HOGA1

HOGA1 is the human gene that encodes the enzyme 4-hydroxy-2-oxoglutarate aldolase. This enzyme participates in the catabolism of hydroxyproline and in the metabolism of glyoxylate, catalyzing the cleavage of 4-hydroxy-2-oxoglutarate into glyoxylate and pyruvate. Through this reaction, HOGA1 links amino acid metabolism to central carbon metabolism and glyoxylate detoxification.

Genetics and clinical significance: Pathogenic variants in HOGA1 cause primary hyperoxaluria type III (PH3), a rare autosomal recessive metabolic disorder. The defect leads to increased production of oxalate, resulting in elevated urinary oxalate excretion and deposition of calcium oxalate in the kidneys. This can manifest as nephrolithiasis (kidney stones), nephrocalcinosis, and, in some individuals, progressive kidney disease or failure. The age of onset and disease severity are variable.

Diagnosis and management: Diagnosis is typically made by genetic testing for HOGA1 mutations, often in the context of suspected primary hyperoxaluria or unexplained oxalate kidney stones. Biochemical evaluation may show elevated urinary oxalate. Management focuses on reducing oxalate burden and protecting kidney function; standard approaches include high fluid intake, dietary oxalate restriction, and measures to inhibit stone formation. The role of pyridoxine is less clear in PH3 compared with other types. In severe or progressive cases, transplantation strategies, such as combined liver-kidney transplantation, may be considered. Ongoing research seeks to clarify genotype-phenotype relationships and to develop targeted therapies.

HOGA1 has homologs in other species, reflecting conservation of hydroxyproline and glyoxylate metabolism across organisms.