ADAM9: A Multifunctional Metalloprotease in Cell Adhesion and Signaling
Comprehensive genomic and proteomic overview of ADAM9, a disintegrin and metalloproteinase domain-containing protein 9, with roles in development, cancer, and neurodegeneration.
Gene Information Card
| Symbol | ADAM9 |
|---|---|
| Full Name | ADAM metallopeptidase domain 9 (meltrin gamma) |
| Gene Type | protein-coding |
| Chromosomal Location | 8p11.22 |
| NCBI Gene ID | 8754 ncbi.nlm.nih.gov/gene/8754 |
| Ensembl ID | ENSG00000168615 |
| UniProt ID | Q13443 |
| OMIM ID | 602713 |
| HGNC ID | 216 |
| Aliases | MDC9, meltrin gamma, MCMP, Mltng, C9orf3 |
Description
ADAM9 (ADAM metallopeptidase domain 9) encodes a member of the ADAM (a disintegrin and metalloprotease) family. The protein is a transmembrane glycoprotein that functions as a metalloprotease and mediates cell-cell and cell-matrix interactions through its disintegrin domain. It is involved in ectodomain shedding of membrane proteins, including growth factors, cytokines, and adhesion molecules. ADAM9 plays roles in fertilization, muscle development, neurogenesis, and cancer progression. Alternative splicing generates multiple transcript variants.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | ADAM9 may contribute to amyloid precursor protein (APP) shedding; altered expression linked to amyloid-beta accumulation. | PMID: 15003161; ClinVar |
| Non-small cell lung cancer | Overexpression of ADAM9 promotes tumor cell invasion and metastasis via shedding of EGFR ligands. | PMID: 15604238; COSMIC |
| Prostate cancer | ADAM9 upregulation correlates with aggressive disease and poor prognosis; involved in androgen receptor signaling. | PMID: 17947247; COSMIC |
| Breast cancer | ADAM9 expression associated with metastasis and reduced survival; mediates shedding of adhesion molecules. | PMID: 16951256; COSMIC |
| Melanoma | ADAM9 promotes melanoma cell migration and invasion through integrin binding. | PMID: 19179469; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Prostate | 15.2 | Medium |
| Breast | 9.1 | Low |
| Colon | 11.4 | Medium |
| Skin | 7.6 | Low |
| Testis | 18.9 | High |
| Placenta | 14.3 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung cancer) | 14.2 | High expression |
| MCF7 (breast cancer) | 9.8 | Moderate expression |
| PC3 (prostate cancer) | 16.5 | High expression |
| SK-MEL-28 (melanoma) | 11.1 | Moderate expression |
| HEK293 (embryonic kidney) | 7.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.158G>A (p.Arg53His) | Missense | <0.01% | Unknown; reported in ClinVar |
| c.1120C>T (p.Arg374Trp) | Missense | <0.01% | Unknown; reported in ClinVar |
| c.1966G>A (p.Val656Met) | Missense | <0.01% | Unknown; reported in ClinVar |
| c.2144G>A (p.Arg715Gln) | Missense | <0.01% | Unknown; reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in ClinVar or COSMIC for ADAM9.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported; overexpression in cancer is likely due to transcriptional upregulation rather than mutation.
Dominant Negative (DN)
No dominant-negative mutations described for ADAM9.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ADAM-mediated ectodomain shedding of EGFR ligands (Reactome: R-HSA-1227986)
• Integrin cell surface interactions (Reactome: R-HSA-216083)
• Alzheimer disease and amyloid precursor protein processing (KEGG: hsa05010)
• Proteoglycans in cancer (KEGG: hsa05205)
Protein Summary
ADAM9 is a 753-amino-acid transmembrane protein with a metalloprotease domain, a disintegrin domain, a cysteine-rich region, and a cytoplasmic tail. The metalloprotease domain catalyzes the shedding of cell surface proteins such as heparin-binding EGF-like growth factor (HB-EGF), tumor necrosis factor alpha (TNF-alpha), and amyloid precursor protein (APP). The disintegrin domain mediates interactions with integrins, influencing cell adhesion and migration. ADAM9 is widely expressed, with highest levels in testis, placenta, and brain. Its dysregulation is implicated in cancer invasion, neurodegeneration, and inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADAM9 Knockout HEK293 Cell Line | EDJ-KQ242 | Human | 8754 | Details Get a Quote |
| ADAM9 Knockout A-549 Cell Line | EDJ-KQ30302 | Human | 8754 | Details Get a Quote |
| ADAM9 Knockout HCT 116 Cell Line | EDJ-KQ30303 | Human | 8754 | Details Get a Quote |
| ADAM9 Knockout HeLa Cell Line | EDJ-KQ30304 | Human | 8754 | Details Get a Quote |
