RNU4-2RNA, U4 small nuclear 2 

Relevance to Autism

Greene et al., 2024 performed a genetic association analysis comparing the burden of rare variants in 41,132 noncoding genes between 5,529 unrelated cases with intellectual disability and 46,401 unrelated controls and identified RNU4-2 as the most strongly associated gene with de novo variants among 47 cases in two regions of RNU4-2 (n.62–70 and n.73–79) in the etiology of a syndrome characterized by intellectual disability, microcephaly, short stature, hypotonia, seizures and motor delay; n.64_65insT was the most common RNU4-2 variant and was observed as a de novo mutation in 33 different families. Chen et al., 2024 subsequently identified an 18 bp region of RNU4-2 that was severely depleted of variation in the general population but in which heterozygous variants in 115 individuals with neurodevelopmental disorders were identified; most of these individuals (77.4%) had the same highly current single base insertion (n.64_65insT), and in 54 individuals where it could be determined, de novo variants were all on the maternal allele. Furthermore, characterization of detailed phenotypic information for a subset of 49 individuals (42 with the n.64_65insT variant) in this report demonstrated that RNU4-2 was responsible for a neurodevelopmental syndrome characterized by global developmental delay, intellectual disability, dysmorphic features, short stature, microcephaly, hypotonia, seizures, structural brain abnormalities detected by brain MRI, and behavioral abnormalities, including autism spectrum disorder in 21/44 individuals (48%).

Molecular Function

RNU4-2 encodes the U4 small nuclear RNA (snRNA) component of the small nuclear ribonuculeoprotein (snRNP) U4, which is one of the five snRNPs of the major spliceosome.

External Links

Human

SFARI Genomic Platforms