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TNFSF18 (tumor necrosis factor (ligand) superfamily, member 18)

Written2010-04Theresa Placke, Hans-Georg Kopp, Benjamin Joachim Schmiedel, Helmut Rainer Salih
Eberhard Karls University of Tuebingen, Department of Hematology/Oncology, Otfried-Mueller-Str. 10, 72076 Tuebingen, Germany

(Note : for Links provided by Atlas : click)

Identity

Alias_namestumor necrosis factor (ligand) superfamily
Alias_symbol (synonym)AITRL
TL6
hGITRL
Other aliasGITRL
MGC138237
HGNC (Hugo) TNFSF18
LocusID (NCBI) 8995
Atlas_Id 42639
Location 1q25.1  [Link to chromosome band 1q25]
Location_base_pair Starts at 173010360 and ends at 173020103 bp from pter ( according to hg19-Feb_2009)  [Mapping TNFSF18.png]
Fusion genes
(updated 2016)
GATAD2B (1q21.3) / TNFSF18 (1q25.1)

DNA/RNA

 
  Figure 1. Schematic illustration of the gene structure of human TNFSF18 on chromosome 1. Both published transcript variants are shown. Red boxes represent the mRNA transcript within the gene. The smaller boxes at the beginning and the end of the transcripts indicate untranslated regions, while the larger boxes display the translated parts.
Description 2 transcript versions published:
mRNA 748 bp: 3 exons (1-223, 224-254, 255-748) -> coding for 199 aa (2-601),
mRNA 610 bp: 3 exons (1-176, 177-207, 208-610) -> coding for 177 aa (21-554).
Transcription Accurate start codon is not clearly defined, 2 transcript versions are published (differing start codons in exon 1).
Pseudogene Unknown.

Protein

 
  Figure 2. Schematic illustration of the structure of TNFSF18 protein versions, according to the two published transcripts.
Description TNFSF18/GITR ligand (GITRL) is a single-pass type II transmembrane protein and contains 2 potential glycosylation sites (predicted at 129 aa and 161 aa). TNFSF18 encompasses 177 or 199 aa and thus has a molecular weight of about 20 kDa. In the 177 aa long version, amino acids 1-28 constitute the cytoplasmic domain, 29-49 the transmembrane domain, and 50-177 the extracellular domain, whereas in the 199 aa long variant the amino acids 1-50 constitute the cytoplasmic domain, 51-71 the transmembrane domain, and 72-199 the extracellular domain.
Expression TNFSF18 is expressed on DC, monocytes, macrophages, B cells, activated T cells, endothelial cells, osteoclasts and various healthy non-lymphoid tissues (e.g., testis, ...). The fact that TNFSF18 is constitutively expressed on resting antigen-presenting cells distinguishes it from most other TNF family members, which are not detectable in resting state and are upregulated following activation.
In addition, TNFSF18 is constitutively expressed and released as soluble form by solid tumors of different histological origin and various hematopoietic malignancies.
Localisation TNFSF18 is a type II transmembrane protein. A soluble form of the molecule has been shown to be released by a yet unknown mechanism e.g. by tumor cells.
Function TNFSF18 is the only known ligand for GITR (TNFRSF18, AITR), which is mainly expressed by lymphatic cells like T lymphocytes and NK cells. Upon interaction with its receptor, TNFSF18 is, like many other TNF family members, capable to transduce bidirectional signals, i.e. in the receptor and the ligand bearing cell. Transduction of signals into TNFSF18 bearing cells has been shown to cause differentiation of osteoclasts, to activate macrophages and to alter cytokine production of healthy myeloid cells, but also of carcinoma and leukemia cells and influences apoptosis. Activation of macrophages via TNFSF18 results in increased secretion of inflammatory mediators like MMP-9, NO and TNF. In healthy macrophages and myeloid leukemia cells, TNFSF18 signaling has been found to involve the MAP kinase pathway.
Binding to TNFRSF18 may induce signaling through this receptor, which, in mice, has been implicated in the development of autoimmune diseases, graft versus host disease and in the immune response against infectious pathogens and tumors.
Available data suggest that TNFRSF18 may mediate different effects in mice and men, and most functional studies regarding the role of TNFRSF18 in tumor immunology have been performed using agonistic antibodies or injection of adenovirus expressing recombinant TNFSF18 into tumors, which might not reflect the consequences of TNFRSF18 interaction with its natural ligand in vivo. In line, studies evaluating immune responses in GITR-/- mice have so far not led to a clear picture of the role of TNFRSF18 in normal physiology.
Homology The TNFSF18 gene is conserved in human, chimpanzee, dog, mouse, and rat. The homology among the other TNF family members is highest with OX40L.

Mutations

Note No published single nucleotide polymorphisms (SNPs).

Implicated in

Note
  
Entity Host-tumor interaction
Note In mice, it has been shown that application of the agonistic GITR antibody DTA-1 delays tumor progression and can even lead to complete tumor rejection. Similar results were obtained by using GITRL-Fc fusion protein. Transfection of tumor cells with GITRL causes rejection of the tumor and prolonged survival, while parental cells cannot be rejected. This effect can be reversed by administration of a blocking GITRL antibody. There is evidence that expression of GITRL promotes the development of tumor-specific T cells. Re-challenge of mice which once successfully rejected GITRL-positive tumor results in complete rejection of both transfected and non-transfected tumors. Several studies showed increased infiltration of CD8+ cells in GITRL-expressing tumors. By the use of depletion experiments and athymic nude mice it has been shown that for GITR-GITRL dependent rejection of tumors both CD4+ and CD8+ T cells as well as NK cells are required.
In humans, controversial data regarding the function of GITR and GITRL in tumor immunology were described. Hanabuchi et al. reported that NK cells are activated by engagement of GITRL on plasmacytoid dendritic cells, which can be blocked by anti-GITRL antibody. In contrast, Baltz et al. and Baessler et al. demonstrated substantial GITRL expression on tumor cells and leukemic blasts resulting in diminished NK cell reactivity. Blockade of GITR-GITRL interaction by anti-GITR antibody abrogated the inhibitory effect of GITRL. Furthermore, stimulation of GITRL substantially induced the production of TGF-beta and IL-10 by tumor cells and leukemic blasts. Additionally, they reported that human GITRL is released by tumor cells in a soluble form which impairs NK cell reactivity alike the membrane-bound form. Thus, GITRL expression seems to affect the interaction of human tumor cells with the immune system by influencing tumor cell immunogenity and metastasis and creating an immunosuppressive cytokine microenvironment. The inhibitory effect of GITRL on human NK cells was further supported by Liu et al., who reported inhibition of NK cell proliferation and cytokine production and increased apoptosis after GITR stimulation. These controversial data regarding the function of GITR on human NK cells may be due to the usage of different reagents and different experimental condition.
The results regarding the role of GITR and GITRL in tumor immunology are controversial in mice and humans. Thus, GITR and GITRL may mediate different effects in mice and men, and in line suppression of human regulatory T cells, in contrast to their murine counterparts, is not inhibited by GITR. Many studies employed agonistic antibodies or recombinant protein for GITR stimulation and not constitutively GITRL-expressing cells. Thus, these studies do not involve possible influences of reverse signaling mediated by GITRL, which may change reaction of GITRL-bearing cells and may in turn alter functions of GITR-bearing cells.
  
