Biochemical Characterization of Disease-Associated Variants of Human Ornithine Transcarbamylase.

ABSTRACT: Human ornithine transcarbamylase deficiency (OTCD) is the most common ureagenesis disorder in the world. OTCD is an X-linked genetic deficiency in which patients experience hyperammonemia to varying degrees depending on the severity of the genetic mutation. More than two-thirds of the known mutations are caused by single nucleotide substitutions. In this paper, partial order optimum likelihood (POOL), a machine learning method, is used to analyze single nucleotide substitutions in OTC with varying disease phenotypes and predicted catalytic efficiencies. Specifically, we used a computed metric, μ₄, a measure of the degree of coupling between an ionizable residue and its neighbors, calculated for the catalytic residues, to identify which protein variants were most likely to have i

SUBMITTER: Micheloni E 

PROVIDER: S-EPMC12090190 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature