CUL4B
Chr XXLRcullin 4B
The encoded protein forms an E3 ubiquitin ligase complex that catalyzes polyubiquitination of specific protein substrates and is required for proteolysis of DNA replication regulators including chromatin licensing and DNA replication factor 1 and cyclin E. Loss-of-function mutations cause X-linked syndromic intellectual developmental disorder, Cabezas type, with X-linked recessive inheritance. The gene is extremely intolerant to loss-of-function variation, consistent with its essential role in protein degradation pathways critical for DNA replication.
Definitive — sufficient evidence for diagnostic panels
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CUL4B · 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
External Resources
Links to major genomics databases and tools