CARD11 (Caspase Recruitment Domain Family Member 11): A Master Regulator of Lymphocyte Activation and Its Role in Immunodeficiency and Lymphoma
Comprehensive gene card for CARD11, covering genomic context, expression, mutations, and clinical significance in B-cell malignancies and primary immunodeficiencies.
Gene Information Card
| Symbol | CARD11 |
|---|---|
| Full Name | Caspase recruitment domain family member 11 |
| Gene Type | Protein coding |
| Chromosomal Location | 7p22.2 |
| NCBI Gene ID | 84433 ncbi.nlm.nih.gov/gene/84433 |
| Ensembl ID | ENSG00000198286 |
| UniProt ID | Q9BXL7 |
| OMIM ID | 607210 |
| HGNC ID | 16393 |
| Aliases | BIMP3, CARMA1, CARD-containing MAGUK protein 1, IMD11 |
Description
CARD11 (Caspase Recruitment Domain Family Member 11), also known as CARMA1, encodes a scaffold protein essential for antigen receptor-mediated NF-kB activation in lymphocytes. It belongs to the membrane-associated guanylate kinase (MAGUK) family and contains an N-terminal CARD domain, a coiled-coil region, and a C-terminal MAGUK domain. Upon T-cell or B-cell receptor engagement, CARD11 is phosphorylated and undergoes a conformational change, recruiting BCL10 and MALT1 to form the CBM complex, which activates the IKK complex and NF-kB transcription factors. This pathway is critical for lymphocyte proliferation, differentiation, and survival. Germline mutations in CARD11 cause primary immunodeficiencies, while somatic mutations are associated with various lymphomas, particularly diffuse large B-cell lymphoma (DLBCL).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Diffuse large B-cell lymphoma (DLBCL) | Somatic gain-of-function mutations in the coiled-coil domain lead to constitutive NF-kB activation, promoting B-cell survival and proliferation. | COSMIC; Lenz et al., 2008 (Science); Ngo et al., 2011 (Nature) |
| Primary immunodeficiency (IMD11) | Loss-of-function mutations impair NF-kB signaling, leading to defective T and B cell activation, causing severe combined immunodeficiency or combined immunodeficiency. | OMIM; Stepensky et al., 2013 (J Allergy Clin Immunol) |
| B-cell lymphoma (other subtypes) | Recurrent mutations in CARD11 are found in activated B-cell-like DLBCL and other lymphomas, contributing to oncogenic NF-kB signaling. | COSMIC; Compagno et al., 2009 (Nature) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 20.6 | High |
| Lymph node | 18.3 | High |
| Blood | 12.1 | Medium |
| Bone marrow | 10.4 | Medium |
| Lung | 4.2 | Low |
| Brain | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Ramos (Burkitt lymphoma) | 25.3 | B-cell line, high expression |
| Jurkat (T-cell leukemia) | 22.7 | T-cell line, high expression |
| K-562 (CML) | 8.5 | Myeloid line, moderate |
| HeLa (cervical carcinoma) | 1.2 | Low expression |
| A549 (lung carcinoma) | 0.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| L225LI (c.673A>C) | Missense | Somatic, recurrent in DLBCL | Gain-of-function, constitutive NF-kB activation |
| G123S (c.367G>A) | Missense | Somatic, rare | Gain-of-function, increased NF-kB activity |
| E134K (c.400G>A) | Missense | Somatic, in DLBCL | Gain-of-function |
| R71W (c.211C>T) | Missense | Germline, loss-of-function | Impaired NF-kB signaling, immunodeficiency |
| Q31* (c.91C>T) | Nonsense | Germline, loss-of-function | Truncated protein, loss of function |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift, or missense in critical domains) impair CARD11's ability to recruit BCL10/MALT1, leading to defective NF-kB activation. These are typically germline and cause primary immunodeficiency (IMD11).
Gain of Function (GOF)
Gain-of-function mutations, often in the coiled-coil domain, promote spontaneous CARD11 oligomerization and constitutive NF-kB signaling, driving lymphomagenesis. These are somatic and recurrent in DLBCL.
Dominant Negative (DN)
Some missense mutations may act as dominant-negative, interfering with wild-type CARD11 function, though evidence is limited. This is less characterized compared to LoF and GoF.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • signal transducer activity |
| • NF-kappaB transcription factor activity | • protein kinase binding |
| • CARD domain binding | • identical protein binding |
| • protein homodimerization activity | • scaffold protein binding |
Pathways
• NF-kappaB signaling pathway (Reactome: R-HSA-1169091)
• T cell receptor signaling pathway (KEGG: hsa04660)
• B cell receptor signaling pathway (KEGG: hsa04662)
• CBM complex signaling (Reactome: R-HSA-1169091)
• Innate immune system (Reactome: R-HSA-168249)
Protein Summary
CARD11 is a 1159-amino-acid scaffold protein (UniProt Q9BXL7) with a molecular weight of ~127 kDa. It contains an N-terminal CARD domain (residues 1-110), a coiled-coil region (residues 130-400), and a C-terminal MAGUK domain (including PDZ, SH3, and GUK domains). The protein is predominantly expressed in lymphoid tissues and is essential for antigen receptor signaling. Upon receptor engagement, CARD11 undergoes phosphorylation (e.g., by PKC) and changes conformation, exposing the coiled-coil domain to recruit BCL10 and MALT1, forming the CBM complex. This complex activates IKK, leading to IkB phosphorylation and degradation, allowing NF-kB to translocate to the nucleus. CARD11 also interacts with other proteins like TRAF6 and TAK1 to modulate signaling. Mutations in CARD11 disrupt this pathway, leading to immunodeficiency or lymphoma.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CARD11 Knockout HEK293 Cell Line | EDJ-KQ138 | Human | 84433 | Details Get a Quote |
| CARD11 Knockout HeLa Cell Line | EDJ-KQ18923 | Human | 84433 | Details Get a Quote |
| CARD11 Knockout A-549 Cell Line | EDJ-KQ66088 | Human | 84433 | Details Get a Quote |
| CARD11 Knockout HCT 116 Cell Line | EDJ-KQ74511 | Human | 84433 | Details Get a Quote |
| CARD11 (p.A968T) Point Mutation in HAP1 Cell Line | EDC03428 | Human | 84433 | Details Get a Quote |
| CARD11 (c.2511-77G>A )Point Mutation in HAP1 Cell Line | EDC03429 | Human | 84433 | Details Get a Quote |
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