CASP12
protein-codingcaspase 12 (gene/pseudogene), the group of Caspases|Caspase recruitment domain containing
Gene summary
Caspases are cysteine proteases that cleave C-terminal aspartic acid residues on their substrate molecules. This gene is most highly related to members of the ICE subfamily of caspases that process inflammatory cytokines. In rodents, the homolog of this gene mediates apoptosis in response to endoplasmic reticulum stress. However, in humans this gene contains a polymorphism for the presence or absence of a premature stop codon. The majority of human individuals have the premature stop codon and produce a truncated non-functional protein. The read-through codon occurs primarily in individuals of African descent and carriers have endotoxin hypo-responsiveness and an increased susceptibility to severe sepsis. Several alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Feb 2011]
- CASP12P1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.0 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 CASP12 variants in ClinVar
No annotated ClinVar phenotypes.
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . 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 | 23 | 1 | 1 | 25 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 23 | 1 | 2 | 26 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| Ensembl | ENSP00000424038.1 | 7 | Standard | |
| Ensembl | ENSP00000424963.1 | 4 | Standard | |
| Ensembl | ENSP00000427437.1 | 4 | Standard | |
| Ensembl | ENSP00000423970.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Prion diseases - Homo sapiens (human)
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- Alzheimer,s disease - Homo sapiens (human)
- Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human)
- NOD-like receptor signaling pathway - Homo sapiens (human)
Biological Process
- proteolysis
- apoptotic process
- activation of cysteine-type endopeptidase activity involved in apoptotic process
- apoptotic signaling pathway
- execution phase of apoptosis
Molecular Function
- cysteine-type endopeptidase activity
- cysteine-type endopeptidase activity involved in apoptotic process
- cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Cellular Component
- cytoplasm
- endoplasmic reticulum
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000422698
- Coding exons
- 7
- Length
- 12953
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.26 | 117 | 162 | 0.722 | 0.00000765 | 2257 |
| Missense (PolyPhen) | 33 | 43.195 | 0.76398 | 630 | ||
| Synonymous | 2.39 | 34 | 56.9 | 0.597 | 0.00000270 | 617 |
| Loss of Function | 1.34 | 8 | 13.3 | 0.603 | 7.04e-7 | 177 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has no protease activity. May reduce cytokine release in response to bacterial lipopolysaccharide during infections. Reduces activation of NF-kappa-B in response to TNF. {ECO:0000269|PubMed:12054529, ECO:0000269|PubMed:15129283}.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |