{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DNAAF6, formerly known as PIH1D3, is a critical dynein axonemal assembly factor that functions in the cytoplasmic preassembly of axonemal dynein arms essential for motile cilia and flagella. In particular, DNAAF6 facilitates the stabilization and complex formation of both outer (ODA) and inner (IDA) dynein arms by interacting with other assembly factors (such as DNAAF2 and DNAAF4) and components of the HSP90 co‐chaperone machinery. Loss‐of‐function mutations or deletions in DNAAF6 disrupt dynein arm assembly, causing absent or diminished dynein arms and yielding immotile cilia and flagella. Clinical consequences of DNAAF6 deficiency include primary ciliary dyskinesia (PCD), which manifests as chronic respiratory disease and laterality defects, as well as male infertility due to impaired sperm flagellar function. Studies in both human patients and animal models have demonstrated that DNAAF6 variants lead to protein degradation and gross ultrastructural defects—including loss of ODA/IDA—thereby elucidating its indispensible role in ciliary and flagellar motility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tamara Paff, Niki T Loges, Isabella Aprea, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesia with Outer and Inner Dynein Arm Defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2016.11.019"}], "href": "https://doi.org/10.1016/j.ajhg.2016.11.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28041644"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28041644"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Fenglan Dong, Kyosuke Shinohara, Yanick Botilde, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pih1d3 is required for cytoplasmic preassembly of axonemal dynein in mouse sperm."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201304076"}], "href": "https://doi.org/10.1083/jcb.201304076"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24421334"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24421334"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ying Wang, Chaofeng Tu, Hongchuan Nie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel DNAAF6 variants identified by whole-exome sequencing cause male infertility and primary ciliary dyskinesia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-020-01735-4"}], "href": "https://doi.org/10.1007/s10815-020-01735-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32170493"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32170493"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shan Wang, Bing Li, Yafei Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Analysis of PIH1D3 variant in a Chinese pedigree affected with primary ciliary dyskinesia]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhonghua Yi Xue Yi Chuan Xue Za Zhi (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3760/cma.j.cn511374-20190722-00361"}], "href": "https://doi.org/10.3760/cma.j.cn511374-20190722-00361"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32820521"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32820521"}]}]}]}