# CBLB

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

## TL;DR

CBLB (E3 ubiquitin-protein ligase CBL-B) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Lung cancer, Skin cancer, Breast cancer and 2 more.

## Summary

E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production.

CIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.69 (direct and indirect evidence; datatypes literature 0.94, genetic association 0.36, somatic mutation 0.85). IntOGen calls it a driver in 2 cohorts (2 activating, 0 loss-of-function), covering Lung Adenocarcinoma, Non-Small Cell Lung Cancer.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: Cbl proto-oncogene B; E3 ubiquitin-protein ligase CBL-B; RNF56; Cbl-b
- Tags: cancer-genes-wave
- Symbol: CBLB
- Class: oncogene
- Biology: E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilisation upon restimulation and promotes anergy. 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 (UniProt). Locus 3q13.11 (HGNC).
- Where found: Lung cancer: Open Targets association 0.57 with lung cancer (MONDO_0008903); Skin cancer: Open Targets association 0.56 with skin cancer (MONDO_0002898); Breast cancer: Open Targets association 0.53 with breast cancer (MONDO_0007254); Non-small-cell lung cancer: CIViC evidence names this disease; IntOGen driver in 2 cohorts (LUAD, NSCLC); Melanoma: Open Targets association 0.56 with melanoma (MONDO_0005105)

## 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: IntOGen calls it an activating (Act) driver in 2 cohorts; CIViC holds 1 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.

## Sources

- HGNC HGNC:1542: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1542
- UniProt Q13191: https://www.uniprot.org/uniprotkb/Q13191/entry
- NCBI Gene 868: https://www.ncbi.nlm.nih.gov/gene/868
- Ensembl ENSG00000114423: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000114423

## 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: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Melanoma](https://onco.cc/cancers/melanoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)

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