{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:09:15Z","timestamp":1792001355373,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200599"],"award-info":[{"award-number":["82200599"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The ankyrin repeat and sterile alpha motif domain containing 6 (<jats:italic>ANKS6<\/jats:italic>) gene, encoding an inversin compartment protein of the primary cilium, was recently reported as a pathogenic gene of nephronophthisis (MIM PS256100). Extrarenal manifestations are frequently observed in this disease, however, potential genotype\u2013phenotype correlations and the underlying mechanisms remain poorly understood. Here we described an infant with kidney failure, hepatobiliary abnormalities, and heart disease, in whom whole exome sequencing identified compound heterozygous variants in <jats:italic>ANKS6<\/jats:italic>, including a novel nonsense variant p.Trp458* and a recurrent splicing variant c.2394+1G\u2009&gt;\u2009A. mRNA expression studies showed that the splicing variant caused aberrant mRNA splicing with exon 13 skipping and the biallelic variants were predicted to cause loss of <jats:italic>ANKS6<\/jats:italic> function. We systematically characterized the clinical and genetic spectra of the disease and revealed that biallelic null variants in <jats:italic>ANKS6<\/jats:italic> cause more severe kidney disease and more extrarenal manifestations, thus establishing a clear genotype\u2013phenotype correlation for the disease. Further evaluations showed that <jats:italic>ANKS6<\/jats:italic> deficiency reduced YAP1 expression in the patient's bile duct epithelium and <jats:italic>ANKS6<\/jats:italic> promotes YAP1 transcriptional activity in a dose\u2010dependent manner, indicating that loss of <jats:italic>ANKS6<\/jats:italic> function causes hepatobiliary abnormalities through YAP1 deficiency during biliary morphogenesis and development, which may offer new therapeutic targets.<\/jats:p>","DOI":"10.1111\/cge.14412","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T08:20:52Z","timestamp":1690878052000},"page":"625-636","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biallelic <i>ANKS6<\/i> null variants cause notable extrarenal phenotypes in a nephronophthisis patient and lead to hepatobiliary abnormalities by <scp>YAP1<\/scp> deficiency"],"prefix":"10.1111","volume":"104","author":[{"given":"Keqiang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, Xinhua Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition  Shanghai China"},{"name":"Shanghai Institute for Pediatric Research  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Xinhua Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Xinhua Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Xinhua Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Xinhua Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beilin","family":"Gu","sequence":"additional","affiliation":[{"name":"Shanghai Institute for Pediatric Research  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Xinhua Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 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