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    GENE:

    CARD11 (Caspase Recruitment Domain Family Member 11)

    i
    Other names: CARD11, Caspase Recruitment Domain Family Member 11, CARMA1, Caspase Recruitment Domain-Containing Protein 11, Bcl10-Interacting Maguk Protein 3, CARD-Containing MAGUK Protein 1, Carma 1, BIMP3, Caspase Recruitment Domain Family, Member 11, Card-Maguk Protein 1, IMD11A, CARD11, BENTA, IMD11, PPBL
    11d
    Leniolisib for Immune Dysregulation in CVID (clinicaltrials.gov)
    P2, N=20, Active, not recruiting, Pharming Technologies B.V. | Recruiting --> Active, not recruiting
    Enrollment closed
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    PTEN (Phosphatase and tensin homolog) • CD20 (Membrane Spanning 4-Domains A1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • IKZF1 (IKAROS Family Zinc Finger 1) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • CARD11 (Caspase Recruitment Domain Family Member 11) • NFKB2 (Nuclear Factor Kappa B Subunit 2) • TNFRSF13C (TNF Receptor Superfamily Member 13C) • CD81 (CD81 Molecule) • SEC61A1 (SEC61 Translocon Subunit Alpha 1) • TNFRSF13B (TNF Receptor Superfamily Member 13B)
    18d
    Diverse transcriptomic and mutational patterns but limited functional pathway alterations in patient-derived Sézary syndrome cells. (PubMed, J Invest Dermatol)
    MALT1 inhibition, which impacts on NF-κB signaling, led to a robust effect in vitro that was partially reproduced in the NSG model. Our investigations revealed the actual possibility of inhibiting downstream TCR signaling by CARD11, BCL10 and MALT1 in SS therapy.
    Journal
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    CARD11 (Caspase Recruitment Domain Family Member 11) • MALT1 (MALT1 Paracaspase)
    2ms
    B cell lymphocytosis and reprogramming due to bi-allelic CARD11 mutations. (PubMed, J Allergy Clin Immunol)
    These results define a novel autosomal recessive form of BENTA disease. Additional analysis of mutation-driven changes in B cell function may shed light on the mechanisms of B lymphomagenesis in patients with germline or somatic CARD11 variants.
    Journal
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    CARD11 (Caspase Recruitment Domain Family Member 11)
    3ms
    Dupilumab for atopic manifestations in pediatric patients with inborn errors of immunity: efficacy and safety in a genetically diverse cohort. (PubMed, Front Immunol)
    Dupilumab is a safe and highly effective therapeutic option for pediatric patients with IEI-associated atopic manifestations, improving clinical outcomes, quality of life, and infection profile while preserving immune function. These findings support broader application of dupilumab in patients with IEI and warrant further investigation in larger, multicenter studies.
    Observational data • Retrospective data • Journal
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    STAT3 (Signal Transducer And Activator Of Transcription 3) • CARD11 (Caspase Recruitment Domain Family Member 11) • DOCK8 (Dedicator Of Cytokinesis 8)
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    Dupixent (dupilumab)
    3ms
    Potentiation of noncanonical NF-κB signaling and marginal zone B cell expansion by CARD11-mediated regulation of p100 processing. (PubMed, Cell Rep)
    We show that active CARD11 variants can inhibit basal NIK-induced p100 processing to p52 independently of their ability to activate canonical NF-κB. Our results reveal an unexpected ability of activated CARD11 to potentiate the noncanonical NF-κB pathway through p100 accumulation, which likely contributes to both normal B cell homeostasis and the dysregulated proliferation of lymphomas that harbor CARD11 GoF variants.
    Journal
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    CARD11 (Caspase Recruitment Domain Family Member 11)
    3ms
    Gene Expression Profiling Provides an Improved Characterization of CD79B-Mutated Diffuse Large B-Cell Lymphomas. (PubMed, J Pers Med)
    TP53 mutation showed an association with poorer overall survival in a secondary analysis, consistent with prior reports, while survival by CD79B/MYD88 mutation status and the differentially expressed genes showed no significant differences in this cohort. In conclusion, the current study identified novel up-regulated genes in CD79B-mutated DLBCLs beyond NF-κB pathway signaling, which may contribute to a better definition of potential therapeutic targets and further improves the characterization of this distinct and aggressive DLBCL subgroup.
    Journal
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    TP53 (Tumor protein P53) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • RUNX1 (RUNX Family Transcription Factor 1) • CD79B (CD79b Molecule) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CARD11 (Caspase Recruitment Domain Family Member 11) • IL10 (Interleukin 10) • CD14 (CD14 Molecule) • PIM1 (Pim-1 Proto-Oncogene) • BCL2A1 (BCL2 Related Protein A1) • GZMB (Granzyme B) • IL7 (Interleukin 7) • RASGRF1 (Ras Protein Specific Guanine Nucleotide Releasing Factor 1) • AFDN (Afadin, Adherens Junction Formation Factor) • HSP90AB1 (Heat Shock Protein 90 Alpha Family Class B Member 1) • WNT11 (Wnt Family Member 11)
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    TP53 mutation
    4ms
    Clinical characteristics and molecular heterogeneity in Follicular lymphoma with extranodal involvement. (PubMed, Genome Med)
    Negative prognostic impact of multiple ENI upon R-chemo therapy could be overcome by R2 therapy in FL. Better understanding of the biological behavior of multiple ENI could provide a potential clinical rationale for future mechanism-based therapy of FL.
    Journal • IO biomarker
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    KMT2D (Lysine Methyltransferase 2D) • B2M (Beta-2-microglobulin) • CREBBP (CREB binding protein) • CARD11 (Caspase Recruitment Domain Family Member 11) • STAT6 (Signal transducer and activator of transcription 6)
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    Rituxan (rituximab) • lenalidomide
    4ms
    Identifying the causal role and therapeutic potential of immune-related genes in bladder cancer: a Mendelian randomization study. (PubMed, Discov Oncol)
    This study elucidates the immune-related pathways influencing bladder cancer, highlighting GSTM1 and other key immune-related genes as potential biomarkers. These discoveries pave the way for innovative therapeutic approaches, advancing personalized medicine strategies in bladder cancer treatment.
    Journal • IO biomarker
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    CARD11 (Caspase Recruitment Domain Family Member 11) • GSTM1 (Glutathione S-transferase mu 1) • NTN1 (Netrin 1)
    4ms
    Accelerated In Silico Discovery of SGR-1505: A Potent MALT1 Allosteric Inhibitor for the Treatment of Mature B-Cell Malignancies. (PubMed, J Med Chem)
    Multiparameter optimization allowed efficient prioritization of molecules with good potency and drug-like properties during lead optimization, which led to the discovery of a highly potent MALT1 inhibitor, SGR-1505, with a well-balanced property profile. It demonstrated strong antitumor activity alone and in combination with BTK inhibitor in multiple in vivo B-cell lymphoma xenograft models and progressed to a phase 1 clinical trial in patients with mature B-cell neoplasms.
    Journal
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    CARD11 (Caspase Recruitment Domain Family Member 11) • MALT1 (MALT1 Paracaspase)
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    SGR-1505
    4ms
    Comparative analysis reveals recurrent molecular alterations in low-risk HPV6 and HPV11-associated squamous cell carcinoma of the uterine cervix and vulva. (PubMed, Mod Pathol)
    We provide evidence that SCCs associated with low-risk HPV are distinct entities, differing from those related to high-risk HPV and more closely resembling HPV-independent neoplasms. Given that low-risk HPV-associated SCCs of the cervix and vulva exhibit unique morphological and molecular features, they should either be described separately within existing classification systems or classified as a distinct new entity.
    Journal
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    TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR2 (Fibroblast growth factor receptor 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1) • TERT (Telomerase Reverse Transcriptase) • ASXL1 (ASXL Transcriptional Regulator 1) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • NOTCH2 (Notch 2) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • CARD11 (Caspase Recruitment Domain Family Member 11) • NOTCH3 (Notch Receptor 3) • STAG2 (Stromal Antigen 2) • KMT2B (Lysine Methyltransferase 2B) • EPHA5 (EPH Receptor A5) • FNDC1 (Fibronectin Type III Domain Containing 1) • BCORL1 (BCL6 Corepressor Like 1)
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    ARID1A mutation • FGFR2 mutation
    5ms
    Pathway-level mutational signatures predict breast cancer outcomes and reveal therapeutic targets. (PubMed, Br J Pharmacol)
    We assembled a comprehensive database of breast cancer samples and used this cohort to identify cancer-specific disruptive mutation signatures linked to altered survival outcomes.
    Journal
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    TP53 (Tumor protein P53) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • CARD11 (Caspase Recruitment Domain Family Member 11)
    5ms
    Lenalidomide-rituximab with high-dose methotrexate for treatment of patients with newly diagnosed primary cns lymphoma: a promising first-line approach. (PubMed, Ann Hematol)
    In conclusion, the R2-MTX regimen showed encouraging efficacy and a manageable safety profile in a small cohort of newly diagnosed PCNSL patients unsuitable for ASCT. These preliminary findings suggest that R2-MTX may be a promising therapeutic alternative, but validation in larger, prospective multicenter studies is warranted.
    Journal
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    CARD11 (Caspase Recruitment Domain Family Member 11)
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    Rituxan (rituximab) • lenalidomide • methotrexate • methotrexate IV