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

Summary

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
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

Genomic context

Location:: 1p36.33

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	1	NC_000001.11 (1211326..1216812, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (1146706..1149703, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

High OX40 expression in Ovarian carcinoma is correlated with chemosensitivity and improved recurrence free survival in Ovarian carcinoma . Patients might therefore benefit from a second line therapy.
Title: High OX40 expression in recurrent ovarian carcinoma is indicative for response to repeated chemotherapy.
Increased OX40 expression is associated with gastric cancer.
Title: Could OX40 agonist antibody promote activation of the anti-tumor immune response in gastric cancer?
this study demonstrates that cSCCs contain an abundance of Tregs which can suppress tumoral effector T cell function and that activation of the costimulatory receptor OX40 enhances tumoral T cell responses.
Title: OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential.
OX40 expression on T cells was positively associated with obesity in humans.
Title: OX40 promotes obesity-induced adipose inflammation and insulin resistance.
Metabolically active CD4+ T cells expressing Glut1 and OX40 preferentially harbor HIV during in vitro infection.
Title: Metabolically active CD4+ T cells expressing Glut1 and OX40 preferentially harbor HIV during in vitro infection.
OX40 and OX40L formed a functional complex, which may facilitate signal transduction from OX40L to OX40 and contribute to the pathogenesis of Grave's disease.
Title: Enhancement of CD4(+) T cell response and survival via coexpressed OX40/OX40L in Graves' disease.
this study investigated whether CD134 is preferentially expressed on CD4 T cells in drug-induced hypersensitivity syndrome .
Title: Preferential expression of CD134, an HHV-6 cellular receptor, on CD4T cells in drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS).
blocking of both OX-40L and 4-1BBL reversed radiation-enhanced T-cell killing of human tumor targets as well as T-cell survival and activation.
Title: Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade.
Low OX40 expression is associated with colorectal cancer.
Title: OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer.
OX40 and its ligand are co stimulators for T lymphocytes.
Title: Lack of Association Between rs17568 Polymorphism in OX40 Gene and Myocardial Infarction, Southern of Iran.

Submit: New GeneRIF Correction See all GeneRIFs (75)

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 16 MedGen: C3810053 OMIM: 615593 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

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 BioSystems

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Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
Downstream signaling in naive CD8+ T cells, organism-specific biosystem (from Pathway Interaction Database)
Downstream signaling in naive CD8+ T cells, organism-specific biosystem
Downstream signaling in naive CD8+ T cells
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
TNFR2 non-canonical NF-kB pathway, organism-specific biosystem (from REACTOME)
TNFR2 non-canonical NF-kB pathway, organism-specific biosystemTumor necrosis factor-alpha (TNFA) exerts a wide range of biological effects through TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). Under normal physiological conditions TNFR2 exhibits more restr...
TNFs bind their physiological receptors, organism-specific biosystem (from REACTOME)
TNFs bind their physiological receptors, organism-specific biosystemMembers of the tumour necrosis factor superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) have crucial roles in both innate and adaptive immunity. These members are implicated in various acquir...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Homologs of the TNFRSF4 gene: The TNFRSF4 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and frog.
Orthologs from Annotation Pipeline: 190 organisms have orthologs with human gene TNFRSF4
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
protein binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
tumor necrosis factor-activated receptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
virus receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
T cell proliferation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
T cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
cellular defense response	IBA Inferred from Biological aspect of Ancestor more info	PubMed
immune response	TAS Traceable Author Statement more info	PubMed
inflammatory response	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of DNA-binding transcription factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of DNA-binding transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of activation-induced cell death of T cells	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of cytokine secretion	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of extrinsic apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of transcription, DNA-templated	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of transcription, DNA-templated	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of B cell proliferation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of B cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of immunoglobulin secretion	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of immunoglobulin secretion	ISS Inferred from Sequence or Structural Similarity more info
regulation of protein kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
tumor necrosis factor-mediated signaling pathway	TAS Traceable Author Statement more info
viral entry into host cell	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cell surface	ISS Inferred from Sequence or Structural Similarity more info
external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
integral component of plasma membrane	TAS Traceable Author Statement more info	PubMed
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

NG_046896.1 RefSeqGene

Range

5486..8299

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Related

ENSP00000368538.3, ENST00000379236.3

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: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p12 Primary Assembly

Range

1211326..1216812 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017002232.1 → XP_016857721.1 tumor necrosis factor receptor superfamily member 4 isoform X4

UniProtKB/Swiss-Prot

P43489

Conserved Domains (1) summary

cd13406
Location:29 → 170

TNFRSF4; Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as CD134 or OXO40
XM_011542076.2 → XP_011540378.1 tumor necrosis factor receptor superfamily member 4 isoform X3

Conserved Domains (1) summary

cl22855
Location:95 → 174

TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)
XM_017002231.1 → XP_016857720.1 tumor necrosis factor receptor superfamily member 4 isoform X2

Conserved Domains (1) summary

cd13406
Location:29 → 170

TNFRSF4; Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as CD134 or OXO40
XM_011542075.2 → XP_011540377.1 tumor necrosis factor receptor superfamily member 4 isoform X2

Conserved Domains (1) summary

cd13406
Location:29 → 170

TNFRSF4; Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as CD134 or OXO40
XM_011542074.2 → XP_011540376.1 tumor necrosis factor receptor superfamily member 4 isoform X1

See identical proteins and their annotated locations for XP_011540376.1

Conserved Domains (1) summary

cl22855
Location:95 → 174

TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)
XM_011542077.2 → XP_011540379.1 tumor necrosis factor receptor superfamily member 4 isoform X5

Conserved Domains (1) summary

cl22855
Location:24 → 70

TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)