CASP8 (Caspase 8) Gene
Key regulator of extrinsic apoptosis and immune signaling
Gene Information Card
| Symbol | CASP8 |
|---|---|
| Full Name | Caspase 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q33.1 |
| NCBI Gene ID | 841 ncbi.nlm.nih.gov/gene/841 |
| Ensembl ID | ENSG00000064012 |
| UniProt ID | Q14790 |
| OMIM ID | 601763 |
| HGNC ID | 1509 |
| Aliases | CAP4, FLICE, MACH, MCH5 |
Description
CASP8 encodes caspase 8, a cysteine-aspartic protease that plays a central role in the extrinsic apoptotic pathway. Upon death receptor (e.g., Fas, TRAIL-R) activation, caspase 8 is recruited to the death-inducing signaling complex (DISC) via FADD, leading to its proteolytic activation. Active caspase 8 then cleaves downstream effector caspases (e.g., caspase 3) to execute apoptosis. Additionally, caspase 8 modulates NF-κB signaling and inflammasome regulation. Loss-of-function mutations are associated with autoimmune lymphoproliferative syndrome (ALPS) and increased cancer susceptibility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune lymphoproliferative syndrome type IIB (ALPS2B) | Defective apoptosis due to CASP8 mutations leads to impaired lymphocyte death, causing lymphoproliferation and autoimmunity. | OMIM #601763; PMID: 10430621 |
| Hepatocellular carcinoma | Reduced CASP8 expression or promoter methylation contributes to evasion of apoptosis in liver cancer cells. | COSMIC; PMID: 15064718 |
| Gastric cancer | Somatic CASP8 mutations (e.g., R248W) impair caspase activity and are associated with microsatellite instability. | COSMIC; PMID: 15199140 |
| Breast cancer | CASP8 polymorphisms (e.g., D302H) modulate apoptosis and influence risk. | ClinVar; PMID: 17999357 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Small intestine | 8.2 | Medium |
| Liver | 6.1 | Low |
| Brain | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 15.2 | High expression; used in apoptosis studies |
| HeLa (cervical carcinoma) | 9.8 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 5.4 | Low expression; often silenced |
| MCF7 (breast carcinoma) | 7.1 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1225C>T (p.R409W) | Missense | <0.1% | Loss of function; associated with ALPS2B |
| c.742G>A (p.D248N) | Missense | <0.1% | Impaired DISC recruitment; reduced apoptosis |
| c.1A>G (p.M1V) | Missense | <0.1% | Start codon loss; complete loss of protein |
| c.1087C>T (p.R363*) | Nonsense | <0.1% | Premature truncation; loss of catalytic domain |
Mutation functional classification
Loss of Function (LOF)
Most CASP8 mutations are loss-of-function, impairing caspase 8 activation or catalytic activity, leading to defective apoptosis and immune dysregulation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in CASP8.
Dominant Negative (DN)
Some missense mutations (e.g., R409W) act in a dominant-negative manner by forming inactive heterodimers with wild-type caspase 8.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type endopeptidase activity involved in apoptotic process (GO:0097153) | • death receptor binding (GO:0035329) |
| • FADD binding (GO:0045259) | • proteolysis (GO:0006508) |
| • extrinsic apoptotic signaling pathway (GO:0097191) | • activation of cysteine-type endopeptidase activity involved in apoptotic process (GO:0006919) |
Pathways
• Extrinsic Apoptosis Pathway (KEGG: hsa04210)
• Fas Signaling Pathway (Reactome: R-HSA-75153)
• TRAIL Signaling Pathway (Reactome: R-HSA-75157)
• NF-kappa B Signaling (Reactome: R-HSA-975138)
Protein Summary
Caspase 8 is a 479-amino acid protein (55 kDa) composed of two death effector domains (DED) at the N-terminus and a C-terminal catalytic cysteine protease domain. The DEDs mediate recruitment to the DISC via interaction with FADD. Proteolytic cleavage between the large and small subunits generates active heterotetramers. Caspase 8 is a key initiator of extrinsic apoptosis and also participates in non-apoptotic functions including cell migration and immune regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CASP8 Knockout HEK293 Cell Line | EDJ-KQ1474 | Human | 841 | Details Get a Quote |
| CASP8AP2 Knockout HEK293 Cell Line | EDJ-KQ12733 | Human | 9994 | Details Get a Quote |
| CASP8 Knockout A-549 Cell Line | EDC07644 | Human | 841 | Details Get a Quote |
| CASP8 Knockout HCT 116 Cell Line | EDJ-KQ21053 | Human | 841 | Details Get a Quote |
| CASP8 Knockout HeLa Cell Line | EDJ-KQ19719 | Human | 841 | Details Get a Quote |
| CASP8AP2 Knockout A-549 Cell Line | EDJ-KQ41833 | Human | 9994 | Details Get a Quote |
| CASP8AP2 Knockout HCT 116 Cell Line | EDJ-KQ41834 | Human | 9994 | Details Get a Quote |
| CASP8AP2 Knockout HeLa Cell Line | EDJ-KQ41835 | Human | 9994 | Details Get a Quote |
| CASP8 Knockout L-02 Cell Line | EDC08136 | Human | 841 | Details Get a Quote |
| CASP8 Knockout A-375 Cell Line | EDC90184 | Human | 841 | Details Get a Quote |
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