PXD065122

PXD065122 is an original dataset announced via ProteomeXchange.

Title	Rare ADAR1 loss-of-function variants alter RNA editing and drive interferondependent inflammation in psoriasis
Description	In 4 unrelated pedigrees, we report rare heterozygous loss-of-function ADAR1 mutations cosegregating with autosomal dominant, early onset psoriasis and increased type I interferon (IFN)-stimulated gene (ISG) transcripts in skin lesions and/or blood. We identified 6 additional variants in a psoriasis cohort. Skin single cell transcriptomics identified keratinocytes and melanocytes as key IFN sources. ADAR1 knockdown in keratinocytes and melanocytes, and transduction of ADAR1G1119R and ADAR1P3A alleles in keratinocytes, led to reduced A-to-I RNA editing and upregulation of ISG expression, reversed by JAK1 and TYK2 inhibition, mirroring their clinical benefit in these patients. This set of data defines a new IFN-dependent psoriasis subtype resulting from inborn errors of ADAR1-dependent RNA editing, leading to IFN constitutive dysregulation, and opens new avenues in precision medicine.
HostingRepository	PRIDE
AnnounceDate	2026-04-27
AnnouncementXML	Submission_2026-04-27_04:43:52.001.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chiara guerrera
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-17 10:26:00	ID requested
⏵ 1	2026-04-27 04:43:52	announced

Dataset with its publication pending

submitter keyword: keratinocyte, melanocyte, timTOF Pro,ADAR1

Ida Chiara Guerrera
contact affiliation	Plateforme protéomique Necker, Université Paris Cité - Structure Fédérative de Recherche Necker, INSERM US24/CNRS UAR3633, Paris 75015, France.
contact email	chiara.guerrera@inserm.fr
lab head
Chiara guerrera
contact affiliation	Necker proteomics, INSERM
contact email	chiara.guerrera@inserm.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/2026/04/PXD065122

PRIDE project URI

• PRIDE
  1. PXD065122
     1. Label: PRIDE project
     2. Name: Rare ADAR1 loss-of-function variants alter RNA editing and drive interferondependent inflammation in psoriasis