Affinage

CFAP70

Cilia- and flagella-associated protein 70 · UniProt Q5T0N1

Length
1121 aa
Mass
125.7 kDa
Annotated
2026-04-28
16 papers in source corpus 7 papers cited in narrative 7 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CFAP70 is a conserved TPR-repeat-containing axonemal protein that functions in motile cilia and flagella by regulating outer dynein arm (ODA) activity and contributing to the structural integrity of the central apparatus C2a projection. Its N-terminus localizes to the base of the ODA, where it interacts with DNAI1 and DNAI2, and it forms a complex with CFAP65 and MYCBPAP that defines the C2a projection of the central pair (PMID:30158508, PMID:33988244, PMID:37458246). During spermiogenesis, CFAP70 assists cytoplasmic preassembly of the calmodulin- and radial spoke-associated complex (CSC), regulates manchette-dependent transport of axonemal proteins, and is required for normal flagellum biogenesis; its loss causes multiple morphological abnormalities of the flagella (MMAF) and male infertility in both mice and humans (PMID:37352829, PMID:31621862).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2018 High

    Establishing that CFAP70 is an axonemal protein anchored at the ODA base that regulates ciliary beat frequency resolved its molecular localization and first functional role in motility.

    Evidence Stepwise axonemal extraction, fluorescence mapping of truncations in mouse ependymal cells, siRNA knockdown with beat frequency measurement, Chlamydomonas fap70 mutant analysis, and cryo-electron tomography

    PMID:30158508

    Open questions at the time
    • Precise binding partners at the ODA base not identified
    • Whether CFAP70 also contributes to central apparatus function was unknown
    • Role in mammalian spermatogenesis not tested
  2. 2019 Medium

    Demonstrating that loss-of-function mutations in CFAP70 eliminate ODA and central pair markers in human sperm linked the gene to human male infertility and suggested a broader role beyond ODA regulation.

    Evidence Whole-exome sequencing and immunofluorescence on patient sperm cells

    PMID:31621862

    Open questions at the time
    • Based on single patient cohort without animal model confirmation
    • Functional relationship between CFAP70 and WDR66 inferred only from co-absence of staining
    • Mechanism of central pair defect not resolved
  3. 2021 High

    Placing FAP70/CFAP70 exclusively in the central apparatus C2a projection and identifying CFAP65 and MYCBPAP as co-complex partners redefined CFAP70's structural role beyond the ODA.

    Evidence Super-resolution SIM, cryo-EM of fap70-1 mutant axonemes, mass spectrometry, and co-immunoprecipitation with HA-tagged FAP70 in Chlamydomonas

    PMID:33988244

    Open questions at the time
    • Apparent discrepancy with 2018 ODA localization not fully reconciled across species
    • Whether CFAP70 has dual localization (ODA and C2a) in mammalian cilia remains unresolved
    • Functional consequence of C2a loss on motility pattern not fully characterized
  4. 2023 High

    Cfap70-knockout mice established that CFAP70 is essential for spermiogenesis by interacting with ODA components DNAI1/DNAI2, assisting CSC preassembly, and controlling manchette-dependent transport of axonemal proteins, providing a comprehensive mechanism for MMAF pathogenesis.

    Evidence CRISPR/Cas9 KO and TPR-truncation mouse models, co-immunoprecipitation of CFAP70 with DNAI1 and DNAI2, TEM, immunofluorescence, and human variant validation

    PMID:37352829 PMID:37458246

    Open questions at the time
    • How CFAP70 regulates QRICH2 expression is mechanistically undefined
    • Whether CFAP70's CSC preassembly function operates through direct protein-protein contacts or scaffolding is unresolved
    • Relative contribution of ODA versus C2a functions to the MMAF phenotype not dissected
  5. 2024 Medium

    Independent interactome studies in transgenic mice confirmed the CFAP70–CFAP65–MYCBPAP complex as a conserved mammalian C2a projection unit and extended it to centrosome-associated functions via CCP110.

