PXD040023

PXD040023 is an original dataset announced via ProteomeXchange.

Title	Proteomic interactome analyses of Glypican 1 and a putative disease modifying variant
Description	In an 8-year-old girl of consanguineous Turkish parents, who developed ataxic gait and polyneuropathy at the age of 3 years, we identified a biallelic missense variant c.424C>T, p.R142W in Glypican 1 (GPC1) by using whole genome sequencing. Up to date, GPC1 has not been associated with a neuromuscular disorder and we hypothesized that this variant, which is predicted as deleterious (CADD score 26.4) may be causative for the disease. Using mass spectrometry-based proteomics, we investigated the interactome of the GPC1 missense variant. We identified 198 proteins interacting with GPC1, of which 16 were altered due to the missense variant. Differentially regulated proteins include members of the vacuolar ATPase (v-ATPase) and mammalian target of rapamycin complex 1 (mTORC1) complexes, whose mis-regulation could have a potential impact on disease severity in the patient. Importantly, these proteins are novel interaction partners of GPC1. At 11 years of age, the patient developed a cardiomyopathy and kyphoscoliosis and a Friedreich’s Ataxia (FRDA) was suspected. Indeed a 104 GAA-repeat expansion in the FXN gene was found. Given the unusually severe phenotype in a patient with FRDA carrying only 104 GAA-repeats, we currently assume that the disturbed function in GPC1 may exacerbate the disease phenotype.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_06:54:26.202.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peter Robert Mosen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidoethyl-L-cysteine
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-10 04:56:46	ID requested
1	2023-08-15 08:32:48	announced
⏵ 2	2023-11-14 06:54:26	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: GPC1, DIA-MS, IP,human

Dominic Winter
contact affiliation	Institute for Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, 53115 Bonn
contact email	Dominic.Winter@uni-bonn.de
lab head
Peter Robert Mosen
contact affiliation	Utrecht University Biomolecular Mass Spectrometry and Proteomics Padualaan 8, 3584 CH Utrecht
contact email	p.r.mosen@uu.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040023
     1. Label: PRIDE project
     2. Name: Proteomic interactome analyses of Glypican 1 and a putative disease modifying variant