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Gene Review

TNFRSF1B  -  tumor necrosis factor receptor superfamily...

Homo sapiens

Synonyms: CD120b, TBPII, TNF-R-II, TNF-R2, TNF-R75, ...
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Disease relevance of TNFRSF1B


Psychiatry related information on TNFRSF1B

  • During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group) [5].
  • Neither the polymorphism in the TNFR1 nor that in the TNFR2 gene was associated with narcolepsy [6].
  • Significant improvements with etanercept in the MOS energy and mental health subscales, current health (from the feeling thermometer), and mental and physical function components of the SF-36 were reported (P < 0.05) [7].
  • Plasma levels of the sTNF-R p55, sTNF-R p75, and sIL-2R did not differ significantly between nocturnal sleep and nocturnal wakefulness [8].
  • (3) Fetuses of patients who delivered within 72 hours of cordocentesis had significantly higher concentrations of TNF-R1 and TNF-R2 receptors than those with longer latency periods (P<.05 for each) [9].

High impact information on TNFRSF1B

  • Infliximab (a mAB), and etanercept (a sTNF-R-Fc fusion protein) have been approved by regulatory authorities in the United States and Europe for treating RA, and they represent a significant new addition to available therapeutic options [10].
  • Cells expressing a noncleavable mutant of p75 sustain DeltaPsim and ATP levels during apoptosis, and ROS production in response to apoptotic stimuli is dampened [11].
  • While cytochrome c release and DNA fragmentation are unaffected by the noncleavable p75 mutant, mitochondrial morphology of dying cells is maintained, and loss of plasma membrane integrity is delayed [11].
  • Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain [11].
  • Successful treatment of Langerhans'-cell histiocytosis with etanercept [12].

Chemical compound and disease context of TNFRSF1B


Biological context of TNFRSF1B

  • Comparison of these data with other published frequencies of TNFRSF1A and TNFRSF1B genotypes according to race suggests that the distribution in African American, Caucasian, and Asian populations differs significantly [18].
  • CONCLUSION: Our data fail to support previous association findings for TNFRSF1B and CLCNKB at the chromosome 1p36 locus implicated in hypertension [2].
  • Thermodynamic modelling of the 3'-untranslated region of TNFRSF1B mRNA predicted that the T1668G variant alters the stem-loop structure and thus the mRNA stability and expression [2].
  • In a patient population (n = 104) of European descent, there were four SNPs within TNFRSF1B and six SNPs within PLOD1 that occurred with greater than 5% frequency [19].
  • These findings strengthen the potential importance of chromosome 1p36.2-1p36.3 in contributing to BMD variation, and are consistent with genetic variation in either PLOD1, TNFRSF1B or nearby genes playing a role in the phenotype [19].

Anatomical context of TNFRSF1B

  • Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice [20].
  • The function of TNF-R2 is less well understood, although there are data supporting a role in T-cell development and the proliferation of cytotoxic T lymphocytes [20].
  • Functional characterization of the human tumor necrosis factor receptor p75 in a transfected rat/mouse T cell hybridoma [21].
  • The addition of BB-2275 to rheumatoid synovial membrane cell cultures totally inhibited MMP activity and also significantly reduced the levels of soluble TNF alpha (P < 0.006), p55 sTNF-R (P < 0.006), and p75 sTNF-R (P < 0.004) [22].
  • Infliximab but not etanercept induced peripheral and lamina propria lymphocyte apoptosis when compared with a control antibody [4].

Associations of TNFRSF1B with chemical compounds

  • This study suggests that one of the genes responsible for UC may be the TNF gene, or an adjacent gene, and that TNFRSF1B gene polymorphisms contribute greatly to the increased onset risk of CD and to the disease behavior [23].
  • These findings may have clinical application through the identification of patients who are most likely to benefit from treatment with methotrexate or etanercept [24].
  • Because distinct molecular components including the serine/threonine protein kinase receptor-interacting protein (RIP) are required, we have referred to this alternative form of cell death as "programmed necrosis." We show that TNFR-2 signaling can potentiate programmed necrosis via TNFR-1 [25].
  • Etanercept reduced the frequency and severity of symptoms in both patients, whereas the levels of serum IgD and urine mevalonate remained unchanged [26].
  • TNFR80 induces no cytotoxicity on its own, but is functional in these transfectants, as selective stimulation activates nuclear factor-kappaB (NF-kappaB) and induces NF-kappaB-dependent cellular responses (IL-6 and manganese superoxide dismutase) [27].

