Affinage

TNFRSF1A

Tumor necrosis factor receptor superfamily member 1A · UniProt P19438

Length
455 aa
Mass
50.5 kDa
Annotated
2026-06-10
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TNFRSF1A (TNFR1/CD120a/p55) is the high-affinity receptor for soluble TNF, binding with ~19 pM affinity owing to the marked stability of the TNF–TNFR1 complex, which explains its predominant role in cellular responses to soluble TNF relative to TNFR2 (PMID:9435233). Its extracellular region comprises four cysteine-rich repeats and, although the receptor lacks intrinsic kinase activity, ligand binding drives signaling through recruited effectors (PMID:1698610). Upon engagement, TNFR1 bifurcates into a death-inducing pathway dependent on FADD and a gene-inductive NF-κB/JNK pathway that proceeds independently of FADD (PMID:9427646), with TRAF2 acting as a rheostat that both restrains and licenses TNFR1-induced cell death (PMID:9743381); cross-linking of TNFR1 alone is necessary and sufficient to activate p42mapk/erk2 and to induce iNOS expression in macrophages (PMID:7636214, PMID:9712914). The receptor's death domain is both necessary and sufficient for partitioning into lipid rafts, a localization required for apoptotic signaling (PMID:11937569). TNFR1 signaling output is tuned by ERK-dependent phosphorylation: p42mapk/erk2 phosphorylates the cytoplasmic domain at Thr-236 and Ser-270 (priming further phosphorylation at Ser-240/Ser-244), redistributing the receptor from the Golgi/plasma membrane into ER-associated tubular structures where it recruits Bcl-2 to suppress apoptosis while preserving NF-κB activation (PMID:10551865, PMID:10702263, PMID:11278725). Mutations in the extracellular cysteine-rich domains cause TNF receptor-associated periodic syndrome (TRAPS) by impairing ectodomain shedding and receptor trafficking, producing surface-deficient, cytoplasmically retained receptor that constitutively drives NF-κB, IL-1β/MAPK, and STAT3 signaling, resists TNF-induced apoptosis, and disrupts NF-κB negative feedback (PMID:10899034, PMID:25888769, PMID:29467762, PMID:16508982). TNFRSF1A is itself a direct STAT3 transcriptional target that mediates basal and TNFα-induced NF-κB activity in breast cancer cells (PMID:29621649).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1990 High

    Established the molecular identity of TNFR1 as a four-cysteine-rich-repeat surface receptor lacking intrinsic kinase activity, defining how it must signal through recruited partners and explaining the origin of soluble receptor.

    Evidence cDNA cloning from soluble TBPI sequence, CHO transfection, and monoclonal antibody characterization

    PMID:1698610

    Open questions at the time
    • Did not identify the kinases or adaptors that mediate phosphorylation downstream
    • Mechanism of soluble receptor generation not resolved
  2. 1994 Medium

    Showed that TNF binding selectively recruits a serine kinase activity to TNFR1 (not TNFR2), beginning to explain how a kinase-deficient receptor transduces phosphorylation signals.

    Evidence Immunoprecipitation of TNFR60 from 32P-labeled U-937 cells with in vitro kinase assay and pharmacological inhibition

    PMID:8089485

    Open questions at the time
    • Identity of the associated kinase not established
    • Substrate proteins (125/97/85/60 kDa) not identified
  3. 1995 Medium

    Demonstrated that TNFR1 cross-linking alone is necessary and sufficient to activate ERK2, attributing a specific MAPK output to this receptor.

    Evidence Receptor-specific agonistic/blocking antibodies and ERK2 tyrosine phosphorylation readout in mouse macrophages

    PMID:7636214

    Open questions at the time
    • Did not map the route from receptor to ERK activation
    • Single cell type
  4. 1997 Medium

    Revealed receptor cross-talk: TNFR1 dominantly signals HIV production, but co-activation with TNFR2 by membrane TNF switches output toward apoptosis, showing ligand form dictates outcome.

    Evidence Receptor-specific antibodies and noncleavable membrane-TNF coculture in HIV-infected T cells

    PMID:8996244

    Open questions at the time
    • Molecular basis of the soluble-vs-membrane TNF switch not defined
    • Single-lab system
  5. 1998 High

    Separated TNFR1's two signaling arms genetically — FADD drives apoptosis but is dispensable for NF-κB/JNK — and identified TRAF2 as a bidirectional regulator of death, establishing the apoptosis-versus-gene-induction dichotomy.

    Evidence Dominant-negative FADD and wild-type/mutant TRAF2 overexpression in HeLa with cell death, NF-κB, and JNK readouts

    PMID:9427646 PMID:9743381

    Open questions at the time
    • Structural basis of FADD vs TRAF2 recruitment not resolved
    • How TRAF2 levels are set in vivo unclear
  6. 1998 High

    Quantified TNFR1 as the high-affinity soluble-TNF receptor and attributed selectivity to complex stability, explaining why TNFR1 dominates responses to soluble ligand.

    Evidence Binding kinetics with association/dissociation rate constants at 37°C for both receptors

    PMID:9435233

    Open questions at the time
    • Does not address membrane-TNF binding behavior
    • No structural model of the stabilized complex
  7. 1998 High

    Showed TNFR1 is necessary and sufficient to induce iNOS/NO in macrophages with TNFR2 augmenting via ligand-passing, mapping an inflammatory effector output to the receptor.

