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    TNFRSF4 TNF receptor superfamily member 4 [ Homo sapiens (human) ]

    Gene ID: 7293, updated on 2-Nov-2024

    Summary

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    Official Symbol
    TNFRSF4provided by HGNC
    Official Full Name
    TNF receptor superfamily member 4provided by HGNC
    Primary source
    HGNC:HGNC:11918
    See related
    Ensembl:ENSG00000186827 MIM:600315; AllianceGenome:HGNC:11918
    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
    OX40; ACT35; CD134; IMD16; TXGP1L
    Summary
    The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been shown to activate NF-kappaB through its interaction with adaptor proteins TRAF2 and TRAF5. Knockout studies in mice suggested that this receptor promotes the expression of apoptosis inhibitors BCL2 and BCL2lL1/BCL2-XL, and thus suppresses apoptosis. The knockout studies also suggested the roles of this receptor in CD4+ T cell response, as well as in T cell-dependent B cell proliferation and differentiation. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in fat (RPKM 2.7), lymph node (RPKM 1.6) and 14 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TNFRSF4 in Genome Data Viewer
    Location:
    1p36.33
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (1211340..1214153, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (639783..642610, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (1146720..1149533, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 43 Neighboring gene TTLL10 antisense RNA 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:1110977-1111495 Neighboring gene tubulin tyrosine ligase like 10 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:1114551-1115050 Neighboring gene MPRA-validated peak5 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 44 Neighboring gene MPRA-validated peak6 silencer Neighboring gene TNF receptor superfamily member 18 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:1143552-1144431 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 47 Neighboring gene stromal cell derived factor 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:1167335-1168016 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:1168017-1168698 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:1169483-1169984 Neighboring gene beta-1,3-galactosyltransferase 6

    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. OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential. Lai C, et al. Clin Cancer Res, 2016 Aug 15. PMID 27034329, Free PMC Article
    2. Structural mapping of CD134 residues critical for interaction with feline immunodeficiency virus. de Parseval A, et al. Nat Struct Mol Biol, 2005 Jan. PMID 15592478
    3. Association of OX40 gene polymorphisms (rs17568G/A and rs229811A/C) with head and neck squamous cell carcinoma. Faghih Z, et al. Mol Biol Rep, 2019 Jun. PMID 30923998
    4. Regulation of OX40 gene expression in graft-versus-host disease. Miura Y, et al. Transplant Proc, 2005 Jan-Feb. PMID 15808546
    5. Costimulatory molecule OX40/OX40L expression in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study. Xie F, et al. Pathol Res Pract, 2010 Nov 15. PMID 20634005

    See all (134) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. An OX-Tra'Ordinary Tale: The Role of OX40 and OX40L in Atopic Dermatitis.
      Title: An OX-Tra'Ordinary Tale: The Role of OX40 and OX40L in Atopic Dermatitis.
    2. Sclerotic-Type Cutaneous Chronic Graft-Versus-Host Disease Exhibits Activation of T Helper 1 and OX40 Cytokines.
      Title: Sclerotic-Type Cutaneous Chronic Graft-Versus-Host Disease Exhibits Activation of T Helper 1 and OX40 Cytokines.
    3. Differential expression of immune checkpoints (OX40/OX40L and PD-1/PD-L1) in decidua of unexplained recurrent spontaneous abortion women.
      Title: Differential expression of immune checkpoints (OX40/OX40L and PD-1/PD-L1) in decidua of unexplained recurrent spontaneous abortion women.
    4. The OX40-TRAF6 axis promotes CTLA-4 degradation to augment antitumor CD8[+] T-cell immunity.
      Title: The OX40-TRAF6 axis promotes CTLA-4 degradation to augment antitumor CD8(+) T-cell immunity.
    5. Elevated expression of TNFRSF4 impacts immune cell infiltration and gene mutation in hepatocellular carcinoma.
      Title: Elevated expression of TNFRSF4 impacts immune cell infiltration and gene mutation in hepatocellular carcinoma.
    6. Expression of the immune checkpoint modulator OX40 indicates poor survival in acute myeloid leukemia.
      Title: Expression of the immune checkpoint modulator OX40 indicates poor survival in acute myeloid leukemia.
    7. The recurrent homozygous translation start site variant in CCDC134 in an individual with severe osteogenesis imperfecta of non-Morrocan ancestry.
      Title: The recurrent homozygous translation start site variant in CCDC134 in an individual with severe osteogenesis imperfecta of non-Morrocan ancestry.
    8. Identification and validation of TNFRSF4 as a high-profile biomarker for prognosis and immunomodulation in endometrial carcinoma.
      Title: Identification and validation of TNFRSF4 as a high-profile biomarker for prognosis and immunomodulation in endometrial carcinoma.
    9. Clinical Significance of OX40 and OX40 Ligand in the Peripheral Blood of Patients with Myasthenia Gravis.
      Title: Clinical Significance of OX40 and OX40 Ligand in the Peripheral Blood of Patients with Myasthenia Gravis.
    10. DNA Methylation and mRNA Expression of OX40 (TNFRSF4) and GITR (TNFRSF18, AITR) in Head and Neck Squamous Cell Carcinoma Correlates With HPV Status, Mutational Load, an Interferon-gamma Signature, Signatures of Immune Infiltrates, and Survival.
      Title: DNA Methylation and mRNA Expression of OX40 (TNFRSF4) and GITR (TNFRSF18, AITR) in Head and Neck Squamous Cell Carcinoma Correlates With HPV Status, Mutational Load, an Interferon-γ Signature, Signatures of Immune Infiltrates, and Survival.
    Submit: New GeneRIF Correction See all GeneRIFs (107)

    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
    Combined immunodeficiency due to OX40 deficiency
    MedGen: C3810053 OMIM: 615593 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    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)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of tumor necrosis factor receptor superfamily, member 4 (TNFRSF4) by siRNA inhibits HIV-1 replication in HeLa P4/R5 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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables tumor necrosis factor receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables virus receptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in T cell proliferation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in immune response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in inflammatory response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of DNA-binding transcription factor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of DNA-templated transcription ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of B cell proliferation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of immunoglobulin production ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in symbiont entry into host cell IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in tumor necrosis factor-mediated signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cell surface ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in external side of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    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 4
    Names
    ACT35 antigen
    ATC35 antigen
    CD134 antigen
    OX40 antigen
    OX40 cell surface antigen
    OX40 homologue
    OX40L receptor
    TAX transcriptionally-activated glycoprotein 1 receptor
    lymphoid activation antigene ACT35
    tax-transcriptionally activated glycoprotein 1 receptor

    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_046896.1 RefSeqGene

      Range
      5486..8299
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1319

    mRNA and Protein(s)

    1. NM_001410709.1 → NP_001397638.1  tumor necrosis factor receptor superfamily member 4 isoform 2 precursor

      Status: REVIEWED

      Source sequence(s)
      AL162741
      Consensus CDS
      CCDS90838.1
      UniProtKB/TrEMBL
      A0A8V8TQH5
      Related
      ENSP00000514730.1, ENST00000699974.1

    2. NM_003327.4 → NP_003318.1  tumor necrosis factor receptor superfamily member 4 isoform 1 precursor

      See identical proteins and their annotated locations for NP_003318.1

      Status: REVIEWED

      Source sequence(s)
      BC105070
      Consensus CDS
      CCDS11.1
      UniProtKB/Swiss-Prot
      P43489, Q13663, Q2M312, Q5T7M0
      UniProtKB/TrEMBL
      A0A8V8TPN6
      Related
      ENSP00000368538.3, ENST00000379236.4
      Conserved Domains (1) summary
      cd13406
      Location:29 → 170
      TNFRSF4; Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as CD134 or OXO40

    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
      1211340..1214153 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011542076.3 → XP_011540378.1  tumor necrosis factor receptor superfamily member 4 isoform X2

      Related
      ENST00000699972.1
      Conserved Domains (1) summary
      cl22855
      Location:95 → 174
      TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)

    2. XM_011542074.3 → XP_011540376.1  tumor necrosis factor receptor superfamily member 4 isoform X1

      See identical proteins and their annotated locations for XP_011540376.1

      Related
      ENST00000497869.5
      Conserved Domains (1) summary
      cl22855
      Location:95 → 174
      TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)

    3. XM_011542077.3 → XP_011540379.1  tumor necrosis factor receptor superfamily member 4 isoform X3

      Conserved Domains (1) summary
      cl22855
      Location:24 → 70
      TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)

    RNA

    1. XR_007063145.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      639783..642610 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054338603.1 → XP_054194578.1  tumor necrosis factor receptor superfamily member 4 isoform X1

    2. XM_054338605.1 → XP_054194580.1  tumor necrosis factor receptor superfamily member 4 isoform X3

    3. XM_054338604.1 → XP_054194579.1  tumor necrosis factor receptor superfamily member 4 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P43489.1 GenPept UniProtKB/Swiss-Prot:P43489

    Gene LinkOut

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

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