Relevance to Autism

Investigation of de novo variants in 50 snRNA-encoding genes in a French cohort of 23,649 individuals with rare disorders and additional cases gathered through international collaborations in Nava et al., 2025 resulted in the identification of 17 individuals with neurodevelopmental disorders (NDD) carrying variants in RNU5B-1 that were clustered within a small region corresponding to the highly conserved U5 5 loop I that was depleted in variants in gnomAD v4.1.0 and UK Biobank; three of these variants (n.39C>G, n.42_43insA and n.44AG) were recurrent (identified in at least three patients), absent from all databases, and defined as likely pathogenic. Additional assessment of detailed clinical data available for nine NDD patients with likely pathogenic RNU5B-1 variants (five with n.39C>G, one with n.42_43inA, and three with n.44A>G) in this report identified a potential neurodevelopmental disorder characterized by moderate/severe developmental delay and/or intellectual disability, abnormal brain MRI findings, and micro- or macrocephaly, among other findings; autism spectrum disorder was observed in three individuals. Lastly, analysis of samples from four patients with RNU5B-1 variants (two n.39C>G, two n.44A>G) for splicing effects in Nava et al., 2025 found that RNU5B-1 n.39C>G mainly affected 5 splice-sites, while RNU5B-1 n.44A>G primarily impacted 3splice-sites. Analysis of R-loop forming regions in ribozyme, snoRNA, and snRNA genes, specifically in rare disease cohorts, in Jackson et al., 2025 identified a total of 9 individuals from the 100,000 Genomes Project, the Genomics England, National Genomics Research Library database, the Centre for Population Genetics in Australia database, and the South Korean Undiagnosed Diseases database with rare RNU5B-1 variants within a region from 30 to 50 bp constrained for variants in gnomAD v4. Phenotypic information was available for 6 of these individuals, who presented with a neurodevelopmental disorder characterized by developmental delay/intellectual disability (6/6 individuals), epilepsy/seizures (5/6), and autism spectrum disorder (4/6), in addition to other non-neurological phenotypes.

Molecular Function

Predicted to be involved in formation of quadruple SL/U4/U5/U6 snRNP and spliceosomal tri-snRNP complex assembly. Predicted to be part of U4/U6 x U5 tri-snRNP complex and U5 snRNP.

External Links

References