    Evidence Endogenous IP-MS from MYCBPAP-tagged and Mycbpap-KO mouse testes, performed by two independent groups

    PMID:39092789 PMID:39704931

    Open questions at the time
    • Functional significance of MYCBPAP–CCP110 association for CFAP70 biology is untested
    • Stoichiometry and direct versus indirect nature of CFAP70 within the mammalian C2a complex not defined
    • Whether the complex has roles outside motile cilia/flagella is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CFAP70 occupies potentially dual localizations (ODA base and C2a projection) in mammalian systems, whether these represent distinct functional pools, and the structural basis of TPR-domain-mediated interactions remain open questions.
  • No high-resolution mammalian structure of CFAP70 in situ
  • Dual localization hypothesis not tested with endogenous tagging in mammalian cilia
  • Upstream signals controlling CFAP70 recruitment to the axoneme are unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3
Localization
GO:0005929 cilium 5 GO:0005856 cytoskeleton 2 GO:0005829 cytosol 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-1474165 Reproduction 2
Partners
CCP110CFAP65DNAI1DNAI2MYCBPAP
Complex memberships
C2a projection complex (CFAP70–CFAP65–MYCBPAP)

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 CFAP70 is an axoneme-binding protein that localizes at the base of the outer dynein arm (ODA) via its N-terminus, and knockdown of CFAP70 in cultured mouse ependyma reduces cilia beating frequency; in Chlamydomonas, the FAP70 ortholog mutant shows defects in ODA activity and reduced flagellar motility, with cryo-electron tomography placing the N-terminus stably at the base of the ODA. Stepwise axonemal protein extraction, fluorescence microscopy of CFAP70 fragments in ependymal cells, siRNA knockdown with cilia beat frequency measurement, Chlamydomonas genetics, cryo-electron tomography Cells High 30158508
2021 In Chlamydomonas, FAP70 (CFAP70 ortholog) is exclusively located in the central apparatus (CA), specifically at the base of the C2a projection; fap70-1 mutant axonemes lack most of the C2a projection and also lose FAP65 (CFAP65) and FAP147 (MYCBPAP); FAP65 and FAP147 co-immunoprecipitate with HA-tagged FAP70, identifying these three proteins as the first defining components of the C2a projection. Super-resolution structured illumination microscopy, cryo-electron microscopy, mass spectrometry of fap70-1 mutant axonemes, co-immunoprecipitation with HA-tagged FAP70 Journal of cell science High 33988244
2019 Loss-of-function mutations in CFAP70 cause absence of ODA markers and central pair complex markers in sperm flagella; immunofluorescence showed absence of CFAP70 protein in flagella of patient carrying splice variant; absence of CFAP70 staining was also seen in sperm from WDR66-mutant patients, suggesting a functional interaction between CFAP70 and WDR66 in axonemal assembly. Whole-exome sequencing, immunofluorescence on patient sperm cells Human reproduction (Oxford, England) Medium 31621862
2023 CFAP70 interacts with outer dynein arm proteins DNAI1 and DNAI2 (shown by co-immunoprecipitation); Cfap70-deficient mice generated by CRISPR/Cas9 show MMAF and spermiogenesis defects including club-shaped sperm heads, abnormal manchette disassembly, and reduced AKAP3 levels in sperm flagella, indicating CFAP70 participates in flagellum assembly and transport of flagellar components. CRISPR/Cas9 knockout mouse generation, co-immunoprecipitation (CFAP70 with DNAI1 and DNAI2), immunofluorescence, western blot Biology of reproduction High 37458246
2023 Cfap70-KO mice are sterile due to oligo-astheno-teratozoospermia; CFAP70 is required for spermatid flagella biogenesis partially by regulating expression of QRICH2, assisting cytoplasmic preassembly of the calmodulin- and radial spoke-associated complex (CSC), and controlling manchette localization of axoneme-related proteins; truncation of the TPR domain region (repeats 5–8) recapitulates the patient phenotype. Cfap70-KO mouse (CRISPR), Cfap70-truncated mouse model, whole-exome sequencing of patient, Sanger sequencing, immunofluorescence, western blot, transmission electron microscopy EBioMedicine High 37352829
2024 MYCBPAP interactome analysis in transgenic mice reveals that MYCBPAP physically associates with CFAP70 and CFAP65 as part of the C2a projection of the central apparatus, and also associates with centrosome-associated protein CCP110; this places CFAP70 in a complex that regulates centrosome-nuclear envelope docking and sperm tail biogenesis. Endogenous immunoprecipitation combined with mass spectrometry using MYCBPAP-tagged transgenic mice Journal of cell science Medium 39092789
2024 MYCBPAP co-immunoprecipitates with CFAP70 and CFAP65 (central apparatus proteins) by endogenous IP with mass spectrometry in mouse testes, confirming CFAP70 as part of the C2a projection complex in the sperm flagellar axoneme. Endogenous immunoprecipitation combined with mass spectrometry in Mycbpap-/- and control mouse testes Science China. Life sciences Medium 39704931

