{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:12:30Z","timestamp":1791238350822,"version":"4.1.0"},"reference-count":56,"publisher":"American Society of Hematology","issue":"2","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/legalcode"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,7,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antithrombin deficiency, the most severe congenital thrombophilia, might be underestimated, as some pathogenic variants are not detected by routine functional methods. We have identified 2 new SERPINC1 variants, p.Glu227Lys and p.Asn224His, in 4 unrelated thrombophilic patients with early and recurrent thrombosis that had normal antithrombin activity. In one case, the mutation was identified by whole genome sequencing, while in the 3 remaining cases, the mutation was identified by sequencing SERPINC1 based on a single functional positive finding supporting deficiency. The 2 variants shared a common functional defect, an impaired or null N-glycosylation of Asn224 according to a eukaryotic expression model. Carriers had normal anti-FXa or anti-FIIa activities but impaired anti-FVIIa activity and a detectable loss of inhibitory function when incubating the plasma for 1 hour at 41\u00b0C. Moreover, the \u03b2 glycoform of the variants, lacking 2 N-glycans, had reduced secretion, increased heparin affinity, no inhibitory activity, and a potential dominant\u2013negative effect. These results explain the increased thrombin generation observed in carriers. Mutation experiments reflected the role that Lysine residues close to the N-glycosylation sequon have in impairing the efficacy of N-glycosylation. Our study shows new elements involved in the regulation of N-glycosylation, a key posttranslational modification that, according to our results, affects folding, secretion, and function, providing new evidence of the pathogenic consequence of an incorrect N-glycosylation of antithrombin. This study supports that antithrombin deficiency is underestimated and encourages the development of new functional and genetic tests to diagnose this severe thrombophilia.<\/jats:p>","DOI":"10.1182\/blood.2021014708","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T20:00:49Z","timestamp":1651262449000},"page":"140-151","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":37,"title":["Two\n                    <i>SERPINC1<\/i>\n                    variants affecting N-glycosylation of Asn224 cause severe thrombophilia not detected by functional assays"],"prefix":"10.1182","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7426-4947","authenticated-orcid":false,"given":"Maria Eugenia","family":"de la Morena-Barrio","sequence":"first","affiliation":[{"name":"1Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Murcia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Suchon","sequence":"additional","affiliation":[{"name":"2Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique - H\u00f4pitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Marie","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"3Department of Haematology and Research Institute of Internal Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Iversen","sequence":"additional","affiliation":[{"name":"4Department of Medical Genetics, Oslo University Hospital, Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Mi\u00f1ano","sequence":"additional","affiliation":[{"name":"1Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Murcia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6696-7762","authenticated-orcid":false,"given":"Bel\u00e9n","family":"de la Morena-Barrio","sequence":"additional","affiliation":[{"name":"1Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Murcia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9794-7847","authenticated-orcid":false,"given":"Carlos","family":"Bravo-P\u00e9rez","sequence":"additional","affiliation":[{"name":"1Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Murcia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1599-7870","authenticated-orcid":false,"given":"Jose","family":"Padilla","sequence":"additional","affiliation":[{"name":"1Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Murcia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Cifuentes","sequence":"additional","affiliation":[{"name":"1Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Murcia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3489-9344","authenticated-orcid":false,"given":"Susana","family":"Asenjo","sequence":"additional","affiliation":[{"name":"5Servicio de Hematolog\u00eda, Hospital Cl\u00ednico San Carlos, Madrid, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Fran\u00e7ois","family":"Deleuze","sequence":"additional","affiliation":[{"name":"6Laboratory of Excellence GENMED (Medical Genomics), Bordeaux, France;"},{"name":"7Universit\u00e9 Paris-Saclay, CEA, Centre National de Recherche en G\u00e9nomique Humaine, Evry, France;"},{"name":"8Centre d\u2019Etude du Polymorphisme Humain, Fondation Jean