CARD10

Chr 22AR

caspase recruitment domain family member 10

Also known as: BIMP1, CARMA3, IMD89

NCBI Gene: 29775ENSG00000100065UniProt: Q9BWT7

The caspase recruitment domain (CARD) is a protein module that consists of 6 or 7 antiparallel alpha helices. It participates in apoptosis signaling through highly specific protein-protein homophilic interactions. Like several other CARD proteins, CARD10 belongs to the membrane-associated guanylate kinase (MAGUK) family and activates NF-kappa-B (NFKB; see MIM 164011) through BCL10 (MIM 603517) (Wang et al., 2001 [PubMed 11259443]).[supplied by OMIM, Mar 2008]

Primary Disease Associations & Inheritance

?Immunodeficiency 89 and autoimmunityMIM #619632
AR
238
ClinVar variants
20
Pathogenic / LP
0.00
pLI score
0
Active trials
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 Pathogenic / Likely Pathogenic· 159 VUS of 238 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.29 (0.19–0.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.69–0.81)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 15 / 51.4Missense obs/exp: 465 / 619.4Syn Z: 0.60

ClinVar Variant Classifications

238 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Immunodeficiency 89 and autoimmunity

MIM #619632

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
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
The role of the CBM complex in allergic inflammation and disease.
DeVore SB et al.·J Allergy Clin Immunol
2022Review
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
Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.
de Boer YS et al.·Gastroenterology
2014
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
Induction of immunomodulatory miR-146a and miR-155 in small intestinal epithelium of Vibrio cholerae infected patients at acute stage of cholera.
Bitar A et al.·PLoS One
2017Cohort
A comprehensive interaction study provides a potential domain interaction network of human death domain superfamily proteins.
Zhou W et al.·Cell Death Differ
2021
Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer.
Piqué L et al.·Oncogene
2019
A Genome-Wide Scan for MicroRNA-Related Genetic Variants Associated With Primary Open-Angle Glaucoma.
Ghanbari M et al.·Invest Ophthalmol Vis Sci
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools