This gene encodes a glycosylated, secreted protein containing a C-terminal fibrinogen domain. The encoded protein is induced by peroxisome proliferation activators and functions as a serum hormone that regulates glucose homeostasis, lipid metabolism, and insulin sensitivity. This protein can also act as an apoptosis survival factor for vascular endothelial cells and can prevent... See more...

Aliases for ANGPTL4 Gene

Aliases for ANGPTL4 Gene

  • Angiopoietin Like 4 2 3 5
  • Hepatic Fibrinogen/Angiopoietin-Related Protein 2 3 4
  • Angiopoietin-Related Protein 4 2 3 4
  • Peroxisome Proliferator-Activated Receptor (PPAR) Gamma Induced Angiopoietin-Related Protein 2 3
  • Hepatic Angiopoietin-Related Protein 2 3
  • PPARG Angiopoietin Related Protein 2 3
  • Fasting-Induced Adipose Factor 2 3
  • HFARP 3 4
  • ARP4 3 4
  • PGAR 3 4
  • Angiopoietin-Like Protein 4 4
  • Angiopoietin-Like 4 2
  • UNQ171 3
  • Pp1158 3
  • TGQTL 3
  • FIAF 3
  • HARP 3
  • NL2 3

External Ids for ANGPTL4 Gene

Previous GeneCards Identifiers for ANGPTL4 Gene

  • GC19P008372
  • GC19P008643
  • GC19P008324
  • GC19P008335
  • GC19P008429
  • GC19P008082

Summaries for ANGPTL4 Gene

Entrez Gene Summary for ANGPTL4 Gene

  • This gene encodes a glycosylated, secreted protein containing a C-terminal fibrinogen domain. The encoded protein is induced by peroxisome proliferation activators and functions as a serum hormone that regulates glucose homeostasis, lipid metabolism, and insulin sensitivity. This protein can also act as an apoptosis survival factor for vascular endothelial cells and can prevent metastasis by inhibiting vascular growth and tumor cell invasion. The C-terminal domain may be proteolytically-cleaved from the full-length secreted protein. Decreased expression of this gene has been associated with type 2 diabetes. Alternative splicing results in multiple transcript variants. This gene was previously referred to as ANGPTL2 but has been renamed ANGPTL4. [provided by RefSeq, Sep 2013]

GeneCards Summary for ANGPTL4 Gene

ANGPTL4 (Angiopoietin Like 4) is a Protein Coding gene. Diseases associated with ANGPTL4 include Plasma Triglyceride Level Quantitative Trait Locus and Gastric Antral Vascular Ectasia. Among its related pathways are Lipoprotein metabolism and Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha). Gene Ontology (GO) annotations related to this gene include enzyme inhibitor activity. An important paralog of this gene is ANGPTL3.

UniProtKB/Swiss-Prot Summary for ANGPTL4 Gene

  • Mediates inactivation of the lipoprotein lipase LPL, and thereby plays a role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism (PubMed:19270337, PubMed:21398697, PubMed:27929370, PubMed:29899144). May also play a role in regulating glucose homeostasis and insulin sensitivity (Probable). Inhibits proliferation, migration, and tubule formation of endothelial cells and reduces vascular leakage (PubMed:14583458, PubMed:17068295). Upon heterologous expression, inhibits the adhesion of endothelial cell to the extracellular matrix (ECM), and inhibits the reorganization of the actin cytoskeleton, formation of actin stress fibers and focal adhesions in endothelial cells that have adhered to ANGPTL4-containing ECM (in vitro) (PubMed:17068295). Depending on context, may modulate tumor-related angiogenesis (By similarity).
  • [ANGPTL4 N-terminal chain]: Mediates inactivation of the lipoprotein lipase LPL, and thereby plays an important role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism (PubMed:19270337, PubMed:21398697, PubMed:27929370, PubMed:29899144). Has higher activity in LPL inactivation than the uncleaved protein (PubMed:19270337, PubMed:21398697).

Gene Wiki entry for ANGPTL4 Gene

Additional gene information for ANGPTL4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ANGPTL4 Gene

Genomics for ANGPTL4 Gene

GeneHancer (GH) Regulatory Elements for ANGPTL4 Gene

Promoters and enhancers for ANGPTL4 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 ANGPTL4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ANGPTL4

Top Transcription factor binding sites by QIAGEN in the ANGPTL4 gene promoter:
  • PPAR-gamma1
  • PPAR-gamma2

Genomic Locations for ANGPTL4 Gene

Genomic Locations for ANGPTL4 Gene
chr19:8,363,289-8,374,375
(GRCh38/hg38)
Size:
11,087 bases
Orientation:
Plus strand
chr19:8,428,173-8,439,257
(GRCh37/hg19)
Size:
11,085 bases
Orientation:
Plus strand

Genomic View for ANGPTL4 Gene

Genes around ANGPTL4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ANGPTL4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ANGPTL4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ANGPTL4 Gene

Proteins for ANGPTL4 Gene

  • Protein details for ANGPTL4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BY76-ANGL4_HUMAN
    Recommended name:
    Angiopoietin-related protein 4
    Protein Accession:
    Q9BY76
    Secondary Accessions:
    • A8MY84
    • B4E089
    • D6W670
    • F5H0I2
    • Q53HQ6
    • Q53HU1
    • Q6UXN0
    • Q9HBV4
    • Q9NZU4
    • Q9Y5B3

    Protein attributes for ANGPTL4 Gene

    Size:
    406 amino acids
    Molecular mass:
    45214 Da
    Quaternary structure:
    • Homooligomer; disulfide-linked via Cys residues in the N-terminal part of the protein (PubMed:19270337). The homooligomer undergoes proteolytic processing to release the ANGPTL4 C-terminal chain, which circulates as a monomer (PubMed:19270337). The homooligomer unprocessed form is able to interact with the extracellular matrix (PubMed:21398697).
    SequenceCaution:
    • Sequence=AAQ88642.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ANGPTL4 Gene

    Alternative splice isoforms for ANGPTL4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ANGPTL4 Gene

Post-translational modifications for ANGPTL4 Gene

  • N-glycosylated.
  • [ANGPTL4 N-terminal chain]: Forms disulfide-linked dimers and tetramers.
  • Cleaved into a smaller N-terminal chain and a larger chain that contains the fibrinogen C-terminal domain; both cleaved and uncleaved forms are detected in the extracellular space. The cleaved form is not present within the cell.
  • Glycosylation at Asn177
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • ANGL4_HUMAN (1918)

No data available for DME Specific Peptides for ANGPTL4 Gene

Domains & Families for ANGPTL4 Gene

Gene Families for ANGPTL4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for ANGPTL4 Gene

Blocks:
  • Fibrinogen, beta/gamma chain, C-terminal globular
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for ANGPTL4 Gene

GenScript: Design optimal peptide antigens:
  • Hepatic fibrinogen/angiopoietin-related protein (ANGL4_HUMAN)
genes like me logo Genes that share domains with ANGPTL4: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for ANGPTL4 Gene

Function for ANGPTL4 Gene

Molecular function for ANGPTL4 Gene

UniProtKB/Swiss-Prot Function:
Mediates inactivation of the lipoprotein lipase LPL, and thereby plays a role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism (PubMed:19270337, PubMed:21398697, PubMed:27929370, PubMed:29899144). May also play a role in regulating glucose homeostasis and insulin sensitivity (Probable). Inhibits proliferation, migration, and tubule formation of endothelial cells and reduces vascular leakage (PubMed:14583458, PubMed:17068295). Upon heterologous expression, inhibits the adhesion of endothelial cell to the extracellular matrix (ECM), and inhibits the reorganization of the actin cytoskeleton, formation of actin stress fibers and focal adhesions in endothelial cells that have adhered to ANGPTL4-containing ECM (in vitro) (PubMed:17068295). Depending on context, may modulate tumor-related angiogenesis (By similarity).
UniProtKB/Swiss-Prot Function:
[ANGPTL4 N-terminal chain]: Mediates inactivation of the lipoprotein lipase LPL, and thereby plays an important role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism (PubMed:19270337, PubMed:21398697, PubMed:27929370, PubMed:29899144). Has higher activity in LPL inactivation than the uncleaved protein (PubMed:19270337, PubMed:21398697).
UniProtKB/Swiss-Prot Induction:
Up-regulated when cells are exposed to severe hypoxia (in vitro).

