4-hydroxy-2-oxoglutarate aldolase 1 (HOGA1)

4-hydroxy-2-oxoglutarate aldolase 1 (HOGA1) is a mitochondrial enzyme that catalyzes the retro-aldol cleavage of 4-hydroxy-2-oxoglutarate into glyoxylate and pyruvate, representing the terminal step of hydroxyproline degradation. This reaction links collagen-derived hydroxyproline metabolism to the cellular glyoxylate pool and downstream oxalate production, which is critical since glyoxylate can be further metabolized into oxalate—a major component of kidney stones[1][2][3][4][5]. HOGA1 is expressed primarily in the liver and kidney. Loss-of-function mutations in the HOGA1 gene underlie primary hyperoxaluria type 3 (PH3), a rare metabolic disorder characterized by excess oxalate production, kidney stones, and progressive kidney disease[3][4]. No specific drugs are known to target HOGA1 directly, but genetic testing for HOGA1 mutations serves as a diagnostic biomarker for PH3[3][4][5].

Other names

4-hydroxy-2-oxoglutarate aldolase, mitochondrialC10orf65DHDPSLDHDPS-like proteinProbable KHG-aldolaseFLJ37472DHDPS2NPL2Dihydrodipicolinate synthase-likeProtein 569272dihydrodipicolinate synthetase homolog 2 (E. coli)N-acetylneuraminate pyruvate lyase 2 (putative)HP3

Not applicable (no approved drugs targeting HOGA1)