Alt. symbols: CARMA1 | BIMP3

Approved name: caspase recruitment domain family member 11
Alt. names: caspase recruitment domain family, member 11 | card-maguk protein 1, bcl10-interacting maguk protein 3

Location: 7p22.2: 2906142 - 3044228 (-)
Gene type: protein_coding, 8 transcripts.

Scores: LoFtool: 0.251000 | pLI: 0.99993928 | LOEUF: 0.227

HGNC: 16393

NCBI: 84433, RefSeq: NG_027759.1

Ensembl: ENSG00000198286.11

LRG_729 | Status: public

OMIM: 607210

Expression | ProteinAtlas

Caspase recruitment domain-containing protein 11 (CARD11), also known as CARD-containing MAGUK protein 1 (Carma 1), belongs to the membrane-associated guanylate kinase (MAGUK) family, a class of proteins that functions as molecular scaffolds for the assembly of multiprotein complexes at specialized regions of the plasma membrane. CARD11, like other members of the CARD protein family, contains a characteristic caspase-associated recruitment domain (CARD), and has a similar structure to that of CARD14. The CARD domains of both proteins have been shown to specifically interact with BCL10, which is a positive regulator of cell apoptosis and NF-kappaB activation. CARD11 acts as a scaffold for NF-kappaB activity in the adaptive immune response, controlling peripheral B-cell differentiation and a variety of critical T-cell effector functions. When overexpressed in cells, CARD11 activates NF-kappaB and induces the phosphorylation of BCL10. When T or B cells recognize a foreign substance, CARD11 forms the CBM signalosome complex with BCL10 and MALT1, which in turn activates NF-kappaB and mTOR complex 1 (mTORC1) signaling, leading to T and B cell differentiation and activation and the mounting of an immune response.

Biallelic null mutations of CARD11, in both humans and mice, lead to a severe T and B-cell immunodeficiency [MIM:615206]. Somatic gain-of-function (GOF) CARD11 mutations are commonly seen in non-Hodgkin B cell lymphomas, whereas germline GOF mutations are associated with BENTA (B cell Expansion with NF-KB and T cell Anergy) [MIM:616452]. Heterozygous hypomorphic/dominant negative (DN) mutations permit sufficient effector function to reveal a strong disposition toward atopic phenotypes, in additi on to variable immune deficiency, leading to the condition Immunodeficiency 11B with atopic dermatitis [MIM:617638]. Patients with monoallelic hypomorphic CARD11 mutations have been reported to develop a broad spectrum of immune dysregulatory features with both immunodeficiency complicated by susceptibility to infections and autoimmunity, and including hypogammaglobulinemia and autoimmune cytopenias (PMID: 30170123). More recently, Desjardins et al. (2018) also reported the identification of a novel heterozygous germline CARD11 mutation c.701-713delinsT (p.His234_Lys238delinsLeu) in a four-generation family with features of both moderate B cell lymphocytosis and atopic dermatitis/allergies (PMID: 30619304). This blended phenotype was consistent with their functional studies showing that this mutation could lead to both GOF and DN signaling effects. The majority of pathogenic or likely pathogenic CARD11 mutations reported to date are missense, though some nonsense and splice site mutations, as well as small intragenic deletions and duplications have also been reported. [Load More]