CUL2
Chr 10cullin 2
The CUL2 protein serves as a core scaffold component of multiple E3 ubiquitin ligase complexes that target specific proteins for degradation, including hypoxia-inducible factors and proteins involved in DNA replication. CUL2 mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, seizures, and dysmorphic features. This gene is extremely constrained against loss-of-function variants, indicating that CUL2 haploinsufficiency is not well tolerated in humans.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
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
131 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 | 8 | 0 | 8 |
Likely Pathogenic | 0 | 1 | 0 | 0 | 1 |
VUS | 0 | 70 | 7 | 0 | 77 |
Likely Benign | 0 | 1 | 6 | 0 | 7 |
Benign | 0 | 0 | 4 | 2 | 6 |
| Total | 0 | 72 | 25 | 2 | 99 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CUL2 · 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