{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Quinodoz M"],"funding":["NEI NIH HHS","Wellcome Trust"],"pagination":["169-179"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12807869"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["58(1)"],"pubmed_abstract":["Small nuclear RNAs (snRNAs) combine with specific proteins to generate small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. U4 snRNA forms a duplex with U6 and, together with U5, contributes to the tri-snRNP spliceosomal complex. Variants in RNU4-2, which encodes U4, have recently been implicated in neurodevelopmental disorders. Here we show that heterozygous inherited and de novo variants in RNU4-2 and in four RNU6 paralogs (RNU6-1, RNU6-2, RNU6-8 and RNU6-9), which encode U6, recur in individuals with nonsyndromic retinitis pigmentosa (RP), a genetic disorder causing progressive blindness. These variants cluster within the three-way junction of the U4/U6 duplex, a site that interacts with tri-snRNP splicing factors also known to cause RP (PRPF3, PRPF8, PRPF3"],"journal":["Nature genetics"],"pubmed_title":["De novo and inherited dominant variants in U4 and U6 snRNA genes cause retinitis pigmentosa."],"pmcid":["PMC12807869"],"funding_grant_id":["UG1 EY033292","UG1 EY033293","P30 EY002162","UG1 EY033286","R01 EY024698","R01 EY030499","T32 EY026590","K99 EY036930","R01 EY018213","R01 EY031663","R24 EY028758","R01 EY030591","P30 EY022589","R01 EY033770","P30 EY019007","R24 EY027285","R01 EY012910","P30 EY014104","R01 EY035717","U01 EY030580"],"pubmed_authors":["Vaclavik V","Lin S","Haack TB","Bernard V","Iglesias-Romero AB","Sarma AS","Dudakova L","Sajiki AF","Jensson BO","Zeuli R","Farrar GJ","Papachristou A","de la Cerda B","Kalatzis V","Holtes LK","Ayyagari R","Arno G","Cancellieri F","Knezy K","Leibu R","Biswas P","Sharon D","Burin des Roziers C","Lamey TM","Corradi Z","Gilissen C","Mukherjee R","Rodriguez-Hidalgo M","Blanco-Kelly F","Pfau M","Valente EM","Tran VH","Vajter M","Scholl HPN","Verhoeven VJM","Bijon J","Martins N","De Roach JN","Sabir AH","Yioti GG","Santos CM","Hitti-Malin RJ","Heon E","Valero R","Cattaneo L","McLaren TL","Webster AR","Hoefsloot LH","Ferraz Sallum JM","Karali M","Yoshitake K","Feltgen N","Griffiths-Jones S","Freund KB","Bremond-Gignac D","Mahroo OA","Ben-Yosef T","Lopez I","Chadderton N","Oldak M","Banin E","Kellner U","Hardcastle AJ","Daiger SP","Leroy BP","Dhaenens CM","AlTalbishi A","Ruiz-Ederra J","Sullivan LS","Vincent AL","de Bruijn SE","Ramesar R","Sulem P","Gardner JC","Mahieu Q","Ullah M","Liskova P","Mansard L","Klaver CCW","Mauring L","Roberts L","De Zaeytijd J","Koenekoop RK","Lee W","Signorini SG","Branham K","Shliaga S","Cremers FPM","Gonzalez-Duarte R","Stefansson K","Bocquet B","De Bruyne M","Lopez-Rodriguez VRJ","Stingl K","Ayuso C","Andreasson S","Ibanez MBB","Bujakowska KM","Manes G","Place E","Gana S","Ellingford JM","Goto K","Rivolta C","Simonelli F","Astuti GDN","van Aerschot J","Ansari G","Landau C","Kominami T","Meunier I","Valleix S","Stanek D","Neveling K","Ramond F","Tsoka P","Boonen EGM","Kaminska K","Stefaniotou M","Szabo V","Jacob AI","Sousa AB","Tsang SH","Cadena EL","Roosing S","Folcher M","De Baere E","Rasquin FA","Birch DG","Hoischen A","Nagy ZZ","Kuhlewein L","Cvackova Z","Jones K","Thiadens AAHJ","Sanchez-Barbero AI","Banfi S","Szaflik JP","Zuleger T","Kamakari S","Millan JM","Quinodoz M","Fernandez-Caballero L","Suga A","Valentine C","Boon CJF","McKibbin M","Zenteno JC","Toomes C","Calzetti G","Hayashi T","Britten-Jones AC","van den Born LI","Van Heetvelde M","Barakat TS","Valeina S","Panneman DM","Duncan JL","Percesepe A","Hoyng CB","Charbel Issa P","Zomer N","Coutinho-Santos L","Taurina G","Garanto A","Haer-Wigman L","Mizobuchi K","Pan Y","Rice GI","Sangermano R","Wissinger B","Pierce EA","Ali M","Michaelides M","Fenner BJ","Oorsprong M","Iwata T","Barboni MTS","Derks R","Scarpato M","Kohl S","Holtan JP","Bauwens M","Tsilimbaris MK","Whelan L","Martin-Gutierrez MP","Rodenburg K","Inglehearn CF"],"additional_accession":[]},"is_claimable":false,"name":"De novo and inherited dominant variants in U4 and U6 snRNA genes cause retinitis pigmentosa.","description":"Small nuclear RNAs (snRNAs) combine with specific proteins to generate small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. U4 snRNA forms a duplex with U6 and, together with U5, contributes to the tri-snRNP spliceosomal complex. Variants in RNU4-2, which encodes U4, have recently been implicated in neurodevelopmental disorders. Here we show that heterozygous inherited and de novo variants in RNU4-2 and in four RNU6 paralogs (RNU6-1, RNU6-2, RNU6-8 and RNU6-9), which encode U6, recur in individuals with nonsyndromic retinitis pigmentosa (RP), a genetic disorder causing progressive blindness. These variants cluster within the three-way junction of the U4/U6 duplex, a site that interacts with tri-snRNP splicing factors also known to cause RP (PRPF3, PRPF8, PRPF3","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-06-06T14:01:37.392Z","creation":"2026-05-31T03:10:16.21Z"},"accession":"S-EPMC12807869","cross_references":{"pubmed":["41513982"],"doi":["10.1038/s41588-025-02451-4"]}}