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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MMP3
matrix metallopeptidase 3
Chromosome 11 · 11q22.2
NCBI Gene: 4314Ensembl: ENSG00000149968.12HGNC: HGNC:7173UniProt: P08254
792PubMed Papers
21Diseases
2Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneProtease
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
Clinical TrialsOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of protein-containing complex assemblynegative regulation of reactive oxygen species metabolic processendopeptidase activityprotein bindingcoronary artery diseaselung canceratherosclerosisAlzheimer disease
✦AI Summary

MMP3 (matrix metallopeptidase 3) is a zinc-dependent metalloproteinase that degrades extracellular matrix components including collagens, fibronectin, and proteoglycans, playing crucial roles in tissue remodeling and pathological processes. The enzyme demonstrates broad substrate specificity and activates other matrix metalloproteinases and growth factors 1. MMP3 exhibits significant clinical relevance in multiple disease contexts. In cancer, MMP3 upregulation via epigenetic mechanisms involving KDM6A promotes brain metastasis in triple-negative breast cancer, with KMT2C-mutant tumors showing elevated MMP3 levels 1. The gene serves as a hub biomarker in head and neck squamous cell carcinomas, associated with poor survival and metastasis 2. Genetic polymorphisms in MMP3, particularly rs679620 and rs520540, influence disease susceptibility with complex associations: these variants show protective effects against ischemic stroke but increased hemorrhagic stroke risk in Chinese populations 3. In musculoskeletal medicine, MMP3 variants affect injury susceptibility, with the rs679620 G allele overrepresented in anterior cruciate ligament ruptures 4 and rs522616 polymorphism influencing muscle strength recovery after exercise in a sex-dependent manner 5. Additionally, MMP3 polymorphisms are associated with coronary artery disease risk and post-PCI outcomes 67.

Sources cited
1
MMP3 upregulation via KDM6A-dependent epigenetic mechanisms drives brain metastasis in TNBC with KMT2C mutations
PMID: 38926506
2
MMP3 serves as a hub gene biomarker associated with poor survival and metastasis in head and neck squamous cell carcinomas
PMID: 37859283
3
MMP3 rs679620 and rs520540 polymorphisms show protective effects against ischemic stroke but increased hemorrhagic stroke risk
PMID: 37986083
4
MMP3 rs679620 G allele is overrepresented in anterior cruciate ligament rupture cases
PMID: 30755371
5
MMP3 rs522616 polymorphism affects muscle strength recovery after eccentric exercise in a sex-dependent manner
PMID: 37471217
6
MMP3 6A/6A genotype is associated with increased risk of acute coronary syndromes
PMID: 29044936
7
MMP3 polymorphisms are associated with in-stent restenosis and repeat revascularization after PCI
PMID: 34860335
Disease Associationsⓘ21
coronary artery diseaseOpen Targets
0.42Moderate
lung cancerOpen Targets
0.37Weak
atherosclerosisOpen Targets
0.36Weak
Alzheimer diseaseOpen Targets
0.36Weak
aneurysmOpen Targets
0.34Weak
aortic aneurysmOpen Targets
0.34Weak
occlusion precerebral arteryOpen Targets
0.31Weak
cerebrovascular disorderOpen Targets
0.31Weak
breast cancerOpen Targets
0.28Weak
Malignant Pancreatic NeoplasmOpen Targets
0.26Weak
pancreatic neoplasmOpen Targets
0.26Weak
peripheral vascular diseaseOpen Targets
0.20Weak
peripheral arterial diseaseOpen Targets
0.19Weak
atopic eczemaOpen Targets
0.17Weak
Abdominal Aortic AneurysmOpen Targets
0.17Weak
chronic obstructive pulmonary diseaseOpen Targets
0.17Weak
strokeOpen Targets
0.13Weak
rheumatoid arthritisOpen Targets
0.12Weak
oral squamous cell carcinomaOpen Targets
0.12Weak
osteoarthritisOpen Targets
0.12Weak
Coronary heart disease 6UniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets2
CTS-1027Phase II
Matrix metalloproteinase 12 inhibitor
hepatitis C virus infection
MARIMASTATPhase III
Matrix metalloproteinase 3 inhibitor
lung cancer
Related Genes
CTSSProtein interaction100%EGFRProtein interaction100%TGFB1Protein interaction100%TIMP1Protein interaction100%FN1Protein interaction100%CXCL1Protein interaction98%
Tissue Expression6 tissues
Lung
100%
Brain
88%
Liver
50%
Ovary
25%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
MMP3CTSSEGFRTGFB1TIMP1FN1CXCL1
PROTEIN STRUCTURE
Preparing viewer…
PDB1HY7 · 1.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.26LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.99 [0.78–1.26]
RankingsWhere MMP3 stands among ~20K protein-coding genes
  • #251of 20,598
    Most Researched792 · top 5%
  • #13,304of 17,882
    Most Constrained (LOEUF)1.26
Genes detectedMMP3
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Loss of Kmt2c or Kmt2d drives brain metastasis via KDM6A-dependent upregulation of MMP3.
PMID: 38926506
Nat Cell Biol · 2024
1.00
2
Association of
PMID: 37471217
J Appl Physiol (1985) · 2023
0.90
3
Evaluation of MMP1 and MMP3 gene polymorphisms in exfoliation syndrome and exfoliation glaucoma.
PMID: 20038976
Mol Vis · 2009
0.84
4
Upregulation of MMP3 Promotes Cisplatin Resistance in Ovarian Cancer.
PMID: 40362252
Int J Mol Sci · 2025
0.80
5
Association of MMP3, MMP14, and MMP25 gene polymorphisms with cerebral stroke risk: a case-control study.
PMID: 37986083
BMC Med Genomics · 2023
0.80