CSTB Gene: Cystatin B Function, Mutations, and Associated Diseases

The CSTB gene encodes cystatin B, a small cysteine protease inhibitor belonging to the cystatin superfamily. It protects cells from inappropriate proteolysis by inhibiting cathepsins L, H, and B. Loss-of-function mutations in CSTB cause progressive myoclonus epilepsy type 1 (EPM1, Unverricht-Lundborg disease), a neurodegenerative disorder characterized by myoclonus, seizures, and ataxia. The gene is widely expressed, with highest levels in the brain, and its promoter contains a dodecamer repeat expansion that is the most common pathogenic mutation.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Lysosome (Reactome: R-HSA-392499)

• Cysteine protease inhibition (UniProt)

• Apoptosis modulation (KEGG: hsa04210)

Cystatin B is a 98-amino-acid, 11-kDa intracellular cysteine protease inhibitor. It forms a tight-binding reversible inhibitor of cathepsins L, H, and B, protecting cells from uncontrolled proteolysis. The protein is localized in the cytosol, nucleus, and lysosomes, and is highly expressed in neurons and glia. Loss of cystatin B leads to increased cathepsin activity, mitochondrial dysfunction, and neuronal death, particularly in the cerebellum and cortex, underlying the pathogenesis of progressive myoclonus epilepsy type 1.