PRSS16 Gene - Thymus-Specific Serine Protease 16 | Function, Mutations & Disease

PRSS16 encodes a serine protease predominantly expressed in the thymus, where it functions as a key enzyme in the processing of self-antigens for MHC class II presentation. This process is critical for negative selection of autoreactive T cells and establishment of central immune tolerance. The protein is localized to the endosomal/lysosomal compartment of thymic epithelial cells and dendritic cells. Genetic variants in PRSS16 have been associated with susceptibility to autoimmune diseases, particularly type 1 diabetes, and altered expression has been observed in certain cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Antigen processing and presentation (KEGG hsa04612)

• Lysosome (KEGG hsa04142)

• Thymic T cell selection (Reactome R-HSA-202430)

PRSS16 encodes thymus-specific serine protease (TSSP), a 42 kDa protein belonging to the S1 family of serine proteases. It is synthesized as a zymogen and activated by proteolytic cleavage. TSSP is localized to endosomes and lysosomes of thymic antigen-presenting cells, where it cleaves invariant chain (CD74) and processes self-antigens for loading onto MHC class II molecules. This activity is essential for proper thymic selection and prevention of autoimmunity. The protein contains a signal peptide, a propeptide, and a catalytic domain with the classic Ser-His-Asp triad. Structural studies indicate a chymotrypsin-like fold.