CASP4 (caspase 4)

Gene

• Entrez ID: 837
• Gene name: Caspase 4
• Gene symbol: CASP4
• Synonyms (NCBI Gene): ICE(rel)II, ICEREL-II, ICH-2, Mih1, Mih1/TX, TX
• Chromosome: 11
• Chromosome location: 11q22.3
• Summary: 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 prod

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT030229	hsa-miR-26b-5p	Microarray	19088304

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001530	Function	Lipopolysaccharide binding	IDA	25119034, 37993712
GO:0002376	Process	Immune system process	IEA
GO:0004197	Function	Cysteine-type endopeptidase activity	IDA	16920334, 26375003, 32109412, 34671164, 37993712, 37993714
GO:0004197	Function	Cysteine-type endopeptidase activity	IEA
GO:0005515	Function	Protein binding	IPI	29077095, 30692621, 33961781
GO:0005576	Component	Extracellular region	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005739	Component	Mitochondrion	IDA	15123740
GO:0005739	Component	Mitochondrion	IEA
GO:0005783	Component	Endoplasmic reticulum	IDA	15123740
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA	23661706
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0006508	Process	Proteolysis	IEA
GO:0006508	Process	Proteolysis	TAS	7797510
GO:0006915	Process	Apoptotic process	IBA
GO:0006915	Process	Apoptotic process	TAS	7743998, 7797510
GO:0006954	Process	Inflammatory response	IEA
GO:0008233	Function	Peptidase activity	IEA
GO:0008234	Function	Cysteine-type peptidase activity	IEA
GO:0008289	Function	Lipid binding	IDA	25119034, 32510692, 37993712
GO:0009306	Process	Protein secretion	IDA	37993712, 37993714
GO:0012501	Process	Programmed cell death	IEA
GO:0016020	Component	Membrane	IEA
GO:0016540	Process	Protein autoprocessing	IDA	32109412, 34671164
GO:0016787	Function	Hydrolase activity	IEA
GO:0032991	Component	Protein-containing complex	IDA	16920334
GO:0032991	Component	Protein-containing complex	IEA
GO:0035655	Process	Interleukin-18-mediated signaling pathway	IDA	14528293, 25500532
GO:0042742	Process	Defense response to bacterium	IDA	25119034, 32510692, 37993712, 37993714
GO:0042981	Process	Regulation of apoptotic process	IEA
GO:0043525	Process	Positive regulation of neuron apoptotic process	IBA
GO:0044546	Process	NLRP3 inflammasome complex assembly	IDA	35114687, 35254907
GO:0045087	Process	Innate immune response	IEA
GO:0050700	Function	CARD domain binding	IPI	16920334
GO:0050727	Process	Regulation of inflammatory response	IDA	32109412
GO:0050729	Process	Positive regulation of inflammatory response	IBA
GO:0050729	Process	Positive regulation of inflammatory response	IDA	33883744
GO:0050729	Process	Positive regulation of inflammatory response	IDA	33377178, 34671164, 37993712, 37993714
GO:0050830	Process	Defense response to Gram-positive bacterium	IDA	33377178
GO:0051604	Process	Protein maturation	IDA	25119034, 26375003, 34671164, 37993712, 37993714
GO:0051604	Process	Protein maturation	IDA	25119034, 26375003, 34671164, 37993712, 37993714
GO:0051604	Process	Protein maturation	IEA
GO:0061702	Component	Canonical inflammasome complex	IEA
GO:0070059	Process	Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IMP	15123740
GO:0070269	Process	Pyroptotic inflammatory response	IDA	33883744
GO:0070269	Process	Pyroptotic inflammatory response	IDA	31268602, 32109412, 34671164
GO:0072558	Component	NLRP1 inflammasome complex	IBA
GO:0097193	Process	Intrinsic apoptotic signaling pathway	IMP	15123740
GO:0141201	Process	Pyroptotic cell death	IDA	32109412, 38632402
GO:0160074	Component	Non-canonical inflammasome complex	IDA	25119034, 31268602
GO:0160075	Process	Non-canonical inflammasome complex assembly	IDA	26375003, 34671164
GO:0160075	Process	Non-canonical inflammasome complex assembly	IDA	25119034, 26375003, 31268602, 32510692, 34671164, 37993712, 37993714
GO:1903265	Process	Positive regulation of tumor necrosis factor-mediated signaling pathway	IDA	16920334
GO:1904646	Process	Cellular response to amyloid-beta	IMP	15123740
GO:2000494	Process	Positive regulation of interleukin-18-mediated signaling pathway	IDA	33377178

