PXD032816-3

PXD032816 is an original dataset announced via ProteomeXchange.

Title	Variants in SART3 cause a novel spliceosomopathy characterised by failure of testis development and neuronal defects
Description	Squamous cell carcinoma antigen recognized by T cells 3 (SART3) is an RNA binding protein that regulates a diverse array of biological processes, including recycling small nuclear ribonucleic acids (snRNAs) back to the spliceosome. Here we describe nine individuals from six independent families with a multisystem disorder, characterised by intellectual disability, developmental delay, brain anomalies and 46, XY-specific gonadal dysgenesis, who harbour recessive variants in the SART3 gene. Knockdown of the fly orthologue of SART3, Rnp4f, demonstrates a conserved role in neuronal and testicular development. Human induced pluripotent stem cells (iPSCs) carrying patient SART3 variants have disrupted neuronal and gonadal differentiation in vitro. These iPSCs have significant disruption to multiple signalling pathways and complexes, including spliceosome components and mRNA splicing. We propose that biallelic variants in the SART3 gene underlie a novel spliceosomopathy characterised by neuronal defects and testicular dysgenesis.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:47:44.063.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ralf Schittenhelm
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-25 08:59:25	ID requested
1	2023-06-11 16:03:11	announced
2	2023-11-14 09:01:05	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 05:47:44	announced	2024-10-22: Updated project metadata.

10.1038/S41467-023-39040-0;

submitter keyword: Gonadal dysgenesis, 46, neurodevelopmental disorder, spliceosome,XY DSD, SART3, Tip110

Katie Ayers
contact affiliation	Murdoch Children’s Research Institute, Melbourne
contact email	katie.ayers@mcri.edu.au
lab head
Ralf Schittenhelm
contact affiliation	Monash University
contact email	ralf.schittenhelm@monash.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/06/PXD032816

PRIDE project URI

• PRIDE
  1. PXD032816
     1. Label: PRIDE project
     2. Name: Variants in SART3 cause a novel spliceosomopathy characterised by failure of testis development and neuronal defects