Affinage

CFAP20

Cilia- and flagella-associated protein 20 · UniProt Q9Y6A4

Length
193 aa
Mass
22.8 kDa
Annotated
2026-06-09
9 papers in source corpus 6 papers cited in narrative 6 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

CFAP20 is a conserved inner junction protein that maintains the structural integrity of the ciliary axoneme by connecting the A and B microtubule doublets (PMID:36329026, PMID:37463209). In C. elegans sensory cilia it is restricted to the middle segment where doublets are present, and its loss disconnects the A and B tubules, defining its role in axoneme differentiation (PMID:37463209); loss-of-function disrupts motile cilia in zebrafish and inner junction architecture in non-motile cilia, linking it to sensory-dependent signalling and development (PMID:36329026). Consistent with a direct role in doublet assembly, co-expression of CFAP20 with CFAP53 is sufficient to drive ectopic microtubule doublet-like structures in HeLa cytoplasm [PMID:bio_10.1101_2025.08.03.668368]. Beyond its structural role, CFAP20 physically interacts with BROMI/TBC1D32 within the CCRK-BROMI-FAM149B1 axis that controls intraflagellar transport turnaround at the ciliary tip; BROMI mutants unable to bind CFAP20 fail to rescue ciliary length and tip IFT-accumulation defects (PMID:35609210). Independently of its ciliary functions, CFAP20 safeguards genome stability in the nucleus by salvaging promoter-proximally arrested RNA Polymerase II to prevent collisions with co-directional replisomes; its loss causes promoter-proximal R-loop accumulation and altered replication dynamics that are rescued by Mediator co-depletion or removal of R-loop-engaged RNAPII (PMID:41535461). A genome-wide screen additionally identified CFAP20 as a repressor of beige adipocyte differentiation (PMID:40176372).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2022 High

    Established that CFAP20 is broadly required for ciliary function and inner junction integrity across motile and non-motile cilia, defining it as a core ciliary structural protein.

    Evidence Loss-of-function in zebrafish and C. elegans with ultrastructural and behavioral readouts

    PMID:36329026

    Open questions at the time
    • Molecular interactions at the inner junction not resolved
    • Did not pinpoint which microtubule contacts CFAP20 mediates
    • No structural model of CFAP20 within the axoneme
  2. 2022 Medium

    Connected CFAP20 to IFT turnaround regulation by showing direct interaction with BROMI/TBC1D32 in the CCRK-BROMI axis, extending its role beyond static structure to dynamic ciliary transport.

    Evidence Co-immunoprecipitation and BROMI binding-defective mutant rescue in BROMI-KO cells with ciliary length/IFT-accumulation phenotyping

    PMID:35609210

    Open questions at the time
    • Single lab, reciprocal interaction shown only by Co-IP
    • Whether CFAP20's IFT role is separable from its inner junction role unclear
    • Direct binding interface not mapped
  3. 2023 High

    Localized CFAP20 to the doublet-containing middle segment and demonstrated that its loss disconnects A and B tubules, establishing it as the determinant of the A-B inner junction.

    Evidence Genetic deletion in C. elegans with fluorescence localization, electron microscopy, and IFT/sensory assays

    PMID:37463209

    Open questions at the time
    • Atomic-level mechanism of A-B tubule bridging not defined
    • Whether human CFAP20 behaves identically not directly tested here
  4. 2025 Medium

    Showed CFAP20 is sufficient, with CFAP53, to nucleate microtubule doublet-like structures ectopically, indicating an active role in B-tubule/inner junction formation rather than passive structural occupancy.

    Evidence Co-expression of CFAP53 and CFAP20 in HeLa cells with fluorescence and ultrastructural analysis (preprint)

    PMID:bio_10.1101_2025.08.03.668368

    Open questions at the time
    • Preprint, single lab, no CFAP20-specific mutagenesis to test sufficiency
    • Whether ectopic structures recapitulate native inner junction geometry unclear
  5. 2025 Medium

    Identified an unexpected non-ciliary role: CFAP20 represses beige adipocyte differentiation, broadening its physiological footprint.

    Evidence Genome-wide CRISPR knockout screen in mouse white adipose progenitors with individual KO validation in vitro and in vivo

    PMID:40176372

    Open questions at the time
    • No molecular mechanism for how CFAP20 represses beiging
    • Relationship to its ciliary or nuclear functions unknown
  6. 2026 High

    Revealed a distinct nuclear function in genome stability, showing CFAP20 rescues promoter-proximally arrested RNAPII to prevent R-loop-mediated transcription-replication collisions.

