CRBN
Chr 3ARcereblon
Also known as: MRT2, MRT2A
CRBN encodes cereblon, a substrate recognition component of a DCX E3 ubiquitin ligase complex that mediates proteasomal degradation of regulatory proteins and maintains presynaptic glutamate release by regulating calcium-activated potassium channels in excitatory neurons. Mutations cause autosomal recessive intellectual developmental disorder, affecting cognitive functions including memory and learning. The gene shows very low constraint against loss-of-function variants (pLI 0.0003), consistent with its recessive inheritance pattern where heterozygous carriers are typically unaffected.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
ClinVar Variant Classifications
132 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 | 4 | 0 | 61 | 0 | 65 |
Likely Pathogenic | 5 | 2 | 7 | 0 | 14 |
VUS | 2 | 12 | 18 | 0 | 32 |
Likely Benign | 0 | 1 | 1 | 6 | 8 |
Benign | 0 | 0 | 3 | 5 | 8 |
Conflicting | — | 5 | |||
| Total | 11 | 15 | 90 | 11 | 132 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CRBN · 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