{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:40:24Z","timestamp":1792885224236,"version":"4.5.0"},"reference-count":108,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea","award":["2021R1A6A1A03038996"],"award-info":[{"award-number":["2021R1A6A1A03038996"]}]},{"name":"National Research Foundation of Korea","award":["RS-2023-00251396"],"award-info":[{"award-number":["RS-2023-00251396"]}]},{"name":"Ministry of Education Korea","award":["2021R1A6A1A03038996"],"award-info":[{"award-number":["2021R1A6A1A03038996"]}]},{"name":"Ministry of Education Korea","award":["RS-2023-00251396"],"award-info":[{"award-number":["RS-2023-00251396"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>TNF-\u03b1-induced protein 3 (TNFAIP3), commonly referred to as A20, is an integral part of the ubiquitin-editing complex that significantly influences immune regulation, apoptosis, and the initiation of diverse immune responses. The A20 protein is characterized by an N-terminal ovarian tumor (OTU) domain and a series of seven zinc finger (ZNF) domains. Mutations in the TNFAIP3 gene are implicated in various immune-related diseases, such as Beh\u00e7et\u2019s disease, polyarticular juvenile idiopathic arthritis, autoimmune thyroiditis, autoimmune hepatitis, and rheumatoid arthritis. These mutations can lead to a spectrum of symptoms, including, but not limited to, recurrent fever, ulcers, rashes, musculoskeletal and gastrointestinal dysfunctions, cardiovascular issues, and respiratory infections. The majority of these mutations are either nonsense (STOP codon) or frameshift mutations, which are typically associated with immune dysfunctions. Nonetheless, missense mutations have also been identified as contributors to these conditions. These genetic alterations may interfere with several biological pathways, notably abnormal NF-\u03baB signaling and dysregulated ubiquitination. Currently, there is no definitive treatment for A20 haploinsufficiency; however, therapeutic strategies can alleviate the symptoms in patients. This review delves into the mutations reported in the TNFAIP3 gene, the clinical progression in affected individuals, potential disease mechanisms, and a brief overview of the available pharmacological interventions for A20 haploinsufficiency. Mandatory genetic testing of the TNFAIP3 gene should be performed in patients diagnosed with autoinflammatory disorders to better understand the genetic underpinnings and guide treatment decisions.<\/jats:p>","DOI":"10.3390\/ijms25158275","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T17:08:34Z","timestamp":1722359314000},"page":"8275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Genetic Mutations Associated With TNFAIP3 (A20) Haploinsufficiency and Their Impact on Inflammatory Diseases"],"prefix":"10.3390","volume":"25","author":[{"given":"Eva","family":"Bagyinszky","sequence":"first","affiliation":[{"name":"Graduate School of Environment Department of Industrial and Environmental Engineering, Gachon University, Seongnam 13120, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8123-6183","authenticated-orcid":false,"given":"Seong Soo A.","family":"An","sequence":"additional","affiliation":[{"name":"Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam 13120, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"key":"ref_1","first-page":"3","article-title":"The biology of A20-like molecules","volume":"809","author":"Enesa","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1084\/jem.20090528","article-title":"TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma","volume":"206","author":"Schmitz","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1182\/blood-2008-12-194852","article-title":"TNFAIP3\/A20 functions as a novel tumor suppressor gene in several subtypes of non-Hodgkin lymphomas","volume":"114","author":"Honma","year":"2009","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s13075-020-02281-1","article-title":"A20: A master regulator of arthritis","volume":"22","author":"Wu","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Martens, A., and van Loo, G. (2020). A20 at the Crossroads of Cell Death, Inflammation, and Autoimmunity. Cold Spring Harb. Perspect. Biol., 12.","DOI":"10.1101\/cshperspect.a036418"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s10875-024-01681-1","article-title":"The Complexity of Being A20: From Biological Functions to Genetic Associations","volume":"44","author":"Karri","year":"2024","journal-title":"J. Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: Making protein folding accessible to all","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1136\/annrheumdis-2017-212403","article-title":"A20 haploinsufficiency (HA20): Clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease","volume":"77","author":"Batu","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41590-020-0621-9","article-title":"Two distinct ubiquitin-binding motifs in A20 mediate its anti-inflammatory and cell-protective activities","volume":"21","author":"Martens","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s12026-015-8677-6","article-title":"Roles of A20 in autoimmune diseases","volume":"64","author":"Zhang","year":"2016","journal-title":"Immunol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s12519-019-00288-6","article-title":"Haploinsufficiency of A20 (HA20): Updates on the genetics, phenotype, pathogenesis and treatment","volume":"16","author":"Yu","year":"2020","journal-title":"World J. Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s10238-004-0033-4","article-title":"Behcet\u2019s disease","volume":"4","author":"Kurokawa","year":"2004","journal-title":"Clin. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1007\/s13311-021-01137-z","article-title":"Haploinsufficiency, Dominant Negative, and Gain-of-Function Mechanisms in Epilepsy: Matching Therapeutic Approach to the Pathophysiology","volume":"18","author":"Carvill","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"110573","DOI":"10.1016\/j.celrep.2022.110573","article-title":"Genome-wide analysis of haploinsufficiency in human embryonic stem cells","volume":"38","author":"Yilmaz","year":"2022","journal-title":"Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e32340","DOI":"10.7554\/eLife.32340","article-title":"IRF4 haploinsufficiency in a family with Whipple\u2019s disease","volume":"7","author":"Kerner","year":"2018","journal-title":"eLife"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/2040-2392-4-17","article-title":"SHANK3 haploinsufficiency: A \u201ccommon\u201d but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders","volume":"4","author":"Betancur","year":"2013","journal-title":"Mol. Autism"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6035","DOI":"10.4049\/jimmunol.1100021","article-title":"FAS Haploinsufficiency Is a Common Disease Mechanism in the Human Autoimmune Lymphoproliferative Syndrome","volume":"186","author":"Kuehn","year":"2011","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9917","DOI":"10.3390\/cimb45120619","article-title":"A Novel Mutation in Sacsin, p.Val1335IIe, May Cause Late-Onset Sacsinopathy Due to Haploinsufficiency","volume":"45","author":"Kim","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.jaci.2017.10.039","article-title":"Haploinsufficiency of A20 causes autoinflammatory and autoimmune disorders","volume":"141","author":"Kadowaki","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e000740","DOI":"10.1136\/rmdopen-2018-000740","article-title":"Haploinsufficiency of A20 impairs protein-protein interactome and leads into caspase-8-dependent enhancement of NLRP3 inflammasome activation","volume":"4","author":"Keskitalo","year":"2018","journal-title":"RMD Open"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1165\/rcmb.2017-0430TR","article-title":"A Beginner\u2019s Guide to Analysis of RNA Sequencing Data","volume":"59","author":"Koch","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1038\/s41590-019-0386-1","article-title":"Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA\/SLE) Consortium. Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways","volume":"20","author":"Der","year":"2019","journal-title":"Nat Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"108441","DOI":"10.1016\/j.clim.2020.108441","article-title":"Immunophenotyping of A20 haploinsufficiency by multicolor flow cytometry","volume":"216","author":"Kadowaki","year":"2020","journal-title":"Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chen, Y., Huang, H., He, Y., Chen, M., Seidler, U., Tian, D., and Xiao, F. (2020). A20 Haploinsufficiency in a Chinese Patient With Intestinal Behcet\u2019s Disease-Like Symptoms: A Case Report. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01414"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12969-023-00947-z","article-title":"A20 haploinsufficiency in a neonate caused by a large deletion on chromosome 6q","volume":"22","author":"Zhang","year":"2024","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kadowaki, T., Kadowaki, S., and Ohnishi, H. (2021). A20 Haploinsufficiency in East Asia. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.780689"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"108853","DOI":"10.1016\/j.clim.2021.108853","article-title":"Large deletion in 6q containing the TNFAIP3 gene associated with autoimmune lymphoproliferative syndrome","volume":"235","author":"Endo","year":"2022","journal-title":"Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41439-020-00128-4","article-title":"Novel TNFAIP3 microdeletion in a girl with infantile-onset inflammatory bowel disease complicated by a severe perianal lesion","volume":"8","author":"Taniguchi","year":"2021","journal-title":"Hum. Genome Var."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1080\/14397595.2020.1719595","article-title":"Haploinsufficiency of A20 with a novel mutation of deletion of exons 2\u20133 of TNFAIP3","volume":"31","author":"Shimizu","year":"2021","journal-title":"Mod. Rheumatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1093\/ckj\/sfac130","article-title":"Novel loss-of-function mutations in TNFAIP3 gene in patients with lupus nephritis","volume":"15","author":"Zhang","year":"2022","journal-title":"Clin. Kidney J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12969-021-00558-6","article-title":"Clinical characteristics and genetic analysis of A20 haploinsufficiency","volume":"19","author":"Zhang","year":"2021","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Tian, Y., Wu, B., Peng, L., Wang, J., and Shen, M. (2022). Three Chinese pedigrees of A20 haploinsufficiency: Clinical, cytokine and molecular characterization. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.955079"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.alit.2016.06.006","article-title":"A Japanese family case with juvenile onset Beh\u00e7et\u2019s disease caused by TNFAIP3 mutation","volume":"66","author":"Ohnishi","year":"2017","journal-title":"Allergol. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s10875-020-00792-9","article-title":"Haploinsufficiency of A20 Due to Novel Mutations in TNFAIP3","volume":"40","author":"He","year":"2020","journal-title":"J. Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1111\/liv.14935","article-title":"Chronic hepatic involvement in the clinical spectrum of A20 haploinsufficiency","volume":"41","author":"Deshayes","year":"2021","journal-title":"Liver Int."},{"key":"ref_36","first-page":"e583","article-title":"A Family With A20 Haploinsufficiency Presenting With Novel Clinical Manifestations and Challenges for Treatment","volume":"27","author":"Hautala","year":"2020","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6721","DOI":"10.1073\/pnas.93.13.6721","article-title":"The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1\/TRAF2 and inhibits NF-kappaB activation","volume":"93","author":"Song","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1093\/rheumatology\/key445","article-title":"Monogenic mimics of Beh\u00e7et\u2019s disease in the young","volume":"58","author":"Papadopoulou","year":"2019","journal-title":"Rheumatology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e25954","DOI":"10.1097\/MD.0000000000025954","article-title":"Mutation analysis of the TNFAIP3 in A20 haploinsufficiency: A case report","volume":"100","author":"Yan","year":"2021","journal-title":"Medicine"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zanatta, L., Biscaro, F., Bresolin, S., Marzaro, M., Sarcognato, S., Cataldo, I., Marzollo, A., and Martelossi, S. (2022). Case Report: An early-onset inflammatory colitis due to a variant in TNFAIP3 causing A20 haploinsufficiency. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.1044007"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e252","DOI":"10.3346\/jkms.2020.35.e252","article-title":"The First Case of an Infant with Familial A20 Haploinsufficiency in Korea","volume":"35","author":"Kim","year":"2020","journal-title":"J. Korean Med. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1111\/1346-8138.15034","article-title":"Coinheritance of generalized pustular psoriasis and familial Beh\u00e7et-like autoinflammatory syndrome with variants in IL36RN and TNFAIP3 in the heterozygous state","volume":"46","author":"Liang","year":"2019","journal-title":"J. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12881-019-0856-1","article-title":"Expanding the spectrum of A20 haploinsufficiency in two Chinese families: Cases report","volume":"20","author":"Li","year":"2019","journal-title":"BMC Med. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e20232","DOI":"10.1097\/MD.0000000000020232","article-title":"Genetic heterogeneity of pediatric systemic lupus erythematosus with lymphoproliferation","volume":"99","author":"Li","year":"2020","journal-title":"Medicine"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1186\/s13075-018-1766-x","article-title":"Juvenile onset autoinflammatory disease due to a novel mutation in TNFAIP3 (A20)","volume":"20","author":"Sato","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1097\/MPG.0000000000002796","article-title":"Comprehensive Targeted Sequencing Identifies Monogenic Disorders in Patients with Early-onset Refractory Diarrhea","volume":"71","author":"Uchida","year":"2020","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, J., Lin, Y., Li, X., Ba, H., He, X., Peng, H., Li, S., and Zhu, L. (2023). Haploinsufficiency of A20 in a Chinese child caused by loss-of-function mutations in TNFAIP3: A case report and review of the literature. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.990008"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/ng.3459","article-title":"Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease","volume":"48","author":"Zhou","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1111\/1756-185X.14564","article-title":"An infant with A20 haploinsufficiency presenting with periodic fever syndrome: A case report","volume":"26","author":"Wakatsuki","year":"2023","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e20193416","DOI":"10.1542\/peds.2019-3416","article-title":"Knee Joint Swelling at Presentation: A Case of Pediatric Crohn Disease With a TNFAIP3 Mutation","volume":"146","author":"Zou","year":"2020","journal-title":"Pediatrics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1097\/MIB.0000000000001269","article-title":"Phenotype and Management of Infantile-onset Inflammatory Bowel Disease: Experience from a Tertiary Care Center in China","volume":"23","author":"Ye","year":"2017","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"E85","DOI":"10.1093\/rheumatology\/keaa206","article-title":"Paediatric-onset haploinsufficiency of A20 associated with a novel and de novo nonsense TNFAIP3 mutation","volume":"59","author":"Endo","year":"2020","journal-title":"Rheumatology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1016\/j.jaci.2016.09.038","article-title":"Haploinsufficiency of TNFAIP3 (A20) by germline mutation is involved in autoimmune lymphoproliferative syndrome","volume":"139","author":"Takagi","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s13075-019-1928-5","article-title":"Haploinsufficiency of A20 caused by a novel nonsense variant or entire deletion of TNFAIP3 is clinically distinct from Beh\u00e7et\u2019s disease","volume":"21","author":"Tsuchida","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_55","first-page":"783","article-title":"Early-onset autoimmune disease due to a heterozygous loss-of-function mutation in TNFAIP3 (A20)","volume":"77","author":"Dinnigan","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Cao, C., Fu, X., and Wang, X. (2023). Case Report: A novel mutation in TNFAIP3 in a patient with type 1 diabetes mellitus and haploinsufficiency of A20. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1131437"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Rossi, M.N., Federici, S., Uva, A., Passarelli, C., Celani, C., Caiello, I., Matteo, V., Petrocchi, S., Mortari, E.P., and De Benedetti, F. (2022). Identification of a Novel Mutation in TNFAIP3 in a Family With Poly-Autoimmunity. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.804401"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Shaheen, Z.R., Williams, S.J.A., and Binstadt, B.A. (2021). Case Report: A Novel TNFAIP3 Mutation Causing Haploinsufficiency of A20 with a Lupus-Like Phenotype. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.629457"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s10875-019-00695-4","article-title":"A De Novo Frameshift Mutation in TNFAIP3 Impairs A20 Deubiquitination Function to Cause Neuropsychiatric Systemic Lupus Erythematosus","volume":"39","author":"Duan","year":"2019","journal-title":"J. Clin. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1136\/annrheumdis-2019-215918","article-title":"Type I interferon signature predicts response to JAK inhibition in haploinsufficiency of A20","volume":"79","author":"Schwartz","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Lawless, D., Pathak, S., Scambler, T.E., Ouboussad, L., Anwar, R., and Savic, S. (2018). A Case of Adult-Onset Still\u2019s Disease Caused by a Novel Splicing Mutation in TNFAIP3 Successfully Treated with Tocilizumab. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01527"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1297\/cpe.28.91","article-title":"Autosomal dominant Hashimoto\u2019s thyroiditis with a mutation in TNFAIP3","volume":"28","author":"Hori","year":"2019","journal-title":"Clin. Pediatr. Endocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1016\/j.jaip.2020.01.026","article-title":"Lipopolysaccharide-induced monocyte death in a novel ZnF7 domain mutation of TNFAIP3","volume":"8","author":"Imai","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12969-022-00735-1","article-title":"TNFAIP3 mutation causing haploinsufficiency of A20 with a hemophagocytic lymphohistiocytosis phenotype: A report of two cases","volume":"20","author":"Aslani","year":"2022","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13075-021-02434-w","article-title":"Functional analysis of novel A20 variants in patients with atypical inflammatory diseases","volume":"23","author":"Kadowaki","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e81280","DOI":"10.7554\/eLife.81280","article-title":"A critical region of A20 unveiled by missense TNFAIP3 variations that lead to autoinflammation","volume":"12","author":"Diab","year":"2023","journal-title":"eLife"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e000223","DOI":"10.1136\/rmdopen-2015-000223","article-title":"Novel heterozygous C243Y A20\/TNFAIP3 gene mutation is responsible for chronic inflammation in autosomal-dominant Beh\u00e7et\u2019s disease","volume":"2","author":"Shigemura","year":"2016","journal-title":"RMD Open"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"104753","DOI":"10.1016\/j.cellimm.2023.104753","article-title":"Haploinsufficiency of A20 caused by a novel pathogenic missense variant of TNFAIP3 and successfully treated with anti-TNF and immunosuppressive therapies","volume":"391\u2013392","author":"Lina","year":"2023","journal-title":"Cell. Immunol."},{"key":"ref_69","first-page":"e9314","article-title":"A Saudi Child with Chronic Immune Thrombocytopenia and Vitiligo","volume":"12","author":"Alhebshi","year":"2020","journal-title":"Cureus"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s10875-019-00604-9","article-title":"Novel Heterogeneous Mutation of TNFAIP3 in a Chinese Patient with Beh\u00e7et-Like Phenotype and Persistent EBV Viremia","volume":"39","author":"Dong","year":"2019","journal-title":"J. Clin. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"104453","DOI":"10.1016\/j.cellimm.2021.104453","article-title":"A novel missense mutation in TNFAIP3 causes haploinsufficiency of A20","volume":"371","author":"Jiang","year":"2022","journal-title":"Cell. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.jaci.2019.05.026","article-title":"Janus kinase 1\/2 inhibition for the treatment of autoinflammation associated with heterozygous TNFAIP3 mutation","volume":"144","author":"Mulhern","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_73","first-page":"89","article-title":"Pseudodominance of autoinflammatory disease in a single Turkish family explained by co-inheritance of haploinsufficiency of A20 and familial Mediterranean fever","volume":"37","author":"Horita","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Chen, Y., Ye, Z., Chen, L., Qin, T., Seidler, U., Tian, D., and Xiao, F. (2020). Association of Clinical Phenotypes in Haploinsufficiency A20 (HA20) With Disrupted Domains of A20. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.574992"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.it.2013.10.005","article-title":"A20 in inflammation and autoimmunity","volume":"35","author":"Catrysse","year":"2014","journal-title":"Trends Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/S0006-2952(00)00404-4","article-title":"A20 and A20-binding proteins as cellular inhibitors of nuclear factor-kappa B-dependent gene expression and apoptosis","volume":"60","author":"Beyaert","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/nature02794","article-title":"De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling","volume":"430","author":"Wertz","year":"2004","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00018-022-04154-z","article-title":"A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-\u03baB signaling in activated T cells","volume":"79","author":"Yin","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7451","DOI":"10.1128\/MCB.01101-07","article-title":"IkappaB kinase beta phosphorylates the K63 deubiquitinase A20 to cause feedback inhibition of the NF-kappaB pathway","volume":"27","author":"Hutti","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e972","DOI":"10.1038\/cddis.2013.494","article-title":"Identification of the NF-\u03baB inhibitor A20 as a key regulator for human adipogenesis","volume":"4","author":"Dorronsoro","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/s41419-019-1937-y","article-title":"A20 protects cells from TNF-induced apoptosis through linear ubiquitin-dependent and -independent mechanisms","volume":"10","author":"Priem","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1038\/cdd.2017.89","article-title":"Pathogen-induced ubiquitin-editing enzyme A20 bifunctionally shuts off NF-\u03baB and caspase-8-dependent apoptotic cell death","volume":"24","author":"Lim","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/ni.3172","article-title":"The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis","volume":"16","author":"Onizawa","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Feoktistova, M., Makarov, R., Brenji, S., Schneider, A.T., Hooiveld, G.J., Luedde, T., Leverkus, M., Yazdi, A.S., and Panayotova-Dimitrova, D. (2020). A20 Promotes Ripoptosome Formation and TNF-Induced Apoptosis via cIAPs Regulation and NIK Stabilization in Keratinocytes. Cells, 9.","DOI":"10.3390\/cells9020351"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1530\/JME-21-0076","article-title":"A20 controls expression of beta-cell regulatory genes and transcription factors","volume":"67","author":"Ratajczak","year":"2021","journal-title":"J. Mol. Endocrinol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5980190","DOI":"10.1155\/2020\/5980190","article-title":"Immune Regulation of TNFAIP3 in Psoriasis through Its Association with Th1 and Th17 Cell Differentiation and p38 Activation","volume":"2020","author":"Jiang","year":"2020","journal-title":"J. Immunol. Res."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Kolodziej, L.E., Lodolce, J.P., Chang, J.E., Schneider, J.R., Grimm, W.A., Bartulis, S.J., Zhu, X., Messer, J.S., Murphy, S.F., and Reddy, N. (2011). TNFAIP3 Maintains Intestinal Barrier Function and Supports Epithelial Cell Tight Junctions. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026352"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1080\/15548627.2019.1628549","article-title":"The anti-inflammatory protein TNFAIP3\/A20 binds the WD40 domain of ATG16L1 to control the autophagic response, NFKB\/NF-\u03baB activation and intestinal homeostasis","volume":"15","author":"Slowicka","year":"2019","journal-title":"Autophagy"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Toyofuku, E., Takeshita, K., Ohnishi, H., Kiridoshi, Y., Masuoka, H., Kadowaki, T., Nishikomori, R., Nishimura, K., Kobayashi, C., and Ebato, T. (2022). Dysregulation of the Intestinal Microbiome in Patients with Haploinsufficiency of A20. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.787667"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1093\/ckj\/sfac152","article-title":"Gain-of-function TLR7 and loss-of-function A20 gene variants identify a novel pathway for Mendelian lupus and lupus nephritis","volume":"15","author":"Villalvazo","year":"2022","journal-title":"Clin. Kidney J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.semnephrol.2015.08.002","article-title":"Genetics of Lupus Nephritis: Clinical Implications","volume":"35","author":"Munroe","year":"2015","journal-title":"Semin. Nephrol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/bpa.12906","article-title":"Overexpression of the ubiquitin-editing enzyme A20 in the brain lesions of Multiple Sclerosis patients: Moving from systemic to central nervous system inflammation","volume":"31","author":"Perga","year":"2021","journal-title":"Brain Pathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.jid.2023.12.007","article-title":"A20 Haploinsufficiency: A Systematic Review of 177 Cases","volume":"144","author":"Elhani","year":"2024","journal-title":"J. Investig. Dermatol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/sj.bjp.0706736","article-title":"How corticosteroids control inflammation: Quintiles Prize Lecture 2005","volume":"148","author":"Barnes","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jacc.2024.04.044","article-title":"Inflammation, Colchicine, and Atherosclerotic Disease: Is Familial Mediterranean Fever an Exception That Proves the Rule?","volume":"84","author":"Nidorf","year":"2024","journal-title":"J. Am. Coll Cardiol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"van der Houwen, T., and van Laar, J. (2020). Beh\u04abet\u2019s Disease, and the Role of TNF-\u03b1 and TNF-\u03b1 Blockers. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093072"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.semarthrit.2010.09.002","article-title":"Anti-TNF agents for Beh\u00e7et\u2019s disease: Analysis of published data on 369 patients","volume":"41","author":"Arida","year":"2011","journal-title":"Semin Arthritis Rheum."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jaut.2015.06.005","article-title":"Efficacy of anti-TNF alpha in severe and\/or refractory Beh\u00e7et\u2019s disease: Multicenter study of 124 patients","volume":"62","author":"Vallet","year":"2015","journal-title":"J. Autoimmun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/1756-185X.12139","article-title":"Methotrexate in ocular manifestations of Behcet\u2019s disease: A longitudinal study up to 15 years","volume":"16","author":"Davatchi","year":"2013","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0022-510X(98)00165-8","article-title":"Low-dose weekly methotrexate for progressive neuropsychiatric manifestations in Behcet\u2019s disease","volume":"159","author":"Hirohata","year":"1998","journal-title":"J. Neurol. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"443","DOI":"10.7326\/0003-4819-128-6-199803150-00004","article-title":"Thalidomide in the treatment of the mucocutaneous lesions of the Beh\u00e7et syndrome. A randomized, double-blind, placebo-controlled trial","volume":"128","author":"Hamuryudan","year":"1998","journal-title":"Ann. Intern. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e193","DOI":"10.1093\/rheumatology\/keac634","article-title":"A case of A20 haploinsufficiency in which intestinal inflammation improved with thalidomide","volume":"62","author":"Mitsunaga","year":"2023","journal-title":"Rheumatology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.immuni.2014.12.031","article-title":"A20 Restricts Ubiquitination of Pro-Interleukin-1\u03b2 Protein Complexes and Suppresses NLRP3 Inflammasome Activity","volume":"42","author":"Duong","year":"2015","journal-title":"Immunity"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1007\/s10067-015-3004-0","article-title":"Efficacy and safety profile of anti-interleukin-1 treatment in Beh\u00e7et\u2019s disease: A multicenter retrospective study","volume":"35","author":"Emmi","year":"2016","journal-title":"Clin. Rheumatol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1172\/JCI98814","article-title":"JAK1\/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies","volume":"128","author":"Sanchez","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1161\/ATVBAHA.118.311504","article-title":"Calcification Induced by Type I Interferon in Human Aortic Valve Interstitial Cells Is Larger in Males and Blunted by a Janus Kinase Inhibitor","volume":"38","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"432","DOI":"10.3345\/cep.2022.01186","article-title":"Systemic autoinflammatory disorders","volume":"66","author":"Jeong","year":"2023","journal-title":"Clin. Exp. Pediatr."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Zammit, N.W., Gray, P.E., Siggs, O.M., Yap, J.Y., Russell, A., Cultrone, D., Warren, J., Walters, S.N., Brink, R., and Zahra, D. (2022). Environmental and genetic disease modifiers of haploinsufficiency of A20. bioRxiv.","DOI":"10.1101\/2022.03.19.485004"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8275\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:25:54Z","timestamp":1760109954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,29]]},"references-count":108,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158275"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158275","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,29]]}}}