Genomes and Genes
Gene Symbol: TNFR1
Description: TNF receptor superfamily member 1A
Alias: CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55, TNFAR, TNFR1, TNFR55, TNFR60, p55, p55-R, p60, tumor necrosis factor receptor superfamily member 1A, TNF-R1, TNF-RI, TNFR-I, tumor necrosis factor binding protein 1, tumor necrosis factor receptor 1A isoform beta, tumor necrosis factor receptor type 1, tumor necrosis factor-alpha receptor
- Simon A, van der Meer J, Vesely R, Myrdal U, Yoshimura K, Duys P, et al. Approach to genetic analysis in the diagnosis of hereditary autoinflammatory syndromes. Rheumatology (Oxford). 2006;45:269-73 pubmed..High-prevalence low-penetrant mutations from autoinflammatory genes do not occur more frequently in patients with hereditary autoinflammatory syndromes compared with the general population. ..
- Al Lamki R, Sadler T, Wang J, Reid M, Warren A, Movassagh M, et al. Tumor necrosis factor receptor expression and signaling in renal cell carcinoma. Am J Pathol. 2010;177:943-54 pubmed publisher..TNF signals via two distinct receptors (TNFRs). TNFR1, expressed in normal kidney primarily on endothelial cells, activates apoptotic signaling kinase 1 and nuclear ..
- Newton K, Matsumoto M, Wertz I, Kirkpatrick D, Lill J, Tan J, et al. Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies. Cell. 2008;134:668-78 pubmed publisher..Polyubiquitin editing may therefore be a general mechanism for attenuating innate immune signaling. ..
- Johnson B, Wang J, Taylor E, Caillier S, Herbert J, Khan O, et al. Multiple sclerosis susceptibility alleles in African Americans. Genes Immun. 2010;11:343-50 pubmed publisher..The results are consistent with shared disease genetic mechanisms among individuals of European and African ancestry. ..
- Poirier O, Nicaud V, Gariepy J, Courbon D, Elbaz A, Morrison C, et al. Polymorphism R92Q of the tumour necrosis factor receptor 1 gene is associated with myocardial infarction and carotid intima-media thickness--the ECTIM, AXA, EVA and GENIC Studies. Eur J Hum Genet. 2004;12:213-9 pubmed..70 (0.09) vs 0.67 (0.13), P=0.02). No significant association of the 92Q allele was found with BI in the GENIC Study. Overall, these results may suggest that carriers of the 92Q allele may be at increased risk of atherosclerosis. ..
- Steenholdt C, Enevold C, Ainsworth M, Brynskov J, Thomsen O, Bendtzen K. Genetic polymorphisms of tumour necrosis factor receptor superfamily 1b and fas ligand are associated with clinical efficacy and/or acute severe infusion reactions to infliximab in Crohn's disease. Aliment Pharmacol Ther. 2012;36:650-9 pubmed publisher..Moreover, FASLG and TNFRSF1B polymorphisms may confer genetic susceptibility to severe infusion reactions. These findings could potentially aid clinical decisions if confirmed in larger studies. ..
- Li J, McQuade T, Siemer A, Napetschnig J, Moriwaki K, Hsiao Y, et al. The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell. 2012;150:339-50 pubmed publisher..The current study provides insight into the structural changes that occur when RIP kinases are triggered to execute different signaling outcomes and expands the realm of amyloids to complex formation and signaling...
- Goris A, Fockaert N, Cosemans L, Clysters K, Nagels G, Boonen S, et al. TNFRSF1A coding variants in multiple sclerosis. J Neuroimmunol. 2011;235:110-2 pubmed publisher..26 (95% CI 1.41-3.61)], which appears independent of an established common risk variant in the same gene. No other non-synonymous variants in the same allele frequency range influencing risk of MS were observed. ..
- Glossop J, Nixon N, Dawes P, Hassell A, Mattey D. No association of polymorphisms in the tumor necrosis factor receptor I and receptor II genes with disease severity in rheumatoid arthritis. J Rheumatol. 2003;30:1406-9 pubmed..Our data suggest that neither the +36 TNFRSF1A SNP nor the +196 TNFRSF1B SNP is associated with RA severity in a population of Caucasian patients with RA. ..
- Varfolomeev E, Goncharov T, Fedorova A, Dynek J, Zobel K, Deshayes K, et al. c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. J Biol Chem. 2008;283:24295-9 pubmed publisher..c-IAP1 and c-IAP2 are recruited to tumor necrosis factor receptor 1 (TNFR1)-associated complexes where they can regulate receptor-mediated signaling...
- Cantarini L, Lucherini O, Cimaz R, Baldari C, Bellisai F, Rossi Paccani S, et al. Idiopathic recurrent pericarditis refractory to colchicine treatment can reveal tumor necrosis factor receptor-associated periodic syndrome. Int J Immunopathol Pharmacol. 2009;22:1051-8 pubmed..A poor response to colchicine treatment and/or a steroid-dependence may be the clue to investigate TNFRSF1A mutations in patients with idiopathic recurrent pericarditis. ..
- Gupta R, Sharma S, Das S. Association of TNF-alpha and TNFR1 promoters and 3' UTR region of TNFR2 gene polymorphisms with genetic susceptibility to tobacco-related oral carcinoma in Asian Indians. Oral Oncol. 2008;44:455-63 pubmed publisher..We assessed SNPs in TNF-alpha(-308, -238) and TNF receptor 1 (TNFR1; -609) promoters by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and at four ..
- Kümpfel T, Hohlfeld R. Multiple sclerosis. TNFRSF1A, TRAPS and multiple sclerosis. Nat Rev Neurol. 2009;5:528-9 pubmed publisher..This locus is of special interest because the R92Q substitution was previously detected in a group of multiple sclerosis patients who had additional symptoms compatible with the autoinflammatory syndrome TRAPS. ..
- Dobrzycka B, Terlikowski S, Kowalczuk O, Kinalski M. Circulating levels of TNF-alpha and its soluble receptors in the plasma of patients with epithelial ovarian cancer. Eur Cytokine Netw. 2009;20:131-4 pubmed publisher..Thus, the clinical value of an activated TNF system in EOC needs to be further investigated. ..
- Wertz I, O Rourke K, Zhou H, Eby M, Aravind L, Seshagiri S, et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature. 2004;430:694-9 pubmed..ubiquitin chains from receptor interacting protein (RIP), an essential mediator of the proximal TNF receptor 1 (TNFR1) signalling complex...
- Hasegawa M, Nishii C, Ohashi A, Tomita M, Nakai S, Murakami K, et al. Expression of tumor necrosis factor receptors on granulocytes in patients with myeloperoxidase anti-neutrophil cytoplasmic autoantibody-associated vasculitis. Nephron Clin Pract. 2009;113:c222-33 pubmed publisher..cytoplasmic autoantibody (ANCA)-associated vasculitis, we evaluated the cell surface expression of TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2)...
- Rigante D, Cantarini L, Imazio M, Lucherini O, Sacco E, Galeazzi M, et al. Autoinflammatory diseases and cardiovascular manifestations. Ann Med. 2011;43:341-6 pubmed publisher..Pericardial diseases are the most represented cardiovascular abnormalities, though the role of MEFV and TNFRSF1A in the initiation of heart involvement has not been demonstrated formally and will be discussed herein. ..
- Mahul Mellier A, Pazarentzos E, Datler C, Iwasawa R, Abuali G, Lin B, et al. De-ubiquitinating protease USP2a targets RIP1 and TRAF2 to mediate cell death by TNF. Cell Death Differ. 2012;19:891-9 pubmed publisherComponents of the TNFR1 complex are subject to dynamic ubiquitination that impacts on their effects as signalling factors...