    Evidence Receptor-specific antibodies, knockout mice, and iNOS mRNA/protein/NO2- quantification

    PMID:9712914

    Open questions at the time
    • Intracellular pathway linking TNFR1 to iNOS not fully traced
  8. 1999 High

    Identified ERK2 as the kinase phosphorylating the TNFR1 cytoplasmic domain at multiple Ser/Thr sites, with phosphorylation driving relocation from plasma membrane/Golgi into ER tubules — linking covalent modification to receptor trafficking.

    Evidence GST-CD120a in vitro kinase assay, 32P labeling, site-directed mutagenesis, and confocal microscopy in COS-7 cells

    PMID:10551865

    Open questions at the time
    • Functional consequence of ER relocation not yet shown
    • Sequence/identity of phospho-sites not yet mapped at this stage
  9. 2000 High

    Pinpointed Thr-236 and Ser-270 as primary ERK phosphorylation sites priming secondary Ser-240/Ser-244 phosphorylation, providing residue-level resolution of the trafficking switch.

    Evidence Deletional/site-directed mutagenesis, 32P phospho-mapping, and TNF-receptor-deficient mice

    PMID:10702263

    Open questions at the time
    • The phosphatase reversing these modifications unknown
    • Stoichiometry of phosphorylation in vivo unclear
  10. 2001 High

    Established the functional output of ERK phosphorylation: relocated TNFR1 recruits Bcl-2 in ER tubules to block apoptosis while preserving NF-κB, defining a phosphorylation-controlled pro-survival switch.

    Evidence ERK2 overexpression, antisense Bcl-2 knockdown, localization, and apoptosis/NF-κB assays

    PMID:11278725

    Open questions at the time
    • Direct TNFR1–Bcl-2 interaction interface not defined
    • Generality across cell types not established
  11. 2002 High

    Showed the death domain is necessary and sufficient for TNFR1 lipid-raft localization and that raft partitioning is required for apoptosis, tying a specific subdomain to a specific signaling compartment.

    Evidence Deletion/point mutagenesis (including lpr L351N), chimeric receptors, sucrose-gradient fractionation, confocal imaging, and apoptosis assays

    PMID:11937569

    Open questions at the time
    • Raft components recruited by the DD not identified
    • Relationship between raft and ER-tubule pools unresolved
  12. 2006 Medium

    Demonstrated that structural (cysteine/threonine) TRAPS mutations, but not R92Q, impair TNFR1-mediated apoptosis with absent caspase-8 activation, linking specific mutation classes to defective death signaling.

    Evidence TNFα+cycloheximide stimulation of patient neutrophils with annexin V and caspase-8 assays

    PMID:16508982

    Open questions at the time
    • Mechanism connecting structural mutation to caspase-8 failure not defined
    • Small mutation-type cohort
  13. 2000 Medium

    Proposed impaired ectodomain shedding as a TRAPS mechanism, where CRD mutations reduce production of the antagonistic soluble receptor.

    Evidence Functional shedding assays in patient cells with extracellular-domain mutational analysis

    PMID:10899034

    Open questions at the time
    • Shedding defect does not explain all TRAPS mutations
    • Quantitative contribution to disease unclear
  14. 2007 Medium

    Linked a specific splice/CRD3 mutation to reduced soluble and surface TNFR1 with elevated basal NF-κB, refining the trafficking-defect model of TRAPS.

    Evidence Western blot, sTNFR1 ELISA, surface FACS, and NF-κB transcription-factor assay in patient PBMCs

    PMID:18086728

    Open questions at the time
    • Mechanism connecting retention to constitutive NF-κB not established
    • Single mutation
  15. 2013 Medium

    Showed the MS-associated rs1800693(G) allele produces a soluble TNFRSF1A Δ6 isoform lacking transmembrane/cytoplasmic domains and enhances TNF-driven CXCL10 induction in monocytes, connecting a common variant to altered TNF responsiveness.

    Evidence Isoform RT-PCR, serum sTNFR1 ELISA, and monocyte transcriptional profiling in genotyped donors

    PMID:24174586

    Open questions at the time
    • How the Δ6 isoform alters signaling mechanistically unclear
    • No change in serum soluble receptor detected
  16. 2015 Medium

    Demonstrated that an S59P TRAPS mutation causes cytoplasmic receptor retention and constitutive activation of NF-κB, IL-1β, MAPK, and SRC/JAK/STAT3 pathways with apoptosis resistance, broadening the multi-pathway hyperactivation model.

    Evidence HEK-293 transfection, immunofluorescence, immunoblotting, cytokine arrays, and patient PBMC stimulation

    PMID:25888769

    Open questions at the time
    • Mechanism converting trafficking defect to constitutive multi-pathway activation undefined
    • Single mutation
  17. 2015 Medium

    Extended TRAPS signaling dysregulation to adaptive immunity, showing high-penetrance mutations hyperactivate ERK/STAT/mTOR/NF-κB in CD4+ T cells and impair regulatory T cells.

    Evidence Phosphoflow cytometry and Treg frequency/function assays in patient peripheral blood

    PMID:26598380

    Open questions at the time
    • Cell-intrinsic vs systemic causes of Treg defect not separated
    • Penetrance-dependent mechanism not resolved
  18. 2018 Medium

    Connected TRAPS receptor deficiency to failed miRNA-based NF-κB feedback via an IRE1/UPR–IL-1β axis, providing a mechanistic basis for cytokine hyperresponsiveness.

    Evidence Patient-derived fibroblasts, RT-qPCR for miR-146a/miR-155, IRE1 inhibitor 4u8C, and cytokine ELISA

    PMID:29467762

    Open questions at the time
    • How TNFR1 deficiency triggers UPR not defined
    • In vivo relevance to flares unclear
  19. 2018 Medium

    Identified TNFRSF1A as a direct STAT3 transcriptional target driving basal and TNFα-induced NF-κB in triple-negative breast cancer, placing the receptor downstream of an oncogenic transcription factor.

    Evidence STAT3 inhibition with expression analysis, STAT3 chromatin-binding assay, TNFRSF1A siRNA, and NF-κB reporter assays

    PMID:29621649

    Open questions at the time
    • STAT3-binding element not finely mapped
    • In vivo tumor relevance not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the lipid-raft (death-inducing) and ER-tubule (Bcl-2-protective) receptor pools are dynamically partitioned, and how this balance is dysregulated by TRAPS mutations to drive constitutive inflammation, remains unresolved.
  • No unified model linking phospho-trafficking, raft localization, and TRAPS pathology
  • Phosphatases and shedding proteases not characterized in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-5357801 Programmed Cell Death 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
BCL2FADDSTAT3TNFTRAF2

