FBXO32 Gene (Atrogin-1) – Function, Mutations, and Disease Associations

FBXO32 (F-box protein 32), also known as Atrogin-1 or MAFbx, encodes a member of the F-box protein family that functions as the substrate-recognition component of the SCF (SKP1-CUL1-F-box) ubiquitin ligase complex. It is highly expressed in skeletal and cardiac muscle and plays a critical role in muscle atrophy by targeting proteins such as MyoD, eIF3-f, and calcineurin for ubiquitin-mediated degradation. FBXO32 is induced during catabolic states (e.g., fasting, denervation, cancer cachexia) and is a key mediator of muscle wasting.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• SCF ubiquitin ligase complex pathway

• FoxO signaling pathway (induction of FBXO32 during atrophy)

• NF-κB signaling pathway (cachexia-induced FBXO32)

• IGF-1/PI3K/Akt pathway (FBXO32 repression by Akt)

• Ubiquitin-proteasome pathway (muscle proteolysis)

FBXO32 (Atrogin-1) is a 355-amino-acid F-box protein that serves as the substrate recognition subunit of the SCF ubiquitin ligase complex. It contains an N-terminal F-box domain (required for SKP1 binding) and a C-terminal substrate-binding domain. The protein is predominantly expressed in skeletal and cardiac muscle and is rapidly induced under catabolic conditions. Its targets include MyoD (myogenic transcription factor), eIF3-f (translation initiation factor), and calcineurin (phosphatase), whose ubiquitination and degradation promote muscle atrophy. FBXO32 is a central node in the signaling pathways that control muscle mass and is a potential therapeutic target for cachexia and sarcopenia.