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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CASP1
caspase 1
Chromosome 11 · 11q22.3
NCBI Gene: 834Ensembl: ENSG00000137752.26HGNC: HGNC:1499UniProt: A8K249
416PubMed Papers
20Diseases
3Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneProtease
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of tumor necrosis factor-mediated signaling pathwaycysteine-type endopeptidase activityprotein bindingpositive regulation of canonical NF-kappaB signal transductionsevere acute respiratory syndromeAbnormality of the genital systeminfectionneoplasm
✦AI Summary

CASP1 (caspase-1) is a cysteine protease that functions as a central mediator of inflammasome-driven inflammatory responses rather than apoptosis 1. The protein operates primarily through the NLRP3, NLRP1, and AIM2 inflammasome complexes, where it processes pro-inflammatory cytokine precursors into their active forms, particularly interleukin-1β and interleukin-18 1. CASP1 activation is regulated by ubiquitin-proteasome pathways, with USP22-mediated deubiquitination providing negative regulation 2. CASP1 has significant disease relevance across multiple pathologies. In Alzheimer's disease, enhanced CASP1 expression in affected brains drives neuroinflammation through NLRP3 activation; Casp1-knockout mice showed protection from cognitive decline and reduced amyloid-β pathology 1. CASP1 also contributes to necroptotic cell death programs in psoriasis and atherosclerosis, functioning alongside ferroptosis-related pathways 3. In allergic rhinitis, house dust mite allergens trigger CASP1 activation via mtDNA-STING signaling 4, while genetic variants in CASP1 are associated with restenosis risk following coronary intervention 5. Clinically, CASP1 represents a therapeutic target for inflammasome-related diseases. Kaempferol treatment of rheumatoid arthritis operates through CASP1 inhibition within the NLRP3/CASP1/GSDMD pyroptotic axis 6. Emerging evidence suggests potential involvement in aspartame-induced hepatotoxicity through CASP1 modulation 7, highlighting the protein's diverse pathogenic roles.

Sources cited
1
CASP1 functions in NLRP3 inflammasome-driven IL-1β maturation and is elevated in Alzheimer's disease; Casp1-knockout mice show protection from cognitive decline
PMID: 23254930
2
CASP1 activation is regulated by USP22-mediated NLRP3 degradation through autophagy pathways in inflammasome regulation
PMID: 35900990
3
CASP1 is a differentially expressed necroptosis-related gene involved in immune and inflammatory pathways in psoriasis and atherosclerosis
PMID: 39072329
4
CASP1 is activated downstream of the mtDNA-STING pathway in house dust mite-induced allergic rhinitis through NLRP3 inflammasome
PMID: 39799434
5
CASP1 polymorphisms (rs501192 and rs580253) are associated with increased restenosis risk after coronary stenting
PMID: 35740890
6
Kaempferol treats rheumatoid arthritis by inhibiting CASP1 within the NLRP3/CASP1/GSDMD pyroptotic axis
PMID: 39388897
7
CASP1 is identified as a risk factor for aspartame-induced liver cancer through binding and modulation of necroptotic pathways
PMID: 40139029
Disease Associationsⓘ20
severe acute respiratory syndromeOpen Targets
0.37Weak
Abnormality of the genital systemOpen Targets
0.26Weak
infectionOpen Targets
0.11Weak
neoplasmOpen Targets
0.11Weak
cirrhosis of liverOpen Targets
0.11Weak
SepsisOpen Targets
0.10Weak
hepatocellular carcinomaOpen Targets
0.10Weak
COVID-19Open Targets
0.10Suggestive
colorectal carcinomaOpen Targets
0.10Suggestive
epilepsyOpen Targets
0.10Suggestive
depressive disorderOpen Targets
0.10Suggestive
HypocalcemiaOpen Targets
0.10Suggestive
Hepatic fibrosisOpen Targets
0.10Suggestive
subarachnoid hemorrhageOpen Targets
0.10Suggestive
congenital rubellaOpen Targets
0.09Suggestive
ulcerative colitisOpen Targets
0.09Suggestive
leukemiaOpen Targets
0.09Suggestive
psoriasisOpen Targets
0.09Suggestive
hepatitis C virus infectionOpen Targets
0.09Suggestive
non-alcoholic steatohepatitisOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets3
BELNACASANPhase II
Caspase-1 inhibitor
epilepsy
EMRICASANPhase II
Caspase inhibitor
Hepatic fibrosis
NIVOCASANPhase II
Caspase-1 inhibitor
fibrosis
Related Genes
RIPK1Protein interaction100%FADDProtein interaction100%AIM2Protein interaction100%CTSSProtein interaction100%IL1RNProtein interaction100%MEFVProtein interaction100%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
40%
Liver
21%
Ovary
16%
Heart
14%
Brain
6%
Gene Interaction Network
Click a node to explore
CASP1RIPK1FADDAIM2CTSSIL1RNMEFV
PROTEIN STRUCTURE
Preparing viewer…
PDB8WRA · 1.45 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.82LoF Tolerant
pLIⓘ
0.02Tolerant
Observed/Expected LoF0.51 [0.33–0.82]
RankingsWhere CASP1 stands among ~20K protein-coding genes
  • #683of 20,598
    Most Researched416 · top 5%
  • #6,887of 17,882
    Most Constrained (LOEUF)0.82
Genes detectedCASP1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice.
PMID: 23254930
Nature · 2013
1.00
2
USP22 suppresses the NLRP3 inflammasome by degrading NLRP3 via ATG5-dependent autophagy.
PMID: 35900990
Autophagy · 2023
0.90
3
Exploration of ferroptosis and necroptosis-related genes and potential molecular mechanisms in psoriasis and atherosclerosis.
PMID: 39072329
Front Immunol · 2024
0.80
4
LAMP3 inhibits autophagy and contributes to cell death by lysosomal membrane permeabilization.
PMID: 34802379
Autophagy · 2022
0.70
5
FLT4/VEGFR3 activates AMPK to coordinate glycometabolic reprogramming with autophagy and inflammasome activation for bacterial elimination.
PMID: 34632918
Autophagy · 2022
0.64