Affinage

TNFAIP3

Tumor necrosis factor alpha-induced protein 3 · UniProt P21580

Length
790 aa
Mass
89.6 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TNFAIP3 encodes A20, a ubiquitin-editing enzyme that restrains NF-κB-driven inflammation by removing Lys63-linked ubiquitin chains from the signaling components TRAF6, NEMO, and RIP1 through its N-terminal OTU deubiquitinase domain, while its C-terminal zinc-finger domain promotes Lys48-linked ubiquitination of substrates for proteasomal degradation by recruiting E3 ligases such as Itch and RNF11 (PMID:26642243, PMID:20599425). Loss-of-function truncating mutations act through haploinsufficiency, failing to clear K63 chains and producing excess IκBα degradation and nuclear translocation of NF-κB p65, the molecular basis of A20 haploinsufficiency (HA20) inflammatory disease (PMID:26642243, PMID:35411038). A20 activity is tuned by IKK-dependent phosphorylation at non-catalytic OTU residues: partial phosphorylation-deficient alleles heighten immunity without overt inflammation, whereas near-complete loss (C243Y) causes spontaneous inflammatory disease, and the C243Y substitution impairs suppression of Nod2-driven NF-κB activation (PMID:31534238, PMID:27175295). Beyond canonical NF-κB control, A20 carries out tissue-specific regulatory functions: it directly deubiquitinates and inactivates ASK1 in hepatocytes to limit NASH (PMID:29227477), deubiquitinates occludin to preserve intestinal tight-junction integrity (PMID:22031828), binds and restrains the mTOR complex to license autophagy in CD4 T cells (PMID:26043155), partners with DEPTOR via its zinc fingers to drive early autophagy and prevent NLRP3 inflammasome assembly (PMID:29940800), and inhibits the E3 ligase RNF168 independently of its catalytic activity to shape the DNA-damage response toward homologous recombination (PMID:29233925). A20 also restrains T-cell receptor signaling to specify NKT cell sublineages (PMID:27551157) and is itself an inducible feedback node controlled transcriptionally by NF-κB/C/EBPβ, STAT3, and glucocorticoid receptor, and post-transcriptionally by METTL14-deposited m6A read by YTHDF2 (PMID:24023826, PMID:35841281, PMID:37327357, PMID:35582627).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2010 Medium

    Established the dual ubiquitin-editing architecture of A20, distinguishing its K63-deubiquitinase OTU domain from its K48-promoting zinc-finger module, framing how a single protein both removes and adds ubiquitin marks.

    Evidence Review integrating in vitro deubiquitinase assays, domain mutagenesis, and E3-ligase (Itch, RNF11) interaction studies

    PMID:20599425

    Open questions at the time
    • Synthesized from prior work rather than new primary data
    • Does not establish in vivo substrate specificity quantitatively
  2. 2010 Medium

    Showed that a natural DUB-domain polymorphism (A125V) alters enzymatic activity and partitions disease risk, linking catalytic tuning to opposing autoimmune phenotypes.

    Evidence In vitro DUB activity assay of A125V vs. wild-type, OTU structural modeling, case-control association

    PMID:20483768

    Open questions at the time
    • Limited methodological detail
    • Mechanism connecting altered DUB activity to divergent SLE vs. IBD outcomes not resolved
  3. 2011 High

    Extended A20 function beyond immune signaling by demonstrating it deubiquitinates occludin to maintain epithelial barrier integrity.

    Evidence Knockout and villin-transgenic mice, in vivo permeability assays, in vitro deubiquitination of occludin

    PMID:22031828

    Open questions at the time
    • Ubiquitin linkage type on occludin not specified
    • Single-lab finding
  4. 2013 Medium

    Defined how Tnfaip3 itself is induced, showing co-regulation by NF-κB and p38-dependent C/EBPβ as a transcriptional feedback loop.

    Evidence ChIP for C/EBPβ promoter binding, p38 inhibition, IKK depletion, C/EBPβ knockout macrophages

    PMID:24023826

    Open questions at the time
    • Relative contribution of NF-κB vs. C/EBPβ not quantified
    • Does not address post-transcriptional control
  5. 2015 High

    Demonstrated that human loss-of-function mutations cause disease through haploinsufficiency and failure to strip K63 chains from TRAF6/NEMO/RIP1, anchoring the molecular pathology of HA20.

    Evidence Patient-derived cells, overexpression, ubiquitin chain analysis, IκBα and p65 nuclear translocation assays

    PMID:26642243

    Open questions at the time
    • Does not address whether some alleles act dominant-negatively in other contexts
    • Tissue-specific consequences not dissected
  6. 2015 High

    Connected A20 to metabolic and autophagy control by showing it binds the mTOR complex to restrain mTOR activity and sustain T-cell autophagy and survival.

