Ask about this productRelated genes to: UBE3A Blocking Peptide
- Gene:
- SNHG14 NIH gene
- Name:
- small nucleolar RNA host gene 14
- Previous symbol:
- UBE3A-AS1
- Synonyms:
- NCRNA00214, UBE3A-AS, UBE3A-ATS
- Chromosome:
- 15q11.2
- Locus Type:
- RNA, long non-coding
- Date approved:
- 2009-10-16
- Date modifiied:
- 2018-08-23
- Gene:
- UBE3A NIH gene
- Name:
- ubiquitin protein ligase E3A
- Previous symbol:
- EPVE6AP, HPVE6A
- Synonyms:
- AS, ANCR, E6-AP, FLJ26981
- Chromosome:
- 15q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1993-10-21
- Date modifiied:
- 2019-04-23
Related products to: UBE3A Blocking Peptide
Related articles to: UBE3A Blocking Peptide
- Pigs (Sus scrofa domesticus) are used as biomedical and preclinical models for their comparable anatomy, physiology, and neurodevelopment to humans. Angelman syndrome is a rare genetic neurodevelopmental disorder, caused by the loss of the maternal Ubiquitin protein ligase E3A (UBE3A) allele, that was recently modelled and characterized in Yorkshire/Landrace pigs. The paternal UBE3A allele is intact but silenced in neurons of the central nervous system by the long non-coding RNA and polycistronic transcription unit Small Nuclear Host Gene 14 (SNHG14). Targeting SNHG14 to reactivate the paternal UBE3A allele is a therapeutic approach for Angelman syndrome currently under investigation. However, the current pig reference genome (Sscrofa11.1) misassembles the highly complex SNHG14 locus, hindering accurate targeting and regulatory studies in this model. Using PacBio HiFi and Hi-C sequencing, we generated a chromosome-level assembly for an Angelman syndrome pig model and fully resolved the SNHG14 locus without gaps. We show that the current pig reference genome contains extensive tandem repeat collapse within SNHG14, misrepresenting both its size and organization. The resolved locus reveals a previously unknown bipartite architecture of SNORD116 tandem repeats, comprising two distinct groups in both sequence and structure. This resolution and genome resource remove the genomic hindrance to SNHG14-focused studies in pigs. - Source: PubMed
Publication date: 2026/03/09
Taylor Alasdair JFoley Nicole MChilders Isabella RMurphy William JDindot Scott V - Angelman syndrome is a devastating neurogenetic disorder for which there is currently no effective treatment. It is caused by mutations or epimutations affecting the expression or function of the maternally inherited allele of the ubiquitin-protein ligase E3A () gene. The paternal allele is imprinted in neurons of the central nervous system (CNS) by the antisense () transcript, which represents the distal end of the small nucleolar host gene 14 () transcription unit. Reactivating the expression of the paternal allele in the CNS has long been pursued as a therapeutic option for Angelman syndrome. Here, we described the development of an antisense oligonucleotide (ASO) therapy for Angelman syndrome that targets an evolutionarily conserved region demarcating the start of the transcript. We designed and chemically optimized gapmer ASOs targeting specific sequences at the start of the human transcript. We showed that ASOs targeting this region precisely and efficiently repress the transcription of , reactivating the expression of the paternal allele in neurotypical and Angelman syndrome induced pluripotent stem cell-derived neurons. We further showed that human-targeted ASOs administered to the CNS of cynomolgus macaques by lumbar intrathecal injection repress and reactivate the expression of the paternal allele throughout the CNS. These findings support the advancement of this investigational molecular therapy for Angelman syndrome into clinical development (ClinicalTrials.gov, NCT04259281). - Source: PubMed
Publication date: 2023/03/22
Dindot Scott VChristian SarahMurphy William JBerent AllysonPanagoulias JenniferSchlafer AnnaliseBallard JohnathanRadeva KameliaRobinson RuthMyers LukeJepp ThomasShaheen HillaryHillman PaulKonganti KrantiHillhouse AndrewBredemeyer Kevin RBlack LaurenDouville Julie - The Small Nucleolar Host Gene 14 () is a host gene for small non-coding RNAs, including the small nucleolar C/D box RNA encoding locus. Large deletions of the locus, as well as microdeletions of the locus, lead to the neurodevelopmental genetic disorder Prader-Willi syndrome. This review will focus on the gene, its expression patterns, its role in human cancer, and the possibility that single nucleotide variants within the locus contribute to human phenotypes in the general population. This review will also include new in silico data analyses of the locus and new in situ RNA expression patterns of the Snhg14 RNA in mouse midbrain and hindbrain regions. - Source: PubMed
Publication date: 2022/12/29
Ariyanfar ShadiGood Deborah J - Angelman syndrome (AS) is a rare neurogenetic imprinting disorder caused by the loss of function of UBE3A. In ~3-5% of AS patients, the disease is due to an imprinting defect (ID). These patients lack DNA methylation of the maternal SNRPN promotor so that a large SNRPN sense/UBE3A antisense transcript (SNHG14) is expressed, which silences UBE3A. In very rare cases, the ID is caused by a deletion of the AS imprinting centre (AS-IC). To search for sequence alterations, we sequenced this region in 168 patients without an AS-IC deletion, but did not detect any sequence alteration. However, the AS-IC harbours six common variants (five single nucleotide variants and one TATG insertion/deletion variant), which constitute five common haplotypes. To determine if any of these haplotypes is associated with an increased risk for an ID, we investigated 119 informative AS-ID trios with the transmission disequilibrium test, which is a family-based association test that measures the over-transmission of an allele or haplotype from heterozygous parents to affected offspring. By this we observed maternal over-transmission of haplotype H-AS3 (p = 0.0073). Interestingly, H-AS3 is the only haplotype that includes the TATG deletion allele. We conclude that this haplotype and possibly the TATG deletion, which removes a SOX2 binding site, increases the risk for a maternal ID and AS. Our data strengthen the notion that the AS-IC is important for establishing and/or maintaining DNA methylation at the SNRPN promotor and show that common genetic variation can affect genomic imprinting. - Source: PubMed
Publication date: 2020/03/09
Beygo JasminGrosser ChristianKaya SabineMertel ClaudiaBuiting KarinHorsthemke Bernhard - Genomic imprinting is an epigenetic phenomenon resulting in parent-of-origin-specific gene expression that is regulated by a differentially methylated region. Gene mutations or failures in the imprinting process lead to the development of imprinting disorders, such as Angelman syndrome. The symptoms of Angelman syndrome are caused by the absence of functional UBE3A protein in neurons of the brain. To create a human neuronal model for Angelman syndrome, we reprogrammed dermal fibroblasts of a patient carrying a defined three-base pair deletion in UBE3A into induced pluripotent stem cells (iPSCs). In these iPSCs, both parental alleles are present, distinguishable by the mutation, and express UBE3A. Detailed characterization of these iPSCs demonstrated their pluripotency and exceptional stability of the differentially methylated region regulating imprinted UBE3A expression. We observed strong induction of SNHG14 and silencing of paternal UBE3A expression only late during neuronal differentiation, in vitro. This new Angelman syndrome iPSC line allows to study imprinted gene regulation on both parental alleles and to dissect molecular pathways affected by the absence of UBE3A protein. - Source: PubMed
Publication date: 2016/08/03
Stanurova JanaNeureiter AnikaHiber Michaelade Oliveira Kessler HannahStolp KristinGoetzke RomanKlein DianaBankfalvi AgnesKlump HannesSteenpass Laura