{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:16:11Z","timestamp":1790630171655,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T00:00:00Z","timestamp":1592179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T00:00:00Z","timestamp":1592179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T00:00:00Z","timestamp":1592179200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>RAC2 is a GTPase that is exclusively expressed in hematopoietic cells. Animal models have suggested important roles for RAC2 in the biology of different cell types, such as neutrophils and lymphocytes. Primary immunodeficiencies represent \u201cexperimentum naturae\u201d and offer priceless insight on the function of the human immune system. Mutations in RAC2 have been identified in a small number of patients giving rise to different forms of primary immunodeficiencies ranging from granulocyte defects caused by dominant negative mutations to combined immunodeficiency due to dominant activating mutations. This review will focus on the clinical and immunologic phenotype of patients with germline mutations in RAC2.<\/jats:p>","DOI":"10.1002\/jlb.5mr0520-194rr","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T21:19:10Z","timestamp":1592255950000},"page":"687-696","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["RAC2 and primary human immune deficiencies"],"prefix":"10.1093","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2303-9533","authenticated-orcid":true,"given":"Vassilios","family":"Lougaris","sequence":"first","affiliation":[{"name":"Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST\u2014Spedali Civili of Brescia , Brescia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Baronio","sequence":"additional","affiliation":[{"name":"Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST\u2014Spedali Civili of Brescia , Brescia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Gazzurelli","sequence":"additional","affiliation":[{"name":"Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST\u2014Spedali Civili of Brescia , Brescia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Benvenuto","sequence":"additional","affiliation":[{"name":"Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST\u2014Spedali Civili of Brescia , Brescia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Plebani","sequence":"additional","affiliation":[{"name":"Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST\u2014Spedali Civili of Brescia , Brescia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"key":"2023032108162654600_jlb10724-cit-0001","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1093\/molbev\/msl145","article-title":"Evolution of the Rho family of Ras-like GTPases in eukaryotes","volume":"24","author":"Boureux","year":"2007","journal-title":"Mol Biol Evol"},{"issue":"31","key":"2023032108162654600_jlb10724-cit-0002","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.1038\/onc.2013.362","article-title":"Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease","volume":"33","author":"Cook","year":"2014","journal-title":"Oncogene"},{"key":"2023032108162654600_jlb10724-cit-0003","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/348125a0","article-title":"The GTPase superfamily: a conserved switch for diverse cell functions","volume":"348","author":"Bourne","year":"1990","journal-title":"Nature"},{"issue":"15","key":"2023032108162654600_jlb10724-cit-0004","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1016\/j.yexcr.2013.07.002","article-title":"Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders","volume":"319","author":"Troeger","year":"2013","journal-title":"Exp Cell Res"},{"key":"2023032108162654600_jlb10724-cit-0005","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.cell.2007.05.018","article-title":"GEFs and GAPs: critical elements in the control of small G proteins","volume":"129","author":"Bos","year":"2007","journal-title":"Cell"},{"key":"2023032108162654600_jlb10724-cit-0006","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1097\/MOH.0000000000000199","article-title":"Small GTPases and their guanine-nucleotide exchange factors and GTPase-activating proteins in neutrophil recruitment","volume":"23","author":"Baker","year":"2016","journal-title":"Curr Opin Hematol"},{"issue":"17","key":"2023032108162654600_jlb10724-cit-0007","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1016\/j.yexcr.2007.07.022","article-title":"Taking Rho GTPases to the next level: the cellular functions of atypical Rho GTPases","volume":"313","author":"Aspenstrom","year":"2007","journal-title":"Exp Cell Res"},{"key":"2023032108162654600_jlb10724-cit-0008","article-title":"Off the beaten paths: alternative and crosstalk regulation of Rho GTPases","author":"Boulter","year":"2011","journal-title":"FASEB J"},{"issue":"8","key":"2023032108162654600_jlb10724-cit-0009","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/nrm.2016.67","article-title":"Regulating Rho GTPases and their regulators","volume":"17","author":"Hodge","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"6","key":"2023032108162654600_jlb10724-cit-0010","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1128\/MCB.16.6.2689","article-title":"Identification of a novel human Rho protein with unusual properties: GTPase deficiency and in vivo farnesylation.","volume":"16","author":"Foster","year":"1996","journal-title":"Mol Cell Biol"},{"issue":"Pt 2","key":"2023032108162654600_jlb10724-cit-0011","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1042\/bj20031041","article-title":"Rho GTPases have diverse effects on the organization of the actin filament system","volume":"377","author":"Aspenstrom","year":"2004","journal-title":"Biochem J"},{"key":"2023032108162654600_jlb10724-cit-0012","doi-asserted-by":"crossref","first-page":"12175","DOI":"10.1038\/ncomms12175","article-title":"Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells","volume":"7","author":"Baptista","year":"2016","journal-title":"Nat Commun"},{"issue":"2","key":"2023032108162654600_jlb10724-cit-0013","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1080\/21541248.2016.1275363","article-title":"Activation of compensatory pathways via Rac2 in the absence of the Cdc42 effector Wiskott-Aldrich syndrome protein in Dendritic cells","volume":"10","author":"Baptista","year":"2017","journal-title":"Small GTPases"},{"issue":"1","key":"2023032108162654600_jlb10724-cit-0014","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3324\/haematol.2009.015511","article-title":"Rac GTPases play multiple roles in erythropoiesis","volume":"95","author":"Ji","year":"2010","journal-title":"Haematologica"},{"issue":"39","key":"2023032108162654600_jlb10724-cit-0015","doi-asserted-by":"crossref","first-page":"37916","DOI":"10.1074\/jbc.M301437200","article-title":"Structural basis for the signaling specificity of RhoG and Rac1 GTPases","volume":"200278","author":"Prieto-S\u00e1nchez","year":"2003","journal-title":"J Biol Chem"},{"issue":"Pt 20","key":"2023032108162654600_jlb10724-cit-0016","first-page":"4572","article-title":"Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation","volume":"126","author":"Steffen","year":"2013","journal-title":"J Cell Sci"},{"issue":"5","key":"2023032108162654600_jlb10724-cit-0017","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1182\/blood.V100.5.1679.h81702001679_1679_1688","article-title":"The TRQQKRP motif located near the C-terminus of Rac2 is essential for Rac2 biologic functions and intracellular localization","volume":"100","author":"Tao","year":"2002","journal-title":"Blood"},{"issue":"7","key":"2023032108162654600_jlb10724-cit-0018","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/ni1081","article-title":"Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophils","volume":"5","author":"Filippi","year":"2004","journal-title":"Nat Immunol"},{"issue":"2","key":"2023032108162654600_jlb10724-cit-0019","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1074\/jbc.M408820200","article-title":"Rac GTPase isoform-specific regulation of NADPH oxidase and chemotaxis in murine neutrophils in vivo","volume":"280","author":"Yamauchi","year":"2005","journal-title":"J Biol Chem"},{"issue":"4","key":"2023032108162654600_jlb10724-cit-0020","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.4049\/jimmunol.0900849","article-title":"Human neutrophils coordinate chemotaxis by differential activation of Rac1 and Rac2","volume":"183","author":"Zhang","year":"2009","journal-title":"J Immunol"},{"issue":"5644","key":"2023032108162654600_jlb10724-cit-0021","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1126\/science.1088485","article-title":"Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases","volume":"302","author":"Gu","year":"2003","journal-title":"Science"},{"issue":"2","key":"2023032108162654600_jlb10724-cit-0022","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S1074-7613(00)80019-9","article-title":"Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense","volume":"10","author":"Roberts","year":"1999","journal-title":"Immunity"},{"issue":"9","key":"2023032108162654600_jlb10724-cit-0023","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1097\/00043426-200212000-00027","article-title":"RAC2 GTPase deficiency and myeloid cell dysfunction in human and mouse","volume":"24","author":"Gu","year":"2002","journal-title":"J Pediatr Hematol Oncol"},{"issue":"5","key":"2023032108162654600_jlb10724-cit-0024","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S1074-7613(00)80207-1","article-title":"Rac2 stimulates Akt activation affecting BAD\/Bcl-XL expression while mediating survival and actin function in primary mast cells","volume":"12","author":"Yang","year":"2000","journal-title":"Immunity"},{"key":"2023032108162654600_jlb10724-cit-0025","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0042563","article-title":"Rho GTPase expression in human myeloid cells","author":"van Helden","year":"2012","journal-title":"PLoS One"},{"issue":"5687","key":"2023032108162654600_jlb10724-cit-0026","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1126\/science.1099159","article-title":"Requirement of Rac1 and Rac2 expression by mature dendritic cells for T cell priming","volume":"305","author":"Benvenuti","year":"2004","journal-title":"Science"},{"key":"2023032108162654600_jlb10724-cit-0027","doi-asserted-by":"crossref","DOI":"10.1016\/j.immuni.2009.01.013","article-title":"The small GTPase Rac2 controls phagosomal alkalinization and antigen crosspresentation selectively in CD8+ dendritic cells","author":"Savina","year":"2009","journal-title":"Immunity"},{"issue":"7","key":"2023032108162654600_jlb10724-cit-0028","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1084\/jem.194.7.915","article-title":"Deficiency of small GTPase Rac2 affects T cell activation","volume":"194","author":"Yu","year":"2001","journal-title":"J Exp Med"},{"issue":"5","key":"2023032108162654600_jlb10724-cit-0029","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1182\/blood-2008-01-132068","article-title":"Rac GTPase isoforms Rac1 and Rac2 play a redundant and crucial role in T-cell development","volume":"12","author":"Guo","year":"2008","journal-title":"Blood"},{"issue":"17","key":"2023032108162654600_jlb10724-cit-0030","doi-asserted-by":"crossref","first-page":"3990","DOI":"10.1182\/blood-2008-09-181180","article-title":"Rac GTPases play critical roles in early T-cell development","volume":"113","author":"Dumont","year":"2009","journal-title":"Blood"},{"issue":"2","key":"2023032108162654600_jlb10724-cit-0031","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1128\/MCB.24.2.719-729.2004","article-title":"Immunological function in mice lacking the Rac-related GTPase RhoG","volume":"24","author":"Vigorito","year":"2004","journal-title":"Mol Cell Biol"},{"issue":"7","key":"2023032108162654600_jlb10724-cit-0032","doi-asserted-by":"crossref","first-page":"3376","DOI":"10.4049\/jimmunol.168.7.3376","article-title":"The Rac2 guanosine triphosphatase regulates B lymphocyte antigen receptor responses and chemotaxis and is required for establishment of B-1a and marginal zone B lymphocytes","volume":"168","author":"Croker","year":"2002","journal-title":"J Immunol"},{"issue":"5644","key":"2023032108162654600_jlb10724-cit-0033","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1126\/science.1089709","article-title":"Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling","volume":"302","author":"Walmsley","year":"2003","journal-title":"Science"},{"issue":"9","key":"2023032108162654600_jlb10724-cit-0034","doi-asserted-by":"crossref","first-page":"4654","DOI":"10.1073\/pnas.080074897","article-title":"Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation","volume":"m97","author":"Ambruso","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5","key":"2023032108162654600_jlb10724-cit-0035","first-page":"1646","article-title":"Dominant negative mutation of the hematopoietic specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency","volume":"96","author":"Williams","year":"2000","journal-title":"Blood"},{"key":"2023032108162654600_jlb10724-cit-0036","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jaci.2010.10.013","article-title":"Human phagocyte defect caused by a Rac2 mutation detected by means of neonatal screening for T-cell lymphopenia","volume":"127","author":"Accetta","year":"2011","journal-title":"J Allergy Clin Immunol"},{"key":"2023032108162654600_jlb10724-cit-0037","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1067\/mpd.2001.114718","article-title":"Clinical features of a human Rac2 mutation: a complex neutrophil dysfunction disease","volume":"139","author":"Kurkchubasche","year":"2001","journal-title":"J Pediatr"},{"issue":"19","key":"2023032108162654600_jlb10724-cit-0038","doi-asserted-by":"crossref","first-page":"15929","DOI":"10.1074\/jbc.M010445200","article-title":"Biochemical and biological characterization of a human Rac2 GTPase mutant associated with phagocytic immunodeficiency","volume":"276","author":"Gu","year":"2001","journal-title":"J Biol Chem"},{"issue":"Pt 2","key":"2023032108162654600_jlb10724-cit-0039","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1242\/jcs.00853","article-title":"Rac2D57N, a dominant inhibitory Rac2 mutant that inhibits p38 kinase signaling and prevents surface ruffling in bone-marrow-derived macrophages","volume":"117","author":"Abell","year":"2004","journal-title":"J Cell Sci"},{"issue":"5","key":"2023032108162654600_jlb10724-cit-0040","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1016\/j.jaci.2014.10.039","article-title":"RAC2 loss-of-function mutation in 2 siblings with characteristics of common variable immunodeficiency","volume":"135","author":"Alkhairy","year":"2015","journal-title":"J Allergy Clin Immunol"},{"issue":"4","key":"2023032108162654600_jlb10724-cit-0041","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1016\/j.jaci.2019.01.001","article-title":"A monoallelic activating mutation in RAC2 resulting in a combined immunodeficiency","volume":"143","author":"Lougaris","year":"2019","journal-title":"J Allergy Clin Immunol"},{"issue":"18","key":"2023032108162654600_jlb10724-cit-0042","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1182\/blood-2018-11-886028","article-title":"Dominant activating RAC2 mutation with lymphopenia, immunodeficiency, and cytoskeletal defects","volume":"133","author":"Hsu","year":"2019","journal-title":"Blood"},{"key":"2023032108162654600_jlb10724-cit-0043","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clim.2019.05.003","article-title":"Heterozygous activating mutation in RAC2 causes infantile-onset combined immunodeficiency with susceptibility to viral infections","volume":"205","author":"Sharapova","year":"2019","journal-title":"Clin Immunol"},{"key":"2023032108162654600_jlb10724-cit-0044","doi-asserted-by":"crossref","first-page":"108257","DOI":"10.1016\/j.clim.2019.108257","article-title":"The RAC2-PI3K axis regulates human NK cell maturation and function","volume":"208","author":"Tabellini","year":"2019","journal-title":"Clin Immunol"},{"issue":"3-4","key":"2023032108162654600_jlb10724-cit-0045","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1155\/2010\/380291","article-title":"Rac GTPases in human diseases","volume":"29","author":"Pai","year":"2010","journal-title":"Dis Markers"},{"key":"2023032108162654600_jlb10724-cit-0046","article-title":"A dominant activating RAC2 variant associated with immunodeficiency and pulmonary disease","author":"Smits","year":"2019","journal-title":"Clin Immunol"},{"key":"2023032108162654600_jlb10724-cit-0047","article-title":"A gain-of-function RAC2 mutation is associated with bone-marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency","author":"Lagresle-Peyrou","year":"2020","journal-title":"Haematologica"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2FJLB.5MR0520-194RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/JLB.5MR0520-194RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/JLB.5MR0520-194RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/108\/2\/687\/49458649\/jlb10724.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/108\/2\/687\/49458649\/jlb10724.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T20:35:36Z","timestamp":1679430936000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/108\/2\/687\/6884409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,15]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,6,15]]},"published-print":{"date-parts":[[2020,8,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jlb.5mr0520-194rr","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,8]]},"published":{"date-parts":[[2020,6,15]]},"assertion":[{"value":"2019-09-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}