HGFAC Gene - Hepatocyte Growth Factor Activator: Function, Mutations, and Disease

The HGFAC gene encodes hepatocyte growth factor activator, a serine protease that converts pro-hepatocyte growth factor (pro-HGF) into its active form. This activation is critical for HGF/c-Met signaling, which regulates cell proliferation, migration, morphogenesis, and tissue regeneration, particularly in the liver. HGFAC is primarily expressed in the liver and circulates as an inactive zymogen; its activation is tightly controlled by coagulation factors and inhibitors. Dysregulation of HGFAC is implicated in liver disease, cancer invasion, and metastasis.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• HGF/c-Met signaling pathway (Reactome: R-HSA-6806834)

• Activation of Matrix Metalloproteinases (Reactome: R-HSA-1592389)

• Plasminogen activating cascade (Reactome: R-HSA-75205)

HGF activator (HGFA) is a 96 kDa serine protease synthesized primarily in the liver and secreted into plasma as an inactive zymogen. It is activated by thrombin or factor XIa through proteolytic cleavage. Active HGFA specifically cleaves pro-HGF at a single site to generate mature, biologically active HGF. HGFA activity is regulated by specific inhibitors such as HAI-1 and HAI-2. The protein consists of an N-terminal fibronectin type II domain, two kringle domains, and a C-terminal serine protease domain. Its structure enables binding to cell surfaces and extracellular matrix, facilitating localized HGF activation during tissue repair and cancer invasion.