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    ANGPTL4 angiopoietin like 4 [ Homo sapiens (human) ]

    Gene ID: 51129, updated on 2-Nov-2024

    Summary

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    Official Symbol
    ANGPTL4provided by HGNC
    Official Full Name
    angiopoietin like 4provided by HGNC
    Primary source
    HGNC:HGNC:16039
    See related
    Ensembl:ENSG00000167772 MIM:605910; AllianceGenome:HGNC:16039
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    NL2; ARP4; FIAF; HARP; PGAR; HFARP; TGQTL; UNQ171; pp1158
    Summary
    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]
    Expression
    Broad expression in liver (RPKM 42.4), fat (RPKM 23.7) and 17 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ANGPTL4 in Genome Data Viewer
    Location:
    19p13.2
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (8364155..8374370)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (8350623..8360841)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (8429039..8439254)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:8387283-8388248 Neighboring gene ribosomal protein S28 Neighboring gene KN motif and ankyrin repeat domains 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10016 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10017 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10018 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10019 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:8405154-8405654 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:8407589-8408380 Neighboring gene ribosomal protein L17 pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13913 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13914 Neighboring gene RAB11B antisense RNA 1 Neighboring gene uncharacterized LOC124904632 Neighboring gene microRNA 4999

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Fatty acids and hypoxia stimulate the expression and secretion of the adipokine ANGPTL4 (angiopoietin-like protein 4/ fasting-induced adipose factor) by human adipocytes. González-Muniesa P, et al. J Nutrigenet Nutrigenomics, 2011. PMID 21709421
    2. Serum angiopoietin-like 4 protein levels and expression in adipose tissue are inversely correlated with obesity in monozygotic twins. Robciuc MR, et al. J Lipid Res, 2011 Aug. PMID 21596930, Free PMC Article
    3. The association of angiopoietin-like peptide 4 levels with obesity and hepatosteatosis in adolescents. Dikker O, et al. Cytokine, 2020 Jan. PMID 31419758
    4. Knockdown of ANGPTL-4 inhibits inflammatory response and extracellular matrix accumulation in glomerular mesangial cells cultured under high glucose condition. Qin L, et al. Artif Cells Nanomed Biotechnol, 2019 Dec. PMID 31387395
    5. Beyond Rare-Variant Association Testing: Pinpointing Rare Causal Variants in Case-Control Sequencing Study. Lin WY. Sci Rep, 2016 Feb 23. PMID 26903168, Free PMC Article

    See all (288) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. ANGPTL4 plays a paradoxical role in gastric cancer through the LGALS7 and Hedgehog pathways.
      Title: ANGPTL4 plays a paradoxical role in gastric cancer through the LGALS7 and Hedgehog pathways.
    2. ANGPTL4 Suppresses Clear Cell Renal Cell Carcinoma via Inhibition of Lysosomal Acid Lipase.
      Title: ANGPTL4 Suppresses Clear Cell Renal Cell Carcinoma via Inhibition of Lysosomal Acid Lipase.
    3. Impact of loss-of-function in angiopoietin-like 4 on the human phenome.
      Title: Impact of loss-of-function in angiopoietin-like 4 on the human phenome.
    4. Renal lipid accumulation and aging linked to tubular cells injury via ANGPTL4.
      Title: Renal lipid accumulation and aging linked to tubular cells injury via ANGPTL4.
    5. Characterization of sexual dimorphism in ANGPTL4 levels and function.
      Title: Characterization of sexual dimorphism in ANGPTL4 levels and function.
    6. Attenuating Epithelial-to-Mesenchymal Transition in Cancer through Angiopoietin-Like 4 Inhibition in a 3D Tumor Microenvironment Model.
      Title: Attenuating Epithelial-to-Mesenchymal Transition in Cancer through Angiopoietin-Like 4 Inhibition in a 3D Tumor Microenvironment Model.
    7. T266M variants of ANGPTL4 improve lipid metabolism by modifying their binding affinity to acetyl-CoA carboxylase in obstructive sleep apnea.
      Title: T266M variants of ANGPTL4 improve lipid metabolism by modifying their binding affinity to acetyl-CoA carboxylase in obstructive sleep apnea.
    8. Correlation between the serum FABP4, ANGPTL3, and ANGPTL4 levels and coronary artery disease.
      Title: Correlation between the serum FABP4, ANGPTL3, and ANGPTL4 levels and coronary artery disease.
    9. Correlation of serum VEGF-C, ANGPTL4, and activin A levels with frailty.
      Title: Correlation of serum VEGF-C, ANGPTL4, and activin A levels with frailty.
    10. Serum ANGPTL4 and SIRT1 factor levels and the Carotid Atherosclerotic plaque stability relationship analysis.
      Title: Serum ANGPTL4 and SIRT1 factor levels and the Carotid Atherosclerotic plaque stability relationship analysis.
    Submit: New GeneRIF Correction See all GeneRIFs (238)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Plasma triglyceride level quantitative trait locus
    MedGen: C4014553 OMIM: 615881 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Biological, clinical and population relevance of 95 loci for blood lipids.
    EBI GWAS Catalog
    Common variants at 30 loci contribute to polygenic dyslipidemia.
    EBI GWAS Catalog
    Discovery and refinement of loci associated with lipid levels.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables enzyme inhibitor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables enzyme inhibitor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in angiogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in endothelial cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in lipid metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of endothelial cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of lipoprotein lipase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of angiogenesis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in protein unfolding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to hypoxia NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in triglyceride homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in triglyceride homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in blood microparticle HDA PubMed 
    is_active_in collagen-containing extracellular matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular region IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    angiopoietin-related protein 4
    Names
    PPARG angiopoietin related protein
    fasting-induced adipose factor
    hepatic angiopoietin-related protein
    hepatic fibrinogen/angiopoietin-related protein
    peroxisome proliferator-activated receptor (PPAR) gamma induced angiopoietin-related protein