    Evidence Tnfaip3-deficient T cells, Co-IP with mTOR complex, LC3/mitochondrial/ROS assays, Torin1 and Atg5 epistasis

    PMID:26043155

    Open questions at the time
    • Which mTOR complex component is the ubiquitination target unclear
    • Role of catalytic vs. scaffold function not separated
  7. 2016 High

    Showed A20 restrains TCR signaling to specify NKT1/NKT2 sublineages, broadening its role into lymphocyte developmental programming.

    Evidence T-cell-specific conditional knockout, NKT subset flow cytometry, MALT1 double-knockout epistasis

    PMID:27551157

    Open questions at the time
    • Direct substrates in the TCR pathway not identified
    • Why NKT17 is spared unexplained
  8. 2016 Medium

    Identified glucocorticoid receptor/NF-κB cooperative induction of A20 via an intronic enhancer, mechanistically linking A20 to glucocorticoid anti-inflammatory action.

    Evidence ChIP, intronic enhancer reporter assay, A20 siRNA, A20/TNIP1 overexpression in airway smooth muscle

    PMID:27371733

    Open questions at the time
    • Generalizability beyond airway smooth muscle untested
    • TNIP1 mechanistic contribution undefined
  9. 2016 Medium

    Characterized the C243Y OTU-domain mutation as impairing suppression of Nod2-mediated NF-κB, providing a defined disease allele.

    Evidence Whole-exome sequencing, WT vs. C243Y transfection, NF-κB luciferase, cytokine measurement

    PMID:27175295

    Open questions at the time
    • Whether C243Y affects catalysis or another property not resolved here
  10. 2017 High

    Revealed a hepatocyte-specific role: A20 directly deubiquitinates and inactivates ASK1 to protect against NASH.

    Evidence Co-IP/interaction screen, hepatocyte-specific knockout mice, in vivo deubiquitination, ASK1-dependent rescue

    PMID:29227477

    Open questions at the time
    • Ubiquitin linkage on ASK1 not specified
    • Crosstalk with A20's NF-κB role in liver not delineated
  11. 2017 Medium

    Placed A20 downstream of TNFR2 in CD4 T cells, showing it suppresses p38/PKC to block IL-17A, explaining anti-TNF-induced derepression.

    Evidence siRNA knockdown, p38/PKC kinase assays, TNFR2-specific antibodies, patient samples

    PMID:29248493

    Open questions at the time
    • Direct ubiquitin substrates linking A20 to kinase suppression not identified
  12. 2017 Medium

    Identified a non-catalytic A20 function: inhibition of E3 ligase RNF168 to limit 53BP1 recruitment and bias DNA repair toward homologous recombination.

    Evidence Reciprocal Co-IP, activity-dead A20 mutants, 53BP1/RNF168 foci, NHEJ vs. HR reporters

    PMID:29233925

    Open questions at the time
    • Structural basis of RNF168-H2A disruption unresolved
    • Physiological relevance in vivo untested
  13. 2017 Medium

    Showed STAT3 induction of A20 acts as a brake on TNF-induced chemokine output, adding another inducible feedback input.

    Evidence STAT3-KO MEFs, RNA-seq, Jak2 inhibition, A20 overexpression rescue

    PMID:35841281

    Open questions at the time
    • Direct STAT3 binding to the Tnfaip3 locus not shown
  14. 2018 Medium

    Demonstrated A20 partners with DEPTOR through its zinc fingers to drive early autophagy and prevent NLRP3 inflammasome assembly.

    Evidence GST pull-down, yeast two-hybrid, Co-IP, electron microscopy, RFP-GFP-LC3 reporter in ankylosing spondylitis monocytes

    PMID:29940800

    Open questions at the time
    • Whether A20 ubiquitin-editing acts on DEPTOR or NLRP3 components unclear
  15. 2018 High

    Defined cis-regulatory architecture controlling A20 expression, showing a sub-TAD with autoimmunity-associated enhancers governs inflammatory tone in vivo.

    Evidence Humanized BAC transgenics, genome editing of sub-TAD/enhancer, autoimmunity phenotyping, allele-specific reporters

    PMID:29440643

    Open questions at the time
    • Trans-acting factors at each enhancer not fully mapped
  16. 2019 High

    Established that IKK-dependent phosphorylation at non-catalytic OTU residues activates A20 and that allelic variation in this phosphorylation tunes the immunity–inflammation balance across species.

    Evidence Genomic analysis of Denisovan/human/mouse alleles, IKK phosphorylation assays, LPS tolerance, poxvirus challenge, disease phenotyping

    PMID:31534238

    Open questions at the time
    • How phosphorylation mechanistically enhances catalysis or substrate engagement not fully resolved
  17. 2019 Low

    Linked A20 to tumor biology by showing it drives ubiquitin-mediated degradation of EMT factors Snail and ZEB1, restraining gastric cancer migration.

    Evidence siRNA knockdown, overexpression, Snail/ZEB1 ubiquitination and migration/invasion assays

    PMID:31153693

    Open questions at the time
    • Limited methodological detail; not independently confirmed
    • Direct vs. indirect ubiquitination not distinguished
  18. 2022 Medium

    Demonstrated post-transcriptional control of TNFAIP3 by m6A: METTL14 deposition stabilizes its mRNA while YTHDF2 reading destabilizes it, tuning NF-κB output in disease.

    Evidence MeRIP-seq, RIP, METTL14/YTHDF2 knockdown, mRNA stability and reporter assays in RA and glioblastoma models

    PMID:35582627 PMID:37327357

    Open questions at the time
    • Which m6A site dominates regulation unclear
    • Interplay between METTL14 writing and YTHDF2 reading not co-analyzed
  19. 2022 Medium

    Extended HA20 pathology to interferon signaling, showing A20 deficiency elevates STAT1 and CXCL9/CXCL10 in addition to NF-κB hyperactivation.

    Evidence NGS, patient PBMC LPS stimulation, NF-κB and STAT1 phospho-readouts, CXCL9/10 serum measurement

    PMID:35154120

    Open questions at the time
    • Whether A20 acts directly on the IFNγ/STAT1 axis or indirectly via NF-κB unresolved
  20. 2022 Low

    Implicated Tnfaip3 downregulation in timing a late phase of injury-induced microglial proliferation in the CNS.

    Evidence Single-cell RNA-seq, flow cytometry, immunohistochemistry, Tnfaip3 manipulation in sciatic nerve injury model

    PMID:35411038

    Open questions at the time
    • Largely correlative; mechanism of how Tnfaip3 loss drives proliferation undefined
  21. 2023 Low

    Proposed HIF1A-mediated transcriptional repression of TNFAIP3 under cadmium stress, reversible by alpha-ketoglutarate-driven HIF1A degradation.

    Evidence Hepatocyte-specific TNFAIP3 overexpression AAV, HIF1A rescue transfection, cadmium/AKG treatment in mice and cells

    PMID:36996991

    Open questions at the time
    • Direct HIF1A binding to the TNFAIP3 promoter not demonstrated
    • Mechanism inferred from overexpression/rescue only

Open questions

Synthesis pass · forward-looking unresolved questions
  • How A20's catalytic (OTU deubiquitination, zinc-finger-directed K48 ubiquitination) and non-catalytic scaffold activities are selectively deployed across its many substrates and tissue contexts remains unresolved.
  • No unified structural model coupling phosphorylation, substrate choice, and catalytic vs. scaffold output
  • Linkage specificity on several substrates (occludin, ASK1, mTOR complex) undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016787 hydrolase activity 3 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 1
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-8953854 Metabolism of RNA 2 R-HSA-9612973 Autophagy 2 R-HSA-73894 DNA Repair 1
Partners
ASK1DEPTORIKBKGMTOROCLNRIPK1RNF168TRAF6

