PXD035840-2
PXD035840 is an original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: pulldown,NUDCD3, proteomics, Omenn syndrome |
Contact List
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 |
Full Dataset Link List
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 |
Repository Record List
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