PXD053534

PXD053534 is an original dataset announced via ProteomeXchange.

Title	Extensive hypoglycosylation of serum N-glycoproteins in SRD5A3 deficiency
Description	Polyprenol reductase is an enzyme encoded by the SRD5A3 gene, which catalyzes the synthesis of dolichol from polyprenols. Dolichol serves as a carrier for glycan precursors in N-linked glycosylation or monosaccharides in O-glycosylation, C-mannosylation, and GPI anchor biosynthesis. Pathogenic variants in SRD5A3 can result in a congenital disorder of glycosylation (CDG), SRD5A3-CDG, which is inherited in an autosomal recessive manner. Most serum proteins undergo glycosylation and changes in the glycosylation levels of numerous serum glycoproteins have been associated with pathological consequences. Despite the critical role of SRD5A3 in glycosylation, the impact of its deficiency on the glycosylation of serum proteins remains largely unexplored. In this study, we used tandem mass tags (TMT)-based multiplexed quantitation approach to analyze serum N-glycoproteins and proteins in SRD5A3-CDG patients and controls. We quantified 2,200 serum N-glycopeptides from 359 N-glycosites from 204 serum proteins. Extensive hypoglycosylation of serum proteins was observed in patients, with 245 of 291 dysregulated glycopeptides showing hypoglycosylation. These significantly changing glycopeptides belonged to several known abundant serum glycoproteins including haptoglobin, plasma serine protease inhibitor, alpha-1-B glycoprotein, alpha-2-macroglobulin and ceruloplasmin. We also detected changes in glycopeptides from albumin which has recently been shown to be glycosylated. Overall, our study provides novel insights into alterations in the glycosylation status of serum proteins in SRD5A3-CDG that could facilitate further investigations into diagnostics and therapeutics aspects of this CDG.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-07_17:26:52.171.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Akhilesh Pandey
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	complex glycosylation; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-01 13:40:23	ID requested
⏵ 1	2026-06-07 17:26:52	announced

10.1016/j.ymgme.2026.109846;

Garapati K, Jain A, Joshi N, Sachdeva GS, Nam D, Saraswat M, Pasupuleti RR, Schultz MJ, Kozicz T, Morava E, Pandey A, Albumin as a glycoprotein biomarker in congenital disorders of glycosylation. Mol Genet Metab, 147(4):109846(2026) [pubmed]

submitter keyword: SRD5A3-CDG, Glycosylation, Rare diseases, Orbitrap Eclipse Tribrid,Polyprenol reductase, Type 1 CDG, Complex glycans

Akhilesh Pandey
contact affiliation	Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota
contact email	pandey.akhilesh@mayo.edu
lab head
Akhilesh Pandey
contact affiliation	Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905
contact email	pandey.akhilesh@mayo.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053534
     1. Label: PRIDE project
     2. Name: Extensive hypoglycosylation of serum N-glycoproteins in SRD5A3 deficiency