Protein / target
Protein cereblon
Protein at a glance
Biological role
Transmembrane transporter binding
Primary system
Nervous system
Strongest disease association
congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
3 approved · 1 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2, ILF2 or GLUL (PubMed:26990986, PubMed:33009960). Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8 (PubMed:20223979, PubMed:24328678, PubMed:25043012, PubMed:25108355). Maintains presynaptic glutamate release and consequently cognitive functions, such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons (PubMed:18414909, PubMed:29530986). Likely to function by regulating the assembly and neuronal surface expression of BK channels via its interaction with KCNT1 (PubMed:18414909). May also be involved in regulating anxiety-like behaviors via a BK channel-independent mechanism (By similarity). Plays a negative role in TLR4 signaling by interacting with TRAF6 and ECSIT, leading to inhibition of ECSIT ubiquitination, an important step of the signaling (PubMed:31620128)
Subcellular location
Domains and Gene Ontology detail (18)Hide
Domains & features
Gene Ontology
- CCul4A-RING E3 ubiquitin ligase complex
- Ccytoplasm
- Ccytosol
- Cmembrane
- Cnucleus
- Cperinuclear region of cytoplasm
- Fmetal ion binding
- Ftransmembrane transporter binding
- Plimb development
- Plocomotory exploration behavior
- Pnegative regulation of monoatomic ion transmembrane transport
- Pnegative regulation of protein-containing complex assembly
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Synaptic signalling
- ·Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex tha…
Ion channel gating
- ·negative regulation of monoatomic ion transmembrane transport
Motor control
- ·locomotory exploration behavior
View underlying pathways (1)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
CRL4(CRBN) E3 ubiquitin ligase inhibitor
Appears in clinical studies involving plasma cell myeloma, immune system disorder, prostate cancer, non-small cell lung carcinoma
CRL4(CRBN) E3 ubiquitin ligase inhibitor
Appears in clinical studies involving anemia, mantle cell lymphoma, myelodysplastic syndrome, plasma cell myeloma
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 926 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 4 total
anemia · mantle cell lymphoma · myelodysplastic syndrome
plasma cell myeloma · immune system disorder · prostate cancer
plasma cell myeloma · systemic sclerosis · immune system disorder
plasma cell myeloma · sarcoidosis · systemic lupus erythematosus
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Label change
Label change: LENALIDOMIDE (NDA021880)
- Industry developmentAdvanced hierarchical ZnFe-LDH@MnO₂ nanostructures for sensitive voltammetric determination of lenalidomide
- Label change
Label change: LENALIDOMIDE (ANDA201452)
- Label change
Label change: LENALIDOMIDE (ANDA201452)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (ANDA201452)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (NDA021880)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (ANDA201452)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (NDA021880)
- Regulatory approval
Approval: LENALIDOMIDE (ANDA201452)
- Regulatory approval
Approval: Thalidomide Lipomed (EMA)
- Label change
Label change: LENALIDOMIDE (NDA021880)
- Label change
Label change: LENALIDOMIDE (NDA021880)
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.