SERPINB9 Gene: Serpin Family B Member 9 (PI-9) - Function, Mutations, and Disease

SERPINB9 encodes a member of the serpin family of protease inhibitors, specifically the ovalbumin-like (ov-serpin) subfamily. The protein, also known as proteinase inhibitor 9 (PI-9), is a potent inhibitor of granzyme B, a key effector protease released by cytotoxic T lymphocytes and natural killer cells. By inhibiting granzyme B, SERPINB9 protects cells from granzyme B-mediated apoptosis. It is expressed in various tissues, including immune-privileged sites, and plays a role in regulating immune responses. Dysregulation of SERPINB9 has been implicated in cancer, autoimmune diseases, and viral infections.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Granzyme B signaling pathway

• Apoptosis modulation by serpins

• Immune evasion in cancer

SERPINB9 (PI-9) is a 42 kDa intracellular serpin that irreversibly inhibits granzyme B. It contains a conserved serpin domain with a reactive center loop that acts as a bait for granzyme B. Upon cleavage, the inhibitor undergoes a conformational change, trapping the protease. PI-9 is expressed in immune-privileged tissues (e.g., testis, placenta) and in various immune cells. Its primary function is to protect cells from unintended granzyme B-mediated damage during immune responses. In cancer, overexpression of SERPINB9 is a mechanism of immune evasion, making it a potential therapeutic target.