SERPINA6 Gene: Corticosteroid-Binding Globulin (CBG) – Function, Mutations, and Clinical Significance

SERPINA6 (serpin family A member 6) encodes corticosteroid-binding globulin (CBG), a 52–55 kDa glycoprotein primarily synthesized in the liver. CBG binds cortisol, progesterone, and other corticosteroids with high affinity, regulating their plasma transport, half-life, and tissue delivery. It belongs to the serpin superfamily but lacks protease inhibitory activity. CBG undergoes conformational changes upon cleavage by neutrophil elastase, releasing cortisol at sites of inflammation. Mutations in SERPINA6 can cause CBG deficiency, associated with fatigue, hypotension, and altered stress responses.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• REACT:111102 – Corticosteroid-binding globulin (CBG) mediated cortisol transport

• WP:WP2898 – Glucocorticoid metabolism

• WP:WP4754 – Serpin family signaling

Corticosteroid-binding globulin (CBG) is a 405-amino-acid glycoprotein (UniProt P08185) belonging to the serpin superfamily. It is synthesized primarily in the liver and secreted into plasma, where it binds ~80–90% of circulating cortisol with high affinity (Kd ~10⁻⁸ M). CBG also binds progesterone and some synthetic corticosteroids. Upon proteolytic cleavage by neutrophil elastase at inflammatory sites, CBG undergoes a conformational change (stressed-to-relaxed transition) that reduces cortisol affinity, releasing the hormone locally. CBG is not a functional protease inhibitor despite its serpin fold. Post-translational modifications include N-glycosylation at Asn9, Asn74, and Asn308, which affect stability and binding. The protein has a half-life of ~5 days in circulation.