CARD9: Caspase Recruitment Domain Family Member 9
Key Adaptor in Innate Immunity and Fungal Defense
Gene Information Card
| Symbol | CARD9 |
|---|---|
| Full Name | Caspase Recruitment Domain Family Member 9 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q34.3 |
| NCBI Gene ID | 64170 ncbi.nlm.nih.gov/gene/64170 |
| Ensembl ID | ENSG00000187796 |
| UniProt ID | Q9H257 |
| OMIM ID | 607212 |
| HGNC ID | 16391 |
| Aliases | hCARD9, CARD9L, MGC111021 |
Description
CARD9 encodes a caspase recruitment domain-containing protein that functions as an adaptor molecule in innate immune signaling pathways. It mediates NF-kB activation downstream of pattern recognition receptors, particularly C-type lectin receptors such as Dectin-1 and Dectin-2, and is essential for antifungal immunity. CARD9 also plays roles in intestinal homeostasis and inflammatory responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic mucocutaneous candidiasis (CMC) | Loss-of-function mutations impair CARD9-dependent signaling, leading to defective Th17 responses and susceptibility to Candida infections. | OMIM #212050; NCBI Gene |
| Invasive fungal infections (e.g., aspergillosis, dermatophytosis) | Deficient CARD9 disrupts neutrophil and macrophage antifungal activity, increasing risk of deep-seated mycoses. | OMIM #607212; ClinVar |
| Inflammatory bowel disease (IBD) | CARD9 variants (e.g., rs4077515) alter NF-kB activation and cytokine production, contributing to intestinal inflammation. | NCBI Gene; OMIM #612278 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.3 | Medium |
| Lung | 8.7 | Medium |
| Small intestine | 7.5 | Medium |
| Whole blood | 6.2 | Low |
| Bone marrow | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | High expression |
| HL-60 (neutrophil) | 10.8 | Moderate expression |
| Jurkat (T-cell) | 4.3 | Low expression |
| HeLa (cervical) | 2.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.819_820delTG (p.Cys274*) | Frameshift/nonsense | Rare | Loss of function; associated with CMC |
| c.883C>T (p.Gln295*) | Nonsense | Rare | Loss of function; associated with invasive candidiasis |
| c.143T>C (p.Leu48Pro) | Missense | Rare | Loss of function; impaired NF-kB activation |
| rs4077515 (p.Ser12Asn) | Missense | Common (MAF ~0.3) | Modulates NF-kB activity; linked to IBD risk |
Mutation functional classification
Loss of Function (LOF)
Homozygous or compound heterozygous loss-of-function mutations (e.g., nonsense, frameshift) cause CARD9 deficiency, leading to impaired antifungal immunity and chronic mucocutaneous candidiasis.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in CARD9.
Dominant Negative (DN)
Some missense mutations (e.g., p.Leu48Pro) may exert dominant-negative effects by disrupting CARD9-BCL10 interaction, though autosomal recessive inheritance is typical.
View complete mutation data：
Gene Ontology (GO)
| • CARD domain binding | • protein homodimerization activity |
| • NF-kappaB-inducing kinase activity | • signal transduction |
| • innate immune response | • positive regulation of NF-kappaB transcription factor activity |
| • inflammatory response | • fungal defense response |
Pathways
• C-type lectin receptor signaling pathway (KEGG hsa04624)
• NF-kappa B signaling pathway (KEGG hsa04064)
• NOD-like receptor signaling pathway (KEGG hsa04621)
• Toll-like receptor signaling pathway (KEGG hsa04620)
Protein Summary
CARD9 is a 213-amino acid adaptor protein containing an N-terminal caspase recruitment domain (CARD) and a coiled-coil region. It forms a complex with BCL10 and MALT1 to activate NF-kB and MAPK pathways upon stimulation of C-type lectin receptors. The protein is predominantly expressed in myeloid cells and plays a critical role in antifungal immunity, intestinal homeostasis, and inflammatory responses.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CARD9 Knockout HEK293 Cell Line | EDJ-KQ12725 | Human | 64170 | Details Get a Quote |
| CARD9 Knockout HeLa Cell Line | EDJ-KQ57038 | Human | 64170 | Details Get a Quote |
| CARD9 Knockout A-549 Cell Line | EDJ-KQ65545 | Human | 64170 | Details Get a Quote |
| CARD9 Knockout HCT 116 Cell Line | EDJ-KQ73977 | Human | 64170 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
