CARD11

Last update 08 May 2025

Basic Info

Synonyms

BIMP3, CARD-containing MAGUK protein 1, CARD11

+ [4]

Introduction

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).

100 Clinical Results associated with CARD11

100 Translational Medicine associated with CARD11

0 Patents (Medical) associated with CARD11

624

Literatures (Medical) associated with CARD11

01 Dec 2025·Journal of Clinical Immunology

Successful Treatment with Sirolimus of a Patient with a Novel CARD11 Germline Mutation in B-Cell Expansion with Nuclear Factor Kappa B and T-Cell Anergy: Case Report and Literature Review

Review

Author: Kataoka, Shinsuke ; Tsumura, Yusuke ; Narita, Kotaro ; Fukasawa, Tatsuya ; Yamamori, Ayako ; Sajiki, Daichi ; Miyajima, Yuji ; Yamashita, Daiki ; Nishio, Nobuhiro ; Muramatsu, Hideki ; Narita, Atsushi ; Nishinosono, Tsubasa ; Maemura, Ryo ; Wakamatsu, Manabu ; Takahashi, Yoshiyuki ; Shirakawa, Yuichi

PURPOSEB-cell expansion with nuclear factor kappa B and T-cell anergy (BENTA) is an inborn error of immunity characterized by congenital polyclonal B-cell lymphocyte expansion. In this report, we present a case of a girl diagnosed with BENTA carrying a novel CARD11 germline mutation, aiming to clarify the clinical presentation of BENTA by conducting a literature review.METHODSGenetic analysis, including whole-exome sequencing, was performed using genomic DNA extracted from the patient's peripheral blood, oral mucosa, and fingernails. Additionally, a comprehensive literature review of cases with BENTA was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.RESULTSA p.Leu251Pro germline variant in the CARD11 gene was identified in an 18-month-old girl with a genetic diagnosis of BENTA. She required adenoidectomy and tonsillectomy due to airway obstruction causing wheezing. Her symptoms improved with prednisolone and sirolimus. The literature review we conducted identified a total of 34 cases of BENTA. Among these cases, 15 were either asymptomatic or showed improvement without requiring any specific treatment. However, all six reported deaths were diagnosed before the age of 3 years, with two attributed to refractory hemophagocytic syndrome and four caused by opportunistic infections.CONCLUSIONWe present a case of BENTA with life-threatening respiratory symptoms caused by a novel CARD11 germline mutation. The patient showed a positive response to immunosuppressive therapy, including sirolimus. While BENTA is typically regarded as a benign disorder, a literature review revealed that infants with BENTA are at high risk of severe outcomes and require therapeutic intervention.

01 Oct 2025·Immunology Letters

BENTA disease or CARD11 gain-of-function? A novel variant with atypical features and a literature review

Review

Author: Keller, Bärbel ; Baldini, Letizia ; Montin, Davide ; Passarelli, Chiara ; Warnatz, Klaus ; Dewitte, Lisa ; Bossuyt, Xavier ; Licciardi, Francesco ; Ginevrino, Monia ; Carli, Diana

INTRODUCTIONThe CARD11 (Caspase Recruitment Domain Family Member 11) gene encodes a scaffold protein critical for NF-κB signaling, regulating B-cell differentiation and T-cell effector functions. Gain-of-function (GOF) mutations in CARD11 cause BENTA disease (B cell Expansion with NF-κB and T cell Anergy), an autosomal dominant disorder typically presenting with early-onset polyclonal B-cell lymphocytosis, splenomegaly, lymphadenopathy, and recurrent infections.METHODSWe describe three related patients harboring a novel CARD11-GOF mutation (D357E), presenting with a BENTA phenotype with atypical features, including high IgM levels and a normal B-cell count, with life-threatening HLH in one case. Additionally, we conducted a systematic literature review using PubMed and EMBASE to identify previously reported cases of CARD11 GOF mutations.RESULTSIn vitro functional analysis demonstrated that the D357E variant activates the NF-κB signaling pathway in primary lymphocytes and in HEK293T cells transfected with mutant CARD11. Our literature review identified 13 studies describing 29 patients. Notably, HLH emerged as a common complication of CARD11 GOF mutations (18.8 %), while B-lymphocytosis -though frequent- was not universally present.CONCLUSIONWe identified a novel pathogenic CARD11 variant and described its atypical phenotype, further expanding the clinical spectrum of CARD11 GOF disorders. These findings underscore the need for increased awareness of HLH risk in patients with CARD11 GOF mutations.

