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
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Genomic context

Location:: 1p36.33

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	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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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 Functions

What's a GeneRIF?

The OX40 Axis is Associated with Both Systemic and Local Involvement in Atopic Dermatitis.
Title: The OX40 Axis is Associated with Both Systemic and Local Involvement in Atopic Dermatitis.
OX40 and LAG3 are associated with better prognosis in advanced gastric cancer patients treated with anti-programmed death-1 antibody.
Title: OX40 and LAG3 are associated with better prognosis in advanced gastric cancer patients treated with anti-programmed death-1 antibody.
high OX-40 expression in the immune cell infiltrate is associated with better OS in patients with surgically resected stage I-III NSCLC.
Title: High OX-40 expression in the tumor immune infiltrate is a favorable prognostic factor of overall survival in non-small cell lung cancer.
These results identify OX40 as an amplifier of activation-induced cell death of human blood Mucosal-Associated Invariant T Cells and shed new light on the regulation of Mucosal-Associated Invariant T Cells in the phase of immune responses in type 2 diabetes.
Title: Activation-Induced Cell Death of Mucosal-Associated Invariant T Cells Is Amplified by OX40 in Type 2 Diabetic Patients.
Investigated a costimulatory molecule OX40-OX40L acting as an upstream regulator to regulate the nuclear factor of activated T cell (NFAT) in the acute phase of Kawasaki disease. The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased before IVIG and decreased after IVIG.
Title: Kawasaki disease OX40-OX40L axis acts as an upstream regulator of NFAT signaling pathway.
High OX40 and OX40L levels are associated with poor prognosis and may reflect the immune-exhausted status against lung adenocarcinoma.
Title: High Serum OX40 and OX40 Ligand (OX40L) Levels Correlate with Reduced Survival in Patients with Advanced Lung Adenocarcinoma.
Results suggest that high blood levels of sOX40 were correlated with a reduced survival time in patients with advanced colorectal cancer, possibly associated with the suppression of antitumor immunity by sOX40.
Title: High blood levels of soluble OX40 (CD134), an immune costimulatory molecule, indicate reduced survival in patients with advanced colorectal cancer.
Enhanced sOX40 and sOX40L expression and reduced mOX40 and mOX40L levels in Type 1 Diabetes patients correlated with the clinical characteristics and inflammatory factors.
Title: Enhancement of the Soluble Form of OX40 and OX40L Costimulatory Molecules but Reduction of the Membrane Form in Type 1 Diabetes (T1D).
We saw increased risk for squamous cell carcinoma development among individuals who inherited GG genotype at rs17568 region. rs2298211 SNP, AA genotype was also observed with higher frequency, in comparison with other two genotypes (AC or CC), among patients with HNSCC. Patients with C allele at this locus (AC and CC genotypes) have tumors with significantly higher histological grade.
Title: Association of OX40 gene polymorphisms (rs17568G/A and rs229811A/C) with head and neck squamous cell carcinoma.
Data from this study indicate that OX40L-OX40 interactions play a central role in the pathogenesis of aGVHD induced by human T cells. Therapeutic strategies that can efficiently interrupt OX40L-OX40 interaction in patients might have potential to provide patients with an improved clinical benefit.
Title: Central Roles of OX40L-OX40 Interaction in the Induction and Progression of Human T Cell-Driven Acute Graft-versus-Host Disease.

Submit: New GeneRIF Correction See all GeneRIFs (89)

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
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. GeneReviews: Not available
Immunodeficiency 16 MedGen: C3810053 OMIM: 615593 GeneReviews: Not available	Compare labs

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

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: 251 organisms have orthologs with human gene TNFRSF4
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
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	ISS Inferred from Sequence or Structural Similarity more info
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	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of transcription, DNA-templated	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of B cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of immunoglobulin production	ISS Inferred from Sequence or Structural Similarity more info
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

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GenBank, FASTA, Sequence Viewer (Graphics), LRG_1319

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, ENST00000379236.4

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: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p13 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

Related

ENST00000497869.5

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)