CBLB
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
No product in this corpus aims at CBLB yet. Drugs fit a pocket that exists only in one shape of the mutant protein and hold it there, off.
External identifiers
Sources: HGNC HGNC:1542 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q13191 (protein name, function text, keywords and locations (REST API)); CIViC gene CBLB (1 evidence items, 0 assertions, 1 variants; diseases: Lung Non-small Cell Carcinoma (GraphQL API, CC0)); Open Targets ENSG00000114423 (association with cancer (MONDO_0004992) 0.69; per-cancer scores at or above 0.5: melanoma 0.56, skin cancer 0.56, breast cancer 0.53, lung cancer 0.57 (GraphQL API, CC0)); IntOGen CBLB (driver in 2 cohorts (Act 2, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
- 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
top- 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.
Latest papers
topQuery for this target: (TITLE:"CBLB" OR ABSTRACT:"CBLB" OR TITLE:"Cbl proto-oncogene B" OR ABSTRACT:"Cbl proto-oncogene B" OR TITLE:"E3 ubiquitin-protein ligase CBL-B" OR ABSTRACT:"E3 ubiquitin-protein ligase CBL-B" OR TITLE:"RNF56" OR ABSTRACT:"RNF56" OR TITLE:"Cbl-b" OR ABSTRACT:"Cbl-b") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CBLB, not a curated reading list.
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