CUL4A
Chr 13cullin 4A
CUL4A encodes a scaffold protein that serves as the core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes, which target specific proteins for degradation and regulate processes including DNA repair, cell cycle progression, and circadian rhythms. Mutations cause X-linked intellectual disability with growth retardation and malformations in males, with an X-linked inheritance pattern. The gene is highly intolerant to loss-of-function variants, reflecting its essential cellular functions.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Moderately missense-constrained (top ~2.5%)
ClinVar Variant Classifications
230 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 | 114 | 0 | 114 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 67 | 11 | 0 | 78 |
Likely Benign | 0 | 3 | 0 | 0 | 3 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 70 | 128 | 0 | 198 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CUL4A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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