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 TNFRSF1A (TNF-R1/CD120a/TNFR60) is the high-affinity receptor for soluble TNF, with a Kd of ~19 pM at 37°C, approximately 20-fold higher affinity than TNFR2 (Kd ~420 pM). The high affinity is primarily due to the marked stability of the TNF–TNFR1 complex, explaining the predominant role of TNFR1 in cellular responses to soluble TNF. Binding kinetics (association and dissociation rate constants) measured at 37°C for both TNF receptors Proceedings of the National Academy of Sciences of the United States of America High 9435233
1990 The extracellular domain of TNFRSF1A contains four cysteine-rich repeats homologous to NGF receptor and CDw40. The receptor lacks intrinsic protein kinase activity yet can signal phosphorylation of specific cellular proteins. Soluble forms of the receptor are structurally identical to the extracellular cytokine-binding domain and are derived from the same transcripts encoding the cell-surface receptor. cDNA cloning using NH2-terminal amino acid sequence of soluble TBPI; transfection of CHO cells; immunological characterization with monoclonal antibodies The EMBO journal High 1698610
1994 TNF binding to TNFRSF1A (TNFR60/CD120a) induces rapid, ligand-concentration-dependent association of a serine protein kinase activity with TNFR60 immune complexes, along with several phosphoproteins. The TNFR60-associated kinase activity phosphorylates proteins of 125, 97, 85, and 60 kDa and is inhibited by staurosporine but not by PKA/PKC inhibitors. TNFR80 did not show similar kinase association. Immunoprecipitation of TNFR60 from 32P-labeled U-937 cells; in vitro kinase assay on immune complexes; pharmacological inhibition Journal of immunology Medium 8089485
1995 Cross-linking of TNFRSF1A (CD120a/p55) alone, but not CD120b (p75), is both necessary and sufficient for activation of p42mapk/erk2 in mouse macrophages, as determined using blocking and agonistic receptor-specific antibodies. Specific agonistic and blocking antibodies against each TNF receptor; p42mapk/erk2 activation measured by tyrosine phosphorylation in mouse macrophages Journal of immunology Medium 7636214
1998 FADD (dominant-negative mutant) is part of the TNFR60-initiated apoptotic pathway but does not play a role in TNFR60-mediated NF-κB or JNK gene induction. GFP-ΔFadd expression in HeLa cells inhibited TNFR60-, Fas/Apo1- and TRAIL-R/Apo2-mediated cell death without affecting TNF-mediated NF-κB or JNK activation. Stable expression of GFP-tagged dominant-negative FADD in HeLa cells; NF-κB and JNK activation assays; apoptosis assays Current biology High 9427646
1998 TNFR-associated factor 2 (TRAF2) is critically involved in both negative and positive regulation of TNFR60-induced cell death. TNFR80 costimulation enhances TNFR60-induced cell death selectively (not Fas/TRAIL/ceramide/daunorubicin-mediated death) through TNFR80-mediated depletion of antiapoptotic TRAF2 function. Overexpression of TRAF2 desensitized TNFR60-induced cell death, while a TRAF2 NF-κB-activation-deficient mutant enhanced it. Overexpression of wild-type and mutant TRAF2 in HeLa cells; receptor-specific antibody costimulation; JNK activation assays; cell death assays Journal of immunology High 9743381
1998 Cross-linking of TNFRSF1A (CD120a/p55) is necessary and sufficient to induce iNOS mRNA expression and NO2- production in mouse macrophages, while CD120b (p75) augments this response by ligand-passing to CD120a and by initiating a separate sustained signaling event. Simultaneous ligation of both receptors leads to markedly prolonged iNOS mRNA/protein expression and potentiated nitric oxide production. Receptor-specific antibody-mediated cross-linking; anti-receptor blocking antibodies; CD120a- and CD120b-deficient mice; iNOS mRNA, protein, and NO2- quantification The Journal of biological chemistry High 9712914
1999 p42mapk/erk2 phosphorylates the cytoplasmic domain of TNFRSF1A (CD120a/p55) at multiple Ser/Thr residues. Phosphorylation was induced by TNFα, GM-CSF, M-CSF, and zymosan in macrophages and blocked by immunodepletion of p42mapk/erk2 or PD098059. As a consequence of phosphorylation, CD120a expression at the plasma membrane and Golgi apparatus is lost and the receptor accumulates in intracellular tubular structures associated with the endoplasmic reticulum. Mutation of the four ERK consensus phosphorylation sites to Ala prevented ER-tubular redistribution. GST-CD120a fusion protein as substrate for in vitro phosphorylation; 32P metabolic labeling; COS-7 cell transfection with CD120a and constitutively active MEK-1; site-directed mutagenesis; confocal microscopy The Journal of biological chemistry High 10551865
2000 The preferred phosphorylation sites on TNFRSF1A (CD120a/p55) by p42mapk/erk2 are Thr-236 and Ser-270 within the membrane proximal region; primary phosphorylation at these sites enables subsequent phosphorylation at Ser-240 and Ser-244. CD120a (p55) itself is necessary and sufficient for induction of ERK kinase activity, as demonstrated using receptor-deficient mice. Deletional and site-directed mutagenesis of CD120a cytoplasmic domain; 32P phosphorylation mapping; mice deficient in CD120a, CD120b, or both The Journal of biological chemistry High 10702263
2001 Phosphorylation of TNFRSF1A (CD120a) by p42mapk/erk2 inhibits the apoptotic activity of the receptor while preserving its ability to activate NF-κB. Phosphorylated CD120a is re-localized from the Golgi to tubular ER structures where it recruits Bcl-2. Antisense-mediated knockdown of Bcl-2 reversed the protection from apoptosis conferred by receptor phosphorylation. p42mapk/erk2 overexpression; antisense Bcl-2 knockdown; subcellular localization; apoptosis and NF-κB assays The Journal of biological chemistry High 11278725
