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Aliases for CRBN Gene

Aliases for CRBN Gene

  • Cereblon 2 3 5
  • Mental Retardation, Non-Syndromic, Autosomal Recessive, 2A 2
  • Protein Cereblon 3
  • Protein X 0001 3
  • MRT2A 3
  • MRT2 3

External Ids for CRBN Gene

Previous HGNC Symbols for CRBN Gene

  • MRT2A

Summaries for CRBN Gene

Entrez Gene Summary for CRBN Gene

  • 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 mental retardation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

GeneCards Summary for CRBN Gene

CRBN (Cereblon) is a Protein Coding gene. Diseases associated with CRBN include Mental Retardation, Autosomal Recessive 2 and Autosomal Recessive Non-Syndromic Intellectual Disability. GO annotations related to this gene include ATP-dependent peptidase activity.

UniProtKB/Swiss-Prot for CRBN Gene

  • 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. Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8. May play a role in memory and learning by regulating the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1. Binding of pomalidomide and other thalidomide-related drugs changes the substrate specificity of the human protein, leading to decreased degradation of MEIS2 and other target proteins and increased degradation of MYC, IRF4, IKZF1 and IKZF3.

Gene Wiki entry for CRBN Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CRBN Gene

Genomics for CRBN Gene

Regulatory Elements for CRBN Gene

Enhancers for CRBN Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH03F003125 1.1 ENCODE 21.6 +52.4 52394 3.0 CREB3L1 WRNIP1 ARID4B SIN3A DMAP1 ZNF2 FOS KLF13 ZNF263 SP3 CRBN TRNT1 GC03P003130
GH03F003177 1.1 ENCODE 18.9 +0.7 741 2.7 MLX ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 ZNF207 ZNF143 CRBN TRNT1 ENSG00000271870
GH03F003170 0.9 Ensembl ENCODE 21 +6.2 6177 6.2 CTCF IRF2 ZNF654 RAD21 GATA3 ZNF316 HNF4G ZBTB33 IRF1 MAFK TRNT1 CRBN IL5RA ENSG00000271870
GH03F003191 1.4 FANTOM5 Ensembl ENCODE 3.8 -12.4 -12378 1.7 HDAC1 ATF1 TBL1XR1 GATA2 CREM ZBTB2 ZBTB11 KLF16 SMARCA4 PBX2 TRNT1 IL5RA CRBN GC03M003375
GH03F003209 0.2 ENCODE 11.1 -30.2 -30212 1.5 CRBN TRNT1 GC03M003375
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around CRBN on UCSC Golden Path with GeneCards custom track

Promoters for CRBN Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001844621 217 1401 MLX ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 ZNF207 ZNF143

Genomic Location for CRBN Gene

Chromosome:
3
Start:
3,148,992 bp from pter
End:
3,179,717 bp from pter
Size:
30,726 bases
Orientation:
Minus strand

Genomic View for CRBN Gene

Genes around CRBN on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CRBN Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CRBN Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CRBN Gene

Proteins for CRBN Gene

  • Protein details for CRBN Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96SW2-CRBN_HUMAN
    Recommended name:
    Protein cereblon
    Protein Accession:
    Q96SW2
    Secondary Accessions:
    • B2R6H4
    • C9IZA9
    • C9JAH6
    • Q6AI62
    • Q6NVZ0
    • Q9UHW4

    Protein attributes for CRBN Gene

    Size:
    442 amino acids
    Molecular mass:
    50546 Da
    Quaternary structure:
    • Interacts with KCNT1 (By similarity). Component of a DCX (DDB1-CUL4-X-box) protein ligase complex, at least composed of CRBN, CUL4A, DDB1 and RBX1. Interacts directly with DDB1 (PubMed:25043012, PubMed:25108355). Interacts (in pomalidomide-bound form) with IKZF1 and IKZF3 (PubMed:24328678).
    Miscellaneous:
    • Thalidomide was widely prescribed to pregnant women in the late 1950s as a sedative and as treatment against morning sickness. Thalidomide was found to be teratogenic, causing multiple birth defects. Recently, thalidomide use has increased for the treatment of multiple myeloma and erythema nodosum leprosum, a painful complication of leprosy. Thalidomide binding leads to a change in substrate specificity of the human DCX (DDB1-CUL4-X-box) E3 protein ligase complex, and this is probably the underlying cause of the teratogenic activity of thalidomide, possibly due to abnormal regulation of the BMP and FGF8 signaling pathways (PubMed:20223979). The thalidomide-induced change in substrate specificity leads to increased degradation of MYC, IRF4, IKZF1 and IKZF3, and this is probably the reason for the anti-proliferative and immunomodulatory effects of thalidomide and related drugs (PubMed:25108355). Thalidomide is also teratogenic in chicken and zebrafish, but not in mice.
    SequenceCaution:
    • Sequence=AAF17211.1; Type=Frameshift; Positions=347, 397, 401; Evidence={ECO:0000305}; Sequence=BAG35471.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAG35471.1; Type=Frameshift; Positions=347; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for CRBN Gene

    Alternative splice isoforms for CRBN Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CRBN Gene

Post-translational modifications for CRBN Gene

  • Ubiquitinated, ubiquitination is mediated by its own DCX protein ligase complex.
  • Ubiquitination at Lys 43, Lys 166, and Lys 300
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for CRBN Gene

Domains & Families for CRBN Gene

Protein Domains for CRBN Gene

Suggested Antigen Peptide Sequences for CRBN Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q96SW2

UniProtKB/Swiss-Prot:

CRBN_HUMAN :
  • The CULT domain binds thalidomide and related drugs, such as pomalidomide and lenalidomide. Drug binding leads to a change in substrate specificity of the human DCX (DDB1-CUL4-X-box) E3 protein ligase complex, while no such change is observed in rodents.
  • Belongs to the CRBN family.
Domain:
  • The CULT domain binds thalidomide and related drugs, such as pomalidomide and lenalidomide. Drug binding leads to a change in substrate specificity of the human DCX (DDB1-CUL4-X-box) E3 protein ligase complex, while no such change is observed in rodents.
  • Contains 1 CULT domain.
  • Contains 1 Lon N-terminal domain.
Family:
  • Belongs to the CRBN family.
genes like me logo Genes that share domains with CRBN: view

No data available for Gene Families for CRBN Gene

Function for CRBN Gene

Molecular function for CRBN Gene

UniProtKB/Swiss-Prot 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. Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8. May play a role in memory and learning by regulating the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1. Binding of pomalidomide and other thalidomide-related drugs changes the substrate specificity of the human protein, leading to decreased degradation of MEIS2 and other target proteins and increased degradation of MYC, IRF4, IKZF1 and IKZF3.

Gene Ontology (GO) - Molecular Function for CRBN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 20223979
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with CRBN: view
genes like me logo Genes that share phenotypes with CRBN: view

Human Phenotype Ontology for CRBN Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CRBN Gene

MGI Knock Outs for CRBN:

Animal Model Products

miRNA for CRBN Gene

miRTarBase miRNAs that target CRBN

Inhibitory RNA Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CRBN Gene

Localization for CRBN Gene

Subcellular locations from UniProtKB/Swiss-Prot for CRBN Gene

Cytoplasm. Nucleus. Membrane; Peripheral membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CRBN gene
Compartment Confidence
nucleus 5
cytosol 2
extracellular 1
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for CRBN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 20223979
GO:0005730 nucleolus IDA --
GO:0005737 cytoplasm IEA,IDA 20223979
GO:0016020 membrane IEA --
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex IDA 20223979
genes like me logo Genes that share ontologies with CRBN: view

Pathways & Interactions for CRBN Gene

No Data Available

UniProtKB/Swiss-Prot Q96SW2-CRBN_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for CRBN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0016567 protein ubiquitination IMP 20223979
GO:0032463 negative regulation of protein homooligomerization IEA --
GO:0034766 negative regulation of ion transmembrane transport IEA --
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process IMP 20223979
genes like me logo Genes that share ontologies with CRBN: view

No data available for Pathways by source and SIGNOR curated interactions for CRBN Gene

Drugs & Compounds for CRBN Gene

(5) Drugs for CRBN Gene - From: DrugBank and FDA Approved Drugs

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Lenalidomide Approved Pharma Target, inhibitor Anti-angiogenic. 718
Pomalidomide Approved Pharma Target, inhibitor 123
Thalidomide Approved, Investigational, Withdrawn Pharma Target, inhibitor Immunomodulatory agent,sedative drug,angiogenesis inhibitor, Immunomodulatory agents, TNF-alpha synthesis inhibitor 1105
Pomalyst Approved February 2013 Pharma 0
Revlimid Approved June 2013 Pharma 0
genes like me logo Genes that share compounds with CRBN: view

Transcripts for CRBN Gene

Unigene Clusters for CRBN Gene

Cereblon:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for CRBN Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c · 3d ^ 4a · 4b · 4c ^ 5a · 5b ^ 6a · 6b · 6c · 6d ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11 ^ 12a · 12b
SP1: - - - - - - -
SP2: - - - - - - -
SP3: -
SP4: -
SP5: - - -
SP6: - - - -
SP7: - - -
SP8: - - -
SP9: - - - -
SP10:
SP11: - - - - -
SP12: - -
SP13: - - - -
SP14:
SP15: -

Relevant External Links for CRBN Gene

GeneLoc Exon Structure for
CRBN
ECgene alternative splicing isoforms for
CRBN

Expression for CRBN Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CRBN Gene

Protein differential expression in normal tissues from HIPED for CRBN Gene

This gene is overexpressed in Fetal Brain (11.7), Testis (8.2), and Frontal cortex (6.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for CRBN Gene



Protein tissue co-expression partners for CRBN Gene

NURSA nuclear receptor signaling pathways regulating expression of CRBN Gene:

CRBN

SOURCE GeneReport for Unigene cluster for CRBN Gene:

Hs.18925

mRNA Expression by UniProt/SwissProt for CRBN Gene:

Q96SW2-CRBN_HUMAN
Tissue specificity: Widely expressed. Highly expressed in brain.
genes like me logo Genes that share expression patterns with CRBN: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for CRBN Gene

Orthologs for CRBN Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CRBN Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CRBN 34 35
  • 97.51 (n)
dog
(Canis familiaris)
Mammalia CRBN 34 35
  • 92.37 (n)
rat
(Rattus norvegicus)
Mammalia Crbn 34
  • 90.33 (n)
cow
(Bos Taurus)
Mammalia CRBN 34 35
  • 89.34 (n)
mouse
(Mus musculus)
Mammalia Crbn 34 16 35
  • 88.89 (n)
oppossum
(Monodelphis domestica)
Mammalia CRBN 35
  • 87 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CRBN 35
  • 87 (a)
OneToOne
chicken
(Gallus gallus)
Aves CRBN 34 35
  • 81.4 (n)
lizard
(Anolis carolinensis)
Reptilia CRBN 35
  • 82 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia crbn 34
  • 68.65 (n)
Str.19548 34
zebrafish
(Danio rerio)
Actinopterygii crbn 34 35
  • 68.09 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005299 34
  • 43.96 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG3925 35
  • 20 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea M18.6 35
  • 22 (a)
OneToOne
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G25740 34
  • 49.28 (n)
rice
(Oryza sativa)
Liliopsida Os01g0743600 34
  • 49.28 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 35 (a)
OneToOne
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.157 34
Species where no ortholog for CRBN was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CRBN Gene

ENSEMBL:
Gene Tree for CRBN (if available)
TreeFam:
Gene Tree for CRBN (if available)

Paralogs for CRBN Gene

Pseudogenes.org Pseudogenes for CRBN Gene

genes like me logo Genes that share paralogs with CRBN: view

No data available for Paralogs for CRBN Gene

Variants for CRBN Gene

Sequence variations from dbSNP and Humsavar for CRBN Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type
rs121918368 Pathogenic 3,150,939(-) TAACG(C/T)GATCT intron-variant, nc-transcript-variant, downstream-variant-500B, reference, utr-variant-3-prime, stop-gained
rs606231291 Pathogenic 3,147,991(+) CAGTG(-/ATGT)GTCCA nc-transcript-variant, downstream-variant-500B, reference, frameshift-variant
rs876661298 Pathogenic 3,148,101(+) AAAAA(-/A)GTGGT nc-transcript-variant, downstream-variant-500B, reference, frameshift-variant
rs878853266 Pathogenic 3,148,101(+) AAAAA(-/A)GTGGT nc-transcript-variant, downstream-variant-500B, reference, frameshift-variant
rs797045036 Likely pathogenic 3,151,023(-) CCCAG(C/T)GTAAG intron-variant, nc-transcript-variant, downstream-variant-500B, reference, missense, utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for CRBN Gene

Variant ID Type Subtype PubMed ID
nsv834604 CNV gain 17160897
nsv589371 CNV loss 21841781
nsv521796 CNV loss 19592680
nsv481430 CNV novel sequence insertion 20440878
nsv3676 CNV insertion 18451855
nsv1142352 CNV tandem duplication 24896259
esv2751994 CNV gain 17911159
esv2422274 CNV duplication 17116639
dgv4636n100 CNV gain 25217958

Variation tolerance for CRBN Gene

Residual Variation Intolerance Score: 16.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.96; 19.91% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CRBN Gene

Human Gene Mutation Database (HGMD)
CRBN
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CRBN

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CRBN Gene

Disorders for CRBN Gene

MalaCards: The human disease database

(5) MalaCards diseases for CRBN Gene - From: OMIM, ClinVar, GeneTests, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
mental retardation, autosomal recessive 2
  • mrt2
autosomal recessive non-syndromic intellectual disability
  • autosomal recessive mental retardation
3p- syndrome
  • chromosome 3pter-p25 deletion syndrome
birth defects
multiple myeloma
  • myeloma, multiple amyloidosis, systemic, included
- elite association - COSMIC cancer census association via MalaCards
Search CRBN in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CRBN_HUMAN
  • Mental retardation, autosomal recessive 2A (MRT2A) [MIM:607417]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Non-syndromic mental retardation patients do not manifest other clinical signs. MRT2A patients display mild mental retardation with a standard IQ ranged from 50 to 70. IQ scores are lower in males than females. Developmental milestones are mildly delayed. There are no dysmorphic or autistic features. {ECO:0000269 PubMed:15557513}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for CRBN

Genetic Association Database (GAD)
CRBN
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CRBN
genes like me logo Genes that share disorders with CRBN: view

No data available for Genatlas for CRBN Gene

Publications for CRBN Gene

  1. A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation. (PMID: 15557513) Higgins J.J. … Rooney J.P. (Neurology 2004) 2 3 4 22 64
  2. Primary function analysis of human mental retardation related gene CRBN. (PMID: 17380424) Xin W. … Qihan W. (Mol. Biol. Rep. 2008) 3 4 22 64
  3. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.). (PMID: 24328678) Gandhi A.K. … Chopra R. (Br. J. Haematol. 2014) 3 4 64
  4. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. (PMID: 25043012) Fischer E.S. … Thoma N.H. (Nature 2014) 3 4 64
  5. Structure of the human cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. (PMID: 25108355) Chamberlain P.P. … Cathers B.E. (Nat. Struct. Mol. Biol. 2014) 3 4 64

Products for CRBN Gene

Sources for CRBN Gene

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