{"id":"https://openalex.org/W2107724201","doi":"https://doi.org/10.1093/hmg/10.11.1215","title":"Mutations in the gamma2 subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis","display_name":"Mutations in the gamma2 subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis","publication_year":2001,"publication_date":"2001-05-01","ids":{"openalex":"https://openalex.org/W2107724201","doi":"https://doi.org/10.1093/hmg/10.11.1215","mag":"2107724201","pmid":"https://pubmed.ncbi.nlm.nih.gov/11371514"},"language":"en","primary_location":{"id":"doi:10.1093/hmg/10.11.1215","doi":"https://doi.org/10.1093/hmg/10.11.1215","is_oa":false,"landing_page_url":"https://doi.org/10.1093/hmg/10.11.1215","pdf_url":null,"source":{"id":"https://openalex.org/S166515463","display_name":"Human Molecular Genetics","issn_l":"0964-6906","issn":["0964-6906","1460-2083"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"public-domain","license_id":"https://openalex.org/licenses/public-domain","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Human Molecular Genetics","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"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/A5113041744","display_name":"Edward M. Blair","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1336263701","display_name":"Centre for Human Genetics","ror":"https://ror.org/01rjnta51","country_code":"GB","type":"facility","lineage":["https://openalex.org/I1336263701","https://openalex.org/I40120149"]},{"id":"https://openalex.org/I40120149","display_name":"University of Oxford","ror":"https://ror.org/052gg0110","country_code":"GB","type":"education","lineage":["https://openalex.org/I40120149"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"E. Blair","raw_affiliation_strings":["Department of Cardiovascular Medicine and Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Cardiovascular Medicine and Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK","institution_ids":["https://openalex.org/I1336263701","https://openalex.org/I40120149"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5113041744"],"corresponding_institution_ids":["https://openalex.org/I1336263701","https://openalex.org/I40120149"],"apc_list":{"value":4390,"currency":"USD","value_usd":4390},"apc_paid":null,"fwci":28.9215,"has_fulltext":false,"cited_by_count":531,"citation_normalized_percentile":{"value":0.99763537,"is_in_top_1_percent":true,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":98,"max":100},"biblio":{"volume":"10","issue":"11","first_page":"1215","last_page":"1220"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10882","display_name":"Cardiomyopathy and Myosin Studies","score":0.9955999851226807,"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":0.9955999851226807,"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":0.002199999988079071,"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/T11922","display_name":"Cardiovascular Effects of Exercise","score":0.00019999999494757503,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/familial-hypertrophic-cardiomyopathy","display_name":"familial hypertrophic cardiomyopathy","score":0.9959999918937683},{"id":"https://openalex.org/keywords/prkag2","display_name":"PRKAG2","score":0.8799999952316284},{"id":"https://openalex.org/keywords/ampk","display_name":"AMPK","score":0.9490000009536743},{"id":"https://openalex.org/keywords/gamma2-subunit","display_name":"gamma2 subunit","score":0.8880000114440918},{"id":"https://openalex.org/keywords/energy-homeostasis","display_name":"energy homeostasis","score":0.7580000162124634},{"id":"https://openalex.org/keywords/atp-depletion","display_name":"ATP depletion","score":0.8339999914169312},{"id":"https://openalex.org/keywords/myocardial-energy-metabolism","display_name":"myocardial energy metabolism","score":0.5519999861717224},{"id":"https://openalex.org/keywords/preexcitation","display_name":"preexcitation","score":0.6869999766349792},{"id":"https://openalex.org/keywords/wolff-parkinson-white-syndrome","display_name":"Wolff-Parkinson-White syndrome","score":0.972000002861023},{"id":"https://openalex.org/keywords/atrioventricular-conduction-defects","display_name":"atrioventricular conduction defects","score":0.7239999771118164},{"id":"https://openalex.org/keywords/sarcomere-mutations","display_name":"sarcomere gene mutations","score":0.5799999833106995},{"id":"https://openalex.org/keywords/sudden-cardiac-death","display_name":"sudden cardiac death","score":0.5960000157356262},{"id":"https://openalex.org/keywords/cardiomyopathy","display_name":"cardiomyopathy","score":0.4790000021457672}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.8574100732803345},{"id":"https://openalex.org/C104292427","wikidata":"https://www.wikidata.org/wiki/Q899781","display_name":"Protein subunit","level":3,"score":0.6368545889854431},{"id":"https://openalex.org/C2780942790","wikidata":"https://www.wikidata.org/wiki/Q372016","display_name":"Pathogenesis","level":2,"score":0.6280975937843323},{"id":"https://openalex.org/C2780185194","wikidata":"https://www.wikidata.org/wiki/Q1364270","display_name":"Hypertrophic