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 Truncated A20 proteins from loss-of-function TNFAIP3 mutations act through haploinsufficiency (not dominant-negative effect) and fail to remove Lys63-linked ubiquitin from TRAF6, NEMO, and RIP1 after TNF stimulation, resulting in increased IκBα degradation and nuclear translocation of NF-κB p65. Overexpression experiments in patient-derived cells, immunoblotting for IκBα degradation, NF-κB p65 nuclear translocation assays, ubiquitin chain analysis of TRAF6/NEMO/RIP1 Nature genetics High 26642243
2017 TNFAIP3 directly interacts with and deubiquitinates ASK1 in hepatocytes, suppressing ASK1 activation; hepatocyte-specific ablation of Tnfaip3 exacerbates NASH phenotypes in an ASK1-dependent manner. Co-immunoprecipitation/protein interaction screen, hepatocyte-specific knockout mice, in vivo deubiquitination assay, ASK1-dependent rescue experiments Nature medicine High 29227477
2010 A20 deubiquitinates K63-polyubiquitin chains via its N-terminal OTU deubiquitinase domain and promotes K48-polyubiquitination (targeting substrates for proteasomal degradation) via its C-terminal zinc-finger ubiquitin-binding domain, which recruits E3 ligases such as Itch and RNF11. Review integrating in vitro deubiquitinase assays, domain mutagenesis, and protein interaction studies from multiple primary publications Biochemical pharmacology Medium 20599425
2011 TNFAIP3 deubiquitinates polyubiquitinated occludin in intestinal epithelial cells, maintaining tight junction integrity; TNFAIP3-/- mice show increased intestinal permeability while villin-TNFAIP3 transgenic mice are protected from LPS-induced barrier disruption. Knockout and transgenic mouse models, in vivo permeability assays, immunohistochemistry, in vitro deubiquitination assay on occludin PloS one High 22031828
2015 TNFAIP3 binds to the mTOR complex and restricts mTOR activity by preventing enhanced ubiquitination of the mTOR complex; Tnfaip3-deficient CD4 T cells show enhanced mTOR activity and defective autophagy (reduced LC3 puncta, increased mitochondrial content, elevated ROS), leading to impaired survival rescued by mTOR inhibitor Torin1 in an Atg5-dependent manner. Tnfaip3-deficient mouse T cells, Co-IP of TNFAIP3 with mTOR complex, LC3 puncta assays, mitochondrial content measurement, ROS assay, Torin1 rescue experiment, Atg5 double-KO epistasis Autophagy High 26043155
2019 TNFAIP3 alleles encoding A20 proteins with substitutions at non-catalytic OTU domain residues (T108A;I207L from Denisovans; I325N from ENU-mutagenized mice; C243Y from rare human variant) diminish IκB kinase-dependent phosphorylation and activation of A20, tuning immunity; partial phosphorylation-deficient variants increase immunity without spontaneous inflammation, while near-complete loss (C243Y, ~95% phosphorylation loss) causes spontaneous inflammatory disease. Genomic analysis of Denisovan/modern human/mouse TNFAIP3 alleles, IKK phosphorylation assays, LPS tolerance assays, poxvirus challenge in I325N mice, inflammatory disease phenotyping in C243Y mice and humans Nature immunology High 31534238
2017 A20/TNFAIP3 binds and inhibits the E3 ubiquitin ligase RNF168 in a manner independent of its own enzymatic activity, disrupting RNF168-H2A interaction and inhibiting accumulation of RNF168 and 53BP1 at DNA damage sites; A20 deletion increases error-prone NHEJ and decreases error-free homologous recombination. Co-IP of A20 with RNF168, enzymatic activity-dead A20 mutants, 53BP1/RNF168 foci assays by immunofluorescence, NHEJ vs. HR reporter assays Cancer research Medium 29233925
2018 TNFAIP3 (A20) forms a complex with DEPTOR via its zinc-finger domains and together they promote early-onset autophagy after LPS stimulation to prevent NLRP3 inflammasome formation; in ankylosing spondylitis monocytes, deficiency of both TNFAIP3 and DEPTOR facilitates inflammasome activation. GST pull-down, yeast two-hybrid, confocal microscopy, Co-IP, transmission electron microscopy, RFP-GFP-LC3 autophagy reporter, LC3 immunoblot Autophagy Medium 29940800
2013 Tnfaip3 transcription in LPS-stimulated macrophages is co-regulated by NF-κB and p38-dependent C/EBPβ; chromatin immunoprecipitation demonstrated C/EBPβ binding to the Tnfaip3 promoter, and C/EBPβ-ablated macrophages showed reduced Tnfaip3 expression. Chromatin immunoprecipitation (ChIP), microarray, p38 inhibitor treatment, IKK-depleted macrophages, C/EBPβ knockout macrophages PloS one Medium 24023826
2016 A20 is required for NKT cell sublineage specification; it controls differentiation and survival of NKT1 and NKT2 (but not NKT17) sublineages through negative regulation of TCR signaling. Compound deficiency of MALT1 (a downstream TCR signaling component) restored defective NKT development in A20-deficient mice. T-cell-specific A20 conditional knockout mice, flow cytometry of NKT subsets, cytokine production assays after TCR ligation in vitro, MALT1/A20 double-knockout epistasis The Journal of experimental medicine High 27551157
2016 Glucocorticoid receptor (GR) and NF-κB cooperatively regulate A20 (TNFAIP3) expression in human airway smooth muscle through direct binding to an intronic enhancer; A20, together with TNIP1, is required for maximal cytokine repression by glucocorticoids. Chromatin immunoprecipitation (ChIP), reporter gene assay for intronic enhancer, siRNA knockdown of A20, overexpression of A20 and TNIP1 in human airway smooth muscle cells American journal of physiology. Lung cellular and molecular physiology Medium 27371733
