Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

E3 ubiquitin-protein ligase CBL

The CBL gene encodes a ubiquitin which is involved in degradation of proteins. It is known as a proto-oncogene. Mutations cause an autosomal dominant Noonan syndrome-like disorder and juvenile myelomonocytic leukemia.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Research Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Noonan syndrome-like disorder and juvenile myelomonocytic leukemia
CBL

References:

1.

Shen Y et. al. (2000) InIB-dependent internalization of Listeria is mediated by the Met receptor tyrosine kinase.

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2.

Veiga E et. al. (2005) Listeria hijacks the clathrin-dependent endocytic machinery to invade mammalian cells.

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3.

Savage PD et. al. (1991) Relationship of the human protooncogene CBL2 on 11q23 to the t(4;11), t(11;22), and t(11;14) breakpoints.

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4.

Wei S et. al. (1990) Physical mapping of the human chromosome 11q23 region containing the ataxia-telangiectasia locus.

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5.

Langdon WY et. al. (1989) v-cbl, an oncogene from a dual-recombinant murine retrovirus that induces early B-lineage lymphomas.

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6.

Mastick CC et. al. (1995) Insulin stimulates the tyrosine phosphorylation of caveolin.

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7.

Jones C et. al. (1995) Association of a chromosome deletion syndrome with a fragile site within the proto-oncogene CBL2.

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8.

Yoon CH et. al. (1995) Similarity of sli-1, a regulator of vulval development in C. elegans, to the mammalian proto-oncogene c-cbl.

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9.

Jones C et. al. (1994) Physical linkage of the fragile site FRA11B and a Jacobsen syndrome chromosome deletion breakpoint in 11q23.3.

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10.

Joazeiro CA et. al. (1999) The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase.

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11.

Baumann CA et. al. (2000) CAP defines a second signalling pathway required for insulin-stimulated glucose transport.

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12.

Thien CB et. al. (2001) RING finger mutations that abolish c-Cbl-directed polyubiquitination and downregulation of the EGF receptor are insufficient for cell transformation.

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13.

Soubeyran P et. al. (2002) Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors.

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14.

Petrelli A et. al. (2002) The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met.

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15.

Naramura M et. al. (2002) c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation.

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16.

Fu JF et. al. (2003) Identification of CBL, a proto-oncogene at 11q23.3, as a novel MLL fusion partner in a patient with de novo acute myeloid leukemia.

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17.

Nau MM et. al. (2003) Comparative genomic organization of the cbl genes.

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18.

Molero JC et. al. (2004) c-Cbl-deficient mice have reduced adiposity, higher energy expenditure, and improved peripheral insulin action.

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19.

Dragone LL et. al. (2006) Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner.

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20.

Loh ML et. al. (2009) Mutations in CBL occur frequently in juvenile myelomonocytic leukemia.

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21.

Sanada M et. al. (2009) Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms.

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22.

Muramatsu H et. al. (2010) Mutations of an E3 ubiquitin ligase c-Cbl but not TET2 mutations are pathogenic in juvenile myelomonocytic leukemia.

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23.

Rathinam C et. al. (2010) c-Cbl deficiency leads to diminished lymphocyte development and functions in an age-dependent manner.

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24.

Pérez B et. al. (2010) Germline mutations of the CBL gene define a new genetic syndrome with predisposition to juvenile myelomonocytic leukaemia.

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25.

Martinelli S et. al. (2010) Heterozygous germline mutations in the CBL tumor-suppressor gene cause a Noonan syndrome-like phenotype.

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26.

Niemeyer CM et. al. (2010) Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia.

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27.

Martin HC et. al. (2014) Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis.

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28.

Pathak A et. al. (2015) Juvenile myelomonocytic leukemia due to a germline CBL Y371C mutation: 35-year follow-up of a large family.

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Update: Sept. 26, 2018