CCNF
Chr 16ADcyclin F
Also known as: FBX1, FBXO1, FTDALS5
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.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is gain-of-function.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CCNF · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools