SERPINF1 Gene: Pigment Epithelium-Derived Factor (PEDF) – Function, Mutations & Clinical Significance

SERPINF1 encodes pigment epithelium-derived factor (PEDF), a 50 kDa secreted glycoprotein belonging to the serpin (serine protease inhibitor) family. Despite its serpin fold, PEDF lacks protease inhibitory activity and functions primarily as a potent anti-angiogenic, neurotrophic, and neuroprotective factor. It is widely expressed in the eye, liver, adipose tissue, bone, and brain. Loss-of-function mutations in SERPINF1 cause autosomal recessive osteogenesis imperfecta type VI (OI6), characterized by bone fragility, defective mineralization, and absence of PEDF in serum.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• REACT:R-HSA-194138 – Signaling by VEGF

• REACT:R-HSA-9006934 – Regulation of angiogenesis by PEDF

• REACT:R-HSA-1474244 – Extracellular matrix organization

PEDF is a 418-amino-acid secreted glycoprotein with a serpin fold but no protease inhibitory activity. It is a major anti-angiogenic factor in the eye and a neurotrophic factor in the retina and brain. PEDF binds to cell surface receptors (e.g., PNPLA2, LRP6) to exert its effects. In bone, PEDF promotes osteoblast differentiation and mineralization. Loss of PEDF leads to osteogenesis imperfecta type VI, characterized by undermineralized bone, fish-scale lamellae, and elevated alkaline phosphatase.