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    TNFSF15 TNF superfamily member 15 [ Homo sapiens (human) ]

    Gene ID: 9966, updated on 2-Nov-2024

    Summary

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    Official Symbol
    TNFSF15provided by HGNC
    Official Full Name
    TNF superfamily member 15provided by HGNC
    Primary source
    HGNC:HGNC:11931
    See related
    Ensembl:ENSG00000181634 MIM:604052; AllianceGenome:HGNC:11931
    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
    TL1; TL1A; VEGI; TNLG1B; VEGI192A
    Summary
    The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is abundantly expressed in endothelial cells, but is not expressed in either B or T cells. The expression of this protein is inducible by TNF and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 and decoy receptor TNFRSF21/DR6. It can activate NF-kappaB and MAP kinases, and acts as an autocrine factor to induce apoptosis in endothelial cells. This cytokine is also found to inhibit endothelial cell proliferation, and thus may function as an angiogenesis inhibitor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]
    Expression
    Broad expression in duodenum (RPKM 4.3), urinary bladder (RPKM 3.6) and 17 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TNFSF15 in Genome Data Viewer
    Location:
    9q32
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (114784635..114806039, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (126977075..126998476, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (117546915..117568319, complement)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr9:117452852-117454051 Neighboring gene testis expressed 48 Neighboring gene uncharacterized LOC105376231 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28876 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28877 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28878 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr9:117480617-117481816 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28880 Neighboring gene pre-mRNA processing factor kinase PRP4K pseudogene Neighboring gene Sharpr-MPRA regulatory region 6981 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr9:117656118-117657317 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:117669626-117670248 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr9:117670249-117670870 Neighboring gene TNF superfamily member 8 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:117691965-117692524

    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. Fine-mapping analysis revealed complex pleiotropic effect and tissue-specific regulatory mechanism of TNFSF15 in primary biliary cholangitis, Crohn's disease and leprosy. Sun Y, et al. Sci Rep, 2016 Aug 10. PMID 27507062, Free PMC Article
    2. Association of TNFSF15 polymorphisms in Korean children with Crohn's disease. Lee YJ, et al. Pediatr Int, 2015 Dec. PMID 25998826
    3. TNFSF15 is an ethnic-specific IBD gene. Picornell Y, et al. Inflamm Bowel Dis, 2007 Nov. PMID 17663424, Free PMC Article
    4. Soluble TNF-like cytokine (TL1A) production by immune complexes stimulated monocytes in rheumatoid arthritis. Cassatella MA, et al. J Immunol, 2007 Jun 1. PMID 17513783
    5. Association of Genetic Variations in TNFSF15 With Acute Anterior Uveitis in Chinese Han. Li H, et al. Invest Ophthalmol Vis Sci, 2015 Jul. PMID 26200500

