Immunodeficiency 11b with atopic dermatitis

Summary

Immunodeficiency 11b with atopic dermatitis (MONDO:0054697) is a disease caused by CARD11 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: CARD11 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 57

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 11b with atopic dermatitis
Mondo ID	MONDO:0054697
OMIM	617638
DOID	DOID:0111958
NCIT	C176630
UMLS	C4539957
MedGen	1627819
Is cancer (heuristic)	no

Also known as: IMD11B

Data availability: 57 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › immunodeficiency 11b with atopic dermatitis

Related subtypes (94): B cell deficiency, T-cell immunodeficiency, complement deficiency, myalgic encephalomeyelitis/chronic fatigue syndrome, hypoproteinemia, hypercatabolic, X-linked lymphoproliferative syndrome, Wiskott-Aldrich syndrome, autosomal dominant form, immunodeficiency due to CD25 deficiency, immunodeficiency 67, primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency, immunodeficiency 35, pyogenic bacterial infections due to MyD88 deficiency, lymphoproliferative syndrome 1, FADD-related immunodeficiency, immunodeficiency 31B, Wiskott-Aldrich syndrome 2, cryptosporidiosis-chronic cholangitis-liver disease syndrome, idiopathic CD4 lymphocytopenia, immunodeficiency 23, DOCK2 deficiency, immunodeficiency 45, TFRC-related combined immunodeficiency, combined immunodeficiency, autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome, immunodeficiency due to selective anti-polysaccharide antibody deficiency, immunodeficiency 57, immunodeficiency 14b, autosomal recessive, immunodeficiency 98 with autoinflammation, X-linked, immunodeficiency 102, immunodeficiency 74, COVID-19-related, X-linked, immunodeficiency 66, immunodeficiency 80 with or without congenital cardiomyopathy, immunodeficiency 81, immunodeficiency 82 with systemic inflammation, immunodeficiency 84, immunodeficiency 85 and autoimmunity, immunodeficiency 86, immunodeficiency 87 and autoimmunity, immunodeficiency 88, immunodeficiency 89 and autoimmunity, immunodeficiency 91 and hyperinflammation, immunodeficiency 92, immunodeficiency 93 and hypertrophic cardiomyopathy, immunodeficiency 95, immunodeficiency 96, immunodeficiency 97 with autoinflammation, immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias, immunodeficiency 101 (varicella zoster virus-specific), immunodeficiency 75, immunodeficiency 76, immunodeficiency 106, susceptibility to viral infections, immunodeficiency 78 with autoimmunity and developmental delay, immunodeficiency 77, immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, immunodeficiency 15a, immunodeficiency 60, immunodeficiency 62, immunodeficiency 63 with lymphoproliferation and autoimmunity, immunodeficiency 64, immunodeficiency 65, susceptibility to viral infections, immunodeficiency 69, immunodeficiency 70, immunodeficiency 72 with autoinflammation, GATA2 deficiency with susceptibility to MDS/AML, Shwachman-Diamond syndrome 1, immunodeficiency 53, IKBKG-related immunodeficiency with or without ectodermal dysplasia, FNIP1-associated syndrome, FASLG-related immunodeficiency, TNFRSF9-related immunodeficiency, DNAJC21-related Shwachman Diamond syndrome, IRF4-related immune disorder, PTEN harmartoma tumor syndrome with immune disorder, primary immunodeficiency due to calcium channel deficiency, chronic mucocutaneous candidiasis and connective tissue disease due to JNK1 haploinsufficiency, immune deficiency due to impaired neutrophil phagocytosis and migration, hatipoglu immunodeficiency syndrome, immunodeficiency 112, immunodeficiency 113 with autoimmunity and autoinflammation, immunodeficiency 114, folate-responsive, immunodeficiency 115 with autoinflammation, immunodeficiency 117, immunodeficiency 118, immunodeficiency 119, immunodeficiency 121 with autoinflammation, immunodeficiency 122, immunodeficiency 123 with HPV-related verrucosis, immunodeficiency 125, immunodeficiency 126, susceptibility to, immunodeficiency 127, immunodeficiency 128, immunodeficiency 132b, immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy, immunodeficiency 134 (Epstein-Barr virus-specific)

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

57 retrieved; paginated sample, class counts are floors:

