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50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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MMP14
matrix metallopeptidase 14
Chromosome 14 Β· 14q11.2
NCBI Gene: 4323Ensembl: ENSG00000157227.15HGNC: HGNC:7160UniProt: P50281
609PubMed Papers
21Diseases
2Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedProtease
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
Clinical TrialsOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
macropinosomeregulation of protein localization to plasma membranenegative regulation of GDF15-GFRAL signaling pathwayendodermal cell differentiationTorg-Winchester syndromeDupuytren Contracturemulticentric osteolysis-nodulosis-arthropathy spectrumprostate carcinoma
✦AI Summary

MMP14 (matrix metalloproteinase 14) is a membrane-anchored endopeptidase that degrades extracellular matrix components, particularly collagen, and is essential for pericellular collagenolysis and connective tissue modeling 1. As a key activator of progelatinase A/MMP2, MMP14 promotes cell growth and migration while regulating fibrovascular tissue formation 2. Beyond proteolysis, MMP14 functions as a multivalent signaling regulator: it cleaves PTK7 to modulate actin cytoskeleton reorganization, inhibits Notch signaling through DLL1 cleavage, releases vasculostatin-40 from ADGRB1 to suppress angiogenesis, and inactivates GFRAL to regulate GDF15 signaling 3456. Pathologically, MMP14 overexpression is associated with poor prognosis in gastric cancer, correlating with tumor invasion, metastasis, and advanced stage 78. In melanoma, VPS35/Retromer-mediated regulation of MMP14 subcellular localization controls metastatic dissemination 9. MMP14 also influences sarcoma progression through tumor microenvironment remodeling 10. Additionally, MMP14 integrin interactions within the tumor secretome regulate invasion and proteolytic modification of extracellular components 11. Gene polymorphisms in MMP14 associate with hepatocellular carcinoma capsule formation and cerebral stroke risk 1213.

Sources cited
1
MMP14 (matrix metalloproteinase 14) is a membrane-anchored endopeptidase that degrades extracellular matrix components, particularly collagen, and is essential for pericellular collagenolysis and connective tissue modeling .
PMID: 8015608
2
As a key activator of progelatinase A/MMP2, MMP14 promotes cell growth and migration while regulating fibrovascular tissue formation .
PMID: 22065321
3
In melanoma, VPS35/Retromer-mediated regulation of MMP14 subcellular localization controls metastatic dissemination .
PMID: 40347217
4
MMP14 also influences sarcoma progression through tumor microenvironment remodeling .
PMID: 31466240
5
Additionally, MMP14 integrin interactions within the tumor secretome regulate invasion and proteolytic modification of extracellular components .
PMID: 39828138
Disease Associationsβ“˜21
Torg-Winchester syndromeOpen Targets
0.60Moderate
Dupuytren ContractureOpen Targets
0.37Weak
multicentric osteolysis-nodulosis-arthropathy spectrumOpen Targets
0.37Weak
prostate carcinomaOpen Targets
0.31Weak
prostate cancerOpen Targets
0.29Weak
non-small cell lung carcinomaOpen Targets
0.28Weak
pericarditisOpen Targets
0.27Weak
Kaposi's sarcomaOpen Targets
0.26Weak
Abnormality of the skeletal systemOpen Targets
0.26Weak
heart diseaseOpen Targets
0.25Weak
alcohol drinkingOpen Targets
0.25Weak
fibroblastic disorderOpen Targets
0.24Weak
coronary artery diseaseOpen Targets
0.24Weak
coronary atherosclerosisOpen Targets
0.24Weak
frozen shoulderOpen Targets
0.23Weak
Palmar FibromatosisOpen Targets
0.20Weak
genetic disorderOpen Targets
0.19Weak
lumbar disc herniationOpen Targets
0.17Weak
Peyronie diseaseOpen Targets
0.16Weak
adolescent idiopathic scoliosisOpen Targets
0.15Weak
Winchester syndromeUniProt
Pathogenic Variants2
NM_004995.4(MMP14):c.332G>A (p.Arg111His)Pathogenic
Winchester syndrome
β˜†β˜†β˜†β˜†2024β†’ Residue 111
NM_004995.4(MMP14):c.50C>G (p.Thr17Arg)Pathogenic
Winchester syndrome
β˜†β˜†β˜†β˜†2012β†’ Residue 17
View on ClinVar β†—
Drug Targets2
CTS-1027Phase II
Matrix metalloproteinase 12 inhibitor
hepatitis C virus infection
REBIMASTATPhase III
Matrix metalloproteinase 13 inhibitor
Kaposi's sarcoma
Related Genes
MMP13Protein interaction100%EGFRProtein interaction100%TIMP2Protein interaction100%CAV1Protein interaction100%TIMP1Protein interaction100%HBEGFProtein interaction100%
Tissue Expression6 tissues
Lung
100%
Ovary
97%
Heart
23%
Brain
19%
Liver
14%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
MMP14MMP13EGFRTIMP2CAV1TIMP1HBEGF
PROTEIN STRUCTURE
Preparing viewer…
PDB3C7X Β· 1.70 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.31Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.20 [0.13–0.31]
RankingsWhere MMP14 stands among ~20K protein-coding genes
  • #386of 20,598
    Most Researched609 Β· top 5%
  • #4,192of 5,498
    Most Pathogenic Variants2
  • #1,231of 17,882
    Most Constrained (LOEUF)0.31 Β· top 10%
Genes detectedMMP14
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
The MMP14-caveolin axis and its potential relevance for lipoedema.
PMID: 32792644
Nat Rev Endocrinol Β· 2020
1.00
2
LncRNA-like MMP14 RNA facilitates colorectal cancer metastasis by suppressing H3K27cr at the STARD13 promoter region.
PMID: 41053540
Cell Mol Biol Lett Β· 2025
0.96
3
Association of MMP3, MMP14, and MMP25 gene polymorphisms with cerebral stroke risk: a case-control study.
PMID: 37986083
BMC Med Genomics Β· 2023
0.90
4
MMP-14 degrades tropoelastin and elastin.
PMID: 31278967
Biochimie Β· 2019
0.90
5
MMP14-Dependent Activation of TGF-Ξ² Signaling Enhances Malignancies via Promoting Necroptosis in Glioblastoma.
PMID: 41384860
FASEB J Β· 2025
0.86