{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CFAP251, also known as WDR66, encodes an axonemal protein that is predominantly expressed in the testis and plays a critical role in sperm flagellum structure and function. Multiple studies have demonstrated that CFAP251 localizes to the calmodulin‐ and spoke‐associated complex at the base of radial spoke 3 in the axoneme, where it is essential for proper assembly and/or stability of the central pair complex. Disruption of CFAP251 by loss‐of‐function mutations causes multiple morphological abnormalities of the sperm flagella (MMAF), which are characterized by shortened, coiled, absent, or irregular flagella and lead to severe asthenozoospermia and male infertility. Functional analyses in both human patients and model organisms have confirmed that mutations in CFAP251 impair flagellar movement and corroborate its role as a key structural and regulatory component of the sperm flagellum. In addition, CFAP251 has been shown to interact with other components of the calmodulin‐ and spoke‐associated complex—such as CFAP91—further emphasizing its importance in coordinating the intricate protein architecture necessary for flagellar motility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Although aberrant expression of WDR66 has also been observed in several carcinomas—suggesting potential roles in cell adhesion, migration, and the epithelial-to-mesenchymal transition—in these contexts its function appears distinct from that in sperm cell biology. In essence, the primary and best‐characterized role of CFAP251/WDR66 is to maintain the structural integrity and proper motility of sperm flagella, thereby ensuring male fertility.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zine-Eddine Kherraf, Amir Amiri-Yekta, Denis Dacheux, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Homozygous Ancestral SVA-Insertion-Mediated Deletion in WDR66 Induces Multiple Morphological Abnormalities of the Sperm Flagellum and Male Infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2018.07.014"}], "href": "https://doi.org/10.1016/j.ajhg.2018.07.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30122540"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30122540"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Weiyu Li, Xiaojin He, Shenmin Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic mutations of CFAP251 cause sperm flagellar defects and human male infertility."}]}, {"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/s10038-018-0520-1"}], "href": "https://doi.org/10.1038/s10038-018-0520-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30310178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30310178"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yasmina Auguste, Valérie Delague, Jean-Pierre Desvignes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of Calmodulin- and Radial-Spoke-Associated Complex Protein CFAP251 Leads to Immotile Spermatozoa Lacking Mitochondria and Infertility in Men."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2018.07.013"}], "href": "https://doi.org/10.1016/j.ajhg.2018.07.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30122541"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30122541"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Guillaume Martinez, Julie Beurois, Denis Dacheux, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic variants in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "MAATS1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " encoding CFAP91, a calmodulin-associated and spoke-associated complex protein, cause severe astheno-teratozoospermia and male infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2019-106775"}], "href": "https://doi.org/10.1136/jmedgenet-2019-106775"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32161152"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32161152"}]}]}]}