FGA Gene - Fibrinogen Alpha Chain: Function, Mutations, and Associated Diseases

The FGA gene encodes the alpha chain of fibrinogen, a plasma glycoprotein essential for blood coagulation. Fibrinogen is a hexamer composed of two sets of three chains (Aα, Bβ, γ) linked by disulfide bonds. The alpha chain contains a central coiled-coil region and a C-terminal globular domain. During coagulation, thrombin cleaves fibrinopeptide A from the Aα chain, initiating fibrin polymerization. FGA mutations can lead to quantitative (afibrinogenemia, hypofibrinogenemia) or qualitative (dysfibrinogenemia) fibrinogen deficiencies, associated with bleeding or thrombosis.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• KEGG hsa04610 - Complement and coagulation cascades

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

• Reactome R-HSA-114608 - Platelet degranulation

Fibrinogen alpha chain (UniProt P02671) is a 866-amino acid protein (including signal peptide) with a molecular weight of ~95 kDa. It contains a coiled-coil region and a C-terminal fibrinogen-related domain (FReD). The alpha chain is heavily glycosylated and contains multiple phosphorylation sites. It is synthesized primarily in hepatocytes and secreted into plasma. Upon thrombin cleavage, it releases fibrinopeptide A and participates in fibrin clot formation. The alpha chain also contains binding sites for factor XIIIa, which crosslinks fibrin polymers, and for integrin receptors on platelets.