UBR5
Chr 8ADubiquitin protein ligase E3 component n-recognin 5
Also known as: DD5, EDD, EDD1, HYD, NEDSBH
UBR5 encodes an E3 ubiquitin-protein ligase that targets specific proteins for degradation through the ubiquitin-proteasome system, playing critical roles in protein quality control, DNA damage response, and transcriptional regulation. Mutations cause autosomal dominant neurodevelopmental disorder with speech delay and behavioral abnormalities. This gene is highly constrained against loss-of-function variants (pLI=1, LOEUF=0.073), indicating that functional copies are essential for normal development.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
300 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 | 1 | 3 | 4 | 0 | 8 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 149 | 3 | 0 | 152 |
Likely Benign | 0 | 6 | 7 | 24 | 37 |
Benign | 0 | 0 | 1 | 4 | 5 |
| Total | 1 | 158 | 15 | 28 | 202 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
UBR5 · 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