Autoinflammatory disorders
Gene: UBA1
VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) Syndrome is observed in males, manifesting in the fifth decade of life or later, characterized by systemic inflammation and progressive bone marrow failure. Common inflammatory features include fever, chondritis, vasculitis, neutrophilic dermatosis and sterile alveolitis.
VEXAS is caused by loss of function somatic mutations in the UBA1 gene.Created: 18 Oct 2023, 5:08 p.m. | Last Modified: 18 Oct 2023, 5:08 p.m.
Panel Version: 1.1
Mode of inheritance
Other
Phenotypes
ever; chondritis; vasculitis; neutrophilic dermatosis; sterile alveolitis; progressive bone marrow failure; cytopenia
Publications
Mode of pathogenicity
Other
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Following further discussions with the GMS specialist group, it was agreed that the coverage of this test does include somatic variant detection. Therefore, the rating of this gene has been updated to green and the mode of inheritance set to "Other" following NHS Genomic Medicine Service approval.Created: 29 Nov 2023, 2:11 p.m. | Last Modified: 29 Nov 2023, 2:11 p.m.
Panel Version: 1.10
Added 'to_be_confirmed_NHSE' tag - gene to be further discussed due to somatic pathogenesisCreated: 16 Feb 2022, 11:37 a.m. | Last Modified: 16 Feb 2022, 11:37 a.m.
Panel Version: 0.32
Somatic variants (mostly at the M41 residue) cause an autoinflammatory disorder named VEXAS which exclusively affects men, with the exception of two female patients identified to date who acquired X monosomy in the bone marrow karyotype. Sufficient cases described in literature to support a gene-disease association but coverage of this test for somatic variant detection should be discussed with the test evaluation group prior to inclusion of UBA1 on this panel.Created: 11 Jan 2022, 2:50 p.m. | Last Modified: 11 Jan 2022, 2:50 p.m.
Panel Version: 0.7
Phenotypes
VEXAS syndrome, somatic, OMIM:301054
Publications
Publications for gene: UBA1 were set to 33108101; 33690815; 34048852; 34077651; 34196684
Tag to_be_confirmed_NHSE was removed from gene: UBA1.
Gene: uba1 has been classified as Green List (High Evidence).
Mode of pathogenicity for gene: UBA1 was changed from to Other
Tag to_be_confirmed_NHSE tag was added to gene: UBA1.
Source NHS GMS was added to UBA1.
Publications for gene: UBA1 were set to 34048852; 33108101
Tag somatic tag was added to gene: UBA1.
gene: UBA1 was added gene: UBA1 was added to Autoinflammatory disorders. Sources: Expert Review Red Mode of inheritance for gene: UBA1 was set to Other Publications for gene: UBA1 were set to 34048852; 33108101 Phenotypes for gene: UBA1 were set to VEXAS syndrome, somatic, OMIM:301054