Physical interactions of TNFRSF1B


Regulatory relationships of TNFRSF1B


Other interactions of TNFRSF1B


Analytical, diagnostic and therapeutic context of TNFRSF1B


  1. Comment: the methionine 196 arginine polymorphism in exon 6 of the TNF receptor 2 gene (TNFRSF1B) is associated with the polycystic ovary syndrome and hyperandrogenism. Peral, B., San Millán, J.L., Castello, R., Moghetti, P., Escobar-Morreale, H.F. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  2. No association with hypertension of CLCNKB and TNFRSF1B polymorphisms at a hypertension locus on chromosome 1p36. Speirs, H.J., Wang, W.Y., Benjafield, A.V., Morris, B.J. J. Hypertens. (2005) [Pubmed]
  3. A human tumor necrosis factor (TNF) alpha mutant that binds exclusively to the p55 TNF receptor produces toxicity in the baboon. Van Zee, K.J., Stackpole, S.A., Montegut, W.J., Rogy, M.A., Calvano, S.E., Hsu, K.C., Chao, M., Meschter, C.L., Loetscher, H., Stüber, D. J. Exp. Med. (1994) [Pubmed]
  4. Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease. Van den Brande, J.M., Braat, H., van den Brink, G.R., Versteeg, H.H., Bauer, C.A., Hoedemaeker, I., van Montfrans, C., Hommes, D.W., Peppelenbosch, M.P., van Deventer, S.J. Gastroenterology (2003) [Pubmed]
  5. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. van der Heijde, D., Klareskog, L., Rodriguez-Valverde, V., Codreanu, C., Bolosiu, H., Melo-Gomes, J., Tornero-Molina, J., Wajdula, J., Pedersen, R., Fatenejad, S. Arthritis Rheum. (2006) [Pubmed]
  6. Polymorphisms of the tumor necrosis factor receptors: no association with narcolepsy in German patients. Wieczorek, S., Dahmen, N., Jagiello, P., Epplen, J.T., Gencik, M. J. Mol. Med. (2003) [Pubmed]
  7. Health-related quality of life and functional status of patients with rheumatoid arthritis randomly assigned to receive etanercept or placebo. Mathias, S.D., Colwell, H.H., Miller, D.P., Moreland, L.W., Buatti, M., Wanke, L. Clinical therapeutics. (2000) [Pubmed]
  8. Diurnal and sleep-wake dependent variations of soluble TNF- and IL-2 receptors in healthy volunteers. Haack, M., Pollmächer, T., Mullington, J.M. Brain Behav. Immun. (2004) [Pubmed]
  9. Further observations on the fetal inflammatory response syndrome: a potential homeostatic role for the soluble receptors of tumor necrosis factor alpha. Romero, R., Maymon, E., Pacora, P., Gomez, R., Mazor, M., Yoon, B.H., Berry, S.M. Am. J. Obstet. Gynecol. (2000) [Pubmed]
  10. Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? Feldmann, M., Maini, R.N. Annu. Rev. Immunol. (2001) [Pubmed]
  11. Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain. Ricci, J.E., Muñoz-Pinedo, C., Fitzgerald, P., Bailly-Maitre, B., Perkins, G.A., Yadava, N., Scheffler, I.E., Ellisman, M.H., Green, D.R. Cell (2004) [Pubmed]
  12. Successful treatment of Langerhans'-cell histiocytosis with etanercept. Henter, J.I., Karlén, J., Calming, U., Bernstrand, C., Andersson, U., Fadeel, B. N. Engl. J. Med. (2001) [Pubmed]
  13. Exclusive tumor necrosis factor (TNF) signaling by the p75TNF receptor triggers inflammatory ischemia in the CNS of transgenic mice. Akassoglou, K., Douni, E., Bauer, J., Lassmann, H., Kollias, G., Probert, L. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  14. Etanercept (Enbrel): update on therapeutic use. Spencer-Green, G. Ann. Rheum. Dis. (2000) [Pubmed]
  15. Evidence of a mechanism by which etanercept increased TNF-alpha in multiple myeloma: new insights into the biology of TNF-alpha giving new treatment opportunities--the role of bupropion. Kast, R.E. Leuk. Res. (2005) [Pubmed]
