CASP1 (Caspase-1): Inflammasome Regulator, Pyroptosis Mediator, and Inflammatory Disease Biomarker
A comprehensive biomedical overview of the CASP1 gene, its protein product, expression patterns, mutations, and clinical significance in inflammatory and infectious diseases.
Gene Information Card
| Symbol | CASP1 |
|---|---|
| Full Name | Caspase 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 11q22.3 |
| NCBI Gene ID | 834 ncbi.nlm.nih.gov/gene/834 |
| Ensembl ID | ENSG00000137752 |
| UniProt ID | P29466 |
| OMIM ID | 147678 |
| HGNC ID | 1499 |
| Aliases | ICE, IL1BC, P45 |
Description
CASP1 encodes caspase-1, a cysteine-aspartic acid protease that plays a central role in the innate immune response. It is a key component of the inflammasome complex, where it is activated by various danger signals. Once activated, caspase-1 cleaves pro-IL-1β and pro-IL-18 into their mature, secreted forms, and also induces pyroptosis, a pro-inflammatory form of cell death. This gene is critical for host defense against pathogens but also contributes to inflammatory and autoimmune diseases when dysregulated.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoinflammatory syndromes (e.g., familial Mediterranean fever-like conditions) | Gain-of-function mutations in inflammasome components lead to excessive caspase-1 activation and IL-1β production. | ClinVar and OMIM list pathogenic variants in CASP1 associated with autoinflammatory phenotypes. |
| Sepsis | Caspase-1-mediated pyroptosis and IL-1β release contribute to systemic inflammation and organ damage. | Elevated CASP1 expression and activity observed in septic patients; animal models show protective effects of inhibition. |
| Inflammatory bowel disease (IBD) | Dysregulated inflammasome activation and IL-1β production exacerbate intestinal inflammation. | Genetic association studies and expression analyses link CASP1 variants to IBD susceptibility. |
| Cancer (e.g., gastric, breast) | Caspase-1 can have dual roles: promoting inflammation-induced tumorigenesis or suppressing tumor growth via pyroptosis. | COSMIC database reports somatic mutations in CASP1 across various cancers; functional studies vary. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 12.4 | Medium |
| Spleen | 10.1 | Medium |
| Lung | 8.3 | Low |
| Liver | 5.2 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | 18.5 | High expression; commonly used for inflammasome studies. |
| HeLa (cervical cancer) | 3.2 | Low expression; inducible by stimuli. |
| A549 (lung carcinoma) | 6.7 | Moderate expression; responsive to inflammatory signals. |
| HepG2 (hepatocellular carcinoma) | 2.8 | Low expression; minimal basal activity. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Leu265Ser (rs580253) | Missense | 1-2% in some populations | May alter enzyme activity; clinical significance uncertain. |
| p.Arg240His (rs1799762) | Missense | 5-10% in European populations | Associated with altered IL-1β processing; possible link to inflammatory diseases. |
| c.285+1G>A | Splice site | Rare | Predicted to disrupt splicing; loss of function. |
| p.Gly122Arg | Missense | Somatic in cancer (COSMIC) | Potential gain-of-function; observed in gastric cancer. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CASP1 are rare and may impair IL-1β and IL-18 processing, leading to immunodeficiency or reduced inflammatory responses. ClinVar lists some variants with uncertain significance.
Gain of Function (GOF)
Gain-of-function mutations can lead to enhanced inflammasome activity, excessive IL-1β production, and autoinflammatory symptoms. Such variants are often somatic in cancer or rare germline in inflammatory disorders.
Dominant Negative (DN)
Dominant-negative mutations in CASP1 have been proposed to inhibit wild-type caspase-1 activity, potentially reducing inflammation. However, documented cases are limited and require further validation.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type endopeptidase activity | • caspase activity |
| • protein homodimerization activity | • interleukin-1 beta processing |
| • interleukin-18 processing | • pyroptosis |
| • inflammatory response | • regulation of apoptotic process |
Pathways
• Inflammasome pathway (NLRP3
• NLRC4
• AIM2)
• IL-1 family signaling
• Pyroptosis pathway
• Apoptosis and survival
Protein Summary
Caspase-1 is synthesized as a zymogen (pro-caspase-1) that requires proteolytic cleavage to become active. It forms a complex with inflammasome sensors and adaptor proteins (e.g., ASC) to mediate its activation. Active caspase-1 consists of p20 and p10 subunits and cleaves pro-IL-1β and pro-IL-18, as well as gasdermin D, leading to pyroptosis. It is expressed mainly in immune cells and tissues with high inflammatory activity. Dysregulation of caspase-1 is implicated in various inflammatory diseases, making it a therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CASP1 Knockout HEK293 Cell Line | EDJ-KQ1456 | Human | 834 | Details Get a Quote |
| CASP10 Knockout HEK293 Cell Line | EDJ-KQ1476 | Human | 843 | Details Get a Quote |
| CASP14 Knockout HEK293 Cell Line | EDJ-KQ2785 | Human | 23581 | Details Get a Quote |
| CASP12 Knockout HEK293 Cell Line | EDJ-KQ7663 | Human | 100506742 | Details Get a Quote |
| CASP10 Knockout A-549 Cell Line | EDJ-KQ21054 | Human | 843 | Details Get a Quote |
| CASP10 Knockout HCT 116 Cell Line | EDJ-KQ21055 | Human | 843 | Details Get a Quote |
| CASP10 Knockout HeLa Cell Line | EDJ-KQ21056 | Human | 843 | Details Get a Quote |
| CASP12 Knockout A-549 Cell Line | EDJ-KQ33020 | Human | 100506742 | Details Get a Quote |
| CASP12 Knockout HCT 116 Cell Line | EDJ-KQ33021 | Human | 100506742 | Details Get a Quote |
| CASP12 Knockout HeLa Cell Line | EDJ-KQ33022 | Human | 100506742 | Details Get a Quote |
| CASP1 Knockout HeLa Cell Line | EDJ-KQ22323 | Human | 834 | Details Get a Quote |
| CASP14 Knockout HeLa Cell Line | EDJ-KQ55776 | Human | 23581 | Details Get a Quote |
| CASP1 Knockout A-549 Cell Line | EDJ-KQ61258 | Human | 834 | Details Get a Quote |
| CASP14 Knockout A-549 Cell Line | EDJ-KQ64271 | Human | 23581 | Details Get a Quote |
| CASP1 Knockout HCT 116 Cell Line | EDJ-KQ69754 | Human | 834 | Details Get a Quote |
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