FBXO31 Gene – F-box Protein 31: Function, Mutations, and Disease Associations

FBXO31 (F-box protein 31) is a member of the F-box protein family, characterized by an F-box domain that mediates protein-protein interactions in SCF (SKP1-CUL1-F-box) ubiquitin ligase complexes. FBXO31 functions as the substrate-recognition component, targeting specific proteins for ubiquitination and subsequent proteasomal degradation. It plays critical roles in cell cycle regulation, particularly in G1 phase arrest following DNA damage, by promoting the degradation of cyclin D1. FBXO31 also participates in DNA repair pathways and has been implicated as a tumor suppressor in several cancers, including breast, liver, and gastric cancers. Germline mutations in FBXO31 are associated with autosomal recessive intellectual disability and microcephaly.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• SCF ubiquitin ligase complex pathway (Reactome: R-HSA-8951664)

• G1/S transition (Reactome: R-HSA-69206)

• p53-independent DNA damage response (PMID: 19287373)

FBXO31 encodes a 538-amino acid protein containing an N-terminal F-box domain (residues 36–79) and a C-terminal substrate-binding region. It assembles with SKP1, CUL1, and RBX1 to form the SCF(FBXO31) E3 ubiquitin ligase complex. The protein is predominantly cytoplasmic but can translocate to the nucleus upon DNA damage. Key substrates include cyclin D1 (for G1 arrest) and Snail (for EMT suppression). FBXO31 is widely expressed, with highest levels in testis and brain. Post-translational modifications include phosphorylation, which may regulate its stability and activity.