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TNFSF18 TNF superfamily member 18 [ Homo sapiens (human) ]

Gene ID: 8995, updated on 14-Nov-2024

Summary

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Official Symbol
TNFSF18provided by HGNC
Official Full Name
TNF superfamily member 18provided by HGNC
Primary source
HGNC:HGNC:11932
See related
Ensembl:ENSG00000120337 MIM:603898; AllianceGenome:HGNC:11932
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
TL6; AITRL; GITRL; TNLG2A; hGITRL
Summary
The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for receptor TNFRSF18/AITR/GITR. It has been shown to modulate T lymphocyte survival in peripheral tissues. This cytokine is also found to be expressed in endothelial cells, and is thought to be important for interaction between T lymphocytes and endothelial cells. [provided by RefSeq, Jul 2008]
Expression
Broad expression in gall bladder (RPKM 1.2), brain (RPKM 1.0) and 16 other tissues See more
Orthologs
mouse all
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Genomic context

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See TNFSF18 in Genome Data Viewer
Location:
1q25.1
Exon count:
3
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (173039202..173050941, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (172397315..172409046, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (173008342..173020081, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371618 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:172812249-172812966 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2097 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:172875963-172877162 Neighboring gene aminoacyl tRNA synthetase complex interacting multifunctional protein 1 pseudogene 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:173091817-173092382 Neighboring gene Sharpr-MPRA regulatory region 615 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:173133798-173134358 Neighboring gene GOT2 pseudogene 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2098 Neighboring gene TNF superfamily member 4 Neighboring gene uncharacterized LOC100506023 Neighboring gene uncharacterized LOC124904846

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. Osteostat/tumor necrosis factor superfamily 18 inhibits osteoclastogenesis and is selectively expressed by vascular endothelial cells. Nardelli B, et al. Endocrinology, 2006 Jan. PMID 16179414
  2. Neutralization of tumor-derived soluble glucocorticoid-induced TNFR-related protein ligand increases NK cell anti-tumor reactivity. Baltz KM, et al. Blood, 2008 Nov 1. PMID 18689545
  3. Expression of AITR and AITR ligand in breast cancer patients. Kim YS, et al. Oncol Rep, 2007 Nov. PMID 17914571
  4. An isoleucine-zipper motif enhances costimulation of human soluble trimeric GITR ligand. Cui D, et al. Cell Mol Immunol, 2010 Jul. PMID 20228835, Free PMC Article
  5. Expression of human GITRL on myeloid dendritic cells enhances their immunostimulatory function but does not abrogate the suppressive effect of CD4+CD25+ regulatory T cells. Tuyaerts S, et al. J Leukoc Biol, 2007 Jul. PMID 17449724

See all (55) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. A GITRL-mTORC1-GM-CSF Positive Loop Promotes Pathogenic Th17 Response in Primary Sjogren Syndrome.
    Title: A GITRL-mTORC1-GM-CSF Positive Loop Promotes Pathogenic Th17 Response in Primary Sjögren Syndrome.
  2. Type I interferons drive the maturation of human DC3s with a distinct costimulatory profile characterized by high GITRL.
    Title: Type I interferons drive the maturation of human DC3s with a distinct costimulatory profile characterized by high GITRL.
  3. Structures of mouse and human GITR-GITRL complexes reveal unique TNF superfamily interactions.
    Title: Structures of mouse and human GITR-GITRL complexes reveal unique TNF superfamily interactions.
  4. our studies have demonstrated a critical role of GITRL in modulating the suppressive function of myeloid-derived suppressor cells
    Title: Increased GITRL Impairs the Function of Myeloid-Derived Suppressor Cells and Exacerbates Primary Sjögren Syndrome.
  5. Cultured HCN-2 neurons were incubated at different times with GITRL and/or TRAIL, and thereafter nucleic acid and protein expression were measured. HCN-2 cells do not express GITRL mRNA, but the latter is induced after treatment with TRAIL. Cells did not express the GITRL receptor GITR mRNA, neither in control cultures, nor after treatment with TRAIL. TRAIL, when associated to GITRL, exerted additive toxic effects.
    Title: The Proinflammatory Cytokine GITRL Contributes to TRAIL-mediated Neurotoxicity in the HCN-2 Human Neuronal Cell Line.
  6. GITRL levels are significantly elevated in rheumatoid arthritis serum and synovial fluid and are positively correlated with autoantibody production in rheumatoid arthritis, suggesting a role of GITRL in the development of rheumatoid arthritis.
    Title: GITRL is associated with increased autoantibody production in patients with rheumatoid arthritis.
  7. GITRL modulates the activities of p38 MAPK and STAT3 to promote Th17 cell differentiation in autoimmune arthritis.
    Title: GITRL modulates the activities of p38 MAPK and STAT3 to promote Th17 cell differentiation in autoimmune arthritis.
  8. An increase in GITRL may impair the balance of Th17/Treg, and contribute to the pathopoiesis of Hashimoto's thyroiditis.
    Title: Th17/Treg cells imbalance and GITRL profile in patients with Hashimoto's thyroiditis.
  9. Our findings indicate the possible involvement of GITR-GITRL pathway in the pathogenesis of pSS.
    Title: Correlation of increased blood levels of GITR and GITRL with disease severity in patients with primary Sjögren's syndrome.
  10. Serum GITRL levels were higher in SLE patients.
    Title: Correlation of circulating glucocorticoid-induced TNFR-related protein ligand levels with disease activity in patients with systemic lupus erythematosus.
Submit: New GeneRIF Correction See all GeneRIFs (32)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus.
EBI GWAS Catalog
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
EBI GWAS Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
EBI GWAS Catalog
Multiple common variants for celiac disease influencing immune gene expression.
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)

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

  • MGC138237

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables cytokine activity IEA
Inferred from Electronic Annotation
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 
enables signaling receptor binding TAS
Traceable Author Statement
more info
 PubMed 
enables tumor necrosis factor receptor superfamily binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables tumor necrosis factor receptor superfamily binding ISS
Inferred from Sequence or Structural Similarity
more info
  
Process Evidence Code Pubs
involved_in T cell proliferation involved in immune response IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in T cell proliferation involved in immune response ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in adaptive immune response IEA
Inferred from Electronic Annotation
more info
  
involved_in cell-cell signaling TAS
Traceable Author Statement
more info
 PubMed 
involved_in negative regulation of T-helper 17 cell lineage commitment IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of apoptotic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of NF-kappaB transcription factor activity ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of cell adhesion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of inflammatory response IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of leukocyte migration IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of macrophage chemotaxis IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of monocyte chemotaxis IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of tyrosine phosphorylation of STAT protein IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of T cell proliferation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of T cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of dendritic cell chemotaxis IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of protein-containing complex assembly IEA
Inferred from Electronic Annotation
more info
  
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in tumor necrosis factor-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in tumor necrosis factor-mediated signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
is_active_in cell surface IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cell surface ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in extracellular space IEA
Inferred from Electronic Annotation
more info
  
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 18
Names
AITR ligand
GITR ligand
activation-inducible TNF-related ligand
glucocorticoid-induced TNF-related ligand
glucocorticoid-induced TNFR-related protein ligand
tumor necrosis factor (ligand) superfamily, member 18
tumor necrosis factor ligand 2A
tumor necrosis factor superfamily member 18

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.

mRNA and Protein(s)

  1. NM_005092.4 → NP_005083.3  tumor necrosis factor ligand superfamily member 18

    Status: REVIEWED

    Source sequence(s)
    AL031599
    Consensus CDS
    CCDS1305.3
    UniProtKB/Swiss-Prot
    A9IQG8, O95852, Q6ISV1, Q9UNG2
    UniProtKB/TrEMBL
    A0A0U5JXL4
    Related
    ENSP00000385470.4, ENST00000404377.5

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_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    173039202..173050941 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    172397315..172409046 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UNG2.3 GenPept UniProtKB/Swiss-Prot:Q9UNG2

Gene LinkOut

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