CASP1
protein-codingcaspase 1, the group of Caspase recruitment domain containing|Caspases
Gene summary
This gene encodes a protein which is 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 2 subunits, large and small, that dimerize to form the active enzyme. This gene was identified by its ability to proteolytically cleave and activate the inactive precursor of interleukin-1, a cytokine involved in the processes such as inflammation, septic shock, and wound healing. This gene has been shown to induce cell apoptosis and may function in various developmental stages. Studies of a similar gene in mouse suggest a role in the pathogenesis of Huntington disease. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012]
- IL1BC
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.9 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 CASP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001257118.3. 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 | 1 | 3 | 1 | 5 | ||
| missense | 52 | 9 | 2 | 63 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 56 | 12 | 3 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001244047.1 | 9 | MANE Select | |
| Ensembl | ENSP00000433138.1 | 9 | MANE Select | |
| RefSeq | NP_001214.1 | 8 | Standard | |
| RefSeq | NP_001244048.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pertussis - Homo sapiens (human)
- Salmonella infection - Homo sapiens (human)
- Legionellosis - Homo sapiens (human)
- Influenza A - Homo sapiens (human)
- Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human)
Biological Process
- proteolysis
- apoptotic process
- activation of cysteine-type endopeptidase activity involved in apoptotic process
- signal transduction
- protein autoprocessing
Molecular Function
- endopeptidase activity
- cysteine-type endopeptidase activity
- protein binding
- cysteine-type endopeptidase activator activity involved in apoptotic process
- kinase binding
Cellular Component
- cytoplasm
- cytosol
- protein-containing complex
- IPAF inflammasome complex
- NLRP1 inflammasome complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000533400
- Coding exons
- 9
- Length
- 75989
- Individuals with no LoFs
- 125703
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 39
- Defined
- 125742
- p
- 0.000155
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0593 | 226 | 224 | 1.01 | 0.0000119 | 2669 |
| Missense (PolyPhen) | 71 | 83.158 | 0.8538 | 1024 | ||
| Synonymous | 0.154 | 76 | 77.7 | 0.978 | 0.00000410 | 761 |
| Loss of Function | 1.81 | 10 | 18.4 | 0.545 | 8.68e-7 | 229 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00058 | 0.00058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.00027 | 0.00026 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis. Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive (PubMed:28314590). {ECO:0000269|PubMed:15498465, ECO:0000269|PubMed:1574116, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:7876192}.;
Recessive Scores
- pRec
- 0.586
Intolerance Scores
- LoFtool
- 0.831
- RVIS EVS
- 0.44
- RVIS percentile EVS
- 77.8
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.509
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |