CASP12 (Caspase 12)
Gene encoding a cysteine-aspartic protease involved in endoplasmic reticulum stress-induced apoptosis and inflammation.
Gene Information Card
| Symbol | CASP12 |
|---|---|
| Full Name | caspase 12 (gene/pseudogene) |
| Gene Type | protein-coding (pseudogene in most human populations) |
| Chromosomal Location | 11q22.3 |
| NCBI Gene ID | 100506742 ncbi.nlm.nih.gov/gene/100506742 |
| Ensembl ID | ENSG00000204442 |
| UniProt ID | Q6UXS9 |
| OMIM ID | 608633 |
| HGNC ID | 19004 |
| Aliases | CASP12P1, CASP-12, caspase 12 pseudogene 1 |
Description
CASP12 encodes a cysteine-aspartic protease (caspase 12) that is primarily involved in endoplasmic reticulum (ER) stress-induced apoptosis. In most human populations, the gene carries a frameshift mutation resulting in a truncated, non-functional protein (pseudogene). A functional variant exists in some individuals of African descent and is associated with altered inflammatory responses and susceptibility to sepsis. CASP12 is located on chromosome 11q22.3 within the caspase gene cluster.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sepsis | Functional CASP12 attenuates the inflammatory response by inhibiting caspase-1 activation and IL-1β production, reducing sepsis severity. | ClinVar, OMIM |
| Alzheimer disease | CASP12 activation in ER stress contributes to neuronal apoptosis; polymorphisms may modulate risk. | NCBI Gene, OMIM |
| Inflammatory bowel disease | Loss-of-function variants may alter cytokine responses, affecting disease susceptibility. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 0.2 | Low |
| Kidney | 0.1 | Low |
| Brain | 0.3 | Low |
| Lung | 0.1 | Low |
| Colon | 0.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 0.1 | Low expression; pseudogene status |
| HeLa | 0.2 | Low expression |
| HepG2 | 0.3 | Low expression |
| THP-1 | 0.4 | Slightly higher; monocytic lineage |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.125C>T (p.Thr42Ile) | Missense | Rare | Unknown functional impact |
| c.184_185insT (frameshift) | Insertion | Common (non-functional allele) | Loss of function; pseudogene conversion |
Mutation functional classification
Loss of Function (LOF)
The common frameshift insertion (c.184_185insT) results in a premature stop codon, producing a truncated, non-functional protein. This is the predominant allele in non-African populations.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CASP12.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for CASP12.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type endopeptidase activity (GO:0004197) | • proteolysis (GO:0006508) |
| • apoptotic process (GO:0006915) | • intrinsic apoptotic signaling pathway in response to ER stress (GO:0008629) |
| • endoplasmic reticulum unfolded protein response (GO:0030968) | • defense response to virus (GO:0051607) |
Pathways
• Endoplasmic reticulum stress pathway (UniProt)
• Caspase activation via ER stress (Reactome: R-HSA-140534)
Protein Summary
Caspase 12 is a cysteine-aspartic protease that localizes to the endoplasmic reticulum. It is activated by ER stress (e.g., unfolded protein response) and mediates apoptosis by cleaving downstream substrates. In humans, most individuals carry a loss-of-function allele due to a frameshift mutation, rendering the protein inactive. The functional variant, found primarily in individuals of African ancestry, can modulate inflammatory responses by inhibiting caspase-1 and IL-1β production. The protein contains a caspase recruitment domain (CARD) and a catalytic cysteine domain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CASP12 Knockout HEK293 Cell Line | EDJ-KQ7663 | Human | 100506742 | Details Get a Quote |
| CASP12 Knockout A-549 Cell Line | EDJ-KQ33020 | Human | 100506742 | Details Get a Quote |
| CASP12 Knockout HCT 116 Cell Line | EDJ-KQ33021 | Human | 100506742 | Details Get a Quote |
| CASP12 Knockout HeLa Cell Line | EDJ-KQ33022 | Human | 100506742 | Details Get a Quote |
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