PXD071983

PXD071983 is an original dataset announced via ProteomeXchange.

Title	GGC repeat expansions within novel open reading frames are translated into toxic polyglycine proteins in oculopharyngodistal myopathy
Description	3 to 6% of the human genome is composed of microsatellite sequences, which are short DNA elements composed of 2 to 6 nucleotide motifs repeated in tandem. Expansion of a subset of these microsatellites is the leading cause of >60 diseases. However, most of these mutations are located in sequences annotated as non-coding, thus questioning how they are pathogenic. Here, we found that GGC repeat expansions causing oculopharyngodistal myopathy with or without leukoencephalopathy (OPDM/OPML) are located within previously unrecognized open reading frames (ORFs), resulting in their translation into novel polyglycine-containing proteins. Antibodies developed against these proteins stain the p62-positive inclusions typical of these diseases. Moreover, expression of these polyglycine proteins causes locomotor and skeletal muscle alterations associated with neurodegeneration in cell, fly and mouse models. Finally, we identified a compound, the cationic porphyrin TMPyP4, targeting expression of these polyglycine proteins, raising hope to develop a therapy for these disorders. Overall, this work highlights the complexity and richness of the human genome and the importance of mutations in yet unrecognized small ORFs.
HostingRepository	PRIDE
AnnounceDate	2026-02-03
AnnouncementXML	Submission_2026-02-03_10:45:42.909.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	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-14 19:08:54	ID requested
⏵ 1	2026-02-03 10:45:43	announced

10.1038/S41588-026-02507-Z;

submitter keyword: polyglycine protein,oculopharyngodistal myopathy , microsatellite sequences

Nicolas Charlet-Berguerand
contact affiliation	Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, CNRS UMR 7104, Inserm UMR-S 1258, Illkirch, France.
contact email	ncharlet@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/2026/02/PXD071983

PRIDE project URI

• PRIDE
  1. PXD071983
     1. Label: PRIDE project
     2. Name: GGC repeat expansions within novel open reading frames are translated into toxic polyglycine proteins in oculopharyngodistal myopathy