PROS1 Gene: Protein S Function, Mutations, and Associated Diseases

The PROS1 gene encodes Protein S, a vitamin K-dependent plasma glycoprotein that functions as a cofactor for activated protein C (APC) in the inactivation of coagulation factors Va and VIIIa. Protein S also has direct anticoagulant activity independent of APC. Mutations in PROS1 cause hereditary protein S deficiency, a risk factor for venous thromboembolism. The gene is located on chromosome 3q11.2 and spans approximately 80 kb.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• KEGG hsa04610 - Complement and coagulation cascades

• Reactome R-HSA-140837 - Intrinsic pathway of fibrin clot formation

• Reactome R-HSA-140877 - Formation of Fibrin Clot (Clotting Cascade)

Protein S is a 635-amino acid vitamin K-dependent glycoprotein synthesized primarily in the liver. It contains an N-terminal Gla domain, four EGF-like domains, and a C-terminal sex hormone-binding globulin (SHBG)-like domain. Protein S circulates in plasma in two forms: free (40%) and bound to C4b-binding protein (60%). Only free Protein S acts as a cofactor for activated protein C. It also has direct anticoagulant activity by inhibiting the prothrombinase and tenase complexes. Deficiency of Protein S is associated with increased risk of thrombosis.