{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:32:03Z","timestamp":1793644323061,"version":"4.5.1"},"reference-count":133,"publisher":"American Society of Hematology","issue":"21","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,11,21]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Coagulation factor IX plays a central role in hemostasis through interaction with factor VIIIa to form a factor X\u2013activating complex at the site of injury. The absence of factor IX activity results in the bleeding disorder hemophilia B. This absence of activity can arise either from a lack of circulating factor IX protein or mutations that decrease the activity of factor IX. This review focuses on analyzing the structure of factor IX with respect to molecular mechanisms that are at the basis of factor IX function. The proteolytic activation of factor IX to form activated factor IX(a) and subsequent structural rearrangements are insufficient to generate the fully active factor IXa. Multiple specific interactions between factor IXa, the cofactor VIIIa, and the physiological substrate factor X further alter the factor IXa structure to achieve the full enzymatic activity of factor IXa. Factor IXa also interacts with inhibitors, extravascular proteins, and cellular receptors that clear factor IX(a) from the circulation. Hemophilia B is treated by replacement of the missing factor IX by plasma-derived protein, a recombinant bioequivalent, or via gene therapy. An understanding of how the function of factor IX is tied to structure leads to modified forms of factor IX that have increased residence time in circulation, higher functional activity, protection from inhibition, and even activity in the absence of factor VIIIa. These modified forms of factor IX have the potential to significantly improve therapy for patients with hemophilia B.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2023023276","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T16:02:17Z","timestamp":1720800137000},"page":"2198-2210","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":17,"title":["Blood coagulation factor IX: structural insights impacting hemophilia B therapy"],"prefix":"10.1182","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-817X","authenticated-orcid":false,"given":"Mettine H. A.","family":"Bos","sequence":"first","affiliation":[{"name":"1Department of Internal Medicine, Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6572-4681","authenticated-orcid":false,"given":"Rianne E.","family":"van Diest","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine, Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0493-2943","authenticated-orcid":false,"given":"Dougald M.","family":"Monroe","sequence":"additional","affiliation":[{"name":"2Department of Medicine and UNC Blood Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"4799","key":"2024112116205823700_bib1","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1136\/bmj.2.4799.1378","article-title":"Christmas disease: a condition previously mistaken for haemophilia","volume":"2","author":"Biggs","year":"1952","journal-title":"Br Med J"},{"issue":"2","key":"2024112116205823700_bib2","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1074\/mcp.M113.035600","article-title":"Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics","volume":"13","author":"Fagerberg","year":"2014","journal-title":"Mol Cell Proteomics"},{"issue":"1","key":"2024112116205823700_bib3","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1038\/s41598-020-59058-4","article-title":"Production and control of coagulation proteins for factor X activation in human endothelial cells and fibroblasts","volume":"10","author":"Cohen","year":"2020","journal-title":"Sci Rep"},{"issue":"1-3","key":"2024112116205823700_bib4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3727\/215517912X639496","article-title":"Hepatocyte is a sole cell type responsible for the production of coagulation factor IX in\u00a0vivo","volume":"3","author":"Tatsumi","year":"2012","journal-title":"Cell Med"},{"issue":"5038","key":"2024112116205823700_bib5","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1126\/science.1749935","article-title":"Cloning and expression of the cDNA for human gamma-glutamyl carboxylase","volume":"254","author":"Wu","year":"1991","journal-title":"Science"},{"issue":"7","key":"2024112116205823700_bib6","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.1073\/pnas.71.7.2730","article-title":"Vitamin K dependent modifications of glutamic acid residues in prothrombin","volume":"71","author":"Stenflo","year":"1974","journal-title":"Proc\u00a0Natl Acad Sci U S A"},{"issue":"1","key":"2024112116205823700_bib7","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/pro.5560060121","article-title":"gamma-Carboxyglutamic acids 36 and 40 do not contribute to human factor IX function","volume":"6","author":"Gillis","year":"1997","journal-title":"Protein Sci"},{"issue":"12","key":"2024112116205823700_bib8","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\u00a0Thromb Haemost"},{"issue":"12","key":"2024112116205823700_bib9","doi-asserted-by":"crossref","first-page":"5260","DOI":"10.1073\/pnas.74.12.5260","article-title":"Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation","volume":"74","author":"Osterud","year":"1977","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"suppl 1","key":"2024112116205823700_bib10","doi-asserted-by":"crossref","first-page":"S48","DOI":"10.1016\/j.thromres.2014.03.020","article-title":"The mechanism underlying activation of factor IX by factor XIa","volume":"133","author":"Gailani","year":"2014","journal-title":"Thromb Res"},{"issue":"6","key":"2024112116205823700_bib11","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1016\/S0021-9258(19)62334-3","article-title":"Activation