PXD035840

PXD035840 is an original dataset announced via ProteomeXchange.

Title	NUDCD3 deficiency disrupts V(D)J recombination to cause SCID/Omenn syndrome
Description	Inborn errors of T cell development present a pediatric emergency in which timely curative therapy is informed by molecular diagnosis. In 9 affected patients across 3 consanguineous kindreds, we detected homozygosity for a single deleterious missense variant in the gene NudC domain containing 3 (NUDCD3). Two infants lacked T and B lymphocytes altogether (T-B- severe combined immunodeficiency, T-B- SCID) while 7 showed classical features of Omenn syndrome. Restricted antigen receptor gene usage by residual T lymphocytes implied impaired V(D)J recombination. Patient cells showed reduced expression of NUDCD3 protein and diminished ability to support RAG-mediated recombination in vitro, associated with pathologic sequestration of RAG1 in nucleoli. A mouse model bearing the homologous variant phenocopied these abnormalities, confirming a conserved, requisite role for NUDCD3 in V(D)J recombination.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:59:52.011.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthias Trost
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-07 03:04:24	ID requested
1	2024-09-27 05:24:47	announced
⏵ 2	2024-10-22 06:59:52	announced	2024-10-22: Updated project metadata.

10.1126/sciimmunol.ade5705;

Chen R, Lukianova E, van der Loeff IS, Spegarova JS, Willet JDP, James KD, Ryder EJ, Griffin H, IJspeert H, Gajbhiye A, Lamoliatte F, Marin-Rubio JL, Woodbine L, Lemos H, Swan DJ, Pintar V, Sayes K, Ruiz-Morales ER, Eastham S, Dixon D, Prete M, Prigmore E, Jeggo P, Boyes J, Mellor A, Huang L, van der Burg M, Engelhardt KR, Stray-Pedersen A, Erichsen HC, Gennery AR, Trost M, Adams DJ, Anderson G, Lorenc A, Trynka G, Hambleton S, deficiency disrupts V(D)J recombination to cause SCID and Omenn syndrome. Sci Immunol, 9(95):eade5705(2024) [pubmed]

submitter keyword: pulldown,NUDCD3, proteomics, Omenn syndrome

Matthias Trost
contact affiliation	Laboratory for Biological Mass Spectrometry, Biosciences Institute, Newcastle University, Newcastle-upon-Tyne, NE2 4HH, UK
contact email	matthias.trost@newcastle.ac.uk
lab head
Matthias Trost
contact affiliation	Newcastle University
contact email	matthias.trost@ncl.ac.uk
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/2024/09/PXD035840

PRIDE project URI

• PRIDE
  1. PXD035840
     1. Label: PRIDE project
     2. Name: NUDCD3 deficiency disrupts V(D)J recombination to cause SCID/Omenn syndrome