2017 STAT3 activation by TNFR1 signaling induces Tnfaip3/A20 expression, which in turn limits TNF-induced inflammatory chemokine (Ccl2, Cxcl1, Cxcl10) production; STAT3 knockout MEFs fail to upregulate A20 upon TNF stimulation and show greater chemokine induction; enforced A20 expression in STAT3KO cells suppresses chemokine production. STAT3 knockout mouse embryo fibroblasts, RNA sequencing, pharmacological Jak2 inhibition, multiplex cytokine assays, immunoblotting, A20 overexpression rescue Journal of cellular and molecular medicine Medium 35841281
2010 The A125V coding polymorphism in the DUB domain of TNFAIP3 alters the deubiquitinating activity of the protein, as shown by functional DUB activity assays; this variant confers protection from SLE but risk for inflammatory bowel disease. In vitro DUB activity assay of A125V variant vs. wild-type, computer modeling of OTU domain structure, case-control association Journal of immunology Medium 20483768
2022 METTL14-mediated m6A modification of TNFAIP3 mRNA regulates its stability and translational efficiency; reduced METTL14/m6A in RA PBMCs decreases TNFAIP3 expression, promoting NF-κB-mediated inflammation. MeRIP sequencing, RNA immunoprecipitation, METTL14 knockdown in PBMCs and CAIA mouse model, mRNA stability assays Arthritis & rheumatology Medium 37327357
2018 Autoimmunity-associated TNFAIP3 expression in primary immune cells is dependent on a topologically associating subdomain (sub-TAD) containing four enhancers; deletion of this sub-TAD or a specific SLE-associated enhancer (TT>A) results in enhanced inflammatory responses, autoantibody production, and inflammatory arthritis in humanized BAC transgenic mice. BAC transgenics, genome editing (sub-TAD and enhancer deletion), in vivo phenotyping for autoimmunity and inflammation, allele-specific reporter assays Nature communications High 29440643
2019 TNFAIP3 is required for ubiquitination-dependent degradation of the EMT transcription factors Snail and ZEB1; depletion of TNFAIP3 reduces ubiquitin-mediated turnover of these factors, promoting EMT and increasing migration/invasion of gastric cancer cells. siRNA knockdown of TNFAIP3, overexpression, ubiquitination assay for Snail and ZEB1, migration/invasion assays Pathology, research and practice Low 31153693
2017 A20/TNFAIP3 acts as a master regulator downstream of TNFR2 signaling in CD4+ T cells: TNF binding to TNFR2 maintains TNFAIP3/A20 expression, which suppresses p38 MAPK and PKC kinase activity, thereby preventing IL-17A production; anti-TNF treatment inhibits TNFAIP3/A20, derepressing these kinases and promoting IL-17A expression. siRNA knockdown of TNFAIP3, kinase activity assays (p38, PKC), flow cytometry, TNFR2-specific antibody experiments in isolated human CD4+ T cells, ex vivo patient samples The Journal of allergy and clinical immunology Medium 29248493
2022 YTHDF2 binds to m6A sites in the 3'UTR of TNFAIP3 mRNA and decreases its stability, leading to reduced TNFAIP3 expression and consequent activation of NF-κB signaling and TMZ resistance in glioblastoma. RNA immunoprecipitation, dual-luciferase reporter, FISH with immunostaining, mRNA stability assay, YTHDF2 knockdown/overexpression Clinical & translational immunology Medium 35582627
2016 A novel C243Y missense mutation in the OTU domain of A20/TNFAIP3 impairs suppression of Nod2-mediated NF-κB activation; cells transfected with mutant C243Y A20 showed significantly less suppression of inflammatory cytokine secretion compared to wild-type A20. Whole-exome sequencing, transfection of wild-type vs. C243Y mutant A20 in cell lines, NF-κB luciferase reporter assay, cytokine measurement from patient-derived mononuclear cells RMD open Medium 27175295
2022 In HA20 patients with a novel frameshift mutation (p.His577Alafs*95), A20 haploinsufficiency leads to increased p65 NF-κB phosphorylation and proinflammatory cytokine production; additionally, A20 modulates the IFNγ/STAT1 pathway, as patient monocytes show elevated basal STAT1 and enhanced phospho-STAT1 upon IFNγ stimulation, with elevated circulating CXCL9 and CXCL10. Next-generation sequencing, ex vivo LPS stimulation of patient PBMCs, NF-κB phosphorylation immunoblot, cytokine ELISA, STAT1 immunoblot, phospho-STAT1 flow cytometry, CXCL9/CXCL10 serum measurement Frontiers in immunology Medium 35154120
2022 Tnfaip3 downregulation mediates a late phase of microglia proliferation after nerve injury in mouse spinal cord; restoring Tnfaip3 to baseline terminates this proliferative phase, and the late phase suppresses the early Myc-mediated phase. Single-cell RNA sequencing, flow cytometry, immunohistochemistry, sciatic nerve injury mouse model; Tnfaip3 expression manipulation Cell discovery Low 35411038
2023 HIF1A directly suppresses the TNFAIP3 promoter under cadmium exposure; alpha-ketoglutarate (AKG) promotes HIF1A hydroxylation and degradation, preventing HIF1A-mediated TNFAIP3 repression and thereby maintaining NF-κB suppression in hepatocytes. AAV-mediated hepatocyte-specific TNFAIP3 overexpression, HIF1A pcDNA transfection rescue, in vivo mouse and cell experiments with cadmium and AKG treatment The Science of the total environment Low 36996991

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease. Nature genetics 501 26642243
2009 The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. Trends in immunology 391 19643665
2009 TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. The Journal of experimental medicine 373 19380639
2009 TNFAIP3/A20 functions as a novel tumor suppressor gene in several subtypes of non-Hodgkin lymphomas. Blood 250 19608751
2010 Expression, biological activities and mechanisms of action of A20 (TNFAIP3). Biochemical pharmacology 188 20599425
2017 The deubiquitinating enzyme TNFAIP3 mediates inactivation of hepatic ASK1 and ameliorates nonalcoholic steatohepatitis. Nature medicine 166 29227477
2010 B cells lacking the tumor suppressor TNFAIP3/A20 display impaired differentiation and hyperactivation and cause inflammation and autoimmunity in aged mice. Blood 161 21088135
2009 Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling. Gut 158 19240061
2011 TNFAIP3 gene polymorphisms are associated with response to TNF blockade in psoriasis. The Journal of investigative dermatology 144 22113471
2018 Zinc Inhibits Phosphate-Induced Vascular Calcification through TNFAIP3-Mediated Suppression of NF-κB. Journal of the American Society of Nephrology : JASN 142 29654213
2011 miR-29c targets TNFAIP3, inhibits cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma. Biochemical and biophysical research communications 125 21763284
2015 TNFAIP3 promotes survival of CD4 T cells by restricting MTOR and promoting autophagy. Autophagy 118 26043155
2011 Sequencing of TNFAIP3 and association of variants with multiple autoimmune diseases. Genes and immunity 102 21326317
2013 Germline and somatic genetic variations of TNFAIP3 in lymphoma complicating primary Sjogren's syndrome. Blood 101 24159176
2020 TNFAIP3 Interacting Protein 3 Overexpression Suppresses Nonalcoholic Steatohepatitis by Blocking TAK1 Activation. Cell metabolism 92 32268115
2011 Genetic relationships between A20/TNFAIP3, chronic inflammation and autoimmune disease. Biochemical Society transactions 86 21787353
2010 African-derived genetic polymorphisms in TNFAIP3 mediate risk for autoimmunity. Journal of immunology (Baltimore, Md. : 1950) 83 20483768
2007 A20/TNFAIP3, a new estrogen-regulated gene that confers tamoxifen resistance in breast cancer cells. Oncogene 82 17297453
2016 MicroRNA-19b-3p regulates nasopharyngeal carcinoma radiosensitivity by targeting TNFAIP3/NF-κB axis. Journal of experimental & clinical cancer research : CR 77 27919278
2016 A long noncoding RNA, lincRNA-Tnfaip3, acts as a coregulator of NF-κB to modulate inflammatory gene transcription in mouse macrophages. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 72 27979905
2014 miR-125b controls apoptosis and temozolomide resistance by targeting TNFAIP3 and NKIRAS2 in glioblastomas. Cell death & disease 72 24901050
2009 Meta-analysis and imputation identifies a 109 kb risk haplotype spanning TNFAIP3 associated with lupus nephritis and hematologic manifestations. Genes and immunity 71 19387456
2008 TNFAIP3 is the target gene of chromosome band 6q23.3-q24.1 loss in ocular adnexal marginal zone B cell lymphoma. Genes, chromosomes & cancer 71 17886247
2016 Novel heterozygous C243Y A20/TNFAIP3 gene mutation is responsible for chronic inflammation in autosomal-dominant Behçet's disease. RMD open 70 27175295
2012 Gene-gene interaction of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in systemic lupus erythematosus. Arthritis and rheumatism 70 21905002
2021 Mesenchymal stem cell-originated exosomal lncRNA HAND2-AS1 impairs rheumatoid arthritis fibroblast-like synoviocyte activation through miR-143-3p/TNFAIP3/NF-κB pathway. Journal of orthopaedic surgery and research 66 33549125
2010 Functional evaluation of TNFAIP3 (A20) in rheumatoid arthritis. Clinical and experimental rheumatology 64 20822710
2011 TNFAIP3 maintains intestinal barrier function and supports epithelial cell tight junctions. PloS one 61 22031828
2017 Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2, TNFAIP3 and MYD88 mutations in splenic diffuse red pulp small B-cell lymphoma. Haematologica 59 28751561
2018 Regulators of A20 (TNFAIP3): new drug-able targets in inflammation. American journal of physiology. Lung cellular and molecular physiology 58 30543305
2019 Denisovan, modern human and mouse TNFAIP3 alleles tune A20 phosphorylation and immunity. Nature immunology 57 31534238
2018 Nedd4-Binding Protein 1 and TNFAIP3-Interacting Protein 1 Control MHC-1 Display in Neuroblastoma. Cancer research 54 30213788
2018 Keratinocyte Expression of A20/TNFAIP3 Controls Skin Inflammation Associated with Atopic Dermatitis and Psoriasis. The Journal of investigative dermatology 52 30118730
2011 A failure of TNFAIP3 negative regulation maintains sustained NF-κB activation in Sjögren's syndrome. Histochemistry and cell biology 49 21604024
2019 TNFAIP3 Gene Polymorphisms in Three Common Autoimmune Diseases: Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Primary Sjogren Syndrome-Association with Disease Susceptibility and Clinical Phenotypes in Italian Patients. Journal of immunology research 48 31534975
2018 TNFAIP3-DEPTOR complex regulates inflammasome secretion through autophagy in ankylosing spondylitis monocytes. Autophagy 45 29940800
2020 Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features. Nature communications 44 32144282
2018 Mesenchymal stem cell deficiency influences megakaryocytopoiesis through the TNFAIP3/NF-κB/SMAD pathway in patients with immune thrombocytopenia. British journal of haematology 43 29327472
2012 Associations between TNFAIP3 gene polymorphisms and rheumatoid arthritis: a meta-analysis. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 42 22402800
2021 TNFAIP3 Interacting Protein 3 Is an Activator of Hippo-YAP Signaling Protecting Against Hepatic Ischemia/Reperfusion Injury. Hepatology (Baltimore, Md.) 39 34133792
2017 A20/TNFAIP3 Regulates the DNA Damage Response and Mediates Tumor Cell Resistance to DNA-Damaging Therapy. Cancer research 36 29233925
2017 TNF-α-induced protein 3 (TNFAIP3)/A20 acts as a master switch in TNF-α blockade-driven IL-17A expression. The Journal of allergy and clinical immunology 36 29248493
2013 Association studies of TNFSF4, TNFAIP3 and FAM167A-BLK polymorphisms with primary Sjogren's syndrome in Han Chinese. Journal of human genetics 36 23635951
2023 METTL14-Mediated m6A Modification of TNFAIP3 Involved in Inflammation in Patients With Active Rheumatoid Arthritis. Arthritis & rheumatology (Hoboken, N.J.) 35 37327357
2020 Circ-ATP5H Induces Hepatitis B Virus Replication and Expression by Regulating miR-138-5p/TNFAIP3 Axis. Cancer management and research 34 33173336
2016 NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNFAIP3/A20. The Journal of experimental medicine 33 27551157
2015 Recurrent alterations of TNFAIP3 (A20) in T-cell large granular lymphocytic leukemia. International journal of cancer 33 26199174
2013 Transcription of Tnfaip3 is regulated by NF-κB and p38 via C/EBPβ in activated macrophages. PloS one 33 24023826
2018 Loss of TNFAIP3 enhances MYD88L265P-driven signaling in non-Hodgkin lymphoma. Blood cancer journal 32 30301877
2014 Meta-analysis of the TNFAIP3 region in psoriasis reveals a risk haplotype that is distinct from other autoimmune diseases. Genes and immunity 32 25521225
2018 Dissection and function of autoimmunity-associated TNFAIP3 (A20) gene enhancers in humanized mouse models. Nature communications 31 29440643
2017 TNFAIP3 downregulation mediated by histone modification contributes to T-cell dysfunction in systemic lupus erythematosus. Rheumatology (Oxford, England) 31 28158872
2014 Single nucleotide polymorphisms at the TNFAIP3/A20 locus and susceptibility/resistance to inflammatory and autoimmune diseases. Advances in experimental medicine and biology 29 25302371
2020 Haploinsufficiency of A20 Due to Novel Mutations in TNFAIP3. Journal of clinical immunology 27 32514655
2019 The potential role of TNFAIP3 in malignant transformation of gastric carcinoma. Pathology, research and practice 26 31153693
2016 Glucocorticoid and TNF signaling converge at A20 (TNFAIP3) to repress airway smooth muscle cytokine expression. American journal of physiology. Lung cellular and molecular physiology 26 27371733
2014 Genetic association study of TNFAIP3, IFIH1, IRF5 polymorphisms with polymyositis/dermatomyositis in Chinese Han population. PloS one 26 25337792
2011 A20 (TNFAIP3) genetic alterations in EBV-associated AIDS-related lymphoma. Blood 26 21406721
2022 Distinct phases of adult microglia proliferation: a Myc-mediated early phase and a Tnfaip3-mediated late phase. Cell discovery 25 35411038
2018 Association of ITGAM, TNFSF4, TNFAIP3 and STAT4 gene polymorphisms with risk of systemic lupus erythematosus in a North Indian population. Lupus 25 30041578
2013 A20 (TNFAIP3) deletion in Epstein-Barr virus-associated lymphoproliferative disorders/lymphomas. PloS one 25 23418597
2022 STAT3 regulates inflammatory cytokine production downstream of TNFR1 by inducing expression of TNFAIP3/A20. Journal of cellular and molecular medicine 24 35841281
2022 Novel loss-of-function mutations in TNFAIP3 gene in patients with lupus nephritis. Clinical kidney journal 24 36325013
2019 Novel Heterogeneous Mutation of TNFAIP3 in a Chinese Patient with Behçet-Like Phenotype and Persistent EBV Viremia. Journal of clinical immunology 24 30810840
2019 miR-605-5p promotes invasion and proliferation by targeting TNFAIP3 in non-small-cell lung cancer. Journal of cellular biochemistry 24 31452243
2012 Expression of TNFAIP3 in intestinal epithelial cells protects from DSS- but not TNBS-induced colitis. American journal of physiology. Gastrointestinal and liver physiology 24 22595989
2023 Alpha-ketoglutarate alleviates cadmium-induced inflammation by inhibiting the HIF1A-TNFAIP3 pathway in hepatocytes. The Science of the total environment 23 36996991
2018 TNFAIP3 F127C Coding Variation in Greek Primary Sjogren's Syndrome Patients. Journal of immunology research 23 30662920
