PXD076523 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | De novo heterozygous variants in EHMT2 cause a novel Kleefstra related syndrome via loss of G9a methyltransferase activity |
| Description | EHMT1 and EHMT2 genes encode human euchromatin histone lysine methyltransferase 1 and 2 (EHMT1 alias GLP; EHMT2 alias G9a) that form heteromeric GLP/G9a complexes with essential roles in epigenetic regulation of gene expression. While EHMT1 haploinsufficiency has been established as the cause of Kleefstra syndrome 1, the pathogenesis of G9a dysfunction in human disease remains largely unknown. We identified seven de novo EHMT2 variants in patients with clinical presentation, episignatures, histone modifications and transcriptomic profiles similar to those of Kleefstra syndrome 1. In vitro studies revealed that these variants encode for structurally stable G9a proteins that are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. Heterozygous mice carrying a patient-derived variant exhibited growth retardation, facial/skull dysmorphia and aberrant behavior. Here we report pathogenic EHMT2 variants that likely exert dominant-negative effect on GLP/G9a complexes and thus genocopy the EHMT1 haploinsufficiency via a distinct molecular mechanism. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-07-03 |
| AnnouncementXML | Submission_2026-07-03_06:40:22.289.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Petr Pompach |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | iodoacetamide derivatized residue |
| Instrument | timsTOF SCP |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2026-04-02 12:08:55 | ID requested | |
| ⏵ 1 | 2026-07-03 06:40:22 | announced | |
Publication List
Keyword List
| submitter keyword: EHMT2, Kleefstra syndrome 1, G9a proteins,EHMT1 |
Contact List
| Ales Hnizda |
|---|
| contact affiliation | Research Unit for Rare Diseases, Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic |
| contact email | Ales.Hnizda@lf1.cuni.cz |
| lab head | |
| Petr Pompach |
|---|
| contact affiliation | Intitute of Biotechnology |
| contact email | petr.pompach@ibt.cas.cz |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD076523
- Label: PRIDE project
- Name: De novo heterozygous variants in EHMT2 cause a novel Kleefstra related syndrome via loss of G9a methyltransferase activity
