RNU5B-1RNA, U5B small nuclear 1
Autism Reports / Total Reports
0 / 2Rare Variants / Common Variants
9 / 0Aliases
-Associated Syndromes
-Chromosome Band
15q22.31Associated Disorders
-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.
SFARI Genomic Platforms
Reports related to RNU5B-1 (2 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Primary | - | Caroline Nava et al. (2025) | No | ASD, stereotypy, epilepsy/seizures |
| 2 | Recent Recommendation | - | Adam Jackson et al. (2025) | No | ASD |
Rare Variants (9)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| n.37G>C | - | non_coding_transcript_variant | De novo | - | - | 40442284 | Adam Jackson et al. (2025) | |
| n.44A>G | - | non_coding_transcript_variant | De novo | - | - | 40442284 | Adam Jackson et al. (2025) | |
| n.24G>C | - | non_coding_transcript_variant | De novo | - | - | 40379786 | Caroline Nava et al. (2025) | |
| n.74T>C | - | non_coding_transcript_variant | De novo | - | - | 40379786 | Caroline Nava et al. (2025) | |
| n.39_40insT | - | non_coding_transcript_variant | De novo | - | - | 40442284 | Adam Jackson et al. (2025) | |
| n.42_43insA | - | non_coding_transcript_variant | De novo | - | - | 40442284 | Adam Jackson et al. (2025) | |
| n.39C>G | - | non_coding_transcript_variant | De novo | - | Simplex | 40379786 | Caroline Nava et al. (2025) | |
| n.44A>G | - | non_coding_transcript_variant | De novo | - | Simplex | 40379786 | Caroline Nava et al. (2025) | |
| n.42_43insA | - | non_coding_transcript_variant | De novo | - | Simplex | 40379786 | Caroline Nava et al. (2025) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence, Syndromic
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
7/1/2025
Initial score established: 1S
Krishnan Probability Score
Score 0.44380429759941
Ranking 16434/25841 scored genes
[Show Scoring Methodology]