# CARD11

Source: https://onco.cc/targets/card11/  
OnCo record `card11` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CIViC 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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: caspase recruitment domain family member 11; Caspase recruitment domain-containing protein 11; CARMA1; BIMP3
- Tags: cancer-genes-wave
- Symbol: CARD11
- Class: oncogene
- 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).
- Where found: 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)

## 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.

## Sources

- HGNC HGNC:16393: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:16393
- UniProt Q9BXL7: https://www.uniprot.org/uniprotkb/Q9BXL7/entry
- NCBI Gene 84433: https://www.ncbi.nlm.nih.gov/gene/84433
- Ensembl ENSG00000198286: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000198286
- Davis et al., Nature 2010: chronic active B-cell receptor signalling in diffuse large B-cell lymphoma: https://doi.org/10.1038/nature08638
- Kataoka et al., Nat Genet 2015: integrated molecular analysis of 426 adult T-cell leukaemia/lymphoma cases: https://doi.org/10.1038/ng.3415

## 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: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)
- pathways: [B-cell receptor / BTK signalling (to NF-κB)](https://onco.cc/pathways/bcr-signalling/), [Inflammation & NF-κB](https://onco.cc/pathways/inflammation-nfkb/), [Oncogenic viruses](https://onco.cc/pathways/oncogenic-viruses/)
- terms: [HTLV-1, Tax and HBZ in adult T-cell leukaemia/lymphoma](https://onco.cc/terms/lymphoma-bio-htlv1/)

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JSON: https://onco.cc/api/v1/entities/card11.json