AGXT

AGXT is the gene that encodes alanine-glyoxylate aminotransferase (AGT), a liver peroxisomal enzyme involved in glyoxylate detoxification. AGT catalyzes the transamination of glyoxylate and alanine to form glycine and pyruvate, thereby limiting the amount of glyoxylate available for conversion to oxalate. In healthy individuals AGT is mainly localized to hepatic peroxisomes via a C-terminal peroxisomal targeting signal, though some mutations can cause mislocalization to the cytosol or mitochondria and reduce peroxisomal activity.

Genetics and expression: AGXT is located on chromosome 2q37.3 and is inherited in an autosomal recessive manner. The gene is most highly expressed in liver, with activity also detected in kidney. Numerous disease-causing mutations have been described that impair enzyme function or disrupt proper targeting to peroxisomes.

Clinical significance: Deficiency or dysfunction of AGT leads to primary hyperoxaluria type 1 (PH1), a rare metabolic disorder characterized by excessive oxalate production and urinary excretion. Oxalate combines with calcium to form calcium oxalate crystals, causing nephrocalcinosis, kidney stones, and progressively worsening kidney failure. Some AGXT mutations confer partial responsiveness to pyridoxine (vitamin B6), which can stabilize certain AGT variants.

Diagnosis and treatment: PH1 is diagnosed by elevated urinary oxalate and confirmation of AGXT mutations through genetic testing. Management includes high fluid intake, crystallization inhibitors such as citrate, and treatment of kidney stones; advanced disease may require liver transplantation or combined liver-kidney transplantation. Emerging therapies aim to lower oxalate production by targeting downstream metabolic pathways.