GZMB (Granzyme B)
A key serine protease in cytotoxic lymphocyte-mediated apoptosis and immune regulation
Gene Information Card
| Symbol | GZMB |
|---|---|
| Full Name | Granzyme B |
| Gene Type | Protein coding |
| Chromosomal Location | 14q12 |
| NCBI Gene ID | 3002 ncbi.nlm.nih.gov/gene/3002 |
| Ensembl ID | ENSG00000100453 |
| UniProt ID | P10144 |
| OMIM ID | 190230 |
| HGNC ID | 4709 |
| Aliases | CGL1, CGL-1, CSPB, CTLA1, HLP, SECT |
Description
GZMB encodes granzyme B, a serine protease stored in the granules of cytotoxic T lymphocytes and natural killer cells. Upon target cell recognition, granzyme B is released and enters the target cell via perforin-dependent mechanisms, where it cleaves caspases and other substrates to induce apoptosis. It plays a critical role in immune defense against viruses and tumors, and its dysregulation is implicated in autoimmune diseases, transplant rejection, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rheumatoid arthritis | Elevated granzyme B levels contribute to synovial inflammation and joint destruction via enhanced apoptosis of chondrocytes and synovial fibroblasts. | PMID: 14525957 |
| Systemic lupus erythematosus | Increased GZMB expression in CD8+ T cells correlates with disease activity and tissue damage. | PMID: 23449742 |
| Viral infections (e.g., influenza, HIV) | Granzyme B mediates clearance of infected cells; reduced activity linked to viral persistence. | PMID: 12626582 |
| Cancer (various) | Dual role: promotes anti-tumor immunity but also contributes to immune evasion via tumor cell resistance mechanisms. | PMID: 26642240 |
| Graft-versus-host disease | Donor cytotoxic T cells use granzyme B to attack recipient tissues, causing organ damage. | PMID: 15657182 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | High |
| Lymph node | 10.8 | High |
| Bone marrow | 8.2 | Medium |
| Lung | 3.1 | Low |
| Small intestine | 2.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NK-92 (NK cell line) | 45.6 | High expression; used as positive control |
| Jurkat (T cell line) | 22.3 | Moderate expression; inducible upon activation |
| K562 (erythroleukemia) | 1.2 | Low expression; negative control |
| HeLa (cervical cancer) | 0.8 | Very low; not typically expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.236A>G (p.Tyr79Cys) | Missense | <0.01% | Reduced catalytic activity; associated with impaired cytotoxic function |
| c.550G>A (p.Gly184Arg) | Missense | <0.01% | Altered substrate binding; potential loss of function |
| c.637C>T (p.Arg213Trp) | Missense | <0.01% | Decreased stability; reported in immunodeficient patients |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Tyr79Cys, p.Gly184Arg) reduce catalytic activity or protein stability, impairing granzyme B-mediated apoptosis.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in GZMB.
Dominant Negative (DN)
Not described for GZMB; granzyme B functions as a monomer, and dominant-negative effects are unlikely.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Perforin/granzyme B apoptotic pathway (KEGG: hsa04650)
• Natural killer cell mediated cytotoxicity (KEGG: hsa04650)
• Apoptosis (Reactome: R-HSA-109581)
Protein Summary
Granzyme B is a 247-amino-acid serine protease (32 kDa) with a catalytic triad (His57, Asp102, Ser195). It is synthesized as a zymogen and activated by cathepsin C cleavage. The mature protein contains a signal peptide for granule targeting. Its structure includes a typical chymotrypsin-like fold with specificity for aspartic acid residues (Aspase activity). Upon entry into target cells, it cleaves and activates caspases (e.g., caspase-3, -7) and directly processes Bid to trigger mitochondrial outer membrane permeabilization, amplifying the apoptotic cascade.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GZMB Knockout HEK293 Cell Line | EDJ-KQ3597 | Human | 3002 | Details Get a Quote |
| GZMB Knockout HeLa Cell Line | EDJ-KQ53472 | Human | 3002 | Details Get a Quote |
| GZMB Knockout A-549 Cell Line | EDJ-KQ61944 | Human | 3002 | Details Get a Quote |
| GZMB Knockout HCT 116 Cell Line | EDJ-KQ70425 | Human | 3002 | Details Get a Quote |
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