CASP4
caspase 4, the group of Caspase recruitment domain containing|Caspases
Basic information
Region (hg38): 11:104942866-104969366
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (44 variants)
- not_provided (3 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CASP4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001225.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 40 | 46 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 40 | 4 | 3 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CASP4 | protein_coding | protein_coding | ENST00000444739 | 8 | 26571 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.05e-8 | 0.525 | 125521 | 1 | 204 | 125726 | 0.000816 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.176 | 201 | 208 | 0.966 | 0.0000107 | 2497 |
| Missense in Polyphen | 57 | 68.298 | 0.83458 | 855 | ||
| Synonymous | -1.32 | 88 | 73.5 | 1.20 | 0.00000384 | 691 |
| Loss of Function | 1.01 | 14 | 18.7 | 0.747 | 9.80e-7 | 221 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000370 | 0.000369 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000272 | 0.000272 |
| Finnish | 0.00555 | 0.00551 |
| European (Non-Finnish) | 0.000653 | 0.000642 |
| Middle Eastern | 0.000272 | 0.000272 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000166 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Inflammatory caspase (PubMed:7797510, PubMed:23516580, PubMed:25119034). Essential effector of NLRP3 inflammasome- dependent CASP1 activation and IL1B and IL18 secretion in response to non-canonical activators, such as UVB radiation, cholera enterotoxin subunit B and cytosolic LPS (PubMed:22246630, PubMed:26174085, PubMed:26173988, PubMed:26508369, PubMed:25964352). Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, and IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators (PubMed:24879791, PubMed:25964352). Plays a crucial role in the restriction of Salmonella typhimurium replication in colonic epithelial cells during infection (PubMed:25121752). In later stages of the infection, LPS from cytosolic Salmonella triggers CASP4 activation, which ultimately results in pyroptosis of infected cells and their extrusion into the gut lumen, as well as in IL18 secretion. Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation. Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity (PubMed:26508369). Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found Alzheimer's patient brains (PubMed:15123740, PubMed:22246630, PubMed:23661706). Activated by direct binding to LPS without the need of an upstream sensor (PubMed:25119034). Does not directly process IL1B (PubMed:7743998, PubMed:7797592, PubMed:7797510). 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:15123740, ECO:0000269|PubMed:22246630, ECO:0000269|PubMed:23516580, ECO:0000269|PubMed:23661706, ECO:0000269|PubMed:24879791, ECO:0000269|PubMed:25119034, ECO:0000269|PubMed:25121752, ECO:0000269|PubMed:25964352, ECO:0000269|PubMed:26173988, ECO:0000269|PubMed:26174085, ECO:0000269|PubMed:26508369, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:7743998, ECO:0000269|PubMed:7797510, ECO:0000269|PubMed:7797592}.;
- Pathway
- NOD-like receptor signaling pathway - Homo sapiens (human);Apoptosis Modulation and Signaling;Apoptosis;Apoptotic Signaling Pathway;caspase cascade in apoptosis;internal ribosome entry pathway;NOD1/2 Signaling Pathway;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;DroToll-like;Innate Immune System;Immune System
(Consensus)
Recessive Scores
- pRec
- 0.246
Intolerance Scores
- loftool
- 0.981
- rvis_EVS
- 0.22
- rvis_percentile_EVS
- 68.44
Haploinsufficiency Scores
- pHI
- 0.262
- hipred
- N
- hipred_score
- 0.318
- ghis
- 0.529
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.909
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Casp4
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; immune system phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm;
Gene ontology
- Biological process
- proteolysis;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;inflammatory response;innate immune response;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress;intrinsic apoptotic signaling pathway;execution phase of apoptosis;positive regulation of tumor necrosis factor-mediated signaling pathway;cellular response to amyloid-beta
- Cellular component
- extracellular region;cytoplasm;mitochondrion;endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;plasma membrane;protein-containing complex;inflammasome complex
- Molecular function
- cysteine-type endopeptidase activity;CARD domain binding;cysteine-type endopeptidase activity involved in apoptotic process;cysteine-type endopeptidase activity involved in apoptotic signaling pathway