PXD009272

PXD009272 is an original dataset announced via ProteomeXchange.

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 response to 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 acquired molecular knowledge to the pre-clinical testing of a therapeutic intervention concept.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:20:48.113.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	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-21 01:08:55	ID requested
1	2021-04-06 07:01:53	announced
2	2021-04-06 22:10:50	announced	2021-04-07: Updated project metadata.
⏵ 3	2024-10-22 05:20:49	announced	2024-10-22: Updated project metadata.

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]

curator keyword: Biomedical

submitter keyword: L-serine, INPP5K, BiP, PHGDH,SIL1

Dr. Andreas Roos
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

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/2021/04/PXD009272

PRIDE project URI

• PRIDE
  1. PXD009272
     1. Label: PRIDE project
     2. Name: INPP5K and SIL1 associated pathologies with overlapping clinical phenotypes converge through dysregulation of PHGDH