  16. The role of tumor necrosis factor antagonism in clinical practice. Keystone, E.C. The Journal of rheumatology. Supplement. (1999) [Pubmed]
  17. Etanercept Immunex. Yung, R.L. Current opinion in investigational drugs (London, England : 2000) (2001) [Pubmed]
  18. Single-nucleotide polymorphisms in tumor necrosis factor receptor genes: definition of novel haplotypes and racial/ethnic differences. Bridges, S.L., Jenq, G., Moran, M., Kuffner, T., Whitworth, W.C., McNicholl, J. Arthritis Rheum. (2002) [Pubmed]
  19. Association analysis of bone mineral density and single nucleotide polymorphisms in two candidate genes on chromosome 1p36. Spotila, L.D., Rodriguez, H., Koch, M., Tenenhouse, H.S., Tenenhouse, A., Li, H., Devoto, M. Calcif. Tissue Int. (2003) [Pubmed]
  20. Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice. Erickson, S.L., de Sauvage, F.J., Kikly, K., Carver-Moore, K., Pitts-Meek, S., Gillett, N., Sheehan, K.C., Schreiber, R.D., Goeddel, D.V., Moore, M.W. Nature (1994) [Pubmed]
  21. Functional characterization of the human tumor necrosis factor receptor p75 in a transfected rat/mouse T cell hybridoma. Vandenabeele, P., Declercq, W., Vercammen, D., Van de Craen, M., Grooten, J., Loetscher, H., Brockhaus, M., Lesslauer, W., Fiers, W. J. Exp. Med. (1992) [Pubmed]
  22. Paradoxical effects of a synthetic metalloproteinase inhibitor that blocks both p55 and p75 TNF receptor shedding and TNF alpha processing in RA synovial membrane cell cultures. Williams, L.M., Gibbons, D.L., Gearing, A., Maini, R.N., Feldmann, M., Brennan, F.M. J. Clin. Invest. (1996) [Pubmed]
  23. Polymorphisms of the TNF gene and the TNF receptor superfamily member 1B gene are associated with susceptibility to ulcerative colitis and Crohn's disease, respectively. Sashio, H., Tamura, K., Ito, R., Yamamoto, Y., Bamba, H., Kosaka, T., Fukui, S., Sawada, K., Fukuda, Y., Tamura, K., Satomi, M., Shimoyama, T., Furuyama, J. Immunogenetics (2002) [Pubmed]
  24. The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept. Criswell, L.A., Lum, R.F., Turner, K.N., Woehl, B., Zhu, Y., Wang, J., Tiwari, H.K., Edberg, J.C., Kimberly, R.P., Moreland, L.W., Seldin, M.F., Bridges, S.L. Arthritis Rheum. (2004) [Pubmed]
  25. A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses. Chan, F.K., Shisler, J., Bixby, J.G., Felices, M., Zheng, L., Appel, M., Orenstein, J., Moss, B., Lenardo, M.J. J. Biol. Chem. (2003) [Pubmed]
  26. Favorable preliminary experience with etanercept in two patients with the hyperimmunoglobulinemia D and periodic fever syndrome. Takada, K., Aksentijevich, I., Mahadevan, V., Dean, J.A., Kelley, R.I., Kastner, D.L. Arthritis Rheum. (2003) [Pubmed]
  27. Enhancement of TNF receptor p60-mediated cytotoxicity by TNF receptor p80: requirement of the TNF receptor-associated factor-2 binding site. Weiss, T., Grell, M., Hessabi, B., Bourteele, S., Müller, G., Scheurich, P., Wajant, H. J. Immunol. (1997) [Pubmed]
  28. Study of etanercept, a tumor necrosis factor-alpha inhibitor, in recurrent ovarian cancer. Madhusudan, S., Muthuramalingam, S.R., Braybrooke, J.P., Wilner, S., Kaur, K., Han, C., Hoare, S., Balkwill, F., Ganesan, T.S. J. Clin. Oncol. (2005) [Pubmed]
  29. TNF receptor-associated factor-2 binding site is involved in TNFR75-dependent enhancement of TNFR55-induced cell death. Fang, L., Fang, J., Chen, C.Q. Cell Res. (2001) [Pubmed]
  30. Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding. Cui, X., Hawari, F., Alsaaty, S., Lawrence, M., Combs, C.A., Geng, W., Rouhani, F.N., Miskinis, D., Levine, S.J. J. Clin. Invest. (2002) [Pubmed]
  31. Human TNF mutants with selective activity on the p55 receptor. Van Ostade, X., Vandenabeele, P., Everaerdt, B., Loetscher, H., Gentz, R., Brockhaus, M., Lesslauer, W., Tavernier, J., Brouckaert, P., Fiers, W. Nature (1993) [Pubmed]
  32. Ankyrin repeat and SOCS box 3 (ASB3) mediates ubiquitination and degradation of tumor necrosis factor receptor II. Chung, A.S., Guan, Y.J., Yuan, Z.L., Albina, J.E., Chin, Y.E. Mol. Cell. Biol. (2005) [Pubmed]
  33. Interleukin-10 upregulates tumor necrosis factor receptor type-II (p75) gene expression in endotoxin-stimulated human monocytes. Dickensheets, H.L., Freeman, S.L., Smith, M.F., Donnelly, R.P. Blood (1997) [Pubmed]
  34. Tumor necrosis factor (TNF) up-regulates the expression of p75 but not p55 TNF receptors, and both receptors mediate, independently of each other, up-regulation of transforming growth factor alpha and epidermal growth factor receptor mRNA. Kalthoff, H., Roeder, C., Brockhaus, M., Thiele, H.G., Schmiegel, W. J. Biol. Chem. (1993) [Pubmed]
  35. TNF-induced superoxide anion production in adherent human neutrophils involves both the p55 and p75 TNF receptor. Richter, J., Gullberg, U., Lantz, M. J. Immunol. (1995) [Pubmed]
  36. Enhanced expression of tumor necrosis factor receptor mRNA and protein in mononuclear cells isolated from rheumatoid arthritis synovial joints. Brennan, F.M., Gibbons, D.L., Mitchell, T., Cope, A.P., Maini, R.N., Feldmann, M. Eur. J. Immunol. (1992) [Pubmed]
  37. The effect of etanercept and infliximab on the production of tumour necrosis factor alpha, interferon-gamma and GM-CSF in in vivo activated intestinal T lymphocyte cultures. Agnholt, J., Dahlerup, J.F., Kaltoft, K. Cytokine (2003) [Pubmed]
  38. Regulated commitment of TNF receptor signaling: a molecular switch for death or activation. Pimentel-Muiños, F.X., Seed, B. Immunity (1999) [Pubmed]
  39. The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex. Shu, H.B., Takeuchi, M., Goeddel, D.V. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  40. Regulation of surface and soluble TNF receptor expression on human monocytes and synovial fluid macrophages by IL-4 and IL-10. Hart, P.H., Hunt, E.K., Bonder, C.S., Watson, C.J., Finlay-Jones, J.J. J. Immunol. (1996) [Pubmed]
  41. Caveolin-1 associates with TRAF2 to form a complex that is recruited to tumor necrosis factor receptors. Feng, X., Gaeta, M.L., Madge, L.A., Yang, J.H., Bradley, J.R., Pober, J.S. J. Biol. Chem. (2001) [Pubmed]
  42. No association of polymorphisms in the tumor necrosis factor receptor I and receptor II genes with disease severity in rheumatoid arthritis. Glossop, J.R., Nixon, N.B., Dawes, P.T., Hassell, A.B., Mattey, D.L. J. Rheumatol. (2003) [Pubmed]
  43. Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-alpha. Mitoma, H., Horiuchi, T., Hatta, N., Tsukamoto, H., Harashima, S., Kikuchi, Y., Otsuka, J., Okamura, S., Fujita, S., Harada, M. Gastroenterology (2005) [Pubmed]
  44. Dysregulation of membrane-bound tumor necrosis factor-alpha and tumor necrosis factor receptors on mononuclear cells in human immunodeficiency virus type 1 infection: low percentage of p75-tumor necrosis factor receptor positive cells in patients with advanced disease and high viral load. Hestdal, K., Aukrust, P., Müller, F., Lien, E., Bjerkeli, V., Espevik, T., Frøland, S.S. Blood (1997) [Pubmed]
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