Affinage

CFAP46

Cilia- and flagella-associated protein 46 · UniProt Q8IYW2

Length
2715 aa
Mass
303.5 kDa
Annotated
2026-06-09
10 papers in source corpus 2 papers cited in narrative 2 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 2/2 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CFAP46 encodes a component of the C1d projection of the ciliary central apparatus, and its loss disrupts effective ciliary clearance (PMID:39362668). In affected individuals, pathogenic CFAP46 variants cause primary ciliary dyskinesia in which mucociliary transport is defective in vitro despite normal nasal nitric oxide, normal ciliary ultrastructure by TEM, and a normal ciliary beating pattern by high-speed videomicroscopy, indicating a functional defect in central-apparatus output rather than a gross structural or motility lesion (PMID:39362668). Beyond its assignment to the C1d projection and its co-evolutionary linkage with the other C1d component WDR93 (PMID:39362668, PMID:37621660), no further molecular or biochemical detail of CFAP46 has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2023 Low

    Whether CFAP46 belongs to a specific central-apparatus substructure was unknown; coordinate evolutionary loss with a known C1d component placed it within the C1d projection.

    Evidence comparative genomics across ~500 vertebrate genomes plus transcript analysis showing concurrent loss of CFAP46 and WDR93 in independent bird lineages

    PMID:37621660

    Open questions at the time
    • Inference is evolutionary/correlative with no direct biochemical or cell-biological assay of CFAP46 protein
    • Physical interaction between CFAP46 and WDR93 not demonstrated
    • Subcellular localization of the CFAP46 protein not shown directly
  2. 2024 Medium

    Whether CFAP46 loss causes human ciliary disease was unknown; identifying pathogenic variants in PCD patients tied CFAP46 to a defective C1d projection and impaired ciliary clearance.

    Evidence high-throughput sequencing of C1d genes plus in vitro ciliary transport assays, TEM, and high-speed videomicroscopy in affected individuals

    PMID:39362668

    Open questions at the time
    • Mechanism by which CFAP46 supports the C1d projection at the protein level is undefined
    • Normal beating and ultrastructure leave the link between C1d defect and impaired transport mechanistically unexplained
    • No reconstitution or structural characterization of CFAP46 within the central apparatus

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CFAP46 assembles into the C1d projection, what proteins it directly binds, and how its loss translates into defective ciliary transport remain unresolved.
  • No direct interaction partners biochemically defined
  • No structural model of CFAP46 in the central apparatus
  • Mechanistic coupling between C1d integrity and mucociliary clearance unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005929 cilium 2
Partners
WDR93
Complex memberships
ciliary central apparatus C1d projection

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2024 Pathogenic variants in CFAP46 cause primary ciliary dyskinesia (PCD) characterized by a defective C1d projection of the ciliary central apparatus, leading to insufficient ciliary clearance as demonstrated by in vitro ciliary transport assays, despite normal nasal nitric oxide levels, normal ciliary ultrastructure by TEM, and normal ciliary beating by high-speed videomicroscopy. High-throughput sequencing of C1d component genes, in vitro ciliary transport assays, transmission electron microscopy, high-speed videomicroscopy analysis The European respiratory journal Medium 39362668
2023 CFAP46 encodes a component of the ciliary central apparatus C1d projection, as evidenced by its concurrent loss alongside WDR93 (another C1d component) in phylogenetically independent bird lineages through large segmental deletions, and confirmed by absence of transcripts in species with gene-disrupting changes. Comparative genomic analysis of ~500 vertebrate genomes, transcript expression analysis in species with and without intact CFAP46 gene Royal Society open science Low 37621660

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 The DNA methylome in panic disorder: a case-control and longitudinal psychotherapy-epigenetic study. Translational psychiatry 35 31754096
2021 Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects. Journal of medical genetics 25 34215651
2019 Exome sequencing of cases with neural tube defects identifies candidate genes involved in one-carbon/vitamin B12 metabolisms and Sonic Hedgehog pathway. Human genetics 18 31139930
2024 Pathogenic variants in CFAP46, CFAP54, CFAP74 and CFAP221 cause primary ciliary dyskinesia with a defective C1d projection of the central apparatus. The European respiratory journal 15 39362668
2023 Concurrent loss of ciliary genes WDR93 and CFAP46 in phylogenetically distant birds. Royal Society open science 7 37621660
2022 Newborn DNA methylation and asthma acquisition across adolescence and early adulthood. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 6 34995380
2019 Detection of Novel Fusion Transcript VTI1A-CFAP46 in Hepatocellular Carcinoma. Gastrointestinal tumors 4 31602373
2024 Effect of body mass index on semen quality, sperm chromatin integrity and sperm DNA methylation. Obesity research & clinical practice 2 39358131
2026 The Molecular Landscape of CASTLE: A Rare Thymus-like Head and Neck Cancer. International journal of molecular sciences 0 42074143
2025 Genetic characteristics of primary bone marrow large B-cell lymphoma. Pathology, research and practice 0 40774060

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