GZMH
protein-codinggranzyme H, the group of Granule associated serine proteases of immune defence
Gene summary
This gene encodes a member of the peptidase S1 family of serine proteases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate a chymotrypsin-like protease. This protein is reported to be constitutively expressed in the NK (natural killer) cells of the immune system and may play a role in the cytotoxic arm of the innate immune response by inducing target cell death and by directly cleaving substrates in pathogen-infected cells. This gene is present in a gene cluster with another member of the granzyme subfamily on chromosome 14. [provided by RefSeq, Nov 2015]
- CTSGL2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.2 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 GZMH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_033423.5. 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 | 1 | 1 | ||||
| missense | 39 | 5 | 44 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 41 | 5 | 0 | 46 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_219491.1 | 5 | MANE Select | |
| Ensembl | ENSP00000216338.4 | 5 | MANE Select | |
| RefSeq | NP_001257709.1 | 5 | Standard | |
| RefSeq | NP_001257710.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Peptide hormone metabolism
- Metabolism of proteins
- Metabolism of Angiotensinogen to Angiotensins
- Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
Biological Process
- proteolysis
- apoptotic process
- granzyme-mediated apoptotic signaling pathway
- cytolysis
Molecular Function
- serine-type endopeptidase activity
Cellular Component
- cytoplasm
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000216338
- Coding exons
- 5
- Length
- 3220
- Individuals with no LoFs
- 125703
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 45
- Defined
- 125748
- p
- 0.000179
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.596 | 157 | 137 | 1.14 | 0.00000728 | 1590 |
| Missense (PolyPhen) | 57 | 45.35 | 1.2569 | 545 | ||
| Synonymous | -1.50 | 67 | 53.1 | 1.26 | 0.00000267 | 490 |
| Loss of Function | -0.309 | 10 | 9.00 | 1.11 | 3.81e-7 | 110 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0014 | 0.0014 | notable |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000089 | 0.000088 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cytotoxic chymotrypsin-like serine protease with preference for bulky and aromatic residues at the P1 position and acidic residues at the P3' and P4' sites. Probably necessary for target cell lysis in cell-mediated immune responses. Participates in the antiviral response via direct cleavage of several proteins essential for viral replication. {ECO:0000269|PubMed:22156497, ECO:0000269|PubMed:23269243}.;
Recessive Scores
- pRec
- 0.135
Intolerance Scores
- LoFtool
- 0.358
- RVIS EVS
- 0.31
- RVIS percentile EVS
- 72.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.00000215
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |