OTC leader sequence variants cause OTC deficiency

Ornithine transcarbamylase is a mitochondrially localized protein that is encoded by a nuclear gene and translated on free ribosomes in the cytosol. Targeting to the mitochondria depends on a 33 amino acid leader sequence at the N-terminus of the newly synthesized protein that is cleaved during transit through the mitochondrial membranes. Mutations in the N-terminal leader sequence destabilize the mRNA, decrease overall protein levels and interfere with correct localization and function.

Summary from Reactome (R-HSA-9956551), read 2026-09-23.