{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:43:48Z","timestamp":1791164628686,"version":"4.1.0"},"reference-count":35,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,11,6]],"date-time":"2022-11-06T00:00:00Z","timestamp":1667692800000},"content-version":"vor","delay-in-days":3111,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["PG\/06\/038"],"award-info":[{"award-number":["PG\/06\/038"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["RG\/09\/007\/27917"],"award-info":[{"award-number":["RG\/09\/007\/27917"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["jthjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Thrombosis and Haemostasis"],"published-print":{"date-parts":[[2014,5]]},"DOI":"10.1111\/jth.12539","type":"journal-article","created":{"date-parts":[[2014,2,25]],"date-time":"2014-02-25T02:21:06Z","timestamp":1393294866000},"page":"716-725","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":47,"title":["A novel mutation in the P2Y12 receptor and a function\u2010reducing polymorphism in protease\u2010activated receptor\u00a01 in a patient with chronic bleeding"],"prefix":"10.1016","volume":"12","author":[{"given":"Y.M.","family":"Patel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7418-6766","authenticated-orcid":false,"given":"M.","family":"Lordkipanidz\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.C.","family":"Lowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.P.","family":"Nisar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Garner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Stockley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.E.","family":"Daly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.P.","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.K.","family":"Austin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.J.","family":"Mundell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1111\/jth.12539_bb0010","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s11302-011-9247-6","article-title":"P2 receptors and platelet function","volume":"7","author":"Hechler","year":"2011","journal-title":"Purinergic Signal"},{"key":"10.1111\/jth.12539_bb0015","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1074\/jbc.273.4.2030","article-title":"Molecular basis for ADP\u2010induced platelet activation. II. The P2Y1 receptor mediates ADP\u2010induced intracellular calcium mobilization and shape change in platelets","volume":"273","author":"Jin","year":"1998","journal-title":"J Biol Chem"},{"key":"10.1111\/jth.12539_bb0020","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1182\/blood.V92.1.152.413k27_152_159","article-title":"The P2Y1 receptor is necessary for adenosine 5\u2032\u2010diphosphate\u2010induced platelet aggregation","volume":"92","author":"Hechler","year":"1998","journal-title":"Blood"},{"key":"10.1111\/jth.12539_bb0025","doi-asserted-by":"crossref","first-page":"8070","DOI":"10.1073\/pnas.95.14.8070","article-title":"Coactivation of two different G\u00a0protein\u2010coupled receptors is essential for ADP\u2010induced platelet aggregation","volume":"95","author":"Jin","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1111\/jth.12539_bb0030","doi-asserted-by":"crossref","first-page":"5641","DOI":"10.1182\/blood-2011-02-336826","article-title":"An intact PDZ motif is essential for correct P2Y12 purinoceptor traffic in human platelets","volume":"118","author":"Nisar","year":"2011","journal-title":"Blood"},{"key":"10.1111\/jth.12539_bb0035","doi-asserted-by":"crossref","first-page":"4110","DOI":"10.1182\/blood-2008-11-190850","article-title":"Identification and characterization of a novel P2Y\u00a012 variant in a patient diagnosed with type\u00a01 von Willebrand disease in the European MCMDM\u20101VWD study","volume":"113","author":"Daly","year":"2009","journal-title":"Blood"},{"key":"10.1111\/jth.12539_bb0040","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1111\/j.1742-4658.2011.08410.x","article-title":"Identification and analysis of functionally important amino acids in human purinergic\u00a012 receptor using a Saccharomyces cerevisiae expression system","volume":"279","author":"Ignatovica","year":"2012","journal-title":"FEBS J"},{"key":"10.1111\/jth.12539_bb0045","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1124\/mol.112.082198","article-title":"Identification of determinants required for agonistic and inverse agonistic ligand properties at the ADP receptor P2Y12","volume":"83","author":"Schmidt","year":"2013","journal-title":"Mol Pharmacol"},{"key":"10.1111\/jth.12539_bb0050","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1182\/blood-2009-08-236976","article-title":"A novel thromboxane\u00a0A2 receptor D304N variant that abrogates ligand binding in a patient with a bleeding diathesis","volume":"115","author":"Mumford","year":"2010","journal-title":"Blood"},{"key":"10.1111\/jth.12539_bb0055","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1073\/pnas.0437879100","article-title":"Molecular bases of defective signal transduction in the platelet P2Y12 receptor of a patient with congenital bleeding","volume":"100","author":"Cattaneo","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1111\/jth.12539_bb0060","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1124\/pr.110.003350","article-title":"The significance of G\u00a0protein\u2010coupled receptor crystallography for drug discovery","volume":"63","author":"Salon","year":"2011","journal-title":"Pharmacol Rev"},{"key":"10.1111\/jth.12539_bb0065","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.tips.2009.02.006","article-title":"Ligand binding and micro\u2010switches in 7TM receptor structures","volume":"30","author":"Nygaard","year":"2009","journal-title":"Trends Pharmacol Sci"},{"key":"10.1111\/jth.12539_bb0070","doi-asserted-by":"crossref","first-page":"5041","DOI":"10.1182\/blood-2012-07-444281","article-title":"Evaluation of participants with suspected heritable platelet function disorders including recommendation and validation of a streamlined agonist panel","volume":"120","author":"Dawood","year":"2012","journal-title":"Blood"},{"key":"10.1111\/jth.12539_bb0075","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1538-7836.2004.01063.x","article-title":"Flow cytometric analysis of intraplatelet VASP phosphorylation for the detection of clopidogrel resistance in patients with ischemic cardiovascular diseases","volume":"3","author":"Aleil","year":"2005","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.12539_bb0080","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1124\/mol.106.023549","article-title":"Distinct roles for protein kinase\u00a0C isoforms in regulating platelet purinergic receptor function","volume":"70","author":"Mundell","year":"2006","journal-title":"Mol Pharmacol"},{"key":"10.1111\/jth.12539_bb0085","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1182\/blood-2004-07-2893","article-title":"P2Y1 and P2Y12 receptors for ADP desensitize by distinct kinase\u2010dependent mechanisms","volume":"105","author":"Hardy","year":"2005","journal-title":"Blood"},{"key":"10.1111\/jth.12539_bb0090","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1111\/j.1600-0854.2006.00469.x","article-title":"Distinct clathrin\u2010coated pits sort different G\u00a0protein\u2010coupled receptor cargo","volume":"7","author":"Mundell","year":"2006","journal-title":"Traffic"},{"key":"10.1111\/jth.12539_bb0095","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1111\/j.1471-4159.2004.02387.x","article-title":"Agonist\u2010independent internalization of metabotropic glutamate receptor\u00a01a is arrestin\u2010 and clathrin\u2010dependent and is suppressed by receptor inverse agonists","volume":"89","author":"Pula","year":"2004","journal-title":"J Neurochem"},{"key":"10.1111\/jth.12539_bb0100","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1182\/blood-2002-07-2149","article-title":"An intronic polymorphism in the PAR\u20101 gene is associated with platelet receptor density and the response to SFLLRN","volume":"101","author":"Dupont","year":"2003","journal-title":"Blood"},{"key":"10.1111\/jth.12539_bb0105","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1080\/00207230500120294","article-title":"PAR\u20101 genotype influences platelet aggregation and procoagulant responses in patients with coronary artery disease prior to and during clopidogrel therapy","volume":"16","author":"Smith","year":"2005","journal-title":"Platelets"},{"key":"10.1111\/jth.12539_bb0110","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1111\/j.1538-7836.2008.03039.x","article-title":"Rapid resensitization of purinergic receptor function in human platelets","volume":"6","author":"Mundell","year":"2008","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.12539_bb0115","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1055\/s-0037-1617145","article-title":"Phenotypic approaches to gene mapping in platelet function disorders \u2013 identification of new variant of P2Y12, TxA2 and GPVI receptors","volume":"30","author":"Watson","year":"2010","journal-title":"Hamostaseologie"},{"key":"10.1111\/jth.12539_bb0120","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1182\/blood-2010-08-263111","article-title":"The platelet P2Y(1)(2) receptor for adenosine diphosphate: congenital and drug\u2010induced defects","volume":"117","author":"Cattaneo","year":"2011","journal-title":"Blood"},{"key":"10.1111\/jth.12539_bb0125","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.tips.2012.11.002","article-title":"GPCR activation: a mutagenic spotlight on crystal structures","volume":"34","author":"Hulme","year":"2013","journal-title":"Trends Pharmacol Sci"},{"key":"10.1111\/jth.12539_bb0130","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.tips.2011.02.005","article-title":"Structural