2016 Identification of an Association of TNFAIP3 Polymorphisms With Matrix Metalloproteinase Expression in Fibroblasts in an Integrative Study of Systemic Sclerosis-Associated Genetic and Environmental Factors. Arthritis & rheumatology (Hoboken, N.J.) 23 26474180
2014 Polymorphisms of the TNFAIP3 region and Graves' disease. Autoimmunity 23 24798189
2022 The A20/TNFAIP3-CDC20-CASP1 Axis Promotes Inflammation-mediated Metastatic Disease in Triple-negative Breast Cancer. Anticancer research 22 35093867
2020 Immune Regulation of TNFAIP3 in Psoriasis through Its Association with Th1 and Th17 Cell Differentiation and p38 Activation. Journal of immunology research 22 32280718
2020 DNGR1-Cre-mediated Deletion of Tnfaip3/A20 in Conventional Dendritic Cells Induces Pulmonary Hypertension in Mice. American journal of respiratory cell and molecular biology 22 32755457
2011 The association between BANK1 and TNFAIP3 gene polymorphisms and systemic lupus erythematosus: a meta-analysis. International journal of immunogenetics 22 21208380
2020 TNFAIP3 ameliorates the degeneration of inflammatory human nucleus pulposus cells by inhibiting mTOR signaling and promoting autophagy. Aging 21 33226960
2021 Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway. Frontiers in immunology 20 33981308
2015 Association of TNFAIP3 and TNFRSF1A variation with multiple sclerosis in a German case-control cohort. International journal of immunogenetics 19 25684197
2024 Genetic Mutations Associated With TNFAIP3 (A20) Haploinsufficiency and Their Impact on Inflammatory Diseases. International journal of molecular sciences 18 39125844
2022 Identification of a Novel Mutation in TNFAIP3 in a Family With Poly-Autoimmunity. Frontiers in immunology 18 35154120
2020 The impact of DNA demethylation on the upregulation of the NRN1 and TNFAIP3 genes associated with advanced gastric cancer. Journal of molecular medicine (Berlin, Germany) 18 32285140
2020 TNFAIP3 Plays a Role in Aging of the Hematopoietic System. Frontiers in immunology 18 33224133
2014 TNFAIP3 gene polymorphisms associated with differential susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Korean population. Rheumatology (Oxford, England) 18 24489017
2019 Low TNFAIP3 expression in psoriatic skin promotes disease susceptibility and severity. PloS one 17 31120955
2019 Autosomal dominant Hashimoto's thyroiditis with a mutation in TNFAIP3. Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology 17 31384100
2018 TNFAIP3 mRNA Level Is Associated with Psychological Anxiety in Major Depressive Disorder. Neuroimmunomodulation 17 29486471
2014 Intestinal epithelial expression of TNFAIP3 results in microbial invasion of the inner mucus layer and induces colitis in IL-10-deficient mice. American journal of physiology. Gastrointestinal and liver physiology 17 25234043
2012 Role of nuclear factor-κB regulators TNFAIP3 and CARD11 in Middle Eastern diffuse large B-cell lymphoma. Leukemia & lymphoma 17 22397314
2012 Associations between TNFAIP3 gene polymorphisms and systemic lupus erythematosus: a meta-analysis. Genetic testing and molecular biomarkers 17 22924496
2010 Mutation analysis of the TNFAIP3 (A20) tumor suppressor gene in CLL. International journal of cancer 17 20533286
2023 The impact of the cytoplasmic ubiquitin ligase TNFAIP3 gene variation on transcription factor NF-κB activation in acute kidney injury. Kidney international 16 37097268
2022 MEG3 alleviates ankylosing spondylitis by suppressing osteogenic differentiation of mesenchymal stem cells through regulating microRNA-125a-5p-mediated TNFAIP3. Apoptosis : an international journal on programmed cell death 15 36587050
2021 A novel missense mutation in TNFAIP3 causes haploinsufficiency of A20. Cellular immunology 15 34808442
2020 Tnfaip3 expression in pulmonary conventional type 1 Langerin-expressing dendritic cells regulates T helper 2-mediated airway inflammation in mice. Allergy 15 32329078
2019 DNGR1-mediated deletion of A20/Tnfaip3 in dendritic cells alters T and B-cell homeostasis and promotes autoimmune liver pathology. Journal of autoimmunity 15 31151831
2017 TNFAIP3 inhibits migration and invasion in nasopharyngeal carcinoma by suppressing epithelial mesenchymal transition. Neoplasma 15 28253718
2015 TNFAIP3 and TNIP1 polymorphisms confer psoriasis risk in South Indian Tamils. British journal of biomedical science 15 26738398
2023 Aberrant Histone Modification of TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 in Major Depressive Disorder. Molecular neurobiology 14 37148522
2022 YTHDF2 promotes temozolomide resistance in glioblastoma by activation of the Akt and NF-κB signalling pathways via inhibiting EPHB3 and TNFAIP3. Clinical & translational immunology 14 35582627
2022 TNFAIP3 mutation causing haploinsufficiency of A20 with a hemophagocytic lymphohistiocytosis phenotype: a report of two cases. Pediatric rheumatology online journal 14 36064566
2020 Identification of TNFAIP3 as relapse biomarker and potential therapeutic target for MOG antibody associated diseases. Scientific reports 14 32709905

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