Affinage

DNAH10

Dynein axonemal heavy chain 10 · UniProt Q8IVF4

Length
4471 aa
Mass
514.8 kDa
Annotated
2026-04-28
24 papers in source corpus 8 papers cited in narrative 8 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNAH10 is an inner dynein arm heavy chain essential for motile cilia and flagellar beating, left-right body patterning, and spermiogenesis. DNAH10 assembles with CFAP57, DYNLL1, and CCDC73 into the double-headed inner dynein arm f (IDAf) complex; loss of DNAH10 destabilizes these subunits, disrupts IDA ultrastructure, and causes ciliary dysfunction in respiratory epithelia, ependymal cells, and sperm flagella (PMID:40898283, PMID:34657236, PMID:37314648). Beyond its structural role in the axoneme, DNAH10 bridges the deubiquitinase UCHL3 to PACRG, stabilizing PACRG via deubiquitination and facilitating intra-manchette transport during sperm head and flagellum shaping (PMID:41058558). Bi-allelic loss-of-function mutations in DNAH10 cause primary ciliary dyskinesia with chronic respiratory disease, male infertility (MMAF/asthenoteratozoospermia), hydrocephalus, and situs defects, while ependymal monocilia dysfunction leads to Reissner fiber disassembly and scoliosis (PMID:37314648, PMID:34915022, PMID:29843777).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2019 Medium

    Before any ciliary role was defined, a Drosophila screen linked the DNAH10 ortholog to triglyceride homeostasis, raising the possibility of non-canonical functions for this dynein heavy chain.

    Evidence RNAi knockdown in Drosophila with triglyceride quantification

    PMID:30778226

    Open questions at the time
    • Mechanism connecting a ciliary dynein to lipid metabolism is unknown
    • Not replicated in vertebrate systems
    • Single phenotypic readout without mechanistic dissection
  2. 2021 High

    Genetic and ultrastructural studies in humans and zebrafish established DNAH10 as an IDA heavy chain required for sperm flagellar motility, ciliary-driven left-right patterning, and ependymal monocilia function, revealing that its loss causes MMAF/asthenoteratozoospermia, cardiac laterality defects, Reissner fiber disassembly, and scoliosis.

    Evidence Whole-exome sequencing in infertile men with TEM/SEM/IF; zebrafish CRISPR mutants with monocilia beat frequency measurement, Reissner fiber imaging, and in situ hybridization for laterality markers

    PMID:29843777 PMID:34657236 PMID:34915022

    Open questions at the time
    • Identity of the specific IDA sub-complex containing DNAH10 was unknown
    • Whether DNAH10 functions beyond the axoneme (e.g. during spermiogenesis) was not addressed
    • Human respiratory cilia phenotype had not yet been characterized
  3. 2023 High

    Extension to respiratory cilia and mouse genetics demonstrated that DNAH10 deficiency causes primary ciliary dyskinesia with IDA loss in both respiratory cilia and sperm, confirmed by knockout and knockin mouse models recapitulating chronic infection, hydrocephalus, and infertility.

    Evidence Exome sequencing in PCD patients; Dnah10-KO and knockin mice with immunostaining and TEM

    PMID:37314648

    Open questions at the time
    • Subunit composition of the DNAH10-containing IDA complex remained unresolved
    • Whether DNAH10 has roles outside the axonemal beat machinery was not explored
  4. 2024 Medium

    Correlative evidence in bovine sperm showed that axonemal DNAH10 protein levels decline under cryodamage in parallel with motility loss, supporting its functional requirement for flagellar beating.

    Evidence Western blot quantification and TEM in freeze-thawed bovine sperm with motility analysis

    PMID:38593909

    Open questions at the time
    • Correlative design; no causal manipulation of DNAH10 in bovine sperm
    • Does not distinguish whether DNAH10 loss is cause or consequence of structural collapse
  5. 2025 High

    Biochemical and proteomic work defined DNAH10 as a subunit of the double-headed IDAf complex (with CFAP57, DYNLL1, CCDC73) and revealed a second, non-axonemal function: DNAH10 bridges UCHL3 to PACRG, stabilizing PACRG via deubiquitination to support intra-manchette transport during spermiogenesis.

    Evidence Co-IP, proteomic analysis, immunostaining, and Dnah10-KO mice for IDAf complex; Co-IP and protein interaction assays with deubiquitination readouts in manchette studies

    PMID:40898283 PMID:41058558

    Open questions at the time
    • Structural basis of IDAf assembly and DNAH10 motor domain architecture remain unresolved
    • Whether the UCHL3-PACRG bridging function is independent of or integrated with axonemal assembly is unclear
    • Downstream cargo of DNAH10-dependent manchette transport not fully cataloged

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the atomic-resolution structure of the IDAf complex, the full catalog of DNAH10-dependent manchette cargo, and whether the triglyceride phenotype observed in Drosophila reflects a conserved metabolic role or a secondary consequence of ciliary defects.
  • No cryo-EM or crystal structure of DNAH10 or the IDAf complex
  • Lipid metabolism link lacks vertebrate replication or mechanistic explanation
  • Genotype-phenotype correlations across different DNAH10 mutations (missense vs. null) not systematically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 5 GO:0060090 molecular adaptor activity 1
Localization
GO:0005929 cilium 4 GO:0005856 cytoskeleton 3
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-1266738 Developmental Biology 2 R-HSA-1474165 Reproduction 2
Partners
CCDC73CFAP57DNAH1DNALI1DYNLL1PACRGUCHL3
Complex memberships
DNAH10-UCHL3-PACRG deubiquitination/bridging complexIDAf (inner dynein arm f complex)

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 DNAH10 encodes an inner dynein arm (IDA) heavy chain protein in sperm flagella; bi-allelic loss-of-function variants in humans cause significant IDA deficiency in sperm flagella along with loss of DNAH1 protein, resulting in MMAF and asthenoteratozoospermia Whole-exome sequencing, immunofluorescence, transmission electron microscopy, scanning electron microscopy Journal of assisted reproduction and genetics High 34657236
2023 DNAH10 deficiency causes primary ciliary dyskinesia (PCD) in humans and mice; loss of DNAH10 results in absence of DNAH10 and DNALI1 in respiratory cilia, disordered 9+2 axoneme architecture, and IDA defects in both respiratory cilia and sperm flagella; Dnah10-knockout and knockin mice recapitulate PCD phenotypes including chronic respiratory infection, male infertility, and hydrocephalus Exome sequencing, immunostaining, transmission electron microscopy, Dnah10-knockout and knockin mouse models Frontiers of medicine High 37314648
2025 DNAH10 interacts with CFAP57, DYNLL1, and CCDC73 to form a double-headed inner dynein arm f (IDAf) complex in cilia; loss of DNAH10 leads to reduced expression of CFAP57, DYNLL1, and CCDC73, improper IDAf assembly, ciliary dysfunction, and pulmonary fibrosis Co-immunoprecipitation, immunostaining, Dnah10-knockout mouse model, proteomic analysis, scanning electron microscopy Orphanet journal of rare diseases High 40898283
2025 DNAH10 acts as a bridging protein that enhances the interaction between UCHL3 and PACRG; UCHL3 stabilizes PACRG via deubiquitination, and the DNAH10-UCHL3-PACRG complex facilitates intra-manchette transport during spermiogenesis; DNAH10 deficiency causes abnormal sperm head and flagella morphology, impaired manchette function, and aberrant localization of axonemal proteins Co-immunoprecipitation, immunofluorescence, protein interaction assays, loss-of-function studies in mice Development (Cambridge, England) High 41058558
2021 Morpholino knockdown and CRISPR/Cas9-mediated mutation of dnah10 in zebrafish disrupts cardiac looping and causes abnormal expression of left-right patterning markers lefty2 and pitx2, implicating DNAH10 in left-right body patterning Zebrafish morpholino knockdown, CRISPR/Cas9 mutation, in situ hybridization for lefty2/pitx2 Genome medicine Medium 29843777
2021 Disruption of dnah10 in zebrafish causes ependymal monocilia dysfunction (reduced beat frequency), disassembly of the Reissner fiber, and adult-viable scoliosis; monocilia function driven by dnah10 contributes to Reissner fiber polymerization and spine straightening F0 CRISPR screening, stable dnah10 mutant zebrafish, monocilia beat frequency measurement, Reissner fiber imaging Developmental biology High 34915022
2019 RNAi knockdown of the DNAH10 Drosophila ortholog results in a significant increase in total body triglyceride levels, implicating DNAH10 in lipid/triglyceride homeostasis Drosophila RNAi knockdown, triglyceride quantification Nature genetics Medium 30778226
2024 Repeated freeze-thaw cycles in bovine sperm significantly decrease DNAH10 protein levels in the axoneme (9+2 structure disrupted), correlating with reduced sperm motility, establishing DNAH10 as a functional axonemal component required for sperm motility Transmission electron microscopy, western blot/protein quantification, motility analysis Cryobiology Medium 38593909

Source papers

Stage 0 corpus · 24 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution. Nature genetics 83 30778226
2023 DNALI1 deficiency causes male infertility with severe asthenozoospermia in humans and mice by disrupting the assembly of the flagellar inner dynein arms and fibrous sheath. Cell death & disease 42 36792588
2021 Whole-exome sequencing of a cohort of infertile men reveals novel causative genes in teratozoospermia that are chiefly related to sperm head defects. Human reproduction (Oxford, England) 37 34791246
2015 Alterations of the spindle checkpoint pathway in clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas. International journal of cancer 37 26061684
2018 Rare copy number variants analysis identifies novel candidate genes in heterotaxy syndrome patients with congenital heart defects. Genome medicine 34 29843777
2021 Bi-allelic variants in DNAH10 cause asthenoteratozoospermia and male infertility. Journal of assisted reproduction and genetics 29 34657236
2020 DNAH10 mutation correlates with cisplatin sensitivity and tumor mutation burden in small-cell lung cancer. Aging 27 31959735
2014 Identification of four novel genes contributing to familial elevated plasma HDL cholesterol in humans. Journal of lipid research 21 24891332
2020 Identification of rare variants in novel candidate genes in pulmonary atresia patients by next generation sequencing. Computational and structural biotechnology journal 17 32128068
2021 The axonemal dynein heavy chain 10 gene is essential for monocilia motility and spine alignment in zebrafish. Developmental biology 15 34915022
2023 Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice. Frontiers of medicine 14 37314648
2015 Variants in the genes DCTN2, DNAH10, LRIG3, and MYO1A are associated with intermediate Charcot-Marie-Tooth disease in a Norwegian family. Acta neurologica Scandinavica 13 26517670
2022 FUS-P525L Juvenile Amyotrophic Lateral Sclerosis and Intellectual Disability: Evidence for Association and Oligogenic Inheritance. Neurology. Genetics 10 35812163
2023 Comparative transcriptome analysis identified crucial genes and pathways affecting sperm motility in the reproductive tract of drakes with different libido. Poultry science 7 36881978
2024 The effects of repeated freezing and thawing on bovine sperm morphometry and function. Cryobiology 5 38593909
2024 Prenatal EDC exposure, DNA Methylation, and early childhood growth: A prospective birth cohort study. Environment international 5 38986426
2025 Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility. Asian journal of andrology 4 39996363
2019 Discovery of increased epidermal DNAH10 expression after regeneration of dermis in a randomized with-in person trial - reflections on psoriatic inflammation. Scientific reports 4 31836722
2024 Novel variants in DNAH9 are present in two infertile patients with severe asthenospermia. Journal of human genetics 3 39523437
2015 Exome sequencing in a patient with Catel-Manzke-like syndrome excludes the involvement of the known genes and reveals a possible candidate. European journal of medical genetics 3 26420031
2024 Identification of competing endogenous RNA networks associated with circRNA and lncRNA in TCDD-induced cleft palate development. Toxicology letters 1 39270811
2025 Establishment and clinical significance of genetic factor screening method for patients with nonobstructive azoospermia based on whole exon sequencing technology. Translational andrology and urology 0 40376536
2025 DNAH10 mutation cause primary ciliary dyskinesia with defects of IDAf complex assembly and lung fibrosis manifestation. Orphanet journal of rare diseases 0 40898283
2025 DNAH10 interacts with UCHL3-PACRG complex to coordinate sperm head and flagella development during spermiogenesis. Development (Cambridge, England) 0 41058558