{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:47:39Z","timestamp":1753868859560,"version":"3.41.2"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Heterotaxy (HTX) is characterized by an abnormality in the organ arrangement along the Left\u2010Right (LR) axis and is caused by the disruption of LR patterning in early development. LR asymmetry is critical for multiple organs. Specifically, proper LR patterning is crucial for cardiac function and is a cause of congenital heart disease (CHD). <jats:italic>CACNA1G<\/jats:italic> is a candidate gene identified in patients with CHD and HTX. This gene encodes a T\u2010type, low\u2010voltage\u2010activated calcium channel and is a member of the Cav3.1 channel family. However, its function in cardiac or embryonic development remains unknown. Here, we show that abnormal <jats:italic>cacna1g<\/jats:italic> expression in <jats:styled-content style=\"fixed-case\"><jats:italic>Xenopus tropicalis<\/jats:italic><\/jats:styled-content> recapitulates the HTX phenotype found in the patient cohort. By examining early LR patterning markers, including <jats:italic>pitx2c<\/jats:italic> and <jats:italic>dand5<\/jats:italic>, we discovered that both markers are expressed abnormally, suggesting that LR patterning is disrupted at the earliest stages of the LR signaling cascade. Since cilia have been described as key regulators of LR asymmetry, we checked the process of cilia formation in <jats:italic>cacna1g<\/jats:italic> crispants. The LR Organizer (LRO) contained reduced cilia quantity in the <jats:italic>cacna1g<\/jats:italic> crispants, which may explain the LR defects. In conclusion, the abnormal expression of <jats:italic>cacna1g<\/jats:italic> affects cilia in the LRO, leading to abnormal LR patterning and cardiac looping.<\/jats:p>","DOI":"10.1002\/dvg.70009","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T22:56:42Z","timestamp":1741647402000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp><i>CACNA1G<\/i><\/scp>, A Heterotaxy Candidate Gene, Plays a Role in Ciliogenesis and Left\u2010Right Patterning in <scp><i>Xenopus tropicalis<\/i><\/scp>"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3405-7518","authenticated-orcid":false,"given":"Valentyna","family":"Kostiuk","sequence":"first","affiliation":[{"name":"Pediatric Genomics Discovery Program, Departments of Pediatrics and Genetics Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakib","family":"Kabir","sequence":"additional","affiliation":[{"name":"Pediatric Genomics Discovery Program, Departments of Pediatrics and Genetics Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rashid","family":"Akbari","sequence":"additional","affiliation":[{"name":"Pediatric Genomics Discovery Program, Departments of Pediatrics and Genetics Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Rushing","sequence":"additional","affiliation":[{"name":"Pediatric Genomics Discovery Program, Departments of Pediatrics and Genetics Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delfina P.","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Pediatric Genomics Discovery Program, Departments of Pediatrics and Genetics Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelina","family":"Kim","sequence":"additional","affiliation":[{"name":"Pediatric Genomics Discovery Program, Departments of Pediatrics and Genetics Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Kim","sequence":"additional","affiliation":[{"name":"Pediatric Genomics Discovery Program, Departments of Pediatrics and Genetics Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Zenisek","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustafa K.","family":"Khokha","sequence":"additional","affiliation":[{"name":"Pediatric Genomics Discovery Program, Departments of Pediatrics and Genetics Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2694"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201076049\u20107"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21855"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12723"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy145"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/crispr.2021.0113"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.09.007"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u201061779\u2010992\u20101_3"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq7317"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2019.07.019"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1050\u20101738(03)00039\u20102"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.12703\/P6\u2010110"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac9396"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00953"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3970"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq8148"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.10184"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2021.03.005"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP274756"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010018\u20100549\u2010y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104419\u20101399\u20109_63"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000225862.14314.49"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56551"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041\u2010015\u20100180\u20104"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000521765"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092\u20108674(00)00013\u20101"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2010.02.061"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm800419w"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502506102"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.09.011"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201004394\u2010w"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/19336950.2017.1401688"}],"container-title":["genesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvg.70009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T13:35:49Z","timestamp":1741700149000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dvg.70009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/dvg.70009"],"URL":"https:\/\/doi.org\/10.1002\/dvg.70009","archive":["Portico"],"relation":{},"ISSN":["1526-954X","1526-968X"],"issn-type":[{"type":"print","value":"1526-954X"},{"type":"electronic","value":"1526-968X"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"2024-01-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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