein (apo) A-IV gene are associated with changes in the concentration of apo B- and apo A-I-containing lipoproteins in a normal population. (PMID: 1349197) von Eckardstein A … Assmann G (American journal of human genetics 1992) 3 4 23 41 54
  2. Distribution and effect of apo A-IV genotype on plasma lipid and apolipoprotein levels in a Chinese population. (PMID: 18664021) Bai H … Liu BW (Acta cardiologica 2008) 3 23 41 54
  3. Genetic and environmental factors affecting the response to statin therapy in patients with molecularly defined familial hypercholesterolaemia. (PMID: 15864114) Miltiadous G … Elisaf M (Pharmacogenetics and genomics 2005) 3 23 41 54
  4. Population genetics of apolipoproteins A-IV, E, and H, and the angiotensin converting enzyme (ACE): associations with lipids, and apolipoprotein levels in American Samoans. (PMID: 15252864) Crews DE … Kamboh MI (American journal of physical anthropology 2004) 3 23 41 54
  5. The APOA4 T347S variant is associated with reduced plasma TAOS in subjects with diabetes mellitus and cardiovascular disease. (PMID: 15175360) Wong WM … Talmud PJ (Journal of lipid research 2004) 3 23 41 54

Products for APOA4 Gene

Sources for APOA4 Gene