insights into adrenergic receptor function and pharmacology","volume":"32","author":"Kobilka","year":"2011","journal-title":"Trends Pharmacol Sci"},{"key":"10.1111\/jth.12539_bb0135","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1124\/mol.106.029470","article-title":"The highly conserved DRY motif of class\u00a0A G\u00a0protein\u2010coupled receptors: beyond the ground state","volume":"71","author":"Rovati","year":"2007","journal-title":"Mol Pharmacol"},{"key":"10.1111\/jth.12539_bb0140","doi-asserted-by":"crossref","first-page":"13030","DOI":"10.1016\/S0021-9258(19)38614-4","article-title":"Nephrogenic diabetes insipidus. A V2 vasopressin receptor unable to stimulate adenylyl cyclase","volume":"268","author":"Rosenthal","year":"1993","journal-title":"J Biol Chem"},{"key":"10.1111\/jth.12539_bb0145","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1159\/000098147","article-title":"Molecular genetic analysis of normosmic hypogonadotropic hypogonadism in a Turkish population: identification and detailed functional characterization of a novel mutation in the gonadotropin\u2010releasing hormone receptor gene","volume":"84","author":"Topaloglu","year":"2006","journal-title":"Neuroendocrinology"},{"key":"10.1111\/jth.12539_bb0150","first-page":"2680","article-title":"Two novel mutations in the gonadotropin\u2010releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction","volume":"86","author":"Costa","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1111\/jth.12539_bb0155","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1124\/jpet.109.163220","article-title":"Impact of the DRY motif and the missing \u2018ionic lock\u2019 on constitutive activity and G\u2010protein coupling of the human histamine H4 receptor","volume":"333","author":"Schneider","year":"2010","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1111\/jth.12539_bb0160","doi-asserted-by":"crossref","first-page":"25406","DOI":"10.1074\/jbc.271.41.25406","article-title":"Modulation of GDP release from transducin by the conserved Glu134\u2010Arg135 sequence in rhodopsin","volume":"271","author":"Acharya","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1111\/jth.12539_bb0165","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1073\/pnas.98.1.93","article-title":"Constitutive arrestin\u2010mediated desensitization of a human vasopressin receptor mutant associated with nephrogenic diabetes insipidus","volume":"98","author":"Barak","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1111\/jth.12539_bb0170","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1128\/MCB.26.8.3231-3242.2006","article-title":"Clathrin adaptor AP2 regulates thrombin receptor constitutive internalization and endothelial cell resensitization","volume":"26","author":"Paing","year":"2006","journal-title":"Mol Cell Biol"},{"key":"10.1111\/jth.12539_bb0175","doi-asserted-by":"crossref","first-page":"7079","DOI":"10.1074\/jbc.M009375200","article-title":"Role of the differentially spliced carboxyl terminus in thromboxane\u00a0A2 receptor trafficking: identification of a distinct motif for tonic internalization","volume":"276","author":"Parent","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1111\/jth.12539_bb0180","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1146\/annurev.pharmtox.48.113006.094646","article-title":"G\u00a0protein\u2010coupled receptor sorting to endosomes and lysosomes","volume":"48","author":"Marchese","year":"2008","journal-title":"Annu Rev Pharmacol Toxicol"}],"container-title":["Journal of Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjth.12539","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjth.12539","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783622039290?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783622039290?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/onlinelibrary.wiley.com\/wol1\/doi\/10.1111\/jth.12539\/fullpdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T03:09:23Z","timestamp":1761534563000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1538783622039290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5]]},"references-count":35,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,5]]}},"alternative-id":["S1538783622039290"],"URL":"https:\/\/doi.org\/10.1111\/jth.12539","relation":{},"ISSN":["1538-7836"],"issn-type":[{"value":"1538-7836","type":"print"}],"subject":[],"published":{"date-parts":[[2014,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A novel mutation in the P2Y12 receptor and a function\u2010reducing polymorphism in protease\u2010activated receptor\u00a01 in a patient with chronic bleeding","name":"articletitle","label":"Article Title"},{"value":"Journal of Thrombosis and Haemostasis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1111\/jth.12539","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}