CCNF

Chr 16

cyclin F

Also known as: FBX1, FBXO1, FTDALS5

NCBI Gene: 899 ENSG00000162063 UniProt: P41002

This protein functions as a substrate recognition component of SCF E3 ubiquitin ligase complexes that target cell cycle regulatory proteins for degradation, including CP110, RRM2, and CDC6. Mutations cause frontotemporal dementia and/or amyotrophic lateral sclerosis 5 with autosomal dominant inheritance. The gene shows significant constraint against loss-of-function variants (LOEUF 0.419), indicating that such variants are likely pathogenic.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the cyclin family. Cyclins are important regulators of cell cycle transitions through their ability to bind and activate cyclin-dependent protein kinases. This member also belongs to the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class and it was one of the first proteins in which the F-box motif was identified. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtFrontotemporal dementia and/or amyotrophic lateral sclerosis 5

Clinical highlights

Gene-disease validity (ClinGen)

frontotemporal dementia and/or amyotrophic lateral sclerosis 5 · ADLimitednot for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.42

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

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