SAA1 Gene – Serum Amyloid A1: Function, Mutations, and Disease Associations

SAA1 (Serum Amyloid A1) encodes a major acute-phase protein, serum amyloid A (SAA), which is primarily synthesized by the liver in response to inflammation, infection, or tissue injury. SAA1 is a precursor of amyloid A (AA) fibrils that deposit in tissues, leading to secondary (AA) amyloidosis. The protein also plays roles in lipid metabolism, chemotaxis, and immune modulation. Polymorphisms in SAA1 are associated with susceptibility to amyloidosis and inflammatory diseases.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Acute phase response (Reactome: R-HSA-6785807)

• IL-6 signaling (KEGG: hsa04630)

• Lipid metabolism and HDL remodeling (Reactome: R-HSA-8963896)

Serum amyloid A1 (SAA1) is a 122-amino acid secreted protein (12.5 kDa) that circulates as a component of high-density lipoprotein (HDL) during acute inflammation. It is predominantly produced by hepatocytes under transcriptional control of IL-1, IL-6, and TNF-α. SAA1 has multiple functions: it acts as a chemoattractant for immune cells, modulates cholesterol transport, and can form amyloid fibrils in chronic inflammatory states. The protein structure includes an N-terminal region critical for amyloidogenesis. SAA1 polymorphisms influence susceptibility to AA amyloidosis, particularly in patients with chronic inflammatory diseases such as rheumatoid arthritis and familial Mediterranean fever.