TNFSF18 (TNF superfamily member 18)

Gene

• Entrez ID: 8995
• Gene name: TNF superfamily member 18
• Gene symbol: TNFSF18
• Synonyms (NCBI Gene): AITRL, GITRL, TL6, TNLG2A, hGITRL
• Chromosome: 1
• Chromosome location: 1q25.1
• 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 cytoki

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1443519	hsa-miR-1470	CLIP-seq
MIRT1443520	hsa-miR-4287	CLIP-seq
MIRT1443521	hsa-miR-4469	CLIP-seq
MIRT1443522	hsa-miR-4667-3p	CLIP-seq
MIRT1443523	hsa-miR-4685-3p	CLIP-seq
MIRT1443524	hsa-miR-4713-5p	CLIP-seq
MIRT1443525	hsa-miR-942	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002250	Process	Adaptive immune response	IEA
GO:0002309	Process	T cell proliferation involved in immune response	IBA
GO:0002309	Process	T cell proliferation involved in immune response	IEA
GO:0002309	Process	T cell proliferation involved in immune response	ISS
GO:0002376	Process	Immune system process	IEA
GO:0002687	Process	Positive regulation of leukocyte migration	IEA
GO:0002687	Process	Positive regulation of leukocyte migration	IMP	23892569
GO:0005102	Function	Signaling receptor binding	IEA
GO:0005102	Function	Signaling receptor binding	TAS	10074428
GO:0005125	Function	Cytokine activity	IEA
GO:0005164	Function	Tumor necrosis factor receptor binding	IEA
GO:0005515	Function	Protein binding	IPI	18040044, 18378892, 32296183
GO:0005615	Component	Extracellular space	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006955	Process	Immune response	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007165	Process	Signal transduction	TAS	10074428
GO:0007267	Process	Cell-cell signaling	TAS	10074428
GO:0009986	Component	Cell surface	IBA
GO:0009986	Component	Cell surface	IEA
GO:0009986	Component	Cell surface	ISS
GO:0010759	Process	Positive regulation of macrophage chemotaxis	IEA
GO:0016020	Component	Membrane	IEA
GO:0032813	Function	Tumor necrosis factor receptor superfamily binding	IBA
GO:0032813	Function	Tumor necrosis factor receptor superfamily binding	IEA
GO:0032813	Function	Tumor necrosis factor receptor superfamily binding	ISS
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IBA
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IEA
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	ISS
GO:0042129	Process	Regulation of T cell proliferation	IBA
GO:0042129	Process	Regulation of T cell proliferation	IEA
GO:0042129	Process	Regulation of T cell proliferation	ISS
GO:0042531	Process	Positive regulation of tyrosine phosphorylation of STAT protein	IMP	23892569
GO:0042802	Function	Identical protein binding	IEA
GO:0042802	Function	Identical protein binding	IPI	18040044, 18378892
GO:0043066	Process	Negative regulation of apoptotic process	TAS	10074428
GO:0043254	Process	Regulation of protein-containing complex assembly	IEA
GO:0045785	Process	Positive regulation of cell adhesion	IEA
GO:0045785	Process	Positive regulation of cell adhesion	IMP	23892569
GO:0050729	Process	Positive regulation of inflammatory response	IEA
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	ISS
GO:0060255	Process	Regulation of macromolecule metabolic process	IEA
GO:0080090	Process	Regulation of primary metabolic process	IEA
GO:0090026	Process	Positive regulation of monocyte chemotaxis	IEA
GO:2000329	Process	Negative regulation of T-helper 17 cell lineage commitment	IEA
GO:2000508	Process	Regulation of dendritic cell chemotaxis	IEA

Other IDs

• MIM: 603898
• HGNC: 11932
• e!Ensembl: ENSG00000120337

Protein

• UniProt ID: Q9UNG2
• Protein name: Tumor necrosis factor ligand superfamily member 18 (Activation-inducible TNF-related ligand) (AITRL) (Glucocorticoid-induced TNF-related ligand) (hGITRL)
• Protein function: Cytokine that binds to TNFRSF18/AITR/GITR. Regulates T-cell responses. Can function as costimulator and lower the threshold for T-cell activation and T-cell proliferation. Important for interactions between activated T-lymphocytes and endothelia
• PDB: 2Q1M, 2R30, 2R32, 3B93, 3B94, 7KHD, 7LAW
• Tissue specificity: TISSUE SPECIFICITY: Expressed at high levels in the small intestine, ovary, testis, kidney and endothelial cells.
• Sequence:

  MTLHPSPITCEFLFSTALISPKMCLSHLENMPLSHSRTQGAQRSSWKLWLFCSIVMLLFL
  CSFSWLIFIFLQLETAKEPCMAKFGPLPSKWQMASSEPPCVNKVSDWKLEILQNGLYLIY
  GQVAPNANYNDVAPFEVRLYKNKDMIQTLTNKSKIQNVGGTYELHVGDTIDLIFNSEHQV
  LKNNTYWGIILLANPQFIS

• Sequence length: 199

Pathways

KEGG:

Cytokine-cytokine receptor interaction

Reactome:

TNFs bind their physiological receptors

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CELIAC DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CROHN'S DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INFLAMMATORY BOWEL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL INFARCTION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RHEUMATOID ARTHRITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ULCERATIVE COLITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	23935647, 28681901, 34239365	Associate	★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune disease	Pubtator	17963343	Associate	★☆☆☆☆ Found in Text Mining only
Breast adenocarcinoma	Breast Adenocarcinoma	BEFREE	30675308		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	17914571		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	33538861	Associate	★☆☆☆☆ Found in Text Mining only
Celiac Disease	Celiac disease	Pubtator	26859134	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	23380816		★☆☆☆☆ Found in Text Mining only
Dermatitis Atopic	Atopic dermatitis	Pubtator	16955181	Associate	★☆☆☆☆ Found in Text Mining only
Dermatitis, Atopic	Dermatitis	LHGDN	16955181		★☆☆☆☆ Found in Text Mining only
Eosinophilic Esophagitis	Eosinophilia	Pubtator	37972740	Associate	★☆☆☆☆ Found in Text Mining only
Gastritis	Gastritis	Pubtator	34589088	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	36766715	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	36766715	Associate	★☆☆☆☆ Found in Text Mining only
Hashimoto Disease	Hashimoto Disease	BEFREE	25429429		★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory bowel disease	Pubtator	30689765	Associate	★☆☆☆☆ Found in Text Mining only
Intervertebral disc disease	Intervertebral disc disease	Pubtator	17963343	Stimulate	★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Displacement	Intervertebral disc displacement	Pubtator	17963343	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	23380816	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	23380816	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	23380816		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung Neoplasms	BEFREE	31040163		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus Systemic	Systemic lupus erythematosus	Pubtator	23935647, 34239365	Stimulate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	17914571		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	LHGDN	17914571		★☆☆☆☆ Found in Text Mining only
Mesothelioma	Mesothelioma	BEFREE	30642542		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	30642542		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	36124532	Associate	★☆☆☆☆ Found in Text Mining only
Sjogren's Syndrome	Sjogren syndrome	Pubtator	23935647	Stimulate	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	32548602	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	40320925	Associate	★☆☆☆☆ Found in Text Mining only
Thyroiditis Autoimmune	Thyroiditis	Pubtator	23935647	Associate	★☆☆☆☆ Found in Text Mining only