cardiomyopathy","level":2,"score":0.5600177049636841},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.5393218398094177},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.5229264497756958},{"id":"https://openalex.org/C97029542","wikidata":"https://www.wikidata.org/wiki/Q281417","display_name":"Protein kinase A","level":3,"score":0.49154552817344666},{"id":"https://openalex.org/C2778797674","wikidata":"https://www.wikidata.org/wiki/Q847583","display_name":"Cardiomyopathy","level":3,"score":0.4464056193828583},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.4355512261390686},{"id":"https://openalex.org/C2780074459","wikidata":"https://www.wikidata.org/wiki/Q389735","display_name":"Heart disease","level":2,"score":0.43247273564338684},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.3985152542591095},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.37601029872894287},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.26175937056541443},{"id":"https://openalex.org/C2778198053","wikidata":"https://www.wikidata.org/wiki/Q181754","display_name":"Heart failure","level":2,"score":0.15493756532669067},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.14247450232505798},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.08721837401390076},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.07829341292381287}],"mesh":[{"descriptor_ui":"D000595","descriptor_name":"Amino Acid Sequence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002312","descriptor_name":"Cardiomyopathy, Hypertrophic","qualifier_ui":"Q000209","qualifier_name":"etiology","is_major_topic":false},{"descriptor_ui":"D002312","descriptor_name":"Cardiomyopathy, Hypertrophic","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D004252","descriptor_name":"DNA Mutational Analysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004562","descriptor_name":"Electrocardiography","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005091","descriptor_name":"Exons","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007438","descriptor_name":"Introns","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008969","descriptor_name":"Molecular Sequence Data","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D010375","descriptor_name":"Pedigree","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011494","descriptor_name":"Protein Kinases","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D011494","descriptor_name":"Protein Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D017386","descriptor_name":"Sequence Homology, Amino Acid","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020022","descriptor_name":"Genetic Predisposition to Disease","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1093/hmg/10.11.1215","doi":"https://doi.org/10.1093/hmg/10.11.1215","is_oa":false,"landing_page_url":"https://doi.org/10.1093/hmg/10.11.1215","pdf_url":null,"source":{"id":"https://openalex.org/S166515463","display_name":"Human Molecular Genetics","issn_l":"0964-6906","issn":["0964-6906","1460-2083"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"public-domain","license_id":"https://openalex.org/licenses/public-domain","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Human Molecular Genetics","raw_type":"journal-article"},{"id":"pmid:11371514","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/11371514","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Human molecular genetics","raw_type":"Journal Article"},{"id":"pmh:oai:pure.atira.dk:openaire_cris_publications/a1cbd99e-f413-4a63-946d-088803b595d1","doi":null,"is_oa":false,"landing_page_url":"https://research.manchester.ac.uk/en/publications/a1cbd99e-f413-4a63-946d-088803b595d1","pdf_url":null,"source":{"id":"https://openalex.org/S4306400662","display_name":"Research Explorer (The University of Manchester)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I28407311","host_organization_name":"University of Manchester","host_organization_lineage":["https://openalex.org/I28407311"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Blair, E, Redwood, C, Ashrafian, H, Oliveira, M, Brotholme, J, Kerr, B, Salmon, A, Ostman-Smith, I & Watkins, H 2001, 'Mutations in the y2 subunit of AMP-activated protein kinase case familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis', Human Molecular Genetics, vol. 10.","raw_type":"article"},{"id":"mag:2752157129","doi":null,"is_oa":false,"landing_page_url":"https://hmg.oxfordjournals.org/content/10/11/1215.full.pdf","pdf_url":null,"source":{"id":"https://openalex.org/S112540174","display_name":"Journal of Medical Genetics","issn_l":"0022-2593","issn":["0022-2593","1468-6244"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319945","host_organization_name":"BMJ","host_organization_lineage":["https://openalex.org/P4310319945"],"host_organization_lineage_names":["BMJ"],"type":"journal"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":"Journal of Medical Genetics","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9391000270843506,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320314140","display_name":"Family Process Institute","ror":"https://ror.org/03vd52t28"},{"id":"https://openalex.org/F4320319992","display_name":"British Heart Foundation","ror":"https://ror.org/02wdwnk04"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":35,"referenced_works":["https://openalex.org/W150160820","https://openalex.org/W1565979608","https://openalex.org/W1593732853","https://openalex.org/W1876043561","https://openalex.org/W1965042960","https://openalex.org/W1966093898","https://openalex.org/W1968754807","https://openalex.org/W1973816983","https://openalex.org/W1974847389","https://openalex.org/W1974870493","https://openalex.org/W1976261899","https://openalex.org/W1977204209","https://openalex.org/W1993538210","https://openalex.org/W1995697852","https://openalex.org/W1997997206","https://openalex.org/W2006641764","https://openalex.org/W2009641633","https://openalex.org/W2062419041","https://openalex.org/W2067142765","https://openalex.org/W2068251811","https://openalex.org/W2070485708","https://openalex.org/W2083655799","https://openalex.org/W2087561447","https://openalex.org/W2087806880","https://openalex.org/W2096913221","https://openalex.org/W2101527214","https://openalex.org/W2111946082","https://openalex.org/W2129727255","https://openalex.org/W2134535786","https://openalex.org/W2140586775","https://openalex.org/W2144577182","https://openalex.org/W2149422196","https://openalex.org/W2168013509","https://openalex.org/W2169691331","https://openalex.org/W2325990028"],"related_works":["https://openalex.org/W2783598645","https://openalex.org/W2053492543","https://openalex.org/W2076781429","https://openalex.org/W7111604304","https://openalex.org/W1989891006","https://openalex.org/W2788198493","https://openalex.org/W2062901651","https://openalex.org/W7202408805","https://openalex.org/W2783398209","https://openalex.org/W4232094550"],"abstract_inverted_index":{"Familial":[0],"hypertrophic":[1],"cardiomyopathy":[2],"(HCM)":[3],"has":[4,20],"been":[5,21],"widely":[6],"studied":[7],"as":[8,23,194,219],"a":[9,24,174,195,220],"genetic":[10],"model":[11],"of":[12,26,46,65,74,78,88,130,183,202,222,232],"cardiac":[13,17,28],"hypertrophy":[14],"and":[15,141,160,213],"sudden":[16],"death.":[18],"HCM":[19,140,237],"defined":[22],"disease":[25,37,235],"the":[27,33,71,79,101,118,127,229],"sarcomere,":[29],"but":[30],"mutations":[31,81,123],"in":[32,42,52,85,114,117,124,135,148,167,199],"known":[34],"contractile":[35,53],"protein":[36,132],"genes":[38,112],"are":[39,55],"not":[40,69],"found":[41],"up":[43],"to":[44,83,94,146,228],"one-third":[45],"cases.":[47],"Further,":[48],"no":[49],"consistent":[50],"changes":[51],"properties":[54],"shared":[56],"by":[57,215],"these":[58,189],"mutant":[59],"proteins,":[60],"implying":[61],"that":[62,91,178,188,236],"an":[63,92],"abnormality":[64],"force":[66],"generation":[67],"may":[68,99],"be":[70,100,226],"underlying":[72],"mechanism":[73,177,198],"disease.":[75],"Instead,":[76],"all":[77,200],"sarcomeric":[80],"appear":[82],"result":[84],"inefficient":[86],"use":[87],"ATP,":[89],"suggesting":[90],"inability":[93],"maintain":[95],"normal":[96],"ATP":[97,184],"levels":[98],"central":[102,175],"abnormality.":[103],"To":[104],"test":[105],"this":[106,211],"hypothesis":[107],"we":[108,186],"have":[109],"examined":[110],"candidate":[111],"involved":[113],"energy":[115,192,217],"homeostasis":[116],"heart.":[119],"We":[120],"now":[121],"describe":[122],"PRKAG2,":[125],"encoding":[126],"gamma(2)":[128],"subunit":[129],"AMP-activated":[131],"kinase":[133],"(AMPK),":[134],"two":[136],"families":[137],"with":[138],"severe":[139],"aberrant":[142],"conduction":[143],"from":[144,181],"atria":[145],"ventricles":[147],"some":[149],"affected":[150],"individuals":[151],"(pre-excitation":[152],"or":[153],"Wolff-Parkinson-White":[154],"syndrome).":[155],"The":[156],"mutations,":[157],"one":[158,161],"missense":[159],"in-frame":[162],"single":[163],"codon":[164],"insertion,":[165],"occur":[166],"highly":[168],"conserved":[169],"regions.":[170],"Because":[171],"AMPK":[172],"provides":[173],"sensing":[176],"protects":[179],"cells":[180],"exhaustion":[182],"supplies,":[185],"propose":[187],"data":[190],"substantiate":[191],"compromise":[193],"unifying":[196],"pathogenic":[197],"forms":[201,231],"HCM.":[203],"This":[204],"conclusion":[205],"should":[206,225],"radically":[207],"redirect":[208],"thinking":[209],"about":[210],"disorder":[212],"also,":[214],"establishing":[216],"depletion":[218],"cause":[221],"myocardial":[223],"dysfunction,":[224],"relevant":[227],"acquired":[230],"heart":[233],"muscle":[234],"models.":[238]},"counts_by_year":[{"year":2026,"cited_by_count":8},{"year":2025,"cited_by_count":6},{"year":2024,"cited_by_count":6},{"year":2023,"cited_by_count":7},{"year":2022,"cited_by_count":8},{"year":2021,"cited_by_count":12},{"year":2020,"cited_by_count":12},{"year":2019,"cited_by_count":13},{"year":2018,"cited_by_count":14},{"year":2017,"cited_by_count":25},{"year":2016,"cited_by_count":19},{"year":2015,"cited_by_count":9},{"year":2014,"cited_by_count":12},{"year":2013,"cited_by_count":18},{"year":2012,"cited_by_count":29}],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2016-06-24T00:00:00"}