CARD11

caspase recruitment domain family member 11, the group of Caspase recruitment domain containing|PDZ domain containing|Membrane associated guanylate kinases|CBM complex

Basic information

Region (hg38): 7:2906142-3044228

Links

ENSG00000198286 ∙ NCBI:84433 ∙ OMIM:607210 ∙ HGNC:16393 ∙ Uniprot:Q9BXL7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 11b with atopic dermatitis (Strong), mode of inheritance: AD
• severe combined immunodeficiency due to CARD11 deficiency (Supportive), mode of inheritance: AR
• BENTA disease (Supportive), mode of inheritance: AD
• BENTA disease (Strong), mode of inheritance: AD
• severe combined immunodeficiency due to CARD11 deficiency (Strong), mode of inheritance: AR
• immunodeficiency 11b with atopic dermatitis (Strong), mode of inheritance: AD
• BENTA disease (Definitive), mode of inheritance: AD
• severe combined immunodeficiency due to CARD11 deficiency (Definitive), mode of inheritance: AR
• immunodeficiency 11b with atopic dermatitis (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
B-cell expansion with NFKB and T-cell anergy; Immunodeficiency 11B with atopic dermatitis; Immunodeficiency 11A	AD/AR	Allergy/Immunology/Infectious; Oncologic	For Immunodeficiency 11A and 11B and B-cell expansion with NFKB and T-cell anergy, individuals may be prone to frequent infections, and prophylactic measures, as well as early and aggressive treatment of infections may be beneficial; For B-cell expansion with NFKB and T-cell anergy, individuals may be predisposed to B cell malignancy, and awareness may allow early recognition and management; HSCT has been described in Congenital B cell lymphocytosis	Allergy/Immunology/Infectious; Dermatologic; Oncologic	23129749; 23374270; 23561803; 25352053; 25930198

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CARD11 gene.

• BENTA disease;Severe combined immunodeficiency due to CARD11 deficiency (9 variants)
• Severe combined immunodeficiency due to CARD11 deficiency;BENTA disease (9 variants)
• BENTA disease (3 variants)
• not provided (2 variants)
• Immunodeficiency 11b with atopic dermatitis (2 variants)
• Splenomegaly;Osteopenia;Asthma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CARD11 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	225	22	250
missense	5	3	323	76	4	411
nonsense	7	1	2			10
start loss			2			2
frameshift	5		2			7
inframe indel			9			9
splice donor/acceptor (+/-2bp)	1	7	1			9
splice region			31	47	2	80
non coding			8	128	24	160
Total	18	11	350	429	50

Highest pathogenic variant AF is 0.00000657

Variants in CARD11

This is a list of pathogenic ClinVar variants found in the CARD11 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-2906634-C-T		BENTA disease	Uncertain significance (Nov 06, 2018)
7-2906649-C-T		not specified • BENTA disease;Severe combined immunodeficiency due to CARD11 deficiency • BENTA disease;Immunodeficiency 11b with atopic dermatitis;Severe combined immunodeficiency due to CARD11 deficiency	Likely benign (Dec 09, 2023)
7-2906653-G-A		Severe combined immunodeficiency due to CARD11 deficiency;BENTA disease	Likely benign (Apr 18, 2023)
7-2906664-T-G		Severe combined immunodeficiency due to CARD11 deficiency;BENTA disease	Uncertain significance (Jan 06, 2022)
7-2906671-G-A		BENTA disease;Severe combined immunodeficiency due to CARD11 deficiency	Likely benign (Oct 22, 2023)
7-2906672-C-T		BENTA disease;Severe combined immunodeficiency due to CARD11 deficiency	Likely benign (Jul 20, 2023)
7-2906680-C-T		Severe combined immunodeficiency due to CARD11 deficiency;BENTA disease	Likely benign (Nov 28, 2023)
7-2906682-C-T		BENTA disease;Severe combined immunodeficiency due to CARD11 deficiency	Uncertain significance (Oct 04, 2023)
7-2906683-G-A		Severe combined immunodeficiency due to CARD11 deficiency;BENTA disease	Likely benign (Oct 25, 2022)
7-2906685-C-T		Severe combined immunodeficiency due to CARD11 deficiency;BENTA disease • CARD11-related disorder	Conflicting classifications of pathogenicity (Sep 12, 2023)
7-2906686-G-A		BENTA disease;Severe combined immunodeficiency due to CARD11 deficiency	Likely benign (May 22, 2018)
7-2906693-T-A		BENTA disease;Severe combined immunodeficiency due to CARD11 deficiency • BENTA disease	Conflicting classifications of pathogenicity (May 22, 2023)
7-2906701-A-T		Severe combined immunodeficiency due to CARD11 deficiency;BENTA disease	Likely benign (Feb 03, 2021)
7-2906703-C-T		BENTA disease;Severe combined immunodeficiency due to CARD11 deficiency	Uncertain significance (Dec 02, 2022)
7-2906704-G-A		Severe combined immunodeficiency due to CARD11 deficiency;BENTA disease	Benign (Jan 29, 2024)
7-2906704-G-T		BENTA disease;Severe combined immunodeficiency due to CARD11 deficiency	Likely benign (Jul 01, 2022)
7-2906705-C-T		Severe combined immunodeficiency due to CARD11 deficiency;BENTA disease	Likely benign (May 22, 2023)
7-2906707-G-A		Severe combined immunodeficiency due to CARD11 deficiency;BENTA disease	Benign (Dec 29, 2023)
7-2906713-C-T		BENTA disease;Severe combined immunodeficiency due to CARD11 deficiency	Likely benign (Sep 24, 2022)
7-2906715-C-T		Severe combined immunodeficiency due to CARD11 deficiency;BENTA disease	Uncertain significance (May 25, 2023)
7-2906721-C-T		Severe combined immunodeficiency due to CARD11 deficiency;BENTA disease • Severe combined immunodeficiency due to CARD11 deficiency;Immunodeficiency 11b with atopic dermatitis;BENTA disease	Conflicting classifications of pathogenicity (Oct 08, 2023)
7-2906723-C-T		BENTA disease;Severe combined immunodeficiency due to CARD11 deficiency	Uncertain significance (Nov 03, 2023)
7-2906726-C-T		Inborn genetic diseases	Uncertain significance (Aug 02, 2023)
7-2906729-C-G		BENTA disease;Severe combined immunodeficiency due to CARD11 deficiency	Uncertain significance (Nov 11, 2019)
7-2906732-A-G		Severe combined immunodeficiency due to CARD11 deficiency;BENTA disease	Uncertain significance (Oct 30, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CARD11	protein_coding	protein_coding	ENST00000396946	24	137805

