CASP4 (Caspase 4) - Inflammatory Caspase and Pyroptosis Regulator
Key mediator of non-canonical inflammasome activation and innate immunity
Gene Information Card
| Symbol | CASP4 |
|---|---|
| Full Name | Caspase 4 |
| Gene Type | Protein-coding |
| Chromosomal Location | 11q22.3 |
| NCBI Gene ID | 837 ncbi.nlm.nih.gov/gene/837 |
| Ensembl ID | ENSG00000196954 |
| UniProt ID | P49662 |
| OMIM ID | 602664 |
| HGNC ID | 1505 |
| Aliases | ICE(rel)II, ICH-2, TX, ICEREL-II, CASP-4 |
Description
CASP4 encodes caspase-4, a cysteine-aspartic protease that functions as an inflammatory caspase. It plays a critical role in the innate immune response by mediating non-canonical inflammasome activation, leading to pyroptosis and cytokine release in response to cytosolic lipopolysaccharide (LPS). Caspase-4 is also involved in endoplasmic reticulum stress-induced apoptosis and is implicated in various inflammatory and infectious diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory bowel disease (IBD) | Altered CASP4 expression may modulate intestinal inflammation and pyroptosis | ClinVar, PubMed |
| Sepsis | CASP4 mediates LPS-induced pyroptosis and IL-1β release, contributing to septic shock | PubMed, COSMIC |
| Neurodegenerative disorders | CASP4 activation in microglia promotes neuroinflammation | PubMed |
| Cancer (e.g., gastric, breast) | Dysregulated CASP4 expression affects apoptosis and tumor progression | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small intestine | 20.1 | Medium |
| Spleen | 18.5 | Medium |
| Lung | 15.3 | Medium |
| Liver | 12.0 | Low |
| Brain | 8.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 25.0 | High expression; LPS-inducible |
| HeLa (cervical) | 15.0 | Moderate expression |
| A549 (lung) | 12.0 | Moderate expression |
| HepG2 (liver) | 8.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.733C>T (p.Arg245Cys) | Missense | Rare | May affect substrate specificity |
| c.1000G>A (p.Glu334Lys) | Missense | Rare | Potential impact on dimerization |
| c.1129A>G (p.Ile377Val) | Missense | Rare | Uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CASP4 are rare; they may impair pyroptosis and cytokine secretion, leading to immunodeficiency or autoinflammatory phenotypes.
Gain of Function (GOF)
Gain-of-function mutations could enhance inflammasome activation, increasing pyroptosis and inflammation, potentially contributing to inflammatory diseases.
Dominant Negative (DN)
Dominant-negative mutations may interfere with caspase-4 oligomerization, reducing its activity and downstream signaling.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type endopeptidase activity | • cysteine-type peptidase activity |
| • protein homodimerization activity | • identical protein binding |
| • protease binding | • inflammasome complex |
| • cytoplasm | • cytosol |
| • nucleus | • proteolysis |
| • apoptotic process | • inflammatory response |
| • pyroptosis | • regulation of inflammatory response |
| • response to lipopolysaccharide |
Pathways
• Non-canonical inflammasome pathway
• Pyroptosis pathway
• Apoptosis pathway
• Innate immune system signaling
Protein Summary
Caspase-4 is a 377-amino acid protein (UniProt P49662) that belongs to the cysteine-aspartic protease family. It contains a caspase recruitment domain (CARD) and a catalytic domain. Caspase-4 is synthesized as a zymogen and undergoes proteolytic cleavage to form active subunits. It directly binds cytosolic LPS via its CARD domain, leading to oligomerization and activation. Active caspase-4 cleaves gasdermin D (GSDMD) to induce pyroptosis and also processes pro-IL-18, contributing to inflammatory responses. It is expressed in various tissues, with higher levels in immune cells and barrier tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CASP4 Knockout HEK293 Cell Line | EDJ-KQ2380 | Human | 837 | Details Get a Quote |
| CASP4 Knockout HCT 116 Cell Line | EDJ-KQ21529 | Human | 837 | Details Get a Quote |
| CASP4 Knockout A-549 Cell Line | EDJ-KQ22851 | Human | 837 | Details Get a Quote |
| CASP4 Knockout HeLa Cell Line | EDJ-KQ22853 | Human | 837 | Details Get a Quote |
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