Source papers

Stage 0 corpus · 16 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 CFAP70 mutations lead to male infertility due to severe astheno-teratozoospermia. A case report. Human reproduction (Oxford, England) 49 31621862
2022 Identifying pleiotropic variants and candidate genes for fertility and reproduction traits in Holstein cattle via association studies based on imputed whole-genome sequence genotypes. BMC genomics 47 35484513
2018 CFAP70 Is a Novel Axoneme-Binding Protein That Localizes at the Base of the Outer Dynein Arm and Regulates Ciliary Motility. Cells 37 30158508
2023 CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile men. EBioMedicine 22 37352829
2020 Absence of murine CFAP61 causes male infertility due to multiple morphological abnormalities of the flagella. Science bulletin 22 36659204
2021 Chlamydomonas FAP70 is a component of the previously uncharacterized ciliary central apparatus projection C2a. Journal of cell science 18 33988244
2021 Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families. Asian journal of andrology 14 34100391
2016 The transcription factor, Nuclear factor, erythroid 2 (Nfe2), is a regulator of the oxidative stress response during Danio rerio development. Aquatic toxicology (Amsterdam, Netherlands) 14 27716579
2023 Experimental and molecular support for Cfap70 as a causative gene of 'multiple morphological abnormalities of the flagella' with male infertility†. Biology of reproduction 11 37458246
2024 Cilia Plays a Pivotal Role in the Hypersecretion of Airway Mucus in Mice. Current molecular pharmacology 5 40231527
2024 Integrated miRNA and mRNA Sequencing Reveals the Sterility Mechanism in Hybrid Yellow Catfish Resulting from Pelteobagrus fulvidraco (♀) × Pelteobagrus vachelli (♂). Animals : an open access journal from MDPI 3 38891632
2024 MYCBPAP is a central apparatus protein required for centrosome-nuclear envelope docking and sperm tail biogenesis in mice. Journal of cell science 3 39092789
2024 Comprehensive analysis of chromosomal breakpoints and candidate genes associated with male infertility: insights from cytogenetic studies and expression analyses. Mammalian genome : official journal of the International Mammalian Genome Society 3 39358566
2024 Homozygous deleterious variants in MYCBPAP induce asthenoteratozoospermia involving abnormal acrosome biogenesis, manchette structure and sperm tail assembly in humans and mice. Science China. Life sciences 2 39704931
2025 The essential role of cytoskeleton and ciliary abnormalities in the development of congenital pulmonary airway malformations. Pediatric surgery international 0 41264116
2025 Potential Therapeutic Targets for Neuroblastoma Screened through Mendelian Randomization Analysis. Archives of Iranian medicine 0 41778435