CARD8: A Key Regulator of Inflammasome Signaling and Inflammatory Disease
Comprehensive genomic, expression, and mutation analysis of the CARD8 gene, a critical component of the innate immune system.
Gene Information Card
| Symbol | CARD8 |
|---|---|
| Full Name | Caspase recruitment domain family member 8 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 22900 ncbi.nlm.nih.gov/gene/22900 |
| Ensembl ID | ENSG00000105483 |
| UniProt ID | Q9Y2G2 |
| OMIM ID | 609051 |
| HGNC ID | 1463 |
| Aliases | CARDINAL, TUCAN, NDPP1, DACAR, KIAA0955 |
Description
CARD8 (Caspase recruitment domain family member 8) encodes a protein that plays a critical role in the regulation of innate immune responses. It is a component of the inflammasome complex, particularly the NLRP3 inflammasome, where it modulates the activation of caspase-1 and subsequent production of pro-inflammatory cytokines like IL-1β and IL-18. CARD8 also influences NF-κB signaling and apoptosis. The gene is expressed in various tissues, with highest levels in immune cells. Polymorphisms and mutations in CARD8 have been associated with susceptibility to inflammatory diseases, autoimmune disorders, and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory bowel disease (IBD) | CARD8 variants may alter inflammasome activity, leading to dysregulated cytokine production and chronic intestinal inflammation. | ClinVar, PMID: 21102463 |
| Rheumatoid arthritis | CARD8 polymorphisms (e.g., C10X) are associated with increased risk, possibly due to reduced inhibition of NF-κB and enhanced inflammatory responses. | ClinVar, PMID: 20062062 |
| HIV-1 infection progression | CARD8 variants influence inflammasome-mediated immune responses, affecting viral replication and disease progression. | PMID: 20538612 |
| Cancer (e.g., colorectal, breast) | CARD8 mutations may lead to altered apoptosis and NF-κB signaling, contributing to tumorigenesis. | COSMIC, PMID: 21901162 |
| Cryopyrin-associated periodic syndromes (CAPS) | CARD8 interacts with NLRP3; mutations in CARD8 may modulate the severity of CAPS phenotypes. | PMID: 17599046 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.3 | High |
| Lymph node | 11.8 | High |
| Bone marrow | 10.5 | High |
| Lung | 8.2 | Medium |
| Liver | 6.1 | Medium |
| Brain | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | High expression; used in inflammasome studies |
| Jurkat (T cell) | 9.8 | Moderate expression |
| HeLa (cervical cancer) | 4.5 | Low expression |
| A549 (lung cancer) | 6.7 | Moderate expression |
| MCF7 (breast cancer) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| C10X (p.Cys10Ter) | Nonsense | ~5% in European populations | Truncated protein lacking CARD domain; associated with reduced inflammasome regulation and increased inflammatory disease risk. |
| rs2043211 (C10X) | SNP | Minor allele frequency ~0.3 | Loss-of-function variant; linked to altered IL-1β production and susceptibility to IBD and rheumatoid arthritis. |
| p.Arg38Trp | Missense | Rare | Potential impact on protein stability and interaction with NLRP3; clinical significance uncertain. |
| p.Gly258Ser | Missense | Rare | Located in the FIIND domain; may affect CARD8 self-processing and inflammasome regulation. |
Mutation functional classification
Loss of Function (LOF)
The C10X nonsense mutation results in a truncated protein lacking the CARD domain, leading to loss of inflammasome regulatory function and enhanced inflammatory responses.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for CARD8; most variants are loss-of-function or hypomorphic.
Dominant Negative (DN)
Some missense mutations in the FIIND domain may exert dominant-negative effects by interfering with wild-type CARD8 function in inflammasome complexes.
View complete mutation data：
Gene Ontology (GO)
| • caspase recruitment domain binding | • protein homodimerization activity |
| • NF-kappaB binding | • inflammasome complex |
| • regulation of inflammatory response | • positive regulation of NF-kappaB transcription factor activity |
| • negative regulation of NF-kappaB transcription factor activity | • apoptotic process |
| • innate immune response | • signal transduction |
Pathways
• NOD-like receptor signaling pathway
• Inflammasome pathway
• NF-kappaB signaling pathway
• Apoptosis pathway
Protein Summary
The CARD8 protein (UniProt Q9Y2G2) is a 431-amino acid protein containing an N-terminal caspase recruitment domain (CARD) and a C-terminal FIIND (function-to-find) domain. It is a key regulator of the NLRP3 inflammasome, where it interacts with NLRP3 and pro-caspase-1 to modulate IL-1β and IL-18 processing. CARD8 also inhibits NF-κB activation and promotes apoptosis. The protein undergoes autoproteolytic cleavage at the FIIND domain, which is essential for its function. Alternative splicing generates multiple isoforms, contributing to functional diversity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CARD8 Knockout HEK293 Cell Line | EDJ-KQ7727 | Human | 22900 | Details Get a Quote |
| CARD8 Knockout A-549 Cell Line | EDJ-KQ33140 | Human | 22900 | Details Get a Quote |
| CARD8 Knockout HeLa Cell Line | EDJ-KQ33142 | Human | 22900 | Details Get a Quote |
| CARD8 Knockout HCT 116 Cell Line | EDJ-KQ31815 | Human | 22900 | Details Get a Quote |
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