Dausset, Paris, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9084-7800","authenticated-orcid":false,"given":"David Alexandre","family":"Tr\u00e9gou\u00ebt","sequence":"additional","affiliation":[{"name":"6Laboratory of Excellence GENMED (Medical Genomics), Bordeaux, France;"},{"name":"7Universit\u00e9 Paris-Saclay, CEA, Centre National de Recherche en G\u00e9nomique Humaine, Evry, France;"},{"name":"8Centre d\u2019Etude du Polymorphisme Humain, Fondation Jean Dausset, Paris, France; and"},{"name":"9Univeristy of Bordeaux, INSERM, BPH, U1219, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3148-7037","authenticated-orcid":false,"given":"Maria Luisa","family":"Lozano","sequence":"additional","affiliation":[{"name":"1Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Murcia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4278-3264","authenticated-orcid":false,"given":"Vicente","family":"Vicente","sequence":"additional","affiliation":[{"name":"1Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Murcia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5556-8099","authenticated-orcid":false,"given":"Per Morten","family":"Sandset","sequence":"additional","affiliation":[{"name":"3Department of Haematology and Research Institute of Internal Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9065-722X","authenticated-orcid":false,"given":"Pierre Emmanuel","family":"Morange","sequence":"additional","affiliation":[{"name":"2Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique - H\u00f4pitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0288-1107","authenticated-orcid":false,"given":"Javier","family":"Corral","sequence":"additional","affiliation":[{"name":"1Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Murcia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2022071415265466000_B1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-1-4615-5391-5_3","article-title":"Antithrombin. A bloody important serpin","volume":"425","author":"Bj\u00f6rk","year":"1997","journal-title":"Adv Exp Med Biol."},{"issue":"9","key":"2022071415265466000_B2","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1111\/j.1538-7836.2012.04858.x","article-title":"Low borderline plasma levels of antithrombin, protein C and protein S are risk factors for venous thromboembolism","volume":"10","author":"Bucciarelli","year":"2012","journal-title":"J Thromb Haemost."},{"issue":"7","key":"2022071415265466000_B3","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1172\/JCI10489","article-title":"Complete antithrombin deficiency in mice results in embryonic lethality","volume":"106","author":"Ishiguro","year":"2000","journal-title":"J Clin Invest."},{"issue":"1","key":"2022071415265466000_B4","doi-asserted-by":"crossref","first-page":"e.32","DOI":"10.1111\/bjh.16963","article-title":"Genotype\u2013phenotype gradient of SERPINC1 variants in a single family reveals a severe compound antithrombin deficiency in a dead embryo","volume":"191","author":"Bravo-P\u00e9rez","year":"2020","journal-title":"Br. J. Haematol."},{"key":"2022071415265466000_B5","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.thromres.2018.07.008","article-title":"The genetics of antithrombin","volume":"169","author":"Corral","year":"2018","journal-title":"Thromb Res."},{"issue":"21","key":"2022071415265466000_B6","doi-asserted-by":"crossref","first-page":"5314","DOI":"10.1182\/blood-2008-10-184879","article-title":"Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives","volume":"113","author":"Lijfering","year":"2009","journal-title":"Blood."},{"issue":"6","key":"2022071415265466000_B7","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1111\/j.1538-7836.2010.03840.x","article-title":"A prospective cohort study on the absolute risks of venous thromboembolism and predictive value of screening asymptomatic relatives of patients with hereditary deficiencies of protein S, protein C or antithrombin","volume":"8","author":"Mahmoodi","year":"2010","journal-title":"J Thromb Haemost."},{"issue":"6","key":"2022071415265466000_B8","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1080\/17474086.2019.1611424","article-title":"Management of antithrombin deficiency: an update for clinicians","volume":"12","author":"Bravo-P\u00e9rez","year":"2019","journal-title":"Expert Rev Hematol."},{"issue":"1","key":"2022071415265466000_B9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/jth.14648","article-title":"Recommendations for clinical laboratory testing for antithrombin deficiency; communication from the SSC of the ISTH","volume":"18","author":"Van Cott","year":"2020","journal-title":"J Thromb Haemost."},{"issue":"6","key":"2022071415265466000_B10","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.thromres.2015.04.012","article-title":"Puzzling questions on antithrombin: diagnostic limitations and real incidence in venous and arterial thrombosis","volume":"135","author":"Corral","year":"2015","journal-title":"Thromb Res."