Alt. symbols: TXGP1L | ACT35 | OX40 | CD134

Approved name: TNF receptor superfamily member 4
Alt. names: tumor necrosis factor receptor superfamily, member 4

Location: 1p36.33: 1211326 - 1214153 (-)
Gene type: protein_coding, 14 transcripts.

Scores: LoFtool: | pLI: 0.00720933 | LOEUF: 1.322

HGNC: 11918

NCBI: 7293, RefSeq: NG_046896.1

Ensembl: ENSG00000186827.12

LRG_1319 | Status: public

OMIM: 600315

Expression | ProteinAtlas

Gene Ontology (GO)

• Molecular function: tumor necrosis factor receptor activity [GO:0005031]
• Cell component: external side of plasma membrane [GO:0009897]
• Biological process: inflammatory response [GO:0006954]

Normal function

TNFRSF4 encodes for the protein OX40, a member of the TNF-receptor superfamily. OX40 has been shown to activate NF-kappaB through its interaction with adaptor proteins TRAF2 and TRAF5. Knockout studies in mice suggested that OX40 promotes the expression of the apoptosis inhibitors BCL2 and BCL2lL1/BCL2-XL, and thus suppresses apoptosis. Knockout studies also suggested the roles of OX40 in the CD4+ T cell response, as well as in T cell-dependent B cell proliferation and differentiation.

Dysfunction and disease

Biallelic mutations in TNFRSF4 have been recently found in patients with autosomal recessive Immunodeficiency associated with classic Kaposi sarcoma of childhood and poor T-cell responses due to complete functional OX40 deficiency (PMID:23897980). This condition, namely Immunodeficiency 16 [MIM:615593], has only been reported in the literature in one patient so far. This woman was found to carry a homozygous p.R65C mutation in OX40 and presented with low proportion of effector memory CD4+ T cell s in peripheral blood, but less diminished proportion of effector memory CD8+ T cells. Her proportion of circulating memory B cells was low, but the antibody response in vivo was intact, including the response to a vaccine boost (PMID:23897980). [Load More]