Other IDs

• MIM: 602664
• HGNC: 1505
• e!Ensembl: ENSG00000196954

Protein

• UniProt ID: P49662
• Protein name: Caspase-4 (CASP-4) (EC 3.4.22.57) (ICE and Ced-3 homolog 2) (ICH-2) (ICE(rel)-II) (Mih1) (Protease TX) [Cleaved into: Caspase-4 subunit p10; Caspase-4 subunit p20]
• Protein function: Inflammatory caspase that acts as the effector of the non-canonical inflammasome by mediating lipopolysaccharide (LPS)-induced pyroptosis (PubMed:25119034, PubMed:26375003, PubMed:32109412, PubMed:34671164, PubMed:37001519, PubMed:37993712, PubM
• PDB: 6KMZ, 6NRY, 7WR0, 7WR1, 7WR4, 7WR5, 7WR6, 8J6K, 8SPB
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00619	CARD	3 → 87	Caspase recruitment domain	Domain
  PF00656	Peptidase_C14	136 → 373		Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed, including in keratinocytes and colonic and small intestinal epithelial cells (at protein level). Not detected in brain. {ECO:0000269|PubMed:10986288, ECO:0000269|PubMed:22246630, ECO:0000269|PubMed:25121752, ECO:00002
• Sequence:

  MAEGNHRKKPLKVLESLGKDFLTGVLDNLVEQNVLNWKEEEKKKYYDAKTEDKVRVMADS
  MQEKQRMAGQMLLQTFFNIDQISPNKKAHPNMEAGPPESGESTDALKLCPHEEFLRLCKE
  RAEEIYPIKERNNRTRLALIICNTEFDHLPPRNGADFDITGMKELLEGLDYSVDVEENLT
  ARDMESALRAFATRPEHKSSDSTFLVLMSHGILEGICGTVHDEKKPDVLLYDTIFQIFNN
  RNCLSLKDKPKVIIVQACRGANRGELWVRDSPASLEVASSQSSENLEEDAVYKTHVEKDF
  IAFCSSTPHNVSWRDSTMGSIFITQLITCFQKYSWCCHLEEVFRKVQQSFETPRAKAQMP
  TIERLSMTRYFYLFPGN

• Sequence length: 377

Pathways

KEGG:

Neutrophil extracellular trap formation
NOD-like receptor signaling pathway
Pathogenic Escherichia coli infection
Shigellosis
Salmonella infection

Reactome:

