Early onset or syndromic epilepsy

Gene: UBR5

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 11 Mar 2026, 3:39 p.m. | Last Modified: 11 Mar 2026, 3:39 p.m.

Panel Version: 8.134

Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.

Created: 22 Jul 2025, 10:29 a.m. | Last Modified: 22 Jul 2025, 10:29 a.m.

Panel Version: 8.12

PMID:39721588 reported 29 unrelated individuals with a complex neurodevelopmental syndrome, which includes developmental delay (26/28), autism (16/26), intellectual disability (14/25), epilepsy (11/27), movement disorders (6/26) and/ or genital anomalies (4/25) as presenting phenotypes. They were all identified with variants in UBR5 gene, of which 28 had monoallelic inheritance (24 with de novo, 1 with maternal, 1 with maternal mosaic and 2 with unknown inheritance), while one had recessive inheritance.

Of the 28 patients with monoallelic variants, 16 had global developmental delay, 13 had ID and 10 patients had epilepsy/ seizures. The single patient with biallelic variant had severe/ profound ID, developmental delay and epileptic encephalopathy.

Functional evidence is also available from C. elegans and in vitro ubiquitination assays.

This gene is associated with phenotype in Gene2Phenotype (with 'moderate' rating on the DD panel), but not yet in OMIM.
Sources: Literature

Created: 22 Jul 2025, 10:26 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
complex neurodevelopmental disorder, MONDO:0100038

Publications

• 39721588