},{"issue":"1","key":"2022071415265466000_B11","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1365-2141.1994.tb04878.x","article-title":"Prevalence of antithrombin deficiency in the healthy population","volume":"87","author":"Tait","year":"1994","journal-title":"Br J Haematol."},{"issue":"3","key":"2022071415265466000_B12","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/nrcardio.2013.211","article-title":"Inherited risk factors for venous thromboembolism","volume":"11","author":"Martinelli","year":"2014","journal-title":"Nat Rev Cardiol."},{"issue":"3","key":"2022071415265466000_B13","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1055\/s-0038-1655986","article-title":"Laboratory evaluation and clinical characteristics of 2,132 consecutive unselected patients with venous thromboembolism--results of the Spanish multicentric study on thrombophilia (EMET-study)","volume":"77","author":"Mateo","year":"1997","journal-title":"Thromb Haemost."},{"issue":"5-6","key":"2022071415265466000_B14","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1159\/000073575","article-title":"The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability","volume":"32","author":"Hemker","year":"2002","journal-title":"Pathophysiol Haemost Thromb."},{"issue":"16","key":"2022071415265466000_B15","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"issue":"4","key":"2022071415265466000_B16","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"MutationTaster2: mutation prediction for the deep-sequencing age","volume":"11","author":"Schwarz","year":"2014","journal-title":"Nat Methods."},{"issue":"8","key":"2022071415265466000_B17","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.3324\/haematol.2009.015487","article-title":"Antithrombin Murcia (K241E) causing antithrombin deficiency: a possible role for altered glycosylation","volume":"95","author":"Mart\u00ednez-Mart\u00ednez","year":"2010","journal-title":"Haematologica."},{"issue":"26","key":"2022071415265466000_B18","doi-asserted-by":"crossref","first-page":"8433","DOI":"10.1021\/bi00026a026","article-title":"Partial glycosylation of antithrombin III asparagine-135 is caused by the serine in the third position of its N-glycosylation consensus sequence and is responsible for production of the beta-antithrombin III isoform with enhanced heparin affinity","volume":"34","author":"Picard","year":"1995","journal-title":"Biochemistry."},{"issue":"3","key":"2022071415265466000_B19","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/S0022-2836(02)01382-7","article-title":"Structure of beta-antithrombin and the effect of glycosylation on antithrombin\u2019s heparin affinity and activity","volume":"326","author":"McCoy","year":"2003","journal-title":"J Mol Biol."},{"issue":"5","key":"2022071415265466000_B20","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.jmb.2009.01.028","article-title":"The critical role of hinge-region expulsion in the induced-fit heparin binding mechanism of antithrombin","volume":"386","author":"Langdown","year":"2009","journal-title":"J Mol Biol."},{"issue":"15","key":"2022071415265466000_B21","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1002\/elps.1150181505","article-title":"SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling","volume":"18","author":"Guex","year":"1997","journal-title":"Electrophoresis."},{"issue":"18","key":"2022071415265466000_B22","doi-asserted-by":"crossref","first-page":"10037","DOI":"10.1073\/pnas.181342398","article-title":"Electrostatics of nanosystems: application to microtubules and the ribosome","volume":"98","author":"Baker","year":"2001","journal-title":"Proc Natl Acad Sci USA."},{"issue":"1","key":"2022071415265466000_B23","first-page":"57","article-title":"Python: a programming language for software integration and development","volume":"17","author":"Sanner","year":"1999","journal-title":"J Mol Graph Model."},{"issue":"6","key":"2022071415265466000_B24","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1086\/316903","article-title":"Genetic susceptibility to thrombosis and its relationship to physiological risk factors: the GAIT study. Genetic analysis of idiopathic thrombophilia","volume":"67","author":"Souto","year":"2000","journal-title":"Am J Hum Genet."},{"issue":"5","key":"2022071415265466000_B25","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1097\/MOH.0000000000000165","article-title":"Dissecting the genetic determinants of hemostasis and thrombosis","volume":"22","author":"Desch","year":"2015","journal-title":"Curr Opin Hematol."},{"issue":"6475","key":"2022071415265466000_B26","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/369064a0","article-title":"Mutation in blood coagulation factor V associated with resistance to activated protein C","volume":"369","author":"Bertina","year":"1994","journal-title":"Nature."},{"issue":"4","key":"2022071415265466000_B27","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/gepi.22187","article-title":"A large-scale exome array analysis of venous thromboembolism","volume":"43","author":"Lindstr\u00f6m","year":"2019","journal-title":"Genet Epidemiol."},{"issue":"11","key":"2022071415265466000_B28","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1038\/s41588-019-0519-3","article-title":"Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease","volume":"51","author":"Klarin","year":"2019","journal-title":"Nat Genet."},{"issue":"17","key":"2022071415265466000_B29","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1056\/NEJMoa0904377","article-title":"X-linked thrombophilia with a mutant factor IX (factor IX Padua)","volume":"361","author":"Simioni","year":"2009","journal-title":"N Engl J Med."},{"issue":"17","key":"2022071415265466000_B30","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1182\/blood.2020008168","article-title":"Partial F8 gene duplication (factor VIII Padua) associated with high factor VIII levels and familial thrombophilia","volume":"137","author":"Simioni","year":"2021","journal-title":"Blood."},{"issue":"25","key":"2022071415265466000_B31","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1056\/NEJMoa1201994","article-title":"Thrombosis from a prothrombin mutation conveying antithrombin resistance","volume":"366","author":"Miyawaki","year":"2012","journal-title":"N Engl J Med."},{"issue":"16","key":"2022071415265466000_B32","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1182\/bloodadvances.2017005249","article-title":"Whole-exome sequencing in evaluation of patients with venous thromboembolism","volume":"1","author":"Lee","year":"2017","journal-title":"Blood Adv."},{"issue":"5","key":"2022071415265466000_B33","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1182\/blood.2019004161","article-title":"Whole-exome sequencing identifies rare variants in STAB2 associated with venous thromboembolic disease","volume":"136","author":"Desch","year":"2020","journal-title":"Blood."},{"issue":"2","key":"2022071415265466000_B34","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0049-3848(87)90294-5","article-title":"Regulation of factor VIIa activity in plasma: evidence that antithrombin III is the sole plasma protease inhibitor of human factor VIIa","volume":"46","author":"Kondo","year":"1987","journal-title":"Thromb Res."},{"issue":"10","key":"2022071415265466000_B35","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1182\/blood.V81.10.2600.2600","article-title":"Binding of factor VIIa to tissue factor permits rapid antithrombin III\/heparin inhibition of factor VIIa","volume":"81","author":"Rao","year":"1993","journal-title":"Blood."},{"issue":"2","key":"2022071415265466000_B36","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/S0021-9258(18)53998-3","article-title":"Complex-dependent inhibition of factor VIIa by antithrombin III and heparin","volume":"268","author":"Lawson","year":"1993","journal-title":"J Biol Chem."},{"issue":"6","key":"2022071415265466000_B37","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1182\/blood.V87.6.2301.bloodjournal8762301","article-title":"Initiation of the tissue factor pathway of coagulation in the presence of heparin: control by antithrombin III and tissue factor pathway inhibitor","volume":"87","author":"Jesty","year":"1996","journal-title":"Blood."},{"issue":"5","key":"2022071415265466000_B38","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1182\/blood.V82.5.1679.1679","article-title":"Inhibition of factor VIIa\/tissue factor by antithrombin III and tissue factor pathway inhibitor","volume":"82","author":"Broze","year":"1993","journal-title":"Blood."},{"issue":"4","key":"2022071415265466000_B39","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1515\/cclm-2016-0399","article-title":"Factor VIIa-antithrombin complex: a possible new biomarker for activated coagulation","volume":"55","author":"Spiezia","year":"2017","journal-title":"Clin Chem Lab Med."},{"issue":"16","key":"2022071415265466000_B40","doi-asserted-by":"crossref","first-page":"13688","DOI":"10.1074\/jbc.M300062200","article-title":"Deletion of P1 arginine in a novel antithrombin variant (antithrombin London) abolishes inhibitory activity but enhances heparin affinity and is associated with early onset thrombosis","volume":"278","author":"Raja","year":"2003","journal-title":"J Biol Chem."},{"issue":"3","key":"2022071415265466000_B41","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s10719-015-9626-2","article-title":"Human plasma protein N-glycosylation","volume":"33","author":"Clerc","year":"2016","journal-title":"Glycoconj J."},{"issue":"12","key":"2022071415265466000_B42","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1111\/j.1538-7836.2005.01478.x","article-title":"Post-translational modifications in proteins involved in blood coagulation","volume":"3","author":"Hansson","year":"2005","journal-title":"J Thromb Haemost."},{"issue":"1","key":"2022071415265466000_B43","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ymgme.2013.02.006","article-title":"Thrombotic complications in patients with PMM2-CDG","volume":"109","author":"Linssen","year":"2013","journal-title":"Mol Genet Metab."