02 Jun 2025·Journal of Experimental Medicine

Dominant interfering CARD11 variants disrupt JNK signaling to promote GATA3 expression in T cells

Article

Author: Cooper, Megan A. ; Stinson, Jeffrey R. ; Dalgard, Clifton L. ; Milner, Joshua D. ; Chan, Alice Y. ; Huang, Lei Haley ; Sukumar, Gauthaman ; Saucier, Nermina ; Bauman, Bradly M. ; Frank, Andrew M. ; Kallarakal, Melissa A. ; Snow, Andrew L.

Several “primary atopic disorders” are linked to monogenic defects that attenuate TCR signaling, favoring T helper type 2 (TH2) cell differentiation. Patients with CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease suffer from severe atopy, caused by germline loss-of-function/dominant interfering (LOF/DI) CARD11 variants. The CARD11 scaffold enables TCR-induced activation of NF-κB, mTORC1, and JNK signaling, yet the function of CARD11-dependent JNK signaling in T cells remains nebulous. Here we show that CARD11 is critical for TCR-induced activation of JNK1 and JNK2, as well as canonical JUN/FOS AP-1 family members. Patient-derived CARD11 DI variants attenuated WT CARD11 JNK signaling, mirroring effects on NF-κB. Transcriptome profiling revealed JNK inhibition upregulated TCR-induced expression of GATA3 and NFATC1, key transcription factors for TH2 cell development. Further, impaired CARD11-JNK signaling was linked to enhanced GATA3 expression in CADINS patient T cells. Our findings reveal a novel intrinsic mechanism connecting impaired CARD11-dependent JNK signaling to enhanced GATA3/NFAT2 induction and TH2 cell differentiation in CADINS patients.

News (Medical) associated with CARD11

14 Apr 2022

·www.biospace.com

Exelixis Announces Initiation of First-In-Human Phase 1 Trial Evaluating XL114 Monotherapy in Patients with Non-Hodgkin’s Lymphoma

Exelixis, Inc. (Nasdaq: EXEL) today announced initiation of the dose-escalation stage of the first-in-human phase 1 trial of XL114, a novel anti-cancer compound that inhibits the CARD11-BCL10-MALT1 complex, as a monotherapy in patients with non-Hodgkin’s lymphoma (NHL) who have received prior standard therapies. The objectives of the study are to determine the recommended dose and/or the maximum tolerated dose of XL114 and to evaluate the safety and preliminary efficacy of XL114 in patients with NHL. “The initiation of the dose-escalation stage of our first-in-human phase 1 trial of XL114 marks an important milestone in our early efforts to identify treatments for people with blood cancers, such as non-Hodgkin’s lymphoma, who have exhausted known life-prolonging treatment options and are thus facing poor prognoses,” said Vicki L. Goodman, M.D., Executive Vice President, Product Development and Medical Affairs, and Chief Medical Officer, Exelixis. “Based on preclinical data demonstrating activity in lymphoma cell lines that are resistant to therapies that inhibit Bruton's tyrosine kinase, we are encouraged by the potential XL114 holds and look forward to advancing to the expansion stage once the appropriate dose is identified.” The dose-escalation stage will determine the recommended dose of XL114 in patients with advanced B- and T-cell NHL. In the cohort-expansion stage, the safety and preliminary efficacy of XL114 will be further evaluated in B-cell NHL-specific expansion cohorts, including patients with activated B-cell-like diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. The primary endpoint of the expansion stage will be objective response rate based on lymphoma-specific response criteria as assessed by the investigator. As announced last year, Exelixis in-licensed XL114 from Aurigene Discovery Technologies Limited under the companies’ July 2019 collaboration, option and license agreement. Exelixis assumed responsibility for the future clinical development, commercialization and global manufacturing of XL114.

XL-114Non-Hodgkin Lymphoma

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CARD11

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