{"entity":{"id":"card11","kind":"target","name":"CARD11","aka":["caspase recruitment domain family member 11","Caspase recruitment domain-containing protein 11","CARMA1","BIMP3"],"tldr":"CARD11 (Caspase recruitment domain-containing protein 11) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Hepatocellular carcinoma, Skin cancer and 5 more.","summary":"Adapter protein that plays a key role in adaptive immune response by transducing the activation of NF-kappa-B downstream of T-cell receptor (TCR) and B-cell receptor (BCR) engagement. Transduces signals downstream TCR or BCR activation via the formation of a multiprotein complex together with BCL10 and MALT1 that induces NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways. Upon activation in response to TCR or BCR triggering, CARD11 homooligomerises to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerisation of BCL10 and subsequent recruitment of MALT1: this leads to I-kappa-B kinase (IKK) phosphorylation and degradation, and release of NF-kappa-B proteins for nuclear translocation.\n\nCIViC holds 2 clinical evidence items and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.68 (direct and indirect evidence; datatypes literature 0.84, animal model 0.54, genetic association 0.00, somatic mutation 0.87). IntOGen calls it a driver in 11 cohorts (9 activating, 2 loss-of-function), covering Burkitt Lymphoma, Colorectal Adenocarcinoma, Diffuse Large B-Cell Lymphoma, NOS, Hepatocellular Carcinoma, Malignant Lymphoma, Non-Hodgkin Lymphoma and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:16393","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:16393"},{"label":"UniProt Q9BXL7","url":"https://www.uniprot.org/uniprotkb/Q9BXL7/entry"},{"label":"NCBI Gene 84433","url":"https://www.ncbi.nlm.nih.gov/gene/84433"},{"label":"Ensembl ENSG00000198286","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000198286"},{"label":"Davis et al., Nature 2010: chronic active B-cell receptor signalling in diffuse large B-cell lymphoma","url":"https://doi.org/10.1038/nature08638"},{"label":"Kataoka et al., Nat Genet 2015: integrated molecular analysis of 426 adult T-cell leukaemia/lymphoma cases","url":"https://doi.org/10.1038/ng.3415"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["non-hodgkin-lymphoma","hcc","skin-cancer","colorectal","ovarian","leukaemia","lung-cancer","gastric"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["bcr-signalling","inflammation-nfkb","oncogenic-viruses"],"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 9 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts; CIViC holds 2 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.","Lymphoma, Chronic active B-cell receptor signalling, and BTK: The B-cell receptor normally signals only when it meets antigen. In activated B-cell-like lymphoma it signals continuously: the receptors cluster in the membrane and diffuse slowly, exactly as they do in an antigen-stimulated normal B cell, and knocking down IgM, Ig-kappa, CD79A, CD79B or BTK kills the cell. The signal runs CD79a/b to SYK to BTK to PLC-gamma-2 to protein kinase C beta to the CARD11-BCL10-MALT1 complex and into NF-kB. Mutations of the ITAM module of CD79B raise surface receptor expression and blunt LYN, the feedback brake (Davis 2010). Frequency: Mutations of the first ITAM tyrosine of CD79B in 18% of activated B-cell-like cases, frequent in that subtype and rare in other diffuse large B-cell lymphomas, absent from Burkitt and MALT lymphoma; activating CARD11 mutations in roughly 10% of activated B-cell-like cases (Davis 2010). What it changes about treatment: This is the one pathway in lymphoma where the biology picks the drug today. BTK inhibitors are standard in mantle cell lymphoma and Waldenstrom macroglobulinaemia and have activity in primary CNS lymphoma and in the MCD genetic subtype of diffuse large B-cell lymphoma; they do little in germinal-centre disease.","Lymphoma, HTLV-1, Tax and HBZ: Human T-lymphotropic virus 1 integrates into the genome of a CD4 T cell and expresses Tax, which switches on NF-kB and interferes with the DNA-damage response and the spindle checkpoint, and HBZ, encoded on the opposite strand, which is retained when Tax expression is switched off under immune pressure. The host genome then acquires the rest of the lesions, and they are not random: the alterations found across 426 cases overlap significantly with the proteins Tax itself binds, and are concentrated in T-cell receptor and NF-kB signalling, T-cell trafficking and immune surveillance, with activating mutations in PLCG1, PRKCB, CARD11, VAV1, IRF4, FYN, CCR4 and CCR7, CTLA4-CD28 and ICOS-CD28 fusions, and intragenic deletions of IKZF2, CARD11 and TP73 (Kataoka 2015). Frequency: Across 426 adult T-cell leukaemia/lymphoma cases analysed by whole-genome, exome, transcriptome and targeted sequencing with copy-number and methylation arrays (Kataoka 2015). Most people infected with HTLV-1 never develop the disease, and the latency between infection, usually in infancy through breastfeeding, and the leukaemia is measured in decades. What it changes about treatment: The CCR4 finding is the practical one: CCR4 is both frequently expressed and frequently mutated, and mogamulizumab is used in this disease. The virus itself is not a drug target, and antiretroviral treatment does not cure the leukaemia."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"CARD11","role":["oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:16393","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:16393","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9BXL7","url":"https://www.uniprot.org/uniprotkb/Q9BXL7/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CARD11","url":"https://civicdb.org/features/16180","note":"2 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000198286","url":"https://platform.opentargets.org/target/ENSG00000198286/associations","note":"association with cancer (MONDO_0004992) 0.68; per-cancer scores at or above 0.5: colorectal cancer 0.55, gastric cancer 0.51, melanoma 0.54, diffuse large B-cell lymphoma 0.63, non-Hodgkin lymphoma 0.70, skin cancer 0.58 (GraphQL API, CC0)"},{"label":"IntOGen CARD11","url":"https://www.intogen.org/search?gene=CARD11","note":"driver in 11 cohorts (Act 9, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-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), 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 CARD11: RNA tissue enhanced (intestine 17 nTPM, lymphoid tissue 38 nTPM); no normal tissue stained high; highest cancer staining lymphoma (1 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Hepatocellular carcinoma, Skin cancer (all types), Colorectal cancer, Ovarian cancer, Leukaemia, Lung cancer (all types) and more); Open Targets associates it with 1 specific cancer type at or above 0.5 (diffuse large B-cell lymphoma). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt Q9BXL7","url":"https://www.uniprot.org/uniprotkb/Q9BXL7/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CARD11","url":"https://civicdb.org/features/16180","note":"2 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma (GraphQL API, CC0)"},{"label":"IntOGen CARD11","url":"https://www.intogen.org/search?gene=CARD11","note":"driver in 11 cohorts (Act 9, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas CARD11 tissue","url":"https://www.proteinatlas.org/ENSG00000198286-CARD11/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000198286 associations","url":"https://platform.opentargets.org/target/ENSG00000198286/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:16393","ensembl":"ENSG00000198286","uniprot":"Q9BXL7","entrez":"84433","firstDescribed":2001,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Bertin et al, J. Biol. Chem, 2001, \"CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with Bcl10 and activate NF-kappaB\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/11278692/","biology":"Adapter protein that plays a key role in adaptive immune response by transducing the activation of NF-kappa-B downstream of T-cell receptor (TCR) and B-cell receptor (BCR) engagement. Transduces signals downstream TCR or BCR activation via the formation of a multiprotein complex together with BCL10 and MALT1 that induces NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways. Upon activation in response to TCR or BCR triggering, CARD11 homooligomerises to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerisation of BCL10 and subsequent recruitment of MALT1: this leads to I-kappa-B kinase (IKK) phosphorylation and degradation, and release of NF-kappa-B proteins for nuclear translocation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Promotes linear ubiquitination of BCL10 by promoting the targeting of BCL10 to RNF31/HOIP. Stimulates the phosphorylation of BCL10. Location: Cytoplasm; Membrane raft (UniProt). Locus 7p22.2 (HGNC).","whereFound":["Non-Hodgkin lymphoma: Open Targets association 0.70 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 2 cohorts (MLYM, NHL)","Hepatocellular carcinoma: IntOGen driver in 2 cohorts (HCC)","Skin cancer: Open Targets association 0.58 with skin cancer (MONDO_0002898)","Colorectal cancer: Open Targets association 0.55 with colorectal cancer (MONDO_0005575); IntOGen driver in 1 cohort (COADREAD)","Ovarian cancer: IntOGen driver in 1 cohort (OVT)","Leukaemia: Open Targets association 0.53 with leukaemia (MONDO_0005059)"],"targetClass":"oncogene","prevalence":[]},"route":"/targets/card11/","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":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"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":"oncogenic-viruses","kind":"pathway","name":"Oncogenic viruses","route":"/pathways/oncogenic-viruses/"}],"term":[{"id":"lymphoma-bio-htlv1","kind":"term","name":"HTLV-1, Tax and HBZ in adult T-cell leukaemia/lymphoma","route":"/terms/lymphoma-bio-htlv1/"}]}}