MMP12 Gene (Macrophage Metalloproteinase-12): Function, Disease Associations, and Expression
Comprehensive biomedical overview of MMP12, including genomic context, protein function, tissue expression, disease links, and mutation data.
Gene Information Card
| Symbol | MMP12 |
|---|---|
| Full Name | Matrix metalloproteinase 12 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q22.2 |
| NCBI Gene ID | 4321 ncbi.nlm.nih.gov/gene/4321 |
| Ensembl ID | ENSG00000135318 |
| UniProt ID | P39900 |
| OMIM ID | 601046 |
| HGNC ID | 7157 |
| Aliases | HME, ME, MMP-12, MGC138187, MGC138188 |
Description
MMP12 encodes a member of the matrix metalloproteinase (MMP) family, which are zinc-dependent endopeptidases involved in extracellular matrix degradation, tissue remodeling, and inflammatory processes. MMP12, also known as macrophage metalloelastase, is primarily expressed in macrophages and plays a key role in elastin degradation, macrophage migration, and immune responses. It has been implicated in various diseases, including chronic obstructive pulmonary disease (COPD), atherosclerosis, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic Obstructive Pulmonary Disease (COPD) | MMP12 degrades elastin and other extracellular matrix components, contributing to alveolar wall destruction and emphysema. | Association studies and functional evidence from mouse models; ClinVar lists variants associated with COPD susceptibility. |
| Atherosclerosis | MMP12 promotes plaque instability by degrading extracellular matrix in the arterial wall, leading to rupture. | Expression studies in human atherosclerotic plaques; mouse knockout models show reduced lesion progression. |
| Lung Cancer | MMP12 expression in tumor-associated macrophages facilitates invasion and metastasis by remodeling the tumor microenvironment. | Immunohistochemistry and gene expression studies; COSMIC lists somatic mutations in lung cancer. |
| Emphysema | MMP12-mediated elastin degradation is a hallmark of emphysema, leading to loss of lung elasticity. | Mouse models overexpressing MMP12 develop emphysema; human studies show elevated MMP12 in lung tissue. |
| Asthma | MMP12 contributes to airway remodeling and inflammation, potentially exacerbating asthma severity. | Elevated MMP12 levels in bronchoalveolar lavage fluid of asthmatic patients; genetic association studies. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | High | High |
| Spleen | Medium | Medium |
| Bone Marrow | Medium | Medium |
| Liver | Low | Low |
| Blood | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Macrophages | High | Primary expression site; involved in elastin degradation. |
| Monocytes | Medium | Precursor cells; expression increases upon differentiation to macrophages. |
| THP-1 (monocytic leukemia) | Medium | Can be induced with PMA to differentiate into macrophages. |
| A549 (lung carcinoma) | Low | Low basal expression; may be induced by inflammatory stimuli. |
| HeLa (cervical carcinoma) | Low | Minimal expression; not a typical cell line for MMP12 studies. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2276109 | SNP (promoter region) | Allele frequency varies by population (e.g., ~10-20% in Europeans) | Associated with reduced MMP12 expression and decreased risk of COPD. |
| rs652438 | SNP (missense, p.Asn357Ser) | Minor allele frequency ~5-10% | May affect enzyme activity; linked to asthma susceptibility in some studies. |
| c.538G>A (p.Gly180Arg) | Missense | Rare (not well characterized) | Potential loss of function; reported in ClinVar as variant of uncertain significance. |
| c.1045C>T (p.Arg349Trp) | Missense | Rare | Predicted damaging; associated with altered proteolytic activity. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in MMP12 are rare but may reduce elastin degradation, potentially protecting against emphysema but impairing macrophage migration and tissue remodeling.
Gain of Function (GOF)
Gain-of-function mutations or overexpression of MMP12 lead to excessive extracellular matrix degradation, contributing to tissue destruction in COPD and cancer invasion.
Dominant Negative (DN)
No dominant-negative mutations have been reported for MMP12; the enzyme functions as a monomer, and such effects are unlikely.
View complete mutation data：
Gene Ontology (GO)
| • metalloendopeptidase activity | • zinc ion binding |
| • extracellular matrix organization | • proteolysis |
| • collagen catabolic process | • elastin catabolic process |
| • macrophage migration | • inflammatory response |
Pathways
• Matrix metalloproteinase pathway
• Extracellular matrix degradation
• TNF-alpha signaling pathway
• IL-17 signaling pathway
• Leukocyte transendothelial migration
Protein Summary
MMP12 is a secreted zinc-dependent endopeptidase that degrades elastin, collagen, and other extracellular matrix components. It is synthesized as a preproenzyme and processed to the active form by cleavage. MMP12 is primarily produced by macrophages and plays a critical role in tissue remodeling, inflammation, and immune responses. Its activity is regulated by tissue inhibitors of metalloproteinases (TIMPs). Dysregulation of MMP12 is implicated in chronic inflammatory diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MMP12 Knockout HEK293 Cell Line | EDJ-KQ5230 | Human | 4321 | Details Get a Quote |
| MMP12 Knockout HeLa Cell Line | EDJ-KQ53887 | Human | 4321 | Details Get a Quote |
| MMP12 Knockout A-549 Cell Line | EDJ-KQ62379 | Human | 4321 | Details Get a Quote |
| MMP12 Knockout HCT 116 Cell Line | EDJ-KQ70848 | Human | 4321 | Details Get a Quote |
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