# CBL

Source: https://onco.cc/targets/cbl/  
OnCo record `cbl` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

CBL (E3 ubiquitin-protein ligase CBL) is an enzyme. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Myeloproliferative neoplasms, Leukaemia, Skin cancer and 5 more.

## Summary

E3 ubiquitin-protein ligase that acts as a negative regulator of many signalling pathways by mediating ubiquitination of cell surface receptors. Accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognises activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, CSF1R, EPHA8 and KDR and mediates their ubiquitination to terminate signalling.

CIViC holds 8 clinical evidence items and 0 assertions across 9 variants, naming SU11274. Open Targets scores its association with cancer at 0.86 (direct and indirect evidence; datatypes genetic literature 0.76, affected pathway 0.81, literature 0.98, genetic association 0.81, somatic mutation 0.90, animal model 0.61). IntOGen calls it a driver in 3 cohorts (1 activating, 2 loss-of-function), covering Acute Lymphoblastic Leukaemia, Acute Myeloid Leukaemia, Oesophageal Adenocarcinoma.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: Cbl proto-oncogene; E3 ubiquitin-protein ligase CBL; RNF55; c-Cbl; CBL2
- Tags: cancer-genes-wave
- Symbol: CBL
- Class: enzyme
- Biology: E3 ubiquitin-protein ligase that acts as a negative regulator of many signalling pathways by mediating ubiquitination of cell surface receptors. Accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognises activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, CSF1R, EPHA8 and KDR and mediates their ubiquitination to terminate signalling. Recognises membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation. Ubiquitinates EGFR and SPRY2. Involved in LAG3-mediated inhibition of TCR signalling: following ligand-binding to LAG3, catalyses 'Lys-63'-linked ubiquitination of LAG3, unleashing the LAG3 C-terminus from the membrane, and initiating a signalling that prevents TCR activation. Location: Cytoplasm; Cell membrane; Cell projection, cilium; Golgi apparatus (UniProt). Locus 11q23.3 (HGNC).
- Where found: Myeloproliferative neoplasms: Open Targets association 0.81 with myeloproliferative neoplasm (MONDO_0020076); Leukaemia: Open Targets association 0.80 with leukaemia (MONDO_0005059); Skin cancer: Open Targets association 0.58 with skin cancer (MONDO_0002898); Oesophageal cancer: IntOGen driver in 1 cohort (ESCA); Ovarian cancer: Open Targets association 0.56 with ovarian cancer (MONDO_0008170); Sarcomas: Open Targets association 0.52 with sarcoma (MONDO_0005089)

## Notes

- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 1 therapies; IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts; CIViC holds 8 clinical evidence items on its variants. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Juvenile Myelomonocytic Leukaemia.

## Sources

- HGNC HGNC:1541: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1541
- UniProt P22681: https://www.uniprot.org/uniprotkb/P22681/entry
- NCBI Gene 867: https://www.ncbi.nlm.nih.gov/gene/867
- Ensembl ENSG00000110395: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000110395

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Myeloproliferative neoplasms (PV, ET, myelofibrosis)](https://onco.cc/cancers/myeloproliferative-neoplasms/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)
- pathways: [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)

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JSON: https://onco.cc/api/v1/entities/cbl.json