PXD066823

PXD066823 is an original dataset announced via ProteomeXchange.

Title	Dual molecular mechanisms and functional compensation by RBMXL1 retrocopy underlie RBMX-associated neurodevelopmental syndrome
Description	Genetic variants in RBMX may cause X-linked neurodevelopmental syndromes, but their pathogenicity and mechanisms remain unclear. Here, we provide definitive evidence from nine unrelated families that RBMX variants lead to neurodevelopmental disorders characterised by intellectual disability, brain malformations, microcephaly, and microphthalmia. Combining in vitro and in vivo experiments in human and mouse models, we show that RBMX pathogenic variants disrupt cortical development through both loss- and gain-of-function mechanisms. Despite severe phenotypes in humans, Rbmx-deficient mice display only mild cortical abnormalities, which we attribute to partial compensation by Rbmxl1, a retrocopy that arose independently in mice and humans. We demonstrate that RBMX and RBMXL1 share protein and RNA partners and act redundantly during brain development, with RBMXL1 buffering the effect of RBMX loss. Our findings reveal that RBMX-related neurodevelopmental syndromes result from the interplay of opposing molecular mechanisms and retrocopy compensation, highlighting a previously unrecognized role for retrocopies in modulating disease severity.
HostingRepository	PRIDE
AnnounceDate	2026-07-28
AnnouncementXML	Submission_2026-07-28_06:31:08.119.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bastien Morlet
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-31 15:12:52	ID requested
⏵ 1	2026-07-28 06:31:08	announced

10.1093/brain/awag218;

Tilliole P, Mattausch C, Tilly P, Leit, ã, o E, Boutaud L, Lehalle D, An I, Argilli E, Aufox S, Callewaert B, Charles P, Cinkornpumin JK, Courtin T, Vecchia MD, Davis EE, Dimitrov BI, Dobyns W, Epifanova E, Grandgirard E, Jung M, Jurgensmeyer Langas S, Kaya S, Keren B, Khan TN, Lejeune E, Li M, Marie Y, Morlet B, Nava C, Pastor WA, Plassard D, Prada CE, Rastetter A, Schwaller N, Sestan N, Sherr E, Temple SL, Tenywa JF, Tielens S, van Haeringen A, Whitley H, Nguyen L, Steenpa, ß L, Rhinn M, Collins SC, H, é, ron D, Cormier-Daire V, Attie-Bitach T, Yalcin B, Depienne C, Godin JD, RBMX functional retrocopy safeguards brain development in a species-dependent context. Brain, ():(2026) [pubmed]

submitter keyword: neurodevelopmental disorder, evolution, splicing,RBMX, RBMXL1 retrocopy

Dr Juliette D. Godin
contact affiliation	IGBMC, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France, UMR7104, UMR-S 1258.
contact email	godin@igbmc.fr
lab head
Bastien Morlet
contact affiliation	IGBMC - CNRS UMR 7104 - Inserm U1258
contact email	morletb@igbmc.fr
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/2026/07/PXD066823

PRIDE project URI

• PRIDE
  1. PXD066823
     1. Label: PRIDE project
     2. Name: Dual molecular mechanisms and functional compensation by RBMXL1 retrocopy underlie RBMX-associated neurodevelopmental syndrome