Structural and functional consequences of aspartate/asparagine-β-hydroxylase variants causing Traboulsi syndrome.

ABSTRACT: Traboulsi syndrome is an autosomal recessive hereditary disease associated with developmental defects, in particular of the ocular system. SNPs affecting the ASPH gene, which encodes for the 2-oxoglutarate (2OG)-dependent oxygenase aspartate/asparagine-β-hydroxylase (AspH), are associated with Traboulsi syndrome. AspH catalyzes hydroxylations of conserved aspartate/asparagine residues in epidermal growth factor-like domain (EGFD) proteins. We report studies on the clinically observed Traboulsi syndrome-associated R688Q, R735Q, and R735W AspH variants. The results reveal that pathogenic active site substitutions substantially reduce, though do not ablate, EGFD hydroxylase activity compared with wt AspH. They imply that efficient AspH-catalyzed EGFD hydroxylation is important during human de

SUBMITTER: Hou CX 

PROVIDER: S-EPMC12816917 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature