| HGNC Family | Caspases (CASP) |
| Name | caspase 12 (gene/pseudogene) |
| Description | Caspases are cysteine proteases that cleave C-terminal aspartic acid residues on their substrate molecules. This gene is most highly related to members of the ICE subfamily of caspases that process inflammatory cytokines. In rodents, the homolog of this gene mediates apoptosis in response to endoplasmic reticulum stress. However, in humans this gene contains a polymorphism for the presence or absence of a premature stop codon. The majority of human individuals have the premature stop codon and produce a truncated non-functional protein. The read-through codon occurs primarily in individuals of African descent and carriers have endotoxin hypo-responsiveness and an increased susceptibility to severe sepsis. Several alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Feb 2011] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCaspase‐12 has been implicated as a key mediator of endoplasmic reticulum (ER) stress–induced apoptosis in a variety of pathological settings. In experimental models of prion disease, misfolded prion protein triggers ER calcium release, up‐regulates ER chaperones, and leads to caspase‐12 activation that contributes to neuronal death. Similar mechanisms have been observed in studies addressing β‐cell homeostasis, BIK‐mediated cell death, cystic fibrosis–associated ER stress, albumin‐induced tubular apoptosis in diabetic nephropathy, hepatocyte injury following ethanol exposure, and hypoxic–ischemic encephalopathy. In these settings, caspase‐12 undergoes autoproteolytic processing that appears to initiate an apoptotic cascade distinct from the classical executioner caspase pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its apoptotic functions, caspase‐12 modulates the inflammatory and innate immune responses. Although its expression in most humans is abolished by a frame‐shift mutation, the full‐length allele—found predominantly in individuals of African descent—has been shown to attenuate lipopolysaccharide‐induced cytokine production and alter sepsis susceptibility. Experimental studies indicate that caspase‐12 can act as a dominant–negative regulator of caspase‐1, thereby down‐regulating proinflammatory cytokine maturation. Further work has demonstrated that caspase‐12 influences outcomes in fungal infections, modulates metabolic inflammation, and is subject to hormonal and environmental regulation; for example, estrogen reduces its expression in immune cells and cigarette smoke can affect its downstream signaling. Collectively, these findings underscore a complex role for caspase‐12 in immune homeostasis and host defense, even though its presence does not invariably correlate with disease severity in certain conditions such as community–acquired pneumonia or systemic lupus erythematosus."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCaspase‐12 expression has also been examined in various tissue and neoplastic contexts. In ocular tissues, studies in retinal pigment epithelial cells and lens epithelial cells have explored its regulation under stress conditions relevant to diabetic retinopathy. In the cancer arena, caspase‐12 has emerged as a hub gene: its expression correlates with prognosis in skin cutaneous melanoma and its differential expression in cervical cancer holds promise as a diagnostic and prognostic biomarker. Moreover, in human nasopharyngeal carcinoma cells, overexpression of caspase‐12 has been linked to enhanced NF–κB activation and increased tumor cell invasion, suggesting that caspase‐12 may bridge inflammatory signaling and cancer aggressiveness."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Heinz Fischer, Ulrich Koenig, Leopold Eckhart, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Human Caspase 12 Enhances NF-κB Activity through Activation of IKK in Nasopharyngeal Carcinoma Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms22094610"}], "href": "https://doi.org/10.3390/ijms22094610"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33924755"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33924755"}]}]}]}
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| Synonyms | CASP12P1, CASP-12 |
| Proteins | CASPC_HUMAN |
| NCBI Gene ID | 100506742 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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CASP12 has 2,555 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 71 datasets.
Click the + buttons to view associations for CASP12 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of CASP12 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of CASP12 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of CASP12 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of CASP12 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| BioGPS Mouse Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of CASP12 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of CASP12 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 CASP12 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| CellMarker Gene-Cell Type Associations | cell types associated with CASP12 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 CASP12 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of CASP12 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 CASP12 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of CASP12 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with CASP12 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| CTD Gene-Chemical Interactions | chemicals interacting with CASP12 gene/protein from the curated CTD Gene-Chemical Interactions dataset. | |
| CTD Gene-Disease Associations | diseases associated with CASP12 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
| DGIdb Drug Targets 2026 | interacting drugs for CASP12 protein from the DGIdb Drug Targets 2026 dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with CASP12 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with CASP12 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 CASP12 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 CASP12 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of CASP12 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 CASP12 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
| GAD Gene-Disease Associations | diseases associated with CASP12 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with CASP12 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing CASP12 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of CASP12 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of CASP12 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of CASP12 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of CASP12 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of CASP12 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving CASP12 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving CASP12 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving CASP12 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing CASP12 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by CASP12 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2023 | molecular functions performed by CASP12 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by CASP12 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of CASP12 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of CASP12 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GTEx Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of CASP12 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with CASP12 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of CASP12 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of CASP12 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Protein Expression Profiles | tissues with high or low expression of CASP12 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
| HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of CASP12 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| Hub Proteins Protein-Protein Interactions | interacting hub proteins for CASP12 from the curated Hub Proteins Protein-Protein Interactions dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with CASP12 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for CASP12 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of CASP12 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of CASP12 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of CASP12 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| KEGG Pathways 2026 | pathways involving CASP12 protein from the KEGG Pathways 2026 dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of CASP12 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of CASP12 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain CASP12 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by CASP12 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of CASP12 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| MoTrPAC Rat Endurance Exercise Training | tissue samples with high or low expression of CASP12 gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset. | |
| MPO Gene-Phenotype Associations | phenotypes of transgenic mice caused by CASP12 gene mutations from the MPO Gene-Phenotype Associations dataset. | |
| OMIM Gene-Disease Associations | phenotypes associated with CASP12 gene from the curated OMIM Gene-Disease Associations dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for CASP12 from the Pathway Commons Protein-Protein Interactions dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving CASP12 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving CASP12 protein from the Wikipathways PFOCR 2024 dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at CASP12 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of CASP12 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of CASP12 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of CASP12 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of CASP12 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of CASP12 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of CASP12 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| WikiPathways Pathways 2014 | pathways involving CASP12 protein from the Wikipathways Pathways 2014 dataset. | |