of bovine factor IX (Christmas factor) by factor XIa (activated plasma thromboplastin antecedent) and a protease from Russell's viper venom","volume":"253","author":"Lindquist","year":"1978","journal-title":"J\u00a0Biol Chem"},{"issue":"1","key":"2024112116205823700_bib12","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1172\/JCI111694","article-title":"Characterization of the clotting activities of structurally different forms of activated factor IX. Enzymatic properties of normal human factor IXa alpha, factor IXa beta, and activated factor IX Chapel Hill","volume":"75","author":"Griffith","year":"1985","journal-title":"J\u00a0Clin Invest"},{"issue":"11","key":"2024112116205823700_bib13","doi-asserted-by":"crossref","first-page":"3467","DOI":"10.1002\/j.1460-2075.1989.tb08511.x","article-title":"The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment","volume":"8","author":"Bode","year":"1989","journal-title":"EMBO J"},{"issue":"3","key":"2024112116205823700_bib14","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1021\/ar50123a006","article-title":"Structural basis of the activation and action of trypsin","volume":"11","author":"Huber","year":"1978","journal-title":"Acc Chem Res"},{"issue":"6","key":"2024112116205823700_bib15","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1172\/JCI110393","article-title":"Characterization of the defect in activation of factor IX Chapel Hill by human factor XIa","volume":"68","author":"Braunstein","year":"1981","journal-title":"J\u00a0Clin Invest"},{"issue":"6","key":"2024112116205823700_bib16","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1182\/blood.V73.6.1540.1540","article-title":"Functional consequences of an arginine180 to glutamine mutation in factor IX Hilo","volume":"73","author":"Monroe","year":"1989","journal-title":"Blood"},{"issue":"12","key":"2024112116205823700_bib17","doi-asserted-by":"crossref","first-page":"4501","DOI":"10.1021\/cr000033x","article-title":"Serine protease mechanism and specificity","volume":"102","author":"Hedstrom","year":"2002","journal-title":"Chem Rev"},{"issue":"27","key":"2024112116205823700_bib18","doi-asserted-by":"crossref","first-page":"25032","DOI":"10.1074\/jbc.M302174200","article-title":"Contribution of basic residues of the autolysis loop to the substrate and inhibitor specificity of factor IXa","volume":"278","author":"Yang","year":"2003","journal-title":"J\u00a0Biol Chem"},{"issue":"52","key":"2024112116205823700_bib19","doi-asserted-by":"crossref","first-page":"50756","DOI":"10.1074\/jbc.M208485200","article-title":"Localization of the heparin binding exosite of factor IXa","volume":"277","author":"Yang","year":"2002","journal-title":"J\u00a0Biol Chem"},{"issue":"1","key":"2024112116205823700_bib20","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1073\/pnas.89.1.152","article-title":"Antibody-probed conformational transitions in the protease domain of human factor IX upon calcium binding and zymogen activation: putative high-affinity Ca(2+)-binding site in the protease domain","volume":"89","author":"Bajaj","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"20","key":"2024112116205823700_bib21","doi-asserted-by":"crossref","first-page":"10653","DOI":"10.1073\/pnas.93.20.10653","article-title":"Residue 225 determines the Na(+)-induced allosteric regulation of catalytic activity in serine proteases","volume":"93","author":"Dang","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"2024112116205823700_bib22","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/jth.14401","article-title":"Sodium-site in serine protease domain of human coagulation factor IXa: evidence from the crystal structure and molecular dynamics simulations study","volume":"17","author":"Vadivel","year":"2019","journal-title":"J\u00a0Thromb Haemost"},{"issue":"25","key":"2024112116205823700_bib23","doi-asserted-by":"crossref","first-page":"7398","DOI":"10.1021\/bi992735q","article-title":"Insertion loop 256-268 in coagulation factor IX restricts enzymatic activity in the absence but not in the presence of factor VIII","volume":"39","author":"Kolkman","year":"2000","journal-title":"Biochemistry"},{"issue":"7","key":"2024112116205823700_bib24","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.1016\/S0021-9258(19)69627-4","article-title":"The role of phospholipid and factor VIIIa in the activation of bovine factor X","volume":"256","author":"van Dieijen","year":"1981","journal-title":"J\u00a0Biol Chem"},{"issue":"3","key":"2024112116205823700_bib25","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1055\/s-0038-1660091","article-title":"The role of factor VIII in the activation of human blood coagulation factor X by activated factor IX","volume":"54","author":"Mertens","year":"1985","journal-title":"Thromb Haemost"},{"issue":"24","key":"2024112116205823700_bib26","doi-asserted-by":"crossref","first-page":"17012","DOI":"10.1016\/S0021-9258(18)41886-8","article-title":"The active site of factor IXa is located far above the membrane surface and its conformation is altered upon association with factor VIIIa. a fluorescence study","volume":"267","author":"Mutucumarana","year":"1992","journal-title":"J\u00a0Biol Chem"},{"issue":"23","key":"2024112116205823700_bib27","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1182\/blood.2020005593","article-title":"Factor VIII-driven changes in activated factor IX explored by hydrogen-deuterium exchange mass spectrometry","volume":"136","author":"Freato","year":"2020","journal-title":"Blood"},{"issue":"6","key":"2024112116205823700_bib28","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1111\/jth.15288","article-title":"Probing activation-driven changes in coagulation factor IX by mass spectrometry","volume":"19","author":"Freato","year":"2021","journal-title":"J\u00a0Thromb Haemost"},{"issue":"5","key":"2024112116205823700_bib29","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1182\/bloodadvances.2019000405","article-title":"Evolutionary insights into coagulation factor IX Padua and other high-specific-activity variants","volume":"5","author":"Samelson-Jones","year":"2021","journal-title":"Blood Adv"},{"issue":"9","key":"2024112116205823700_bib30","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1111\/j.1538-7836.2005.01527.x","article-title":"Molecular models of the procoagulant factor VIIIa-factor IXa complex","volume":"3","author":"Autin","year":"2005","journal-title":"J\u00a0Thromb Haemost"},{"issue":"4","key":"2024112116205823700_bib31","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.str.2008.03.001","article-title":"Crystal structure of human factor VIII: implications for the formation of the factor IXa-factor VIIIa complex","volume":"16","author":"Ngo","year":"2008","journal-title":"Structure"},{"issue":"3","key":"2024112116205823700_bib32","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.bbrc.2014.08.078","article-title":"Structural insights into the interaction of blood coagulation co-factor VIIIa with factor IXa: a computational protein-protein docking and molecular dynamics refinement study","volume":"452","author":"Venkateswarlu","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"issue":"11","key":"2024112116205823700_bib33","doi-asserted-by":"crossref","first-page":"3240","DOI":"10.1182\/bloodadvances.2021005874","article-title":"SAXS analysis of the intrinsic tenase complex bound to a lipid nanodisc highlights intermolecular contacts between factors VIIIa\/IXa","volume":"6","author":"Childers","year":"2022","journal-title":"Blood Adv"},{"issue":"39","key":"2024112116205823700_bib34","doi-asserted-by":"crossref","first-page":"6123","DOI":"10.1021\/acs.biochem.5b00417","article-title":"Membrane interaction of the factor VIIIa discoidin domains in atomistic detail","volume":"54","author":"Madsen","year":"2015","journal-title":"Biochemistry"},{"issue":"16","key":"2024112116205823700_bib35","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1182\/blood-2013-06-511733","article-title":"Crystal structure of the prothrombinase complex from the venom of Pseudonaja textilis","volume":"122","author":"Lechtenberg","year":"2013","journal-title":"Blood"},{"issue":"24","key":"2024112116205823700_bib36","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1182\/blood.2022015807","article-title":"Cryo-EM structure of the prothrombin-prothrombinase complex","volume":"139","author":"Ruben","year":"2022","journal-title":"Blood"},{"issue":"1","key":"2024112116205823700_bib37","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1074\/jbc.273.1.222","article-title":"Blood coagulation factor IX residues Glu78 and Arg94 provide a link between both epidermal growth factor-like domains that is crucial in the interaction with factor VIII light chain","volume":"273","author":"Christophe","year":"1998","journal-title":"J\u00a0Biol Chem"},{"issue":"1","key":"2024112116205823700_bib38","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1074\/jbc.275.1.229","article-title":"Hydrophobic contact between the two epidermal growth factor-like domains of blood coagulation factor IX contributes to enzymatic activity","volume":"275","author":"Celie","year":"2000","journal-title":"J\u00a0Biol Chem"},{"issue":"19","key":"2024112116205823700_bib39","doi-asserted-by":"crossref","first-page":"16302","DOI":"10.1074\/jbc.M011680200","article-title":"Factor IXa:factor VIIIa interaction. helix 330-338 of factor ixa interacts with residues 558-565 and spatially adjacent regions of the a2 subunit of factor VIIIa","volume":"276","author":"Bajaj","year":"2001","journal-title":"J\u00a0Biol Chem"},{"issue":"23","key":"2024112116205823700_bib40","doi-asserted-by":"crossref","first-page":"20214","DOI":"10.1074\/jbc.M108446200","article-title":"The connecting segment between both epidermal growth factor-like domains in blood coagulation factor IX contributes to stimulation by factor VIIIa and its isolated A2 domain","volume":"277","author":"Celie","year":"2002","journal-title":"J\u00a0Biol Chem"},{"issue":"33","key":"2024112116205823700_bib41","doi-asserted-by":"crossref","first-page":"31297","DOI":"10.1074\/jbc.M302840200","article-title":"The Gla domain of factor IXa binds to factor VIIIa in the tenase complex","volume":"278","author":"Blostein","year":"2003","journal-title":"J\u00a0Biol Chem"},{"issue":"35","key":"2024112116205823700_bib42","doi-asserted-by":"crossref","first-page":"10777","DOI":"10.1021\/bi060451h","article-title":"The interface between the EGF2 domain and the protease domain in blood coagulation factor IX contributes to factor VIII binding and factor X activation","volume":"45","author":"Fribourg","year":"2006","journal-title":"Biochemistry"},{"issue":"6","key":"2024112116205823700_bib43","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1074\/jbc.M804955200","article-title":"The factor VIIIa C2 domain (residues 2228-2240) interacts with the factor IXa Gla domain in the factor Xase complex","volume":"284","author":"Soeda","year":"2009","journal-title":"J\u00a0Biol Chem"},{"issue":"36","key":"2024112116205823700_bib44","doi-asserted-by":"crossref","first-page":"26105","DOI":"10.1074\/jbc.M113.500884","article-title":"A3 domain region 1803-1818 contributes to the stability of activated factor VIII and includes a binding site for activated factor IX","volume":"288","author":"Bloem","year":"2013","journal-title":"J\u00a0Biol Chem"},{"issue":"21","key":"2024112116205823700_bib45","doi-asserted-by":"crossref","first-page":"15057","DOI":"10.1074\/jbc.M113.456467","article-title":"Factor VIIIa A2 subunit shows a high affinity interaction with factor IXa: contribution of A2 subunit residues 707-714 to the interaction with factor IXa","volume":"288","author":"Griffiths","year":"2013","journal-title":"J\u00a0Biol Chem"},{"issue":"8","key":"2024112116205823700_bib46","doi-asserted-by":"crossref","first-page":"130381","DOI":"10.1016\/j.bbagen.2023.130381","article-title":"Factor VIII A3 domain residues 1793-1795 represent a factor IXa-interactive site in the tenase complex","volume":"1867","author":"Takeyama","year":"2023","journal-title":"Biochim Biophys Acta Gen Subj"},{"issue":"6","key":"2024112116205823700_bib47","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1074\/jbc.M210722200","article-title":"Physiological fIXa activation involves a cooperative conformational rearrangement of the 99-loop","volume":"278","author":"Sichler","year":"2003","journal-title":"J\u00a0Biol Chem"},{"issue":"12","key":"2024112116205823700_bib48","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1002\/1873-3468.14321","article-title":"Site-specific functional roles of the factor X activation peptide in the intrinsic tenase-mediated factor X activation","volume":"596","author":"Carnbring Bonde","year":"2022","journal-title":"FEBS Lett"},{"issue":"5","key":"2024112116205823700_bib49","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.jtha.2023.02.005","article-title":"An updated interactive database for 1692 genetic variants in coagulation factor IX provides detailed insights into hemophilia B","volume":"21","author":"Xu","year":"2023","journal-title":"J\u00a0Thromb Haemost"},{"issue":"5","key":"2024112116205823700_bib50","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.3390\/ijms23052762","article-title":"The molecular basis of FIX deficiency in hemophilia B","volume":"23","author":"Shen","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"5","key":"2024112116205823700_bib51","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1136\/jmedgenet-2016-104072","article-title":"Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B","volume":"54","author":"Simhadri","year":"2017","journal-title":"J\u00a0Med Genet"},{"issue":"7","key":"2024112116205823700_bib52","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/humu.24377","article-title":"Effects of 14 F9 synonymous codon variants on hemophilia B expression: alteration of splicing along with protein expression","volume":"43","author":"Zhang","year":"2022","journal-title":"Hum Mutat"},{"issue":"4","key":"2024112116205823700_bib53","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.jtha.2023.12.031","article-title":"Pleiotropic effects of different exonic nucleotide changes at the same position contribute to hemophilia B phenotypic variation","volume":"22","author":"Zhang","year":"2024","journal-title":"J\u00a0Thromb Haemost"},{"issue":"4","key":"2024112116205823700_bib54","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/mgg3.30","article-title":"Craig Hooper W. The CDC hemophilia B mutation project mutation list: a new online resource","volume":"1","author":"Li","year":"2013","journal-title":"Mol Genet Genomic Med"},{"issue":"2","key":"2024112116205823700_bib55","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/hae.13947","article-title":"The European Association for Haemophilia and Allied Disorders (EAHAD) coagulation factor variant databases: important resources for haemostasis clinicians and researchers","volume":"26","author":"McVey","year":"2020","journal-title":"Haemophilia"},{"issue":"9","key":"2024112116205823700_bib56","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1111\/jth.15805","article-title":"Results of genetic analysis of 11\u2009341 participants enrolled in the my life, our future hemophilia genotyping initiative in the United States","volume":"20","author":"Johnsen","year":"2022","journal-title":"J\u00a0Thromb Haemost"},{"issue":"15","key":"2024112116205823700_bib57","doi-asserted-by":"crossref","first-page":"3893","DOI":"10.1182\/bloodadvances.2023012432","article-title":"Multimodal mechanisms of pathogenic variants in the signal peptide of FIX leading to hemophilia B","volume":"8","author":"Gao","year":"2024","journal-title":"Blood Adv"},{"key":"2024112116205823700_bib58","doi-asserted-by":"publisher","DOI":"10.1101\/2024.04.01.587474","article-title":"Multiplex, multimodal mapping of variant effects in secreted proteins","author":"Popp","year":"1  2024","journal-title":"bioRxiv"},{"issue":"13","key":"2024112116205823700_bib59","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1182\/bloodadvances.2016002923","article-title":"Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the my life, our future initiative","volume":"1","author":"Johnsen","year":"2017","journal-title":"Blood Adv"},{"issue":"1","key":"2024112116205823700_bib60","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3324\/haematol.2019.239160","article-title":"Inhibitor incidence in an unselected cohort of previously untreated patients with severe haemophilia B: a PedNet study","volume":"106","author":"Male","year":"2021","journal-title":"Haematologica"},{"issue":"1","key":"2024112116205823700_bib61","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/hae.14665","article-title":"Factor IX inhibitors in haemophilia B: a report of National Haemophilia Registry in China","volume":"29","author":"Dou","year":"2023","journal-title":"Haemophilia"},{"issue":"5879","key":"2024112116205823700_bib62","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/299178a0","article-title":"Molecular cloning of the gene for human anti-haemophilic factor IX","volume":"299","author":"Choo","year":"1982","journal-title":"Nature"},{"issue":"1","key":"2024112116205823700_bib63","doi-asserted-by":"crossref","first-page":"15449","DOI":"10.1038\/s41598-019-51984-2","article-title":"Effects of codon optimization on coagulation factor IX translation and structure: implications for protein and gene therapies","volume":"9","author":"Alexaki","year":"2019","journal-title":"Sci Rep"},{"issue":"13","key":"2024112116205823700_bib64","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1182\/bloodadvances.2022007094","article-title":"Structural, functional, and immunogenicity implications of F9 gene recoding","volume":"6","author":"Katneni","year":"2022","journal-title":"Blood Adv"},{"issue":"4","key":"2024112116205823700_bib65","doi-asserted-by":"crossref","first-page":"102461","DOI":"10.1016\/j.rpth.2024.102461","article-title":"Inhibitor development according to concentrate after 50 exposure days in severe haemophilia: data from the European HAemophilia Safety Surveillance (EUHASS)","volume":"8","author":"Fischer","year":"2024","journal-title":"Res Pract Thromb Haemost"},{"key":"2024112116205823700_bib66","unstructured":"Clark\n              D\n            \n          . Current products for hemophilia B treatment. May 2024. Accessed 5 June 2024. https:\/\/www.hemob.org\/resource-library\/current-products-for-hemophilia-b-treatment-may-2024."},{"key":"2024112116205823700_bib67","first-page":"2017","volume-title":"Williams Hematology","author":"Bos","year":"2021","edition":"10th ed"},{"issue":"4","key":"2024112116205823700_bib68","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.bbrc.2013.09.001","article-title":"Hepatocyte clearance and pharmacokinetics of recombinant factor IX glycosylation variants","volume":"440","author":"Blasko","year":"2013","journal-title":"Biochem Biophys Res Commun"},{"issue":"6","key":"2024112116205823700_bib69","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1160\/TH04-03-0201","article-title":"An important role for the activation peptide domain in controlling factor IX levels in the blood of haemophilia B mice","volume":"94","author":"Begbie","year":"2005","journal-title":"Thromb Haemost"},{"issue":"8","key":"2024112116205823700_bib70","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1182\/blood-2011-02-336172","article-title":"Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated on native N-glycans in the activation peptide","volume":"118","author":"Ostergaard","year":"2011","journal-title":"Blood"},{"issue":"11","key":"2024112116205823700_bib71","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1111\/j.1538-7836.2012.04911.x","article-title":"Hyperglycosylation prolongs the circulation of coagulation factor IX","volume":"10","author":"Bolt","year":"2012","journal-title":"J\u00a0Thromb Haemost"},{"issue":"26","key":"2024112116205823700_bib72","doi-asserted-by":"crossref","first-page":"6539","DOI":"10.1021\/bi00077a007","article-title":"Identification and structural analysis of the tetrasaccharide NeuAc alpha(2--&gt;6)Gal beta(1--&gt;4)GlcNAc beta(1--&gt;3)Fuc alpha 1--&gt;O-linked to serine 61 of human factor IX","volume":"32","author":"Harris","year":"1993","journal-title":"Biochemistry"},{"issue":"2","key":"2024112116205823700_bib73","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/oxfordjournals.jbchem.a022738","article-title":"Structural analysis of N-linked sugar chains of human blood clotting factor IX","volume":"128","author":"Makino","year":"2000","journal-title":"J\u00a0Biochem"},{"key":"2024112116205823700_bib74","first-page":"7678901","article-title":"Characterization of IXINITY(R) (Trenonacog alfa), a recombinant factor IX with primary sequence corresponding to the threonine-148 polymorph","volume":"2016","author":"Monroe","year":"2016","journal-title":"Adv Hematol"},{"issue":"6","key":"2024112116205823700_bib75","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/nm1760","article-title":"The Ashwell receptor mitigates the lethal coagulopathy of sepsis","volume":"14","author":"Grewal","year":"2008","journal-title":"Nat Med"},{"issue":"10","key":"2024112116205823700_bib76","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.1182\/blood.V96.10.3459","article-title":"Activation of factor IX zymogen results in exposure of a binding site for low-density lipoprotein receptor-related protein","volume":"96","author":"Neels","year":"2000","journal-title":"Blood"},{"issue":"10","key":"2024112116205823700_bib77","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.1182\/blood-2002-07-2081","article-title":"Elevated plasma factor VIII in a mouse model of low-density lipoprotein receptor-related protein deficiency","volume":"101","author":"Bovenschen","year":"2003","journal-title":"Blood"},{"issue":"10","key":"2024112116205823700_bib78","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1182\/blood-2009-08-239665","article-title":"Prolonged activity of factor IX as a monomeric Fc fusion protein","volume":"115","author":"Peters","year":"2010","journal-title":"Blood"},{"issue":"17","key":"2024112116205823700_bib79","doi-asserted-by":"crossref","first-page":"6363","DOI":"10.1074\/jbc.M117.817064","article-title":"Half-life-extended recombinant coagulation factor IX-albumin fusion protein is recycled via the FcRn-mediated pathway","volume":"293","author":"Chia","year":"2018","journal-title":"J\u00a0Biol Chem"},{"issue":"12","key":"2024112116205823700_bib80","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1055\/s-0038-1675787","article-title":"Fusion of factor IX to factor XIII-B sub-unit improves the pharmacokinetic profile of factor IX","volume":"118","author":"Le Quellec","year":"2018","journal-title":"Thromb Haemost"},{"issue":"6","key":"2024112116205823700_bib81","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1111\/hae.14855","article-title":"Characterization of a recombinant factor IX molecule fused to coagulation factor XIII-B subunit","volume":"29","author":"Desage","year":"2023","journal-title":"Haemophilia"},{"issue":"2","key":"2024112116205823700_bib82","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/bjh.17559","article-title":"Fusion of engineered albumin with factor IX Padua extends half-life and improves coagulant activity","volume":"194","author":"Lombardi","year":"2021","journal-title":"Br J Haematol"},{"issue":"20","key":"2024112116205823700_bib83","doi-asserted-by":"crossref","first-page":"11068","DOI":"10.1073\/pnas.93.20.11068","article-title":"Identification of the endothelial cell binding site for factor IX","volume":"93","author":"Cheung","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"29","key":"2024112116205823700_bib84","doi-asserted-by":"crossref","first-page":"20529","DOI":"10.1016\/S0021-9258(19)36713-4","article-title":"The binding of human factor IX to endothelial cells is mediated by residues 3-11","volume":"267","author":"Cheung","year":"1992","journal-title":"J\u00a0Biol Chem"},{"issue":"27","key":"2024112116205823700_bib85","doi-asserted-by":"crossref","first-page":"16717","DOI":"10.1074\/jbc.272.27.16717","article-title":"Human factor IX binds to specific sites on the collagenous domain of collagen IV","volume":"272","author":"Wolberg","year":"1997","journal-title":"J\u00a0Biol Chem"},{"issue":"1","key":"2024112116205823700_bib86","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1182\/blood.V100.1.153","article-title":"Circulating and binding characteristics of wild-type factor IX and certain Gla domain mutants in\u00a0vivo","volume":"100","author":"Gui","year":"2002","journal-title":"Blood"},{"issue":"8","key":"2024112116205823700_bib87","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1055\/a-2090-9739","article-title":"Modulation of extravascular binding of recombinant factor IX Impacts the duration of efficacy in mouse models","volume":"123","author":"Machado","year":"2023","journal-title":"Thromb Haemost"},{"issue":"11","key":"2024112116205823700_bib88","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1111\/j.1538-7836.2009.03545.x","article-title":"Abnormal hemostasis in a knock-in mouse carrying a variant of factor IX with impaired binding to collagen type IV","volume":"7","author":"Gui","year":"2009","journal-title":"J\u00a0Thromb Haemost"},{"issue":"22","key":"2024112116205823700_bib89","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1182\/blood.2018884015","article-title":"Dysfunctional endogenous FIX impairs prophylaxis in a mouse hemophilia B model","volume":"133","author":"Cooley","year":"2019","journal-title":"Blood"},{"issue":"3","key":"2024112116205823700_bib90","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.jtha.2023.11.023","article-title":"Extravascular factor IX pool fed by prophylaxis is a true hemostatic barrier against bleeding","volume":"22","author":"Leuci","year":"2024","journal-title":"J\u00a0Thromb Haemost"},{"issue":"5","key":"2024112116205823700_bib91","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/ejh.14176","article-title":"Recombinant factor IX Fc for the treatment of hemophilia B","volume":"112","author":"Ljung","year":"2024","journal-title":"Eur J Haematol"},{"issue":"6","key":"2024112116205823700_bib92","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/MBC.0000000000001230","article-title":"Biodistribution of recombinant factor IX, extended half-life recombinant factor IX Fc fusion protein, and glycoPEGylated recombinant factor IX in hemophilia B mice","volume":"34","author":"van der Flier","year":"2023","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"2","key":"2024112116205823700_bib93","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1182\/blood-2016-01-696104","article-title":"Prophylactic efficacy of BeneFIX vs Alprolix in hemophilia B mice","volume":"128","author":"Cooley","year":"2016","journal-title":"Blood"},{"issue":"12","key":"2024112116205823700_bib94","doi-asserted-by":"crossref","first-page":"3678","DOI":"10.1182\/blood.V95.12.3678.012k45_3678_3682","article-title":"High levels of factor IX increase the risk of venous thrombosis","volume":"95","author":"van Hylckama Vlieg","year":"2000","journal-title":"Blood"},{"issue":"17","key":"2024112116205823700_bib95","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\u00a0Engl J Med"},{"issue":"1","key":"2024112116205823700_bib96","doi-asserted-by":"crossref","first-page":"264","DOI":"10.3324\/haematol.2019.216713","article-title":"Factor IX alteration p.Arg338Gln (FIX Shanghai) potentiates FIX clotting activity and causes thrombosis","volume":"106","author":"Wu","year":"2021","journal-title":"Haematologica"},{"issue":"14","key":"2024112116205823700_bib97","doi-asserted-by":"crossref","first-page":"e128683","DOI":"10.1172\/jci.insight.128683","article-title":"Hyperactivity of factor IX Padua (R338L) depends on factor VIIIa cofactor activity","volume":"5","author":"Samelson-Jones","year":"2019","journal-title":"JCI Insight"},{"issue":"6","key":"2024112116205823700_bib98","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1182\/blood-2004-08-2990","article-title":"Factor IX variants improve gene therapy efficacy for hemophilia B","volume":"105","author":"Schuettrumpf","year":"2005","journal-title":"Blood"},{"issue":"4","key":"2024112116205823700_bib99","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s40265-023-01845-0","article-title":"Etranacogene dezaparvovec: first approval","volume":"83","author":"Heo","year":"2023","journal-title":"Drugs"},{"issue":"10","key":"2024112116205823700_bib100","doi-asserted-by":"crossref","first-page":"e0240896","DOI":"10.1371\/journal.pone.0240896","article-title":"Preclinical evaluation of a next-generation, subcutaneously administered, coagulation factor IX variant, dalcinonacog alfa","volume":"15","author":"Nichols","year":"2020","journal-title":"PLoS One"},{"issue":"21","key":"2024112116205823700_bib101","doi-asserted-by":"crossref","first-page":"2902","DOI":"10.1182\/blood.2020006005","article-title":"Gene therapy for hemophilia B using CB 2679d-GT: a novel factor IX variant with higher potency than factor IX Padua","volume":"137","author":"Nair","year":"2021","journal-title":"Blood"},{"issue":"4","key":"2024112116205823700_bib102","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/hae.14315","article-title":"Efficacy and safety of subcutaneous prophylaxis with dalcinonacog alfa in adults with haemophilia B","volume":"27","author":"Mahlangu","year":"2021","journal-title":"Haemophilia"},{"issue":"4","key":"2024112116205823700_bib103","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1111\/jth.15259","article-title":"Safety, pharmacokinetics, and pharmacodynamics of a next-generation subcutaneously administered coagulation factor IX variant, dalcinonacog alfa, in previously treated hemophilia B patients","volume":"19","author":"You","year":"2021","journal-title":"J\u00a0Thromb Haemost"},{"issue":"6","key":"2024112116205823700_bib104","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1111\/jth.12572","article-title":"Oral gene therapy for hemophilia B using chitosan-formulated FIX mutants","volume":"12","author":"Quade-Lyssy","year":"2014","journal-title":"J\u00a0Thromb Haemost"},{"issue":"8","key":"2024112116205823700_bib105","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1111\/j.1538-7836.2010.03913.x","article-title":"Generation of a novel factor IX with augmented clotting activities in\u00a0vitro and in\u00a0vivo","volume":"8","author":"Lin","year":"2010","journal-title":"J\u00a0Thromb Haemost"},{"issue":"2","key":"2024112116205823700_bib106","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1160\/TH13-02-0154","article-title":"Incorporation of the factor IX Padua mutation into FIX-Triple improves clotting activity in\u00a0vitro and in\u00a0vivo","volume":"110","author":"Kao","year":"2013","journal-title":"Thromb Haemost"},{"issue":"3","key":"2024112116205823700_bib107","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.jtha.2023.11.010","article-title":"Humanization and functional characterization of enhanced coagulation factor IX variants identified through ancestral sequence reconstruction","volume":"22","author":"Coyle","year":"2024","journal-title":"J\u00a0Thromb Haemost"},{"issue":"16","key":"2024112116205823700_bib108","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1182\/blood.2022018083","article-title":"Factor IXa variants resistant to plasma inhibitors enhance clot formation in\u00a0vivo","volume":"141","author":"Ivanciu","year":"2023","journal-title":"Blood"},{"issue":"37","key":"2024112116205823700_bib109","doi-asserted-by":"crossref","first-page":"23418","DOI":"10.1074\/jbc.272.37.23418","article-title":"Interaction of factor IXa with factor VIIIa. Effects of protease domain Ca2+ binding site, proteolysis in the autolysis loop, phospholipid, and factor X","volume":"272","author":"Mathur","year":"1997","journal-title":"J\u00a0Biol Chem"},{"issue":"6","key":"2024112116205823700_bib110","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1111\/jth.12960","article-title":"Selective disruption of heparin and antithrombin-mediated regulation of human factor IX","volume":"13","author":"Westmark","year":"2015","journal-title":"J\u00a0Thromb Haemost"},{"issue":"10","key":"2024112116205823700_bib111","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1161\/ATVBAHA.112.250928","article-title":"Inhibition of intrinsic Xase by protein S: a novel regulatory role of protein S independent of activated protein C","volume":"32","author":"Chattopadhyay","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"2","key":"2024112116205823700_bib112","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1182\/bloodadvances.2023010819","article-title":"Protein S antibody as an adjunct therapy for hemophilia B","volume":"8","author":"Wilson","year":"2024","journal-title":"Blood Adv"},{"issue":"12","key":"2024112116205823700_bib113","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1182\/blood-2017-09-800326","article-title":"Targeting anticoagulant protein S to improve hemostasis in hemophilia","volume":"131","author":"Prince","year":"2018","journal-title":"Blood"},{"issue":"4","key":"2024112116205823700_bib114","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1161\/ATVBAHA.117.310588","article-title":"Anticoagulant protein S targets the factor IXa heparin-binding exosite to prevent thrombosis","volume":"38","author":"Plautz","year":"2018","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"40","key":"2024112116205823700_bib115","doi-asserted-by":"crossref","first-page":"33819","DOI":"10.1074\/jbc.M506502200","article-title":"Down-regulation of factor IXa in the factor Xase complex by protein Z-dependent protease inhibitor","volume":"280","author":"Heeb","year":"2005","journal-title":"J\u00a0Biol Chem"},{"issue":"5","key":"2024112116205823700_bib116","doi-asserted-by":"crossref","first-page":"2540","DOI":"10.1172\/JCI116863","article-title":"Protease nexin-2\/amyloid beta protein precursor. A tight-binding inhibitor of coagulation factor IXa","volume":"92","author":"Schmaier","year":"1993","journal-title":"J\u00a0Clin Invest"},{"issue":"4","key":"2024112116205823700_bib117","doi-asserted-by":"crossref","first-page":"100179","DOI":"10.1016\/j.rpth.2023.100179","article-title":"Antithrombin lowering in hemophilia: a closer look at fitusiran","volume":"7","author":"Young","year":"2023","journal-title":"Res\u00a0Pract Thromb Haemost"},{"issue":"11","key":"2024112116205823700_bib118","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1111\/jth.12731","article-title":"Next generation FIX muteins with FVIII-independent activity for alternative treatment of hemophilia A","volume":"12","author":"Quade-Lyssy","year":"2014","journal-title":"J\u00a0Thromb Haemost"},{"issue":"2","key":"2024112116205823700_bib119","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1182\/blood-2011-05-353672","article-title":"Engineered factor IX variants bypass FVIII and correct hemophilia A phenotype in mice","volume":"119","author":"Milanov","year":"2012","journal-title":"Blood"},{"issue":"6","key":"2024112116205823700_bib120","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.jtha.2023.02.019","article-title":"A\u00a0factor IX variant that functions independently of factor VIII mitigates the\u00a0hemophilia A phenotype in patient plasma","volume":"21","author":"Strijbis","year":"2023","journal-title":"J\u00a0Thromb Haemost"},{"issue":"7","key":"2024112116205823700_bib121","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1160\/TH17-01-0030","article-title":"Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX\/IXa and X\/Xa, emicizumab, depends on its ability to bridge the antigens","volume":"117","author":"Kitazawa","year":"2017","journal-title":"Thromb Haemost"},{"issue":"10","key":"2024112116205823700_bib122","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1038\/nm.2942","article-title":"A\u00a0bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model","volume":"18","author":"Kitazawa","year":"2012","journal-title":"Nat Med"},{"issue":"16","key":"2024112116205823700_bib123","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1182\/blood.2020009217","article-title":"Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies","volume":"137","author":"Callaghan","year":"2021","journal-title":"Blood"},{"issue":"2","key":"2024112116205823700_bib124","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.jtha.2023.09.034","article-title":"A\u00a0bispecific antibody NXT007 exerts a hemostatic activity in hemophilia A monkeys enough to keep a nonhemophilic state","volume":"22","author":"Teranishi-Ikawa","year":"2024","journal-title":"J\u00a0Thromb Haemost"},{"issue":"4","key":"2024112116205823700_bib125","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.jtha.2023.12.016","article-title":"FRONTIER1: a partially randomized phase 2 study assessing the safety, pharmacokinetics, and pharmacodynamics of Mim8, a factor VIIIa mimetic","volume":"22","author":"Lentz","year":"2024","journal-title":"J\u00a0Thromb Haemost"},{"issue":"14","key":"2024112116205823700_bib126","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1182\/blood.2020010331","article-title":"A\u00a0factor VIIIa-mimetic bispecific antibody, Mim8, ameliorates bleeding upon severe vascular challenge in hemophilia A mice","volume":"138","author":"Ostergaard","year":"2021","journal-title":"Blood"},{"issue":"12","key":"2024112116205823700_bib127","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1080\/17474086.2023.2293096","article-title":"Efficacy\/effectiveness and safety of emicizumab prophylaxis of people with hemophilia A: a systematic review and meta-analysis","volume":"16","author":"Muniz","year":"2023","journal-title":"Expert Rev Hematol"},{"issue":"10","key":"2024112116205823700_bib128","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1021\/bi00462a025","article-title":"Kinetics of coagulation factor X activation by platelet-bound factor IXa","volume":"29","author":"Rawala-Sheikh","year":"1990","journal-title":"Biochemistry"},{"issue":"19","key":"2024112116205823700_bib129","doi-asserted-by":"crossref","first-page":"11120","DOI":"10.1074\/jbc.271.19.11120","article-title":"Activation of the factor VIIIa-factor IXa enzyme complex of blood coagulation by membranes containing phosphatidyl-L-serine","volume":"271","author":"Gilbert","year":"1996","journal-title":"J\u00a0Biol Chem"},{"issue":"37","key":"2024112116205823700_bib130","doi-asserted-by":"crossref","first-page":"11261","DOI":"10.1021\/bi010262t","article-title":"The distinct roles that Gln-192 and Glu-217 of factor IX play in selectivity for macromolecular substrates and inhibitors","volume":"40","author":"Hsu","year":"2001","journal-title":"Biochemistry"},{"issue":"1","key":"2024112116205823700_bib131","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jmb.2005.04.052","article-title":"Na+ site in blood coagulation factor IXa: effect on catalysis and factor VIIIa binding","volume":"350","author":"Schmidt","year":"2005","journal-title":"J\u00a0Mol Biol"},{"issue":"6","key":"2024112116205823700_bib132","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/humu.22981","article-title":"HGVS recommendations for the description of sequence variants: 2016 update","volume":"37","author":"den Dunnen","year":"2016","journal-title":"Hum Mutat"},{"issue":"5","key":"2024112116205823700_bib133","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1002\/j.1460-2075.1984.tb01926.x","article-title":"The gene structure of human anti-haemophilic factor IX","volume":"3","author":"Anson","year":"1984","journal-title":"EMBO J"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/144\/21\/2198\/2314049\/blood_bld-2023-023276-c-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/144\/21\/2198\/2314049\/blood_bld-2023-023276-c-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T11:21:31Z","timestamp":1732188091000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/144\/21\/2198\/517006\/Blood-coagulation-factor-IX-structural-insights"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,21]]},"references-count":133,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2024,11,21]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2023023276","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,21]]}}}