Affinage

DNAH7

Dynein axonemal heavy chain 7 · UniProt Q8WXX0

Length
4024 aa
Mass
461.2 kDa
Annotated
2026-06-09
30 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

DNAH7 is an inner dynein arm (IDA) heavy chain that powers the motility of both respiratory cilia and sperm flagella, where its activity drives directional fluid flow required for normal left-right organ laterality (PMID:11877439, PMID:24930722). It was first identified as an IDA component of human respiratory cilia that is absent from primary ciliary dyskinesia cells lacking inner dynein arms; in these cells DNAH7 protein is synthesized in the cytoplasm but fails to assemble into the axoneme, establishing that its function depends on intact axonemal assembly machinery rather than on its own expression alone (PMID:11877439). This assembly dependence is borne out by several upstream factors: the CCDC39/CCDC40 molecular ruler complex is required for incorporation of DNAH7-containing IDAs into respiratory axonemes (PMID:39056782), and in sperm flagella DNAH7 is a component of the IDA subspecies defined by the light intermediate chain DNALI1, whose loss strips DNAH7 from the flagellum (PMID:36792588). Correct axonemal retention of DNAH7 in sperm additionally requires TBC1D21, in whose absence DNAH7 detaches and disperses outside the axoneme (PMID:32976492). Bi-allelic loss-of-function mutations in DNAH7 cause asthenozoospermia with selective loss of inner dynein arms while outer dynein arm components are preserved, producing severely impaired sperm motility and, in some patients, multiple morphological abnormalities of the flagella including mitochondrial sheath defects (PMID:34476482, PMID:35543642, PMID:40810911).

Mechanistic history

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

    Established DNAH7 as an inner dynein arm heavy chain of human respiratory cilia and showed its absence from the axoneme is an assembly defect, not a synthesis defect.

    Evidence Mass spectrometry of purified cilia proteins comparing normal vs PCD bronchial epithelial cells, with cDNA cloning and immunohistochemistry

    PMID:11877439

    Open questions at the time
    • Does not identify which assembly factors recruit DNAH7
    • No structural placement within the 96 nm repeat
    • Catalytic/motor activity not directly assayed
  2. 2014 High

    Demonstrated that DNAH7-dependent cilia motility drives directional fluid flow and is required for correct left-right organ laterality during development.

    Evidence Zebrafish dnah7 morpholino knockdown with live imaging of cilia and fluid flow, laterality tracking, and computational fluid dynamics simulation

    PMID:24930722

    Open questions at the time
    • Morpholino knockdown not confirmed with a genetic mutant
    • Human laterality phenotype from DNAH7 loss not documented
    • Does not address sperm flagellar role
  3. 2021 Medium

    Linked DNAH7 loss-of-function to human asthenozoospermia through selective inner dynein arm deficiency, distinguishing it from outer dynein arm components.

    Evidence Whole-exome sequencing, TEM of sperm axonemes, and immunofluorescence in patient spermatozoa

    PMID:34476482

    Open questions at the time
    • Single lab, no functional rescue
    • Mechanism of IDA-specific loss not resolved
    • Genotype-phenotype across larger cohorts not established
  4. 2022 Medium

    Extended the sperm phenotype to flagellar morphological abnormalities, showing DNAH7 loss perturbs not only IDAs but mitochondrial sheath organization in the mid-piece.

    Evidence Whole-exome sequencing, TEM, and immunofluorescence of patient spermatozoa

    PMID:35543642

    Open questions at the time
    • Causal link between IDA loss and mitochondrial detachment unclear
    • Single patient
    • No animal model confirmation
  5. 2020 Medium

    Identified TBC1D21 as a factor required for correct axonemal retention of DNAH7 in sperm, the first partner shown to control DNAH7 localization.

    Evidence Co-immunofluorescence, Tbc1d21 knockout mouse, and proteomic analysis of TBC1D21 interactors

    PMID:32976492

    Open questions at the time
    • Direct physical interaction not biochemically resolved
    • Whether TBC1D21 acts during assembly or maintenance unclear
    • Respiratory cilia not examined
  6. 2023 Medium

    Placed DNAH7 within a defined IDA subspecies by showing the light intermediate chain DNALI1 is required for DNAH7 (and DNAH1) but not DNAH10 retention in sperm flagella.

    Evidence Immunofluorescence of patient and Dnali1-/- mouse sperm, co-immunoprecipitation from testis lysates, and western blotting

    PMID:36792588

    Open questions at the time
    • Direct DNALI1-DNAH7 binding interface not mapped
    • Stoichiometry of the subspecies unknown
    • Respiratory cilia subspecies composition not addressed
  7. 2024 Medium

    Positioned DNAH7-containing IDAs downstream of the CCDC39/CCDC40 molecular ruler in respiratory ciliary axoneme assembly.

    Evidence Next-generation sequencing of 51 PCD patients with CCDC39/CCDC40 variants and immunofluorescence of respiratory cilia

    PMID:39056782

    Open questions at the time
    • Whether the ruler binds DNAH7 directly or sets repeat spacing is not distinguished
    • Sperm flagellar dependence on ruler not tested
    • No structural data
  8. 2025 Medium

    Confirmed DNAH7 is specifically required for IDA assembly in human sperm flagella, with IDA but not ODA markers lost upon DNAH7 deficiency.

    Evidence Whole-exome sequencing, TEM, and immunofluorescence with a panel of IDA (DNAH3, DNAH6) and ODA (DNAH8, DNAH11, DNAH17, DNAI1) markers in patient spermatozoa

    PMID:40810911

    Open questions at the time
    • Hierarchy among co-lost IDA chains unresolved
    • No rescue experiment
    • Two patients only
  9. 2025 Low

    Suggested spatial coupling of DNAH7-containing IDAs to radial spoke 1, as IQUB/RS1 deficiency secondarily reduces DNAH7.

    Evidence Whole-exome sequencing, mass spectrometry, western blotting, and immunofluorescence in patient and Iqub-/- mouse sperm

    PMID:39849482

    Open questions at the time
    • DNAH7 reduction is a secondary, indirect observation in an IQUB study
    • Direct DNAH7-RS1 contact not demonstrated
    • Causal direction unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The motor/ATPase activity of DNAH7, its structural placement within the axonemal 96 nm repeat, and the direct molecular interactions governing its recruitment remain undefined.
  • No reconstituted motility or ATPase assay
  • No cryo-EM placement of DNAH7 in the IDA
  • Direct binding partners not biochemically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005929 cilium 3 GO:0005829 cytosol 1
Pathway
GO:0005929 cilium 1
Partners
DNALI1TBC1D21
Complex memberships
DNALI1-containing IDA subspeciesaxonemal inner dynein arm

