PXD009297
PXD009297 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | INPP5K and SIL1 associated pathologies with overlapping clinical phenotypes converge through dysregulation of PHGDH |
Description | In this study, we describe new patients suffering from INPP5K mutations and hereby expand the mutational and clinical spectrum of the underlying disease. Pathogenicity of a new INPP5K missense mutation has been functionally confirmed. In addition, we systematically addressed the need to identify common molecular key players to link phenotypically similar rare diseases. For this purpose, utilizing cells derived from INPP5K and SIL1 patients, we performed proteomic profiling and identified PHGDH, as a protein significantly altered in abundance in the in vitro systems of both diseases. Prompted by the striking molecular link between MSS, INPP5K- and PHGDH-phenotypes and the fact that PHGDH-patients notoriously respond to L-serine treatment, respective zebrafish models have been generated and responseto L-serine treatment has been addressed in vivo. Apart from the biochemical link between MSS, INPP5K-and PHGDH-phenotypes, affection of CDK9, a protein modulating the activity of CTDP1 biochemically links the INPP5K-phenotype to CCFDN. Thus, our study not only allowed to build molecular bridges between four phenotypically overlapping rare diseases but more importantly allowed to transfer the acquiredmolecular knowledge to the pre-clinical testing of a therapeutic intervention concept. |
HostingRepository | PRIDE |
AnnounceDate | 2021-04-07 |
AnnouncementXML | Submission_2021-04-06_22:12:43.016.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Laxmikanth Kollipara |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iTRAQ4plex-116 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2018-03-22 04:39:38 | ID requested | |
1 | 2021-04-06 07:05:55 | announced | |
⏵ 2 | 2021-04-06 22:12:43 | announced | 2021-04-07: Updated project metadata. |
Publication List
10.1093/BRAIN/AWAB133; |
Hathazi D, Cox D, D'Amico A, Tasca G, Charlton R, Carlier RY, Baumann J, Kollipara L, Zahedi RP, Feldmann I, Deleuze JF, Torella A, Cohn R, Robinson E, Ricci F, Jungbluth H, Fattori F, Boland A, O'Connor E, Horvath R, Barresi R, Lochm, ü, ller H, Urtizberea A, Jacquemont ML, Nelson I, Swan L, Bonne G, Roos A, INPP5K and SIL1 associated pathologies with overlapping clinical phenotypes converge through dysregulation of PHGDH. Brain, 144(8):2427-2442(2021) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: L-serine, INPP5K, BiP, PHGDH,SIL1 |
Contact List
Dr. Andreas Roos | |
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contact affiliation | Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Otto-Hahn-Str. 6b, 44227 Dortmund, Germany. Tel: ++49-231-13924232; Fax: ++49-231-13924850 |
contact email | andreas.roos@isas.de |
lab head | |
Laxmikanth Kollipara | |
contact affiliation | Leibniz – Institut für Analytische Wissenschaften - ISAS - e.V. |
contact email | laxmikanth.kollipara@isas.de |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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