UBE3A (Ubiquitin-protein ligase E3A) variants and mutations

UBE3A (also known as Ubiquitin-protein ligase E3A) is a human protein-coding gene encoding an ubiquitin-protein ligase E3A protein. Its ubiquitin-ligase activity controls turnover of selected neuronal proteins and is subject to maternal-specific expression in many neurons. Loss of the maternal allele causes Angelman syndrome, while increased dosage contributes to neurodevelopmental abnormalities in 15q11-q13 duplication. This analysis covers 481 UBE3A variants and mutations. Of these, 63% have computational variant effect predictions. Disease context includes Angelman syndrome, hereditary disease, and Intellectual disability. Example UBE3A variants include K3R, Q6P, and W9*.

Variant analysis overview

Gene: UBE3A
Protein: Ubiquitin-protein ligase E3A
UniProt accession: Q05086
Organism: Homo sapiens
Variants analyzed: 481
Variant scope: all variants
Completed: 2026-08-18

Variant and mutation evidence

Variant composition: 233 unspecified-consequence records; 1 stop retained variant; 3 stop lost; 95 synonymous variants; 138 missense variants; 1 frameshift variants; 4 stop-gained variants; 1 in-frame deletions; 3 splice-region variants; 2 substitution
Prediction scores: 305 variants have prediction scores (63% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: Angelman syndrome, hereditary disease, Intellectual disability, neurodevelopmental disorder, Epileptic encephalopathy, Global developmental delay, Seizure, Abnormal corpus callosum morphology, Expressive language delay, Poor speech, EEG abnormality, keloid.

Protein structure and variant hotspots

Protein features: 1 domains; 2 post-translational modification sites.
Structural context: 110 variants have structural context.
Experimental data: 57 protein positions have experimental scores. Source: binding assays.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable UBE3A variants

Examples include K3R, Q6P, W9*, G12V, E20V, R23Q, L32Q, I33M. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

UBE3A analysis run — UBE3A (481 variants) — completed 2026-08-18