AGXT Gene: Function, Mutations, and Primary Hyperoxaluria Type 1

The AGXT gene encodes alanine–glyoxylate aminotransferase, a peroxisomal enzyme that catalyzes the transamination of glyoxylate to glycine using alanine as the amino donor. This reaction is critical for detoxifying glyoxylate and preventing its conversion to oxalate. Mutations in AGXT cause primary hyperoxaluria type 1 (PH1), a rare autosomal recessive disorder characterized by excessive oxalate production, leading to kidney stones, nephrocalcinosis, and end-stage renal disease.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Glyoxylate and dicarboxylate metabolism (KEGG: hsa00630)

• Peroxisomal protein import (Reactome: R-HSA-9033241)

• Metabolism of amino acids and derivatives (Reactome: R-HSA-71291)

Alanine–glyoxylate aminotransferase (AGT) is a 392-amino-acid homodimeric peroxisomal enzyme encoded by AGXT. It uses pyridoxal phosphate as a cofactor to catalyze the transamination of glyoxylate to glycine, preventing oxalate formation. AGT is primarily expressed in the liver. Mislocalization to mitochondria due to mutations (e.g., p.Gly170Arg) is a known pathogenic mechanism in PH1. The protein has two domains: an N-terminal peroxisomal targeting signal (PTS1) and a C-terminal catalytic domain.