Affinage

DNAH10

Dynein axonemal heavy chain 10 · UniProt Q8IVF4

Length
4471 aa
Mass
514.8 kDa
Annotated
2026-06-09
26 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNAH10 encodes an inner dynein arm (IDA) heavy chain required for the motility of motile cilia and sperm flagella, where its loss disrupts the 9+2 axonemal architecture and IDA assembly, causing primary ciliary dyskinesia and multiple morphological abnormalities of the sperm flagella (MMAF) (PMID:37314648, PMID:34657236). It assembles into a double-headed inner dynein arm f (IDAf) complex with CFAP57, DYNLL1, and CCDC73, and its loss destabilizes all three partners and abolishes IDAf assembly (PMID:40898283); DNAH10 defines an IDA subspecies distinct from the DNALI1-dependent arms, since DNALI1 loss does not affect DNAH10 (PMID:36792588). Beyond the axoneme, DNAH10 bridges the UCHL3–PACRG complex within the manchette during spermiogenesis to support intra-manchette transport and proper sperm head and flagellar morphogenesis (PMID:41058558). In vivo loss-of-function across zebrafish and mice links DNAH10 to ciliary motility-dependent processes including left-right laterality determination (PMID:29843777), Reissner fiber polymerization and spine alignment via ependymal monocilia beating (PMID:34915022), and primary cilia-mediated Hedgehog signaling in skeletal development (PMID:42086325). Biallelic DNAH10 variants cause this spectrum of human disease, encompassing PCD with respiratory and laterality defects (PMID:37314648), male infertility with MMAF (PMID:34657236), and skeletal developmental abnormalities (PMID:42086325).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2018 High

    Placed DNAH10 upstream of vertebrate left-right axis determination, the first functional readout connecting it to ciliary patterning before its dynein role was molecularly defined.

    Evidence Morpholino knockdown and CRISPR/Cas9 mutation of dnah10 in zebrafish with lefty2/pitx2 in situ hybridization

    PMID:29843777

    Open questions at the time
    • Did not define DNAH10's molecular activity or its position within the dynein arm
    • Cardiac looping phenotype not connected to a specific ciliary subcompartment
  2. 2021 High

    Established DNAH10 as required for IDA assembly in sperm, defining its first human disease association (MMAF) and showing co-dependence with other IDA components.

    Evidence Whole-exome sequencing of MMAF patients with SEM/TEM and immunofluorescence showing reduced DNAH10 and DNAH1 in sperm

    PMID:34657236

    Open questions at the time
    • Did not resolve direct binding partners within the IDA complex
    • Mechanism of co-loss of DNAH1 not established
  3. 2021 High

    Extended DNAH10 function to ependymal monocilia, linking its motility role to Reissner fiber polymerization and spine alignment.

    Evidence CRISPR F0 screen and stable zebrafish mutant with cilia beat-frequency imaging and Reissner fiber immunostaining

    PMID:34915022

    Open questions at the time
    • Did not establish how reduced beat frequency mechanistically drives Reissner fiber disassembly
    • DNAH10's molecular interactions in monocilia not defined
  4. 2023 High

    Confirmed DNAH10 as an IDA heavy chain subunit in respiratory cilia and showed loss causes PCD ultrastructural defects, unifying the cilia and sperm phenotypes in mammalian models.

    Evidence Exome sequencing of a PCD patient, TEM, immunostaining, and Dnah10 knockin/knockout mice

    PMID:37314648

    Open questions at the time
    • Specific IDA complex composition not yet defined
    • Co-loss of DNALI1 mechanism not resolved
  5. 2023 Medium

    Distinguished DNAH10 as belonging to a DNALI1-independent IDA subspecies, refining the architecture of inner dynein arm heterogeneity.

    Evidence Immunofluorescence in DNALI1-deficient patient and Dnali1-KO mouse sperm showing DNAH10 unaffected while DNAH1/DNAH7 lost

    PMID:36792588

    Open questions at the time
    • Negative result defines independence but not the positive assembly pathway for DNAH10
    • Which adaptor stabilizes the DNAH10 subspecies not identified
  6. 2025 High

    Defined the molecular complex DNAH10 assembles into, identifying its direct partners and the IDAf complex it builds.

    Evidence Reciprocal Co-IP for CFAP57, DYNLL1, CCDC73, with Dnah10-KO mice and proteomics showing reduced partner expression and defective IDAf assembly

    PMID:40898283

    Open questions at the time
    • Stoichiometry and structural arrangement of the double-headed IDAf complex not resolved
    • Order of complex assembly not established
  7. 2025 High

    Revealed a non-axonemal role: DNAH10 bridges the UCHL3-PACRG deubiquitination module at the manchette to support sperm head and flagellar morphogenesis.

    Evidence Co-IP establishing the ternary complex plus immunofluorescence and loss-of-function in patient and mouse models

    PMID:41058558

    Open questions at the time
    • How DNAH10 enhances the UCHL3-PACRG interaction biochemically not defined
    • Connection between manchette bridging and axonemal IDA role not integrated
  8. 2026 Medium

    Implicated DNAH10 in primary (non-motile) cilia and Hedgehog signaling, expanding its role beyond motile ciliogenesis to skeletal development.

    Evidence Whole-exome sequencing, in vitro variant abundance assay, Dnah10-KO mice with primary cilia morphology and Hedgehog pathway assays

    PMID:42086325

    Open questions at the time
    • Primary cilia role is a single-study finding
    • How an inner dynein arm heavy chain functions in non-motile primary cilia not mechanistically explained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DNAH10's distinct activities — axonemal IDAf motor, manchette bridging factor, and primary cilia/Hedgehog regulator — are mechanistically reconciled within one protein remains unresolved.
  • No structural model of DNAH10 or the IDAf complex
  • Direct interaction partners of DNAH10 in primary cilia not identified
  • Regulation of DNAH10 by intraflagellar transport (DNAI4/IFT144) only inferred indirectly

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 3 GO:0140657 ATP-dependent activity 2
Localization
GO:0005929 cilium 4 GO:0005856 cytoskeleton 2
Pathway
R-HSA-1266738 Developmental Biology 2 R-HSA-1474165 Reproduction 2 R-HSA-162582 Signal Transduction 1
Partners
CCDC73CFAP57DYNLL1PACRGUCHL3
Complex memberships
inner dynein arm f (IDAf) complex

