PXD058947-1

PXD058947 is an original dataset announced via ProteomeXchange.

Title	Multiomics analyses reveal B cell differentiation arrest and neutrophil hypogranulation in a patient with an immunodeficiency caused by a novel homozygous missense variant in HYOU1
Description	The Hypoxia Upregulated Protein 1 (HYOU1) encodes an endoplasmic reticulum chaperone which is expressed in response to endoplasmic reticulum stress and contributes to cellular protection by restoring cell homeostasis. In this study, we report a patient with a novel homozygous variant in HYOU1 (NM_001130991.3:c.1331C>A, p.Pro444His), who was born to related parents and presented with combined immunodeficiency, failure to thrive, and hypoglycemia. We undertook a multiomics analysis combining transcriptomics, proteomics, and single cell RNA sequencing analyses, demonstrating a drastic reduction in B cell count and hypogranulation of neutrophils in conformity with the findings of immunophenotyping. Additionally, we showed that despite the HYOU1 transcript being expressed and stable, the patient has HYOU1 deficiency at the protein level. Moreover, single cell RNA sequencing of bone marrow revealed that the B cell differentiation process is prematurely arrested at pre-pro B cell stage. In conclusion, this work brings new insights into genotype-phenotype correlations by providing a detailed characterization of the B-cell deficiency and neutrophil hypogranulation as phenotypic features of an immunodeficiency due to HYOU1 variants.
HostingRepository	PRIDE
AnnounceDate	2026-08-18
AnnouncementXML	Submission_2026-08-18_01:57:55.340.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Aurélie Hirschler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-17 08:22:28	ID requested
⏵ 1	2026-08-18 01:57:55	announced

Dataset with its publication pending

submitter keyword: B cell deficiency, multiomics, neutrophil hypogranulation,HYOU1, Immunodeficiency

Carapito Christine
contact affiliation	IPHC-LSMBO
contact email	ccarapito@unistra.fr
lab head
Aurélie Hirschler
contact affiliation	LSMBO, IPHC
contact email	aurelie.hirschler@unistra.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/2026/08/PXD058947

PRIDE project URI

• PRIDE
  1. PXD058947
     1. Label: PRIDE project
     2. Name: Multiomics analyses reveal B cell differentiation arrest and neutrophil hypogranulation in a patient with an immunodeficiency caused by a novel homozygous missense variant in HYOU1