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000472	125733	0	14	125747	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.54	481	755	0.637	0.0000518	7561
Missense in Polyphen		97	231.77	0.41851		2312
Synonymous	-1.32	354	324	1.09	0.0000235	2223
Loss of Function	6.45	8	63.5	0.126	0.00000364	674

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000934	0.0000924
European (Non-Finnish)	0.0000804	0.0000791
Middle Eastern	0.000109	0.000109
South Asian	0.0000333	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the costimulatory signal essential for T- cell receptor (TCR)-mediated T-cell activation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Activates NF-kappa-B via BCL10 and IKK. Stimulates the phosphorylation of BCL10. Also activates the TORC1 signaling pathway. {ECO:0000269|PubMed:11278692, ECO:0000269|PubMed:11356195, ECO:0000269|PubMed:12356734, ECO:0000269|PubMed:28628108}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:23129749, ECO:0000269|PubMed:28628108}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:23374270, ECO:0000269|PubMed:23561803}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:28628108}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: T cell receptor signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);B Cell Receptor Signaling Pathway;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;T-Cell antigen Receptor (TCR) Signaling Pathway;B cell receptor signaling;Downstream TCR signaling;TCR signaling;Activation of NF-kappaB in B cells;Signaling by the B Cell Receptor (BCR);Fc epsilon receptor (FCERI) signaling;TCR;Innate Immune System;Immune System;Adaptive Immune System;Downstream signaling events of B Cell Receptor (BCR);BCR;BCR signaling pathway;FCERI mediated NF-kB activation;TCR signaling in naïve CD8+ T cells;TCR signaling in naïve CD4+ T cells;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.273

Intolerance Scores

• loftool: 0.251
• rvis_EVS: -1.39
• rvis_percentile_EVS: 4.33

Haploinsufficiency Scores

• pHI: 0.0961
• hipred: Y
• hipred_score: 0.792
• ghis: 0.517

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.810

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Card11
• Phenotype: immune system phenotype; hematopoietic system phenotype; respiratory system phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: positive regulation of cytokine production;stimulatory C-type lectin receptor signaling pathway;immunoglobulin production;I-kappaB kinase/NF-kappaB signaling;B cell differentiation;positive regulation of B cell proliferation;T cell costimulation;Fc-epsilon receptor signaling pathway;TORC1 signaling;B cell proliferation;positive regulation of T cell proliferation;regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;thymic T cell selection;positive regulation of interleukin-2 biosynthetic process;regulation of B cell differentiation;regulation of T cell differentiation;GMP metabolic process;GDP metabolic process;homeostasis of number of cells;T cell receptor signaling pathway;positive regulation of NF-kappaB transcription factor activity;interleukin-2 secretion
• Cellular component: immunological synapse;cytoplasm;cytosol;plasma membrane;CBM complex;membrane raft;extracellular exosome
• Molecular function: guanylate kinase activity;protein binding;CARD domain binding