FDPS Gene: Farnesyl Diphosphate Synthase - Function, Mutations & Disease

FDPS encodes farnesyl diphosphate synthase, a key enzyme in the mevalonate pathway that catalyzes the sequential condensation of dimethylallyl diphosphate with two molecules of isopentenyl diphosphate to form farnesyl diphosphate (FPP). FPP is a precursor for cholesterol, dolichols, ubiquinone, and heme A, and is essential for protein prenylation. The enzyme is the molecular target of nitrogen-containing bisphosphonates used to treat osteoporosis and Paget disease of bone.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Mevalonate pathway (KEGG: hsa00900)

• Terpenoid backbone biosynthesis (KEGG: hsa00900)

• Cholesterol metabolism (Reactome: R-HSA-191273)

• Protein prenylation (Reactome: R-HSA-597592)

Farnesyl diphosphate synthase (FDPS) is a 419-amino acid homodimeric enzyme localized in the cytosol and peroxisomes. It catalyzes the head-to-tail condensation of isopentenyl diphosphate (IPP) with dimethylallyl diphosphate (DMAPP) to form geranyl diphosphate (GPP), and then condenses GPP with another IPP to produce farnesyl diphosphate (FPP). FPP is a branch-point metabolite used for cholesterol synthesis, dolichol production, and protein prenylation (farnesylation and geranylgeranylation). The enzyme is inhibited by nitrogen-containing bisphosphonates (e.g., alendronate, zoledronate), which bind to the dimethylallyl diphosphate substrate site. FDPS is highly expressed in liver and steroidogenic tissues.