UBR5 loss-of-function variants in autism spectrum disorder and intellectual disability: case series and review of the literature

UBR5 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.

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Publication Details

Journal
npj Genomic Medicine
Published
2025-11-29
DOI
https://doi.org/10.1038/s41525-025-00536-x
Primary Topic
Ubiquitin and proteasome pathways
Type
article
Field-Weighted Citation Impact
0.00

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article

UBR5 loss-of-function variants in autism spectrum disorder and intellectual disability: case series and review of the literature

Marla Mendes de Aquino, Jennifer Howe, Miriam S. Reuter, Ege Sarikaya et al.
npj Genomic Medicine
Ubiquitin and proteasome pathways
article

UBR5 loss-of-function variants in autism spectrum disorder and intellectual disability: case series and review of the literature

Marla Mendes de Aquino, Jennifer Howe, Miriam S. Reuter, Ege Sarikaya, Guiomar Oliveira, Bhooma Thiruvahindrapuram, Stephen W. Scherer, Christine M. Freitag, Brett Trost, Thanuja Selvanayagam, Ny Hoang, Astrid M. Vicente, Nelson Bautista Salazar
article en

Abstract

UBR5 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.

npj Genomic MedicineVol. 11(1)
Goethe University Frankfurt (DE), University of Toronto (CA), Hospital for Sick Children (CA), Hospitais da Universidade de Coimbra (PT), University Hospital Frankfurt (DE), Instituto Nacional de Saúde (MZ), SickKids Foundation (CA), University of Coimbra (PT)
Autism Speaks, University of Toronto, Hospital for Sick Children
Openalex Percentile: Top 66%
Ubiquitin and proteasome pathways
DOIOpen Access PDFOpenAlex
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