HAO1 Gene - Hydroxyacid Oxidase 1 | Function, Mutations & Clinical Significance

HAO1 encodes hydroxyacid oxidase 1, a peroxisomal enzyme that catalyzes the oxidation of glycolate to glyoxylate and glyoxylate to oxalate. It is a key enzyme in the metabolic pathway leading to oxalate production. Loss-of-function mutations in HAO1 cause primary hyperoxaluria type 1 (PH1), a rare autosomal recessive disorder characterized by excessive oxalate production and kidney stone formation. HAO1 is also a therapeutic target for RNA interference (RNAi) therapy in PH1.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Glyoxylate and dicarboxylate metabolism (KEGG: hsa00630)

• Peroxisomal beta-oxidation of fatty acids

• Oxalate biosynthesis pathway

Hydroxyacid oxidase 1 (HAO1) is a 370-amino acid peroxisomal flavoprotein that functions as a homotetramer. It uses FMN as a cofactor to catalyze the oxidation of glycolate to glyoxylate and glyoxylate to oxalate, with concomitant reduction of molecular oxygen to hydrogen peroxide. The enzyme is highly expressed in the liver and plays a central role in oxalate metabolism. Deficiency due to biallelic mutations causes primary hyperoxaluria type 1, a severe kidney stone disease. HAO1 is the target of the RNAi therapeutic lumasiran, which reduces hepatic HAO1 expression to lower oxalate production in PH1 patients.