{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:48:54Z","timestamp":1791946134314,"version":"4.3.4"},"reference-count":193,"publisher":"The Company of Biologists","issue":"5","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"crossref","award":["OCENW.GROOT.2019.029"],"award-info":[{"award-number":["OCENW.GROOT.2019.029"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The sinoatrial node (SAN) is the primary pacemaker of the mammalian heart, initiating its electrical activation and ensuring that the heart's functional cardiac output meets physiological demand. SAN dysfunction (SND) can cause complex cardiac arrhythmias that can manifest as severe sinus bradycardia, sinus arrest, chronotropic incompetence and increased susceptibility to atrial fibrillation, among other cardiac conditions. SND has a complex aetiology, with both pre-existing disease and heritable genetic variation predisposing individuals to this pathology. In this Review, we summarize the current understanding of the genetic contributions to SND and the insights that they provide into this disorder's underlying molecular mechanisms. With an improved understanding of these molecular mechanisms, we can improve treatment options for SND patients and develop new therapeutics.<\/jats:p>","DOI":"10.1242\/dmm.050101","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T11:03:07Z","timestamp":1684321387000},"source":"Crossref","is-referenced-by-count":22,"title":["Genetics of sinoatrial node function and heart rate disorders"],"prefix":"10.1242","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6686-4029","authenticated-orcid":false,"given":"Lieve E.","family":"van der Maarel","sequence":"first","affiliation":[{"name":"Amsterdam Cardiovascular Sciences, Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam 1 Department of Medical Biology , , Amsterdam 1105 AZ , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4874-2487","authenticated-orcid":false,"given":"Alex V.","family":"Postma","sequence":"additional","affiliation":[{"name":"Amsterdam Cardiovascular Sciences, Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam 1 Department of Medical Biology , , Amsterdam 1105 AZ , The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences, Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam 2 Department of Human Genetics , , Amsterdam 1105 AZ , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4131-2636","authenticated-orcid":false,"given":"Vincent M.","family":"Christoffels","sequence":"additional","affiliation":[{"name":"Amsterdam Cardiovascular Sciences, Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam 1 Department of Medical Biology , , Amsterdam 1105 AZ , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"2023051711025256000_DMM050101C1","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1111\/jce.15306","article-title":"Mutational spectrum of congenital long QT syndrome in Turkey; identification of 12 novel mutations across KCNQ1, KCNH2, SCN5A, KCNJ2, CACNA1C, and CALM1","volume":"33","author":"Akgun-Dogan","year":"2022","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"2023051711025256000_DMM050101C2","doi-asserted-by":"publisher","first-page":"e71100","DOI":"10.1371\/journal.pone.0071100","article-title":"Popeye domain containing 1 (Popdc1\/Bves) is a caveolae-associated protein involved in ischemia tolerance","volume":"8","author":"Alcalay","year":"2013","journal-title":"PLoS One"},{"key":"2023051711025256000_DMM050101C3","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1001\/jama.1983.03340160046030","article-title":"Arrhythmias associated with sinus node dysfunction. Pathogenesis, recognition, and management","volume":"250","author":"Alpert","year":"1983","journal-title":"JAMA"},{"key":"2023051711025256000_DMM050101C4","doi-asserted-by":"publisher","first-page":"10039","DOI":"10.1038\/s41598-020-66671-w","article-title":"Early-onset atrial fibrillation patients show reduced left ventricular ejection fraction and increased atrial fibrosis","volume":"10","author":"Andreasen","year":"2020","journal-title":"Sci. Rep."},{"key":"2023051711025256000_DMM050101C5","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/nn.2694","article-title":"Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy with bradycardia and congenital deafness","volume":"14","author":"Baig","year":"2011","journal-title":"Nat. Neurosci."},{"key":"2023051711025256000_DMM050101C6","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1161\/CIRCRESAHA.107.169565","article-title":"Transcription factor Tbx3 is required for the specification of the atrioventricular conduction system","volume":"102","author":"Bakker","year":"2008","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C7","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.pbiomolbio.2009.01.012","article-title":"Caveolae, ion channels and cardiac arrhythmias","volume":"98","author":"Balijepalli","year":"2008","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"2023051711025256000_DMM050101C8","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.yjmcc.2012.05.013","article-title":"A caveolin-binding domain in the HCN4 channels mediates functional interaction with caveolin proteins","volume":"53","author":"Barbuti","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"2023051711025256000_DMM050101C9","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/ng0197-30","article-title":"Mutations in human TBX5 (corrected) cause limb and cardiac malformation in Holt-Oram syndrome","volume":"15","author":"Basson","year":"1997","journal-title":"Nat. Genet."},{"key":"2023051711025256000_DMM050101C10","doi-asserted-by":"publisher","first-page":"419","DOI":"10.3389\/fphys.2016.00419","article-title":"The autonomic nervous system regulates the heart rate through cAMP-PKA dependent and independent coupled-clock pacemaker cell mechanisms","volume":"7","author":"Behar","year":"2016","journal-title":"Front. Physiol."},{"key":"2023051711025256000_DMM050101C11","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1038\/ng.2712","article-title":"Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death","volume":"45","author":"Bezzina","year":"2013","journal-title":"Nat. Genet."},{"key":"2023051711025256000_DMM050101C12","doi-asserted-by":"publisher","first-page":"a037408","DOI":"10.1101\/cshperspect.a037408","article-title":"Development of the cardiac conduction system","volume":"12","author":"Bhattacharyya","year":"2020","journal-title":"Cold Spring Harb. Perspect Biol."},{"key":"2023051711025256000_DMM050101C13","doi-asserted-by":"publisher","first-page":"3243","DOI":"10.1093\/eurheartj\/ehy142","article-title":"A rare missense mutation in MYH6 associates with non-syndromic coarctation of the aorta","volume":"39","author":"Bjornsson","year":"2018","journal-title":"Eur. Heart J."},{"key":"2023051711025256000_DMM050101C14","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1161\/CIRCULATIONAHA.106.637819","article-title":"Targeted mutation reveals essential functions of the homeodomain transcription factor Shox2 in sinoatrial and pacemaking development","volume":"115","author":"Blaschke","year":"2007","journal-title":"Circulation"},{"key":"2023051711025256000_DMM050101C15","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/j.tcm.2015.02.005","article-title":"The past, present, and future of pacemaker therapies","volume":"25","author":"Boink","year":"2015","journal-title":"Trends Cardiovasc. Med."},{"key":"2023051711025256000_DMM050101C16","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1161\/CIRCRESAHA.110.219949","article-title":"Mechanistic links between Na+ channel (SCN5A) mutations and impaired cardiac pacemaking in sick sinus syndrome","volume":"107","author":"Butters","year":"2010","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C17","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/j.bbrc.2007.10.106","article-title":"Characterizations of a loss-of-function mutation in the Kir3.4 channel subunit","volume":"364","author":"Calloe","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023051711025256000_DMM050101C18","doi-asserted-by":"publisher","first-page":"424","DOI":"10.3389\/fgene.2020.00424","article-title":"From GWAS to function: using functional genomics to identify the mechanisms underlying complex diseases","volume":"11","author":"Cano-Gamez","year":"2020","journal-title":"Front. Genet."},{"key":"2023051711025256000_DMM050101C19","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1186\/s13023-022-02542-z","article-title":"Whole exome sequencing in Brugada and long QT syndromes revealed novel rare and potential pathogenic mutations related to the dysfunction of the cardiac sodium channel","volume":"17","author":"Chen","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"2023051711025256000_DMM050101C20","doi-asserted-by":"publisher","first-page":"840337","DOI":"10.3389\/fcvm.2022.840337","article-title":"Atrial lesions in a pedigree With PRKAG2 cardiomyopathy: involvement of disrupted AMP-activated protein kinase signaling","volume":"9","author":"Chen","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"2023051711025256000_DMM050101C21","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1038\/ng.3113","article-title":"Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm","volume":"46","author":"Chetaille","year":"2014","journal-title":"Nat. Genet."},{"key":"2023051711025256000_DMM050101C22","doi-asserted-by":"publisher","first-page":"2354","DOI":"10.1001\/jama.2018.18179","article-title":"Association between titin loss-of-function variants and early-onset atrial fibrillation","volume":"320","author":"Choi","year":"2018","journal-title":"JAMA"},{"key":"2023051711025256000_DMM050101C23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11357-021-00420-3","article-title":"Slowing down as we age: aging of the cardiac pacemaker's neural control","volume":"44","author":"Choi","year":"2022","journal-title":"Geroscience"},{"key":"2023051711025256000_DMM050101C24","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1161\/01.RES.0000227571.84189.65","article-title":"Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18","volume":"98","author":"Christoffels","year":"2006","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C25","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1161\/CIRCRESAHA.109.205419","article-title":"Development of the pacemaker tissues of the heart","volume":"106","author":"Christoffels","year":"2010","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C26","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/nrcardio.2017.165","article-title":"Next-generation pacemakers: from small devices to biological pacemakers","volume":"15","author":"Cingolani","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"2023051711025256000_DMM050101C27","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1002\/ajmg.a.61571","article-title":"Wolff-Parkinson-White syndrome: De novo variants and evidence for mutational burden in genes associated with atrial fibrillation","volume":"182","author":"Coban-Akdemir","year":"2020","journal-title":"Am. J. Med. Genet. A"},{"key":"2023051711025256000_DMM050101C28","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.pbiomolbio.2015.12.011","article-title":"Human sinoatrial node structure: 3D microanatomy of sinoatrial conduction pathways","volume":"120","author":"Csepe","year":"2016","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"2023051711025256000_DMM050101C29","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1242\/dev.00431","article-title":"Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome","volume":"130","author":"Davenport","year":"2003","journal-title":"Development"},{"key":"2023051711025256000_DMM050101C30","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nature12753","article-title":"Topology of mammalian developmental enhancers and their regulatory landscapes","volume":"502","author":"de Laat","year":"2013","journal-title":"Nature"},{"key":"2023051711025256000_DMM050101C31","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1136\/jmedgenet-2020-107015","article-title":"Inhibition of G-protein signalling in cardiac dysfunction of intellectual developmental disorder with cardiac arrhythmia (IDDCA) syndrome","volume":"58","author":"De Nittis","year":"2021","journal-title":"J. Med. Genet."},{"key":"2023051711025256000_DMM050101C32","doi-asserted-by":"publisher","first-page":"2551","DOI":"10.1161\/hc4601.099466","article-title":"Molecular basis of downregulation of G-protein-coupled inward rectifying K(+) current (I(K,ACh) in chronic human atrial fibrillation: decrease in GIRK4 mRNA correlates with reduced I(K,ACh) and muscarinic receptor-mediated shortening of action potentials","volume":"104","author":"Dobrev","year":"2001","journal-title":"Circulation"},{"key":"2023051711025256000_DMM050101C33","doi-asserted-by":"publisher","first-page":"9247541","DOI":"10.1155\/2021\/9247541","article-title":"Whole-exome sequencing identifies a novel TRPM4 mutation in a chinese family with atrioventricular block","volume":"2021","author":"Dong","year":"2021","journal-title":"Biomed. Res. Int."},{"key":"2023051711025256000_DMM050101C34","doi-asserted-by":"publisher","first-page":"40","DOI":"10.3390\/jcdd8040040","article-title":"Assembly of the cardiac pacemaking complex: electrogenic principles of sinoatrial node morphogenesis","volume":"8","author":"Easterling","year":"2021","journal-title":"J. Cardiovasc. Dev. Dis."},{"key":"2023051711025256000_DMM050101C35","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1038\/ng.3708","article-title":"Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality","volume":"48","author":"Eppinga","year":"2016","journal-title":"Nat. Genet."},{"key":"2023051711025256000_DMM050101C36","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.ydbio.2011.05.663","article-title":"Ectopic expression of Nkx2.5 suppresses the formation of the sinoatrial node in mice","volume":"356","author":"Espinoza-Lewis","year":"2011","journal-title":"Dev. Biol."},{"key":"2023051711025256000_DMM050101C37","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.ydbio.2008.12.028","article-title":"Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5","volume":"327","author":"Espinoza-Lewis","year":"2009","journal-title":"Dev. Biol."},{"key":"2023051711025256000_DMM050101C38","doi-asserted-by":"publisher","first-page":"5555","DOI":"10.1038\/s41467-020-19304-9","article-title":"cAMP-dependent regulation of HCN4 controls the tonic entrainment process in sinoatrial node pacemaker cells","volume":"11","author":"Fenske","year":"2020","journal-title":"Nat. Commun."},{"key":"2023051711025256000_DMM050101C39","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1111\/pedi.12512","article-title":"A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia","volume":"18","author":"Flanagan","year":"2017","journal-title":"Pediatr. Diabetes"},{"key":"2023051711025256000_DMM050101C40","doi-asserted-by":"publisher","first-page":"E154","DOI":"10.1073\/pnas.1115165109","article-title":"Lethal arrhythmias in Tbx3-deficient mice reveal extreme dosage sensitivity of cardiac conduction system function and homeostasis","volume":"109","author":"Frank","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"2023051711025256000_DMM050101C41","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1002\/dvdy.21431","article-title":"Expression pattern of Popdc2 during mouse embryogenesis and in the adult","volume":"237","author":"Froese","year":"2008","journal-title":"Dev. Dyn."},{"key":"2023051711025256000_DMM050101C42","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1172\/JCI59410","article-title":"Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice","volume":"122","author":"Froese","year":"2012","journal-title":"J. Clin. Invest."},{"key":"2023051711025256000_DMM050101C43","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1126\/science.aau0320","article-title":"Developmental enhancers and chromosome topology","volume":"361","author":"Furlong","year":"2018","journal-title":"Science"},{"key":"2023051711025256000_DMM050101C44","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1161\/CIRCRESAHA.120.317145","article-title":"ATAC-Seq reveals an Isl1 enhancer that regulates sinoatrial node development and function","volume":"127","author":"Galang","year":"2020","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C45","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1161\/CIRCRESAHA.118.314578","article-title":"Transcriptomic profiling of the developing cardiac conduction system at single-cell resolution","volume":"125","author":"Goodyer","year":"2019","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C46","doi-asserted-by":"publisher","first-page":"zqab031","DOI":"10.1093\/function\/zqab031","article-title":"The organization of the sinoatrial node microvasculature varies regionally to match local myocyte excitability","volume":"2","author":"Grainger","year":"2021","journal-title":"Function"},{"key":"2023051711025256000_DMM050101C47","doi-asserted-by":"publisher","first-page":"160","DOI":"10.3390\/jcdd8120160","article-title":"The role of POPDC proteins in cardiac pacemaking and conduction","volume":"8","author":"Gruscheski","year":"2021","journal-title":"J. Cardiovasc. Dev. Dis."},{"key":"2023051711025256000_DMM050101C48","doi-asserted-by":"publisher","first-page":"4349","DOI":"10.3892\/mmr.2016.5043","article-title":"TBX5 loss-of-function mutation contributes to atrial fibrillation and atypical Holt-Oram syndrome","volume":"13","author":"Guo","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"2023051711025256000_DMM050101C49","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1038\/emboj.2008.3","article-title":"Cardiac pacemaker function of HCN4 channels in mice is confined to embryonic development and requires cyclic AMP","volume":"27","author":"Harzheim","year":"2008","journal-title":"EMBO J."},{"key":"2023051711025256000_DMM050101C50","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1161\/CIRCGENETICS.113.000137","article-title":"The role of CAV3 in long-QT syndrome: clinical and functional assessment of a caveolin-3\/Kv11.1 double heterozygote versus caveolin-3 single heterozygote","volume":"6","author":"Hedley","year":"2013","journal-title":"Circ. Cardiovasc. Genet."},{"key":"2023051711025256000_DMM050101C51","doi-asserted-by":"publisher","first-page":"1384139","DOI":"10.1155\/2019\/1384139","article-title":"A rare case of the digenic inheritance of long QT syndrome type 2 and type 6","volume":"2019","author":"Heida","year":"2019","journal-title":"Case Rep. Med."},{"key":"2023051711025256000_DMM050101C52","doi-asserted-by":"publisher","first-page":"4423","DOI":"10.1038\/sj.emboj.7601868","article-title":"HCN4 provides a \u2018depolarization reserve\u2019 and is not required for heart rate acceleration in mice","volume":"26","author":"Herrmann","year":"2007","journal-title":"EMBO J."},{"key":"2023051711025256000_DMM050101C53","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.yjmcc.2008.04.008","article-title":"Tamoxifen-inducible gene deletion in the cardiac conduction system","volume":"45","author":"Hoesl","year":"2008","journal-title":"J. Mol. Cell. Cardiol."},{"key":"2023051711025256000_DMM050101C54","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1007\/s00395-016-0557-2","article-title":"Coding and non-coding variants in the SHOX2 gene in patients with early-onset atrial fibrillation","volume":"111","author":"Hoffmann","year":"2016","journal-title":"Basic Res. Cardiol."},{"key":"2023051711025256000_DMM050101C55","doi-asserted-by":"publisher","first-page":"648","DOI":"10.3389\/fgene.2019.00648","article-title":"Functional characterization of rare variants in the SHOX2 gene identified in sinus node dysfunction and atrial fibrillation","volume":"10","author":"Hoffmann","year":"2019","journal-title":"Front. Genet."},{"key":"2023051711025256000_DMM050101C56","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/ng.781","article-title":"A rare variant in MYH6 is associated with high risk of sick sinus syndrome","volume":"43","author":"Holm","year":"2011","journal-title":"Nat. Genet."},{"key":"2023051711025256000_DMM050101C57","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1101\/gad.416007","article-title":"Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria","volume":"21","author":"Hoogaars","year":"2007","journal-title":"Genes Dev."},{"key":"2023051711025256000_DMM050101C58","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.jacc.2014.04.032","article-title":"Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome","volume":"64","author":"Hu","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"2023051711025256000_DMM050101C59","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1007\/s11596-020-2207-z","article-title":"Familial atrial enlargement, conduction disorder and symmetric cardiac hypertrophy are early signs of PRKAG2 R302Q","volume":"40","author":"Hu","year":"2020","journal-title":"Curr. Med. Sci."},{"key":"2023051711025256000_DMM050101C60","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1152\/physrev.00007.2016","article-title":"Murine electrophysiological models of cardiac arrhythmogenesis","volume":"97","author":"Huang","year":"2017","journal-title":"Physiol. Rev."},{"key":"2023051711025256000_DMM050101C61","doi-asserted-by":"publisher","first-page":"845973","DOI":"10.3389\/fcvm.2022.845973","article-title":"A rare case of isolated right ventricular non-compaction with the novel TTN mutation","volume":"9","author":"Huang","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"2023051711025256000_DMM050101C62","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1161\/CIRCEP.114.002534","article-title":"Novel mutation in the alpha-myosin heavy chain gene is associated with sick sinus syndrome","volume":"8","author":"Ishikawa","year":"2015","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"2023051711025256000_DMM050101C63","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1111\/pace.13030","article-title":"Sinus node dysfunction and atrial fibrillation: a reversible phenomenon?","volume":"40","author":"Jackson","year":"2017","journal-title":"Pacing Clin. Electrophysiol."},{"key":"2023051711025256000_DMM050101C64","doi-asserted-by":"publisher","first-page":"103527","DOI":"10.1016\/j.ejmg.2018.08.008","article-title":"TRPM4 mutations to cause autosomal recessive and not autosomal dominant Brugada type 1 syndrome","volume":"62","author":"Janin","year":"2019","journal-title":"Eur. J. Med. Genet."},{"key":"2023051711025256000_DMM050101C65","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.jacc.2014.03.056","article-title":"Incidence of and risk factors for sick sinus syndrome in the general population","volume":"64","author":"Jensen","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"2023051711025256000_DMM050101C66","doi-asserted-by":"publisher","first-page":"e20200142","DOI":"10.1590\/1678-4685-gmb-2020-0142","article-title":"A novel TBX5 mutation predisposes to familial cardiac septal defects and atrial fibrillation as well as bicuspid aortic valve","volume":"43","author":"Jiang","year":"2020","journal-title":"Genet. Mol. Biol."},{"key":"2023051711025256000_DMM050101C67","doi-asserted-by":"publisher","first-page":"1892","DOI":"10.1161\/CIRCULATIONAHA.116.018011","article-title":"Sinus node and atrial arrhythmias","volume":"133","author":"John","year":"2016","journal-title":"Circulation"},{"key":"2023051711025256000_DMM050101C68","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s42826-021-00102-3","article-title":"A comparative review on heart ion channels, action potentials and electrocardiogram in rodents and human: extrapolation of experimental insights to clinic","volume":"37","author":"Joukar","year":"2021","journal-title":"Lab. Anim. Res."},{"key":"2023051711025256000_DMM050101C69","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1161\/CIRCULATIONAHA.120.051583","article-title":"Fibroblast-specific proteotranscriptomes reveal distinct fibrotic signatures of human sinoatrial node in nonfailing and failing hearts","volume":"144","author":"Kalyanasundaram","year":"2021","journal-title":"Circulation"},{"key":"2023051711025256000_DMM050101C70","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.hrthm.2022.08.039","article-title":"Three-dimensional functional anatomy of the human sinoatrial node for epicardial and endocardial mapping and ablation","volume":"20","author":"Kalyanasundaram","year":"2023","journal-title":"Heart Rhythm"},{"key":"2023051711025256000_DMM050101C71","doi-asserted-by":"publisher","first-page":"e003123","DOI":"10.1161\/CIRCGEN.120.003123","article-title":"Novel gain-of-function variant in CACNA1C associated with timothy syndrome, multiple accessory pathways, and noncompaction cardiomyopathy","volume":"13","author":"Kelu Bisabu","year":"2020","journal-title":"Circ. Genom. Precis. Med."},{"key":"2023051711025256000_DMM050101C72","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/j.ydbio.2012.01.015","article-title":"The Popeye domain containing 2 (popdc2) gene in zebrafish is required for heart and skeletal muscle development","volume":"363","author":"Kirchmaier","year":"2012","journal-title":"Dev. Biol."},{"key":"2023051711025256000_DMM050101C73","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1212\/WNL.0000000000000239","article-title":"A Kir3.4 mutation causes Andersen-Tawil syndrome by an inhibitory effect on Kir2.1","volume":"82","author":"Kokunai","year":"2014","journal-title":"Neurology"},{"key":"2023051711025256000_DMM050101C74","doi-asserted-by":"publisher","first-page":"e002238","DOI":"10.1161\/CIRCGEN.118.002238","article-title":"Familial sinus node disease caused by a gain of GIRK (G-Protein activated inwardly rectifying K(+) channel) channel function","volume":"12","author":"Kuss","year":"2019","journal-title":"Circ. Genom. Precis. Med."},{"key":"2023051711025256000_DMM050101C75","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1016\/j.jacc.2018.10.043","article-title":"2018 ACC\/AHA\/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay: executive summary: a report of the american college of cardiology\/american heart association task force on clinical practice guidelines, and the heart rhythm society","volume":"74","author":"Kusumoto","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"2023051711025256000_DMM050101C76","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.3389\/fphys.2018.01686","article-title":"Functional microdomains in heart's pacemaker: a step beyond classical electrophysiology and remodeling","volume":"9","author":"Lang","year":"2018","journal-title":"Front. Physiol."},{"key":"2023051711025256000_DMM050101C77","doi-asserted-by":"publisher","first-page":"15617","DOI":"10.1073\/pnas.0805500105","article-title":"Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes human sinus node disease","volume":"105","author":"Le","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"2023051711025256000_DMM050101C78","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1113\/jphysiol.2005.083188","article-title":"Sinus node dysfunction following targeted disruption of the murine cardiac sodium channel gene Scn5a","volume":"567","author":"Lei","year":"2005","journal-title":"J. Physiol."},{"key":"2023051711025256000_DMM050101C79","doi-asserted-by":"publisher","first-page":"eaam5607","DOI":"10.1126\/scitranslmed.aam5607","article-title":"Redundant and diverse intranodal pacemakers and conduction pathways protect the human sinoatrial node from failure","volume":"9","author":"Li","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"2023051711025256000_DMM050101C80","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.7150\/ijms.27424","article-title":"A SHOX2 loss-of-function mutation underlying familial atrial fibrillation","volume":"15","author":"Li","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"2023051711025256000_DMM050101C81","doi-asserted-by":"publisher","first-page":"dev178145","DOI":"10.1242\/dev.178145","article-title":"Nkx2-5 defines a subpopulation of pacemaker cells and is essential for the physiological function of the sinoatrial node in mice","volume":"146","author":"Li","year":"2019","journal-title":"Development"},{"key":"2023051711025256000_DMM050101C82","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/s41467-019-14039-8","article-title":"Impaired neuronal sodium channels cause intranodal conduction failure and reentrant arrhythmias in human sinoatrial node","volume":"11","author":"Li","year":"2020","journal-title":"Nat. Commun."},{"key":"2023051711025256000_DMM050101C83","doi-asserted-by":"publisher","first-page":"20417314221127908","DOI":"10.1177\/20417314221127908","article-title":"Molecular and electrophysiological evaluation of human cardiomyocyte subtypes to facilitate generation of composite cardiac models","volume":"13","author":"Li","year":"2022","journal-title":"J. Tissue Eng."},{"key":"2023051711025256000_DMM050101C84","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/ng0197-21","article-title":"Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family","volume":"15","author":"Li","year":"1997","journal-title":"Nat. Genet."},{"key":"2023051711025256000_DMM050101C85","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1161\/CIRCRESAHA.113.301588","article-title":"HCN4 dynamically marks the first heart field and conduction system precursors","volume":"113","author":"Liang","year":"2013","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C86","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41467-020-20448-x","article-title":"Cellular and molecular landscape of mammalian sinoatrial node revealed by single-cell RNA sequencing","volume":"12","author":"Liang","year":"2021","journal-title":"Nat. Commun."},{"key":"2023051711025256000_DMM050101C87","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/s10038-018-0542-8","article-title":"Identification of CACNA1D variants associated with sinoatrial node dysfunction and deafness in additional Pakistani families reveals a clinical significance","volume":"64","author":"Liaqat","year":"2019","journal-title":"J. Hum. Genet."},{"key":"2023051711025256000_DMM050101C88","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.jelectrocard.2021.01.022","article-title":"KCNE2 gene mutation and Brugada syndrome","volume":"65","author":"Liatakis","year":"2021","journal-title":"J. Electrocardiol."},{"key":"2023051711025256000_DMM050101C89","doi-asserted-by":"publisher","first-page":"4271","DOI":"10.3892\/mmr.2018.9455","article-title":"Genetic mutation of familial dilated cardiomyopathy based on next-generation semiconductor sequencing","volume":"18","author":"Lin","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"2023051711025256000_DMM050101C90","doi-asserted-by":"publisher","first-page":"2889","DOI":"10.1038\/s41467-019-10709-9","article-title":"Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking","volume":"10","author":"Linscheid","year":"2019","journal-title":"Nat. Commun."},{"key":"2023051711025256000_DMM050101C91","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1161\/CIRCGENETICS.109.930867","article-title":"Gain-of-function mutations in TRPM4 cause autosomal dominant isolated cardiac conduction disease","volume":"3","author":"Liu","year":"2010","journal-title":"Circ. Cardiovasc. Genet."},{"key":"2023051711025256000_DMM050101C92","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.ajhg.2016.06.025","article-title":"GNB5 mutations cause an autosomal-recessive multisystem syndrome with sinus bradycardia and cognitive disability","volume":"99","author":"Lodder","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"2023051711025256000_DMM050101C93","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1016\/j.bpj.2018.03.024","article-title":"Positive feedback mechanisms among local ca releases, NCX, and I(CaL) ignite pacemaker action potentials","volume":"114","author":"Lyashkov","year":"2018","journal-title":"Biophys. J."},{"key":"2023051711025256000_DMM050101C94","doi-asserted-by":"publisher","first-page":"809","DOI":"10.3389\/fphys.2020.00809","article-title":"Sinoatrial node structure, mechanics, electrophysiology and the chronotropic response to stretch in rabbit and mouse","volume":"11","author":"Macdonald","year":"2020","journal-title":"Front. Physiol."},{"key":"2023051711025256000_DMM050101C95","doi-asserted-by":"publisher","first-page":"681","DOI":"10.36660\/abc.20210792","article-title":"Atrial flutter in PRKAG2 syndrome: clinical and electrophysiological characteristics","volume":"119","author":"Magalhaes","year":"2022","journal-title":"Arq. Bras. Cardiol."},{"key":"2023051711025256000_DMM050101C96","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1161\/CIRCULATIONAHA.121.054083","article-title":"Variant intronic enhancer controls SCN10A-short expression and heart conduction","volume":"144","author":"Man","year":"2021","journal-title":"Circulation"},{"key":"2023051711025256000_DMM050101C97","doi-asserted-by":"publisher","first-page":"712666","DOI":"10.3389\/fphys.2021.712666","article-title":"Transcriptional and epigenetic landscape of cardiac pacemaker cells: insights into cellular specialization in the sinoatrial node","volume":"12","author":"Mandla","year":"2021","journal-title":"Front. Physiol."},{"key":"2023051711025256000_DMM050101C98","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/jcdd8020015","article-title":"Atrial and sinoatrial node development in the zebrafish heart","volume":"8","author":"Martin","year":"2021","journal-title":"J. Cardiovasc. Dev. Dis."},{"key":"2023051711025256000_DMM050101C99","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1126\/science.1222794","article-title":"Systematic localization of common disease-associated variation in regulatory DNA","volume":"337","author":"Maurano","year":"2012","journal-title":"Science"},{"key":"2023051711025256000_DMM050101C100","doi-asserted-by":"publisher","first-page":"4664","DOI":"10.1038\/ncomms5664","article-title":"Cardiac arrhythmia induced by genetic silencing of \u2018funny\u2019 (f) channels is rescued by GIRK4 inactivation","volume":"5","author":"Mesirca","year":"2014","journal-title":"Nat. Commun."},{"key":"2023051711025256000_DMM050101C101","doi-asserted-by":"publisher","first-page":"E932","DOI":"10.1073\/pnas.1517181113","article-title":"G protein-gated IKACh channels as therapeutic targets for treatment of sick sinus syndrome and heart block","volume":"113","author":"Mesirca","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051711025256000_DMM050101C102","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1146\/annurev-pharmtox-031120-115815","article-title":"Pharmacologic approach to sinoatrial node dysfunction","volume":"61","author":"Mesirca","year":"2021","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"2023051711025256000_DMM050101C103","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.jacc.2014.05.045","article-title":"HCN4 mutations in multiple families with bradycardia and left ventricular noncompaction cardiomyopathy","volume":"64","author":"Milano","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"2023051711025256000_DMM050101C104","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1111\/jcmm.13340","article-title":"Telocytes in the human sinoatrial node","volume":"22","author":"Mitrofanova","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"2023051711025256000_DMM050101C105","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.2169\/internalmedicine.9843-17","article-title":"Bradycardia is a specific phenotype of catecholaminergic polymorphic ventricular tachycardia induced by RYR2 mutations","volume":"57","author":"Miyata","year":"2018","journal-title":"Intern. Med."},{"key":"2023051711025256000_DMM050101C106","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1161\/01.RES.0000258019.74591.b3","article-title":"Molecular pathway for the localized formation of the sinoatrial node","volume":"100","author":"Mommersteeg","year":"2007","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C107","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1161\/CIRCRESAHA.107.161182","article-title":"Pitx2c and Nkx2-5 are required for the formation and identity of the pulmonary myocardium","volume":"101","author":"Mommersteeg","year":"2007","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C108","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1093\/cvr\/cvq033","article-title":"The sinus venosus progenitors separate and diversify from the first and second heart fields early in development","volume":"87","author":"Mommersteeg","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"2023051711025256000_DMM050101C109","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1152\/physrev.00006.2003","article-title":"Cardiac chamber formation: development, genes and evolution","volume":"83","author":"Moorman","year":"2003","journal-title":"Physiol. Rev."},{"key":"2023051711025256000_DMM050101C110","doi-asserted-by":"publisher","first-page":"354ra115","DOI":"10.1126\/scitranslmed.aaf4891","article-title":"Pitx2 modulates a Tbx5-dependent gene regulatory network to maintain atrial rhythm","volume":"8","author":"Nadadur","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"2023051711025256000_DMM050101C111","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1111\/jce.12163","article-title":"An LQTS6 MiRP1 mutation suppresses pacemaker current and is associated with sinus bradycardia","volume":"24","author":"Nawathe","year":"2013","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"2023051711025256000_DMM050101C113","doi-asserted-by":"publisher","first-page":"557","DOI":"10.2217\/bmm.13.137","article-title":"Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation","volume":"8","author":"Nielsen","year":"2014","journal-title":"Biomark Med."},{"key":"2023051711025256000_DMM050101C114","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1038\/s41588-018-0171-3","article-title":"Biobank-driven genomic discovery yields new insight into atrial fibrillation biology","volume":"50","author":"Nielsen","year":"2018","journal-title":"Nat. Genet."},{"key":"2023051711025256000_DMM050101C115","doi-asserted-by":"publisher","first-page":"15805","DOI":"10.1038\/ncomms15805","article-title":"Genetic loci associated with heart rate variability and their effects on cardiac disease risk","volume":"8","author":"Nolte","year":"2017","journal-title":"Nat. Commun."},{"key":"2023051711025256000_DMM050101C116","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1016\/j.hrthm.2021.12.032","article-title":"Role of CACNA1C in Brugada syndrome: prevalence and phenotype of probands referred for genetic testing","volume":"19","author":"Novelli","year":"2022","journal-title":"Heart Rhythm"},{"key":"2023051711025256000_DMM050101C117","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.1038\/s41467-020-15706-x","article-title":"Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction","volume":"11","author":"Ntalla","year":"2020","journal-title":"Nat. Commun."},{"key":"2023051711025256000_DMM050101C118","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1093\/europace\/euac218","article-title":"Familial atrial fibrillation mutation M1875T-SCN5A increases early sodium current and dampens the effect of flecainide","volume":"25","author":"O'Reilly","year":"2022","journal-title":"Europace"},{"key":"2023051711025256000_DMM050101C119","doi-asserted-by":"publisher","first-page":"258","DOI":"10.3390\/genes13020258","article-title":"The role of TRPM4 gene mutations in causing familial progressive cardiac conduction disease: a further contribution","volume":"13","author":"Palladino","year":"2022","journal-title":"Genes"},{"key":"2023051711025256000_DMM050101C120","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s13059-021-02322-1","article-title":"Mechanisms of enhancer action: the known and the unknown","volume":"22","author":"Panigrahi","year":"2021","journal-title":"Genome Biol."},{"key":"2023051711025256000_DMM050101C121","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3390\/jcdd4020007","article-title":"Development and function of the cardiac conduction system in health and disease","volume":"4","author":"Park","year":"2017","journal-title":"J. Cardiovasc. Dev. Dis."},{"key":"2023051711025256000_DMM050101C122","doi-asserted-by":"publisher","first-page":"477","DOI":"10.3390\/genes13030477","article-title":"Clinical presentation of left ventricular noncompaction cardiomyopathy and bradycardia in three families carrying HCN4 pathogenic variants","volume":"13","author":"Paszkowska","year":"2022","journal-title":"Genes"},{"key":"2023051711025256000_DMM050101C123","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1146\/annurev-physiol-021119-034453","article-title":"Cardiac pacemaker activity and aging","volume":"82","author":"Peters","year":"2020","journal-title":"Annu. Rev. Physiol."},{"key":"2023051711025256000_DMM050101C124","doi-asserted-by":"publisher","first-page":"e28872","DOI":"10.1371\/journal.pone.0028872","article-title":"Cardiac alpha-myosin (MYH6) is the predominant sarcomeric disease gene for familial atrial septal defects","volume":"6","author":"Posch","year":"2011","journal-title":"PLoS One"},{"key":"2023051711025256000_DMM050101C125","doi-asserted-by":"publisher","first-page":"e21","DOI":"10.1161\/01.RES.0000038886.18992.6B","article-title":"Absence of calsequestrin 2 causes severe forms of catecholaminergic polymorphic ventricular tachycardia","volume":"91","author":"Postma","year":"2002","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C126","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1136\/jmg.2004.028993","article-title":"Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients","volume":"42","author":"Postma","year":"2005","journal-title":"J. Med. Genet."},{"key":"2023051711025256000_DMM050101C127","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1161\/CIRCRESAHA.107.168294","article-title":"A gain-of-function TBX5 mutation is associated with atypical Holt-Oram syndrome and paroxysmal atrial fibrillation","volume":"102","author":"Postma","year":"2008","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C128","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nbt.3745","article-title":"Sinoatrial node cardiomyocytes derived from human pluripotent cells function as a biological pacemaker","volume":"35","author":"Protze","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"2023051711025256000_DMM050101C129","doi-asserted-by":"publisher","first-page":"e12708","DOI":"10.1016\/j.heliyon.2022.e12708","article-title":"Characterization of diverse populations of sinoatrial node cells and their proliferation potential at single nucleus resolution","volume":"9","author":"Qu","year":"2023","journal-title":"Heliyon"},{"key":"2023051711025256000_DMM050101C130","doi-asserted-by":"publisher","first-page":"1944","DOI":"10.1038\/s41467-019-09770-1","article-title":"Identification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies","volume":"10","author":"Rajendran","year":"2019","journal-title":"Nat. Commun."},{"key":"2023051711025256000_DMM050101C131","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1038\/s41467-018-04148-1","article-title":"Thirty loci identified for heart rate response to exercise and recovery implicate autonomic nervous system","volume":"9","author":"Ramirez","year":"2018","journal-title":"Nat. Commun."},{"key":"2023051711025256000_DMM050101C132","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.pbiomolbio.2018.06.008","article-title":"Ionic basis of cardiac electrophysiology in zebrafish compared to human hearts","volume":"138","author":"Ravens","year":"2018","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"2023051711025256000_DMM050101C133","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.yjmcc.2020.06.005","article-title":"POPDC2 a novel susceptibility gene for conduction disorders","volume":"145","author":"Rinne","year":"2020","journal-title":"J. Mol. Cell. Cardiol."},{"key":"2023051711025256000_DMM050101C134","doi-asserted-by":"publisher","first-page":"14215","DOI":"10.3390\/ijms232214215","article-title":"Whole exome sequencing identifies a heterozygous variant in the Cav1.3 gene CACNA1D associated with familial sinus node dysfunction and focal idiopathic epilepsy","volume":"23","author":"Rinne","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2023051711025256000_DMM050101C135","doi-asserted-by":"publisher","first-page":"e31","DOI":"10.1016\/j.hlc.2014.09.013","article-title":"Ankyrin-B syndrome: a case of sinus node dysfunction, atrial fibrillation and prolonged QT in a young adult","volume":"24","author":"Robaei","year":"2015","journal-title":"Heart Lung Circ."},{"key":"2023051711025256000_DMM050101C136","doi-asserted-by":"publisher","first-page":"3171","DOI":"10.1172\/JCI125538","article-title":"Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy","volume":"129","author":"Roberts","year":"2019","journal-title":"J. Clin. Invest."},{"key":"2023051711025256000_DMM050101C137","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1038\/s41588-018-0133-9","article-title":"Multi-ethnic genome-wide association study for atrial fibrillation","volume":"50","author":"Roselli","year":"2018","journal-title":"Nat. Genet."},{"key":"2023051711025256000_DMM050101C138","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1172\/JCI79562","article-title":"POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking","volume":"126","author":"Schindler","year":"2016","journal-title":"J. Clin. Invest."},{"key":"2023051711025256000_DMM050101C139","doi-asserted-by":"publisher","first-page":"12990","DOI":"10.3390\/ijms222312990","article-title":"Identification of SCN5a p.C335R variant in a large family with dilated cardiomyopathy and conduction disease","volume":"22","author":"Sedaghat-Hamedani","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2023051711025256000_DMM050101C140","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1038\/ng.716","article-title":"Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction","volume":"42","author":"Sotoodehnia","year":"2010","journal-title":"Nat. Genet."},{"key":"2023051711025256000_DMM050101C141","doi-asserted-by":"publisher","first-page":"e33","DOI":"10.1161\/CIRCRESAHA.116.310112","article-title":"A mutation in the G-protein gene GNB2 causes familial sinus node and atrioventricular conduction dysfunction","volume":"120","author":"Stallmeyer","year":"2017","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C142","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1002\/humu.21599","article-title":"Mutational spectrum in the Ca(2+)--activated cation channel gene TRPM4 in patients with cardiac conductance disturbances","volume":"33","author":"Stallmeyer","year":"2012","journal-title":"Hum. Mutat."},{"key":"2023051711025256000_DMM050101C143","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/bs.ctdb.2016.08.008","article-title":"TBX5: a key regulator of heart development","volume":"122","author":"Steimle","year":"2017","journal-title":"Curr. Top. Dev. Biol."},{"key":"2023051711025256000_DMM050101C144","doi-asserted-by":"publisher","first-page":"15235","DOI":"10.1073\/pnas.2434235100","article-title":"The hyperpolarization-activated channel HCN4 is required for the generation of pacemaker action potentials in the embryonic heart","volume":"100","author":"Stieber","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051711025256000_DMM050101C145","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1253\/circj.71.1606","article-title":"Association of atrial arrhythmia and sinus node dysfunction in patients with catecholaminergic polymorphic ventricular tachycardia","volume":"71","author":"Sumitomo","year":"2007","journal-title":"Circ. J."},{"key":"2023051711025256000_DMM050101C146","doi-asserted-by":"publisher","first-page":"e001537","DOI":"10.1161\/CIRCGENETICS.116.001537","article-title":"Novel variant in the ANK2 membrane-binding domain is associated with ankyrin-B syndrome and structural heart disease in a first nations population with a high rate of long QT syndrome","volume":"10","author":"Swayne","year":"2017","journal-title":"Circ. Cardiovasc. Genet."},{"key":"2023051711025256000_DMM050101C147","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13072-015-0050-4","article-title":"Making sense of GWAS: using epigenomics and genome engineering to understand the functional relevance of SNPs in non-coding regions of the human genome","volume":"8","author":"Tak","year":"2015","journal-title":"Epigenetics Chromatin"},{"key":"2023051711025256000_DMM050101C148","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/nrg.2017.101","article-title":"Genetic architecture: the shape of the genetic contribution to human traits and disease","volume":"19","author":"Timpson","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"2023051711025256000_DMM050101C149","doi-asserted-by":"publisher","first-page":"e003480","DOI":"10.1161\/CIRCGEN.121.003480","article-title":"Intrinsic atrial myopathy precedes left ventricular dysfunction and predicts atrial fibrillation in lamin A\/C cardiomyopathy","volume":"16","author":"Tremblay-Gravel","year":"2022","journal-title":"Circ. Genom. Precis. Med."},{"key":"2023051711025256000_DMM050101C150","doi-asserted-by":"publisher","first-page":"596832","DOI":"10.3389\/fphys.2021.596832","article-title":"cAMP-dependent signaling restores AP firing in dormant SA node cells via enhancement of surface membrane currents and calcium coupling","volume":"12","author":"Tsutsui","year":"2021","journal-title":"Front. Physiol."},{"key":"2023051711025256000_DMM050101C151","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1113\/JP276014","article-title":"Long QT syndrome caveolin-3 mutations differentially modulate K(v) 4 and Ca(v) 1.2 channels to contribute to action potential prolongation","volume":"597","author":"Tyan","year":"2019","journal-title":"J. Physiol."},{"key":"2023051711025256000_DMM050101C152","doi-asserted-by":"publisher","first-page":"e17113","DOI":"10.7554\/eLife.17113","article-title":"Calcium handling precedes cardiac differentiation to initiate the first heartbeat","volume":"5","author":"Tyser","year":"2016","journal-title":"Elife"},{"key":"2023051711025256000_DMM050101C153","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.tig.2020.08.009","article-title":"Where are the disease-associated eQTLs?","volume":"37","author":"Umans","year":"2021","journal-title":"Trends Genet."},{"key":"2023051711025256000_DMM050101C154","doi-asserted-by":"publisher","first-page":"e002865","DOI":"10.1161\/JAHA.115.002865","article-title":"Two-pore K+ channel TREK-1 regulates sinoatrial node membrane excitability","volume":"5","author":"Unudurthi","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"2023051711025256000_DMM050101C155","doi-asserted-by":"publisher","first-page":"e005800","DOI":"10.1161\/CIRCEP.117.005800","article-title":"Inward rectifier potassium channels (Kir2.x) and caveolin-3 domain-specific interaction: implications for purkinje cell-dependent ventricular arrhythmias","volume":"11","author":"Vaidyanathan","year":"2018","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"2023051711025256000_DMM050101C156","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.1172\/JCI62613","article-title":"T-box targets SCN5A\/10A are functionally affected by a genetic variation","volume":"122","author":"van den Boogaard","year":"2012","journal-title":"J. Clin. Invest"},{"key":"2023051711025256000_DMM050101C157","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1172\/JCI73140","article-title":"A common genetic variant within SCN10A modulates cardiac SCN5A expression","volume":"124","author":"van den Boogaard","year":"2014","journal-title":"J. Clin. Invest."},{"key":"2023051711025256000_DMM050101C158","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1007\/s00018-019-03079-4","article-title":"Genetics and the heart rate response to exercise","volume":"76","author":"van de Vegte","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"2023051711025256000_DMM050101C159","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1038\/nrcardio.2017.197","article-title":"Transcriptional regulation of the cardiac conduction system","volume":"15","author":"Van Eif","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"2023051711025256000_DMM050101C160","doi-asserted-by":"publisher","first-page":"dev173161","DOI":"10.1242\/dev.173161","article-title":"Transcriptome analysis of mouse and human sinoatrial node cells reveals a conserved genetic program","volume":"146","author":"Van Eif","year":"2019","journal-title":"Development"},{"key":"2023051711025256000_DMM050101C161","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1161\/CIRCRESAHA.120.317054","article-title":"Genome-wide analysis identifies an essential human TBX3 pacemaker enhancer","volume":"127","author":"Van Eif","year":"2020","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C162","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1161\/CIRCRESAHA.119.316006","article-title":"Identification of functional variant enhancers associated with atrial fibrillation","volume":"127","author":"van Ouwerkerk","year":"2020","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C163","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1161\/CIRCULATIONAHA.121.054347","article-title":"Patient-specific TBX5-G125R variant induces profound transcriptional deregulation and atrial dysfunction","volume":"145","author":"van Ouwerkerk","year":"2022","journal-title":"Circulation"},{"key":"2023051711025256000_DMM050101C164","doi-asserted-by":"publisher","first-page":"2904","DOI":"10.1038\/s41467-018-04766-9","article-title":"PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity","volume":"9","author":"van Setten","year":"2018","journal-title":"Nat. Commun."},{"key":"2023051711025256000_DMM050101C165","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1161\/CIRCRESAHA.115.303591","article-title":"A large permissive regulatory domain exclusively controls Tbx3 expression in the cardiac conduction system","volume":"115","author":"van Weerd","year":"2014","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C166","doi-asserted-by":"publisher","first-page":"2104","DOI":"10.1161\/CIRCULATIONAHA.106.635268","article-title":"Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome","volume":"114","author":"Vatta","year":"2006","journal-title":"Circulation"},{"key":"2023051711025256000_DMM050101C167","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1161\/CIRCRESAHA.116.305913","article-title":"RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells","volume":"116","author":"Vedantham","year":"2015","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C168","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1161\/01.CIR.97.16.1623","article-title":"Distribution of atrial and nodal cells within the rabbit sinoatrial node: models of sinoatrial transition","volume":"97","author":"Verheijck","year":"1998","journal-title":"Circulation"},{"key":"2023051711025256000_DMM050101C169","doi-asserted-by":"publisher","first-page":"201","DOI":"10.7150\/ijbs.5.201","article-title":"Is sodium current present in human sinoatrial node cells?","volume":"5","author":"Verkerk","year":"2009","journal-title":"Int. J. Biol. Sci."},{"key":"2023051711025256000_DMM050101C170","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1038\/s41467-018-03395-6","article-title":"Genetic study links components of the autonomous nervous system to heart-rate profile during exercise","volume":"9","author":"Verweij","year":"2018","journal-title":"Nat. Commun."},{"key":"2023051711025256000_DMM050101C171","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1093\/cvr\/cvx104","article-title":"RHOA-ROCK signalling is necessary for lateralization and differentiation of the developing sinoatrial node","volume":"113","author":"Vicente-Steijn","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"2023051711025256000_DMM050101C172","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.cell.2015.01.006","article-title":"Enhancer evolution across 20 mammalian species","volume":"160","author":"Villar","year":"2015","journal-title":"Cell"},{"key":"2023051711025256000_DMM050101C173","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1161\/CIRCRESAHA.110.220517","article-title":"Sarcoplasmic reticulum Ca2+ pumping kinetics regulates timing of local Ca2+ releases and spontaneous beating rate of rabbit sinoatrial node pacemaker cells","volume":"107","author":"Vinogradova","year":"2010","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C174","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1080\/19336950.2015.1121335","article-title":"Zebrafish heart as a model for human cardiac electrophysiology","volume":"10","author":"Vornanen","year":"2016","journal-title":"Channels"},{"key":"2023051711025256000_DMM050101C175","doi-asserted-by":"publisher","first-page":"654925","DOI":"10.3389\/fgene.2021.654925","article-title":"Genetic complexity of sinoatrial node dysfunction","volume":"12","author":"Wallace","year":"2021","journal-title":"Front. Genet."},{"key":"2023051711025256000_DMM050101C176","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1016\/j.hrthm.2013.07.022","article-title":"The phenotype characteristics of type 13 long QT syndrome with mutation in KCNJ5 (Kir3.4-G387R)","volume":"10","author":"Wang","year":"2013","journal-title":"Heart Rhythm"},{"key":"2023051711025256000_DMM050101C177","doi-asserted-by":"publisher","first-page":"9753","DOI":"10.1073\/pnas.0912585107","article-title":"Pitx2 prevents susceptibility to atrial arrhythmias by inhibiting left-sided pacemaker specification","volume":"107","author":"Wang","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051711025256000_DMM050101C178","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1161\/CIRCRESAHA.108.187062","article-title":"Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by tbx18 and tbx3","volume":"104","author":"Wiese","year":"2009","journal-title":"Circ. Res."},{"key":"2023051711025256000_DMM050101C179","doi-asserted-by":"publisher","first-page":"e17113","DOI":"10.7554\/eLife.76781","article-title":"A single cell transcriptional roadmap of human pacemaker cell differentiation","volume":"11","author":"Wiesinger","year":"2022","journal-title":"Elife"},{"key":"2023051711025256000_DMM050101C180","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.jacep.2018.03.006","article-title":"Clinical spectrum of SCN5A mutations: long QT syndrome, brugada syndrome, and cardiomyopathy","volume":"4","author":"Wilde","year":"2018","journal-title":"JACC Clin. Electrophysiol."},{"key":"2023051711025256000_DMM050101C181","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1177\/2047487319890763","article-title":"Heritability of a resting heart rate in a 20-year follow-up family cohort with GWAS data: Insights from the STANISLAS cohort","volume":"28","author":"Xhaard","year":"2021","journal-title":"Eur. J. Prev. Cardiol."},{"key":"2023051711025256000_DMM050101C182","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1161\/CIRCULATIONAHA.118.036761","article-title":"Mutant KCNJ3 and KCNJ5 potassium channels as novel molecular targets in bradyarrhythmias and atrial fibrillation","volume":"139","author":"Yamada","year":"2019","journal-title":"Circulation"},{"key":"2023051711025256000_DMM050101C183","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1016\/j.ajhg.2010.04.017","article-title":"Identification of a Kir3.4 mutation in congenital long QT syndrome","volume":"86","author":"Yang","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"2023051711025256000_DMM050101C184","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.1242\/dev.120220","article-title":"A common Shox2-Nkx2-5 antagonistic mechanism primes the pacemaker cell fate in the pulmonary vein myocardium and sinoatrial node","volume":"142","author":"Ye","year":"2015","journal-title":"Development"},{"key":"2023051711025256000_DMM050101C185","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1111\/j.1540-8167.2011.02191.x","article-title":"Electrophysiological mapping of embryonic mouse hearts: mechanisms for developmental pacemaker switch and internodal conduction pathway","volume":"23","author":"Yi","year":"2012","journal-title":"J Cardiovasc. Electrophysiol."},{"key":"2023051711025256000_DMM050101C186","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1186\/s12872-019-01282-6","article-title":"Case reports of a c.475G&gt;T, p.E159* lamin A\/C mutation with a family history of conduction disorder, dilated cardiomyopathy and sudden cardiac death","volume":"19","author":"Yokokawa","year":"2019","journal-title":"BMC Cardiovasc. Disord."},{"key":"2023051711025256000_DMM050101C187","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1007\/s00380-018-1116-6","article-title":"A mutant HCN4 channel in a family with bradycardia, left bundle branch block, and left ventricular noncompaction","volume":"33","author":"Yokoyama","year":"2018","journal-title":"Heart Vessels"},{"key":"2023051711025256000_DMM050101C188","doi-asserted-by":"publisher","first-page":"e0155421","DOI":"10.1371\/journal.pone.0155421","article-title":"Exome sequencing identifies a novel LMNA splice-site mutation and multigenic heterozygosity of potential modifiers in a family with sick sinus syndrome, dilated cardiomyopathy, and sudden cardiac death","volume":"11","author":"Zaragoza","year":"2016","journal-title":"PLoS One"},{"key":"2023051711025256000_DMM050101C189","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.hlc.2008.12.002","article-title":"The single nucleotide polymorphisms of Kir3.4 gene and their correlation with lone paroxysmal atrial fibrillation in Chinese Han population","volume":"18","author":"Zhang","year":"2009","journal-title":"Heart Lung Circ."},{"key":"2023051711025256000_DMM050101C190","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.bbrc.2015.02.094","article-title":"TBX5 loss-of-function mutation contributes to familial dilated cardiomyopathy","volume":"459","author":"Zhang","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023051711025256000_DMM050101C191","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1536\/ihj.19-650","article-title":"A new TBX5 loss-of-function mutation contributes to congenital heart defect and atrioventricular block","volume":"61","author":"Zhang","year":"2020","journal-title":"Int. Heart J."},{"key":"2023051711025256000_DMM050101C192","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/s12920-022-01361-2","article-title":"Left ventricular non-compaction cardiomyopathy associated with the PRKAG2 mutation","volume":"15","author":"Zhang","year":"2022","journal-title":"BMC Med. Genomics"},{"key":"2023051711025256000_DMM050101C193","doi-asserted-by":"publisher","first-page":"5519","DOI":"10.1073\/pnas.0801779105","article-title":"Tbx5-dependent pathway regulating diastolic function in congenital heart disease","volume":"105","author":"Zhu","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051711025256000_DMM050101C194","doi-asserted-by":"publisher","first-page":"7073","DOI":"10.3892\/mmr.2018.8773","article-title":"Genetic analysis of sick sinus syndrome in a family harboring compound CACNA1C and TTN mutations","volume":"17","author":"Zhu","year":"2018","journal-title":"Mol. Med. Rep."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.050101\/2857382\/dmm050101.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.050101\/2857382\/dmm050101.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T11:03:15Z","timestamp":1684321395000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/16\/5\/dmm050101\/310417\/Genetics-of-sinoatrial-node-function-and-heart"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,1]]},"references-count":193,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.050101","relation":{},"ISSN":["1754-8403","1754-8411"],"issn-type":[{"value":"1754-8403","type":"print"},{"value":"1754-8411","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,1]]},"article-number":"dmm050101"}}