PXD063846

PXD063846 is an original dataset announced via ProteomeXchange.

Title	Dysfunction of a SET3C-like complex underlies a family of related neurological disorders
Description	TBLR1, a subunit of the NCoR corepressor complex, is mutated in a range of neurodevelopmental disorders that only partially align symptomatically with those caused by mutations in its binding partner, MeCP2. In a search for novel TBLR1-binding partners, we identified ANKRD11 and SETD5 – mutations in which are amongst the most frequent genetic causes of neurodevelopmental disorders. Here we report that TBLR1 provides a molecular bridge between ANKRD11, SETD5 and NCoR in a complex with a strikingly resembles the SET3C complex of yeast. Pathogenic missense mutations in TBLR1, ANKRD11 and SETD5 disrupt this mammalian SET3C-like assembly. Mutations of this kind in Ankrd11 and Setd5 genes cause highly correlated changes in gene expression and severe developmental impairments. We present evidence that this complex restrains the expression of highly transcribed genes. Our results demonstrate that failure of transcriptional regulation by SET3C provides a convergent molecular basis for a family of neurodevelopmental disorders.
HostingRepository	PRIDE
AnnounceDate	2026-05-02
AnnouncementXML	Submission_2026-05-01_17:22:14.114.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christos Spanos
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-11 23:14:50	ID requested
⏵ 1	2026-05-01 17:22:14	announced

Dataset with its publication pending

submitter keyword: Human, TBLR1, neurological disorders, ANKRD11, SETD5, SET3C

Matthew Lyst
contact affiliation	University of Edinburgh
contact email	mlyst@exseed.ed.ac.uk
lab head
Christos Spanos
contact affiliation	University of Edinburgh
contact email	spanos.christos@gmail.com
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/2026/05/PXD063846

PRIDE project URI

• PRIDE
  1. PXD063846
     1. Label: PRIDE project
     2. Name: Dysfunction of a SET3C-like complex underlies a family of related neurological disorders