Affinage

DNAH7

Dynein axonemal heavy chain 7 · UniProt Q8WXX0

Length
4024 aa
Mass
461.2 kDa
Annotated
2026-04-28
29 papers in source corpus 11 papers cited in narrative 11 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNAH7 is an axonemal inner dynein arm (IDA) heavy chain essential for motile cilia beat and sperm flagellar motility. It is synthesized during ciliated cell differentiation, assembles into ciliary and flagellar axonemes as part of a specific IDA subspecies that includes the light intermediate chain DNALI1, and its axonemal incorporation depends on the CCDC39/CCDC40 molecular ruler complex and intact radial spoke 1 structures (PMID:11877439, PMID:36792588, PMID:39056782, PMID:39849482). Biallelic loss-of-function mutations in DNAH7 cause selective absence of IDAs—without affecting outer dynein arms—leading to primary ciliary dyskinesia with laterality defects, and to asthenozoospermia with disrupted mitochondrial sheath assembly in the sperm mid-piece (PMID:34476482, PMID:35543642, PMID:24930722, PMID:40810911). Loss of DNAH7 also causes co-reduction of fellow IDA heavy chains DNAH3 and DNAH6, indicating it serves a structural scaffold role within the IDA complex (PMID:40810911).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2002 High

    Identification of DNAH7 as an inner dynein arm heavy chain of human respiratory cilia resolved the molecular identity of IDA components in human motile cilia and linked IDA assembly failure to primary ciliary dyskinesia.

    Evidence Mass spectrometry of isolated cilia proteins, immunohistochemistry, and cDNA cloning from human ciliated epithelium and a PCD patient

    PMID:11877439

    Open questions at the time
    • No causative mutation in DNAH7 identified in this patient
    • Mechanism of IDA assembly failure not determined
    • Expression in non-respiratory motile cilia not assessed
  2. 2014 High

    Zebrafish knockdown established that DNAH7 is required for cilia motility and left-right patterning, moving understanding from correlative loss in PCD to a causal requirement in embryonic symmetry breaking.

    Evidence Morpholino knockdown of dnah7 in zebrafish Kupffer's vesicle with live cilia imaging, fluid dynamics simulation, and in situ hybridization

    PMID:24930722

    Open questions at the time
    • Morpholino knockdown rather than stable genetic mutant
    • No ultrastructural confirmation of IDA loss in zebrafish
    • Mammalian in vivo requirement not yet tested
  3. 2019 Medium

    Discovery of DNAH7 missense variants causing protein mislocalization in a PCD patient with DNAH5 co-mutations raised the possibility of digenic contributions, though the isolated effect of DNAH7 variants remained unclear.

    Evidence Whole-exome sequencing, TEM, and protein localization analysis in a Kartagener syndrome patient

    PMID:31443223

    Open questions at the time
    • Confounding DNAH5 variants preclude attribution of phenotype solely to DNAH7
    • Single patient, not independently replicated
    • No functional rescue experiment
  4. 2020 Medium

    Identification of TBC1D21 as required for DNAH7 axonemal retention in sperm provided the first evidence that accessory proteins regulate DNAH7 localization within the flagellar axoneme.

    Evidence Tbc1d21 knockout mice with immunofluorescence co-localization and proteomic analysis of sperm tails

    PMID:32976492

    Open questions at the time
    • No direct biochemical interaction (e.g., Co-IP) between TBC1D21 and DNAH7 demonstrated
    • Mechanism by which TBC1D21 retains DNAH7 not determined
    • Not confirmed in human sperm
  5. 2021 High

    Biallelic DNAH7 mutations in asthenozoospermic men established DNAH7 as directly required for IDA assembly in human sperm flagella and demonstrated that ODA assembly is spared, defining the specificity of DNAH7 loss.

    Evidence Whole-exome sequencing, TEM, and immunofluorescence of sperm from infertile patients

    PMID:34476482

    Open questions at the time
    • Rescue experiment not performed
    • Whether DNAH7 loss affects respiratory cilia in the same patients not examined
    • Structural position within the 96 nm repeat not mapped
  6. 2022 High

    Extending the flagellar phenotype, DNAH7 disruption was shown to cause mitochondrial sheath disorganization in the sperm mid-piece, revealing that IDA integrity influences extra-axonemal structures.

    Evidence TEM and immunofluorescence of sperm from a patient with biallelic DNAH7 disruption

    PMID:35543642

    Open questions at the time
    • Whether mitochondrial detachment is a direct or secondary consequence of IDA loss is unknown
    • Mechanism linking axoneme defects to mitochondrial sheath not characterized
  7. 2023 High

    DNALI1 was identified as the cognate light intermediate chain of a DNAH7-containing IDA subspecies, establishing the subunit composition of the specific IDA complex that DNAH7 occupies and showing DNALI1 is required for DNAH7 axonemal assembly.

    Evidence Human patient with DNALI1 biallelic mutation, Dnali1 knockout mice, immunoprecipitation, western blot, and immunofluorescence

    PMID:36792588

    Open questions at the time
    • Full stoichiometry and additional subunits of the DNAH7/DNALI1 IDA complex not determined
    • No structural data for the complex
    • Whether DNAH1 and DNAH7 occupy the same or distinct IDA subtypes not fully resolved
  8. 2024 Medium

    The CCDC39/CCDC40 molecular ruler complex was shown to be required for DNAH7 assembly into respiratory ciliary axonemes, placing DNAH7-containing IDAs under the organizational control of the 96 nm axonemal periodicity determinants.

    Evidence Immunofluorescence of respiratory cilia from a cohort of 51 PCD patients with biallelic CCDC39/CCDC40 variants

    PMID:39056782

    Open questions at the time
    • No direct biochemical reconstitution of ruler-dependent IDA docking
    • Whether CCDC39/40 directly scaffold DNAH7 or act indirectly through intermediate structures is unknown
  9. 2025 High

    Loss of DNAH7 was shown to cause co-reduction of DNAH3 and DNAH6 while sparing all ODA heavy chains, defining a DNAH7-dependent IDA sub-complex and suggesting a scaffold function; separately, IQUB/RS1 deficiency was linked to DNAH7 downregulation, connecting radial spoke integrity to IDA stability.

    Evidence Human WES and IF/TEM of sperm (DNAH7 study); human WES and Iqub−/− mice with MS, WB, and EM (IQUB study)

    PMID:39849482 PMID:40810911

    Open questions at the time
    • Whether DNAH7, DNAH3, and DNAH6 form a single complex or are co-dependent but separate IDAs is unresolved
    • The physical basis for RS1-IDA coupling is unknown
    • No cryo-EM or crystal structure of the DNAH7-containing IDA

Open questions

Synthesis pass · forward-looking unresolved questions
  • The precise position of the DNAH7-containing IDA within the 96 nm axonemal repeat, its full subunit composition, and the structural basis for its motor activity and interactions with the molecular ruler and radial spokes remain undefined.
  • No high-resolution structure of the DNAH7-containing IDA complex
  • ATPase/motor activity of DNAH7 not directly measured
  • No conditional or tissue-specific knockout model in mammals

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 3
Localization
GO:0005929 cilium 8
Pathway
R-HSA-1474165 Reproduction 3 R-HSA-1852241 Organelle biogenesis and maintenance 3
Partners
CCDC39CCDC40DNAH3DNAH6DNALI1TBC1D21
Complex memberships
inner dynein arm (IDA) subspecies with DNALI1

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 DNAH7 is an inner dynein arm heavy chain component of human respiratory cilia axonemes. It is synthesized during ciliated cell differentiation but fails to assemble into cilia in a case of primary ciliary dyskinesia (PCD) with absent inner dynein arms, as shown by gel electrophoresis of isolated cilia, mass spectrometry identification, and immunohistochemistry. Gel electrophoresis of cilia proteins, mass spectrometry, immunohistochemistry, cDNA cloning The Journal of biological chemistry High 11877439
2014 Dnah7 knockdown in zebrafish Kupffer's vesicle produces immotile cilia, reducing directional fluid flow and disrupting left-right organ laterality, establishing DNAH7 as required for motile cilia-driven left-right patterning. Mosaic organizers with varying numbers of dnah7 morphant (immotile) and wild-type (motile) cilia revealed that ~30 or more motile cilia are needed for robust asymmetric Charon expression and situs solitus. Zebrafish dnah7 morpholino knockdown, live imaging of cilia motility, fluid dynamics simulation, in situ hybridization for charon expression Developmental cell High 24930722
2021 Biallelic mutations in DNAH7 in human patients with asthenozoospermia cause specific loss of inner dynein arms (IDAs) in sperm flagellar axonemes, impairing axoneme integrity and sperm motility, without affecting outer dynein arms. Whole-exome sequencing, transmission electron microscopy of sperm axonemes, immunofluorescence staining of sperm Acta biochimica et biophysica Sinica High 34476482
2022 DNAH7 disruption in a human patient causes loss of inner dynein arms in sperm flagella axonemes and leads to detachment/dispersal of mitochondria outside the axoneme, causing abnormalities in the mitochondrial sheath of the sperm mid-piece and male infertility. Whole-exome sequencing, transmission electron microscopy, immunofluorescence Clinical genetics High 35543642
2020 TBC1D21 physically co-localizes with DNAH7 in the sperm tail axoneme in vivo, and loss of Tbc1d21 in mice causes DNAH7 to detach and disperse outside the axoneme, indicating TBC1D21 is required for proper axonemal localization of DNAH7. Proteomic analysis, immunofluorescence co-localization in mouse sperm, Tbc1d21 knockout mouse model PLoS genetics Medium 32976492
2023 DNALI1 loss in humans and mice causes absence of DNAH7 (and DNAH1 but not DNAH10) from sperm flagella IDAs, demonstrating that DNALI1 is a light intermediate chain of a specific IDA subspecies that contains DNAH7, and that DNALI1 is required for DNAH7 assembly into the flagellar axoneme. Human patient with DNALI1 bi-allelic mutation, Dnali1 knockout mice, western blot, immunofluorescence, immunoprecipitation Cell death & disease High 36792588
2024 CCDC39 and CCDC40 (components of the 96 nm axonemal ruler complex) are required for assembly of IDA heavy chains DNAH1, DNAH6, and DNAH7 into respiratory ciliary axonemes; disease-causing biallelic variants in CCDC39/CCDC40 result in conspicuous absence of DNAH7 from respiratory cilia, indicating DNAH7 belongs to centrin2 (CETN2)-containing IDAs whose assembly depends on the molecular ruler. Next-generation sequencing (cohort of 51 PCD patients), immunofluorescence analysis of respiratory cilia Cells Medium 39056782
2025 IQUB deficiency causes RS1 (radial spoke 1) defects in sperm flagella and leads to significant downregulation of IDA components DNAH7 and DNAH12, indicating that DNAH7-containing IDAs are spatially proximal to RS1 and their stability or assembly is dependent on intact RS1. Human patient WES, Iqub-/- mice, protein mass spectrometry, western blotting, electron microscopy Cell communication and signaling : CCS Medium 39849482
2014 The BRAF VE1 antibody cross-reacts with epitopes in axonemal dynein heavy chain proteins including DNAH7 in cilia and flagella, as demonstrated by ELISA showing VE1 antibody recognition of DNAH7-derived epitopes, confirming DNAH7 is a major axonemal protein in cilia of bronchial airways, fallopian tubes, and sperm flagella. ELISA, immunohistochemistry, sequence homology analysis Modern pathology Medium 25412847
2019 In a PCD patient with Kartagener syndrome, two novel missense variants in DNAH7 together with disease-causing variants in DNAH5 led to protein mislocalization of DNAH7 and reduced DNAH7 gene expression in respiratory cilia, suggesting potential digenic interaction modulating the PCD phenotype. Whole-exome sequencing, transmission electron microscopy, functional gene expression and protein localization analysis Cells Medium 31443223
2025 Biallelic loss-of-function variants in DNAH7 cause selective loss of inner dynein arms (IDAs) in human sperm flagella, with co-reduction of IDA-associated proteins DNAH3 and DNAH6, but no effect on outer dynein arm proteins (DNAH8, DNAH11, DNAH17, DNAI1), demonstrating DNAH7 is specifically required for IDA assembly in human sperm flagella. Whole-exome sequencing, transmission electron microscopy, immunofluorescence staining of spermatozoa Human genetics High 40810911

