Cellular degradation of 4-hydroxy-2-oxoglutarate aldolase leads to absolute deficiency in primary hyperoxaluria type 3.

Primary hyperoxaluria type-3 is characterized by increased oxalate production caused by mutations in the HOGA1 gene encoding 4-hydroxy-2-oxoglutarate aldolase (HOGA1). How the most commonly occurring mutations affect the cellular fates of the expressed HOGA1 mutants is still unknown. We show that two prevalent recombinant HOGA1 mutants are thermally unstable with evidence for chaperone-mediated degradation when expressed in E.