PXD047896

PXD047896 is an original dataset announced via ProteomeXchange.

Title	Autism mutations rewire protein interaction networks to drive neurodevelopmental pathology
Description	Translating high-confidence (hc) autism spectrum disorder (ASD) genes into viable treatment targets remains elusive. We constructed a foundational protein-protein interaction (PPI) network in HEK293T cells involving 100 hcASD risk genes, revealing over 1,800 PPIs (87% novel). Interactors, expressed in the human brain and enriched for ASD but not schizophrenia genetic risk, converged on protein complexes involved in neurogenesis, tubulin biology, transcriptional regulation, and chromatin modification. A PPI map of 54 patient-derived missense variants identified differential physical interactions, and we leveraged AlphaFold-Multimer predictions to prioritize direct PPIs and specific variants for interrogation in Xenopus tropicalis and human forebrain organoids. A mutation in the transcription factor FOXP1 led to reconfiguration of DNA binding sites and altered development of deep cortical layer neurons in forebrain organoids. This work offers new insights into molecular mechanisms underlying ASD and describes a powerful platform to develop and test therapeutic strategies for many genetically-defined conditions.
HostingRepository	PRIDE
AnnounceDate	2026-09-03
AnnouncementXML	Submission_2026-09-03_13:04:06.761.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Justin McKetney
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-18 03:05:16	ID requested
1	2026-09-03 09:06:12	announced
⏵ 2	2026-09-03 13:04:07	announced	2026-09-03: Updated project metadata.

10.1126/SCIENCE.ADY4523;

submitter keyword: None

Nevan Krogan
contact affiliation	Professor, Cellular and Molecular Pharmacology
contact email	nevan.krogan@ucsf.edu
lab head
Justin McKetney
contact affiliation	University of California, San Francisco
contact email	justinmcketney@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/2026/09/PXD047896

PRIDE project URI

• PRIDE
  1. PXD047896
     1. Label: PRIDE project
     2. Name: Autism mutations rewire protein interaction networks to drive neurodevelopmental pathology