CASP7 (caspase 7, apoptosis-related cysteine peptidase)
2014-06-01 Cláudia Malheiros Coutinho-Camillo , Fernando Augusto Soares AffiliationDepartment of Anatomic Pathology, AC Camargo Cancer Center, Sao Paulo, Brazil
Identity
HGNC
LOCATION
10q25.3
LOCUSID
ALIAS
CASP-7,CMH-1,ICE-LAP3,LICE2,MCH3
FUSION GENES
Abstract
Apoptosis is a selective process for deleting cells in various biological systems and plays an essential role in the development and maintenance of tissue homeostasis in multicellular organisms and inappropriate regulation of apoptosis is believed to be the cause of many human diseases, including cancer (Thompson, 1995).
DNA/RNA
CASP7 transcript variants. Coding exons are marked by blue blocks, and non-coding exons, 5- and 3-UTRs are marked by white blocks.
Description
CASP7 gene contains 8 exons and spans 51.748 Kb of genomic DNA.
Transcription
CASP7 gene has 9 transcripts (splice variants):
- CASP7-201: 2694 bp (8 exons; 7 coding exons)
- CASP7-005: 2659 bp (8 exons; 6 coding exons)
- CASP7-002: 2421 bp (8 exons; 6 coding exons)
- CASP7-003: 2380 bp (8 exons; 7 coding exons)
- CASP7-001: 2377 bp (7 exons; 6 coding exons)
- CASP7-202: 1148 bp (6 exons; 6 coding exons)
- CASP7-004: 834 bp (6 exons; 5 coding exons)
- CASP7-007: 607 bp (3 exons; 0 coding exons)
- CASP7-008: 799 bp (5 exons; 0 coding exons).
- CASP7-201: 2694 bp (8 exons; 7 coding exons)
- CASP7-005: 2659 bp (8 exons; 6 coding exons)
- CASP7-002: 2421 bp (8 exons; 6 coding exons)
- CASP7-003: 2380 bp (8 exons; 7 coding exons)
- CASP7-001: 2377 bp (7 exons; 6 coding exons)
- CASP7-202: 1148 bp (6 exons; 6 coding exons)
- CASP7-004: 834 bp (6 exons; 5 coding exons)
- CASP7-007: 607 bp (3 exons; 0 coding exons)
- CASP7-008: 799 bp (5 exons; 0 coding exons).
Pseudogene
Not identified.
Proteins
Structure of procaspase-7. Numbers below the stick represents the approximate MWs of the resulting subunits and pro-regions. The proenzymes are cleaved at specific Asp residues (Dn, where n is the position in the protein).
Description
Caspase-7 is an effector caspase and plays an central role in the execution phase of the apoptosis.
Expression
Caspase-7 is widely expressed in human tissues. Highly expressed in lung, skeletal muscle, liver, kidney, spleen and heart, and moderately in testis.
Localisation
Mainly in the cytoplasm, but also observed in the nucleus.
Function
Effector caspases are responsible for initiating the hallmarks of the degradation phase of apoptosis, including DNA fragmentation, cell shrinkage and membrane blebbing. Besides its activation during apoptosis, proteolytic maturation of caspase-7 has also been observed under inflammatory conditions.
Homology
CASP7 (P. troglodytes, M. mulatta, C. lupus, B. taurus, G. gallus), Casp7 (M. musculus, R. norvegicus), casp7 (X. tropicalis, D. rerio), Ice (D. melanogaster), Dcp-1 (D. melanogaster), CASPS7 (A. gambiae).
Mutations
Note
Soung et al. (2003) detected CASP7 mutations in 2 of 98 colon carcinomas (2%), 1 of 50 esophageal carcinomas (2%), and 1 of 33 head/neck carcinomas (3%). Expression of the tumor-derived CASP7 mutants in 293T cells showed that apoptosis was reduced compared to the wild-type caspase-7, suggesting that inactivating mutations of CASP7 might contribute to the pathogenesis of some human solid cancers.
Genetic polymorphisms in the CASP7 gene may affect cancer risk through altering expression levels and functions of this gene. Several polymorphisms have been associated with susceptibility of cancer development, as will be discussed later (Yan et al., 2013).
A detailed list of genetic variations could be found at: Ensembl.
Genetic polymorphisms in the CASP7 gene may affect cancer risk through altering expression levels and functions of this gene. Several polymorphisms have been associated with susceptibility of cancer development, as will be discussed later (Yan et al., 2013).
A detailed list of genetic variations could be found at: Ensembl.
Implicated in
Entity name
Lung cancer
Note
Lee et al. (2009) showed that the CASP7 rs2227310 g.C>G polymorphism was associated with the risk of lung cancer.
Yoo et al. (2009) also demonstrated that the CASP7 rs2227310 polymorphism may affect survival in early-stage non-small cell lung cancer (NSCLC), suggesting that the analysis of this polymorphism can help identify patients at high risk for a poor disease outcome.
Qian et al. (2012) also provided evidence that genetic variations of CASP7 may modulate overall survival and progression-free survival of patients with advanced NSCLC treated with platinum-based chemotherapy.
Yoo et al. (2009) also demonstrated that the CASP7 rs2227310 polymorphism may affect survival in early-stage non-small cell lung cancer (NSCLC), suggesting that the analysis of this polymorphism can help identify patients at high risk for a poor disease outcome.
Qian et al. (2012) also provided evidence that genetic variations of CASP7 may modulate overall survival and progression-free survival of patients with advanced NSCLC treated with platinum-based chemotherapy.
Entity name
Esophageal cancer
Note
Liu et al. (2010) described that polymorphisms in CASP7 gene was associated with increased risk of esophageal cancer.
Entity name
Childhood leukemia
Note
Park et al. (2012) suggested that three SNPs in CASP7 acts as a strong apoptosis signal that block or delay the apoptosis of childhood leukemia cancer cells.
Entity name
Colorectal cancer
Note
Palmerini et al. (2001) described a loss of caspase-7 in 84% of colon cancers, suggesting that caspase-7 deficiency might be used as a new immunohistochemical marker of colonic neoplasia.
Chae et al. (2011) reported that CASP7 rs2227310 polymorphism may be useful marker to predict the prognosis of patients with surgically resected colorectal cancer.
Chae et al. (2011) reported that CASP7 rs2227310 polymorphism may be useful marker to predict the prognosis of patients with surgically resected colorectal cancer.
Entity name
Gastric cancer
Note
Entity name
Endometrial cancer
Note
The AA genotype of rs11196445b, the CC genotype of rs3124740, and the GG genotype of rs10787498 in the CASP7 gene were associated with increased risk compared with homozygotes of the major alleles, suggesting that genetic variants in CASP7 may play a role in endometrial cancer susceptibility in a Chinese population (Xu et al., 2009).
Entity name
Renal carcinoma
Note
Vilella-Arias et al. (2013) reported loss of CASP7 protein expression in renal cell carcinoma clear cell subtype (ccRCC) and this loss was associated with the agressiveness of ccRCC, suggesting the potential use of CASP7 as a prognostic marker.
Entity name
Oral squamous cell carcinoma
Note
Coutinho-Camillo et al. (2011) reported that high expression level of CASP7 protein was associated with poor prognosis in oral squamous cell carcinoma (OSCC) patients.
Entity name
Alzheimers disease
Note
Elevated mRNA levels of caspases-7 and 8 measured by a quantitative PCR method were observed in the Alzheimers disease (AD) temporal neocortex as compared to the control brains, suggesting that the transcriptional activation of key components of the apoptotic cascade correlates with accumulation of Abeta42. Thus, a principal caspase pathway from caspase-8 to caspase-3 and/or 7 may contribute to neuron loss in AD brain (Matsui et al., 2006).
Entity name
Huntingtons disease
Note
Hermel et al. (2004) reported that caspase-7 immunoreactivity in post-mortem tissue from Huntingtons disease (HD) patients is dramatically enhanced in the medium spiny neurons of the caudate nucleus and neurons in the putamen when compared to age-matched controls. Caspase-7 is able to bind full-length huntingtin (Htt), accelerating the production of Htt fragments and resulting in the eventual induction of apoptosis both in the neuronal processes and somata.
Entity name
Rheumatoid arthritis
Note
CASP-7 gene is associated with the susceptibility to rheumatoid arthritis (RA). Genotyping of three single nucleotide polymorphisms (SNPs) of the CASP7 gene: rs11593766 (G/T), rs2227310 (C/G) and rs2227309 (G/A) revealed that rs2227309 SNP was found to be associated with susceptibility to RA. Frequency of the G allele was significantly higher among RA patients and a higher frequency of GG homozygous individuals was found in the RA patient group (Garcia-Lozano et al., 2007).
Teixeira et al. (2008) found that CASP7 rs2227309 SNP was not associated with RA in a European Caucasian population. Nevertheless, CASP7 isoforms alpha and beta could be involved in the apoptosis process in RA.
Teixeira et al. (2008) found that CASP7 rs2227309 SNP was not associated with RA in a European Caucasian population. Nevertheless, CASP7 isoforms alpha and beta could be involved in the apoptosis process in RA.
Entity name
Insulin-dependent diabetes mellitus
Note
Babu et al. (2003) studied 18 SNPs in CASP7 and reported that 1 (SNP144692) differed significantly in frequency in the haplotypes found in affected individuals compared to control Bedouin Arab family haplotypes. This same SNP showed evidence of association with diabetes in a subset of patients (DR3/DR4*0302) from Human Biological Data Interchange (HBDI) families, although these results are in conflict with other studies.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 14679087 | 2003 | Caspase 7 is a positional candidate gene for IDDM 17 in a Bedouin Arab family. | Babu SR et al |
| 14644197 | 2003 | Mechanisms of caspase activation. | Boatright KM et al |
| 20567846 | 2011 | RIPK1 and CASP7 polymorphism as prognostic markers for survival in patients with colorectal cancer after complete resection. | Chae YS et al |
| 9337844 | 1997 | Caspases: the executioners of apoptosis. | Cohen GM et al |
| 21755562 | 2011 | Caspase expression in oral squamous cell carcinoma. | Coutinho-Camillo CM et al |
| 12475198 | 2002 | Caspases: keys in the ignition of cell death. | Denault JB et al |
| 17504820 | 2007 | Caspase 7 influences susceptibility to rheumatoid arthritis. | García-Lozano JR et al |
| 14713958 | 2004 | Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease. | Hermel E et al |
| 19782763 | 2010 | Caspase-7: a protease involved in apoptosis and inflammation. | Lamkanfi M et al |
| 19058873 | 2009 | Polymorphisms in the Caspase7 gene and the risk of lung cancer. | Lee WK et al |
| 20453000 | 2010 | A Large-scale genetic association study of esophageal adenocarcinoma risk. | Liu CY et al |
| 16772874 | 2006 | Coordinated expression of caspase 8, 3 and 7 mRNA in temporal cortex of Alzheimer disease: relationship to formic acid extractable abeta42 levels. | Matsui T et al |
| 11381362 | 2001 | Caspase 7 downregulation as an immunohistochemical marker of colonic carcinoma. | Palmerini F et al |
| 22548721 | 2012 | Association between CASP7 and CASP14 genetic polymorphisms and the risk of childhood leukemia. | Park C et al |
| 22441531 | 2012 | Association of CASP7 polymorphisms and survival of patients with non-small cell lung cancer with platinum-based chemotherapy treatment. | Qian J et al |
| 12970753 | 2003 | Inactivating mutations of CASPASE-7 gene in human cancers. | Soung YH et al |
| 18785314 | 2008 | Genetic and expression analysis of CASP7 gene in a European Caucasian population with rheumatoid arthritis. | Teixeira VH et al |
| 7878464 | 1995 | Apoptosis in the pathogenesis and treatment of disease. | Thompson CB et al |
| 23920448 | 2013 | Loss of caspase 7 expression is associated with poor prognosis in renal cell carcinoma clear cell subtype. | Vilella-Arias SA et al |
| 19531679 | 2009 | Polymorphisms and haplotypes in the caspase-3, caspase-7, and caspase-8 genes and risk for endometrial cancer: a population-based, case-control study in a Chinese population. | Xu HL et al |
| 23765963 | 2013 | HuGE systematic review and meta-analysis demonstrate association of CASP-3 and CASP-7 genetic polymorphisms with cancer risk. | Yan S et al |
| 15511269 | 2004 | Loss of caspase-2, -6 and -7 expression in gastric cancers. | Yoo NJ et al |
| 19826114 | 2009 | Polymorphisms in the CASPASE genes and survival in patients with early-stage non-small-cell lung cancer. | Yoo SS et al |
Other Information
Locus ID:
NCBI: 840
MIM: 601761
HGNC: 1508
Ensembl: ENSG00000165806
Variants:
dbSNP: 840
ClinVar: 840
TCGA: ENSG00000165806
COSMIC: CASP7
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA164713176 | Platinum compounds | Chemical | ClinicalAnnotation | associated | PD | 22441531 | |
| PA443622 | Carcinoma, Non-Small-Cell Lung | Disease | ClinicalAnnotation | associated | PD | 22441531 | |
| PA449383 | docetaxel | Chemical | ClinicalAnnotation | associated | PD | 22441531 | |
| PA449748 | gemcitabine | Chemical | ClinicalAnnotation | associated | PD | 22441531 | |
| PA450761 | paclitaxel | Chemical | ClinicalAnnotation | associated | PD | 22441531 | |
| PA451881 | vinorelbine | Chemical | ClinicalAnnotation | associated | PD | 22441531 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37209562 | 2023 | TLR2 and CASP7 as the biomarkers associated with non-alcoholic fatty liver disease and chronic kidney disease. | 1 |
| 37209562 | 2023 | TLR2 and CASP7 as the biomarkers associated with non-alcoholic fatty liver disease and chronic kidney disease. | 1 |
| 32619291 | 2021 | Engineering caspase 7 as an affinity reagent to capture proteolytic products. | 0 |
| 32686156 | 2021 | Combination treatment of Src inhibitor Saracatinib with GMI, a Ganoderma microsporum immunomodulatory protein, induce synthetic lethality via autophagy and apoptosis in lung cancer cells. | 5 |
| 33469117 | 2021 | Role of CASP7 polymorphisms in noise-induced hearing loss risk in Han Chinese population. | 1 |
| 34156061 | 2021 | Characterization of caspase-7 interaction with RNA. | 1 |
| 32619291 | 2021 | Engineering caspase 7 as an affinity reagent to capture proteolytic products. | 0 |
| 32686156 | 2021 | Combination treatment of Src inhibitor Saracatinib with GMI, a Ganoderma microsporum immunomodulatory protein, induce synthetic lethality via autophagy and apoptosis in lung cancer cells. | 5 |
| 33469117 | 2021 | Role of CASP7 polymorphisms in noise-induced hearing loss risk in Han Chinese population. | 1 |
| 34156061 | 2021 | Characterization of caspase-7 interaction with RNA. | 1 |
| 31701491 | 2020 | Endocrine resistant breast cancer cells with loss of ERα expression retain proliferative ability by reducing caspase7-mediated HDAC3 cleavage. | 8 |
| 32051334 | 2020 | Autoimmune inner ear disease patient-associated 28-kDa proinflammatory IL-1β fragment results from caspase-7-mediated cleavage in vitro. | 4 |
| 32951155 | 2020 | The Relevance of SNPs at 3'UTR Region of CASP7 and miR-371b-5p Associated Diseases: A Computational Analysis. | 4 |
| 31701491 | 2020 | Endocrine resistant breast cancer cells with loss of ERα expression retain proliferative ability by reducing caspase7-mediated HDAC3 cleavage. | 8 |
| 32051334 | 2020 | Autoimmune inner ear disease patient-associated 28-kDa proinflammatory IL-1β fragment results from caspase-7-mediated cleavage in vitro. | 4 |
Citation
Cláudia Malheiros Coutinho-Camillo ; Fernando Augusto Soares
CASP7 (caspase 7, apoptosis-related cysteine peptidase)
Atlas Genet Cytogenet Oncol Haematol. 2014-06-01
Online version: http://atlasgeneticsoncology.org/gene/924/casp7-(caspase-7-apoptosis-related-cysteine-peptidase)
