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

Summary

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

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_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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

Variation

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See Variation Viewer (GRCh37.p13)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

TNFSF18_2974 (e-PCR)
- UniSTS:462592

G42290 (e-PCR)
- UniSTS:93963

NoName (e-PCR)
- UniSTS:481590

NoName (e-PCR)
- UniSTS:483482

G42261 (e-PCR)
- UniSTS:93366

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)

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