CASP5
protein-codingcaspase 5, the group of Caspases|Caspase recruitment domain containing
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. Overexpression of the active form of this enzyme induces apoptosis in fibroblasts. Max, a central component of the Myc/Max/Mad transcription regulation network important for cell growth, differentiation, and apoptosis, is cleaved by this protein; this process requires Fas-mediated dephosphorylation of Max. The expression of this gene is regulated by interferon-gamma and lipopolysaccharide. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Aug 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.9 kbGenCC 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 CASP5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004347.5. 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 | 0 | |||||
| missense | 65 | 10 | 75 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 68 | 10 | 0 | 78 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004338.3 | 9 | MANE Select | |
| Ensembl | ENSP00000260315.3 | 9 | MANE Select | |
| RefSeq | NP_001129581.1 | 8 | Standard | |
| RefSeq | NP_001129582.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- NOD-like receptor signaling pathway - Homo sapiens (human)
- Nucleotide-binding Oligomerization Domain (NOD) pathway
- Vitamin D Receptor Pathway
- internal ribosome entry pathway
- DroToll-like
Biological Process
- proteolysis
- apoptotic process
- activation of cysteine-type endopeptidase activity involved in apoptotic process
- substantia nigra development
- cellular response to mechanical stimulus
Molecular Function
- cysteine-type endopeptidase activity
- cysteine-type peptidase activity
- cysteine-type endopeptidase activity involved in apoptotic process
- cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Cellular Component
- cytoplasm
- NLRP1 inflammasome complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393141
- Coding exons
- 9
- Length
- 28934
- Individuals with no LoFs
- 125270
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 474
- Defined
- 125746
- p
- 0.00189
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.468 | 231 | 252 | 0.917 | 0.0000136 | 2960 |
| Missense (PolyPhen) | 58 | 67.072 | 0.86475 | 844 | ||
| Synonymous | -1.60 | 112 | 92.5 | 1.21 | 0.00000538 | 829 |
| Loss of Function | -0.407 | 23 | 21.0 | 1.10 | 0.00000117 | 257 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0021 | 0.0021 | notable |
| Latino/Admixed American | 0.0025 | 0.0024 | notable |
| Ashkenazi Jewish | 0.00089 | 0.00089 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.0027 | 0.0026 | notable |
| South Asian | 0.00083 | 0.00082 | rare |
| Other | 0.0030 | 0.0029 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediator of programmed cell death (apoptosis). During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590). {ECO:0000269|PubMed:28314590}.;
Recessive Scores
- pRec
- 0.115
Intolerance Scores
- LoFtool
- 0.996
- RVIS EVS
- 1.2
- RVIS percentile EVS
- 92.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.235
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |