CASP7 (caspase 7, apoptosis-related cysteine peptidase)

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

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

Identity

HGNC

CASP7

LOCATION

10q25.3

LOCUSID

840

ALIAS

CASP-7,CMH-1,ICE-LAP3,LICE2,MCH3

FUSION GENES

Show Gene Fusions

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).

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.

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.

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.

Entity name

Gastric cancer

Note

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

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.

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

Gene ID	Transcript ID	Uniprot
ENSG00000165806	ENST00000345633	P55210
ENSG00000165806	ENST00000369315	P55210
ENSG00000165806	ENST00000369318	P55210
ENSG00000165806	ENST00000369321	A0A0A0MRL7
ENSG00000165806	ENST00000369331	P55210
ENSG00000165806	ENST00000429617	Q5SVL2
ENSG00000165806	ENST00000452490	P55210
ENSG00000165806	ENST00000614447	P55210
ENSG00000165806	ENST00000621345	P55210
ENSG00000165806	ENST00000621607	P55210

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Apoptosis	KEGG	ko04210
Alzheimer's disease	KEGG	ko05010
Apoptosis	KEGG	hsa04210
Alzheimer's disease	KEGG	hsa05010
Pertussis	KEGG	ko05133
Pertussis	KEGG	hsa05133
Legionellosis	KEGG	ko05134
Legionellosis	KEGG	hsa05134
TNF signaling pathway	KEGG	hsa04668
TNF signaling pathway	KEGG	ko04668
Non-alcoholic fatty liver disease (NAFLD)	KEGG	hsa04932
Non-alcoholic fatty liver disease (NAFLD)	KEGG	ko04932
Apoptotic machinery	KEGG	hsa_M00685
Apoptotic machinery	KEGG	M00685
Programmed Cell Death	REACTOME	R-HSA-5357801
Apoptosis	REACTOME	R-HSA-109581
Intrinsic Pathway for Apoptosis	REACTOME	R-HSA-109606
Apoptotic factor-mediated response	REACTOME	R-HSA-111471
Cytochrome c-mediated apoptotic response	REACTOME	R-HSA-111461
Activation of caspases through apoptosome-mediated cleavage	REACTOME	R-HSA-111459
SMAC-mediated apoptotic response	REACTOME	R-HSA-111469
SMAC binds to IAPs	REACTOME	R-HSA-111463
SMAC-mediated dissociation of IAP:caspase complexes	REACTOME	R-HSA-111464
Apoptotic execution phase	REACTOME	R-HSA-75153
Apoptotic cleavage of cellular proteins	REACTOME	R-HSA-111465
Caspase-mediated cleavage of cytoskeletal proteins	REACTOME	R-HSA-264870
Apoptosis - multiple species	KEGG	ko04215
Apoptosis - multiple species	KEGG	hsa04215

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association	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