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

Gene ID: 7293, updated on 3-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (1211340..1214153, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (639783..642610, complement)
105.20220307 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
  • 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. Elevated expression of TNFRSF4 impacts immune cell infiltration and gene mutation in hepatocellular carcinoma. Wang D, et al. Cancer Biomark, 2023. PMID 36591653
  2. Expression of the immune checkpoint modulator OX40 indicates poor survival in acute myeloid leukemia. Marconato M, et al. Sci Rep, 2022 Sep 23. PMID 36151238, Free PMC Article
  3. Identification and validation of TNFRSF4 as a high-profile biomarker for prognosis and immunomodulation in endometrial carcinoma. Ma H, et al. BMC Cancer, 2022 May 13. PMID 35562682, Free PMC Article
  4. The recurrent homozygous translation start site variant in CCDC134 in an individual with severe osteogenesis imperfecta of non-Morrocan ancestry. Ali TM, et al. Am J Med Genet A, 2022 May. PMID 35019224
  5. The role of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) gene expression in diagnosis and prognosis of acute myeloid leukemia. Gamaleldin MA, et al. Mol Biol Rep, 2021 Oct. PMID 34453673

See all (130) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. The role of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) gene expression in diagnosis and prognosis of acute myeloid leukemia.
    Title: The role of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) gene expression in diagnosis and prognosis of acute myeloid leukemia.
Submit: New GeneRIF Correction See all GeneRIFs (106)

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
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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)

Genotypes

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_2023_10

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

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