{"entity":{"id":"cblb","kind":"target","name":"CBLB","aka":["Cbl proto-oncogene B","E3 ubiquitin-protein ligase CBL-B","RNF56","Cbl-b"],"tldr":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:1542","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1542"},{"label":"UniProt Q13191","url":"https://www.uniprot.org/uniprotkb/Q13191/entry"},{"label":"NCBI Gene 868","url":"https://www.ncbi.nlm.nih.gov/gene/868"},{"label":"Ensembl ENSG00000114423","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000114423"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["lung-cancer","skin-cancer","breast-cancer","nsclc","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"CBLB","role":["oncogene-driver","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:1542","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1542","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q13191","url":"https://www.uniprot.org/uniprotkb/Q13191/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CBLB","url":"https://civicdb.org/features/779","note":"1 evidence items, 0 assertions, 1 variants; diseases: Lung Non-small Cell Carcinoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000114423","url":"https://platform.opentargets.org/target/ENSG00000114423/associations","note":"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)"},{"label":"IntOGen CBLB","url":"https://www.intogen.org/search?gene=CBLB","note":"driver in 2 cohorts (Act 2, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:1542","ensembl":"ENSG00000114423","uniprot":"Q13191","entrez":"868","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).","whereFound":["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)"],"targetClass":"oncogene","prevalence":[]},"route":"/targets/cblb/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}]}}