This gene is a proto-oncogene that encodes a RING finger E3 ubiquitin ligase. The encoded protein is one of the enzymes required for targeting substrates for degradation by the proteasome. This protein mediates the transfer of ubiquitin from ubiquitin conjugating enzymes (E2) to specific substrates. This protein also contains an N-terminal phosphotyrosine binding domain that allows it to interact with numerous tyrosine-phosphorylated substrates and target them for proteasome degradation. As such it functions as a negative regulator of many signal transduction pathways. This gene has been found to be mutated or translocated in many cancers including acute myeloid leukaemia, and expansion of CGG repeats in the 5′ UTR has been associated with Jacobsen syndrome. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Jul 2016]

  • Protein polyubiquitination
  • Ubiquitin-dependent protein catabolic process
  • Protein monoubiquitination
  • Cellular response to DNA damage stimulus
  • Signal transduction
  • Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia
  • Juvenile myelomonocytic leukemia
  • Rasopathy
  • Ovarian germ cell cancer
  • Noonan syndrome 1
  • General Cardiomyopathy
  • Noonan Syndrome

Based on Ayass Bioscience, LLC Data Analysis

Emw. Structure of the CBL protein. Based on PyMOL rendering of PDB 1b47.

Gene Location

HM-VUS Prevalence

% 0.102145045965271

Ratio of samples with at least 1 High/Med VUS variant (Computed from Ayass Bioscience Samples)

High/Med VUS Variants

T=0.000060(15/251364,GnomAD_exome)
T=0.000072(9/125568,TOPMED)
T=0.000066(8/120674,ExAC)
T=0.00019(17/88598,ALFAProject)
T=0.00010(8/78696,PAGE_STUDY)
T=0.00013(4/31398,GnomAD)
T=0.00023(3/12988,GO-ESP)