Submission Details

Autosomal recessive

12/12/2019

The UBE3B gene is located on chromosome 12 at 12q24.11 and encodes ubiquitin protein ligase E3B. The UBE3B gene product plays a role in protein degradation by the ubiquitin proteasome system, which helps to regulate protein levels and remove damaged or abnormal proteins. UBE3A was first reported in relation to autosomal recessive Kaufman oculocerebrofacial syndrome in 2012 (23200864: Basel-Vanagaite et al. 2012). Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included eight variants (one missense, one start-lost, two splice-site, two stop-gained, and two frameshift) reported in six unrelated probands in three publications (23200864: Basel-Vanagaite et al. 2012; 23687348: Flex et al. 2013; 25691420: Pedurupillay et al. 2015). Variants in this gene segregated with disease in two additional family members. More evidence is available in the literature, but the maximum score for genetic evidence has been reached. This gene-disease relationship is supported by a shared biochemical function (ubiquitin-proteasome system) with at least one other gene associated with an intellectual disability syndrome (UBE3A:Angelman syndrome), expression in the central nervous system and craniofacial structures consistent with the disease, and a homozygous null mouse model that recapitulates diverse clinical features observed in human patients (23200864: Basel-Vanagaite et al. 2012). In summary, UBE3B is definitively associated with autosomal recessive Kaufman oculocerebrofacial syndrome. This relationship has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time.

23200864 23687348 25691420