CBLGene

The CBL gene is a protein-coding gene located on chromosome 11q23.3. CBL is the acronym for "Casitas B-Lineage Lymphoma Proto-Oncogene" and which encodes a RING finger E3 ubiquitin ligase, an enzyme required for targeting substrates for degradation by the proteasome. This protein acts as an E3 ubiquitin-protein ligase by accepting ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transferring it to substrates to promote their degradation by the proteasome.

The ligase encoded by the CBL gene functions as a negative regulator of many signal transduction pathways. It is involved in signal transduction in hematopoietic cells and acts as a tumor suppressor in myeloid malignancies (Martinelli S et al. 2015).

Furthermore, it plays His important role in regulating osteoblast differentiation and apoptosis.

An important paralog of this gene is CBLB. Mutations or translocations of this gene have been identified in many cancers, including acute myeloid leukemia.

Diseases associated with CBL include:

Noonan Syndrome: Germline CBL mutations cause a variable phenotype characterized by a relatively high frequency of neurological features, a predisposition to juvenile myelomonocytic leukemia, and a low prevalence of cardiac defects, reduced growth, and cryptorchidism (Martinelli S et al 2015).

• Noonan Syndrome-Like Disorder With Or Without Juvenile Myelomonocytic Leukemia (Martinelli S et al. 2015).
• And
• Juvenile Myelomonocytic Leukemia (Hyakuna N et al. 2015).

1. Hyakuna N et al (2015) Germline mutation of CBL is associated with moyamoya disease in a child with juvenile myelomonocytic leukemia and Noonan syndrome-like disorder. Pediatr Blood Cancer 62:542-544.
2. Martinelli S et al (2015) Molecular Diversity and Associated Phenotypic Spectrum of Germline CBL Mutations. Hum Mutat 36:787-796.