Source papers

Stage 0 corpus · 29 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data. Human genomics 87 33536081
2014 Left-right organizer flow dynamics: how much cilia activity reliably yields laterality? Developmental cell 73 24930722
2002 Identification of dynein heavy chain 7 as an inner arm component of human cilia that is synthesized but not assembled in a case of primary ciliary dyskinesia. The Journal of biological chemistry 57 11877439
2014 Cross-reactivity of the BRAF VE1 antibody with epitopes in axonemal dyneins leads to staining of cilia. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 51 25412847
2020 Network perturbation analysis in human bronchial epithelial cells following SARS-CoV2 infection. Experimental cell research 48 32735892
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
2019 Clinical and Genetic Analysis of Children with Kartagener Syndrome. Cells 31 31443223
2020 Deficiency of the Tbc1d21 gene causes male infertility with morphological abnormalities of the sperm mitochondria and flagellum in mice. PLoS genetics 29 32976492
2022 Loss of function mutation in DNAH7 induces male infertility associated with abnormalities of the sperm flagella and mitochondria in human. Clinical genetics 25 35543642
2018 Whole exome sequencing identifies PLEC, EXO5 and DNAH7 as novel susceptibility genes in testicular cancer. International journal of cancer 24 29761480
2021 Bi-allelic mutations in DNAH7 cause asthenozoospermia by impairing the integrality of axoneme structure. Acta biochimica et biophysica Sinica 21 34476482
2020 Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data. medRxiv : the preprint server for health sciences 21 33200144
2014 Organized chaos in Kupffer's vesicle: how a heterogeneous structure achieves consistent left-right patterning. Bioarchitecture 18 25454897
2023 Skeletal Muscles of Sedentary and Physically Active Aged People Have Distinctive Genic Extrachromosomal Circular DNA Profiles. International journal of molecular sciences 15 36769072
2024 Whole exome sequencing analysis of 167 men with primary infertility. BMC medical genomics 12 39267058
2024 Primary Ciliary Dyskinesia Associated Disease-Causing Variants in CCDC39 and CCDC40 Cause Axonemal Absence of Inner Dynein Arm Heavy Chains DNAH1, DNAH6, and DNAH7. Cells 8 39056782
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
2022 DNAH7 mutations benefit colorectal cancer patients receiving immune checkpoint inhibitors. Annals of translational medicine 7 36660654
2025 IQUB mutation induces radial spoke 1 deficiency causing asthenozoospermia with normal sperm morphology in humans and mice. Cell communication and signaling : CCS 5 39849482
2023 Recombinant Human Adenovirus Type 5 (H101) Intra-Tumor Therapy in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer: Genomic Profiling Relating to Clinical Efficacy. Drug design, development and therapy 5 38046281
2014 A novel mutation of the axonemal dynein heavy chain gene 5 (DNAH5) in a Japanese neonate with asplenia syndrome. Medical molecular morphology 5 24912412
2023 Whole exome sequencing study identifies candidate loss of function variants and locus heterogeneity in familial cholesteatoma. PloS one 3 36920900
2025 A cross-tissue transcriptome-wide association study reveals novel susceptibility genes for erectile dysfunction. Andrology 2 40145662
2025 Prepubertal exposure to 17β-estradiol downregulates motor protein genes, impairs sperm flagella formation, and reduces fertility in Nile tilapia (Oreochromis niloticus). Aquatic toxicology (Amsterdam, Netherlands) 2 40412113
2024 Novel bioinformatic approaches show the role of driver genes in the progression of cervical cancer: An in-silico study. Heliyon 2 39634417
2025 Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans. Human genetics 1 40810911
2025 Gonadal sex differentiation in Eleutheronema tetradactylum: Histological features and transcriptomic insights from mature gonads. Comparative biochemistry and physiology. Part D, Genomics & proteomics 0 40694934
2025 Identifying potential genetic biomarkers for sperm dysfunction through whole-genome sequencing. Scientific reports 0 41115892
2023 COVID-19 progression towards ARDS: a genome wide study reveals host factors underlying critical COVID-19. Genomics & informatics 0 37415451