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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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GZMM
granzyme M
Chromosome 19 · 19p13.3
NCBI Gene: 3004Ensembl: ENSG00000197540.8HGNC: HGNC:4712UniProt: P51124
30PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
ApoptosisProtease
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingmembraneserine-type endopeptidase activityapoptotic processtooth diseaseneoplasmvaricella, severe recurrentMendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency
✦AI Summary

GZMM (granzyme M) is a serine endopeptidase constitutively expressed in natural killer (NK) cells that plays a crucial role in cytotoxic lymphocyte-mediated apoptosis 1. The enzyme cleaves peptide substrates after methionine, leucine, and norleucine residues, with physiological targets including FADD, EZR, alpha-tubulins, and the apoptosis inhibitor BIRC5/Survivin. GZMM induces caspase-dependent apoptosis through a specific mechanism involving FADD cleavage after Met 196, generating truncated FADD that enhances self-association and facilitates procaspase-8 recruitment for auto-processing, ultimately leading to caspase cascade activation 1. The gene is located on chromosome 19.3, closely linked to other serine protease genes 2. GZMM expression serves as a biomarker in multiple cancers, with high expression associated with improved prognosis in endometrial cancer 3 and thyroid cancer 4. In gastric cancer, GZMM is part of a cytolytic T-lymphocyte signature that correlates with better patient outcomes 5. The protein demonstrates cross-cancer effects and represents a potential therapeutic target, with its expression modulated by healthy lifestyle factors 6. GZMM also shows diagnostic value in inflammatory conditions like ankylosing spondylitis 7.

Sources cited
1
GZMM is constitutively expressed in NK cells and induces caspase-dependent apoptosis through FADD cleavage and procaspase-8 activation
PMID: 21979465
2
GZMM gene is located on chromosome 19p13.3 and is closely linked to other serine protease genes
PMID: 7713495
3
High GZMM expression is associated with better prognosis in copy-number high endometrial cancer
PMID: 37857563
4
GZMM is downregulated in thyroid cancer and associated with poor prognosis and immune microenvironment
PMID: 40228756
5
GZMM is part of cytolytic T-lymphocyte signature associated with better survival in gastric cancer
PMID: 38612926
6
GZMM demonstrates cross-cancer effects and can be modulated by healthy lifestyle factors
PMID: 38039160
7
GZMM shows diagnostic value in ankylosing spondylitis and correlates with clinical indicators
PMID: 39759509
Disease Associationsⓘ20
tooth diseaseOpen Targets
0.21Weak
neoplasmOpen Targets
0.09Suggestive
varicella, severe recurrentOpen Targets
0.07Suggestive
immunodeficiency 28Open Targets
0.05Suggestive
Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiencyOpen Targets
0.05Suggestive
immunodeficiency 31BOpen Targets
0.05Suggestive
Susceptibility to viral and mycobacterial infectionsOpen Targets
0.05Suggestive
cancerOpen Targets
0.03Suggestive
insomniaOpen Targets
0.02Suggestive
carcinomaOpen Targets
0.02Suggestive
benign chondrogenic neoplasmOpen Targets
0.02Suggestive
breast cancerOpen Targets
0.02Suggestive
bacteriemiaOpen Targets
0.02Suggestive
breast neoplasmOpen Targets
0.02Suggestive
SepsisOpen Targets
0.01Suggestive
breast carcinomaOpen Targets
0.01Suggestive
leukoplakiaOpen Targets
0.01Suggestive
infectionOpen Targets
0.01Suggestive
obesityOpen Targets
0.01Suggestive
malariaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
BACE1Protein interaction87%GZMHProtein interaction82%OTULINProtein interaction75%PRSS57Shared pathway67%KLK9Shared pathway67%PRSS58Shared pathway67%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
35%
Liver
23%
Heart
12%
Ovary
7%
Brain
4%
Gene Interaction Network
Click a node to explore
GZMMBACE1GZMHOTULINPRSS57KLK9PRSS58
PROTEIN STRUCTURE
Preparing viewer…
PDB2ZGC · 1.96 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.86LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.40 [1.01–1.86]
RankingsWhere GZMM stands among ~20K protein-coding genes
  • #11,937of 20,598
    Most Researched30
  • #16,961of 17,882
    Most Constrained (LOEUF)1.86
Genes detectedGZMM
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer.
PMID: 38612926
Int J Mol Sci · 2024
1.00
2
Single-cell RNA sequencing comparison of CD4+, CD8+ and T-cell receptor γδ+ cutaneous T-cell lymphomas reveals subset-specific molecular phenotypes.
PMID: 39133553
Br J Dermatol · 2025
0.90
3
Exploration of molecular biomarkers in ankylosing spondylitis transcriptomics.
PMID: 39759509
Front Immunol · 2024
0.80
4
The human Met-ase gene (GZMM): structure, sequence, and close physical linkage to the serine protease gene cluster on 19p13.3.
PMID: 7713495
Genomics · 1994
0.70
5
Identification of the prognostic immune subtype in copy-number high endometrial cancer.
PMID: 37857563
J Gynecol Oncol · 2024
0.60