  
Entity Autoimmune disease
Note The influence of GITR and GITRL was tested in different mouse models of autoimmune disease. Onset of autoimmune diabetes in NOD mice is accelerated if they are treated with agonistic GITR mAb, and activation of CD4+ T cells is increased compared to control treated mice. Likewise, application of a blocking GITRL antibody protected from diabetes. In GITR -/- mice, experimental autoimmune diseases take an attenuated course. GITR -/- mice with collagen-induced arthritis show less joint inflammation and bone erosion than wildtype mice. Furthermore, lower concentrations of inflammatory mediators were reported. In line with these findings, GITR triggering antibody exacerbates collagen-induced arthritis in wildtype mice compared to control-treated siblings.
However, all these studies regarding the function of GITR and its ligand in autoimmune disease were performed in mice. Further investigation is needed to elucidate the relevance of GITR and GITR ligand in human autoimmune disease and to clarify the similarities and differences of these molecules in mice and men.
  

Bibliography

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Mol Immunol. 2008 Jan;45(2):523-33. Epub 2007 Jun 28.
PMID 17602748
 
Glucocorticoid-induced tumor necrosis factor receptor-related protein ligand subverts immunosurveillance of acute myeloid leukemia in humans.
Baessler T, Krusch M, Schmiedel BJ, Kloss M, Baltz KM, Wacker A, Schmetzer HM, Salih HR.
Cancer Res. 2009 Feb 1;69(3):1037-45. Epub 2009 Jan 20.
PMID 19155305
 
Neutralization of tumor-derived soluble glucocorticoid-induced TNFR-related protein ligand increases NK cell anti-tumor reactivity.
Baltz KM, Krusch M, Baessler T, Schmiedel BJ, Bringmann A, Brossart P, Salih HR.
Blood. 2008 Nov 1;112(9):3735-43. Epub 2008 Aug 8.
PMID 18689545
 
Glucocorticoid-induced tumour necrosis factor receptor (GITR) and its ligand (GITRL) in atopic dermatitis.
Baumgartner-Nielsen J, Vestergaard C, Thestrup-Pedersen K, Deleuran M, Deleuran B.
Acta Derm Venereol. 2006;86(5):393-8. (REVIEW)
PMID 16955181
 
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PMID 15472713
 
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PMID 19018533
 
Agonist anti-GITR antibody enhances vaccine-induced CD8(+) T-cell responses and tumor immunity.
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Cancer Res. 2006 May 1;66(9):4904-12.
PMID 16651447
 
Genetic and pharmacological inhibition of GITR-GITRL interaction reduces chronic lung injury induced by bleomycin instillation.
Cuzzocrea S, Ronchetti S, Genovese T, Mazzon E, Agostini M, Di Paola R, Esposito E, Muia C, Nocentini G, Riccardi C.
FASEB J. 2007 Jan;21(1):117-29. Epub 2006 Nov 29.
PMID 17135359
 
Immune rejection of mouse tumors expressing mutated self.
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Cancer Res. 2009 Apr 15;69(8):3545-53. Epub 2009 Apr 7.
PMID 19351857
 
Glucocorticoid-induced TNF receptor, a costimulatory receptor on naive and activated T cells, uses TNF receptor-associated factor 2 in a novel fashion as an inhibitor of NF-kappa B activation.
Esparza EM, Arch RH.
J Immunol. 2005 Jun 15;174(12):7875-82.
PMID 15944293
 
Inhibition of murine gammadelta lymphocyte expansion and effector function by regulatory alphabeta T cells is cell-contact-dependent and sensitive to GITR modulation.
Goncalves-Sousa N, Ribot JC, deBarros A, Correia DV, Caramalho I, Silva-Santos B.
Eur J Immunol. 2010 Jan;40(1):61-70.
PMID 19877017
 
Reverse signaling through GITR ligand enables dexamethasone to activate IDO in allergy.
Grohmann U, Volpi C, Fallarino F, Bozza S, Bianchi R, Vacca C, Orabona C, Belladonna ML, Ayroldi E, Nocentini G, Boon L, Bistoni F, Fioretti MC, Romani L, Riccardi C, Puccetti P.
Nat Med. 2007 May;13(5):579-86. Epub 2007 Apr 8.
PMID 17417651
 
Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR.
Gurney AL, Marsters SA, Huang RM, Pitti RM, Mark DT, Baldwin DT, Gray AM, Dowd AD, Brush AD, Heldens AD, Schow AD, Goddard AD, Wood WI, Baker KP, Godowski PJ, Ashkenazi A.
Curr Biol. 1999 Feb 25;9(4):215-8.
PMID 10074428
 
Human plasmacytoid predendritic cells activate NK cells through glucocorticoid-induced tumor necrosis factor receptor-ligand (GITRL).
Hanabuchi S, Watanabe N, Wang YH, Wang YH, Ito T, Shaw J, Cao W, Qin FX, Liu YJ.
Blood. 2006 May 1;107(9):3617-23. Epub 2006 Jan 5.
PMID 16397134
 
GITR ligand-costimulation activates effector and regulatory functions of CD4+ T cells.
Igarashi H, Cao Y, Iwai H, Piao J, Kamimura Y, Hashiguchi M, Amagasa T, Azuma M.
Biochem Biophys Res Commun. 2008 May 16;369(4):1134-8. Epub 2008 Mar 17.
PMID 18346459
 
Cutting edge: the natural ligand for glucocorticoid-induced TNF receptor-related protein abrogates regulatory T cell suppression.
Ji HB, Liao G, Faubion WA, Abadia-Molina AC, Cozzo C, Laroux FS, Caton A, Terhorst C.
J Immunol. 2004 May 15;172(10):5823-7.
PMID 15128759
 
Prevention of chronic graft-versus-host disease by stimulation with glucocorticoid-induced TNF receptor.
Kim J, Choi WS, Kim HJ, Kwon B.
Exp Mol Med. 2006 Feb 28;38(1):94-9.
PMID 16520557
 
Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells.
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J Exp Med. 2005 Oct 3;202(7):885-91. Epub 2005 Sep 26.
PMID 16186187
 
Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand.
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J Biol Chem. 1999 Mar 5;274(10):6056-61.
PMID 10037686
 
Soluble glucocorticoid-induced tumor necrosis factor receptor (sGITR) increased MMP-9 activity in murine macrophage.
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J Cell Biochem. 2003 Apr 1;88(5):1048-56.
PMID 12616541
 
Glucocorticoid-induced tumor necrosis factor receptor negatively regulates activation of human primary natural killer (NK) cells by blocking proliferative signals and increasing NK cell apoptosis.
Liu B, Li Z, Mahesh SP, Pantanelli S, Hwang FS, Siu WO, Nussenblatt RB.
J Biol Chem. 2008 Mar 28;283(13):8202-10. Epub 2008 Jan 29.
PMID 18230609
 
Expression of GITR ligand abrogates immunosuppressive function of ocular tissue and differentially modulates inflammatory cytokines and chemokines.
Mahesh SP, Li Z, Liu B, Fariss RN, Nussenblatt RB.
Eur J Immunol. 2006 Aug;36(8):2128-38.
PMID 16874737
 
GITR activation induces an opposite effect on alloreactive CD4(+) and CD8(+) T cells in graft-versus-host disease.
Muriglan SJ, Ramirez-Montagut T, Alpdogan O, Van Huystee TW, Eng JM, Hubbard VM, Kochman AA, Tjoe KH, Riccardi C, Pandolfi PP, Sakaguchi S, Houghton AN, Van Den Brink MR.
J Exp Med. 2004 Jul 19;200(2):149-57. Epub 2004 Jul 12.
PMID 15249593
 
Regulatory T cell-resistant CD8+ T cells induced by glucocorticoid-induced tumor necrosis factor receptor signaling.
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PMID 18632650
 
A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis.
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PMID 9177197
 
Glucocorticoid-induced TNFR family-related protein (GITR) activation exacerbates murine asthma and collagen-induced arthritis.
Patel M, Xu D, Kewin P, Choo-Kang B, McSharry C, Thomson NC, Liew FY.
Eur J Immunol. 2005 Dec;35(12):3581-90.
PMID 16285015
 
Enhancement of T-cell-mediated anti-tumour immunity via the ectopically expressed glucocorticoid-induced tumour necrosis factor receptor-related receptor ligand (GITRL) on tumours.
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Immunology. 2009 Aug;127(4):489-99.
PMID 19604302
 
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PMID 16709800
 
Glucocorticoid-induced TNFR-related protein lowers the threshold of CD28 costimulation in CD8+ T cells.
Ronchetti S, Nocentini G, Bianchini R, Krausz LT, Migliorati G, Riccardi C.
J Immunol. 2007 Nov 1;179(9):5916-26.
PMID 17947665
 
Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance.
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Nat Immunol. 2002 Feb;3(2):135-42. Epub 2002 Jan 22.
PMID 11812990
 
The soluble glucocorticoid-induced tumor necrosis factor receptor causes cell cycle arrest and apoptosis in murine macrophages.
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Biochem Biophys Res Commun. 2004 Mar 26;316(1):24-32.
PMID 15003506
 
Induction of nitric oxide synthase (NOS) by soluble glucocorticoid induced tumor necrosis factor receptor (sGITR) is modulated by IFN-gamma in murine macrophage.
Shin HH, Lee HW, Choi HS.
Exp Mol Med. 2003 Jun 30;35(3):175-80.
PMID 12858016
 
GITR interacts with the pro-apoptotic protein Siva and induces apoptosis.
Spinicelli S, Nocentini G, Ronchetti S, Krausz LT, Bianchini R, Riccardi C.
Cell Death Differ. 2002 Dec;9(12):1382-4.
PMID 12478477
 
Mouse glucocorticoid-induced tumor necrosis factor receptor ligand is costimulatory for T cells.
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Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15059-64. Epub 2003 Nov 7.
PMID 14608036
 
The GITRL-GITR system alters TLR-4 expression on DC during fungal infection.
Vecchiarelli A, Pericolini E, Gabrielli E, Agostini M, Bistoni F, Nocentini G, Cenci E, Riccardi C.
Cell Immunol. 2009;257(1-2):13-22. Epub 2009 Mar 9.
PMID 19272591
 
TNF/TNFR family members in costimulation of T cell responses.
Watts TH.
Annu Rev Immunol. 2005;23:23-68. (REVIEW)
PMID 15771565
 
Key role of the GITR/GITRLigand pathway in the development of murine autoimmune diabetes: a potential therapeutic target.
You S, Poulton L, Cobbold S, Liu CP, Rosenzweig M, Ringler D, Lee WH, Segovia B, Bach JF, Waldmann H, Chatenoud L.
PLoS One. 2009 Nov 20;4(11):e7848.
PMID 19936238
 
Pivotal roles of CD4+ effector T cells in mediating agonistic anti-GITR mAb-induced-immune activation and tumor immunity in CT26 tumors.
Zhou P, L'italien L, Hodges D, Schebye XM.
J Immunol. 2007 Dec 1;179(11):7365-75.
PMID 18025180
 

Citation

This paper should be referenced as such :
Placke, T ; Kopp, HG ; Schmiedel, BJ ; Salih, HR
TNFSF18 (tumor necrosis factor (ligand) superfamily, member 18)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(1):68-72.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TNFSF18ID42639ch1q25.html


