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Homozygous mutant mice, designated as Wdpcp-Z11, exhibited severe developmental abnormalities, including neural tube defects, craniofacial malformation, anophthalmia and polydactyly. The mutant WDPCP protein was expressed but failed to dock to the apical surface of the cell. Cilia formation and Hh signaling were severely impaired. Structure predictions located these residues at the juncture of two alpha helices in a conserved, but otherwise uncharacterized, region of WDPCP. Their absence was predicted to impair the linker and reduce conformational stability of WDPCP. Rescue experiments demonstrated that restoring both D481 and W482 are required for a phenotypic recovery. Because a variant of W513 (p.Trp513Ser) is associated with Bardet-Beidl syndrome, insight gained into the structure-function relationship may be valuable for understanding WDPCP-associated ciliopathy.<\/jats:p>","DOI":"10.1242\/dmm.052149","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T09:38:51Z","timestamp":1763717931000},"source":"Crossref","is-referenced-by-count":1,"title":["Identification of conserved residues essential for the ciliogenic functions of WDPCP"],"prefix":"10.1242","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6770-8666","authenticated-orcid":false,"given":"Yeon Ja","family":"Choi","sequence":"first","affiliation":[{"name":"Stony Brook University 1 Department of Pathology , , Stony Brook, NY 11794 ,","place":["USA"]},{"name":"College of Pharmacy, Jeju National University 2 Department of Pharmacy , , Jeju 63243 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungbo","family":"Hwang","sequence":"additional","affiliation":[{"name":"Center for Biomimetic Research 3 , Division of Advanced Predictive Research , , Daejeon 34114 ,","place":["Republic of Korea"]},{"name":"Korea Institute of Toxicology 3 , Division of Advanced Predictive Research , , Daejeon 34114 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanjae","family":"Lee","sequence":"additional","affiliation":[{"name":"University of Texas at Austin 4 Department of Molecular Biosciences , , Austin, TX 78712 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqing","family":"Zeng","sequence":"additional","affiliation":[{"name":"Pennsylvania State University 5 Department of Biology , , University Park, PA 16802 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Stony Brook University 6 Department of Dermatology , , Stony Brook, NY 11794 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ukhyun","family":"Jo","sequence":"additional","affiliation":[{"name":"Stony Brook University 7 Department of Pharmacological Sciences , , Stony Brook, NY 11794 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyungjin","family":"Kim","sequence":"additional","affiliation":[{"name":"Stony Brook University 7 Department of Pharmacological Sciences , , Stony Brook, NY 11794 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0099-0879","authenticated-orcid":false,"given":"Aimin","family":"Liu","sequence":"additional","affiliation":[{"name":"Pennsylvania State University 5 Department of Biology , , University Park, PA 16802 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daeui","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Biomimetic Research 3 , Division of Advanced Predictive Research , , Daejeon 34114 ,","place":["Republic of Korea"]},{"name":"Korea Institute of Toxicology 3 , Division of Advanced Predictive Research , , Daejeon 34114 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Wallingford","sequence":"additional","affiliation":[{"name":"University of Texas at Austin 4 Department of Molecular Biosciences , , Austin, TX 78712 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1430-8842","authenticated-orcid":false,"given":"Jiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Stony Brook University 1 Department of Pathology , , Stony Brook, NY 11794 ,","place":["USA"]},{"name":"Stony Brook University 6 Department of Dermatology , , Stony Brook, NY 11794 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"2025112104384559900_DMM052149C1","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.tcb.2016.12.001","article-title":"From planar cell polarity to ciliogenesis and back: the curious tale of the PPE and CPLANE proteins","volume":"27","author":"Adler","year":"2017","journal-title":"Trends Cell Biol."},{"key":"2025112104384559900_DMM052149C2","doi-asserted-by":"publisher","first-page":"154102","DOI":"10.1063\/5.0005188","article-title":"Recent developments in the general atomic and molecular electronic structure system","volume":"152","author":"Barca","year":"2020","journal-title":"J. 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