CBL
  • 0
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
CBL (HGNC:1541) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
Cbl proto-oncogene
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
CBL2
Alias symbols
RNF55, c-Cbl
%HI
3.6(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
0.62(Read more about gnomAD LOEUF score)
Cytoband
11q23.3
Genomic Coordinates
GRCh37/hg19: chr11:119077049-119178859 NCBI Ensembl UCSC
GRCh38/hg38: chr11:119206339-119308149 NCBI Ensembl UCSC
MANE Select Transcript
NM_005188.4 ENST00000264033.6 (Read more about MANE Select)
Function
Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome (PubMed:17094949). Ubiquitinates SPRY2 (PubMed:17094949, PubMed:17974561). Ubiquitinates EGFR (PubMed:17974561). Recognizes activated receptor tyrosine kinases, inc... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-17021
ClinGen Curation ID:
CCID:006794
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
No Evidence for Haploinsufficiency (0)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
02/14/2024

Haploinsufficiency (HI) Score Details

HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence Comments:
Germline variants in CBL have been observed in individuals with a Noonan-like disorder, with and without Juvenile Myelomonocytic Leukemia (JMML). Bulow et al. 2015 (PMID:25358541) describe 2 patients with de novo missense variants and 1 with a de novo splice acceptor site variant. None of the variants suggest loss of function. No functional studies were performed. All three have similar prenatal features and Noonan like disorder. Martinelli et al. 2010 (PMID:20619386) describe patients missense variants. Functional studies on two of the variants suggests a dominant negative mechanism. Martinelli et al. 2015 (PMID:25952305) identified 5 patients with CBL variants (1 in frame deletion, 1 missense, 2 splice site, 1 transversion predicted to cause a premature termination p.Tyr235*). Functional studies of the two splice site variants show complete or partial deletions of exon 8. Western blot analysis of the CBL-Tyr235* showed reduced expression, however cells expressing the CBL-Tyr235* mutant showed enhanced constituative and EGF-induced ERK and AKT phosphorylation, suggesting a dominant negative effect. Additional report Hayakuna et al. 2015 (PMID 25283271) reported a missense mutation. At this time no variants or expression studies appear to support haploinsufficiency as the disease causing mechanism. CBL-related disorder is a genetic condition caused by pathogenic variants in the Cbl ubiquitin ligase gene, (CBL; HGNC:1541). Due to the proposed mechanism indicating the CBL gene's relationship to the RAS-MAPK pathway and the phenotypic presentation similar to that of the RASopathies, CBL-related disorder should be considered a RASopathy disorder.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000011.9) (NC_000011.10)