FBXO11 Gene - F-box Protein 11: Function, Mutations, and Disease Associations

FBXO11 (F-box protein 11) encodes a member of the F-box protein family, which functions as the substrate-recognition component of the SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complex. The protein mediates ubiquitination and subsequent proteasomal degradation of target proteins, including p53, BCL6, and CDT2. FBXO11 also possesses methyltransferase activity (PRMT9) and is involved in alternative splicing regulation. Loss-of-function mutations are associated with intellectual disability, developmental delay, and various cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (Reactome R-HSA-983168)

• p53 pathway (KEGG hsa04115)

• Ubiquitin mediated proteolysis (KEGG hsa04120)

• BCL6 degradation pathway (Reactome R-HSA-8941855)

FBXO11 is a 928-amino acid protein containing an N-terminal F-box domain (required for SKP1 interaction), a zinc finger domain, and a C-terminal substrate-binding region. It functions as the substrate recognition subunit of the SCF E3 ubiquitin ligase complex, targeting proteins such as p53, BCL6, and CDT2 for ubiquitination and degradation. Additionally, FBXO11 has been reported to act as a protein arginine methyltransferase (PRMT9), methylating splicing factors. The protein is predominantly nuclear and is widely expressed, with highest levels in testis and brain. Structural alterations in the F-box or substrate-binding domains impair its tumor suppressor activity.