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 DNAH10 encodes an inner dynein arm (IDA) heavy chain subunit in motile cilia and sperm flagella; loss-of-function DNAH10 variants in a PCD patient caused absence of DNAH10 and DNALI1 in respiratory cilia, with disordered axoneme 9+2 architecture and IDA defects confirmed by transmission electron microscopy. Dnah10-knockin and Dnah10-knockout mice recapitulated PCD phenotypes including chronic respiratory infection, male infertility, and hydrocephalus. Exome sequencing, immunostaining, transmission electron microscopy, Dnah10 knockin/knockout mouse models Frontiers of medicine High 37314648
2021 Bi-allelic DNAH10 variants (homozygous frameshift and compound heterozygous missense) cause MMAF with IDA deficiency in sperm flagella; immunofluorescence showed reduction of both DNAH10 and the IDA-related protein DNAH1 in patient sperm, indicating DNAH10 is required for IDA assembly in sperm. Whole-exome sequencing, H&E staining, scanning electron microscopy, transmission electron microscopy, immunofluorescence Journal of assisted reproduction and genetics High 34657236
2021 Disruption of dnah10 in zebrafish (CRISPR F0 screen and stable mutant) causes recessive adult-viable scoliosis; dnah10 mutant ependymal monocilia lining the hindbrain and spinal canal showed reduced beat frequency, correlating with disassembly of the Reissner fiber and onset of body curvature, placing DNAH10 function in monocilia motility required for Reissner fiber polymerization and spine alignment. CRISPR/Cas9 F0 screen, stable zebrafish mutant, high-speed cilia beat frequency imaging, Reissner fiber immunostaining Developmental biology High 34915022
2018 Morpholino knockdown and CRISPR/Cas9 mutation of dnah10 in zebrafish disrupted cardiac looping and produced abnormal expression of the left-right patterning markers lefty2 and pitx2, establishing DNAH10 function upstream of laterality determination during embryogenesis. Morpholino knockdown, CRISPR/Cas9-mediated mutation, whole-mount in situ hybridization (lefty2, pitx2) in zebrafish Genome medicine High 29843777
2025 DNAH10 interacts with CFAP57, DYNLL1, and CCDC73 to form a double-headed inner dynein arm f (IDAf) complex in cilia; Co-IP confirmed these interactions, and loss of DNAH10 in patients and Dnah10-KO mice led to reduced expression of all three partners and defective IDAf assembly, resulting in ciliary dysfunction and pulmonary fibrosis. Co-immunoprecipitation, immunostaining, Dnah10 knockout mice, scanning electron microscopy, proteomic analysis Orphanet journal of rare diseases High 40898283
2025 DNAH10 exerts a bridging function between UCHL3 and PACRG in the manchette during spermiogenesis; UCHL3 binds PACRG and stabilizes it via deubiquitination, and DNAH10 enhances this UCHL3-PACRG interaction. DNAH10 deficiency leads to impaired manchette function, aberrant localization of axonemal proteins, and abnormal sperm head and flagella morphology. Co-immunoprecipitation, immunofluorescence, genetic loss-of-function analysis in patient and mouse models Development (Cambridge, England) High 41058558
2026 Biallelic DNAH10 variants in humans with skeletal developmental abnormalities are associated with reduced DNAH10 protein; Dnah10-knockout mice showed polydactyly, impaired cartilage development, and abnormal ossification. Mechanistically, Dnah10 loss caused abnormal primary cilia morphology, attenuated Hedgehog signaling, impaired osteoblast differentiation, and defective chondrocyte maturation, revealing a role for DNAH10 in primary cilia-mediated skeletal development. Whole-exome sequencing, in vitro missense variant protein abundance assay, Dnah10-KO mouse model, primary cilia morphology analysis, Hedgehog signaling pathway assay Journal of medical genetics Medium 42086325
2023 DNALI1 loss in patient sperm and Dnali1-KO mice caused loss of DNAH1 and DNAH7 but NOT DNAH10, demonstrating that DNAH10 belongs to a distinct partial IDA subspecies that is independent of DNALI1. Immunofluorescence in patient sperm and Dnali1-KO mouse sperm (negative result for DNAH10 loss) Cell death & disease Medium 36792588
2024 DNAH9 variants in asthenospermia patients led to dysfunction of flagellar ultrastructure-related proteins including DNAH10, as shown by immunofluorescence, indicating DNAH10 protein localization in sperm flagella is dependent on intact DNAH9. Immunofluorescence in patient sperm carrying biallelic DNAH9 variants Journal of human genetics Low 39523437
2024 Repeated freeze-thaw cycles of bovine sperm significantly decreased DNAH10 protein levels and disrupted the 9+2 axonemal structure, as shown by transmission electron microscopy and protein quantification, correlating with reduced sperm motility. Transmission electron microscopy, western blot/protein level quantification after repeated freeze-thaw treatment Cryobiology Low 38593909
2026 DNAI4 deficiency in mice caused a remarkable reduction in DNAH10 in testes and sperm tails, and immunoprecipitation demonstrated that DNAI4 interacts with intraflagellar transport protein IFT144; these data place DNAH10 as a downstream IDA component regulated by DNAI4-dependent intraflagellar transport. Immunoprecipitation, western blot, electron microscopy, Dnai4-KO mouse model Development (Cambridge, England) Low 42083518

Source papers

Stage 0 corpus · 26 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 84 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 44 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) 42 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 30 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 8 36881978
2024 The effects of repeated freezing and thawing on bovine sperm morphometry and function. Cryobiology 6 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
2026 DNAI4 is required for flagellum assembly and male fertility in mice. Development (Cambridge, England) 0 42083518
2026 Biallelic variants in DNAH10 are associated with skeletalf developmental abnormalities and ciliary dysfunction. Journal of medical genetics 0 42086325
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

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