Affinage

CFAP418

Cilia- and flagella-associated protein 418 · UniProt Q96NL8

Length
207 aa
Mass
23.4 kDa
Annotated
2026-06-09
5 papers in source corpus 2 papers cited in narrative 2 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CFAP418 is a cilia-associated protein required for normal ciliary transport and photoreceptor membrane homeostasis, and its disruption underlies retinal degeneration and Bardet-Biedl syndrome-related ciliopathy phenotypes (PMID:27008867). Rather than acting as a stable subunit of a protein complex, CFAP418 binds membrane lipids—specifically phosphatidic acid and the mitochondrion-specific lipid cardiolipin—and its loss perturbs membrane lipid homeostasis and membrane-protein associations (PMID:37971880). Through this lipid-binding activity, CFAP418 supports membrane-remodeling processes across vesicular trafficking pathways, notably ESCRT, maintains mitochondrial integrity, and restrains activity of the phosphatidic acid-binding kinase protein kinase Cα in the retina (PMID:37971880). In vivo, CFAP418 is required for retrograde ciliary transport, consistent with its role as a functional ciliopathy gene (PMID:27008867).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2016 Medium

    Established CFAP418 as a bona fide ciliopathy gene by showing its loss disrupts ciliary function in vivo, addressing whether the gene has a causal cellular role rather than mere disease association.

    Evidence Zebrafish knockdown with rescue and human missense over-expression, scored by visual behavior, Kupffer's vesicle formation, and retrograde transport assays

    PMID:27008867

    Open questions at the time
    • did not define the molecular activity of CFAP418
    • mechanism linking the protein to retrograde transport unresolved
    • knockdown approach not confirmed with a genetic null
  2. 2024 High

    Defined CFAP418's biochemical activity as lipid binding rather than stable protein-complex assembly, explaining how its loss propagates into membrane, vesicular, and mitochondrial defects in photoreceptors.

    Evidence AP-MS, quantitative lipidomics, proteomics, phosphoproteomics, and a Cfap418 knockout mouse

    PMID:37971880

    Open questions at the time
    • structural basis of phosphatidic acid and cardiolipin binding not resolved
    • direct mechanistic link between lipid binding and retrograde transport defect not established
    • whether PKCα activation is a direct or downstream consequence not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CFAP418 lipid binding mechanistically couples to ciliary retrograde transport and ESCRT-mediated membrane remodeling remains unresolved.
  • no structural model of the lipid-binding interface
  • molecular link between membrane lipid homeostasis and transport machinery undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 1
Localization
GO:0005739 mitochondrion 1 GO:0005929 cilium 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 1

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 Knockdown of c8orf37 (CFAP418) in zebrafish resulted in impaired visual behavior and BBS-related phenotypes including defects in Kupffer's vesicle formation and delays in retrograde transport; rescue experiments confirmed specificity, and over-expression of human missense mutations also produced these phenotypes, establishing CFAP418 as a functional ciliopathy gene required for retrograde transport. Zebrafish gene knockdown, rescue experiments, over-expression of human missense mutations, visual behavior assay Human molecular genetics Medium 27008867
2024 CFAP418 protein binds to phosphatidic acid (PA) and mitochondrion-specific cardiolipin but does not form a tight static complex with proteins; loss of Cfap418 in mice disrupts membrane lipid homeostasis and membrane-protein associations, causes mitochondrial defects and membrane-remodeling abnormalities across vesicular trafficking pathways (especially ESCRT) in photoreceptors, and increases activity of PA-binding protein kinase Cα in the retina. Affinity purification coupled with mass spectrometry, quantitative lipidomics, proteomics, phosphoproteomics, Cfap418 knockout mouse model JCI insight High 37971880

Source papers

Stage 0 corpus · 5 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Mutations in C8ORF37 cause Bardet Biedl syndrome (BBS21). Human molecular genetics 85 27008867
2017 Homozygous mutation in CEP19, a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly. Journal of medical genetics 25 29127258
2024 Disruption of CFAP418 interaction with lipids causes widespread abnormal membrane-associated cellular processes in retinal degenerations. JCI insight 3 37971880
2025 Inherited Retinal Diseases with High Myopia: A Review. Genes 2 41153400
2025 Identifying genetic determinants of outer retinal function in mice using a large-scale gene-targeted screen. PLoS genetics 0 41021661

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