CASP7 (caspase 7, apoptosis-related cysteine peptidase)

2014-06-01   Cláudia Malheiros Coutinho-Camillo , Fernando Augusto Soares 

Department of Anatomic Pathology, AC Camargo Cancer Center, Sao Paulo, Brazil




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).


Atlas Image
CASP7 transcript variants. Coding exons are marked by blue blocks, and non-coding exons, 5- and 3-UTRs are marked by white blocks.


CASP7 gene contains 8 exons and spans 51.748 Kb of genomic DNA.


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).


Not identified.


Atlas Image
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).


Caspase-7 is an effector caspase and plays an central role in the execution phase of the apoptosis.


Caspase-7 is widely expressed in human tissues. Highly expressed in lung, skeletal muscle, liver, kidney, spleen and heart, and moderately in testis.


Mainly in the cytoplasm, but also observed in the nucleus.


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.


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).



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.

Implicated in

Entity name
Lung cancer
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.
Entity name
Esophageal cancer
Liu et al. (2010) described that polymorphisms in CASP7 gene was associated with increased risk of esophageal cancer.
Entity name
Childhood leukemia
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
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.
Entity name
Gastric cancer
Yoo et al. (2004) observed loss of capase-2, capase-6 and capase-7 expression in gastric cancers irrespective of depth of invasion and histological subtypes suggesting a role in the development of gastric cancers.
Entity name
Endometrial cancer
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
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
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
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
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
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.
Entity name
Insulin-dependent diabetes mellitus
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.


Pubmed IDLast YearTitleAuthors
146790872003Caspase 7 is a positional candidate gene for IDDM 17 in a Bedouin Arab family.Babu SR et al
146441972003Mechanisms of caspase activation.Boatright KM et al
205678462011RIPK1 and CASP7 polymorphism as prognostic markers for survival in patients with colorectal cancer after complete resection.Chae YS et al
93378441997Caspases: the executioners of apoptosis.Cohen GM et al
217555622011Caspase expression in oral squamous cell carcinoma.Coutinho-Camillo CM et al
124751982002Caspases: keys in the ignition of cell death.Denault JB et al
175048202007Caspase 7 influences susceptibility to rheumatoid arthritis.García-Lozano JR et al
147139582004Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease.Hermel E et al
197827632010Caspase-7: a protease involved in apoptosis and inflammation.Lamkanfi M et al
190588732009Polymorphisms in the Caspase7 gene and the risk of lung cancer.Lee WK et al
204530002010A Large-scale genetic association study of esophageal adenocarcinoma risk.Liu CY et al
167728742006Coordinated 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
113813622001Caspase 7 downregulation as an immunohistochemical marker of colonic carcinoma.Palmerini F et al
225487212012Association between CASP7 and CASP14 genetic polymorphisms and the risk of childhood leukemia.Park C et al
224415312012Association of CASP7 polymorphisms and survival of patients with non-small cell lung cancer with platinum-based chemotherapy treatment.Qian J et al
129707532003Inactivating mutations of CASPASE-7 gene in human cancers.Soung YH et al
187853142008Genetic and expression analysis of CASP7 gene in a European Caucasian population with rheumatoid arthritis.Teixeira VH et al
78784641995Apoptosis in the pathogenesis and treatment of disease.Thompson CB et al
239204482013Loss of caspase 7 expression is associated with poor prognosis in renal cell carcinoma clear cell subtype.Vilella-Arias SA et al
195316792009Polymorphisms 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
237659632013HuGE systematic review and meta-analysis demonstrate association of CASP-3 and CASP-7 genetic polymorphisms with cancer risk.Yan S et al
155112692004Loss of caspase-2, -6 and -7 expression in gastric cancers.Yoo NJ et al
198261142009Polymorphisms 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


dbSNP: 840
ClinVar: 840
TCGA: ENSG00000165806


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Alzheimer's diseaseKEGGko05010
Alzheimer's diseaseKEGGhsa05010
TNF signaling pathwayKEGGhsa04668
TNF signaling pathwayKEGGko04668
Non-alcoholic fatty liver disease (NAFLD)KEGGhsa04932
Non-alcoholic fatty liver disease (NAFLD)KEGGko04932
Apoptotic machineryKEGGhsa_M00685
Apoptotic machineryKEGGM00685
Programmed Cell DeathREACTOMER-HSA-5357801
Intrinsic Pathway for ApoptosisREACTOMER-HSA-109606
Apoptotic factor-mediated responseREACTOMER-HSA-111471
Cytochrome c-mediated apoptotic responseREACTOMER-HSA-111461
Activation of caspases through apoptosome-mediated cleavageREACTOMER-HSA-111459
SMAC-mediated apoptotic responseREACTOMER-HSA-111469
SMAC binds to IAPsREACTOMER-HSA-111463
SMAC-mediated dissociation of IAP:caspase complexesREACTOMER-HSA-111464
Apoptotic execution phaseREACTOMER-HSA-75153
Apoptotic cleavage of cellular proteinsREACTOMER-HSA-111465
Caspase-mediated cleavage of cytoskeletal proteinsREACTOMER-HSA-264870
Apoptosis - multiple speciesKEGGko04215
Apoptosis - multiple speciesKEGGhsa04215

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA164713176Platinum compoundsChemicalClinicalAnnotationassociatedPD22441531
PA443622Carcinoma, Non-Small-Cell LungDiseaseClinicalAnnotationassociatedPD22441531


Pubmed IDYearTitleCitations
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
163854512006A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.69
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
197827632010Caspase-7: a protease involved in apoptosis and inflammation.58
224519312012Caspase-7 uses an exosite to promote poly(ADP ribose) polymerase 1 proteolysis.41
229865252013MicroRNA-106b-25 cluster expression is associated with early disease recurrence and targets caspase-7 and focal adhesion in human prostate cancer.41
146238962004STAT1-induced apoptosis is mediated by caspases 2, 3, and 7.40
128241632003Human caspase-7 activity and regulation by its N-terminal peptide.37
197590582009Proteome-wide substrate analysis indicates substrate exclusion as a mechanism to generate caspase-7 versus caspase-3 specificity.34
211574282011Caspase-8 and caspase-7 sequentially mediate proteolytic activation of acid sphingomyelinase in TNF-R1 receptosomes.30


Cláudia Malheiros Coutinho-Camillo ; Fernando Augusto Soares

CASP7 (caspase 7, apoptosis-related cysteine peptidase)

Atlas Genet Cytogenet Oncol Haematol. 2014-06-01

Online version: