This gene encodes a member of the TNF-receptor superfamily. The encoded receptor has been shown to have increased expression upon T-cell activation, and it is thought to play a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells. Knockout studies in mice also suggest the role of this receptor is in the regulation of CD3-driven T-cell... See more...

Aliases for TNFRSF18 Gene

Aliases for TNFRSF18 Gene

  • TNF Receptor Superfamily Member 18 2 3 5
  • Tumor Necrosis Factor Receptor Superfamily Member 18 3 4
  • Glucocorticoid-Induced TNFR-Related Protein 3 4
  • Activation-Inducible TNFR Family Receptor 3 4
  • AITR 3 4
  • GITR 3 4
  • TNF Receptor Superfamily Activation-Inducible Protein 3
  • Tumor Necrosis Factor Receptor Superfamily, Member 18 2
  • CD357 Antigen 4
  • ENERGEN 3
  • GITR-D 3
  • CD357 3

External Ids for TNFRSF18 Gene

Previous GeneCards Identifiers for TNFRSF18 Gene

  • GC01M000665
  • GC01M000890
  • GC01M001015
  • GC01M001044
  • GC01M001179
  • GC01M001128
  • GC01M000410

Summaries for TNFRSF18 Gene

Entrez Gene Summary for TNFRSF18 Gene

  • This gene encodes a member of the TNF-receptor superfamily. The encoded receptor has been shown to have increased expression upon T-cell activation, and it is thought to play a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells. Knockout studies in mice also suggest the role of this receptor is in the regulation of CD3-driven T-cell activation and programmed cell death. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Feb 2011]

GeneCards Summary for TNFRSF18 Gene

TNFRSF18 (TNF Receptor Superfamily Member 18) is a Protein Coding gene. Diseases associated with TNFRSF18 include Myasthenic Syndrome, Congenital, 7, Presynaptic. Among its related pathways are TRAF Pathway and Cytokine Signaling in Immune system. Gene Ontology (GO) annotations related to this gene include tumor necrosis factor-activated receptor activity. An important paralog of this gene is TNFRSF21.

UniProtKB/Swiss-Prot Summary for TNFRSF18 Gene

  • Receptor for TNFSF18. Seems to be involved in interactions between activated T-lymphocytes and endothelial cells and in the regulation of T-cell receptor-mediated cell death. Mediated NF-kappa-B activation via the TRAF2/NIK pathway.

Gene Wiki entry for TNFRSF18 Gene

Additional gene information for TNFRSF18 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TNFRSF18 Gene

Genomics for TNFRSF18 Gene

GeneHancer (GH) Regulatory Elements for TNFRSF18 Gene

Promoters and enhancers for TNFRSF18 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01J001204 Promoter/Enhancer 2 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 758.1 -0.3 -321 5.3 ZNF785 CTCF ZBTB6 SMARCE1 RUNX1 ZNF362 ZNF133 MYC MAX NFIB TNFRSF18 ENSG00000240731 CCNL2 SLC35E2A INTS11 ENSG00000227775 TMEM240 ENSG00000269737 LINC01409 MXRA8
GH01J001189 Enhancer 0.5 FANTOM5 Ensembl 9.8 +17.3 17308 2 LARP7 SDF4 B3GALT6 MIR200A MIR200B MIR429 UBE2J2 LINC01786 C1QTNF12 TNFRSF18 ENSG00000237094
GH01J001186 Enhancer 0.4 Ensembl 9.2 +20.4 20408 0.2 MLLT1 ATF1 BCOR TNFRSF18 B3GALT6 SDF4 TTLL10-AS1 TTLL10
GH01J001413 Enhancer 0.2 FANTOM5 14.4 -206.6 -206602 0 TNFRSF4 TNFRSF18 ATAD3C TMEM88B piR-40163-001 piR-61857-001
GH01J001076 Enhancer 0.3 Ensembl 5.4 +130.2 130209 0.6 GLIS1 TNFRSF18 RNF223 ENSG00000285812
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TNFRSF18 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TNFRSF18 gene promoter:
  • GR
  • p53
  • STAT1

Genomic Locations for TNFRSF18 Gene

Genomic Locations for TNFRSF18 Gene
chr1:1,203,508-1,206,709
(GRCh38/hg38)
Size:
3,202 bases
Orientation:
Minus strand
chr1:1,138,888-1,142,089
(GRCh37/hg19)
Size:
3,202 bases
Orientation:
Minus strand

Genomic View for TNFRSF18 Gene

Genes around TNFRSF18 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TNFRSF18 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TNFRSF18 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TNFRSF18 Gene

Proteins for TNFRSF18 Gene

  • Protein details for TNFRSF18 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y5U5-TNR18_HUMAN
    Recommended name:
    Tumor necrosis factor receptor superfamily member 18
    Protein Accession:
    Q9Y5U5
    Secondary Accessions:
    • B1AME1
    • O95851
    • Q5U0I4
    • Q9NYJ9

    Protein attributes for TNFRSF18 Gene

    Size:
    241 amino acids
    Molecular mass:
    26000 Da
    Quaternary structure:
    • Binds to TRAF1, TRAF2, and TRAF3, but not TRAF5 and TRAF6. Binds through its C-terminus to SIVA1/SIVA.

    Alternative splice isoforms for TNFRSF18 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TNFRSF18 Gene

Post-translational modifications for TNFRSF18 Gene

  • Glycosylation at Asn146

Other Protein References for TNFRSF18 Gene

Antibody Products

  • Santa Cruz Biotechnology (SCBT) Antibodies for TNFRSF18

Protein Products

No data available for DME Specific Peptides for TNFRSF18 Gene

Domains & Families for TNFRSF18 Gene

Gene Families for TNFRSF18 Gene

Protein Domains for TNFRSF18 Gene

Suggested Antigen Peptide Sequences for TNFRSF18 Gene

GenScript: Design optimal peptide antigens:
  • Tumor necrosis factor receptor superfamily, member 18 (A8WFP4_HUMAN)
  • Tumor necrosis factor receptor superfamily, member 18, isoform CRA_c (B1AME3_HUMAN)
  • Tumor necrosis factor receptor superfamily, member 18, isoform CRA_a (Q5U0I4_HUMAN)
  • Glucocorticoid-induced TNFR-related protein (TNR18_HUMAN)
genes like me logo Genes that share domains with TNFRSF18: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for TNFRSF18 Gene

Function for TNFRSF18 Gene

Molecular function for TNFRSF18 Gene

UniProtKB/Swiss-Prot Function:
Receptor for TNFSF18. Seems to be involved in interactions between activated T-lymphocytes and endothelial cells and in the regulation of T-cell receptor-mediated cell death. Mediated NF-kappa-B activation via the TRAF2/NIK pathway.
UniProtKB/Swiss-Prot Induction:
Up-regulated in peripherical mononuclear cells after antigen stimulation/lymphocyte activation.
GENATLAS Biochemistry:
tumor necrosis factor receptor superfamily,member 18,expressed in normal T lymphocytes from thymus,spleen,lymphonodes,involved in regulation of T cell receptor-mediated cell death

Phenotypes From GWAS Catalog for TNFRSF18 Gene

Gene Ontology (GO) - Molecular Function for TNFRSF18 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005031 tumor necrosis factor-activated receptor activity IEA,TAS --
GO:0005515 protein binding IPI 18040044
genes like me logo Genes that share ontologies with TNFRSF18: view
genes like me logo Genes that share phenotypes with TNFRSF18: view

Animal Models for TNFRSF18 Gene

MGI Knock Outs for TNFRSF18:

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for TNFRSF18 Gene

Localization for TNFRSF18 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TNFRSF18 Gene

Isoform 1: Cell membrane; Single-pass type I membrane protein.
Isoform 2: Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TNFRSF18 gene
Compartment Confidence
plasma membrane 5
extracellular 5
nucleus 1

Gene Ontology (GO) - Cellular Components for TNFRSF18 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IEA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with TNFRSF18: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TNFRSF18 Gene

Pathways & Interactions for TNFRSF18 Gene

PathCards logo

SuperPathways for TNFRSF18 Gene

SuperPathway Contained pathways
1 PEDF Induced Signaling
.51
.47
.43
2 Akt Signaling
.60
.60
.55
3 TGF-Beta Pathway
.60
.57
.51
4 NF-kappaB Signaling
5 T Cell Co-Signaling Pathway: Ligand-Receptor Interactions
genes like me logo Genes that share pathways with TNFRSF18: view

Pathways by source for TNFRSF18 Gene

1 BioSystems pathway for TNFRSF18 Gene
1 KEGG pathway for TNFRSF18 Gene
1 GeneGo (Thomson Reuters) pathway for TNFRSF18 Gene
1 R&D Systems pathway for TNFRSF18 Gene
13 Qiagen pathways for TNFRSF18 Gene
  • Akt Signaling
  • Antioxidant Action of Vitamin-C
  • GITR Pathway
  • Glucocorticoid Receptor Signaling
  • JAK-STAT Pathway
1 Cell Signaling Technology pathway for TNFRSF18 Gene

Gene Ontology (GO) - Biological Process for TNFRSF18 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002687 positive regulation of leukocyte migration IMP 23892569
GO:0006915 apoptotic process IEA --
GO:0007165 signal transduction TAS 10074428
GO:0033209 tumor necrosis factor-mediated signaling pathway TAS --
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein IMP 23892569
genes like me logo Genes that share ontologies with TNFRSF18: view

No data available for SIGNOR curated interactions for TNFRSF18 Gene

Drugs & Compounds for TNFRSF18 Gene

(2) Drugs for TNFRSF18 Gene - From: DGIdb and IUPHAR

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
TL6 Pharma 0
TRX518 Pharma 0
genes like me logo Genes that share compounds with TNFRSF18: view

Transcripts for TNFRSF18 Gene

mRNA/cDNA for TNFRSF18 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for TNFRSF18 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b
SP1:
SP2: -

Relevant External Links for TNFRSF18 Gene

GeneLoc Exon Structure for
TNFRSF18
ECgene alternative splicing isoforms for
TNFRSF18

Expression for TNFRSF18 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for TNFRSF18 Gene

mRNA differential expression in normal tissues according to GTEx for TNFRSF18 Gene

This gene is overexpressed in Cervix - Endocervix (x7.1), Skin - Not Sun Exposed (Suprapubic) (x6.1), Whole Blood (x6.0), and Skin - Sun Exposed (Lower leg) (x4.9).

Protein differential expression in normal tissues from HIPED for TNFRSF18 Gene

This gene is overexpressed in Saliva (65.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TNFRSF18 Gene



Protein tissue co-expression partners for TNFRSF18 Gene

NURSA nuclear receptor signaling pathways regulating expression of TNFRSF18 Gene:

TNFRSF18

SOURCE GeneReport for Unigene cluster for TNFRSF18 Gene:

Hs.212680

mRNA Expression by UniProt/SwissProt for TNFRSF18 Gene:

Q9Y5U5-TNR18_HUMAN
Tissue specificity: Expressed in lymph node, peripheral blood leukocytes and weakly in spleen.

Evidence on tissue expression from TISSUES for TNFRSF18 Gene

  • Blood(4.5)
  • Bone marrow(4.2)
  • Spleen(2.4)
  • Lymph node(2.3)
genes like me logo Genes that share expression patterns with TNFRSF18: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for TNFRSF18 Gene

Orthologs for TNFRSF18 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TNFRSF18 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TNFRSF18 33 32
  • 98.62 (n)
OneToOne
dog
(Canis familiaris)
Mammalia TNFRSF18 33 32
  • 75.11 (n)
OneToOne
cow
(Bos Taurus)
Mammalia TNFRSF18 33 32
  • 73.94 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tnfrsf18 32
  • 71.79 (n)
mouse
(Mus musculus)
Mammalia Tnfrsf18 17 33 32
  • 70.68 (n)
oppossum
(Monodelphis domestica)
Mammalia TNFRSF18 33
  • 26 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TNFRSF18 33
  • 17 (a)
OneToOne
chicken
(Gallus gallus)
Aves TNFRSF18 33 32
  • 47.41 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TNFRSF18 33
  • 23 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii tnfrsf18 33
  • 18 (a)
OneToOne
Species where no ortholog for TNFRSF18 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TNFRSF18 Gene

ENSEMBL:
Gene Tree for TNFRSF18 (if available)
TreeFam:
Gene Tree for TNFRSF18 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TNFRSF18: view image

Paralogs for TNFRSF18 Gene

Variants for TNFRSF18 Gene

Sequence variations from dbSNP and Humsavar for TNFRSF18 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs1000378662 -- 1,206,395(-) G/A/T coding_sequence_variant, synonymous_variant
rs1000538341 -- 1,209,020(-) G/A/T upstream_transcript_variant
rs1000608338 -- 1,209,701(-) G/A upstream_transcript_variant
rs1000679655 -- 1,205,282(-) G/A intron_variant
rs1001151157 -- 1,203,694(-) C/G 3_prime_UTR_variant, coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for TNFRSF18 Gene

Variant ID Type Subtype PubMed ID
dgv24n54 CNV loss 21841781
dgv2n67 CNV gain 20364138
nsv1003578 CNV gain 25217958
nsv10161 CNV gain+loss 18304495
nsv1160644 CNV deletion 26073780
nsv1160772 CNV duplication 26073780
nsv428334 CNV gain 18775914
nsv469848 CNV gain 16826518
nsv470680 CNV loss 18288195
nsv482937 CNV loss 15286789
nsv517709 CNV gain+loss 19592680
nsv544947 CNV loss 21841781
nsv544956 CNV loss 21841781
nsv544960 CNV loss 21841781
nsv950452 CNV deletion 24416366

Variation tolerance for TNFRSF18 Gene

Residual Variation Intolerance Score: 94.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.95; 49.33% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TNFRSF18 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
TNFRSF18

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TNFRSF18 Gene

Disorders for TNFRSF18 Gene

MalaCards: The human disease database

(1) MalaCards diseases for TNFRSF18 Gene - From: DISEASES

Disorder Aliases PubMed IDs
myasthenic syndrome, congenital, 7, presynaptic
  • cms7
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for TNFRSF18

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with TNFRSF18: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TNFRSF18 Gene

Publications for TNFRSF18 Gene

  1. Identification of three novel mRNA splice variants of GITR. (PMID: 10836847) Nocentini G … Riccardi C (Cell death and differentiation 2000) 3 4 23 56
  2. Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand. (PMID: 10037686) Kwon B … Kwon BS (The Journal of biological chemistry 1999) 2 3 4 56
  3. Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR. (PMID: 10074428) Gurney AL … Ashkenazi A (Current biology : CB 1999) 3 4 23 56
  4. Risk of meningioma and common variation in genes related to innate immunity. (PMID: 20406964) Rajaraman P … Inskip PD (Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2010) 3 43 56
  5. Large-scale candidate gene analysis of spontaneous clearance of hepatitis C virus. (PMID: 20331378) Mosbruger TL … Thio CL (The Journal of infectious diseases 2010) 3 43 56

Products for TNFRSF18 Gene

Sources for TNFRSF18 Gene