CARD10

Chr 22AR

caspase recruitment domain family member 10

Also known as: BIMP1, CARMA3, IMD89

NCBI Gene: 29775ENSG00000100065UniProt: Q9BWT7OMIM: 607209

CARD10 encodes a scaffold protein that activates NF-kappa-B signaling through BCL10, playing a critical role in immune system function. Mutations cause immunodeficiency with autoimmunity, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (LOEUF 0.449), suggesting that complete loss of protein function is likely pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.451 OMIM phenotype
Clinical Summary— CARD10
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 159 VUS of 233 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.002
Z-score 4.71
OE 0.29 (0.19–0.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.20Z-score
OE missense 0.75 (0.69–0.81)
465 obs / 619.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.29 (0.19–0.45)
0≤0.351.4
Missense OE0.75 (0.69–0.81)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 15 / 51.4Missense obs/exp: 465 / 619.4Syn Z: 0.60
DN
0.6162th %ile
GOF
0.6932th %ile
LOF
0.3648th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

233 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic1
VUS159
Likely Benign17
Benign21
Conflicting1
19
Pathogenic
1
Likely Pathogenic
159
VUS
17
Likely Benign
21
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
18
0
19
Likely Pathogenic
0
0
1
0
1
VUS
0
155
4
0
159
Likely Benign
0
4
3
10
17
Benign
0
5
4
12
21
Conflicting
—1
Total01653022218

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CARD10 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
The role of the CBM complex in allergic inflammation and disease.
DeVore SB et al.·J Allergy Clin Immunol
2022Review
Lack of association between CARD10/CARMA3 tag SNPs and psoriasis vulgaris in the southern Chinese population.
Shi G et al.·Genet Mol Res
2017
Lack of association between the CARD10 rs6000782 polymorphism and type 1 autoimmune hepatitis in a Japanese population.
Migita K et al.·BMC Res Notes
2015
Molecular basis for the disease-modifying effects of belimumab in systemic lupus erythematosus and molecular predictors of early response: blood transcriptome analysis implicates the innate immunity and DNA damage response pathways.
Moysidou GS et al.·Ann Rheum Dis
2025
Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity.
Pérez de Diego R et al.·J Allergy Clin Immunol
2015Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients