{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang Y"],"funding":["National Collaborative Research Infrastructure Strategy","Cancer Research UK","The Francis Crick Institute","Medical Research Council","National Health and Medical Research Council","Australian Government","National Computational Infrastructure","Wellcome Trust"],"pagination":["e20221080"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10901239"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["221(4)"],"pubmed_abstract":["Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a clear genetic component. While most SLE patients carry rare gene variants in lupus risk genes, little is known about their contribution to disease pathogenesis. Amongst them, SH2B3-a negative regulator of cytokine and growth factor receptor signaling-harbors rare coding variants in over 5% of SLE patients. Here, we show that unlike the variant found exclusively in healthy controls, SH2B3 rare variants found in lupus patients are predominantly hypomorphic alleles, failing to suppress IFNGR signaling via JAK2-STAT1. The generation of two mouse lines carrying patients' variants revealed that SH2B3 is important in limiting the number of immature and transitional B cells. Furthermore, hypomorphic SH2B3 was shown to "],"journal":["The Journal of experimental medicine"],"pubmed_title":["Rare SH2B3 coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity."],"pmcid":["PMC10901239"],"funding_grant_id":["CC2219","CC2228"],"pubmed_authors":["Lee JC","Walters GD","Trnka P","Shen Q","Kershaw NJ","Sestan M","Hatch AM","Wang H","Babon JJ","Meng X","Chuah A","Morris R","Brown GJ","Lorenzo AMD","Fulcher DA","Stanley M","Headley AP","Vinuesa CG","Yu Z","Burgio G","Mallon D","Gross S","Turnbull C","Kiridena P","Enders A","Cappello JY","Fletcher JT","Athanasopoulos V","Ellyard JI","Zhang Y","Cook MC","Lea-Henry T","Jelusic M","Masters SL","Ballard FD"],"additional_accession":[]},"is_claimable":false,"name":"Rare SH2B3 coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity.","description":"Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a clear genetic component. While most SLE patients carry rare gene variants in lupus risk genes, little is known about their contribution to disease pathogenesis. Amongst them, SH2B3-a negative regulator of cytokine and growth factor receptor signaling-harbors rare coding variants in over 5% of SLE patients. Here, we show that unlike the variant found exclusively in healthy controls, SH2B3 rare variants found in lupus patients are predominantly hypomorphic alleles, failing to suppress IFNGR signaling via JAK2-STAT1. The generation of two mouse lines carrying patients' variants revealed that SH2B3 is important in limiting the number of immature and transitional B cells. Furthermore, hypomorphic SH2B3 was shown to ","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-04-30T21:30:38.872Z","creation":"2026-04-07T16:21:04.172Z"},"accession":"S-EPMC10901239","cross_references":{"pubmed":["38417019"],"doi":["10.1084/jem.20221080"]}}