2002 The death domain (DD) of TNFRSF1A (CD120a) is both necessary and sufficient to promote localization of the receptor to lipid rafts. Deletion of the DD, pairwise deletion of individual DD alpha-helices, or introduction of the lpr mutation (L351N) all prevented raft localization and abolished apoptotic signaling. CD120b (which lacks a DD) is absent from the Golgi but present in bulk plasma membrane; a chimeric receptor with the CD120a DD fused to CD120b cytoplasmic domain was predominantly localized to lipid rafts. Confocal microscopy; sucrose density gradient ultracentrifugation; deletion and point mutagenesis; chimeric receptor construction; apoptosis assays Journal of immunology High 11937569
2000 One mechanism of autoinflammation in TRAPS is impaired cleavage/shedding of the TNFRSF1A ectodomain upon cellular activation in patients with certain mutations. Mutations in the extracellular cysteine-rich domains (especially those disrupting disulfide bonds) reduce shedding of the soluble antagonistic form of the receptor. Functional studies of TNFRSF1A shedding in patient cells; mutational analysis of extracellular domain Current opinion in immunology Medium 10899034
2007 A novel splice-site mutation in TNFRSF1A (c.472+1G>A) causes a 45-nucleotide insertion of intronic DNA resulting in an in-frame insertion of 15 amino acids and deletion of Cys129 in CRD3 of the mature TNFR1 protein. This mutation reduces serum soluble TNFR1 levels, decreases surface TNFR1 expression, and increases basal NF-κB activation in PBMCs compared with healthy controls and other TRAPS mutations. Western blot; multiplex bead cytokine immunoassay; ELISA for sTNFR1; FACS for surface TNFR1; NF-κB ELISA-based transcription factor assay Annals of the rheumatic diseases Medium 18086728
2015 The novel S59P TNFRSF1A mutation causes cytoplasmic accumulation/defective trafficking of TNF-R1 and constitutively activates the NF-κB, IL-1β, MAPK, and SRC/JAK/STAT3 pathways and inhibits apoptosis. This mutation also leads to enhanced and persistent IL-6 and IL-8 secretion from PBMCs in response to IL-1β stimulation. HEK-293 cell transfection with mutant constructs; immunofluorescence; immunoblotting for p-IκBα and p65; cytokine array; PBMC stimulation assays Arthritis research & therapy Medium 25888769
2013 The MS susceptibility allele rs1800693(G) in the TNFRSF1A locus generates an RNA isoform, TNFRSF1A Δ6, lacking the transmembrane and cytoplasmic domains. This allele alters monocyte responses, causing a more robust transcriptional induction of CXCL10 and other genes in response to TNF-α, without detectably altering serum levels of soluble TNFRSF1A. Real-time PCR for isoform expression; ELISA for serum sTNFR1; transcriptional profiling of monocytes from genotyped donors; prospective clinical data analysis Neurology Medium 24174586
2018 TNFRSF1A is a direct transcriptional target of STAT3 in breast cancer cells. STAT3 binds directly to a regulatory region within the TNFRSF1A gene, and TNFRSF1A levels depend on STAT3 function in both constitutive and cytokine-induced STAT3 activation models. TNFRSF1A is a major mediator of both basal and TNFα-induced NF-κB activity in triple-negative breast cancer cells. STAT3 inhibitor treatment + gene expression analysis; chromatin binding assay (STAT3 binding to TNFRSF1A regulatory region); siRNA knockdown of TNFRSF1A; NF-κB reporter assays Neoplasia Medium 29621649
2018 In TRAPS patient-derived dermal fibroblasts carrying TNFRSF1A mutations, TNFR1 surface expression is absent/deficient. These cells fail to upregulate miR-146a and miR-155 in response to LPS, leading to hyperresponsive cytokine production. This failure is mechanistically dependent on IRE1 (inositol-requiring enzyme 1): IL-1β produced by unfolded protein response activation downregulates miR-146a and miR-155 in an IRE1-dependent manner, impairing NF-κB negative feedback. Immunofluorescence for TNFR1 surface expression; RT-qPCR for miRNA expression; IRE1 inhibitor (4u8C); ELISA for cytokines; microfluidics miRNA profiling Frontiers in immunology Medium 29467762
2006 Neutrophils from TRAPS patients with cysteine or threonine residue mutations (but not those with the R92Q substitution) display resistance to TNF-induced apoptosis and absent caspase-8 activation, in contrast to normal controls and R92Q carriers, suggesting that structural TNFRSF1A mutations impair TNFR1-mediated apoptotic signaling. Neutrophil stimulation with TNFα + cycloheximide; annexin V binding by flow cytometry; caspase-8 activation assay Arthritis and rheumatism Medium 16508982
1997 In HIV-infected T cells, TNFR60 (TNFRSF1A) dominantly signals HIV production upon selective stimulation, while simultaneous activation of both TNFR60 and TNFR80 by membrane TNF (but not soluble TNF) switches the cellular response from viral production to enhanced apoptosis, demonstrating cooperative/antagonistic signaling between the two TNF receptors. Receptor-specific agonistic and antagonistic antibodies; coculture with cells expressing noncleavable membrane TNF; HIV production measurement; apoptosis assays The Journal of experimental medicine Medium 8996244
2015 High-penetrance TNFRSF1A mutations cause hyperactivation of ERK1/2, STAT1/3/5, mTOR, and NF-κB signaling pathways in conventional CD4+ T cells, and reduce the frequency and suppressive function of peripheral regulatory T cells. Low-penetrance mutations show partial versions of these alterations. Phosphoflow cytometry for signaling pathways; frequency and functional assays of Treg and conventional T cells in TRAPS patient peripheral blood Journal of leukocyte biology Medium 26598380

