CARD9

Chr 9AR

caspase recruitment domain family member 9

Also known as: CANDF2, IMD103, hCARD9

The protein encoded by this gene is a member of the CARD protein family, which is defined by the presence of a characteristic caspase-associated recruitment domain (CARD). CARD is a protein interaction domain known to participate in activation or suppression of CARD containing members of the caspase family, and thus plays an important regulatory role in cell apoptosis. This protein was identified by its selective association with the CARD domain of BCL10, a postive regulator of apoptosis and NF-kappaB activation, and is thought to function as a molecular scaffold for the assembly of a BCL10 signaling complex that activates NF-kappaB. Several alternatively spliced transcript variants have been observed, but their full-length nature is not clearly defined. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Immunodeficiency 103, susceptibility to fungal infectionMIM #212050
AR
0
Active trials
42
Pathogenic / LP
294
ClinVar variants
5
Pubs (1 yr)
Missense Z
LOEUF
Clinical SummaryCARD9
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 108 VUS of 294 total submissions
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Population Genetics & Constraint

Constraint data not available from gnomAD.

DN
0.6358th %ile
GOF
0.6640th %ile
LOF
0.3745th %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

294 submitted variants in ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic4
VUS108
Likely Benign137
Benign5
Conflicting2
38
Pathogenic
4
Likely Pathogenic
108
VUS
137
Likely Benign
5
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
35
0
38
Likely Pathogenic
3
0
1
0
4
VUS
0
99
8
1
108
Likely Benign
0
2
66
69
137
Benign
0
0
5
0
5
Conflicting
2
Total610111570294

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

View in ClinVar →

Protein Context — Lollipop Plot

CARD9 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence