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TNFRSF9 TNF receptor superfamily member 9 [ Homo sapiens (human) ]

Gene ID: 3604, updated on 28-Oct-2024

Summary

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Official Symbol
TNFRSF9provided by HGNC
Official Full Name
TNF receptor superfamily member 9provided by HGNC
Primary source
HGNC:HGNC:11924
See related
Ensembl:ENSG00000049249 MIM:602250; AllianceGenome:HGNC:11924
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
ILA; 4-1BB; CD137; CDw137; IMD109
Summary
The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contributes to the clonal expansion, survival, and development of T cells. It can also induce proliferation in peripheral monocytes, enhance T cell apoptosis induced by TCR/CD3 triggered activation, and regulate CD28 co-stimulation to promote Th1 cell responses. The expression of this receptor is induced by lymphocyte activation. TRAF adaptor proteins have been shown to bind to this receptor and transduce the signals leading to activation of NF-kappaB. [provided by RefSeq, Jul 2008]
Expression
Biased expression in lymph node (RPKM 2.6), appendix (RPKM 1.1) and 6 other tissues See more
Orthologs
mouse all
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Genomic context

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See TNFRSF9 in Genome Data Viewer
Location:
1p36.23
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (7915871..7940839, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (7446742..7471701, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (7975931..8000899, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903833 Neighboring gene period circadian regulator 3 Neighboring gene MPRA-validated peak42 silencer Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:7886590-7887789 Neighboring gene NANOG hESC enhancer GRCh37_chr1:7912645-7913333 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr1:7929285-7930484 Neighboring gene urotensin 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:7935645-7936144 Neighboring gene NANOG hESC enhancer GRCh37_chr1:7970949-7971450 Neighboring gene tRNA-undetermined (NNN) 4-1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 188 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 92 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 93 Neighboring gene H3K27ac hESC enhancers GRCh37_chr1:8020839-8021622 and GRCh37_chr1:8021623-8022406 Neighboring gene Parkinsonism associated deglycase Neighboring gene ATAC-STARR-seq lymphoblastoid active region 98 Neighboring gene NANOG hESC enhancer GRCh37_chr1:8051898-8052428 Neighboring gene uncharacterized LOC124903834 Neighboring gene Sharpr-MPRA regulatory region 3725

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. CD137 ligand, a member of the tumor necrosis factor family, regulates immune responses via reverse signal transduction. Shao Z, et al. J Leukoc Biol, 2011 Jan. PMID 20643812
  2. Biological activities of reverse signal transduction through CD137 ligand. Schwarz H. J Leukoc Biol, 2005 Mar. PMID 15618293
  3. Increased Soluble CD137 Levels and CD4+ T-Cell-Associated Expression of CD137 in Acute Atherothrombotic Stroke. He Y, et al. Clin Transl Sci, 2018 Jul. PMID 29697202, Free PMC Article
  4. CD137: A checkpoint regulator involved in atherosclerosis. Söderström LÅ, et al. Atherosclerosis, 2018 May. PMID 29571029
  5. Novel CD137 Gene Polymorphisms and Susceptibility to Ischemic Stroke in the Northern Chinese Han Population. Zhang S, et al. Neuromolecular Med, 2017 Sep. PMID 28755037

See all (158) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. CD137 expression and signal function drive pleiotropic gammadelta T-cell effector functions that inhibit intracellular M. tuberculosis growth.
    Title: CD137 expression and signal function drive pleiotropic γδ T-cell effector functions that inhibit intracellular M. tuberculosis growth.
  2. Multiplex spatial analysis reveals increased CD137 expression and m-MDSC neighboring tumor cells in refractory classical Hodgkin Lymphoma.
    Title: Multiplex spatial analysis reveals increased CD137 expression and m-MDSC neighboring tumor cells in refractory classical Hodgkin Lymphoma.
  3. Soluble CD137: A Potential Prognostic Biomarker in Critically Ill Patients.
    Title: Soluble CD137: A Potential Prognostic Biomarker in Critically Ill Patients.
  4. Targeting neuropilin-1 abolishes anti-PD-1-upregulated regulatory T cells and synergizes with 4-1BB agonist for liver cancer treatment.
    Title: Targeting neuropilin-1 abolishes anti-PD-1-upregulated regulatory T cells and synergizes with 4-1BB agonist for liver cancer treatment.
  5. Epstein-Barr virus-induced ectopic CD137 expression helps nasopharyngeal carcinoma to escape immune surveillance and enables targeting by chimeric antigen receptors.
    Title: Epstein-Barr virus-induced ectopic CD137 expression helps nasopharyngeal carcinoma to escape immune surveillance and enables targeting by chimeric antigen receptors.
  6. FBXL20-mediated ubiquitination triggers the proteasomal degradation of 4-1BB.
    Title: FBXL20-mediated ubiquitination triggers the proteasomal degradation of 4-1BB.
  7. Galectin-3 Decreases 4-1BBL Bioactivity by Crosslinking Soluble and Membrane Expressed 4-1BB.
    Title: Galectin-3 Decreases 4-1BBL Bioactivity by Crosslinking Soluble and Membrane Expressed 4-1BB.
  8. Early-Onset Parkinson's Disease: A Novel Deletion Comprising the DJ-1 and TNFRSF9 Genes.
    Title: Early-Onset Parkinson's Disease: A Novel Deletion Comprising the DJ-1 and TNFRSF9 Genes.
  9. CD137 (4-1BB) stimulation leads to metabolic and functional reprogramming of human monocytes/macrophages enhancing their tumoricidal activity.
    Title: CD137 (4-1BB) stimulation leads to metabolic and functional reprogramming of human monocytes/macrophages enhancing their tumoricidal activity.
  10. Transient mTOR inhibition rescues 4-1BB CAR-Tregs from tonic signal-induced dysfunction.
    Title: Transient mTOR inhibition rescues 4-1BB CAR-Tregs from tonic signal-induced dysfunction.
Submit: New GeneRIF Correction See all GeneRIFs (117)

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

Associated conditions

Description Tests
Immunodeficiency 109 with lymphoproliferation
MedGen: C5830346 OMIM: 620282 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
Genetics of rheumatoid arthritis contributes to biology and drug discovery.
EBI GWAS Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
EBI GWAS Catalog
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
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)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 upregulates the expression of tumor necrosis factor receptor superfamily, member 9 (TNFRSF9) in human B cells PubMed
Nef nef HIV-1 Nef-stimulated CD8+ T cells upregulate mRNAs expression for IFN-gamma, MIP-1alpha, MIP-1alphaP, MIP-1beta, TNFRSF9, XCL1, and GM-CSF compared to unstimulated cells PubMed
Tat tat HIV-1 Tat upregulates the expression of tumor necrosis factor receptor superfamily, member 9 (TNFRSF9, CD137) in human primary T cells PubMed
capsid gag HIV-1 CA-stimulated CD8+ T cells upregulate mRNAs expression for IFN-gamma, MIP-1alpha, MIP-1alphaP, MIP-1beta, TNFRSF9, XCL1, and GM-CSF compared to unstimulated cells PubMed

Go to the HIV-1, Human Interaction Database

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

  • MGC2172, FLJ43501

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables signaling receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of cell population proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of cell population proliferation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of immature T cell proliferation in thymus IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in external side of plasma membrane 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 receptor superfamily member 9
Names
4-1BB ligand receptor
CD137 antigen
T cell antigen ILA
T-cell antigen 4-1BB homolog
homolog of mouse 4-1BB
induced by lymphocyte activation (ILA)
interleukin-activated receptor, homolog of mouse Ly63
receptor protein 4-1BB

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.

Genomic

  1. NG_052834.1 RefSeqGene

    Range
    7327..32295
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001561.6 → NP_001552.2  tumor necrosis factor receptor superfamily member 9 precursor

    See identical proteins and their annotated locations for NP_001552.2

    Status: REVIEWED

    Source sequence(s)
    AL009183, BC006196, BP381234
    Consensus CDS
    CCDS92.1
    UniProtKB/Swiss-Prot
    Q07011
    Related
    ENSP00000366729.3, ENST00000377507.8
    Conserved Domains (1) summary
    cd13410
    Location:23 → 160
    TNFRSF9; Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), also known as CD137

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
    7915871..7940839 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006710618.4 → XP_006710681.1  tumor necrosis factor receptor superfamily member 9 isoform X1

    Conserved Domains (1) summary
    cd13410
    Location:23 → 160
    TNFRSF9; Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), also known as CD137

  2. XM_047419672.1 → XP_047275628.1  tumor necrosis factor receptor superfamily member 9 isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    7446742..7471701 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054336415.1 → XP_054192390.1  tumor necrosis factor receptor superfamily member 9 isoform X1

  2. XM_054336416.1 → XP_054192391.1  tumor necrosis factor receptor superfamily member 9 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q07011.1 GenPept UniProtKB/Swiss-Prot:Q07011

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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