GZMA
protein-codinggranzyme A, the group of Granule associated serine proteases of immune defence
Gene summary
Cytolytic T lymphocytes (CTL) and natural killer (NK) cells share the remarkable ability to recognize, bind, and lyse specific target cells. They are thought to protect their host by lysing cells bearing on their surface 'nonself' antigens, usually peptides or proteins resulting from infection by intracellular pathogens. The protein described here is a T cell- and natural killer cell-specific serine protease that may function as a common component necessary for lysis of target cells by cytotoxic T lymphocytes and natural killer cells. [provided by RefSeq, Jul 2008]
- HFSP
- CTLA3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GZMA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006144.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 34 | 4 | 1 | 39 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 37 | 4 | 1 | 42 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006135.2 | 5 | MANE Select | |
| Ensembl | ENSP00000274306.6 | 5 | MANE Select | |
| Ensembl | ENSP00000648695.1 | 2 | Standard | |
| Ensembl | ENSP00000771836.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- granzyme a mediated apoptosis pathway
- tsp-1 induced apoptosis in microvascular endothelial cell
- IL12-mediated signaling events
Biological Process
- apoptotic process
- immune response
- response to bacterium
- cytolysis
- negative regulation of endodeoxyribonuclease activity
Molecular Function
- serine-type endopeptidase activity
- protein binding
- protein homodimerization activity
Cellular Component
- immunological synapse
- extracellular region
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000274306
- Coding exons
- 5
- Length
- 7605
- Individuals with no LoFs
- 125625
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125647
- p
- 0.0000876
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.169 | 136 | 142 | 0.960 | 0.00000687 | 1705 |
| Missense (PolyPhen) | 59 | 54.164 | 1.0893 | 664 | ||
| Synonymous | 0.795 | 43 | 50.2 | 0.857 | 0.00000263 | 520 |
| Loss of Function | 0.183 | 9 | 9.61 | 0.936 | 4.69e-7 | 122 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000098 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent cell death with morphological features of apoptosis when delivered into the target cell through the immunological synapse. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. Cleaves the nucleosome assembly protein SET after 'Lys-189', which disrupts its nucleosome assembly activity and allows the SET complex to translocate into the nucleus to nick and degrade the DNA. {ECO:0000269|PubMed:11555662, ECO:0000269|PubMed:12524539, ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:16818237}.;
Recessive Scores
- pRec
- 0.0673
Intolerance Scores
- LoFtool
- 0.494
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 37.32
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.192
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |