CRBN

cereblon

Basic information

Region (hg38): 3:3144628-3179727

Previous symbols: [ "MRT2A" ]

Links

ENSG00000113851

∙ NCBI:51185 ∙ OMIM:609262 ∙ HGNC:30185 ∙ Uniprot:Q96SW2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

intellectual disability, autosomal recessive 2 (Limited), mode of inheritance: AR
autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
intellectual disability, autosomal recessive 2 (Limited), mode of inheritance: AR
intellectual disability (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 2	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	10932263; 15557513; 17036314; 17380424

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRBN gene.

Inborn_genetic_diseases (49 variants)
not_provided (37 variants)
not_specified (19 variants)
Intellectual_disability,_autosomal_recessive_2 (11 variants)
CRBN-related_disorder (7 variants)
Multiple_myeloma (1 variants)
Intellectual_disability (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRBN gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016302.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				13 clinvar	4 clinvar	17
missense		2 clinvar	61 clinvar	7 clinvar		70
nonsense	1 clinvar	5 clinvar				6
start loss						0
frameshift	3 clinvar	1 clinvar	3 clinvar			7
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	5	8	64	20	4

Highest pathogenic variant AF is 0.00000993937

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRBN	protein_coding	protein_coding	ENST00000231948	11	30719

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000289	0.999	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0404	241	239	1.01	0.0000120	2914
Missense in Polyphen		34	50.752	0.66993		616
Synonymous	-1.64	100	81.2	1.23	0.00000409	788
Loss of Function	3.01	11	28.3	0.389	0.00000142	324

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000387	0.000387
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000277	0.000277
European (Non-Finnish)	0.000132	0.000123
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:18414909, ECO:0000269|PubMed:20223979, ECO:0000269|PubMed:24328678, ECO:0000269|PubMed:25043012, ECO:0000269|PubMed:25108355, ECO:0000305}.;
Disease: DISEASE: 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, ECO:0000269|PubMed:28143899}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

loftool: 0.219
rvis_EVS: -0.58
rvis_percentile_EVS: 18.59

Haploinsufficiency Scores

pHI: 0.195
hipred: Y
hipred_score: 0.611
ghis: 0.592

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.807

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Crbn
Phenotype: liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype;

Zebrafish Information Network

Gene name: crbn
Affected structure: pectoral fin
Phenotype tag: abnormal
Phenotype quality: malformed

Gene ontology

Biological process: protein ubiquitination;negative regulation of protein homooligomerization;negative regulation of ion transmembrane transport;proteasome-mediated ubiquitin-dependent protein catabolic process;positive regulation of protein homodimerization activity
Cellular component: nucleus;nucleolus;cytoplasm;membrane;Cul4A-RING E3 ubiquitin ligase complex
Molecular function: protein binding;metal ion binding