{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:25:00Z","timestamp":1793381100124,"version":"4.5.0"},"reference-count":100,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,12,6]]},"abstract":"<jats:p xml:lang=\"en\">\n            Nonischemic dilated cardiomyopathy is a common form of heart muscle disease in which genetic factors play a critical etiological role. In this regard, both rare disease\u2010causing mutations and common disease\u2010susceptible variants, in the Bcl\u20102\u2013associated athanogene 3 (\n            <jats:italic>BAG3<\/jats:italic>\n            ) gene have been reported, highlighting the critical role of\n            <jats:italic>BAG3<\/jats:italic>\n            in cardiomyocytes and in the development of dilated cardiomyopathy. The phenotypic effects of the\n            <jats:italic>BAG3<\/jats:italic>\n            mutations help investigators understand the structure and function of the\n            <jats:italic>BAG3<\/jats:italic>\n            gene. Indeed, we report herein that all of the known pathogenic\/likely pathogenic variants affect at least 1 of 3 protein functional domains, ie, the WW domain, the second IPV (Ile\u2010Pro\u2010Val) domain, or the BAG domain, whereas none of the missense nontruncating pathogenic\/likely pathogenic variants affect the proline\u2010rich repeat (PXXP) domain. A common variant, p.Cys151Arg, associated with reduced susceptibility to dilated cardiomyopathy demonstrated a significant difference in allele frequencies among diverse human populations, suggesting evolutionary selective pressure. As\n            <jats:italic>BAG3<\/jats:italic>\n            \u2010related therapies for heart failure move from the laboratory to the clinic, the ability to provide precision medicine will depend in large part on having a thorough understanding of the potential effects of both common and uncommon genetic variants on these target proteins. The current review article provides a roadmap that investigators can utilize to determine the potential interactions between a patient's genotype, their phenotype, and their response to therapeutic interventions with both gene delivery and small molecules.\n          <\/jats:p>","DOI":"10.1161\/jaha.122.027373","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T13:30:35Z","timestamp":1668605435000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":49,"title":["Genetics of BAG3: A Paradigm for Developing Precision Therapies for Dilated Cardiomyopathies"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9317-4488","authenticated-orcid":false,"given":"Hui\u2010Qi","family":"Qu","sequence":"first","affiliation":[{"name":"The Center for Applied Genomics, Children\u2019s Hospital of Philadelphia Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur M.","family":"Feldman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology The Lewis Katz School of Medicine at Temple University Philadelphia PA"},{"name":"The Center for Neurovirology and Gene Editing The Lewis Katz School of Medicine at Temple University Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-7461","authenticated-orcid":false,"given":"Hakon","family":"Hakonarson","sequence":"additional","affiliation":[{"name":"The Center for Applied Genomics, Children\u2019s Hospital of Philadelphia Philadelphia PA"},{"name":"Department of Pediatrics, The Perelman School of Medicine University of Pennsylvania Philadelphia PA"},{"name":"Division of Human Genetics Children\u2019s Hospital of Philadelphia Philadelphia PA"},{"name":"Division of Pulmonary Medicine Children\u2019s Hospital of Philadelphia Philadelphia PA"},{"name":"Faculty of Medicine University of Iceland Reykjavik Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.174287"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehm342"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200012073432304"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199703133361107"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature23305"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2021.11.2668"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.860171"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1505517"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu050"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.08.079"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.18.12670"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00469.2005"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40657"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1504705112"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23272-z"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1255-9"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24615"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2013.105"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI149415"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20090907"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20091739"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21603"},{"key":"e_1_3_2_24_2","first-page":"245","article-title":"How chaperones fold proteins","volume":"379","author":"Beissinger M","year":"1998","unstructured":"Beissinger M, Buchner J. How chaperones fold proteins. Biol Chem. 1998;379:245\u2013259.","journal-title":"Biol Chem"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1379\/1466-1268(1996)001<0023:AHSGTT>2.3.CO;2"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-004-4464-6"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)03290-2"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.08.092"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2011.24"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.08.2181"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2016.11.013"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201593378"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2020.07.012"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1344-5"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203797"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00177"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(02)00456-1"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986609788490230"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5512"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1322"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01101"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.09.013"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg167"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.37.21472"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.225649"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2010.203"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10102638"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030574"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205483"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/415198a"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2001.104.re15"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.01.015"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26482"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00252"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25476"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2010.05.004"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI94310"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.03.017"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2017.09.009"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/35022604"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.037661"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-015-9487-6"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.01.016"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.117.001763"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-12-192"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2018.2541"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.8.1091"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200011093431908"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.120.003250"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.121.003408"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.9.1183"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.929646"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.12.002"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12453"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0733-8619(05)70181-X"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-014-0121-9"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0747"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.349"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1159"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.12.032"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-1712"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0084-7"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.119.002480"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hft013"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.76.050106.093909"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38087"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21553"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2018.02.004"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.01.009"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.185.4154.862"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2020.09.009"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr105"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.12934"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13690-5"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.04.003"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.041161"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.119.002804"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.121.003460"},{"key":"e_1_3_2_100_2","article-title":"Functional analysis of a common BAG3 allele associated with protection from heart failure","author":"Perez\u2010Bermejo JA","year":"2021","unstructured":"Perez\u2010Bermejo JA, Judge LM, Jensen CL, Wu K, Truong A, Ho JJ, Carter MA, Runyon WV, Kaake RM, Pulido E, et al. Functional analysis of a common BAG3 allele associated with protection from heart failure. bioRxiv. 2021. doi: 10.1101\/2021.10.06.463213","journal-title":"bioRxiv"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.012239"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.122.027373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T12:48:58Z","timestamp":1715604538000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.122.027373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,6]]},"references-count":100,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2022,12,6]]}},"alternative-id":["10.1161\/JAHA.122.027373"],"URL":"https:\/\/doi.org\/10.1161\/jaha.122.027373","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,6]]},"assertion":[{"value":"2022-07-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e027373"}}