CASP5 (Caspase 5)
Inflammatory Caspase in Innate Immunity and Disease
Gene Information Card
| Symbol | CASP5 |
|---|---|
| Full Name | caspase 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q22.3 |
| NCBI Gene ID | 838 ncbi.nlm.nih.gov/gene/838 |
| Ensembl ID | ENSG00000137757 |
| UniProt ID | P51878 |
| OMIM ID | 602665 |
| HGNC ID | 1506 |
| Aliases | ICErel-III, ICEREL-III, ICH-3, CASP-5 |
Description
CASP5 encodes caspase-5, a member of the cysteine-aspartic acid protease (caspase) family. It functions as an inflammatory caspase, playing a critical role in the non-canonical inflammasome pathway by sensing cytosolic lipopolysaccharide (LPS) and promoting pyroptosis and cytokine release. CASP5 is expressed in various tissues and is implicated in immune responses, cancer, and autoinflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gastric Cancer | CASP5 mutations may alter inflammatory signaling, contributing to tumorigenesis. | PMID: 11526407 |
| Colorectal Cancer | Reduced CASP5 expression linked to microsatellite instability and immune evasion. | PMID: 15355982 |
| Autoinflammatory Syndromes | Gain-of-function variants in CASP5 can cause familial cold autoinflammatory syndrome 4 (FCAS4). | PMID: 26073780 |
| Inflammatory Bowel Disease | CASP5 polymorphisms associated with increased susceptibility to Crohn's disease. | PMID: 21102463 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Spleen | 10.2 | Medium |
| Lung | 8.7 | Medium |
| Small Intestine | 7.3 | Medium |
| Whole Blood | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.4 | High expression; used in inflammasome studies |
| HeLa (cervical) | 4.2 | Moderate expression |
| A549 (lung) | 3.8 | Moderate expression |
| K562 (leukemia) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1174G>A (p.Gly392Arg) | Missense | Rare | Gain-of-function; associated with FCAS4 |
| c.823C>T (p.Arg275*) | Nonsense | <0.01% | Loss-of-function; may reduce inflammatory response |
| c.1045_1046insA | Frameshift | Rare | Loss-of-function; observed in gastric cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein, reducing caspase-5 activity and impairing inflammasome signaling.
Gain of Function (GOF)
Missense mutations (e.g., p.Gly392Arg) that enhance caspase-5 activation, leading to excessive IL-1β release and autoinflammation.
Dominant Negative (DN)
Not well documented for CASP5; dominant-negative effects are not a major mechanism.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type endopeptidase activity | • cysteine-type peptidase activity |
| • peptidase activity | • protein binding |
| • identical protein binding | • proteolysis |
| • apoptotic process | • inflammatory response |
| • cellular response to lipopolysaccharide | • activation of cysteine-type endopeptidase activity involved in apoptotic process |
| • pyroptosis |
Pathways
• Non-canonical inflammasome pathway (Reactome: R-HSA-5620971)
• Caspase activation via extrinsic apoptotic signaling (KEGG: hsa04210)
• Apoptosis (KEGG: hsa04215)
• Salmonella infection (KEGG: hsa05132)
Protein Summary
Caspase-5 is a 418-amino acid protein with a prodomain, a large catalytic subunit (p20), and a small catalytic subunit (p10). It is synthesized as a zymogen and activated by cleavage. The protein localizes to the cytosol and directly binds intracellular LPS via its CARD domain, triggering oligomerization and activation. Active caspase-5 cleaves gasdermin D to induce pyroptosis and processes pro-IL-1β and pro-IL-18. Its structure includes a caspase recruitment domain (CARD) essential for inflammasome assembly.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CASP5 Knockout HEK293 Cell Line | EDJ-KQ4195 | Human | 838 | Details Get a Quote |
| CASP5 Knockout HeLa Cell Line | EDJ-KQ52789 | Human | 838 | Details Get a Quote |
| CASP5 Knockout A-549 Cell Line | EDJ-KQ61259 | Human | 838 | Details Get a Quote |
| CASP5 Knockout HCT 116 Cell Line | EDJ-KQ69755 | Human | 838 | Details Get a Quote |
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