ArticleHuman molecular genetics2018
DNAAF1 links heart laterality with the AAA+ ATPase RUVBL1 and ciliary intraflagellar transport.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 33 citations in OpenAlex.
- Review
- A highly abundant circular RNA from the RMST locus plays a role in posterior fossa ependymoma pathogenesis.Brain pathology (Zurich, Switzerland) · 2026Article
- Clinical and Genetic Study of a Pseudo-Dominant Primary Ciliary Dyskinesia Pedigree: The First DNAAF1-Associated Family Reported in Chinese Population.Molecular genetics & genomic medicine · 2026Article
- Exome sequencing-based identification ofFrontiers in molecular biosciences · 2026Article
- Structural diversity and unity amongst axonemal dynein assembly factors.Journal of cell science · 2025Review
- Comparative Analysis of mRNA and lncRNA Expression Profiles in Testicular Tissue of Sexually Immature and Sexually Mature Mongolian Horses.Animals : an open access journal from MDPI · 2024Article
- Gene-knockout by iSTOP enables rapid reproductive disease modeling and phenotyping in germ cells of the founder generation.Science China. Life sciences · 2024Article
- Functions of cilia in cardiac development and disease.Annals of human genetics · 2024Review
- Ruvbl1 is Essential for Ciliary Beating duringDevelopment & reproduction · 2023Article
- Article
- The Role of Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization.Biomolecules · 2022Review
- A change of heart: new roles for cilia in cardiac development and disease.Nature reviews. Cardiology · 2022Review
- The role of SPAG1 in the assembly of axonemal dyneins in human airway epithelia.Journal of cell science · 2022Article
- Clinical and molecular characteristics of primary ciliary dyskinesia: A tertiary care centre experience.International journal of pediatrics & adolescent medicine · 2021Article
- Review
- Motile cilia genetics and cell biology: big results from little mice.Cellular and molecular life sciences : CMLS · 2021Review
- Defects in the cytoplasmic assembly of axonemal dynein arms cause morphological abnormalities and dysmotility in sperm cells leading to male infertility.PLoS genetics · 2021Article
- Novel dynein axonemal assembly factor 1 mutations identified using whole‑exome sequencing in patients with primary ciliary dyskinesia.Molecular medicine reports · 2020Article
- Rsph4a is essential for the triplet radial spoke head assembly of the mouse motile cilia.PLoS genetics · 2020Article
- Coding Variants Coupled With Rapid Modeling in Zebrafish Implicate Dynein Genes,Frontiers in cell and developmental biology · 2020Article
Corrections and comments
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Authors and funding
28 authors at 13 institutions in 4 countries.
Funding
Abstract
DNAAF1 (LRRC50) is a cytoplasmic protein required for dynein heavy chain assembly and cilia motility, and DNAAF1 mutations cause primary ciliary dyskinesia (PCD; MIM 613193). We describe four families with DNAAF1 mutations and complex congenital heart disease (CHD). In three families, all affected individuals have typical PCD phenotypes. However, an additional family demonstrates isolated CHD (heterotaxy) in two affected siblings, but no clinical evidence of PCD. We identified a homozygous DNAAF1 missense mutation, p.Leu191Phe, as causative for heterotaxy in this family. Genetic complementation in dnaaf1-null zebrafish embryos demonstrated the rescue of normal heart looping with wild-type human DNAAF1, but not the p.Leu191Phe variant, supporting the conserved pathogenicity of this DNAAF1 missense mutation. This observation points to a phenotypic continuum between CHD and PCD, providing new insights into the pathogenesis of isolated CHD. In further investigations of the function of DNAAF1 in dynein arm assembly, we identified interactions with members of a putative dynein arm assembly complex. These include the ciliary intraflagellar transport protein IFT88 and the AAA+ (ATPases Associated with various cellular Activities) family proteins RUVBL1 (Pontin) and RUVBL2 (Reptin). Co-localization studies support these findings, with the loss of RUVBL1 perturbing the co-localization of DNAAF1 with IFT88. We show that RUVBL1 orthologues have an asymmetric left-sided distribution at both the mouse embryonic node and the Kupffer's vesicle in zebrafish embryos, with the latter asymmetry dependent on DNAAF1. These results suggest that DNAAF1-RUVBL1 biochemical and genetic interactions have a novel functional role in symmetry breaking and cardiac development.
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