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

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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