External links

Nomenclature
HGNC (Hugo)TNFSF18   11932
Cards
AtlasTNFSF18ID42639ch1q25
Entrez_Gene (NCBI)TNFSF18  8995  tumor necrosis factor superfamily member 18
AliasesAITRL; GITRL; TL6; TNLG2A; 
hGITRL
GeneCards (Weizmann)TNFSF18
Ensembl hg19 (Hinxton)ENSG00000120337 [Gene_View]  chr1:173010360-173020103 [Contig_View]  TNFSF18 [Vega]
Ensembl hg38 (Hinxton)ENSG00000120337 [Gene_View]  chr1:173010360-173020103 [Contig_View]  TNFSF18 [Vega]
ICGC DataPortalENSG00000120337
TCGA cBioPortalTNFSF18
AceView (NCBI)TNFSF18
Genatlas (Paris)TNFSF18
WikiGenes8995
SOURCE (Princeton)TNFSF18
Genetics Home Reference (NIH)TNFSF18
Genomic and cartography
GoldenPath hg19 (UCSC)TNFSF18  -     chr1:173010360-173020103 -  1q23   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TNFSF18  -     1q23   [Description]    (hg38-Dec_2013)
EnsemblTNFSF18 - 1q23 [CytoView hg19]  TNFSF18 - 1q23 [CytoView hg38]
Mapping of homologs : NCBITNFSF18 [Mapview hg19]  TNFSF18 [Mapview hg38]
OMIM603898   
Gene and transcription
Genbank (Entrez)AF117713 AF125303 AK313273 AY358868 BC069111
RefSeq transcript (Entrez)NM_005092
RefSeq genomic (Entrez)NC_000001 NC_018912 NT_004487 NW_004929293
Consensus coding sequences : CCDS (NCBI)TNFSF18
Cluster EST : UnigeneHs.248197 [ NCBI ]
CGAP (NCI)Hs.248197
Alternative Splicing GalleryENSG00000120337
Gene ExpressionTNFSF18 [ NCBI-GEO ]   TNFSF18 [ EBI - ARRAY_EXPRESS ]   TNFSF18 [ SEEK ]   TNFSF18 [ MEM ]
Gene Expression Viewer (FireBrowse)TNFSF18 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)8995
GTEX Portal (Tissue expression)TNFSF18
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UNG2   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9UNG2  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UNG2
Splice isoforms : SwissVarQ9UNG2
PhosPhoSitePlusQ9UNG2
Domains : Interpro (EBI)Tumour_necrosis_fac-like_dom   
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)TNFSF18
DMDM Disease mutations8995
Blocks (Seattle)TNFSF18
PDB (SRS)2Q1M    2R30    2R32    3B93    3B94   
PDB (PDBSum)2Q1M    2R30    2R32    3B93    3B94   
PDB (IMB)2Q1M    2R30    2R32    3B93    3B94   
PDB (RSDB)2Q1M    2R30    2R32    3B93    3B94   
Structural Biology KnowledgeBase2Q1M    2R30    2R32    3B93    3B94   
SCOP (Structural Classification of Proteins)2Q1M    2R30    2R32    3B93    3B94   
CATH (Classification of proteins structures)2Q1M    2R30    2R32    3B93    3B94   
SuperfamilyQ9UNG2
Human Protein AtlasENSG00000120337
Peptide AtlasQ9UNG2
HPRD04874
IPIIPI00935899   IPI00980449   
Protein Interaction databases
DIP (DOE-UCLA)Q9UNG2
IntAct (EBI)Q9UNG2
FunCoupENSG00000120337
BioGRIDTNFSF18
STRING (EMBL)TNFSF18
ZODIACTNFSF18
Ontologies - Pathways
QuickGOQ9UNG2
Ontology : AmiGOadaptive immune response  T cell proliferation involved in immune response  T cell proliferation involved in immune response  positive regulation of leukocyte migration  receptor binding  cytokine activity  extracellular space  plasma membrane  signal transduction  cell-cell signaling  cell surface  cell surface  positive regulation of macrophage chemotaxis  integral component of membrane  tumor necrosis factor receptor superfamily binding  tumor necrosis factor receptor superfamily binding  tumor necrosis factor-mediated signaling pathway  tumor necrosis factor-mediated signaling pathway  tumor necrosis factor-mediated signaling pathway  regulation of T cell proliferation  regulation of T cell proliferation  positive regulation of tyrosine phosphorylation of Stat1 protein  negative regulation of apoptotic process  positive regulation of cell adhesion  positive regulation of inflammatory response  positive regulation of NF-kappaB transcription factor activity  positive regulation of monocyte chemotaxis  positive regulation of protein homodimerization activity  negative regulation of T-helper 17 cell lineage commitment  regulation of dendritic cell chemotaxis  
