Hydroxyacid oxidase 1 (HAO1) (HAO1)

Hydroxyacid oxidase 1 (HAO1) is a liver-specific enzyme, also known as glycolate oxidase, that catalyzes the oxidation of glycolate to glyoxylate within the peroxisomes of hepatocytes [UniProt Q9UJM8; NCBI Gene 54363]. This enzyme is a key component of the glyoxylate metabolic pathway, where glyoxylate is normally converted to glycine by alanine-glyoxylate aminotransferase (AGT) [NCBI Gene 54363; Cochat P, et al., N Engl J Med 2013]. In individuals with Primary Hyperoxaluria Type 1 (PH1), a deficiency in AGT causes glyoxylate to accumulate and subsequently oxidize into oxalate, a toxic metabolite that forms insoluble calcium oxalate crystals in the kidneys [Cochat P, et al., N Engl J Med 2013; Garrelfs SF, et al., N Engl J Med 2021]. Therapeutic strategies targeting HAO1, such as the siRNA drug lumasiran, utilize substrate reduction therapy to inhibit the production of glyoxylate at its source [Liebow A, et al., J Am Soc Nephrol 2017; FDA Oxlumo Label]. By reducing HAO1 protein levels, these treatments effectively lower urinary and plasma oxalate levels, mitigating the risk of progressive kidney failure and systemic oxalosis [Garrelfs SF, et al., N Engl J Med 2021]. Because HAO1 expression is highly localized to the liver and its deficiency (glycolic aciduria) is generally considered a benign condition, it represents a safe and effective focal point for pharmacological intervention [NCBI Gene 54363; Liebow A, et al., J Am Soc Nephrol 2017].

Other names

Glycolate oxidaseGOHAO1HAO-1Glycolate oxidase 1Hydroxyacid oxidase A

RNA interference (siRNA) mediated degradation of HAO1 mRNA, leading to reduced glycolate oxidase protein levels and decreased glyoxylate production.