CARD11

Summary

CARD11 (caspase recruitment domain family member 11, HGNC:16393) is a protein-coding gene on chromosome 7p22.2, encoding Caspase recruitment domain-containing protein 11 (Q9BXL7). 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.

The protein encoded by this gene 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. This protein is also a member of the CARD protein family, which is defined by carrying a characteristic caspase-associated recruitment domain (CARD). This protein has a domain structure similar to that of CARD14 protein. The CARD domains of both proteins have been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. When expressed in cells, this protein activated NF-kappaB and induced the phosphorylation of BCL10.

Source: NCBI Gene 84433 — RefSeq curated summary.

At a glance

• Gene–disease (curated): BENTA disease (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 16
• Clinical variants (ClinVar): 1,364 total — 29 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 30
• Cancer driver (intOGen): activating (oncogene-like) across 7 cancer types
• MANE Select transcript: NM_032415

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16393
Approved symbol	CARD11
Name	caspase recruitment domain family member 11
Location	7p22.2
Locus type	gene with protein product
Status	Approved
Aliases	CARMA1, BIMP3
Ensembl gene	ENSG00000198286
Ensembl biotype	protein_coding
OMIM	607210
Entrez	84433

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 5 retained_intron

ENST00000355508, ENST00000356408, ENST00000396946, ENST00000480332, ENST00000698637, ENST00000698652, ENST00000698654, ENST00000698662, ENST00000888804, ENST00000888805, ENST00000911401, ENST00000911403

RefSeq mRNA: 2 — MANE Select: NM_032415 NM_001324281, NM_032415

CCDS: CCDS5336

Canonical transcript exons

ENST00000396946 — 25 exons

Exon	Start	End
ENSE00001526848	3043667	3043867
ENSE00003631926	2918491	2918587
ENSE00003974265	2932535	2932586
ENSE00003974266	2917290	2917385
ENSE00003974267	2937907	2938032
ENSE00003974268	2919372	2919612
ENSE00003974269	2906142	2906842
ENSE00003974270	2944212	2944537
ENSE00003974271	2913287	2913466
ENSE00003974272	2926739	2926791
ENSE00003974273	2939749	2939928
ENSE00003974274	2937037	2937234
ENSE00003974275	2958500	2958631
ENSE00003974276	2924233	2924365
ENSE00003974277	2945819	2945956
ENSE00003974278	2923132	2923333
ENSE00003974279	2910050	2910165
ENSE00003974280	2912172	2912296
ENSE00003974281	2928598	2928698
ENSE00003974282	2929992	2930074
ENSE00003974283	2947575	2947787
ENSE00003974284	2922634	2922760
ENSE00003974285	2915237	2915372
ENSE00003974286	2938679	2938831
ENSE00003974287	2934453	2934629

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 95.93.

FANTOM5 (CAGE): breadth broad, TPM avg 6.3013 / max 161.9674, expressed in 723 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82528	4.4530	631
82529	0.9198	271
82530	0.6629	234
82531	0.2268	105
82527	0.0388	10

Top tissues by expression

232 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	95.93	gold quality
lymph node	UBERON:0000029	91.38	gold quality
spleen	UBERON:0002106	89.33	gold quality
vermiform appendix	UBERON:0001154	88.35	gold quality
pancreatic ductal cell	CL:0002079	88.29	silver quality
blood	UBERON:0000178	87.45	gold quality
superficial temporal artery	UBERON:0001614	86.09	silver quality
caecum	UBERON:0001153	84.32	gold quality
buccal mucosa cell	CL:0002336	83.68	silver quality
parotid gland	UBERON:0001831	82.62	silver quality
palpebral conjunctiva	UBERON:0001812	81.35	gold quality
amniotic fluid	UBERON:0000173	80.09	gold quality
gall bladder	UBERON:0002110	79.88	gold quality
bone marrow	UBERON:0002371	79.76	gold quality
kidney epithelium	UBERON:0004819	79.75	gold quality
epithelium of nasopharynx	UBERON:0001951	78.99	silver quality
tonsil	UBERON:0002372	78.44	gold quality
trabecular bone tissue	UBERON:0002483	78.28	silver quality
bone marrow cell	CL:0002092	78.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.14	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	78.03	gold quality
lateral nuclear group of thalamus	UBERON:0002736	77.78	gold quality
islet of Langerhans	UBERON:0000006	77.08	gold quality
vastus lateralis	UBERON:0001379	76.76	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.75	gold quality
epithelial cell of pancreas	CL:0000083	76.63	gold quality
medial globus pallidus	UBERON:0002477	76.39	silver quality
quadriceps femoris	UBERON:0001377	75.84	gold quality
thymus	UBERON:0002370	75.79	gold quality
cerebellar vermis	UBERON:0004720	75.05	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	123.53
E-MTAB-9067	yes	14.83
E-ANND-3	yes	9.51
E-MTAB-9801	yes	6.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HAND2, MAF, TP53

miRNA regulators (miRDB)

15 targeting CARD11, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-3657	96.33	66.29	608
HSA-MIR-103B	95.51	66.85	441

Literature-anchored findings (GeneRIF, showing 40)

• CARMA1 is an essential signaling component that mediates TCR-induced NF-kappa B activation. (PMID:12154356)
• CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation and CD28 costimulation-dependent Jnk activation. (PMID:12154360)
• CARD11 mediates factor-specific activation of NF-kappaB by the T cell receptor complex (PMID:12356734)
• CARMA1 and CARMA3 bind to Ikappa kinase gamma-NFkappaB in B and T lymphocytes (PMID:15184390)
• Phosphorylation of CARMA1 plays a critical role in T Cell receptor-mediated NF-kappaB activation. (PMID:16356856)
• CARMA1 complex is required for induction of NF-kappaB by Akt (PMID:16508008)
• These findings suggest that endogenous Nore1B recruits active Ras to the APC-T cell interface and mediates the interaction between Ras and Carma1. (PMID:16520020)
• CaMKII phosphorylates CARMA1 on Ser109 and that the phosphorylation facilitates the interaction between CARMA1 and Bcl10. (PMID:16809782)
• CD26 interacts with CARMA1 in T-cells, resulting in signaling events that lead to activation. (PMID:17287217)
• oligomerization of CARMA1 is through its Coiled-coil domain. Disruption of the predicted structure of the Coiled-coil domain of CARMA1 impaired its oligomerization and, importantly, abrogated CARMA1-mediated NF-kappaB activation (PMID:17428801)
• H-RS cells show a deregulated B cell programme 8 lacking expression of the lymphocyte specific CARMA1 protein. (PMID:18231929)
• results demonstrate that CARD11 is a bona fide oncogene in diffuse large B cell lymphoma (PMID:18323416)
• Data show that the protein kinase C-responsive inhibitory domain of CARD11 functions in NF-kappaB activation to regulate the association of multiple signaling cofactors that differentially depend on Bcl10 and MALT1 for association. (PMID:18625728)
• NF-kappaB pathway activation by CARD11 or tumor necrosis factor-alpha, compensatory IKKalpha activity was also observed with IKKbeta (PMID:19104039)
• T-cell activation triggers the recruitment of the COP9 signalosome (CSN) to the Carma1-Bcl10-Malt1 (CBM) complex, and CSN downregulation impairs TCR-induced IKK activation. (PMID:19444310)
• Results suggest HPK1-mediated phosphorylation of CARMA1 as an additional regulatory mechanism tuning the NF-kappaB response upon TCR stimulation. (PMID:19706536)
• the ADAP CARMA1 binding site is required for IKK gamma ubiquitination; both TAK1 and CARMA1 binding sites are required for IkappaB alpha phosphorylation and degradation and NF-kappaB nuclear translocation (PMID:20164171)
• The mutations of the oncogene CARD11 may contribute to NF-kappaB activation and thereby play a role in the pathogenesis of Primary CNS lymphoma. (PMID:20544211)
• results establish a mechanism that explains how diffuse large B cell lymphoma-associated mutations in CARD11 can initiate spontaneous, receptor-independent activation of NF-kappaB (PMID:20799731)
• PP2A-mediated dephosphorylation of Carma1 is a critical step to limit T-cell activation and effector cytokine production. (PMID:21157432)
• CARM1 is transcriptional coactivators that deposit H3R17me2a and H4R3me2a marks, respectively. (PMID:21172665)
• Very low mutation frequency of exons 5-9 in the CARD11 gene from 186 adult acute leukemia and 31 multiple myeloma samples. (PMID:21176849)
• A20, ABIN-1/2, and CARD11 mutations have prognostic value in gastrointestinal diffuse large B-cell lymphoma (PMID:21266526)
• expression of CARMA1 mRNA is likely associated with the expression of MUM1 and shows male predominance in diffuse large B cell lymphoma. (PMID:21569705)
• genetic polymorphism is associated with common variable immunodeficiency (PMID:21905497)
• A combination of in vitro and in vivo studies demonstrates that the CARMA1 transgene is required for optimal T cell responses to T cell receptor engagement and development of allergic airway inflammation, after activation of T cells in a murine model. (PMID:22075698)
• TLR-dependent TRAF6-MKK3-p38 MAPK signaling pathway synergizes with PKCtheta;-MEK-ERK signaling pathway. CARMA1 plays a crucial role in mediating this synergistic effect via TRAF6. (PMID:22303480)
• In Jurkat cells, CARMA1 is required for induction of Th2 transcription factors, GATA3 and JunB, and controls IL-4, IL-5, and IL-10 production. (PMID:22371397)
• The incidence of CARD11 mutations was 10.7% in Middle Eastern diffuse large B-cell lymphoma. (PMID:22397314)
• distinct CARMA1-dependent control of key cell cycle proteins in T cells is coordinated by ADAP (PMID:22411628)
• PKCdelta is a negative regulator in T cell activation through inhibiting the assembly of CARMA1 signalosome. (PMID:22528498)
• The present study failed to find any mut-ation in MYD88, CARD11 or CD79B in ocular MALT lymphoma. (PMID:22808296)
• Findings show that regulation of CARD11 signaling is a critical switch governing the decision between death and proliferation in antigen-stimulated mature B cells. (PMID:23027925)
• CARD11 mutations may predispose to B but not T lymphoid malignancy. (PMID:23129749)
• CARD11 gain-of-function mutations selectively confer the ability to associate with Bcl10 and induce K63-linked ubiquitination of Bcl10. (PMID:23149938)
• These data provide the first evidence that ubiquitination of CARMA1 by STUB1 promotes TCR-induced NF-kappaB signaling. (PMID:23322406)
• In patients with CARD11 deficiency, the combination of impaired activation and especially upregulation of inducible T-cell costimulator on T cells. (PMID:23374270)
• CARMA1 CARD was then purified to homogeneity and crystallized at 293 K. Finally, X-ray diffraction data were collected to a resolution of 3.2 A from a crystal belonging to space group P2(1)2(1)2(1) (PMID:23545653)
• SMO activates trimeric G proteins and CARMA1-associated signaling complex, leading to NF-kappaB activation and results in diffuse large B-cell lymphoma. (PMID:23632891)
• Combining crystallography, nuclear magnetic resonance, and electron microscopy, we reveal the structure of the Bcl10 CARD filament and the mode of interaction between CARMA1 and Bcl10 (PMID:24074955)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	card11	ENSDARG00000052741
mus_musculus	Card11	ENSMUSG00000036526
rattus_norvegicus	Card11	ENSRNOG00000024277

