{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Chen Y"],"funding":["NICHD NIH HHS","NIMH NIH HHS","NHGRI NIH HHS","NINDS NIH HHS","NIAMS NIH HHS","Wellcome Trust"],"pubmed_abstract":["Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes<sup>1</sup>. Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA <i>RNU4-2</i> as a novel syndromic NDD gene. <i>RNU4-2</i> encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome<sup>2</sup>. We identify an 18 bp region of <i>RNU4-2</i> mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 119 individuals with"],"journal":["medRxiv : the preprint server for health sciences"],"pagination":["2024.04.07.24305438"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11030480"],"repository":["biostudies-literature"],"pubmed_title":["&lt;i&gt;De novo&lt;/i&gt; variants in the non-coding spliceosomal snRNA gene &lt;i&gt;RNU4-2&lt;/i&gt; are a frequent cause of syndromic neurodevelopmental disorders."],"pmcid":["PMC11030480"],"funding_grant_id":["U01 HG007942","U01 NS106845","U01 HG010217","U24 NS131172","U01 MH122681","U01 HG011745","U01 HG011755","U01 NS134358","U24 HG011746","K23 AR083505","R01 MH122681","220134/Z/20/Z","P50 HD103555","U01 HG011762","U01 MH111662","R01 HG009141","R01 MH129751","U01 HG007709","U54 NS115052","R21 HG012397","UM1 HG008900"],"pubmed_authors":["Fraser JL","Bakshi M","Stark Z","Genetti CA","Depienne C","Clair L","Fevre AL","Tifft CJ","White SM","Ezell K","Rubenstein JL","Sachdev R","Walker S","Leitao E","Thorburn DR","Montgomery SB","Pitsava G","Zocche D","Lockhart PJ","O'Leary M","Liebelt JE","Tan NB","Viskochil DH","Berger SI","Adams DR","Wojcik M","Mendez HR","Pysar R","Tan TY","Stenton SL","Whiffin N","Dias KR","Evans CA","Temple SE","Vilain E","Ma AS","Maurer TM","Palmer EE","Reuter CM","Xiao C","Kuechler A","D'Souza EN","Rehm HL","Burrage LC","Macnamara EF","Dong S","Ellingford JM","Elias ER","Ljungdahl A","Rodan L","Fica SM","Chen Y","Roscioli T","Baralle D","Leventer RJ","MacArthur DG","VanNoy GE","Lemire G","Ewans L","Wedd L","Wolfenson Z","Dawes R","Howson JM","Sanders SJ","Brown NJ","Bernstein JA","Compton AG","Rosenfeld JA","Haack T","Rius R","Grant CL","Nassogne MC","Ganesh VS","Gallacher L","Uebergang E","Lalani SR","Martin-Geary AC","Riess A","Phillips J","Wheeler MT","Snell P","Delot EC","Sisodiya SM","O'Donnell-Luria A","Baldwin EE","Neumann S","Wolfe LA","Kim HC","Allan K","D'Souza P","Ma J","Revencu N","Chapman K","Markenscoff-Papadimitriou E","Lord J","Cunningham CA","Simons C"],"additional_accession":[]},"is_claimable":false,"name":"&lt;i&gt;De novo&lt;/i&gt; variants in the non-coding spliceosomal snRNA gene &lt;i&gt;RNU4-2&lt;/i&gt; are a frequent cause of syndromic neurodevelopmental disorders.","description":"Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes<sup>1</sup>. Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA <i>RNU4-2</i> as a novel syndromic NDD gene. <i>RNU4-2</i> encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome<sup>2</sup>. We identify an 18 bp region of <i>RNU4-2</i> mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 119 individuals with","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-04-08T18:57:14.699Z","creation":"2026-04-08T11:06:19.373Z"},"accession":"S-EPMC11030480","cross_references":{"pubmed":["38645094"],"doi":["10.1101/2024.04.07.24305438"]}}