Dardas et al., 2025 described a cohort of 15 individuals from 10 unrelated families with bialleic variants in the UGGT1 gene presenting with a phenotypic spectrum ranging from fetal demise/infantile death and multiorgan system involvement to a complex syndromic neurodevelopmental disorder characterized by severe global developmental delay/intellectual disability, dysmorphic features, microcephaly, seizures, and behavioral traits including autism and stereotyped movements; functional studies of UGGT1 variants identified in affected individuals demonstrated diverse pathogenic mechanisms, inlcuding impaired UGGT1 glucosylation and catalyic activity, disrupted mRNA splicing, or inhibited endoplasmic reticulum retention. Multiple de novo variants in UGGT1, including two de novo loss-of-function variants, have been reported in ASD probands from the Autism Sequencing Consortium, the Simons Simplex Collection, and the SPARK cohort (De Rubeis et al., 2014; Iossifov et al., 2014; Zhou et al., 2022; Trost et al., 2022).
Molecular Function
UDP-glucose:glycoprotein glucosyltransferase (UGT) is a soluble protein of the endoplasmic reticulum (ER) that selectively reglucosylates unfolded glycoproteins, thus providing quality control for protein transport out of the ER.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Bi-allelic UGGT1 variants cause a congenital disorder of glycosylation