Paralogs (3): CARD10 (ENSG00000100065), CARD14 (ENSG00000141527), CARD9 (ENSG00000187796)

Protein

Protein identifiers

Caspase recruitment domain-containing protein 11 — Q9BXL7 (reviewed: Q9BXL7)

Alternative names: CARD-containing MAGUK protein 1

All UniProt accessions (3): E2QRC0, Q9BXL7, H7BY05

UniProt curated annotations — full annotation on UniProt →

Function. 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. 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. 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. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Promotes linear ubiquitination of BCL10 by promoting the targeting of BCL10 to RNF31/HOIP. Stimulates the phosphorylation of BCL10. Also activates the TORC1 signaling pathway.

Subunit / interactions. Homodimer; disulfide-linked. Homomultimer; polymerizes following activation, forming a nucleating helical template that seeds BCL10-filament formation via a CARD-CARD interaction. Interacts (via CARD domain) with BCL10 (via CARD domain); interaction takes place following CARD11 activation and polymerization, leading to the formation of a filamentous CBM complex assembly. Component of a CBM complex (CARD11-BCL10-MALT1) complex involved in NF-kappa-B activation. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. Interacts (via PDZ domain) with DPP4 (via cytoplasmic tail).

Subcellular location. Cytoplasm. Membrane raft.

Tissue specificity. Detected in adult peripheral blood leukocytes, thymus, spleen and liver. Also found in promyelocytic leukemia HL-60 cells, chronic myelogenous leukemia K-562 cells, Burkitt’s lymphoma Raji cells and colorectal adenocarcinoma SW480 cells. Not detected in HeLaS3, MOLT-4, A-549 and G431 cells.

Post-translational modifications. Phosphorylation at Ser-559, Ser-644 and Ser-652 by PRKCB and PRKCQ leads to a shift from an inactive to an active form that activates the NF-kappa-B signaling.

Disease relevance. B-cell expansion with NFKB and T-cell anergy (BENTA) [MIM:616452] An autosomal dominant condition characterized by onset in infancy of splenomegaly and polyclonal expansion of B cells, resulting in peripheral lymphocytosis. Affected individuals also show mild immune dysfunction, including some defective antibody responses and T-cell anergy. There may be a predisposition to the development of B-cell malignancy. The disease is caused by variants affecting the gene represented in this entry. Immunodeficiency 11 A (IMD11A) [MIM:615206] An autosomal recessive primary immunodeficiency characterized by normal numbers of T and B-lymphocytes, but defective intracellular signaling. There is a block in B-cell differentiation with increased numbers of transitional B-cells and hypogammaglobulinemia, as well as decreased numbers of regulatory T-cells and defects in T-cell function. The disease is caused by variants affecting the gene represented in this entry. Immunodeficiency 11B with atopic dermatitis (IMD11B) [MIM:617638] An autosomal dominant disorder of immune dysfunction characterized by onset of moderate to severe atopic dermatitis in early childhood. Some patients may have recurrent infections and other variable immune abnormalities. Laboratory studies show defects in T-cell activation, increased IgE, and eosinophilia. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Maintained in an autoinhibited state via homodimerization in which the CARD domain forms an extensive interaction with the adjacent linker and coiled-coil regions. Activation downstream of T-cell receptor (TCR) by phosphorylation by PRKCB and PRKCQ triggers CARD11 homooligomerization and BCL10 recruitment, followed by activation of NF-kappa-B.

Domain organisation. The linker region, also named autoinhibitory interface, is less inhibitory on its own than that of CARD9. The linker region together with the inhibitory domain (ID) are required to prevent constitutive activation and maintain CARD11 in an autoinhibitory state. Disruption of the inhibitory domain (ID) region triggers polymerization and activation, leading to formation of BCL10-nucleating filaments.

RefSeq proteins (2): NP_001311210, NP_115791* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001315	CARD	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR042141	CARD_CARD11	Domain

Pfam: PF00619

UniProt features (42 total): modified residue 10, sequence variant 8, helix 7, compositionally biased region 5, domain 3, region of interest 3, chain 1, disulfide bond 1, mutagenesis site 1, sequence conflict 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4LWD	X-RAY DIFFRACTION	1.79
4JUP	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXL7-F1	71.83	0.26

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (10): 448, 466, 512, 535, 559, 593, 644, 652, 886, 925

Disulfide bonds (1): 28

Mutagenesis-validated functional residues (1):

Position	Phenotype
28	abolished homodimerization.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-202424	Downstream TCR signaling
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-1168372	Downstream signaling events of B Cell Receptor (BCR)
R-HSA-1280218	Adaptive Immune System
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-202403	TCR signaling
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling
R-HSA-5621481	C-type lectin receptors (CLRs)
R-HSA-983705	Signaling by the B Cell Receptor (BCR)

MSigDB gene sets: 298 (showing top): PID_BCR_5PATHWAY, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_B_CELL_ACTIVATION, GOBP_THYMIC_T_CELL_SELECTION, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_LYMPHOCYTE_COSTIMULATION, GOBP_B_CELL_PROLIFERATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS

GO Biological Process (26): canonical NF-kappaB signal transduction (GO:0007249), B cell differentiation (GO:0030183), positive regulation of B cell proliferation (GO:0030890), T cell costimulation (GO:0031295), positive regulation of interleukin-2 production (GO:0032743), CD4-positive, alpha-beta T cell proliferation (GO:0035739), TORC1 signaling (GO:0038202), B cell proliferation (GO:0042100), regulation of apoptotic process (GO:0042981), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), thymic T cell selection (GO:0045061), regulation of B cell differentiation (GO:0045577), regulation of T cell differentiation (GO:0045580), homeostasis of number of cells (GO:0048872), positive regulation of T cell receptor signaling pathway (GO:0050862), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), protein homooligomerization (GO:0051260), positive regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000563), immune system process (GO:0002376), signal transduction (GO:0007165), T cell activation (GO:0042110), GMP metabolic process (GO:0046037), lymphocyte activation (GO:0046649), GDP metabolic process (GO:0046710), regulation of immune response (GO:0050776), positive regulation of T cell activation (GO:0050870)

GO Molecular Function (3): GMP kinase activity (GO:0004385), CARD domain binding (GO:0050700), protein binding (GO:0005515)

GO Cellular Component (8): immunological synapse (GO:0001772), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), CBM complex (GO:0032449), membrane raft (GO:0045121), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Immune System	2
Adaptive Immune System	2
Innate Immune System	2
Downstream signaling events of B Cell Receptor (BCR)	1
TCR signaling	1
Fc epsilon receptor (FCERI) signaling	1
C-type lectin receptors (CLRs)	1
Signaling by the B Cell Receptor (BCR)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
B cell activation	2
regulation of lymphocyte differentiation	2
intracellular signaling cassette	1
lymphocyte differentiation	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
positive regulation of cytokine production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
CD4-positive, alpha-beta T cell activation	1
alpha-beta T cell proliferation	1
TOR signaling	1
lymphocyte proliferation	1
apoptotic process	1
regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
T cell differentiation in thymus	1
T cell selection	1
B cell differentiation	1
regulation of B cell activation	1
T cell differentiation	1
regulation of T cell activation	1
multicellular organismal-level homeostasis	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
positive regulation of antigen receptor-mediated signaling pathway	1
protein complex oligomerization	1
CD4-positive, alpha-beta T cell proliferation	1
positive regulation of alpha-beta T cell proliferation	1
positive regulation of CD4-positive, alpha-beta T cell activation	1
regulation of CD4-positive, alpha-beta T cell proliferation	1
biological_process	1
cell communication	1

Protein interactions and networks

STRING

3026 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CARD11	BCL10	O95999	999
CARD11	MALT1	Q9UDY8	999
CARD11	IKBKG	Q9Y6K9	960
CARD11	PRKCQ	Q04759	927
CARD11	CD28	P10747	895
CARD11	TRAF6	Q9Y4K3	884
CARD11	CD79B	P40259	855
CARD11	TNFAIP3	P21580	822
CARD11	FYB1	O15117	814
CARD11	IKBKB	O14920	784
CARD11	CD79A	P11912	776
CARD11	BTK	Q06187	763
CARD11	UBE2N	P61088	723
CARD11	CHUK	O15111	716
CARD11	NFKB1	P19838	714

IntAct

474 interactions, top by confidence:

A	B	Type	Score
CARD11	BCL10	psi-mi:“MI:0915”(physical association)	0.860
BCL10	CARD11	psi-mi:“MI:0914”(association)	0.860
BCL10	CARD11	psi-mi:“MI:0915”(physical association)	0.860
CARD11	PRKCD	psi-mi:“MI:0915”(physical association)	0.620
CARD11	MALT1	psi-mi:“MI:0915”(physical association)	0.590
CARD11	CBLB	psi-mi:“MI:0915”(physical association)	0.520
CARD11		psi-mi:“MI:0915”(physical association)	0.520
CBLB	CARD11	psi-mi:“MI:0915”(physical association)	0.520
CSNK1A1	CARD11	psi-mi:“MI:0914”(association)	0.500
CARD11	CSNK1A1	psi-mi:“MI:0915”(physical association)	0.500
CARD11	AKT1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
CREBBP	CARD11	psi-mi:“MI:0407”(direct interaction)	0.440
CARD11	E6	psi-mi:“MI:0407”(direct interaction)	0.440
E6	CARD11	psi-mi:“MI:0407”(direct interaction)	0.440
E	CARD11	psi-mi:“MI:0407”(direct interaction)	0.440
NET1	CARD11	psi-mi:“MI:0407”(direct interaction)	0.440
CARD11	PTEN	psi-mi:“MI:0407”(direct interaction)	0.440
RPS6KA1	CARD11	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (87): CARD11 (Biochemical Activity), CARD11 (Affinity Capture-Western), CARD11 (Affinity Capture-Western), RNF181 (FRET), CARD11 (Affinity Capture-Western), BCL10 (Co-crystal Structure), BCL10 (Reconstituted Complex), PPP2R1A (Affinity Capture-Western), PPP2R1A (Two-hybrid), CARD11 (Affinity Capture-Western), CARD11 (Affinity Capture-Western), PRKCQ (Affinity Capture-Western), CARD11 (Biochemical Activity), CARD11 (Affinity Capture-Western), CARD11 (Affinity Capture-Western)

ESM2 similar proteins: A0A8M2BID5, A0A8M9PQ61, A1Z7A6, D3ZHV2, E9Q557, F1LMV6, F1M0Z1, G3V7L1, O43150, O60229, O60437, O75962, O97592, O97902, P0CE94, P0CE95, P10911, P11530, P11531, P11532, P11533, P15924, P30427, P33175, P46939, Q03001, Q0KL02, Q15149, Q1AAU6, Q1LUA6, Q5GN48, Q6ZWR6, Q7SIG6, Q8CIS0, Q8NF91, Q8WXH0, Q91ZU6, Q92817, Q95RG8, Q9BXL7

Diamond homologs: A2AIV8, P58660, Q8CIS0, Q99KF0, Q9BWT7, Q9BXL6, Q9BXL7, Q9EPY0, Q9H257

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
PDPK1	up-regulates	CARD11	phosphorylation
CARD11	up-regulates	MALT1	binding
PPP2CB	“down-regulates activity”	CARD11	dephosphorylation
PPP2CA	“down-regulates activity”	CARD11	dephosphorylation
PRKCQ	“up-regulates activity”	CARD11	phosphorylation
CARD11	“form complex”	CBM	binding
STUB1	“up-regulates activity”	CARD11	ubiquitination
CARD11	up-regulates	BCL10	binding
AKT1	“up-regulates activity”	CARD11	phosphorylation
MAP4K1	“up-regulates activity”	CARD11	phosphorylation
PRKCQ	“down-regulates activity”	CARD11	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 178 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHOQ GTPase cycle	7	10.6×	5e-04
C-type lectin receptors (CLRs)	5	9.9×	5e-03
Cell death signalling via NRAGE, NRIF and NADE	5	9.2×	6e-03
RHOJ GTPase cycle	5	8.3×	8e-03
Neurexins and neuroligins	5	8.2×	8e-03
p75 NTR receptor-mediated signalling	5	7.8×	9e-03
RHOB GTPase cycle	6	7.7×	5e-03
NRAGE signals death through JNK	5	7.7×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cardiac conduction	5	25.9×	2e-03
positive regulation of excitatory postsynaptic potential	5	16.1×	4e-03
excitatory postsynaptic potential	5	13.6×	8e-03
transport across blood-brain barrier	7	7.7×	8e-03
transmembrane transport	7	7.2×	9e-03
cell-cell adhesion	10	6.2×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 7 cancer types — BL, COADREAD, DLBCLNOS, HCC, MLYM, NHL, OVT.

Clinical variants and AI predictions

ClinVar

1364 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	29
Likely pathogenic	21
Uncertain significance	529
Likely benign	609
Benign	44

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068965	NM_032415.7(CARD11):c.676C>T (p.Gln226Ter)	Pathogenic
1069758	NM_032415.7(CARD11):c.2062C>T (p.Arg688Ter)	Pathogenic
1070449	NM_032415.7(CARD11):c.793C>T (p.Gln265Ter)	Pathogenic
1070810	NM_032415.7(CARD11):c.2437G>T (p.Glu813Ter)	Pathogenic
1074577	NC_000007.13:g.(?2998114)(2998160_?)del	Pathogenic
1378516	NM_032415.7(CARD11):c.2650dup (p.Arg884fs)	Pathogenic
1451672	NM_032415.7(CARD11):c.799del (p.Leu267fs)	Pathogenic
1456913	NC_000007.13:g.(?2972149)(2972240_?)del	Pathogenic
1703009	NM_032415.7(CARD11):c.1030_1032del (p.Lys344del)	Pathogenic
1707407	NM_032415.7(CARD11):c.547_588dup (p.Lys196_Val197insMetLysGluGluArgAspSerTyrAsnAspGluLeuValLys)	Pathogenic
183144	NM_032415.7(CARD11):c.368G>A (p.Gly123Asp)	Pathogenic
1995060	NM_032415.7(CARD11):c.2579del (p.Gly860fs)	Pathogenic
203461	NM_032415.7(CARD11):c.146G>A (p.Cys49Tyr)	Pathogenic
2043569	NM_032415.7(CARD11):c.1663del (p.Arg555fs)	Pathogenic
2931094	NM_032415.7(CARD11):c.2671C>T (p.Arg891Ter)	Pathogenic
2941212	NM_032415.7(CARD11):c.2683del (p.Leu895fs)	Pathogenic
2941343	NM_032415.7(CARD11):c.1893C>G (p.Tyr631Ter)	Pathogenic
3245809	NC_000007.13:g.(?2954851)(2955026_?)del	Pathogenic
433533	NP_115791.3:p.Leu194Pro	Pathogenic
433534	CARD11, GLU57ASP	Pathogenic
433536	NP_115791.3:p.Met183_Lys196dup	Pathogenic
4689357	NM_032415.7(CARD11):c.862C>T (p.Gln288Ter)	Pathogenic
4783897	NM_032415.7(CARD11):c.2662del (p.Arg888fs)	Pathogenic
48647	NM_032415.7(CARD11):c.401A>G (p.Glu134Gly)	Pathogenic
48648	NM_032415.7(CARD11):c.367G>A (p.Gly123Ser)	Pathogenic
48649	NM_032415.7(CARD11):c.2833C>T (p.Gln945Ter)	Pathogenic
48650	NM_032415.5(CARD11):c.2704-890_2839+352del	Pathogenic
540976	NM_032415.7(CARD11):c.2509C>T (p.Arg837Ter)	Pathogenic
830915	NC_000007.14:g.(?2944192)(2947807_?)del	Pathogenic
1013534	NM_032415.7(CARD11):c.2497C>T (p.Pro833Ser)	Likely pathogenic

SpliceAI

4750 predictions. Top by Δscore:

Variant	Effect	Δscore
7:2910045:CCTAC:C	donor_loss	1.0000
7:2910047:TACCT:T	donor_loss	1.0000
7:2910048:A:AT	donor_loss	1.0000
7:2912167:CTCA:C	donor_loss	1.0000
7:2912169:CAC:C	donor_loss	1.0000
7:2912170:A:AC	donor_gain	1.0000
7:2912170:AC:A	donor_gain	1.0000
7:2912171:C:CC	donor_gain	1.0000
7:2912171:CC:C	donor_gain	1.0000
7:2912292:GATAT:G	acceptor_gain	1.0000
7:2912293:ATAT:A	acceptor_gain	1.0000
7:2912294:TAT:T	acceptor_gain	1.0000
7:2912294:TATCT:T	acceptor_loss	1.0000
7:2912295:AT:A	acceptor_gain	1.0000
7:2912297:C:CC	acceptor_gain	1.0000
7:2913282:CTCA:C	donor_loss	1.0000
7:2913286:CCTGA:C	donor_gain	1.0000
7:2913465:CT:C	acceptor_gain	1.0000
7:2913467:C:CC	acceptor_gain	1.0000
7:2913471:C:CT	acceptor_gain	1.0000
7:2915232:TGTA:T	donor_loss	1.0000
7:2915233:GTAC:G	donor_loss	1.0000
7:2915234:TAC:T	donor_loss	1.0000
7:2915235:A:C	donor_loss	1.0000
7:2915236:C:CA	donor_loss	1.0000
7:2915368:ACGAA:A	acceptor_gain	1.0000
7:2915369:CGAA:C	acceptor_gain	1.0000
7:2915369:CGAAC:C	acceptor_gain	1.0000
7:2915370:GAAC:G	acceptor_loss	1.0000
7:2915371:AA:A	acceptor_gain	1.0000

AlphaMissense

7608 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:2919442:A:G	W814R	1.000
7:2919442:A:T	W814R	1.000
7:2937914:C:G	R379P	1.000
7:2937959:C:G	R364P	1.000
7:2938004:A:G	L349P	1.000
7:2939918:A:G	L232P	1.000
7:2944222:A:G	L225P	1.000
7:2944228:C:G	R223P	1.000
7:2944504:A:G	L131P	1.000
7:2945893:A:G	L95P	1.000
7:2945895:G:C	S94R	1.000
7:2945895:G:T	S94R	1.000
7:2945897:T:G	S94R	1.000
7:2945938:A:G	L80P	1.000
7:2945950:A:G	L76P	1.000
7:2947658:A:G	L46P	1.000
7:2919474:A:T	V803D	0.999
7:2937149:A:G	L410P	0.999
7:2937155:C:G	R408P	0.999
7:2937213:C:G	A389P	0.999
7:2937221:C:G	R386P	0.999
7:2937234:C:G	A382P	0.999
7:2937935:A:G	L372P	0.999
7:2938010:A:G	L347P	0.999
7:2938686:C:G	R337P	0.999
7:2938740:A:G	L319P	0.999
7:2938762:C:G	A312P	0.999
7:2938770:C:G	R309P	0.999
7:2938773:T:G	D308A	0.999
7:2944216:A:G	L227P	0.999

dbSNP variants (sampled 300 via entrez): RS1000016904 (7:2910775 G>A,C), RS1000044257 (7:2958300 A>C), RS1000047465 (7:2941670 G>A), RS1000052499 (7:3032352 T>C), RS1000053938 (7:3021507 G>A,T), RS1000092022 (7:2926327 C>T), RS1000102351 (7:3005032 T>A), RS1000106842 (7:2974845 A>G,T), RS1000123159 (7:2905938 G>T), RS1000129268 (7:3026470 A>C), RS1000157060 (7:2947132 T>G), RS1000190363 (7:2914905 C>T), RS1000231346 (7:2947451 C>T), RS1000245037 (7:2906185 G>A), RS1000246956 (7:2948289 T>C)

Disease associations

OMIM: gene MIM:607210 | disease phenotypes: MIM:615206, MIM:616452, MIM:617638

GenCC curated gene-disease

Disease	Classification	Inheritance
severe combined immunodeficiency due to CARD11 deficiency	Definitive	Autosomal recessive
BENTA disease	Definitive	Autosomal dominant
immunodeficiency 11b with atopic dermatitis	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (3)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
BENTA disease	Definitive	AD
severe combined immunodeficiency due to CARD11 deficiency	Definitive	AR
immunodeficiency 11b with atopic dermatitis	Definitive	AD

Mondo (4): severe combined immunodeficiency due to CARD11 deficiency (MONDO:0014081), BENTA disease (MONDO:0014645), immunodeficiency 11b with atopic dermatitis (MONDO:0054697), asthma (MONDO:0004979)

Orphanet (2): Combined immunodeficiency due to CARD11 deficiency (Orphanet:357237), BENTA disease (Orphanet:464336)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001047	Atopic dermatitis
HP:0001744	Splenomegaly
HP:0001880	Increased total eosinophil count
HP:0002028	Chronic diarrhea
HP:0002090	Pneumonia
HP:0002099	Asthma
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0002719	Recurrent infections
HP:0002720	Decreased circulating IgA concentration
HP:0002721	Immunodeficiency
HP:0002850	Decreased circulating total IgM
HP:0003212	Increased circulating IgE concentration
HP:0003593	Infantile onset
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0004432	Agammaglobulinemia
HP:0005404	Increased total B cell count
HP:0012312	Decreased total monocyte count
HP:0020102	Pneumocystis jirovecii pneumonia
HP:0020113	Decreased regulatory T cell proportion
HP:0031402	Reduced antigen-specific T cell proliferation
HP:0031692	Severe cytomegalovirus infection
HP:0031813	Colonic eosinophilia
HP:0032185	Disseminated molluscum contagiosum
HP:0034839	Lymphoid hyperplasia
HP:0100279	Ulcerative colitis
HP:0410299	Decreased specific antibody response to polysaccharide vaccine
HP:0500093	Food allergy

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001709_12	Atopic dermatitis	8.000000e-09
GCST001728_9	Ulcerative colitis	6.000000e-17
GCST001760_3	White matter integrity	5.000000e-06
GCST002936_9	Cadmium levels	7.000000e-06
GCST003487_6	Response to fenofibrate (total cholesterol levels)	4.000000e-06
GCST003518_48	Daytime sleep phenotypes	5.000000e-06
GCST004858_1	Dupuytren’s disease	1.000000e-15
GCST005531_44	Multiple sclerosis	1.000000e-10
GCST005576_21	Intracranial aneurysm	1.000000e-07
GCST009597_25	Multiple sclerosis	1.000000e-18
GCST012292_2	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	6.000000e-07
GCST012295_1	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	6.000000e-07
GCST012298_1	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	9.000000e-07
GCST012299_5	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	4.000000e-06
GCST012301_1	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	9.000000e-07
GCST90014325_31	Asthma	2.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004641	white matter integrity
EFO:0007806	total cholesterol change measurement
EFO:0007828	daytime rest measurement
EFO:0004229	Dupuytren Contracture
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001249	Asthma	C08.127.108; C08.381.495.108; C08.674.095; C20.543.480.680.095

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases mutagenesis	4
(+)-JQ1 compound	decreases expression	3
beauvericin	decreases expression	1
triphenyl phosphate	affects expression	1
ethyl-p-hydroxybenzoate	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
monomethylarsonous acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
Fulvestrant	increases methylation	1
Catechin	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Menthol	decreases expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	increases methylation	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1586	NCI-H740	Cancer cell line	Male
CVCL_8800	OCI-Ly3	Cancer cell line	Male
CVCL_B8CD	Abcam HCT 116 CARD11 KO	Cancer cell line	Male
CVCL_B8T9	Abcam MCF-7 CARD11 KO	Cancer cell line	Female
CVCL_B9EJ	Abcam A-549 CARD11 KO	Cancer cell line	Male
CVCL_D9B1	Ubigene HEK293 CARD11 KO	Transformed cell line	Female
CVCL_D9ZD	Ubigene HeLa CARD11 KO	Cancer cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00070707	PHASE4	COMPLETED	Nasonex Compared With Placebo in Participants With Seasonal Allergic Rhinitis (SAR) and Concomitant Asthma (P03280)
NCT00071552	PHASE4	TERMINATED	Efficacy of QVAR vs Flovent Diskus on Small Airways in Poorly Controlled Asthmatic Adolescents/Adult Patients
NCT00096954	PHASE4	COMPLETED	A Prospective, Randomized, Double-Blind Study of the Efficacy of Omalizumab (Xolair) in Atopic Asthmatics With Good Lung Capacity Who Remain Difficult to Treat (EXACT)
NCT00102765	PHASE4	COMPLETED	Study Of Asthma In Patients Of African Descent
NCT00102882	PHASE4	COMPLETED	Study Of Asthma And Genetics In Patients To Be Treated With Fluticasone Propionate/Salmeterol Or Salmeterol Xinafoate
NCT00124176	PHASE4	COMPLETED	Continuous Levalbuterol for Treatment of Status Asthmaticus in Children
NCT00133042	PHASE4	COMPLETED	The Effect of Omalizumab on Airway Responsiveness to Adenosine in Patients With Poorly Controlled Asthma
NCT00140881	PHASE4	COMPLETED	A Study to Determine the Effect of Montelukast Sodium as an Episode Modifier in the Treatment of Infrequent Episodic Asthma in Children (0476-165)
NCT00140946	PHASE4	COMPLETED	A Study to Assess the Effect of Montelukast Sodium With Concomitant Administration of Inhaled Budesonide in Asthmatic Patients (0476-075)
NCT00148408	PHASE4	COMPLETED	Trial of Asthma Patient Education (TAPE)
NCT00152984	PHASE4	COMPLETED	Efficacy and Safety of Tiotropium in Patients With COPD and Concomitant Diagnosis of Asthma
NCT00153075	PHASE4	COMPLETED	Flow Rate Effect Respimat Inhaler Versus a Metered Dose Inhaler Using Berodual in Patients With Chronic Obstructive Pulmonary Disease (COPD)
NCT00156819	PHASE4	COMPLETED	The Leukotriene Modifier Or Corticosteroid or Corticosteroid-Salmeterol Trial
NCT00157937	PHASE4	COMPLETED	A Study to Compare Effectiveness of Montelukast Sodium With Comparator in Mild to Moderate Persistent Asthmatics (0476-329)
NCT00169546	PHASE4	COMPLETED	Study In Airway Physiology In Children SERETIDE DISKUS ® Inhlaer and FLIXOTIDE® Inhaler Are Trademarks of GSK Group of Companies.
NCT00172341	PHASE4	UNKNOWN	Sublingual Immunotherapy With House Dust Mite Extract in Asthmatic Children
NCT00189436	PHASE4	COMPLETED	Effect of Nebulized Budesonide and Oral Corticosteroids on Wheezing Episode Relapse in Children
NCT00196547	PHASE4	COMPLETED	Montelukast in Modulating Exacerbations of Asthma in Children
NCT00197106	PHASE4	COMPLETED	Treatment Of Symptomatic Asthma In Children
NCT00228475	PHASE4	COMPLETED	A Study to Assess the Concentration of Budesonide in Breast Milk From Asthmatic Women
NCT00234390	PHASE4	COMPLETED	PreAsthmaControl (PAC)
NCT00235053	PHASE4	COMPLETED	Study to Assess the Incidence of Local Oropharyngeal and Laryngeal Adverse Effects of Advair DISKUS 250/50 mcg BID
NCT00237068	PHASE4	UNKNOWN	A Randomized, Double-Blind, Placebo-Controlled Study of Gastroesophageal Reflux Disease Therapy.
NCT00238888	PHASE4	COMPLETED	Randomised Controlled Trial of a Multi-faceted Community-based Intervention to Improve Asthma in Children
NCT00238927	PHASE4	COMPLETED	Clinical Trial of Fluticasone Versus Placebo at the Onset of a Cold for Children With Asthma
NCT00242411	PHASE4	COMPLETED	MONO: Symbicort® Single Inhaler Therapy and Conventional Best Standard Treatment for the Treatment of Persistent Asthma in Adolescents and Adults
NCT00250263	PHASE4	COMPLETED	A Trial of Immunological Outcomes of Sublingual Immunotherapy for House Dust Mite (D. Pteronyssinus) Allergy
NCT00250341	PHASE4	COMPLETED	Non-invasive Measures of Distal Lung Disease in Asthmatics
NCT00257933	PHASE4	COMPLETED	Oral Prednisolone Dosing in Children Hospitalized With Asthma
NCT00262587	PHASE4	COMPLETED	Elite Sport and Development of Asthma
NCT00264849	PHASE4	COMPLETED	Omalizumab in Adult and Adolescent Patients With Severe Persistent Allergic Asthma
NCT00267917	PHASE4	COMPLETED	Evaluation of the Respimat Inhaler vs. a HFA MDI Using Berodual in Patients With COPD With Poor MDI Technique.
NCT00272753	PHASE4	COMPLETED	Effect of Budesonide / Formoterol Combination in Repeated AMP Provocations
NCT00273026	PHASE4	TERMINATED	Study In Asthma Control
NCT00273962	PHASE4	COMPLETED	A Comparison of Combivent UDV (Ipratropium 500mcg and Salbutamol 2.5mg) and Salbutamol UDV Alone (2.5mg)
NCT00291382	PHASE4	COMPLETED	Airway Hyper-responsiveness Study In Asthma Using Salmeterol/Fluticasone Propionate Combination Product
NCT00292838	PHASE4	COMPLETED	Relative Potency of Inhaled Corticosteroids
NCT00296491	PHASE4	COMPLETED	Study Of Allergic Rhinitis In Patients Who Also Have Asthma
NCT00296530	PHASE4	COMPLETED	Study Of Patients With Allergic Rhinitis And Asthma
NCT00307970	PHASE4	COMPLETED	Impact of Anti-static Chamber/Mask