    Evidence RNAPII ChIP-seq, R-loop mapping, replication timing/fork assays, and Mediator co-depletion epistasis in CFAP20-deficient cells

    PMID:41535461

    Open questions at the time
    • How a ciliary inner junction protein is targeted to promoters not established
    • Direct biochemical substrate/binding partner at RNAPII not defined
    • Connection between ciliary and nuclear roles unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CFAP20's structural ciliary role, its IFT-turnaround interactions, and its nuclear genome-stability function are mechanistically and spatially partitioned within the same protein remains unknown.
  • No structural basis for either inner junction bridging or RNAPII salvage
  • No domain mapping separating the two functions
  • Regulation of subcellular partitioning uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005856 cytoskeleton 2 GO:0005929 cilium 2 GO:0005634 nucleus 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-73894 DNA Repair 1
Partners
BROMICFAP53TBC1D32
Complex memberships
CCRK-BROMI-FAM149B1 IFT turnaround complexciliary axoneme inner junction

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 CFAP20 is required for motile cilia function in zebrafish and maintains the structural integrity of non-motile cilia inner junctions in C. elegans, influencing sensory-dependent signalling and development. It functions within a structural/functional hub centered on the inner junction shared between motile and non-motile cilia. Loss-of-function in zebrafish (cfap20 morphants/mutants) and C. elegans (CFAP-20 deletion), ultrastructural analysis of cilia, behavioral/signaling assays Nature communications High 36329026
2023 In C. elegans, CFAP-20 is restricted to the middle segment of sensory cilia (where microtubule doublets are present), and its loss disconnects A and B tubules, demonstrating that CFAP-20 is required for maintaining the A-B tubule inner junction that defines axoneme differentiation. Genetic deletion of CFAP-20 in C. elegans, fluorescence localization, electron microscopy of axonemal ultrastructure, intraflagellar transport and sensory function assays Proceedings of the National Academy of Sciences of the United States of America High 37463209
2022 CFAP20 physically interacts with BROMI/TBC1D32, a component of the IFT turnaround complex. BROMI mutants defective in binding to CFAP20 (and CCRK) fail to rescue ciliary defects (abnormally long cilia, IFT/ICK accumulation at the ciliary tip) in BROMI-KO cells, placing CFAP20 in the CCRK–BROMI–FAM149B1 axis that regulates IFT turnaround under ICK control. Co-immunoprecipitation (BROMI–CFAP20 interaction), BROMI binding-defective mutant rescue assay in BROMI-KO cells, ciliary length and IFT-accumulation phenotyping Molecular biology of the cell Medium 35609210
2026 CFAP20 safeguards genome stability by salvaging arrested RNA Polymerase II (RNAPII) in promoter-proximal regions, preventing collisions with co-directional replisomes. CFAP20-deficient cells accumulate R-loops near promoters, exhibit defects in replication timing and dynamics (accelerated fork speeds, reduced origin activity), and these defects are rescued by co-depletion of the Mediator complex or removal of R-loop-engaged RNAPII. Genome-wide approaches (RNAPII ChIP-seq, R-loop mapping), genetic screens, replication timing/fork speed assays in CFAP20-deficient cells, epistasis via Mediator co-depletion Nature High 41535461
2025 Co-expression of CFAP53 and CFAP20 (an inner junction protein) in HeLa cells induced ectopic microtubule doublet (MTD)-like structures in the cytoplasm, demonstrating that CFAP20 participates in B-tubule assembly/inner junction formation and is sufficient, together with FAP53, to drive ectopic MTD formation outside the normal ciliary context. Co-expression of CFAP53 and CFAP20 in HeLa cells, fluorescence microscopy and ultrastructural analysis of ectopic MTD-like structures bioRxivpreprint Medium bio_10.1101_2025.08.03.668368
2025 Knockout of CFAP20 individually in white adipose progenitors promoted beige adipocyte differentiation in vitro and white adipose tissue beiging in vivo, identifying CFAP20 as a lineage repressor of beige adipocyte formation. Genome-wide CRISPR knockout screen in mouse white adipose progenitors; individual CFAP20 KO with in vitro differentiation and in vivo beiging readouts Obesity (Silver Spring, Md.) Medium 40176372

Source papers

Stage 0 corpus · 9 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2022 The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision. Nature communications 29 36329026
2022 A comprehensive WGS-based pipeline for the identification of new candidate genes in inherited retinal dystrophies. NPJ genomic medicine 17 35246562
2023 Modulation of inner junction proteins contributes to axoneme differentiation. Proceedings of the National Academy of Sciences of the United States of America 15 37463209
2022 BROMI/TBC1D32 together with CCRK/CDK20 and FAM149B1/JBTS36 contributes to intraflagellar transport turnaround involving ICK/CILK1. Molecular biology of the cell 12 35609210
2005 Specific maternal transcripts in bovine oocytes and cleavaged embryos: identification with novel DDRT-PCR methods. Molecular reproduction and development 11 15803458
2023 Genome-Wide Single-Nucleotide Polymorphism-Based Genomic Diversity and Runs of Homozygosity for Selection Signatures in Equine Breeds. Genes 4 37628674
2026 CFAP20 salvages arrested RNAPII from the path of co-directional replisomes. Nature 2 41535461
2005 Analysis of tumor progression by transcriptional profiling of mouse MK16 cell lines transformed with human papillomavirus type 16 E6 and E7 oncogenes and activated H-ras. Oncology reports 2 16273273
2025 Brd9 antagonism induces beige adipocytes in white adipose tissues and protects against diet-induced obesity. Obesity (Silver Spring, Md.) 1 40176372

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