{"id":"https://openalex.org/W4387620898","doi":"https://doi.org/10.1161/res.133.suppl_1.p1023","title":"Abstract P1023: Nonsense Mutations In Atrial Myofilament Regulatory Protein MyBP-HL Are Subject To Proteolytic Degradation And Loss Of Functional Protein","display_name":"Abstract P1023: Nonsense Mutations In Atrial Myofilament Regulatory Protein MyBP-HL Are Subject To Proteolytic Degradation And Loss Of Functional Protein","publication_year":2023,"publication_date":"2023-08-04","ids":{"openalex":"https://openalex.org/W4387620898","doi":"https://doi.org/10.1161/res.133.suppl_1.p1023"},"language":"en","primary_location":{"id":"doi:10.1161/res.133.suppl_1.p1023","doi":"https://doi.org/10.1161/res.133.suppl_1.p1023","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1161/res.133.suppl_1.p1023","pdf_url":null,"source":{"id":"https://openalex.org/S10652568","display_name":"Circulation Research","issn_l":"0009-7330","issn":["0009-7330","1524-4571"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Circulation Research","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5058783190","display_name":"Alejandro \u00c1lvarez-Arce","orcid":"https://orcid.org/0000-0001-9608-3004","observed_orcids":["https://orcid.org/0000-0001-9608-3004"]},"institutions":[{"id":"https://openalex.org/I1925986","display_name":"Loyola University Chicago","ror":"https://ror.org/04b6x2g63","country_code":"US","type":"education","lineage":["https://openalex.org/I1925986"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Alejandro A Alvarez-Arce","raw_affiliation_strings":["Loyola Univ Chicago, Chicago, IL","Alejandro A Alvarez-Arce Loyola Univ Chicago, Chicago, IL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Loyola Univ Chicago, Chicago, IL","institution_ids":["https://openalex.org/I1925986"]},{"raw_affiliation_string":"Alejandro A Alvarez-Arce Loyola Univ Chicago, Chicago, IL","institution_ids":["https://openalex.org/I1925986"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012280791","display_name":"Lucas M. Wittenkeller","orcid":"https://orcid.org/0000-0002-6574-8533","observed_orcids":["https://orcid.org/0000-0002-6574-8533"]},"institutions":[{"id":"https://openalex.org/I1925986","display_name":"Loyola University Chicago","ror":"https://ror.org/04b6x2g63","country_code":"US","type":"education","lineage":["https://openalex.org/I1925986"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lucas Wittenkeller","raw_affiliation_strings":["Loyola Univ Chicago, Minooka, IL","Lucas Wittenkeller Loyola Univ Chicago, Minooka, IL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Loyola Univ Chicago, Minooka, IL","institution_ids":["https://openalex.org/I1925986"]},{"raw_affiliation_string":"Lucas Wittenkeller Loyola Univ Chicago, Minooka, IL","institution_ids":["https://openalex.org/I1925986"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5093060499","display_name":"Hope V. Burnham","orcid":"https://orcid.org/0000-0001-9912-019X","observed_orcids":["https://orcid.org/0000-0001-9912-019X"]},"institutions":[{"id":"https://openalex.org/I1925986","display_name":"Loyola University Chicago","ror":"https://ror.org/04b6x2g63","country_code":"US","type":"education","lineage":["https://openalex.org/I1925986"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Hope Burnham","raw_affiliation_strings":["Loyola Univ Chicago, Chicago, IL","Hope Burnham Loyola Univ Chicago, Chicago, IL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Loyola Univ Chicago, Chicago, IL","institution_ids":["https://openalex.org/I1925986"]},{"raw_affiliation_string":"Hope Burnham Loyola Univ Chicago, Chicago, IL","institution_ids":["https://openalex.org/I1925986"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5090210734","display_name":"David Y. Barefield","orcid":"https://orcid.org/0000-0002-6166-640X","observed_orcids":["https://orcid.org/0000-0002-6166-640X"]},"institutions":[{"id":"https://openalex.org/I1925986","display_name":"Loyola University Chicago","ror":"https://ror.org/04b6x2g63","country_code":"US","type":"education","lineage":["https://openalex.org/I1925986"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David Y Barefield","raw_affiliation_strings":["Loyola Univ Chicago, Maywood, IL","David Y Barefield Loyola Univ Chicago, Maywood, IL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Loyola Univ Chicago, Maywood, IL","institution_ids":["https://openalex.org/I1925986"]},{"raw_affiliation_string":"David Y Barefield Loyola Univ Chicago, Maywood, IL","institution_ids":["https://openalex.org/I1925986"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I1925986"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"133","issue":"Suppl_1","first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10882","display_name":"Cardiomyopathy and Myosin Studies","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10882","display_name":"Cardiomyopathy and Myosin Studies","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10217","display_name":"Cardiac electrophysiology and arrhythmias","score":0.0007999999797903001,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10441","display_name":"Muscle Physiology and Disorders","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/nonsense-mutation","display_name":"nonsense mutation","score":0.9879999756813049},{"id":"https://openalex.org/keywords/proteasomal-degradation","display_name":"proteasomal degradation","score":0.7099999785423279},{"id":"https://openalex.org/keywords/calpain","display_name":"calpain","score":0.9229999780654907},{"id":"https://openalex.org/keywords/atrial-fibrillation","display_name":"atrial fibrillation","score":0.675000011920929},{"id":"https://openalex.org/keywords/dilated-cardiomyopathy","display_name":"dilated cardiomyopathy","score":0.8820000290870667},{"id":"https://openalex.org/keywords/atrial-enlargement","display_name":"atrial enlargement","score":0.8880000114440918},{"id":"https://openalex.org/keywords/cardiac-myosin-binding-protein-c","display_name":"myosin binding protein C","score":0.7450000047683716},{"id":"https://openalex.org/keywords/thick-filaments","display_name":"thick filaments","score":0.5809999704360962},{"id":"https://openalex.org/keywords/cardiomyocytes","display_name":"cardiomyocytes","score":0.6549999713897705}],"concepts":[{"id":"https://openalex.org/C174054327","wikidata":"https://www.wikidata.org/wiki/Q6947920","display_name":"Myofilament","level":3,"score":0.8386125564575195},{"id":"https://openalex.org/C68731436","wikidata":"https://www.wikidata.org/wiki/Q1337087","display_name":"Sarcomere","level":3,"score":0.6605154275894165},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.6595959663391113},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4931451678276062},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3863421380519867},{"id":"https://openalex.org/C6997183","wikidata":"https://www.wikidata.org/wiki/Q271727","display_name":"Myosin","level":2,"score":0.3750993609428406},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.35068345069885254},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.34059077501296997},{"id":"https://openalex.org/C207200792","wikidata":"https://www.wikidata.org/wiki/Q428914","display_name":"Myocyte","level":2,"score":0.1610935628414154},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.13384303450584412}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1161/res.133.suppl_1.p1023","doi":"https://doi.org/10.1161/res.133.suppl_1.p1023","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1161/res.133.suppl_1.p1023","pdf_url":null,"source":{"id":"https://openalex.org/S10652568","display_name":"Circulation Research","issn_l":"0009-7330","issn":["0009-7330","1524-4571"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Circulation Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9391000270843506}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4400356767","https://openalex.org/W4403246138","https://openalex.org/W4312276641","https://openalex.org/W4416378792","https://openalex.org/W4313346149","https://openalex.org/W2915034024","https://openalex.org/W4403246077","https://openalex.org/W4414697462","https://openalex.org/W2151433089","https://openalex.org/W2742391938"],"abstract_inverted_index":{"Background:":[0],"Myosin":[1],"binding":[2,69],"protein-H":[3],"like":[4,54],"(MyBP-HL)":[5],"is":[6,42],"a":[7,82,91,127,163,214,228,271],"recently":[8],"identified":[9,105,213],"atrial":[10,25,27],"myofilament":[11,77,147],"protein":[12,88],"encoded":[13],"by":[14,207],"the":[15,55,60,86,138,171,179,208,252],"gene":[16],"MYBPHL.":[17],"The":[18,260],"Arg255Stop":[19],"mutant":[20],"has":[21],"been":[22],"linked":[23],"to":[24,132,135,258],"enlargement,":[26],"fibrillation,":[28],"and":[29,49,57,79,89,116,145,200],"dilated":[30],"cardiomyopathy.":[31,96],"Deletion":[32],"of":[33,44,59,66,85,94,154,170,263,277],"MYBPHL":[34,104,122,245],"in":[35,76,81,103,106,141,156,162,218],"mice":[36],"recapitulates":[37],"this":[38],"human":[39],"phenotype.":[40],"MyBP-HL":[41,133,143,155,186,199,201,219,222,249,268],"composed":[43],"two":[45],"Immunoglobulin":[46],"domains":[47,64],"(Ig)":[48],"one":[50],"Fibronectin":[51],"domain":[52],"(FnIII),":[53],"structure":[56],"sequence":[58],"last":[61],"three":[62],"C-terminal":[63],"(C8-C9-C10)":[65],"cardiac":[67],"myosin":[68],"protein-C":[70],"(cMyBP-C).":[71],"cMyBP-C":[72],"nonsense":[73,123,173,246],"mutations":[74,102,124,174,203,247],"fail":[75],"incorporation":[78,250],"result":[80],"rapid":[83],"degradation":[84,144],"truncated":[87,142,223],"are":[90,98,204,225,234,256],"major":[92],"cause":[93],"hypertrophic":[95],"There":[97],"9":[99],"premature":[100],"stop":[101],"humans":[107],"(Gln29,":[108],"Trp54,":[109],"Arg113,":[110],"Tyr123,":[111],"Trp158,":[112],"Trp192,":[113],"Lys250,":[114],"Arg255,":[115],"Tyr307).":[117],"Hypothesis:":[118],"We":[119,150,195],"hypothesize":[120],"that":[121,130,197,244],"will":[125],"share":[126],"common":[128],"mechanism":[129,274],"leads":[131],"failing":[134],"integrate":[136],"into":[137,178,251],"sarcomere,":[139],"resulting":[140],"loss":[146],"incorporation.":[148],"Results:":[149],"demonstrate":[151],"heterologous":[152],"expression":[153,262],"neonatal":[157],"rat":[158,182],"cardiomyocytes":[159,183],"can":[160],"incorporate":[161],"similar":[164],"sarcomere":[165],"pattern":[166],"as":[167,227,255],"cMyBP-C.":[168],"Expression":[169],"nine":[172],"do":[175],"not":[176,235],"localize":[177],"sarcomere.":[180],"Neonatal":[181],"transfected":[184],"with":[185,190],"constructs":[187],"were":[188],"treated":[189],"proteasome":[191],"and/or":[192],"calpain":[193,216],"inhibitors.":[194],"observed":[196],"wild-type":[198],"truncating":[202,267],"degraded":[205,226],"mainly":[206],"proteasome,":[209],"although":[210],"we":[211,242],"also":[212],"significant":[215],"involvement":[217],"degradation.":[220,259],"Shorter":[221],"peptides":[224,233],"poisoning":[229],"peptides,":[230],"but":[231],"longer":[232],"degraded.":[236],"Conclusion:":[237],"Based":[238],"on":[239],"these":[240,278],"data,":[241],"demonstrated":[243],"prevent":[248],"thick":[253],"filament":[254],"subject":[257],"differential":[261,272],"short":[264],"vs.":[265],"long":[266],"mutants":[269],"suggest":[270],"pathogenic":[273],"for":[275],"subsets":[276],"mutations.":[279]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2023-10-14T00:00:00"}