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 DNAH7 was identified as a component of the inner dynein arm of human respiratory cilia. Mass spectrometry of cilia proteins from normal versus primary ciliary dyskinesia (PCD) cells identified DNAH7 as absent in PCD cilia. DNAH7 shares 68% similarity with an inner arm dynein heavy chain from Drosophila. In PCD cells lacking inner dynein arms by electron microscopy, DNAH7 protein was synthesized intracellularly but failed to assemble into cilia. Gel electrophoresis and mass spectrometry of purified cilia proteins; immunohistochemistry; cDNA cloning; comparison of normal vs. PCD bronchial epithelial cells The Journal of biological chemistry High 11877439
2014 Zebrafish dnah7 knockdown (morphant) generated mosaic left-right organizers with reduced motile cilia numbers, demonstrating that dnah7-dependent cilia motility is required for directional fluid flow in Kupffer's vesicle and thereby for correct left-right organ laterality. Embryos with fewer motile cilia (due to dnah7 knockdown) showed reduced asymmetric charon expression and increased laterality randomization. Zebrafish dnah7 morpholino knockdown; live imaging of cilia motility and fluid flow; quantitative tracking of organ laterality; computational fluid dynamics simulation Developmental cell High 24930722
2014 The BRAF VE1 antibody cross-reacts with epitopes in DNAH7 (and other axonemal dynein heavy chains including DNAH2 and DNAH12). There is significant sequence homology between the VE1 immunizing peptide (BRAF V600E residues 596-606) and regions of DNAH7. This was confirmed by ELISA showing VE1 antibody recognition of DNAH7 epitopes, and explains VE1 staining of cilia in bronchial airways, fallopian tubes, and other ciliated structures. ELISA; sequence homology analysis; immunohistochemistry of ciliated tissues Modern pathology Medium 25412847
2021 Bi-allelic mutations in DNAH7 in asthenozoospermia patients caused specific loss of inner dynein arms (IDAs) in sperm axonemes, with significantly decreased DNAH7 expression in spermatozoa. Outer dynein arm structure was preserved. Sperm motility was severely impaired but fertilization was achievable by ICSI. Whole-exome sequencing; transmission electron microscopy of sperm axonemes; immunofluorescence/protein expression analysis in patient spermatozoa Acta biochimica et biophysica Sinica Medium 34476482
2022 Loss-of-function mutation in DNAH7 in a human patient caused asthenozoospermia with multiple morphological abnormalities of sperm flagella. TEM revealed loss of inner dynein arms in sperm axonemes, and mitochondria of the sperm flagella detached and dispersed outside the axoneme, causing abnormalities in the mitochondrial sheath in the mid-piece region. Whole-exome sequencing; transmission electron microscopy; immunofluorescence of patient spermatozoa Clinical genetics Medium 35543642
2023 DNALI1 deficiency in humans and mice caused loss of DNAH7 (and DNAH1) but not DNAH10 from sperm flagella, demonstrating that DNALI1 is a light intermediate chain of a partial IDA subspecies that includes DNAH7. Immunoprecipitation showed DNALI1 interacts with cytoplasmic dynein complex proteins in testes. Immunofluorescence of patient and Dnali1-/- mouse sperm; immunoprecipitation from testis lysates; western blotting Cell death & disease Medium 36792588
2024 Disease-causing bi-allelic variants in CCDC39 and CCDC40 (which encode a molecular ruler complex maintaining 96 nm axonemal repeat units) cause conspicuous absence of IDA heavy chains DNAH1, DNAH6, and DNAH7 in respiratory ciliary axonemes, as shown by immunofluorescence. This places DNAH7-containing IDAs downstream of the CCDC39/CCDC40 ruler complex in ciliary axoneme assembly. Next-generation sequencing of 51 PCD patients with CCDC39/CCDC40 variants; immunofluorescence analysis of respiratory cilia Cells Medium 39056782
2019 In a PCD patient (Patient-2) with Kartagener syndrome showing absence of both dynein arms, two novel missense variants in DNAH7 were identified alongside disease-causing variants in DNAH5. Functional data showed reduced DNAH7 gene expression and protein mislocalization in Patient-2 cells, suggesting DNAH7 variants may modulate the PCD phenotype in combination with DNAH5 mutations. Whole-exome sequencing; transmission electron microscopy; RT-PCR; immunofluorescence for protein localization Cells Low 31443223
2020 TBC1D21 physically co-localizes with DNAH7 (an inner arm axoneme component) in mouse sperm in vivo, and in Tbc1d21-deficient sperm, DNAH7 detaches and disperses outside the axoneme instead of aligning with it, linking TBC1D21 to the correct assembly/retention of DNAH7 in the sperm axoneme. Co-immunofluorescence localization in mouse sperm; Tbc1d21 knockout mouse model; proteomic analysis of TBC1D21 interactors PLoS genetics Medium 32976492
2025 Biallelic loss-of-function variants in DNAH7 in two infertile men caused asthenozoospermia with severe IDA loss in sperm flagella. Immunofluorescence showed markedly reduced DNAH7 and other IDA-associated proteins (DNAH3, DNAH6) in patient spermatozoa, while ODA-associated proteins (DNAH8, DNAH11, DNAH17, DNAI1) were unaffected, confirming DNAH7 is specifically required for IDA assembly in human sperm flagella. Whole-exome sequencing; transmission electron microscopy; immunofluorescence of patient spermatozoa Human genetics Medium 40810911
2025 IQUB deficiency caused significant downregulation of DNAH7 (and DNAH12) in sperm flagella alongside radial spoke 1 (RS1) deficiency, establishing that DNAH7-containing IDAs are in close proximity to RS1 and their assembly or stability is dependent on intact RS1 structure. Whole-exome sequencing; protein mass spectrometry; western blotting; immunofluorescence in patient and Iqub-/- mouse sperm Cell communication and signaling Low 39849482

Source papers

Stage 0 corpus · 30 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 74 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 53 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 44 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
2024 Whole exome sequencing analysis of 167 men with primary infertility. BMC medical genomics 17 39267058
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 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 9 39056782
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
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 7 38046281
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 6 39849482
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
2025 A cross-tissue transcriptome-wide association study reveals novel susceptibility genes for erectile dysfunction. Andrology 3 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) 3 40412113
2023 Whole exome sequencing study identifies candidate loss of function variants and locus heterogeneity in familial cholesteatoma. PloS one 3 36920900
2025 Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans. Human genetics 2 40810911
2024 Novel bioinformatic approaches show the role of driver genes in the progression of cervical cancer: An in-silico study. Heliyon 2 39634417
2025 Identifying potential genetic biomarkers for sperm dysfunction through whole-genome sequencing. Scientific reports 1 41115892
2026 Protective Effects of Metformin and Vitamin C on Diabetes-Induced Testicular Dysfunction. Reproduction (Cambridge, England) 0 42172611
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
2023 COVID-19 progression towards ARDS: a genome wide study reveals host factors underlying critical COVID-19. Genomics & informatics 0 37415451

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