Relevance to Autism

A de novo frameshift variant in the UBR5 gene has been identified in an ASD proband from the Simons Simplex Collection (PMID 25961944). A missense mutation in the UBR5 gene was detected in all affected individuals of a Japanese pedigree (6 affected individuals through 4 generations) with familial adult myoclonic epilepsy, but not in any non-affected family members; this variant was also not detected in 85 unrelated healthy residents of the pedigree's community, nor in 24 control individuals of various ethnicities (Kato et al., 2012). More recently, Sabeh et al., 2024 reported UBR5 variants in 29 unrelated individuals presenting with a neurodevelopmental syndrome characterized by developmental delay, autism or autistic features, intellectual disability, epilepsy, movement disorders, and/or genital anomalies; decreased ubiquitination activity was observed in several UBR5 variants described in this report.

Molecular Function

This gene encodes a progestin-induced protein, which belongs to the HECT (homology to E6-AP carboxyl terminus) family. The HECT family proteins function as E3 ubiquitin-protein ligases, targeting specific proteins for ubiquitin-mediated proteolysis. This gene potentially has a role in regulation of cell proliferation or differentiation.

External Links

References