FBXO22 Gene – F-Box Protein 22: Function, Mutations, and Disease Associations

FBXO22 (F-box protein 22) encodes a member of the F-box protein family, characterized by an F-box domain. FBXO22 functions as the substrate-recognition component of the SCF (SKP1-CUL1-F-box) ubiquitin ligase complex, targeting specific proteins for ubiquitination and subsequent proteasomal degradation. It plays critical roles in cell cycle progression, apoptosis, DNA damage response, and epigenetic regulation through the degradation of substrates such as KDM4A and KDM4B. FBXO22 is implicated in multiple cancers, including breast, lung, and colorectal cancer, where it can act as either a tumor suppressor or oncogene depending on cellular context.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• SCF ubiquitin ligase complex pathway

• Ubiquitin-proteasome pathway

• Cell cycle – G1/S transition

• DNA damage response

• Histone methylation regulation (KDM4A/KDM4B degradation)

FBXO22 is a 42 kDa F-box protein that localizes to the nucleus and cytoplasm. It contains an N-terminal F-box domain (residues 30–75) that mediates binding to SKP1, and C-terminal leucine-rich repeats (LRRs) that recognize specific substrates. Through the SCF complex, FBXO22 ubiquitinates histone demethylases KDM4A and KDM4B, thereby regulating chromatin state and gene expression. It also targets other substrates involved in cell cycle and DNA repair. Dysregulation of FBXO22 expression or function contributes to tumorigenesis and chemoresistance.