CARD11

Chr 7ADAR

caspase recruitment domain family member 11

Also known as: BENTA, BIMP3, CARMA1, IMD11, IMD11A, PPBL

NCBI Gene: 84433 ENSG00000198286 UniProt: Q9BXL7 OMIM: 607210

CARD11 encodes an adapter protein that transduces NF-kappa-B activation downstream of T-cell and B-cell receptor signaling by forming multiprotein complexes with BCL10 and MALT1. Mutations cause primary immunodeficiencies including B-cell expansion with NF-kappa-B activation and T-cell anergy, immunodeficiency with atopic dermatitis, and severe combined immunodeficiency, affecting adaptive immune responses. Inheritance can be either autosomal dominant or autosomal recessive depending on the specific variant.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

B-cell expansion with NFKB and T-cell anergyMIM #616452

Immunodeficiency 11AMIM #615206

Immunodeficiency 11B with atopic dermatitisMIM #617638

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.23

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.23LOEUF

pLI 1.000

Z-score 6.45

OE 0.13 (0.07–0.23)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.54Z-score

OE missense 0.64 (0.59–0.69)

481 obs / 755.0 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.23)

0≤0.351.4

Missense OE?0.64 (0.59–0.69)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 8 / 63.5Missense obs/exp: 481 / 755.0Syn Z: -1.32

Background carrier burden — how many people carry a rare variant somewhere in CARD11?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 44

1,271 rare PASS variants

Rare truncating (LoF)

1 in 3,500

81 rare PASS variants

Rare synonymous (reference)

1 in 51

758 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CARD11. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 60	1 in 3,700
South Asian	~43k	1 in 49	1 in 3,600
Remaining (unassigned)	~30k	1 in 31	1 in 6,000
European (Finnish)	~27k	1 in 120	1 in 1,100
Admixed American	~22k	1 in 51	≈ 1 in 7,600
African / African American	~21k	1 in 44	≈ 1 in 4,900
East Asian	~20k	1 in 50	≈ 1 in 4,900
Ashkenazi Jewish	~13k	1 in 170	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 46	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 24 coding exons well covered in gnomAD exomes and genomes.? see exons ↓