- Kim S, Ohoka N, Okuhira K, Sai K, Nishimaki Mogami T, Naito M. Modulation of RIP1 ubiquitylation and distribution by MeBS to sensitize cancer cells to tumor necrosis factor ?-induced apoptosis. Cancer Sci. 2010;101:2425-9 pubmed publisher..These results indicate an important role of RIP1 in apoptosis induced by combined treatment with TNF? and MeBS, suggesting that MeBS sensitizes cancer cells to apoptosis by modulating RIP1 ubiquitylation and distribution. ..
- Safranow K, Dziedziejko V, Rzeuski R, Czyzycka E, Wojtarowicz A, Binczak Kuleta A, et al. Plasma concentrations of TNF-alpha and its soluble receptors sTNFR1 and sTNFR2 in patients with coronary artery disease. Tissue Antigens. 2009;74:386-92 pubmed publisher..Metabolic syndrome and diabetes are associated with higher plasma concentrations of TNF-alpha and its receptors. ..
- Lachmann H, Papa R, Gerhold K, Obici L, Touitou I, Cantarini L, et al. The phenotype of TNF receptor-associated autoinflammatory syndrome (TRAPS) at presentation: a series of 158 cases from the Eurofever/EUROTRAPS international registry. Ann Rheum Dis. 2014;73:2160-7 pubmed publisher..Patients had a median 70 symptomatic days a year, with fever, limb and abdominal pain and rash the commonest symptoms. Overall, there is little evidence of a significant effect of age or genotype on disease features at presentation. ..
- Coelho F, Reis H, Nicolato R, Romano Silva M, Teixeira M, Bauer M, et al. Increased serum levels of inflammatory markers in chronic institutionalized patients with schizophrenia. Neuroimmunomodulation. 2008;15:140-4 pubmed publisher..Inflammatory markers are increased in schizophrenia but they do not correlate with symptom severity. ..
- Dieude P, Osorio J, Petit Teixeira E, Moreno S, Garnier S, Cailleau Moindrault S, et al. A TNFR1 genotype with a protective role in familial rheumatoid arthritis. Arthritis Rheum. 2004;50:413-9 pubmed..in rheumatoid arthritis (RA) have suggested that the tumor necrosis factor receptor I (TNFRI) and TNFRII loci (TNFR1 and TNFR2) are susceptibility loci. A TNFR2 polymorphism was found to be associated with familial RA...
- Lee E, Jeon H, Yoo S, Choi Y, Kang H, Cho S, et al. Polymorphisms in apoptosis-related genes and survival of patients with early-stage non-small-cell lung cancer. Ann Surg Oncol. 2010;17:2608-18 pubmed publisher..The SNPs, and particularly their combined genotypes, can be used to identify patients at high risk for poor disease outcome. ..
- Dieude P, Goossens M, Cornelis F, Michou L, Bardin T, Tchernitchko D. The TNFRSF1A R92Q mutation is frequent in rheumatoid arthritis but shows no evidence for association or linkage with the disease. Ann Rheum Dis. 2007;66:1113-5 pubmed..5%, but no evidence for RA association or linkage to the disease. The R92Q mutation could be considered to be a low-penetrance variant. ..
- Stojanov S, Dejaco C, Lohse P, Huss K, Duftner C, Belohradsky B, et al. Clinical and functional characterisation of a novel TNFRSF1A c.605T>A/V173D cleavage site mutation associated with tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), cardiovascular complications and excellent response to e. Ann Rheum Dis. 2008;67:1292-8 pubmed publisher..T-cell senescence does not seem to have a pathogenetic role in affected patients. ..
- Cho Y, Challa S, Moquin D, Genga R, Ray T, Guildford M, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009;137:1112-23 pubmed publisher..Our findings suggest that RIP3 controls programmed necrosis by initiating the pronecrotic kinase cascade, and that this is necessary for the inflammatory response against virus infections. ..
- Karaderi T, Pointon J, Wordsworth T, Harvey D, Appleton L, Cohen C, et al. Evidence of genetic association between TNFRSF1A encoding the p55 tumour necrosis factor receptor, and ankylosing spondylitis in UK Caucasians. Clin Exp Rheumatol. 2012;30:110-3 pubmed..In view of the previously reported associations of TNFRSF1A with AS, in Caucasians and Chinese, and the biological plausibility of this candidate gene, replication of this finding in well powered studies is clearly indicated. ..
- Nedjai B, Hitman G, Church L, Minden K, Whiteford M, McKee S, et al. Differential cytokine secretion results from p65 and c-Rel NF-?B subunit signaling in peripheral blood mononuclear cells of TNF receptor-associated periodic syndrome patients. Cell Immunol. 2011;268:55-9 pubmed publisher..condition caused by mutations in the TNFRSF1A gene which encodes the tumor necrosis factor (TNF) receptor, TNFR1. We investigated the effect of three high penetrance and three low penetrance TNFRSF1A mutations upon NF-?B ..
- Siebert S, Amos N, Fielding C, Wang E, Aksentijevich I, Williams B, et al. Reduced tumor necrosis factor signaling in primary human fibroblasts containing a tumor necrosis factor receptor superfamily 1A mutant. Arthritis Rheum. 2005;52:1287-92 pubmed..Our data suggest a new hypothesis, in that the C43S TRAPS mutation may cause the inflammatory phenotype by increasing resistance to TNFalpha-induced apoptosis. ..
- Amoura Z, Dode C, Hue S, Caillat Zucman S, Bahram S, Delpech M, et al. Association of the R92Q TNFRSF1A mutation and extracranial deep vein thrombosis in patients with Behçet's disease. Arthritis Rheum. 2005;52:608-11 pubmed..This new finding may help in understanding the complex prothrombotic state in patients with Behçet's disease. ..
- Tarrats N, Moles A, Morales A, Garcia Ruiz C, Fernandez Checa J, Mari M. Critical role of tumor necrosis factor receptor 1, but not 2, in hepatic stellate cell proliferation, extracellular matrix remodeling, and liver fibrogenesis. Hepatology. 2011;54:319-27 pubmed publisher..Using HSCs from wild-type, TNF-receptor-1 (TNFR1) knockout, TNF-receptor-2 (TNFR2) knockout, or TNFR1/R2 double-knockout (TNFR-DKO) mice, we show that loss of both ..
- Branschädel M, Aird A, Zappe A, Tietz C, Krippner Heidenreich A, Scheurich P. Dual function of cysteine rich domain (CRD) 1 of TNF receptor type 1: conformational stabilization of CRD2 and control of receptor responsiveness. Cell Signal. 2010;22:404-14 pubmed publisher..Both TNF receptors, TNFR1 and TNFR2, contain four cysteine rich domains (CRD) in their extracellular parts...
- Rebelo S, Amel Kashipaz M, Radford P, Bainbridge S, Fiets R, Fang J, et al. Novel markers of inflammation identified in tumor necrosis factor receptor-associated periodic syndrome (TRAPS) by transcriptomic analysis of effects of TRAPS-associated tumor necrosis factor receptor type I mutations in an endothelial cell line. Arthritis Rheum. 2009;60:269-80 pubmed publisher..Different mutants have specific expression profiles, indicating mutation-specific effects. The expression of some of these markers was also elevated in samples from TRAPS patients. ..
- Aganna E, Hammond L, Hawkins P, Aldea A, McKee S, van Amstel H, et al. Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes. Arthritis Rheum. 2003;48:2632-44 pubmed..TNFRSF1A mutations are not commonly associated with nonfamilial recurrent fevers of unknown etiology. ..
- Bachetti T, Chiesa S, Castagnola P, Bani D, Di Zanni E, Omenetti A, et al. Autophagy contributes to inflammation in patients with TNFR-associated periodic syndrome (TRAPS). Ann Rheum Dis. 2013;72:1044-52 pubmed publisher..syndrome (TRAPS) is caused by TNFRSF1A mutations, known to induce intracellular retention of the TNF? receptor 1 (TNFR1) protein, defective TNF?-induced apoptosis, and production of reactive oxygen species...
- Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell. 2003;114:181-90 pubmedApoptosis induced by TNF-receptor I (TNFR1) is thought to proceed via recruitment of the adaptor FADD and caspase-8 to the receptor complex...
- Davidson S, Liu Y, Danoy P, Wu X, Thomas G, Jiang L, et al. Association of STAT3 and TNFRSF1A with ankylosing spondylitis in Han Chinese. Ann Rheum Dis. 2011;70:289-92 pubmed publisher..Furthermore, previous findings demonstrating that ERAP1, but not IL23R, is associated with AS in Chinese patients were confirmed. ..
- Pincheira R, Castro A, Ozes O, Idumalla P, Donner D. Type 1 TNF receptor forms a complex with and uses Jak2 and c-Src to selectively engage signaling pathways that regulate transcription factor activity. J Immunol. 2008;181:1288-98 pubmedThe type 1 TNFR (TNFR1) contains a death domain through which it interacts with other death-domain proteins to promote cellular responses...
- Sainz J, Salas Alvarado I, López Fernández E, Olmedo C, Comino A, Garcia F, et al. TNFR1 mRNA expression level and TNFR1 gene polymorphisms are predictive markers for susceptibility to develop invasive pulmonary aspergillosis. Int J Immunopathol Pharmacol. 2010;23:423-36 pubmed..TNF acts through TNF receptor 1 (TNFR1) triggering a pro-inflammatory response, and therefore plays a pivotal role in immune regulation and host immune ..
- Stojanov S, Lohse P, Lohse P, Hoffmann F, Renner E, Zellerer S, et al. Molecular analysis of the MVK and TNFRSF1A genes in patients with a clinical presentation typical of the hyperimmunoglobulinemia D with periodic fever syndrome: a low-penetrance TNFRSF1A variant in a heterozygous MVK carrier possibly influences the p. Arthritis Rheum. 2004;50:1951-8 pubmed
- Culpan D, Cornish A, Love S, Kehoe P, Wilcock G. Protein and gene expression of tumour necrosis factor receptors I and II and their promoter gene polymorphisms in Alzheimer's disease. Exp Gerontol. 2007;42:538-44 pubmed..Our findings suggest that TNF-RI and -RII promoter gene polymorphisms and variations in protein and gene expression of these receptors are unlikely to play a major role in the development of AD. ..
- Lainka E, Neudorf U, Lohse P, Timmann C, Stojanov S, Huss K, et al. Incidence of TNFRSF1A mutations in German children: epidemiological, clinical and genetic characteristics. Rheumatology (Oxford). 2009;48:987-91 pubmed publisher..The R92Q substitution was found in 19 (83%) of 23 cases. The incidence of TRAPS is low and corresponds to 6-10 newly diagnosed patients < or =16 years per year in Germany. ..
- Gattorno M, Sormani M, D Osualdo A, Pelagatti M, Caroli F, Federici S, et al. A diagnostic score for molecular analysis of hereditary autoinflammatory syndromes with periodic fever in children. Arthritis Rheum. 2008;58:1823-32 pubmed publisher..Our results further help to optimize the molecular analysis by suggesting the order in which the genes should be screened. ..
- Aganna E, Hawkins P, Ozen S, Pettersson T, Bybee A, McKee S, et al. Allelic variants in genes associated with hereditary periodic fever syndromes as susceptibility factors for reactive systemic AA amyloidosis. Genes Immun. 2004;5:289-93 pubmed..Although allelic variants in HPFs genes are not major susceptibility factors for AA amyloidosis in chronic inflammatory disease, low-penetrance variants of MEFV and TNFRSF1A may have clinically significant proinflammatory effects. ..
- Mells G, Floyd J, Morley K, Cordell H, Franklin C, Shin S, et al. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat Genet. 2011;43:329-32 pubmed publisher..New candidate genes include STAT4, DENND1B, CD80, IL7R, CXCR5, TNFRSF1A, CLEC16A and NFKB1. This study has considerably expanded our knowledge of the genetic architecture of PBC. ..
- Kümpfel T, Hoffmann L, Rübsamen H, Pöllmann W, Feneberg W, Hohlfeld R, et al. Late-onset tumor necrosis factor receptor-associated periodic syndrome in multiple sclerosis patients carrying the TNFRSF1A R92Q mutation. Arthritis Rheum. 2007;56:2774-83 pubmed..Autoinflammatory syndromes and especially late-onset TRAPS should be considered in MS patients who report symptoms such as arthralgias/arthritis, myalgias, urticarial rash, and severe fatigue. ..
- Dode C, Andre M, Bienvenu T, Hausfater P, Pecheux C, Bienvenu J, et al. The enlarging clinical, genetic, and population spectrum of tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum. 2002;46:2181-8 pubmed..Because an accurate diagnosis in patients with recurrent inflammatory syndromes is crucial for proper clinical management and treatment, genetic screening for TNFRSF1A is warranted. ..
- Storey H, Stewart A, Vandenabeele P, Luzio J. The p55 tumour necrosis factor receptor TNFR1 contains a trans-Golgi network localization signal in the C-terminal region of its cytoplasmic tail. Biochem J. 2002;366:15-22 pubmed..We have shown by immunofluorescence and immunoelectron microscopy that the p55 tumour necrosis factor receptor, TNFR1, is principally localized to the trans-Golgi network in the human breast carcinoma cell line, MCF7...
- Schutze S, Machleidt T, Adam D, Schwandner R, Wiegmann K, Kruse M, et al. Inhibition of receptor internalization by monodansylcadaverine selectively blocks p55 tumor necrosis factor receptor death domain signaling. J Biol Chem. 1999;274:10203-12 pubmed..We show that MDC does not prevent the interaction of the p55 TNF receptor (TR55) with FAN and TRADD...
- Williamson L, Hull D, Mehta R, Reeves W, Robinson B, Toghill P. Familial Hibernian fever. Q J Med. 1982;51:469-80 pubmed..The disease appears to have a benign course and no patient has developed amyloid. ..
- Bridges S, Jenq G, Moran M, Kuffner T, Whitworth W, McNicholl J. Single-nucleotide polymorphisms in tumor necrosis factor receptor genes: definition of novel haplotypes and racial/ethnic differences. Arthritis Rheum. 2002;46:2045-50 pubmed..These striking racial/ethnic differences in TNFR SNP frequencies may influence the likelihood of familial RA, severe disease, or response to TNF inhibitors and may have important evolutionary implications. ..
- Allen R, Lee E, Roberts D, Park B, Pirmohamed M. Polymorphisms in the TNF-alpha and TNF-receptor genes in patients with coronary artery disease. Eur J Clin Invest. 2001;31:843-51 pubmed..Polymorphisms in the TNF-alpha promoter region and TNF-receptor genes are not associated with the development of CAD. ..
- McDermott M, Ogunkolade B, McDermott E, Jones L, Wan Y, Quane K, et al. Linkage of familial Hibernian fever to chromosome 12p13. Am J Hum Genet. 1998;62:1446-51 pubmed
- Hsu H, Huang J, Shu H, Baichwal V, Goeddel D. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity. 1996;4:387-96 pubmedThe death domain of tumor necrosis factor (TNF) receptor-1 (TNFR1) triggers distinct signaling pathways leading to apoptosis and NF-kappa B activation through its interaction with the death domain protein TRADD...