GZMA (Granzyme A) Gene
Cytotoxic T-lymphocyte and NK cell serine protease involved in immune-mediated cell death
Gene Information Card
| Symbol | GZMA |
|---|---|
| Full Name | Granzyme A |
| Gene Type | Protein coding |
| Chromosomal Location | 5q11.2 |
| NCBI Gene ID | 3001 ncbi.nlm.nih.gov/gene/3001 |
| Ensembl ID | ENSG00000145649 |
| UniProt ID | P12544 |
| OMIM ID | 140050 |
| HGNC ID | 4709 |
| Aliases | CTLA3, HFSP, granzyme 1, HuTSP, TSP1 |
Description
GZMA (granzyme A) is a member of the granzyme serine protease family, primarily expressed in cytotoxic T lymphocytes and natural killer (NK) cells. It plays a critical role in immune-mediated target cell death by inducing apoptosis through a caspase-independent pathway. Granzyme A cleaves substrates such as SET complex components, leading to DNA damage and cell death. The gene is located on chromosome 5q11.2 and spans approximately 4.5 kb.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune lymphoproliferative syndrome (ALPS) | Defective granzyme A-mediated apoptosis may contribute to impaired lymphocyte homeostasis | PMID: 12590259 |
| Rheumatoid arthritis | Elevated granzyme A levels in synovial fluid and tissue correlate with inflammation and joint destruction | PMID: 10852722 |
| Viral infections (e.g., influenza, HIV) | Granzyme A contributes to antiviral immunity by inducing apoptosis in infected cells | PMID: 16920955 |
| Cancer (various) | Granzyme A expression in tumor-infiltrating lymphocytes is associated with favorable prognosis in some cancers | PMID: 23589565 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.3 | Medium |
| Lymph node | 15.1 | Medium |
| Bone marrow | 8.7 | Low |
| Lung | 2.4 | Low |
| Small intestine | 1.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NK-92 (NK cell line) | 45.2 | High expression |
| Jurkat (T cell line) | 22.8 | Moderate expression |
| K562 (erythroleukemia) | 3.1 | Low expression |
| HeLa (cervical carcinoma) | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.275G>A (p.Arg92Gln) | Missense | <0.01% | Reduced enzymatic activity in vitro |
| c.487C>T (p.Arg163Trp) | Missense | <0.01% | Unknown functional effect |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Predicted loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Arg92Gln) reduce catalytic activity; start-loss variant p.Met1Val likely abolishes translation.
Gain of Function (GOF)
No gain-of-function mutations reported in GZMA.
Dominant Negative (DN)
No dominant-negative mutations described for GZMA.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Granzyme A-mediated apoptosis pathway (Reactome: R-HSA-202430)
• Cytotoxic T lymphocyte (CTL) mediated apoptosis (KEGG: hsa04650)
• Natural killer cell mediated cytotoxicity (KEGG: hsa04650)
Protein Summary
Granzyme A is a 26 kDa serine protease stored in the cytotoxic granules of T lymphocytes and NK cells. Upon target cell recognition, it is released via exocytosis and enters the target cell through perforin-dependent pores. Once inside, it cleaves the SET complex (including SET, APE1, and NM23-H1), triggering single-strand DNA nicks and cell death independent of caspases. The protein consists of a catalytic triad (His57, Asp102, Ser195) typical of serine proteases. Its structure includes a signal peptide (residues 1-26) and a mature chain (residues 27-262).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GZMA Knockout HEK293 Cell Line | EDJ-KQ4826 | Human | 3001 | Details Get a Quote |
| GZMA Knockout HeLa Cell Line | EDJ-KQ53471 | Human | 3001 | Details Get a Quote |
| GZMA Knockout A-549 Cell Line | EDJ-KQ61943 | Human | 3001 | Details Get a Quote |
| GZMA Knockout HCT 116 Cell Line | EDJ-KQ70424 | Human | 3001 | Details Get a Quote |
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