MMP9 Gene (Matrix Metallopeptidase 9): Function, Expression, and Disease Associations
Comprehensive biomedical overview of MMP9, including genomic context, tissue expression, mutations, and clinical significance.
Gene Information Card
| Symbol | MMP9 |
|---|---|
| Full Name | Matrix metallopeptidase 9 |
| Gene Type | protein-coding |
| Chromosomal Location | 20q13.12 |
| NCBI Gene ID | 4318 ncbi.nlm.nih.gov/gene/4318 |
| Ensembl ID | ENSG00000100985 |
| UniProt ID | P14780 |
| OMIM ID | 120361 |
| HGNC ID | 7176 |
| Aliases | GELB, MANDP2, CLG4B, MMP-9, 92kDa gelatinase, 92kDa type IV collagenase |
Description
The MMP9 gene encodes matrix metallopeptidase 9, a zinc-dependent endopeptidase belonging to the matrix metalloproteinase (MMP) family. MMP9 degrades extracellular matrix components, particularly type IV and V collagens, and plays key roles in tissue remodeling, inflammation, and cell migration. It is involved in various physiological processes and pathological conditions, including cancer metastasis, cardiovascular diseases, and inflammatory disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Metastatic cancer | MMP9 degrades basement membrane collagen IV, facilitating tumor invasion and metastasis. | High expression in tumor tissues correlates with poor prognosis (COSMIC, literature). |
| Rheumatoid arthritis | MMP9 contributes to cartilage and bone destruction by degrading extracellular matrix in joints. | Elevated MMP9 levels in synovial fluid and serum of patients (OMIM). |
| Chronic obstructive pulmonary disease (COPD) | MMP9-mediated elastin degradation leads to alveolar wall destruction and emphysema. | Increased MMP9 activity in lung tissue and bronchoalveolar lavage (NCBI). |
| Aortic aneurysm | MMP9 weakens arterial wall by degrading elastin and collagen, promoting aneurysm formation and rupture. | MMP9 expression is upregulated in aneurysm tissue (OMIM). |
| Multiple sclerosis | MMP9 disrupts blood-brain barrier and facilitates immune cell infiltration into CNS. | Elevated MMP9 in cerebrospinal fluid during relapses (ClinVar). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | High | High expression in myeloid cells. |
| Spleen | Medium | Moderate expression in immune cells. |
| Lung | Medium | Expressed in alveolar macrophages. |
| Liver | Low | Low basal expression. |
| Brain | Low | Low expression in normal brain. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | High | Constitutive expression; induced by PMA. |
| U937 (histiocytic lymphoma) | High | Inducible by cytokines. |
| HeLa (cervical carcinoma) | Medium | Moderate expression. |
| A549 (lung carcinoma) | Medium | Expression increased by inflammatory stimuli. |
| MCF7 (breast carcinoma) | Low | Low basal expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3918242 (C>T in promoter) | SNP | ~15% in some populations | Affects transcription factor binding; associated with increased MMP9 expression and disease risk. |
| rs17576 (Gln279Arg) | Missense | ~20% in global populations | Alters substrate specificity; linked to coronary artery disease. |
| rs2250889 (Pro574Arg) | Missense | ~5% in East Asian populations | May affect enzyme activity; associated with cancer susceptibility. |
| rs2274756 (3' UTR variant) | Regulatory | ~10% in some populations | May influence mRNA stability and expression levels. |
Mutation functional classification
Loss of Function (LOF)
Rare loss-of-function mutations in MMP9 are not well documented; complete deficiency is rare and may impair extracellular matrix remodeling, but no specific pathogenic variants are listed in ClinVar as clearly loss-of-function.
Gain of Function (GOF)
Promoter polymorphisms (e.g., rs3918242) that increase MMP9 expression are considered gain-of-function at the transcriptional level, leading to excessive proteolysis and tissue destruction.
Dominant Negative (DN)
No dominant-negative mutations have been reported for MMP9.
View complete mutation data：
Gene Ontology (GO)
| • metalloendopeptidase activity | • zinc ion binding |
| • calcium ion binding | • extracellular matrix disassembly |
| • proteolysis | • collagen catabolic process |
| • cell migration | • angiogenesis |
| • inflammatory response | • response to hypoxia |
Pathways
• Matrix metalloproteinase pathway
• Extracellular matrix degradation
• TNF-alpha signaling pathway
• IL-17 signaling pathway
• Leukocyte transendothelial migration
• Cancer invasion and metastasis
Protein Summary
MMP9 is synthesized as a preproenzyme of 707 amino acids, with a signal peptide, prodomain, catalytic domain containing zinc-binding motif, and a C-terminal hemopexin-like domain. It is secreted as an inactive zymogen and activated by proteolytic cleavage. MMP9 exists as a monomer or homodimer and can bind to tissue inhibitor of metalloproteinases (TIMPs), particularly TIMP-1. It cleaves gelatin, collagens (IV, V, XI), elastin, and various cytokines, modulating their activity. MMP9 is involved in embryonic development, wound healing, and immune responses, but dysregulation contributes to pathological conditions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MMP9 Knockout HEK293 Cell Line | EDJ-KQ17783 | Human | 4318 | Details Get a Quote |
| MMP9 Knockout HeLa Cell Line | EDJ-KQ53885 | Human | 4318 | Details Get a Quote |
| MMP9 Knockout A-549 Cell Line | EDJ-KQ62376 | Human | 4318 | Details Get a Quote |
| MMP9 Knockout HCT 116 Cell Line | EDJ-KQ70846 | Human | 4318 | Details Get a Quote |
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