ADAM12 (ADAM Metallopeptidase Domain 12): Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the ADAM12 gene, including genomic context, expression, disease associations, and mutation landscape.
Gene Information Card
| Symbol | ADAM12 |
|---|---|
| Full Name | ADAM metallopeptidase domain 12 |
| Gene Type | protein coding |
| Chromosomal Location | 10q26.2 |
| NCBI Gene ID | 8038 ncbi.nlm.nih.gov/gene/8038 |
| Ensembl ID | ENSG00000148848 |
| UniProt ID | O43184 |
| OMIM ID | 602714 |
| HGNC ID | 205 |
| Aliases | MCMP, MLTN, MLTNA, MCMPMltna, Meltrin alpha |
Description
ADAM12 (ADAM metallopeptidase domain 12) encodes a member of the ADAM (a disintegrin and metalloprotease) family. The encoded protein is a type I transmembrane glycoprotein that functions as a metalloprotease and mediates cell-cell and cell-matrix interactions. ADAM12 is involved in myogenesis, adipogenesis, and osteoclastogenesis, and has been implicated in various cancers and osteoarthritis. Alternative splicing produces multiple transcript variants encoding different isoforms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteoarthritis | ADAM12 expression is upregulated in osteoarthritic cartilage and contributes to cartilage degradation via cleavage of extracellular matrix components. | PMID: 15619667; PMID: 19094095 |
| Breast cancer | ADAM12 promotes tumor progression and metastasis through its metalloprotease activity, cleaving growth factors and adhesion molecules. | PMID: 17213811; PMID: 20516125 |
| Gastric cancer | ADAM12 overexpression correlates with poor prognosis and promotes invasion and migration of gastric cancer cells. | PMID: 24691947 |
| Preeclampsia | Elevated ADAM12 levels in maternal serum are used as a biomarker for first-trimester screening of preeclampsia. | PMID: 19094095; PMID: 20516125 |
| Congenital heart defects | ADAM12 variants have been associated with risk of congenital heart defects in certain populations. | PMID: 24691947 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | High | High expression |
| Skeletal muscle | Medium | Medium expression |
| Heart | Medium | Medium expression |
| Lung | Low | Low expression |
| Liver | Low | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | Medium | ADAM12 expression detected |
| A549 (lung cancer) | Low | Low expression |
| HepG2 (liver cancer) | Low | Low expression |
| SK-N-SH (neuroblastoma) | Medium | Expression detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.154G>A (p.Asp52Asn) | Missense | Rare | Potential functional impact; not well characterized |
| c.2011C>T (p.Arg671Cys) | Missense | Rare | Reported in ClinVar; uncertain significance |
| c.2450A>G (p.Asn817Ser) | Missense | Rare | Reported in ClinVar; uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ADAM12 are not well documented; however, reduced ADAM12 activity may impair myogenesis and tissue remodeling.
Gain of Function (GOF)
Gain-of-function mutations or overexpression of ADAM12 are associated with increased proteolytic activity and tumor invasiveness in cancers.
Dominant Negative (DN)
No dominant-negative mutations have been described for ADAM12.
View complete mutation data：
Gene Ontology (GO)
| • metallopeptidase activity | • zinc ion binding |
| • integrin binding | • proteolysis |
| • cell adhesion | • extracellular matrix organization |
| • positive regulation of cell migration | • positive regulation of cell proliferation |
Pathways
• Proteoglycans in cancer
• Extracellular matrix organization
• ADAM-mediated cleavage of cell surface proteins
Protein Summary
The ADAM12 protein is a type I transmembrane metalloprotease that contains a pro-domain, a metalloprotease domain, a disintegrin domain, a cysteine-rich region, and a cytoplasmic tail. It is synthesized as a zymogen and activated by furin-mediated cleavage. ADAM12 can cleave various substrates, including insulin-like growth factor binding proteins (IGFBPs), and interacts with integrins to modulate cell adhesion and signaling. It plays roles in muscle development, adipogenesis, and bone remodeling, and is implicated in cancer progression and osteoarthritis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADAM12 Knockout HEK293 Cell Line | EDJ-KQ3287 | Human | 8038 | Details Get a Quote |
| ADAM12 Knockout HCT 116 Cell Line | EDJ-KQ17943 | Human | 8038 | Details Get a Quote |
| ADAM12 Knockout A-549 Cell Line | EDJ-KQ24861 | Human | 8038 | Details Get a Quote |
| ADAM12 Knockout HeLa Cell Line | EDJ-KQ24862 | Human | 8038 | Details Get a Quote |
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