CRBN

cereblon

Basic information

Region (hg38): 3:3144627-3179727

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.

• not provided (28 variants)
• not specified (21 variants)
• Inborn genetic diseases (20 variants)
• Intellectual disability, autosomal recessive 2 (12 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				9	5	14
missense		1	28	2		31
nonsense	1	4				5
start loss						0
frameshift	1	1	2			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1					1
splice region				1		1
non coding			2		3	5
Total	3	6	33	11	8

Highest pathogenic variant AF is 0.00000657

Variants in CRBN

This is a list of pathogenic ClinVar variants found in the CRBN region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-3144632-A-G		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Jun 23, 2022)
3-3144640-A-T		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Pathogenic (Sep 01, 2023)
3-3144641-AAGTT-A		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome • Retinal dystrophy • TRNT1-related disorder	Pathogenic/Likely pathogenic (Oct 01, 2023)
3-3144645-T-TAA		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Pathogenic (Aug 23, 2023)
3-3144647-G-A		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Jan 24, 2024)
3-3144647-G-C		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Apr 24, 2022)
3-3144651-T-G		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome • Inborn genetic diseases	Uncertain significance (Nov 28, 2023)
3-3144652-G-A		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Mar 25, 2019)
3-3144657-A-C		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Likely benign (Jun 04, 2022)
3-3144658-C-T		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Feb 04, 2022)
3-3144659-A-T		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Sep 13, 2022)
3-3144662-C-T			Uncertain significance (Nov 20, 2018)
3-3144667-C-A		Retinitis pigmentosa and erythrocytic microcytosis	Uncertain significance (Jan 15, 2020)
3-3144667-CAG-C		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Pathogenic (Oct 09, 2023)
3-3144669-G-A		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Likely benign (Dec 24, 2021)
3-3144669-G-T		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome • Retinitis pigmentosa and erythrocytic microcytosis;Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Aug 16, 2022)
3-3144671-G-T		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Pathogenic (Oct 30, 2014)
3-3144680-A-G		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Jul 02, 2022)
3-3144683-A-G		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Oct 19, 2020)
3-3144688-C-G		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Apr 03, 2022)
3-3144692-G-A			Uncertain significance (Feb 01, 2024)
3-3144694-A-C		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Jun 13, 2022)
3-3144700-A-C		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Likely benign (Mar 30, 2023)
3-3144710-G-A		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Likely pathogenic (Jan 19, 2020)
3-3144711-G-A		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Pathogenic (Jan 29, 2021)

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