PXD060960-1

PXD060960 is an original dataset announced via ProteomeXchange.

Title	Characterization of a new variant of SERPINA1 Gene Causing Alpha-1 Antitrypsin Deficiency
Description	Alpha 1-Antitrypsin Deficiency (AATD) is a rare genetic disorder caused by mutations in the SERPINA1 gene, which encodes the Alpha 1-Antitrypsin (AAT) protein. Individuals carrying pathogenic SERPINA1 variants are predisposed to lung and liver damage. The most common AATD-associated SERPINA1 alleles are the S and Z alleles, though additional variants have been identified. This case report describes the discovery of a new SERPINA1 variant detected in two cities in southeastern France. This variant, named PiZmarseille, results from in cis combination of the PiZ allele and a rare variant known as PiZbristol. PiZmarseille has been associated with early-onset liver disease in childhood. To further investigate this new variant, we performed its molecular characterization, revealing that PiZmarseille shares the pathogenic properties of both the PiZ and PiZbristol variants. These properties include its retention in the endoplasmic reticulum as aggregates and its degradation through the autophagy and proteasome pathways. Additionally, we conducted proteomic profiling to explore the association of this mutant with liver disease. Our analysis revealed that the neutrophil degranulation pathway is particularly deregulated in PiZmarseille liver samples. Furthermore, when compared to other AAT genotypes, the proteomic profile of PiZmarseille most closely resembles that of the PiZ variant, rather than other SERPINA1 variants.
HostingRepository	PRIDE
AnnounceDate	2025-12-08
AnnouncementXML	Submission_2025-12-07_16:23:10.135.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dupuy Jean-William
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-19 06:24:27	ID requested
⏵ 1	2025-12-07 16:23:11	announced

Leon C, Odou MF, Roquelaure B, Lebreton L, Ruiz M, Schneider CV, Renoux C, Evrard A, Balduyck M, Dechomet M, Lombard C, Butori-Pepino M, Schneider KM, Marin V, di-Tomasso S, Dourthe C, Dupuy JW, Raymond AA, Collardeau-Frachon S, Haffner A, Fritih R, Goubert E, Geromel V, Joly P, Fabre A, Bouchecareilh M, Characterization of a novel SERPINA1 variant carrying two missense mutations: molecular mechanisms and functional impact. Orphanet J Rare Dis, 20(1):615(2025) [pubmed]

10.1186/s13023-025-04142-z;

submitter keyword: AATD,Alpha 1-Antitrypsin Deficiency, Liver

Marion Bouchecareilh
contact affiliation	University of Bordeaux, CNRS, INSERM, BRIC, U1312, Bordeaux, France
contact email	marion.bouchecareilh@cnrs.fr
lab head
Dupuy Jean-William
contact affiliation	OncoProt plateform, UAR TBMCore CNRS 3427 INSERM US005 University of Bordeaux
contact email	jean-william.dupuy@u-bordeaux.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/2025/12/PXD060960

PRIDE project URI

• PRIDE
  1. PXD060960
     1. Label: PRIDE project
     2. Name: Characterization of a new variant of SERPINA1 Gene Causing Alpha-1 Antitrypsin Deficiency