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*180691
Table of Contents
Alternative titles; symbols
HGNC Approved Gene Symbol: RNU5A-1
Cytogenetic location: 15q22.31 Genomic coordinates (GRCh38) : 15:65,296,051-65,296,167 (from NCBI)
Splicing of nuclear precursor-mRNA (pre-mRNA) is the process by which introns are removed from mRNA precursors to form functional mature mRNAs. The process is mediated by the spliceosome, a complex ribonucleoprotein composed of 5 small nuclear RNAs (U1, 180680; U2, 180690; U3, 180710; U5; and U6, 180692) and numerous proteins. Introns are removed by means of 2 consecutive transesterification reactions. Introns are defined only by 3 short consensus sequences: the 5-prime splice site, the branch point region, and 3-prime splice site. Sontheimer and Steitz (1993) characterized the U5 and U6 snRNAs as components of the active site of the spliceosome. Wise (1993) reviewed the functioning of the spliceosome.
Gross (2023) mapped the RNU5A-1 gene to chromosome 15q22.31 based on an alignment of the RNU5A-1 sequence (GenBank NR_002756) with the genomic sequence (GRCh38).
Associations Pending Confirmation
In an analysis of mutations in 50 snRNA-encoding genes in a French cohort of 23,649 patients with rare disorders, Nava et al. (2025) identified 6 patients with a neurodevelopmental disorder and heterozygous mutation in the RNU5A-1 gene. Clinical data was available for 3 of these patients. Patients 149 and 150 had a heterozygous de novo n.40_41insA mutation (180691.0001). Patient 151, who had a heterozygous de novo n.39del mutation, had mild developmental delay and mildly impaired intellectual development. He also had aortic valve fibrosis, mild mitral and aortic valve insufficiency, a marfanoid body habitus, pectus excavatum, arachnodactyly, and scoliosis. Analysis of alternative splice site abnormalities in patient-derived cultured lymphocytes suggested that the mutation resulted in 3-prime splice site abnormalities.
This variant is classified as a variant of unknown significance because its contribution to a neurodevelopmental disorder has not been confirmed.
In 2 unrelated patients (patients 149 and 150) with a neurodevelopmental disorder, Nava et al. (2025) identified a de novo heterozygous 1-bp insertion (n.40_41insA) in the RNU5A-1 gene. The mutation was identified by analysis of mutations in 50 snRNA-encoding genes in whole-genome sequencing data. Analysis of alternative splice site abnormalities in patient-derived cultured lymphocytes suggested that the mutation may result in both 5-prime and 3-prime splice site abnormalities. Patient 149 had intrauterine growth retardation and difficulty feeding after birth. He had mild developmental delay, an attention disorder, and motor and executive functioning difficulties. He also had seizures. Patient 150 had oligohydramnios in utero, and after birth was noted to have hypotonia and talipes equinovarus. She also had seizures, severe developmental delay, and impaired intellectual development.
Gross, M. B. Personal Communication. Baltimore, Md. 5/2/2023.
Nava, C., Cogne, B., Santini, A., Leitao, E., Lecoquierre, F., Chen, Y., Stenton, S. L., Besnard, T., Heide, S., Baer, S., Jakhar, A., Neuser, S., and 252 others. Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption. Nature Genet. 57: 1374-1388, 2025. [PubMed: 40379786, related citations] [Full Text]
Sontheimer, E. J., Steitz, J. A. The U5 and U6 small nuclear RNAs as active site components of the spliceosome. Science 262: 1989-1996, 1993. Note: Erratum: Science 263: 739 only, 1994. [PubMed: 8266094, related citations] [Full Text]
Wise, J. A. Guides to the heart of the spliceosome. Science 262: 1978-1979, 1993. [PubMed: 8266091, related citations] [Full Text]
Alternative titles; symbols
HGNC Approved Gene Symbol: RNU5A-1
Cytogenetic location: 15q22.31 Genomic coordinates (GRCh38) : 15:65,296,051-65,296,167 (from NCBI)
Splicing of nuclear precursor-mRNA (pre-mRNA) is the process by which introns are removed from mRNA precursors to form functional mature mRNAs. The process is mediated by the spliceosome, a complex ribonucleoprotein composed of 5 small nuclear RNAs (U1, 180680; U2, 180690; U3, 180710; U5; and U6, 180692) and numerous proteins. Introns are removed by means of 2 consecutive transesterification reactions. Introns are defined only by 3 short consensus sequences: the 5-prime splice site, the branch point region, and 3-prime splice site. Sontheimer and Steitz (1993) characterized the U5 and U6 snRNAs as components of the active site of the spliceosome. Wise (1993) reviewed the functioning of the spliceosome.
Gross (2023) mapped the RNU5A-1 gene to chromosome 15q22.31 based on an alignment of the RNU5A-1 sequence (GenBank NR_002756) with the genomic sequence (GRCh38).
Associations Pending Confirmation
In an analysis of mutations in 50 snRNA-encoding genes in a French cohort of 23,649 patients with rare disorders, Nava et al. (2025) identified 6 patients with a neurodevelopmental disorder and heterozygous mutation in the RNU5A-1 gene. Clinical data was available for 3 of these patients. Patients 149 and 150 had a heterozygous de novo n.40_41insA mutation (180691.0001). Patient 151, who had a heterozygous de novo n.39del mutation, had mild developmental delay and mildly impaired intellectual development. He also had aortic valve fibrosis, mild mitral and aortic valve insufficiency, a marfanoid body habitus, pectus excavatum, arachnodactyly, and scoliosis. Analysis of alternative splice site abnormalities in patient-derived cultured lymphocytes suggested that the mutation resulted in 3-prime splice site abnormalities.
This variant is classified as a variant of unknown significance because its contribution to a neurodevelopmental disorder has not been confirmed.
In 2 unrelated patients (patients 149 and 150) with a neurodevelopmental disorder, Nava et al. (2025) identified a de novo heterozygous 1-bp insertion (n.40_41insA) in the RNU5A-1 gene. The mutation was identified by analysis of mutations in 50 snRNA-encoding genes in whole-genome sequencing data. Analysis of alternative splice site abnormalities in patient-derived cultured lymphocytes suggested that the mutation may result in both 5-prime and 3-prime splice site abnormalities. Patient 149 had intrauterine growth retardation and difficulty feeding after birth. He had mild developmental delay, an attention disorder, and motor and executive functioning difficulties. He also had seizures. Patient 150 had oligohydramnios in utero, and after birth was noted to have hypotonia and talipes equinovarus. She also had seizures, severe developmental delay, and impaired intellectual development.
Gross, M. B. Personal Communication. Baltimore, Md. 5/2/2023.
Nava, C., Cogne, B., Santini, A., Leitao, E., Lecoquierre, F., Chen, Y., Stenton, S. L., Besnard, T., Heide, S., Baer, S., Jakhar, A., Neuser, S., and 252 others. Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption. Nature Genet. 57: 1374-1388, 2025. [PubMed: 40379786] [Full Text: https://doi.org/10.1038/s41588-025-02184-4]
Sontheimer, E. J., Steitz, J. A. The U5 and U6 small nuclear RNAs as active site components of the spliceosome. Science 262: 1989-1996, 1993. Note: Erratum: Science 263: 739 only, 1994. [PubMed: 8266094] [Full Text: https://doi.org/10.1126/science.8266094]
Wise, J. A. Guides to the heart of the spliceosome. Science 262: 1978-1979, 1993. [PubMed: 8266091] [Full Text: https://doi.org/10.1126/science.8266091]
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