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nature genetics 641 19525953
2008 TLR-4, IL-1R and TNF-R signaling to NF-kappaB: variations on a common theme. Cellular and molecular life sciences : CMLS 373 18535784
1998 The type 1 receptor (CD120a) is the high-affinity receptor for soluble tumor necrosis factor. Proceedings of the National Academy of Sciences of the United States of America 360 9435233
1990 Soluble forms of tumor necrosis factor receptors (TNF-Rs). The cDNA for the type I TNF-R, cloned using amino acid sequence data of its soluble form, encodes both the cell surface and a soluble form of the receptor. The EMBO journal 347 1698610
2001 The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers. American journal of human genetics 252 11443543
2000 TNFRSF1A mutations and autoinflammatory syndromes. Current opinion in immunology 191 10899034
1998 Dominant-negative FADD inhibits TNFR60-, Fas/Apo1- and TRAIL-R/Apo2-mediated cell death but not gene induction. Current biology : CB 142 9427646
2006 Neutrophils from patients with TNFRSF1A mutations display resistance to tumor necrosis factor-induced apoptosis: pathogenetic and clinical implications. Arthritis and rheumatism 114 16508982
1998 TNFR80-dependent enhancement of TNFR60-induced cell death is mediated by TNFR-associated factor 2 and is specific for TNFR60. Journal of immunology (Baltimore, Md. : 1950) 114 9743381
2014 Polymorphisms in the inflammatory pathway genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG are associated with susceptibility of inflammatory bowel disease in a Danish cohort. PloS one 105 24971461
2007 Bruton's tyrosine kinase mediates NF-kappa B activation and B cell survival by B cell-activating factor receptor of the TNF-R family. Journal of immunology (Baltimore, Md. : 1950) 100 17785824
2010 Association of STAT3 and TNFRSF1A with ankylosing spondylitis in Han Chinese. Annals of the rheumatic diseases 97 21068102
2005 Systemic cytokine levels and the effects of etanercept in TNF receptor-associated periodic syndrome (TRAPS) involving a C33Y mutation in TNFRSF1A. Rheumatology (Oxford, England) 78 16287931
2002 Restricted localization of the TNF receptor CD120a to lipid rafts: a novel role for the death domain. Journal of immunology (Baltimore, Md. : 1950) 74 11937569
2011 Long-term clinical profile of children with the low-penetrance R92Q mutation of the TNFRSF1A gene. Arthritis and rheumatism 73 21225694
1999 Suppressed alloantigen presentation, increased TNF-alpha, IL-1, IL-1Ra, IL-10, and modulation of TNF-R in UV-irradiated human skin. The Journal of investigative dermatology 71 10233758
2008 Association of IL23R, TNFRSF1A, and HLA-DRB1*0103 allele variants with inflammatory bowel disease phenotypes in the Finnish population. Inflammatory bowel diseases 64 18338763
2013 The expanding spectrum of low-penetrance TNFRSF1A gene variants in adults presenting with recurrent inflammatory attacks: clinical manifestations and long-term follow-up. Seminars in arthritis and rheumatism 63 24393624
2012 Pharmacogenetic analysis of TNF, TNFRSF1A, and TNFRSF1B gene polymorphisms and prediction of response to anti-TNF therapy in psoriasis patients in the Greek population. Molecular diagnosis & therapy 63 22111980
2018 The STAT3 Target Gene TNFRSF1A Modulates the NF-κB Pathway in Breast Cancer Cells. Neoplasia (New York, N.Y.) 60 29621649
1997 Membrane tumor necrosis factor (TNF) induced cooperative signaling of TNFR60 and TNFR80 favors induction of cell death rather than virus production in HIV-infected T cells. The Journal of experimental medicine 60 8996244
2005 Association of the R92Q TNFRSF1A mutation and extracranial deep vein thrombosis in patients with Behçet's disease. Arthritis and rheumatism 58 15692984
1995 Both tumor necrosis factor receptors, TNFR60 and TNFR80, are involved in signaling endothelial tissue factor expression by juxtacrine tumor necrosis factor alpha. Blood 57 7544644
1999 Phosphorylation of tumor necrosis factor receptor CD120a (p55) by p42(mapk/erk2) induces changes in its subcellular localization. The Journal of biological chemistry 54 10551865
2002 Hyper IgD syndrome (HIDS) associated with in vitro evidence of defective monocyte TNFRSF1A shedding and partial response to TNF receptor blockade with etanercept. Clinical and experimental immunology 52 12452839
2008 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 etanercept treatment. Annals of the rheumatic diseases 49 18180277
1994 TNF receptor signal transduction. Ligand-dependent stimulation of a serine protein kinase activity associated with (CD120a) TNFR60. Journal of immunology (Baltimore, Md. : 1950) 49 8089485
2016 Brief Report: Association of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome With Gonosomal Mosaicism of a Novel 24-Nucleotide TNFRSF1A Deletion. Arthritis & rheumatology (Hoboken, N.J.) 47 26992170
2012 Differential expression of TNFR1 (CD120a) and TNFR2 (CD120b) on subpopulations of human monocytes. Journal of inflammation (London, England) 46 23039818
2007 Late-onset tumor necrosis factor receptor-associated periodic syndrome in multiple sclerosis patients carrying the TNFRSF1A R92Q mutation. Arthritis and rheumatism 45 17665448
2006 The TNFalpha receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium channel ENaC as modulators in cystic fibrosis. Human genetics 45 16463024
1996 Protection against lethal Escherichia coli bacteremia in baboons (Papio anubis) by pretreatment with a 55-kDa TNF receptor (CD120a)-Ig fusion protein, Ro 45-2081. Journal of immunology (Baltimore, Md. : 1950) 44 8690912
2009 Incidence of TNFRSF1A mutations in German children: epidemiological, clinical and genetic characteristics. Rheumatology (Oxford, England) 43 19541728
1993 Differential regulation of tumour necrosis factor receptors (TNF-R) by IL-4; upregulation of P55 and P75 TNF-R on synovial joint mononuclear cells. Cytokine 42 8218932
2001 Regenerating soleus and extensor digitorum longus muscles of the rat show elevated levels of TNF-alpha and its receptors, TNFR-60 and TNFR-80. Muscle & nerve 41 11439381
2011 Role of tumour necrosis factor (TNF)-α and TNFRSF1A R92Q mutation in the pathogenesis of TNF receptor-associated periodic syndrome and multiple sclerosis. Clinical and experimental immunology 39 22059991
1995 Activation of p42mapk/erk2 following engagement of tumor necrosis factor receptor CD120a (p55) in mouse macrophages. Journal of immunology (Baltimore, Md. : 1950) 39 7636214
2012 Gene network revealed involvements of Birc2, Birc3 and Tnfrsf1a in anti-apoptosis of injured peripheral nerves. PloS one 38 23028454
1994 Soluble intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule-1 (ELAM-1), and tumor necrosis factor receptor (55 kDa TNF-R) in patients with acute Plasmodium falciparum malaria. Clinical immunology and immunopathology 38 7515338
2004 A novel mutation (T61I) in the gene encoding tumour necrosis factor receptor superfamily 1A (TNFRSF1A) in a Japanese patient with tumour necrosis factor receptor-associated periodic syndrome (TRAPS) associated with systemic lupus erythematosus. Rheumatology (Oxford, England) 37 15280569
2015 The novel S59P mutation in the TNFRSF1A gene identified in an adult onset TNF receptor associated periodic syndrome (TRAPS) constitutively activates NF-κB pathway. Arthritis research & therapy 36 25888769
2001 Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a Dutch family: evidence for a TNFRSF1A mutation with reduced penetrance. European journal of human genetics : EJHG 36 11175303
2015 Deletion of angiotensin-converting enzyme 2 exacerbates renal inflammation and injury in apolipoprotein E-deficient mice through modulation of the nephrin and TNF-alpha-TNFRSF1A signaling. Journal of translational medicine 35 26245758
2014 Association of TNF-α, TNFRSF1A and TNFRSF1B gene polymorphisms with the risk of sporadic breast cancer in northeast Chinese Han women. PloS one 35 25010932
2004 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 phenotype of hyperimmunoglobulinemia D with periodic fever syndrome or vice versa. Arthritis and rheumatism 35 15188372
1998 Expression of three members of the TNF-R family of receptors (4-1BB, lymphotoxin-beta receptor, and Fas) in human lung. The European respiratory journal 35 9817170
2006 Leukocyte infiltration and mRNA expression of IL-20, IL-8 and TNF-R P60 in psoriatic skin is driven by TNF-alpha. International journal of immunopathology and pharmacology 34 16831294
2008 Multiple sclerosis and the TNFRSF1A R92Q mutation: clinical characteristics of 21 cases. Neurology 33 19029521
1998 Cooperative signaling by tumor necrosis factor receptors CD120a (p55) and CD120b (p75) in the expression of nitric oxide and inducible nitric oxide synthase by mouse macrophages. The Journal of biological chemistry 32 9712914
2010 Validation of the CD6 and TNFRSF1A loci as risk factors for multiple sclerosis in Spain. Journal of neuroimmunology 31 20430450
2010 Dynamic cross-talk analysis among TNF-R, TLR-4 and IL-1R signalings in TNFalpha-induced inflammatory responses. BMC medical genomics 31 20497537
2008 TNF receptor-associated periodic syndrome (TRAPS): description of a novel TNFRSF1A mutation and response to etanercept. European journal of pediatrics 31 18408954
2017 Disease Phenotype and Outcome Depending on the Age at Disease Onset in Patients Carrying the R92Q Low-Penetrance Variant in TNFRSF1A Gene. Frontiers in immunology 30 28396659
2013 Clinical relevance and functional consequences of the TNFRSF1A multiple sclerosis locus. Neurology 30 24174586
2007 A novel TNFRSF1A splice mutation associated with increased nuclear factor kappaB (NF-kappaB) transcription factor activation in patients with tumour necrosis factor receptor associated periodic syndrome (TRAPS). Annals of the rheumatic diseases 30 18086728
2005 Unexpected high frequency of P46L TNFRSF1A allele in sub-Saharan West African populations. European journal of human genetics : EJHG 30 15586174
2001 Periodic fever (TRAPS) caused by mutations in the TNFalpha receptor 1 (TNFRSF1A) gene of three German patients. European journal of haematology 30 11722598
2004 Two familial cases with tumor necrosis factor receptor-associated periodic syndrome caused by a non-cysteine mutation (T50M) in the TNFRSF1A gene associated with severe multiorganic amyloidosis. The Journal of rheumatology 29 15570662
2002 An Israeli Arab patient with a de novo TNFRSF1A mutation causing tumor necrosis factor receptor-associated periodic syndrome. Arthritis and rheumatism 29 11817598
1995 Neutrophil expression of tumour necrosis factor receptors (TNF-R) and of activation markers (CD11b, CD43, CD63) in rheumatoid arthritis. Clinical and experimental immunology 29 7621589
2019 Genetic polymorphisms in tumour necrosis factor receptors (TNFRSF1A/1B) illustrate differential treatment response to TNFα inhibitors in patients with Crohn's disease. BMJ open gastroenterology 28 30815272
2013 Associations of CD6, TNFRSF1A and IRF8 polymorphisms with risk of inflammatory demyelinating diseases. Neuropathology and applied neurobiology 28 22994200
2019 Cerebellar Fastigial Nucleus Stimulation in a Chronic Unpredictable Mild Stress Rat Model Reduces Post-Stroke Depression by Suppressing Brain Inflammation via the microRNA-29c/TNFRSF1A Signaling Pathway. Medical science monitor : international medical journal of experimental and clinical research 27 31352465
2002 Mutational spectrum in the MEFV and TNFRSF1A genes in patients suffering from AA amyloidosis and recurrent inflammatory attacks. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 27 12105243
2005 "Periodic fever" without fever: two cases of non-febrile TRAPS with mutations in the TNFRSF1A gene presenting with episodes of inflammation or monosymptomatic amyloidosis. Annals of the rheumatic diseases 25 16308343
2001 Phosphorylation of the tumor necrosis factor receptor CD120a (p55) recruits Bcl-2 and protects against apoptosis. The Journal of biological chemistry 25 11278725
2015 Genome-wide haplotype association study identify TNFRSF1A, CASP7, LRP1B, CDH1 and TG genes associated with Alzheimer's disease in Caribbean Hispanic individuals. Oncotarget 24 26621834
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2000 Phosphorylation of the membrane proximal region of tumor necrosis factor receptor CD120a (p55) at ERK consensus sites. The Journal of biological chemistry 24 10702263
2013 TNFRSF1A polymorphisms rs1800693 and rs4149584 in patients with multiple sclerosis. Neurology 23 23624563
2009 Activation of the extrinsic apoptotic pathway by TNF-alpha in human salivary gland (HSG) cells in vitro, suggests a role for the TNF receptor (TNF-R) and intercellular adhesion molecule-1 (ICAM-1) in Sjögren's syndrome-associated autoimmune sialadenitis. Archives of oral biology 23 19716548
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2020 Investigating the Causal Effect of Brain Expression of CCL2, NFKB1, MAPK14, TNFRSF1A, CXCL10 Genes on Multiple Sclerosis: A Two-Sample Mendelian Randomization Approach. Frontiers in bioengineering and biotechnology 20 32432099
2016 miR-29a up-regulation in AR42J cells contributes to apoptosis via targeting TNFRSF1A gene. World journal of gastroenterology 20 27239114
2004 Novel mutations in TNFRSF1A in patients with typical tumor necrosis factor receptor-associated periodic syndrome and with systemic lupus erythematosus in Japanese. International journal of molecular medicine 20 15492850
2015 Association of TNFAIP3 and TNFRSF1A variation with multiple sclerosis in a German case-control cohort. International journal of immunogenetics 19 25684197
2017 Polymorphism of Promoter Region of TNFRSF1A Gene (-610 T > G) as a Novel Predictive Factor for Radiotherapy Induced Oral Mucositis in HNC Patients. Pathology oncology research : POR 18 28401452
2012 Evidence of genetic association between TNFRSF1A encoding the p55 tumour necrosis factor receptor, and ankylosing spondylitis in UK Caucasians. Clinical and experimental rheumatology 18 22272576
2020 Overexpression of miR-29a-3p Suppresses Proliferation, Migration, and Invasion of Vascular Smooth Muscle Cells in Atherosclerosis via Targeting TNFRSF1A. BioMed research international 17 32964047
2020 MiR-29a-3p Enhances the Viability of Rat Neuronal Cells that Injured by Oxygen-Glucose Deprivation/Reoxygenation Treatment Through Targeting TNFRSF1A and Regulating NF-κB Signaling Pathway. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 17 33066952
2018 Inositol-Requiring Enzyme 1-Mediated Downregulation of MicroRNA (miR)-146a and miR-155 in Primary Dermal Fibroblasts across Three TNFRSF1A Mutations Results in Hyperresponsiveness to Lipopolysaccharide. Frontiers in immunology 17 29467762
2015 A Case Presenting with the Clinical Characteristics of Tumor Necrosis Factor (TNF) Receptor-associated Periodic Syndrome (TRAPS) without TNFRSF1A Mutations Successfully Treated with Tocilizumab. Internal medicine (Tokyo, Japan) 17 26278305
2010 Role of the R92Q TNFRSF1A mutation in patients with familial Mediterranean fever. Arthritis care & research 17 20506103
2006 Severe TNF receptor-associated periodic syndrome due to 2 TNFRSF1A mutations including a new F60V substitution. Gastroenterology 17 16401480
2000 Soluble receptors for tumor necrosis factor-alpha (TNF-R p55 and TNF-R p75) in familial combined hyperlipidemia. Atherosclerosis 17 11058695
2016 Efficacy of anakinra in an adult patient with recurrent pericarditis and cardiac tamponade as initial manifestations of tumor necrosis factor receptor-associated periodic syndrome due to the R92Q TNFRSF1A variant. International journal of rheumatic diseases 16 27990755
2013 Expanding spectrum of TNFRSF1A gene mutations among patients with idiopathic recurrent acute pericarditis. Internal medicine journal 16 23745996
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2005 Identification of a novel mevalonate kinase gene mutation in combination with the common MVK V377I substitution and the low-penetrance TNFRSF1A R92Q mutation. European journal of human genetics : EJHG 15 15657603
2019 TNF-α/TNF-R System May Represent a Crucial Mediator of Proliferative Synovitis in Hemophilia A. Journal of clinical medicine 14 31261789
2012 The association of TNFRSF1A gene and MEFV gene mutations with adult onset Still's disease. Rheumatology international 14 23269568
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2011 Candidate genes in patients with autoinflammatory syndrome resembling tumor necrosis factor receptor-associated periodic syndrome without mutations in the TNFRSF1A gene. The Journal of rheumatology 13 21459945
2007 Overlap syndrome between FMF and TRAPS in a patient carrying MEFV and TNFRSF1A mutations. Clinical and experimental rheumatology 13 17949559
2020 Neurological phenotypes in patients with NLRP3-, MEFV-, and TNFRSF1A low-penetrance variants. Journal of neuroinflammation 12 32563262
2017 Other autoinflammatory disease genes in an FMF-prevalent population: a homozygous MVK mutation and a novel heterozygous TNFRSF1A mutation in two different Turkish families with clinical FMF. Clinical and experimental rheumatology 12 29148404
2015 Differential impact of high and low penetrance TNFRSF1A gene mutations on conventional and regulatory CD4+ T cell functions in TNFR1-associated periodic syndrome. Journal of leukocyte biology 12 26598380
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