CASP7

protein-coding

caspase 7, the group of Caspases

Gene summary

This gene encodes 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 which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. The precursor of the encoded protein is cleaved by caspase 3 and 10, is activated upon cell death stimuli and induces apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

MANE transcript

NM_001227.5

Inheritance

—

ClinVar variants

U:52B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr10:113,679,162-113,730,907

External References & Databases

Ensembl (ENSG00000165806)

Transcript & Mutation Effects

hg38 • Region Span ~51.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CASP7 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 49

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001227.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar	1 clinvar	5
missense			50 clinvar	3 clinvar		53
nonsense						0
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	52	7	1	60

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 66 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001227.5	RefSeq	NP_001218.1	6	MANE Select
ENST00000369318.8	Ensembl	ENSP00000358324.4	6	MANE Select
NM_001267056.2	RefSeq	NP_001253985.1	6	Standard
NM_001267057.1	RefSeq	NP_001253986.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pertussis - Homo sapiens (human)
Legionellosis - Homo sapiens (human)
Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
Apoptosis - multiple species - Homo sapiens (human)
Alzheimer,s disease - Homo sapiens (human)

Biological Process

proteolysis
apoptotic process
cellular response to staurosporine
execution phase of apoptosis

Molecular Function

cysteine-type endopeptidase activity
protein binding
peptidase activity
cysteine-type peptidase activity
cysteine-type endopeptidase activity involved in apoptotic process

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369321
Coding exons: 7
Length: 51721
Individuals with no LoFs: 125705
Homozygous LoFs: 0
Heterozygous LoFs: 43
Defined: 125748
p: 0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.703	165	192	0.857	0.0000104	2245
Missense (PolyPhen)		39	55.177	0.70682		665
Synonymous	-0.966	85	74.4	1.14	0.00000463	606
Loss of Function	1.98	10	19.4	0.515	0.00000130	191

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly- 217' bond. Overexpression promotes programmed cell death.;

Recessive Scores

pRec: 0.403

Intolerance Scores

LoFtool: 0.897
RVIS EVS: 0.62
RVIS percentile EVS: 83.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.920

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium