{"entity":{"id":"bcl10","kind":"target","name":"BCL10","aka":["BCL10 immune signaling adaptor","B-cell lymphoma/leukemia 10","CARMEN","CIPER","mE10","c-E10"],"tldr":"BCL10 (B-cell lymphoma/leukaemia 10) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Lung cancer, Diffuse large B-cell lymphoma and 1 more.","summary":"Plays a key role in both adaptive and innate immune signalling by bridging CARD domain-containing proteins to immune activation. Acts by channeling adaptive and innate immune signalling downstream of CARD domain-containing proteins CARD9, CARD11 and CARD14 to activate NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines. Recruited by activated CARD domain-containing proteins: homooligomerised CARD domain-containing proteins form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerisation of BCL10, subsequent recruitment of MALT1 and formation of a CBM complex.\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 0.80, genetic association 0.19, somatic mutation 0.88). IntOGen calls it a driver in 3 cohorts (1 activating, 2 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS, Malignant Lymphoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:989","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:989"},{"label":"UniProt O95999","url":"https://www.uniprot.org/uniprotkb/O95999/entry"},{"label":"NCBI Gene 8915","url":"https://www.ncbi.nlm.nih.gov/gene/8915"},{"label":"Ensembl ENSG00000142867","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000142867"},{"label":"Liu et al., Gastroenterology 2002: t(11;18) marks gastric MALT lymphomas that will not respond to Helicobacter pylori eradication (111 patients)","url":"https://doi.org/10.1053/gast.2002.33047"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["non-hodgkin-lymphoma","lung-cancer","dlbcl","marginal-zone-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["bcr-signalling","inflammation-nfkb","microbiome-tumour"],"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 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts; CIViC holds 1 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Lymphoma, t(11;18) API2-MALT1 and the NF-kB lesions of marginal zone lymphoma: Gastric MALT lymphoma begins as a Helicobacter-driven proliferation that still needs the antigen; removing the bacterium removes the stimulus and the lymphoma regresses. The t(11;18) fuses API2 to MALT1 and produces a protein that activates NF-kB on its own, so the lymphoma no longer needs the antigen and no longer cares whether the bacterium is still there. The related translocations, t(1;14) involving BCL10 and t(14;18) involving MALT1, do the same job by a different route, and inactivation of TNFAIP3 removes the brake. Frequency: Among 111 patients with Helicobacter-positive gastric MALT lymphoma treated with antibiotics, the translocation separated the responders from the non-responders: 47 of the 48 patients who regressed completely were negative for the API2-MALT1 transcript (Liu 2002). What it changes about treatment: Yes, and this is one of the few places where a translocation result changes the first decision. A t(11;18)-positive gastric MALT lymphoma should not be treated with eradication alone, whatever the stage; a negative one usually can be."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"BCL10","role":["oncogene-driver","tumour-suppressor","biomarker","fusion-partner"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:989","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:989","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt O95999","url":"https://www.uniprot.org/uniprotkb/O95999/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene BCL10","url":"https://civicdb.org/features/7074","note":"1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000142867","url":"https://platform.opentargets.org/target/ENSG00000142867/associations","note":"association with cancer (MONDO_0004992) 0.69; per-cancer scores at or above 0.5: diffuse large B-cell lymphoma 0.54, non-Hodgkin lymphoma 0.71, lung cancer 0.50, marginal zone lymphoma 0.58 (GraphQL API, CC0)"},{"label":"IntOGen BCL10","url":"https://www.intogen.org/search?gene=BCL10","note":"driver in 3 cohorts (Act 1, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"few-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance) and a fusion partner (UniProt records a translocation), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA BCL10: RNA low tissue specificity; no normal tissue stained high; highest cancer staining lymphoma (6 of 11 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Lung cancer (all types)); Open Targets associates it with 2 specific cancer types at or above 0.5 (MALT lymphoma, testicular germ cell tumor). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt O95999","url":"https://www.uniprot.org/uniprotkb/O95999/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene BCL10","url":"https://civicdb.org/features/7074","note":"1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"IntOGen BCL10","url":"https://www.intogen.org/search?gene=BCL10","note":"driver in 3 cohorts (Act 1, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas BCL10 tissue","url":"https://www.proteinatlas.org/ENSG00000142867-BCL10/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000142867 associations","url":"https://platform.opentargets.org/target/ENSG00000142867/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:989","ensembl":"ENSG00000142867","uniprot":"O95999","entrez":"8915","firstDescribed":1999,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Willis T.G. et al, Cell, 1999, \"Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9989495/","biology":"Plays a key role in both adaptive and innate immune signalling by bridging CARD domain-containing proteins to immune activation. Acts by channeling adaptive and innate immune signalling downstream of CARD domain-containing proteins CARD9, CARD11 and CARD14 to activate NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines. Recruited by activated CARD domain-containing proteins: homooligomerised CARD domain-containing proteins form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerisation of BCL10, subsequent recruitment of MALT1 and formation of a CBM complex. This leads to activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines. Activated by CARD9 downstream of C-type lectin receptors; CARD9-mediated signals are essential for antifungal immunity. Activated by CARD11 downstream of T-cell receptor (TCR) and B-cell receptor (BCR). Location: Cytoplasm, perinuclear region; Membrane raft (UniProt). Locus 1p22.3 (HGNC).","whereFound":["Non-Hodgkin lymphoma: Open Targets association 0.71 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 1 cohort (MLYM)","Lung cancer: Open Targets association 0.50 with lung cancer (MONDO_0008903)","Diffuse large B-cell lymphoma: Open Targets association 0.54 with diffuse large B-cell lymphoma (MONDO_0018905); CIViC evidence names this disease","Marginal zone lymphoma: Open Targets association 0.58 with marginal zone lymphoma (MONDO_0017604)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/bcl10/","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":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"malt-lymphoma","kind":"cancer","name":"Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)","route":"/cancers/malt-lymphoma/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"marginal-zone-lymphoma","kind":"cancer","name":"Marginal zone lymphoma","route":"/cancers/marginal-zone-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"pathway":[{"id":"bcr-signalling","kind":"pathway","name":"B-cell receptor / BTK signalling (to NF-κB)","route":"/pathways/bcr-signalling/"},{"id":"inflammation-nfkb","kind":"pathway","name":"Inflammation & NF-κB","route":"/pathways/inflammation-nfkb/"},{"id":"microbiome-tumour","kind":"pathway","name":"Microbiome-tumour interactions","route":"/pathways/microbiome-tumour/"}]}}