CARD11 Gene

The CARD11 gene (CARD11 stands for "Caspase Recruitment Domain Family Member 11") is a protein-coding gene located on chromosome 7p22.2. The protein encoded by this gene belongs to the family of membrane-associated guanylate kinases (MAGUK), a class of kinases that function as molecular systems for the assembly of multiprotein complexes in specific regions of the plasma membrane. The enzyme is a member of the CARD protein family, which is characterized by carrying a distinctive caspase-associated recruitment domain (CARD).

The CARD11 protein has a similar domain structure to the CARD14 protein. The CARD domains of both proteins have been shown to interact specifically with the BCL10 protein, which is known to act as a positive regulator of cell apoptosis and NF-kappaB activation. When expressed in cells, this protein activates NF-kappaB and induces phosphorylation of BCL10. The CARD11 protein plays a key role in the adaptive immune response by transducing NF-kappa-B activation downstream of the T-cell receptor (TCR) and B-cell receptor (BCR). It transduces signals after TCR or BCR activation via the formation of a multiprotein complex together with BCL10 and MALT1 that activates NF-kappa-B and MAP kinase p38. Its binding to DPP4 induces T cell proliferation and NF-kappa-B activation in a T cell receptor/CD3-dependent manner. Furthermore, the CARD11 kinase promotes linear ubiquitination of BCL10 by promoting targeting of BCL10 to RNF31/HOIP. Stimulates phosphorylation of BCL10 (PubMed:11356195). Also activates the TORC1 signaling pathway.

Oncogenic CARD11 mutations play an activating role in diffuse large B-cell lymphoma (DLBCL). They may provide a genetic basis for the development of pharmacological inhibitors of the CARD11 pathway for DLBCL therapy (Lenz G et al 2008). Mutants of the CARD11 gene can express dominant-negative and gain-of-function variants associated with various immunodeficiencies (Meitlis I et al. 2020).

Diseases associated with CARD11 include:

• B-cell expansion with Nfkb
• the T-cell energetics
• the immunodeficiency 11.

Related pathways include TCR signaling (REACTOME) and immune response Fc epsilon RI pathway.

1. Lenz G et al (2008) Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 319:1676-1679.
2. Meitlis I et al (2020) Multiplexed Functional Assessment of Genetic Variants in CARD11. Am J Hum Genet 107:1029-1043.