NOD1/2 Signaling Pathway

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	15123740	Associate	★☆☆☆☆ Found in Text Mining only
Alzheimer Disease, Late Onset	Alzheimer disease	BEFREE	27516385		★☆☆☆☆ Found in Text Mining only
AMYOTROPHIC LATERAL SCLEROSIS 1	Lateral Sclerosis	BEFREE	20816908		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis, Familial	Amyotrophic lateral sclerosis	BEFREE	20816908		★☆☆☆☆ Found in Text Mining only
Anodontia	Anodontia	Pubtator	38139378	Stimulate	★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm	Aortic Aneurysm	BEFREE	15876810		★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm Abdominal	Aortic aneurysm	Pubtator	35320939	Associate	★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm Thoracic	Thoracic aortic aneurysm	Pubtator	15876810	Stimulate	★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	Pubtator	24136334	Associate	★☆☆☆☆ Found in Text Mining only
B-Cell Lymphomas	B-Cell Lymphoma	BEFREE	27221781, 29845288		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar disorder	Pubtator	25487697	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	18430458		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	30385776	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	30385776	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	35242200	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	18430458		★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	36647955	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	21781452, 34517553	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	31480859		★☆☆☆☆ Found in Text Mining only
Cerebral Infarction	Cerebral Infarction	BEFREE	27142195		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	BEFREE	29123531, 29721208, 30930781		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	18430458		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	25943872	Associate	★☆☆☆☆ Found in Text Mining only
Diabetic Nephropathies	Diabetic neuropathy	Pubtator	37316538	Associate	★☆☆☆☆ Found in Text Mining only
Dyskinesias	Dyskinesia	Pubtator	21781452	Associate	★☆☆☆☆ Found in Text Mining only
Epithelial ovarian cancer	Ovarian cancer	BEFREE	31480859		★☆☆☆☆ Found in Text Mining only
Gastrointestinal Stromal Tumors	Gastrointestinal stromal tumor	BEFREE	19269008		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	23280445, 36552744	Associate	★☆☆☆☆ Found in Text Mining only
Hypertension	Hypertension	Pubtator	32664164	Associate	★☆☆☆☆ Found in Text Mining only
Hypotension	Hypotension	Pubtator	25487697	Associate	★☆☆☆☆ Found in Text Mining only
Idiopathic Pulmonary Fibrosis	Pulmonary Fibrosis	BEFREE	29675024		★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	27516385		★☆☆☆☆ Found in Text Mining only
Infantile neuronal ceroid lipofuscinosis	Neuronal Ceroid Lipofuscinosis	BEFREE	16644870		★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory bowel disease	Pubtator	25943872	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Failure, Acute	Kidney Failure	BEFREE	30250284		★☆☆☆☆ Found in Text Mining only
Kidney Neoplasms	Kidney neoplasm	Pubtator	19603096	Associate	★☆☆☆☆ Found in Text Mining only
Lip and Oral Cavity Carcinoma	Lip and Oral Cavity Carcinoma	BEFREE	21781452		★☆☆☆☆ Found in Text Mining only
Lung Diseases	Lung disease	Pubtator	17586700	Associate	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung Neoplasms	BEFREE	29721208		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	37194012	Stimulate	★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	37194012	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	29328482		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of mouth	Malignant neoplasm of mouth	BEFREE	21781452		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	19383853, 36068291	Associate	★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	20514521, 30149677		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	25276823		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	32733636	Stimulate	★☆☆☆☆ Found in Text Mining only
Mouth Neoplasms	Mouth neoplasm	Pubtator	21781452	Associate	★☆☆☆☆ Found in Text Mining only
Mucocutaneous Lymph Node Syndrome	Kawasaki disease	BEFREE	28587409		★☆☆☆☆ Found in Text Mining only
Muscular Dystrophy, Duchenne	Duchenne Muscular Dystrophy	BEFREE	24879640		★☆☆☆☆ Found in Text Mining only
Necrosis	Necrosis	Pubtator	21984918	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	29721208		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	25695505, 27339788		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	Pubtator	25695505	Associate	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	22545106	Associate	★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	29721208, 30034638		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	35778597	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	36199146, 37753069	Associate	★☆☆☆☆ Found in Text Mining only
Periapical Periodontitis	Periapical periodontitis	Pubtator	36359010	Associate	★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	37194062	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	CTD_human_DG	21743468		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	Pubtator	25487697	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sepsis	Sepsis	Pubtator	36250055	Associate	★☆☆☆☆ Found in Text Mining only
Septicemia	Septicemia	BEFREE	27697835, 29061850, 29339744, 29780528, 30084208		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of esophagus	Esophagus Neoplasm	BEFREE	28454321		★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple negative breast cancer	Pubtator	21152100, 33297339	Associate	★☆☆☆☆ Found in Text Mining only
Urothelial Carcinoma	Urothelial Carcinoma	BEFREE	22438966		★☆☆☆☆ Found in Text Mining only
Ventricular Remodeling	Ventricular remodeling	Pubtator	32664164	Stimulate	★☆☆☆☆ Found in Text Mining only