},{"issue":"8","key":"2022071415265466000_B44","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1111\/jth.13372","article-title":"Hypoglycosylation is a common finding in antithrombin deficiency in the absence of a SERPINC1 gene defect","volume":"14","author":"de la Morena-Barrio","year":"2016","journal-title":"J Thromb Haemost."},{"issue":"1-2","key":"2022071415265466000_B45","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/0014-5793(88)80183-2","article-title":"New carbohydrate site in mutant antithrombin (7 Ile----Asn) with decreased heparin affinity","volume":"237","author":"Brennan","year":"1988","journal-title":"FEBS Lett."},{"issue":"4","key":"2022071415265466000_B46","first-page":"1023","article-title":"Creation of an additional glycosylation site as a mechanism for type I antithrombin deficiency","volume":"86","author":"Fitches","year":"2001","journal-title":"Thromb Haemost."},{"issue":"3","key":"2022071415265466000_B47","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1046\/j.1365-2141.2000.02245.x","article-title":"Molecular bases of antithrombin deficiency in French families: identification of seven novel mutations in the antithrombin gene","volume":"110","author":"Picard","year":"2000","journal-title":"Br J Haematol."},{"issue":"12","key":"2022071415265466000_B48","doi-asserted-by":"crossref","first-page":"4242","DOI":"10.1182\/blood.V93.12.4242","article-title":"Familial overexpression of beta antithrombin caused by an Asn135Thr substitution","volume":"93","author":"Bayston","year":"1999","journal-title":"Blood."},{"issue":"12","key":"2022071415265466000_B49","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1038\/s41564-019-0559-6","article-title":"A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection","volume":"4","author":"Papareddy","year":"2019","journal-title":"Nat Microbiol."},{"issue":"19","key":"2022071415265466000_B50","doi-asserted-by":"crossref","first-page":"6833","DOI":"10.1021\/bi972217k","article-title":"The amino acid following an asn-X-Ser\/Thr sequon is an important determinant of N-linked core glycosylation efficiency","volume":"37","author":"Mellquist","year":"1998","journal-title":"Biochemistry."},{"issue":"12","key":"2022071415265466000_B51","doi-asserted-by":"crossref","first-page":"e114454","DOI":"10.1371\/journal.pone.0114454","article-title":"Increased N-glycosylation efficiency by generation of an aromatic sequon on N135 of antithrombin","volume":"9","author":"Aguila","year":"2014","journal-title":"PLoS One."},{"key":"2022071415265466000_B52","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3389\/fonc.2018.00029","article-title":"Charge and polarity preferences for N-glycosylation: a genome-wide in silico study and its implications regarding constitutive proliferation and adhesion of carcinoma cells","volume":"8","author":"Manwar Hussain","year":"2018","journal-title":"Front Oncol."},{"issue":"6","key":"2022071415265466000_B53","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1021\/bp0502375","article-title":"Variable site-occupancy classification of N-linked glycosylation using artificial neural networks","volume":"21","author":"Senger","year":"2005","journal-title":"Biotechnol Prog."},{"issue":"2","key":"2022071415265466000_B54","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/ajh.26413","article-title":"Molecular and clinical characterization of transient antithrombin deficiency: a new concept in congenital thrombophilia","volume":"97","author":"Bravo-P\u00e9rez","year":"2022","journal-title":"Am J Hematol."},{"issue":"6","key":"2022071415265466000_B55","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1172\/JCI117589","article-title":"Thromboembolic disease due to thermolabile conformational changes of antithrombin rouen-VI (187 Asn--&gt;Asp)","volume":"94","author":"Bruce","year":"1994","journal-title":"J Clin Invest."},{"issue":"8","key":"2022071415265466000_B56","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1182\/blood.V92.8.2696","article-title":"Antithrombins wibble and wobble (T85M\/K): archetypal conformational diseases with in\u00a0vivo latent-transition, thrombosis, and heparin activation","volume":"92","author":"Beauchamp","year":"1998","journal-title":"Blood."}],"updated-by":[{"DOI":"10.1182\/blood.2024025851","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:00:00Z","timestamp":1723680000000}}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/140\/2\/140\/1906697\/bloodbld2021014708.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/140\/2\/140\/1906697\/bloodbld2021014708.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T11:28:06Z","timestamp":1657798086000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/140\/2\/140\/485127\/Two-SERPINC1-variants-affecting-N-glycosylation-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,14]]},"references-count":56,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,7,14]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2021014708","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742085964.793594713","asserted-by":"object"}]},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,14]]}}}