Ontology : EGO-EBIadaptive immune response  T cell proliferation involved in immune response  T cell proliferation involved in immune response  positive regulation of leukocyte migration  receptor binding  cytokine activity  extracellular space  plasma membrane  signal transduction  cell-cell signaling  cell surface  cell surface  positive regulation of macrophage chemotaxis  integral component of membrane  tumor necrosis factor receptor superfamily binding  tumor necrosis factor receptor superfamily binding  tumor necrosis factor-mediated signaling pathway  tumor necrosis factor-mediated signaling pathway  tumor necrosis factor-mediated signaling pathway  regulation of T cell proliferation  regulation of T cell proliferation  positive regulation of tyrosine phosphorylation of Stat1 protein  negative regulation of apoptotic process  positive regulation of cell adhesion  positive regulation of inflammatory response  positive regulation of NF-kappaB transcription factor activity  positive regulation of monocyte chemotaxis  positive regulation of protein homodimerization activity  negative regulation of T-helper 17 cell lineage commitment  regulation of dendritic cell chemotaxis  
Pathways : KEGGCytokine-cytokine receptor interaction   
REACTOMEQ9UNG2 [protein]
REACTOME Pathways5669034 [pathway]   
NDEx NetworkTNFSF18
Atlas of Cancer Signalling NetworkTNFSF18
Wikipedia pathwaysTNFSF18
Orthology - Evolution
OrthoDB8995
GeneTree (enSembl)ENSG00000120337
Phylogenetic Trees/Animal Genes : TreeFamTNFSF18
HOVERGENQ9UNG2
HOGENOMQ9UNG2
Homologs : HomoloGeneTNFSF18
Homology/Alignments : Family Browser (UCSC)TNFSF18
Gene fusions - Rearrangements
Fusion : MitelmanGATAD2B/TNFSF18 [1q21.3/1q25.1]  [t(1;1)(q21;q25)]  
Fusion: TCGAGATAD2B 1q21.3 TNFSF18 1q25.1 GBM
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTNFSF18 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TNFSF18
dbVarTNFSF18
ClinVarTNFSF18
1000_GenomesTNFSF18 
Exome Variant ServerTNFSF18
ExAC (Exome Aggregation Consortium)TNFSF18 (select the gene name)
Genetic variants : HAPMAP8995
Genomic Variants (DGV)TNFSF18 [DGVbeta]
DECIPHER (Syndromes)1:173010360-173020103  ENSG00000120337
CONAN: Copy Number AnalysisTNFSF18 
Mutations
ICGC Data PortalTNFSF18 
TCGA Data PortalTNFSF18 
Broad Tumor PortalTNFSF18
OASIS PortalTNFSF18 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTNFSF18  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTNFSF18
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TNFSF18
DgiDB (Drug Gene Interaction Database)TNFSF18
DoCM (Curated mutations)TNFSF18 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TNFSF18 (select a term)
intoGenTNFSF18
NCG5 (London)TNFSF18
Cancer3DTNFSF18(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603898   
Orphanet
MedgenTNFSF18
Genetic Testing Registry TNFSF18
NextProtQ9UNG2 [Medical]
TSGene8995
GENETestsTNFSF18
Huge Navigator TNFSF18 [HugePedia]
snp3D : Map Gene to Disease8995
BioCentury BCIQTNFSF18
ClinGenTNFSF18
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD8995
Chemical/Pharm GKB GenePA36624
Clinical trialTNFSF18
Miscellaneous
canSAR (ICR)TNFSF18 (select the gene name)
Probes
Litterature
PubMed45 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTNFSF18
EVEXTNFSF18
GoPubMedTNFSF18
iHOPTNFSF18
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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