{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:46:29Z","timestamp":1787017589368,"version":"build-2736575974"},"reference-count":29,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/501100014890","name":"Qilu University of Technology","doi-asserted-by":"publisher","award":["2020KJC-ZD10"],"award-info":[{"award-number":["2020KJC-ZD10"]}],"id":[{"id":"10.13039\/501100014890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014890","name":"Qilu University of Technology","doi-asserted-by":"publisher","award":["2020KJC-ZD08"],"award-info":[{"award-number":["2020KJC-ZD08"]}],"id":[{"id":"10.13039\/501100014890","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Major Project of Bioengineering Technology Innovation Center of Shandong Province","award":["2019JSWGCCXZX003"],"award-info":[{"award-number":["2019JSWGCCXZX003"]}]},{"name":"Major Project of Bioengineering Technology Innovation Center of Shandong Province","award":["2018JGX114"],"award-info":[{"award-number":["2018JGX114"]}]},{"DOI":"10.13039\/100007785","name":"Jinan Science and Technology Bureau","doi-asserted-by":"publisher","award":["2020GXRC053"],"award-info":[{"award-number":["2020GXRC053"]}],"id":[{"id":"10.13039\/100007785","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["Physiological Genomics"],"published-print":{"date-parts":[[2022,4,1]]},"abstract":"<jats:p>Sick sinus syndrome (SSS) is a term used for a variety of disorders defined by abnormal cardiac impulse formation and by abnormal propagation from the heart\u2019s sinoatrial node. In this study, we present a case from a Chinese family in which two closely related individuals had the symptoms and electrocardiographic evidence of SSS. We hypothesized that multiple individuals affected by the disease in the family was an indication of its genetic predisposition, and thus performed high-throughput sequencing for the participants from the family to detect potential disease-associated variants. One of the potential variants that was identified was a KCNG2 gene variant (NC_000018.9: g.77624068_77624079del). Further bioinformatic analysis showed that the observed variant may be a pathogenic mutation. The results of protein-protein docking and whole cell patch-clamp measurements implied that the deletion variant in KCNG2 could affect its binding the KV2.1 protein, and finally affect the function of Kv channel, which is an important determinant in regulation of heartbeat. Therefore, we inferred that the variable KCNG2 gene may affect the function of Kv channel by changing the binding conformation of KCNG2 and KV2.1 proteins and then adversely affect propagation from the sinoatrial node and cardiac impulse formation by changing the action potential repolarization of heart cells. In summary, our findings suggested that the dominant KCNG2 deletion variant in the examined Chinese family with SSS may be a potential disease-associated variant.<\/jats:p>","DOI":"10.1152\/physiolgenomics.00132.2021","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T11:45:56Z","timestamp":1647258356000},"page":"141-152","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Whole genome sequencing identifies a deletion mutation in the unknown-functional\n                    <i>KCNG2<\/i>\n                    from familial sick sinus syndrome"],"prefix":"10.1152","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8033-1357","authenticated-orcid":true,"given":"Chen","family":"Sun","sequence":"first","affiliation":[{"name":"Key Laboratory for Drug Screening Technology, Key Laboratory for Biosensors of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory for Drug Screening Technology, Key Laboratory for Biosensors of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Yi","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai-Kang","family":"Ba","sequence":"additional","affiliation":[{"name":"Key Laboratory for Drug Screening Technology, Key Laboratory for Biosensors of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan-Shan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Drug Screening Technology, Key Laboratory for Biosensors of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu-Xia","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory for Drug Screening Technology, Key Laboratory for Biosensors of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Qiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory for Drug Screening Technology, Key Laboratory for Biosensors of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Li","family":"Gong","sequence":"additional","affiliation":[{"name":"Key Laboratory for Drug Screening Technology, Key Laboratory for Biosensors of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Chun","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Drug Screening Technology, Key Laboratory for Biosensors of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","first-page":"691","volume":"87","author":"Semelka M","year":"2013","journal-title":"Am Fam Physician"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1017\/S1047951113000991"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.663070"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.789677"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.05.029"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003093421006"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/s0828-282x(07)70750-x"},{"key":"B8","first-page":"640","volume":"84","author":"Gauer RL","year":"2011","journal-title":"Am Fam Physician"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.616011"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18062"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052475"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/ng.781"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/ng.781"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-016-4047-2"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3484"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh377"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10389"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10460"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.39.24371"},{"key":"B24","first-page":"337","volume":"6","author":"Zhu XR","year":"1999","journal-title":"Recept Channels"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1097\/NCI.0000000000000099"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(88)90033-4"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c110047"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2001.1366"},{"key":"B29","first-page":"528","volume-title":"Quantitative Human Physiology: An Introduction","author":"Joseph F","year":"2012","edition":"2"}],"container-title":["Physiological Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/physiolgenomics.00132.2021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T18:14:06Z","timestamp":1648836846000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/physiolgenomics.00132.2021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,1]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4,1]]}},"alternative-id":["10.1152\/physiolgenomics.00132.2021"],"URL":"https:\/\/doi.org\/10.1152\/physiolgenomics.00132.2021","relation":{},"ISSN":["1094-8341","1531-2267"],"issn-type":[{"value":"1094-8341","type":"print"},{"value":"1531-2267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,1]]},"assertion":[{"value":"2021-10-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-09","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}