UBA3
Chr 3ubiquitin like modifier activating enzyme 3
Also known as: NAE2, UBE1C, hUBA3
The UBA3 protein serves as the catalytic subunit of an E1 enzyme that activates NEDD8, a ubiquitin-like protein essential for cell cycle progression and regulation of protein degradation pathways. Mutations cause autosomal recessive developmental delay with seizures and dysmorphic features, typically presenting in infancy or early childhood. This gene shows significant constraint against loss-of-function variants (LOEUF 0.405), indicating that complete loss of UBA3 function is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
ClinVar Variant Classifications
91 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 10 | 0 | 10 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 40 | 4 | 0 | 44 |
Likely Benign | 0 | 1 | 0 | 0 | 1 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 41 | 15 | 0 | 56 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
UBA3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools