UBR5 Loss-of-function Variants In Autism Spectrum Disorder And Intellectual Disability: Case Series And Review Of The Literature

Reuter, Miriam S.Salazar, Nelson BautistaHowe, Jennifer L.Hoang, NySarikaya, EgeSelvanayagam, ThanujaMendes de Aquino, MarlaVicente, Astrid M.Oliveira, GuiomarFreitag, Christine M.Thiruvahindrapuram, BhoomaTrost, BrettScherer, Stephen W.2026-01-292026-01-292025-11-29NPJ Genom Med. 2025 Nov 29;11(1):1. doi: 10.1038/s41525-025-00536-xhttp://hdl.handle.net/10400.18/10782UBR5 encodes an E3 ubiquitin-protein ligase which targets distinct N-terminal residues of proteins for degradation. Heterozygous loss-of-function variants were reported in patients with Autism Spectrum Disorder (ASD) and developmental delay, and recently in a cohort of individuals with neurodevelopmental disorders and variable other features. Here, we report three unrelated individuals with de novo loss-of-function variants in UBR5, presenting with ASD and intellectual disability. We review the literature for other de novo predicted loss-of-function variants in probands with ASD or developmental delay (in total n = 11 variants), providing further evidence that UBR5 haploinsufficiency is associated with ASD and atypical neurodevelopmental trajectories, including developmental delay and intellectual disability.engAutism SpectrumUBR5Neurodevelopmental DisordersUbiquitinationIntellectual DisabilityPerturbações do Desenvolvimento Infantil e Saúde MentalUBR5 Loss-of-function Variants In Autism Spectrum Disorder And Intellectual Disability: Case Series And Review Of The Literaturejournal article10.1038/s41525-025-00536-x2056-794441318701