CARD11

Chr 7ADAR

caspase recruitment domain family member 11

NCBI Gene: 84433 ENSG00000198286 UniProt: Q9BXL7 OMIM: 607210

CARD11 encodes an adapter protein that transduces NF-kappa-B activation downstream of T-cell and B-cell receptor signaling by forming multiprotein complexes with BCL10 and MALT1. Mutations cause primary immunodeficiencies including B-cell expansion with NF-kappa-B activation and T-cell anergy, immunodeficiency with atopic dermatitis, and severe combined immunodeficiency, affecting adaptive immune responses. Inheritance can be either autosomal dominant or autosomal recessive depending on the specific variant.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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 (PubMed:11278692, PubMed:11356195, PubMed:12356734). 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 (PubMed:11356195). Upon activation in response to TCR or BCR triggering, CARD11 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization 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 (PubMed:24074955). Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (PubMed:17287217). Promotes linear ubiquitination of BCL10 by promoting the targeting of BCL10 to RNF31/HOIP (PubMed:27777308). Stimulates the phosphorylation of BCL10 (PubMed:11356195). Also activates the TORC1 signaling pathway (PubMed:28628108)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

B-cell expansion with NFKB and T-cell anergyMIM #616452

Immunodeficiency 11AMIM #615206

Immunodeficiency 11B with atopic dermatitisMIM #617638

Clinical highlights

Gene-disease validity (ClinGen)

BENTA disease · ADDefinitivesufficient evidence for diagnostic panels3 gene-disease associations curated in total

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.23

LOEUF· LoF intol.

Multiple*

Mechanism· predicted