FBXO40 Gene – F-box Protein 40 | Function, Expression & Disease

FBXO40 encodes a member of the F-box protein family, characterized by an F-box domain. F-box proteins are components of the SCF (SKP1-CUL1-F-box) ubiquitin ligase complex, which targets proteins for ubiquitination and subsequent proteasomal degradation. FBXO40 is specifically expressed in skeletal muscle and plays a critical role in sarcomere assembly and muscle growth. It interacts with the sarcomeric protein α-actinin-2 and is involved in the ubiquitination of myosin heavy chain, thereby regulating muscle fiber size and contractile function.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

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

• Ubiquitin-mediated proteolysis (KEGG: hsa04120)

• Muscle contraction and sarcomere assembly (Reactome: R-HSA-397014)

FBXO40 is a 574-amino acid protein containing an N-terminal F-box domain (residues 30–75) and a C-terminal domain that mediates substrate recognition. It is a core component of the SCF ubiquitin ligase complex, where it recruits specific substrates for ubiquitination. In skeletal muscle, FBXO40 targets myosin heavy chain and other sarcomeric proteins for degradation, thereby regulating muscle fiber size and contractile protein turnover. The protein is predominantly localized to the sarcomere and interacts with α-actinin-2.