{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nODAD3—also known as CCDC151—is an evolutionarily conserved coiled‐coil protein that plays an essential role in the assembly and docking of outer dynein arm (ODA) complexes onto the axonemal microtubule scaffold in motile cilia. By mediating the proper integration of ODA components, ODAD3 is critical for generating the mechanical force required for effective ciliary beating, a process vital not only for clearing airways and moving extracellular fluids but also for establishing the left–right asymmetry during embryogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nLoss-of-function mutations in ODAD3 disrupt the axonemal assembly of key dynein arm components—such as DNAH5, CCDC114, and ARMC4—which in turn results in impaired ciliary motion. This molecular defect underlies primary ciliary dyskinesia (PCD), manifesting in clinical phenotypes like chronic respiratory infections, bronchiectasis, and laterality defects (e.g., situs inversus), as demonstrated by genetic studies and functional analyses in human subjects and model organisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAnimal models including zebrafish and mice have further corroborated the significance of ODAD3 in cilia-related processes. Disruption of ODAD3 not only abolishes ODA formation in respiratory cilia but also impairs the function of nodal cilia—key to proper left–right organizer activity—resulting in complex heart defects and other laterality disorders. These findings expand the mutation spectrum associated with ODAD3 and highlight its potential as a diagnostic marker and therapeutic target in ciliopathies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rim Hjeij, Alexandros Onoufriadis, Christopher M Watson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2014.08.005"}], "href": "https://doi.org/10.1016/j.ajhg.2014.08.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25192045"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25192045"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Muslim M Alsaadi, A Mesut Erzurumluoglu, Santiago Rodriguez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nonsense mutation in coiled-coil domain containing 151 gene (CCDC151) causes primary ciliary dyskinesia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22698"}], "href": "https://doi.org/10.1002/humu.22698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25224326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25224326"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Weizhi Zhang, Dongping Li, Shijie Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-exome sequencing identifies a novel CCDC151 mutation, c.325G>T (p.E109X), in a patient with primary ciliary dyskinesia and situs inversus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s10038-018-0540-x"}], "href": "https://doi.org/10.1038/s10038-018-0540-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30504913"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30504913"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sheng Deng, Shan Wu, Hong Xia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a frame shift mutation in the CCDC151 gene in a Han-Chinese family with Kartagener syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20192510"}], "href": "https://doi.org/10.1042/BSR20192510"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32490514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32490514"}]}]}]}