CRBN

Chr 3

cereblon

Also known as: MRT2, MRT2A

NCBI Gene: 51185 ENSG00000113851 UniProt: Q96SW2

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein related to the Lon protease protein family. In rodents and other mammals this gene product is found in the cytoplasm localized with a calcium channel membrane protein, and is thought to play a role in brain development. Mutations in this gene are associated with autosomal recessive nonsyndromic cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal recessive 2

Clinical highlights

Gene-disease validity (ClinGen)

intellectual disability · ARModerateconsider for supplementary testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

314

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

LOEUF

LOF

Mechanism· G2P

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