CASP4 Gene

HGNC Family	Caspases (CASP)
Name	caspase 4, apoptosis-related cysteine peptidase
Description	This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain and a large and small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This caspase is able to cleave and activate its own precursor protein, as well as caspase 1 precursor. When overexpressed, this gene induces cell apoptosis. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "t", "text": "<div>\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Caspase‐4 in human cells functions as a key inflammatory sensor and executioner that bridges pathogen recognition and inflammatory cell death. Multiple studies have demonstrated that caspase‐4 is directly activated by cytosolic lipopolysaccharide and other bacterial components, initiating a cascade that results in the cleavage of gasdermin D to unmask its pore‐forming N-terminal fragment, thereby triggering pyroptosis and promoting the release of pro–inflammatory cytokines such as interleukin–1β (1,2,7). In specific contexts such as UVB irradiation of keratinocytes, caspase–4 is required for the processing of pro–IL–1β and for mediating unconventional protein secretion, indicating its broader role in innate immune responses beyond cell lysis (3). Moreover, during infection by pathogens such as Shigella and Salmonella, caspase–4–dependent pyroptosis acts as an important host defense mechanism; indeed, bacterial effectors like Shigella OspC3 can inhibit caspase–4 activation to delay epithelial cell death and facilitate infection (4). In addition, activation of caspase–4 has been implicated in apoptotic pathways in response to endoplasmic reticulum stress—for example, in lung epithelial cells expressing misfolded mutant proteins, elevated caspase–4 activity contributes to apoptotic cell death (5). Recent work also indicates that regulators such as Gasdermin B can potentiate caspase–4 activity via direct interactions, further amplifying the non‐canonical pyroptosis pathway (6). Collectively, these findings underscore the dual role of caspase–4 as both a sensor of intracellular microbial components and an effector protease that modulates cell lysis, cytokine secretion, and even apoptosis, thereby significantly contributing to innate immunity and the inflammatory response.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n <small>\n (1)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", (2)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", (3)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", (4)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", (5)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", (6)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", (7)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "</small>\n "}]}, {"type": "t", "text": "\n</div>"}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kun Wang, Qi Sun, Xiu Zhong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural Mechanism for GSDMD Targeting by Autoprocessed Caspases in Pyroptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2020.02.002"}], "href": "https://doi.org/10.1016/j.cell.2020.02.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32109412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32109412"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Paul J Baker, Dave Boucher, Damien Bierschenk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase-4 and caspase-5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.201545655"}], "href": "https://doi.org/10.1002/eji.201545655"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26173988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26173988"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Gabriel Sollberger, Gerhard E Strittmatter, Magdalena Kistowska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Caspase-4 is required for activation of inflammasomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1101620"}], "href": "https://doi.org/10.4049/jimmunol.1101620"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22246630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22246630"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Taira Kobayashi, Michinaga Ogawa, Takahito Sanada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Host Microbe (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chom.2013.04.012"}], "href": "https://doi.org/10.1016/j.chom.2013.04.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23684308"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23684308"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Surafel Mulugeta, Jean Ann Maguire, Jennifer L Newitt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Misfolded BRICHOS SP-C mutant proteins induce apoptosis via caspase-4- and cytochrome c-related mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.00025.2007"}], "href": "https://doi.org/10.1152/ajplung.00025.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17586700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17586700"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Qin Chen, Peiliang Shi, Yufang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GSDMB promotes non-canonical pyroptosis by enhancing caspase-4 activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jmcb/mjy056"}], "href": "https://doi.org/10.1093/jmcb/mjy056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30321352"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30321352"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jaye M Platnich, Hyunjae Chung, Arthur Lau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Shiga Toxin/Lipopolysaccharide Activates Caspase-4 and Gasdermin D to Trigger Mitochondrial Reactive Oxygen Species Upstream of the NLRP3 Inflammasome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2018.09.071"}], "href": "https://doi.org/10.1016/j.celrep.2018.09.071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30404007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30404007"}]}]}]}
Synonyms	ICEREL-II, ICH-2, TX, MIH1/TX, Mih1, ICE(REL)II
Proteins	CASP4_HUMAN
NCBI Gene ID	837
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CASP4 has 6,878 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 109 datasets.

Click the + buttons to view associations for CASP4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CASP4 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CASP4 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CASP4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CASP4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CASP4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CASP4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving CASP4 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CASP4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CASP4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CASP4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CASP4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with CASP4 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CASP4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CASP4 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CASP4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CASP4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CASP4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CASP4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CASP4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CASP4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CASP4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CASP4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CASP4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CASP4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CASP4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CASP4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CASP4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CASP4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CASP4 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CASP4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CASP4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CASP4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CASP4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CASP4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CASP4 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CASP4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CASP4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CASP4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CASP4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CASP4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CASP4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.