Phenotypes From GWAS Catalog for ANGPTL4 Gene

Gene Ontology (GO) - Molecular Function for ANGPTL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004857 enzyme inhibitor activity ISS --
GO:0005515 protein binding IPI 21397862
GO:0042802 identical protein binding IPI 19028676
genes like me logo Genes that share ontologies with ANGPTL4: view
genes like me logo Genes that share phenotypes with ANGPTL4: view

Human Phenotype Ontology for ANGPTL4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ANGPTL4 Gene

MGI Knock Outs for ANGPTL4:

Animal Model Products

  • Taconic Biosciences Mouse Models for ANGPTL4

miRNA for ANGPTL4 Gene

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for ANGPTL4 Gene

Localization for ANGPTL4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ANGPTL4 Gene

Secreted. Secreted, extracellular space, extracellular matrix. Note=The unprocessed form interacts with the extracellular matrix (PubMed:17068295, PubMed:21398697). This may constitute a dynamic reservoir, a regulatory mechanism of the bioavailability of ANGPTL4 (Probable). {ECO:0000269 PubMed:17068295, ECO:0000269 PubMed:21398697, ECO:0000305 PubMed:17068295}.

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 ANGPTL4 gene
Compartment Confidence
extracellular 5
plasma membrane 2
cytoskeleton 2
mitochondrion 2
peroxisome 2
nucleus 2
endoplasmic reticulum 2
cytosol 2
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ANGPTL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IDA,IEA 10698685
GO:0072562 blood microparticle HDA 22516433
genes like me logo Genes that share ontologies with ANGPTL4: view

Pathways & Interactions for ANGPTL4 Gene

genes like me logo Genes that share pathways with ANGPTL4: view

Gene Ontology (GO) - Biological Process for ANGPTL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis IEA --
GO:0001666 response to hypoxia NAS 12707035
GO:0006629 lipid metabolic process IEA --
GO:0019216 regulation of lipid metabolic process TAS --
GO:0043066 negative regulation of apoptotic process IEA,IDA 10698685
genes like me logo Genes that share ontologies with ANGPTL4: view

No data available for SIGNOR curated interactions for ANGPTL4 Gene

Drugs & Compounds for ANGPTL4 Gene

(7) Drugs for ANGPTL4 Gene - From: ClinicalTrials and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Inulin Approved, Investigational Nutra 169
Acidophilus Pharma 788
Bifidobacterium Pharma 371

(5) Additional Compounds for ANGPTL4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with ANGPTL4: view

Transcripts for ANGPTL4 Gene

mRNA/cDNA for ANGPTL4 Gene

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

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ANGPTL4 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8 ^ 9
SP1: -
SP2: -
SP3: - -
SP4: -

Relevant External Links for ANGPTL4 Gene

GeneLoc Exon Structure for
ANGPTL4

Expression for ANGPTL4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ANGPTL4 Gene

mRNA differential expression in normal tissues according to GTEx for ANGPTL4 Gene

This gene is overexpressed in Adipose - Subcutaneous (x5.1), Liver (x4.8), and Adipose - Visceral (Omentum) (x4.4).

Protein differential expression in normal tissues from HIPED for ANGPTL4 Gene

This gene is overexpressed in Islet of Langerhans (20.9), Milk (18.4), and Bone marrow mesenchymal stem cell (18.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for ANGPTL4 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ANGPTL4

SOURCE GeneReport for Unigene cluster for ANGPTL4 Gene:

Hs.9613

mRNA Expression by UniProt/SwissProt for ANGPTL4 Gene:

Q9BY76-ANGL4_HUMAN
Tissue specificity: Detected in blood plasma (at protein level) (PubMed:29899519). Detected in liver (PubMed:10698685). Detected in white fat tissue and placenta (PubMed:10866690). Expressed at high levels in the placenta, heart, liver, muscle, pancreas and lung but expressed poorly in the brain and kidney.

Evidence on tissue expression from TISSUES for ANGPTL4 Gene

  • Pancreas(4.4)
  • Skin(4.4)
  • Nervous system(3.1)
  • Liver(2.8)
  • Heart(2.1)
  • Intestine(2.1)
genes like me logo Genes that share expression patterns with ANGPTL4: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for ANGPTL4 Gene

Orthologs for ANGPTL4 Gene

This gene was present in the common ancestor of animals.

Orthologs for ANGPTL4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ANGPTL4 31 30
  • 99.12 (n)
OneToOne
cow
(Bos Taurus)
Mammalia ANGPTL4 31 30
  • 83.25 (n)
OneToOne
dog
(Canis familiaris)
Mammalia ANGPTL4 31 30
  • 82.7 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Angptl4 17 31 30
  • 77.7 (n)
rat
(Rattus norvegicus)
Mammalia Angptl4 30
  • 77.12 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia ANGPTL4 31
  • 59 (a)
OneToOne
chicken
(Gallus gallus)
Aves ANGPTL4 31 30
  • 58.66 (n)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia angptl4 30
  • 51.86 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.10669 30
zebrafish
(Danio rerio)
Actinopterygii angptl4 31 30
  • 55.06 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta sca 32
  • 31 (a)
CG7668 31
  • 21 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea T15B7.1 31
  • 22 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 42 (a)
OneToMany
Species where no ortholog for ANGPTL4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • 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)

Evolution for ANGPTL4 Gene

ENSEMBL:
Gene Tree for ANGPTL4 (if available)
TreeFam:
Gene Tree for ANGPTL4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ANGPTL4: view image

Paralogs for ANGPTL4 Gene

(13) SIMAP similar genes for ANGPTL4 Gene using alignment to 7 proteins:

  • ANGL4_HUMAN
  • F5H0I2_HUMAN
  • M0QZ51_HUMAN
  • M0R0N8_HUMAN
  • M0R2X8_HUMAN
  • M0R369_HUMAN
  • M0R3A2_HUMAN
genes like me logo Genes that share paralogs with ANGPTL4: view

Variants for ANGPTL4 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for ANGPTL4 Gene

ANGL4_HUMAN-Q9BY76
Genetic variations in ANGPTL4 are associated with low plasma triglyceride levels and define the plasma triglyceride level quantitative trait locus (TGQTL) [MIM:615881].

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ANGPTL4 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
730728 Benign: not provided 8,369,213(+) C/T INTRON_VARIANT
744498 Likely Benign: not provided 8,364,441(+) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
768962 Benign: not provided 8,371,316(+) G/A MISSENSE_VARIANT
783818 Benign: not provided 8,366,196(+) TC/T INTRON_VARIANT
783819 Benign: not provided 8,369,216(+) C/T INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for ANGPTL4 Gene

Structural Variations from Database of Genomic Variants (DGV) for ANGPTL4 Gene

Variant ID Type Subtype PubMed ID
esv3643614 CNV gain 21293372
esv3643616 CNV gain 21293372

Variation tolerance for ANGPTL4 Gene

Residual Variation Intolerance Score: 65.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.86; 79.38% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ANGPTL4 Gene

Human Gene Mutation Database (HGMD)
ANGPTL4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ANGPTL4

Disorders for ANGPTL4 Gene

MalaCards: The human disease database

(8) MalaCards diseases for ANGPTL4 Gene - From: OMIM, GTR, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
plasma triglyceride level quantitative trait locus
  • tgqtl
gastric antral vascular ectasia
  • watermelon stomach
endometrial clear cell adenocarcinoma
  • clear cell carcinoma of endometrium
hypobetalipoproteinemia, familial, 2
  • fhbl2
familial lipoprotein lipase deficiency
  • lipoprotein lipase deficiency
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for ANGPTL4

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 ANGPTL4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ANGPTL4 Gene

Publications for ANGPTL4 Gene

  1. Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation. (PMID: 10866690) Yoon JC … Spiegelman BM (Molecular and cellular biology 2000) 2 3 4 23 54
  2. Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis. (PMID: 10698685) Kim I … Koh GY (The Biochemical journal 2000) 2 3 4 23 54
  3. Extracellular matrix-bound angiopoietin-like 4 inhibits endothelial cell adhesion, migration, and sprouting and alters actin cytoskeleton. (PMID: 17068295) Cazes A … Monnot C (Circulation research 2006) 3 4 23 54
  4. [Cloning of a novel gene, ANGPTL4 and the functional study in angiogenesis]. (PMID: 11953136) Zhu H … Gu J (Zhonghua yi xue za zhi 2002) 3 4 23 54
  5. Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease. (PMID: 29713054) Biterova E … Ruddock LW (Scientific reports 2018) 3 4 54

Products for ANGPTL4 Gene

Sources for ANGPTL4 Gene