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| Intellectual disability syndromic and non-syndromic v2.87 | UBE2I | chirag patel Marked gene: UBE2I as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v2.87 | UBE2I | chirag patel Gene: ube2i has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v2.87 | UBE2I | chirag patel Classified gene: UBE2I as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v2.87 | UBE2I | chirag patel Gene: ube2i has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v2.86 | UBE2I |
chirag patel gene: UBE2I was added gene: UBE2I was added to Intellectual disability syndromic and non-syndromic. Sources: Other Mode of inheritance for gene: UBE2I was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: UBE2I were set to Neurodevelopmental disorder, MONDO:0700092, UBE2I-related Review for gene: UBE2I was set to AMBER Added comment: ESHG 2026 10 unrelated individuals with 10 different heterozygous missense variants throughout UBE2I gene (9 confirmed de novo) presenting with developmental delay (10), intellectual disability (4), ASD (5), microcephaly (3), hearing loss (3), and dysmorphism. UBE2I encodes the only human E2 enzyme UBC9. SUMOylation is a critical post-translational modification regulating protein function, localization, and stability through E1, E2, and E3 enzymes. SUMOylation pathway is key regulator of neurodevelopment processes. Structural modeling for all variants suggested possible protein destabilization, disruption of the catalytic core, and altered SUMO binding. LCLs from patient with 2 variants (p.W53L and p.N124I) showed normal UBE2I mRNA levels, whereas protein levels were markedly reduced, and accompanied by decreased global SUMOylation. Yeast-based assays showed reduced protein stability for the p.W53L variant. Sources: Other |
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