    See all (182) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Necroptosis plays a role in TL1A-induced airway inflammation and barrier damage in asthma.
      Title: Necroptosis plays a role in TL1A-induced airway inflammation and barrier damage in asthma.
    2. MicroRNA-141-regulated KLK10 and TNFSF-15 gene expression in hepatoblastoma cells as a novel mechanism in liver carcinogenesis.
      Title: MicroRNA-141-regulated KLK10 and TNFSF-15 gene expression in hepatoblastoma cells as a novel mechanism in liver carcinogenesis.
    3. TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation.
      Title: TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation.
    4. The Relation of VEGFA, VEGFR2, VEGI, and HIF1A Genetic Variants and Their Serum Protein Levels with Breast Cancer in Egyptian Patients.
      Title: The Relation of VEGFA, VEGFR2, VEGI, and HIF1A Genetic Variants and Their Serum Protein Levels with Breast Cancer in Egyptian Patients.
    5. Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries.
      Title: Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries.
    6. Increased Serum Levels of Tumor Necrosis Factor-like Ligand 1A in Atopic Dermatitis.
      Title: Increased Serum Levels of Tumor Necrosis Factor-like Ligand 1A in Atopic Dermatitis.
    7. Immune Checkpoint Inhibitor (ICI) Genes and Aging in Clear Cell Renal Cell Carcinoma (ccRCC): Clinical and Genomic Study.
      Title: Immune Checkpoint Inhibitor (ICI) Genes and Aging in Clear Cell Renal Cell Carcinoma (ccRCC): Clinical and Genomic Study.
    8. Role of TNFSF15 variants in oral cancer development and clinicopathologic characteristics.
      Title: Role of TNFSF15 variants in oral cancer development and clinicopathologic characteristics.
    9. Genome-wide association study identifies TNFSF15 associated with childhood asthma.
      Title: Genome-wide association study identifies TNFSF15 associated with childhood asthma.
    10. Nonylphenol regulates TL1A through the AhR/HDAC2/HNF4alpha pathway in endothelial cells to promote the angiogenesis of colorectal cancer.
      Title: Nonylphenol regulates TL1A through the AhR/HDAC2/HNF4α pathway in endothelial cells to promote the angiogenesis of colorectal cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (151)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies 2 susceptibility Loci for Crohn's disease in a Japanese population.
    EBI GWAS Catalog
    Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy.
    EBI GWAS Catalog
    Genetic predictors of medically refractory ulcerative colitis.
    EBI GWAS Catalog
    Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease.
    EBI GWAS Catalog
    Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population.
    EBI GWAS Catalog
    Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
    EBI GWAS Catalog
    Genomewide association study of leprosy.
    EBI GWAS Catalog
    HLA-Cw*1202-B*5201-DRB1*1502 haplotype increases risk for ulcerative colitis but reduces risk for Crohn's disease.
    EBI GWAS Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    EBI GWAS Catalog
    IgA measurements in over 12 000 Swedish twins reveal sex differential heritability and regulatory locus near CD30L.
    EBI GWAS Catalog
    Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease.
    EBI GWAS Catalog
    Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
    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

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Vif vif HIV-1 Vif upregulates the expression of tumor necrosis factor ligand superfamily, member 15 (TNFSF15) in Vif-expression T cells PubMed
    Vpr vpr HIV-1 Vpr upregulates the gene expression of TNFSF15 in human monocyte-derived dendritic cells PubMed

    Go to the HIV-1, Human Interaction Database

    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

    Clone Names

    • MGC129934, MGC129935

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cytokine activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables cytokine activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables signaling receptor binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables tumor necrosis factor receptor binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    acts_upstream_of_or_within activation of NF-kappaB-inducing kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within activation of cysteine-type endopeptidase activity involved in apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cell surface receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of canonical NF-kappaB signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of extrinsic apoptotic signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in signal transduction NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    tumor necrosis factor ligand superfamily member 15
    Names
    TNF ligand-related molecule 1
    TNF superfamily ligand TL1A
    tumor necrosis factor (ligand) superfamily, member 15
    tumor necrosis factor ligand 1B
    tumor necrosis factor superfamily member 15
    vascular endothelial cell growth inhibitor
    vascular endothelial growth inhibitor-192A

    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_011488.2 RefSeqGene

      Range
      5090..26477
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001204344.1 → NP_001191273.1  tumor necrosis factor ligand superfamily member 15 isoform VEGI-192

      See identical proteins and their annotated locations for NP_001191273.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (VEGI-192) has a shorter and distinct N-terminus compared to isoform VEGI-251.
      Source sequence(s)
      AL390240, AW014795, AY434464
      UniProtKB/Swiss-Prot
      O95150
      Conserved Domains (1) summary
      pfam00229
      Location:58 → 192
      TNF; TNF(Tumour Necrosis Factor) family

    2. NM_005118.4 → NP_005109.2  tumor necrosis factor ligand superfamily member 15 isoform VEGI-251 precursor

      See identical proteins and their annotated locations for NP_005109.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (VEGI-251).
      Source sequence(s)
      AL390240, BC104463
      Consensus CDS
      CCDS6809.1
      UniProtKB/Swiss-Prot
      O95150, Q3SX69, Q5VJK8, Q5VWH1, Q8NFE9
      UniProtKB/TrEMBL
      A0A0U5JA19
      Related
      ENSP00000363157.3, ENST00000374045.5
      Conserved Domains (1) summary
      pfam00229
      Location:117 → 251
      TNF; TNF(Tumour Necrosis Factor) family

    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_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      114784635..114806039 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      126977075..126998476 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O95150.2 GenPept UniProtKB/Swiss-Prot:O95150

    Gene LinkOut

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

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