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012169.1 RefSeqGene

      Range
      5029..15244
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001039667.3 → NP_001034756.1  angiopoietin-related protein 4 isoform b precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The encoded isoform (b) is shorter than isoform a.
      Source sequence(s)
      AF202636, BP397348
      Consensus CDS
      CCDS42493.1
      UniProtKB/Swiss-Prot
      Q9BY76
      Related
      ENSP00000377534.1, ENST00000393962.6
      Conserved Domains (1) summary
      cd00087
      Location:184 → 362
      FReD; Fibrinogen-related domains (FReDs); C terminal globular domain of fibrinogen. Fibrinogen is involved in blood clotting, being activated by thrombin to assemble into fibrin clots. The N-termini of 2 times 3 chains come together to form a globular ...

    2. NM_139314.3 → NP_647475.1  angiopoietin-related protein 4 isoform a precursor

      See identical proteins and their annotated locations for NP_647475.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).
      Source sequence(s)
      AF202636, BP397348
      Consensus CDS
      CCDS12200.1
      UniProtKB/Swiss-Prot
      A8MY84, B4E089, D6W670, F5H0I2, Q53HQ6, Q53HU1, Q6UXN0, Q9BY76, Q9HBV4, Q9NZU4, Q9Y5B3
      Related
      ENSP00000301455.1, ENST00000301455.7
      Conserved Domains (1) summary
      cd00087
      Location:183 → 400
      FReD; Fibrinogen-related domains (FReDs); C terminal globular domain of fibrinogen. Fibrinogen is involved in blood clotting, being activated by thrombin to assemble into fibrin clots. The N-termini of 2 times 3 chains come together to form a globular ...

    RNA

    1. NR_104213.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks four internal exons and uses an alternate splice site in the 3' exon, compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region found in variant 1.
      Source sequence(s)
      AC136469

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      8364155..8374370
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005272484.4 → XP_005272541.1  angiopoietin-related protein 4 isoform X1

      Conserved Domains (1) summary
      cd00087
      Location:183 → 418
      FReD; Fibrinogen-related domains (FReDs); C terminal globular domain of fibrinogen. Fibrinogen is involved in blood clotting, being activated by thrombin to assemble into fibrin clots. The N-termini of 2 times 3 chains come together to form a globular ...

    2. XM_005272485.4 → XP_005272542.1  angiopoietin-related protein 4 isoform X2

      Conserved Domains (1) summary
      cd00087
      Location:184 → 380
      FReD; Fibrinogen-related domains (FReDs); C terminal globular domain of fibrinogen. Fibrinogen is involved in blood clotting, being activated by thrombin to assemble into fibrin clots. The N-termini of 2 times 3 chains come together to form a globular ...

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      8350623..8360841
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054321146.1 → XP_054177121.1  angiopoietin-related protein 4 isoform X1

    2. XM_054321147.1 → XP_054177122.1  angiopoietin-related protein 4 isoform X2

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_016109.2: Suppressed sequence

      Description
      NM_016109.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BY76.2 GenPept UniProtKB/Swiss-Prot:Q9BY76

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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