17 uncertain significance, 16 conflicting classifications of pathogenicity, 7 benign, 7 likely pathogenic, 5 pathogenic, 3 likely benign, 1 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1707407	NM_032415.7(CARD11):c.547_588dup (p.Lys196_Val197insMetLysGluGluArgAspSerTyrAsnAspGluLeuValLys)	CARD11	Pathogenic	no assertion criteria provided
433533	NP_115791.3:p.Leu194Pro	CARD11	Pathogenic	no assertion criteria provided
433534	CARD11, GLU57ASP	CARD11	Pathogenic	no assertion criteria provided
433536	NP_115791.3:p.Met183_Lys196dup	CARD11	Pathogenic	no assertion criteria provided
4689357	NM_032415.7(CARD11):c.862C>T (p.Gln288Ter)	CARD11	Pathogenic	criteria provided, single submitter
473938	NM_032415.7(CARD11):c.88C>T (p.Arg30Trp)	CARD11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184834	NM_032415.7(CARD11):c.215G>T (p.Arg72Leu)	CARD11	Likely pathogenic	no assertion criteria provided
1707410	NM_032415.7(CARD11):c.128C>G (p.Thr43Arg)	CARD11	Likely pathogenic	no assertion criteria provided
2573987	NM_032415.7(CARD11):c.2324C>T (p.Ser775Leu)	CARD11	Likely pathogenic	no assertion criteria provided
3341070	NM_032415.7(CARD11):c.358+1_358+9delinsAACATC	CARD11	Likely pathogenic	criteria provided, single submitter
3594526	NM_032415.7(CARD11):c.143A>C (p.Gln48Pro)	CARD11	Likely pathogenic	criteria provided, single submitter
4686684	NM_032415.7(CARD11):c.119C>A (p.Ala40Asp)	CARD11	Likely pathogenic	criteria provided, single submitter
1174515	NM_032415.7(CARD11):c.377G>A (p.Gly126Asp)	CARD11-AS1	Likely pathogenic	criteria provided, single submitter
1023980	NM_032415.7(CARD11):c.2239G>A (p.Val747Ile)	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1055950	NM_032415.7(CARD11):c.2063G>A (p.Arg688Gln)	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1063627	NM_032415.7(CARD11):c.223C>T (p.Arg75Trp)	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1184833	NM_032415.7(CARD11):c.128C>T (p.Thr43Met)	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1184835	NM_032415.7(CARD11):c.358+1G>A	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
133792	NM_032415.7(CARD11):c.2119C>T (p.Arg707Cys)	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
391814	NM_032415.7(CARD11):c.2900G>A (p.Arg967His)	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
421704	NM_032415.7(CARD11):c.2923C>T (p.Arg975Trp)	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
489270	NM_032415.7(CARD11):c.220+1G>A	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
571975	NM_032415.7(CARD11):c.2735G>A (p.Arg912Gln)	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
581096	NM_032415.7(CARD11):c.2449G>A (p.Ala817Thr)	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626072	NM_032415.7(CARD11):c.1143+10C>G	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
871387	NM_032415.7(CARD11):c.2920C>T (p.Arg974Cys)	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
935604	NM_032415.7(CARD11):c.3382G>A (p.Val1128Ile)	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
967100	NM_032415.7(CARD11):c.2947G>A (p.Val983Met)	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
973623	NM_032415.7(CARD11):c.2899C>T (p.Arg967Cys)	CARD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1445735	NM_032415.7(CARD11):c.3019+5G>A	CARD11	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CARD11	Definitive	Autosomal recessive	severe combined immunodeficiency due to CARD11 deficiency	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CARD11	Orphanet:300324	Persistent polyclonal B-cell lymphocytosis
CARD11	Orphanet:357237	Combined immunodeficiency due to CARD11 deficiency
CARD11	Orphanet:464336	BENTA disease
CARD11	Orphanet:619972	CADINS disease

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CARD11	HGNC:16393	ENSG00000198286	Q9BXL7	Caspase recruitment domain-containing protein 11	gencc,clinvar
CARD11-AS1	HGNC:40766	ENSG00000237286		CARD11 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CARD11	Caspase recruitment domain-containing protein 11	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.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CARD11	Scaffold/PPI	no		CARD, DEATH-like_dom_sf, P-loop_NTPase
CARD11-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
lymph node	1
spleen	1
bone marrow cell	1
colonic epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CARD11	188	broad	marker	granulocyte, lymph node, spleen
CARD11-AS1	66		yes	male germ line stem cell (sensu Vertebrata) in testis, bone marrow cell, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CARD11	3,587
CARD11-AS1	0

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CARD11	Q9BXL7	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Downstream signaling events of B Cell Receptor (BCR)	1	815.7×	0.010	CARD11
TCR signaling	1	496.5×	0.010	CARD11
Signaling by the B Cell Receptor (BCR)	1	346.1×	0.010	CARD11
Fc epsilon receptor (FCERI) signaling	1	271.9×	0.010	CARD11
C-type lectin receptors (CLRs)	1	237.9×	0.010	CARD11
Activation of NF-kappaB in B cells	1	196.9×	0.010	CARD11
FCERI mediated NF-kB activation	1	156.4×	0.010	CARD11
CLEC7A (Dectin-1) signaling	1	142.8×	0.010	CARD11
Downstream TCR signaling	1	128.3×	0.010	CARD11
Adaptive Immune System	1	29.8×	0.040	CARD11
Innate Immune System	1	25.5×	0.043	CARD11
Immune System	1	13.0×	0.077	CARD11

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
thymic T cell selection	1	5617.3×	0.003	CARD11
CD4-positive, alpha-beta T cell proliferation	1	1872.4×	0.003	CARD11
positive regulation of CD4-positive, alpha-beta T cell proliferation	1	1685.2×	0.003	CARD11
regulation of B cell differentiation	1	1296.3×	0.003	CARD11
regulation of T cell differentiation	1	1203.7×	0.003	CARD11
TORC1 signaling	1	802.5×	0.003	CARD11
positive regulation of T cell receptor signaling pathway	1	766.0×	0.003	CARD11
homeostasis of number of cells	1	674.1×	0.003	CARD11
B cell proliferation	1	481.5×	0.004	CARD11
positive regulation of interleukin-2 production	1	468.1×	0.004	CARD11
T cell costimulation	1	374.5×	0.004	CARD11
canonical NF-kappaB signal transduction	1	366.4×	0.004	CARD11
positive regulation of B cell proliferation	1	343.9×	0.004	CARD11
B cell differentiation	1	218.9×	0.006	CARD11
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.006	CARD11
protein homooligomerization	1	122.1×	0.009	CARD11
regulation of apoptotic process	1	83.4×	0.013	CARD11
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.014	CARD11

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CARD11	0	0
CARD11-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	CARD11, CARD11-AS1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CARD11	0	—
CARD11-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.