A2M (Alpha-2-Macroglobulin) Gene: Structure, Function, and Clinical Significance
Comprehensive resource on the A2M gene, encoding a broad-spectrum protease inhibitor involved in coagulation, inflammation, and neurodegenerative disorders.
Gene Information Card
| Symbol | A2M |
|---|---|
| Full Name | alpha-2-macroglobulin |
| Gene Type | protein-coding |
| Chromosomal Location | 12p13.31 |
| NCBI Gene ID | 2 ncbi.nlm.nih.gov/gene/2 |
| Ensembl ID | ENSG00000175899 |
| UniProt ID | P01023 |
| OMIM ID | 103950 |
| HGNC ID | 7 |
| Aliases | CPAMD5, FWP007, S863-7 |
Description
The A2M gene encodes alpha-2-macroglobulin, a large plasma glycoprotein that acts as a broad-spectrum protease inhibitor. It inhibits a wide variety of endopeptidases by entrapping them within a molecular cage, followed by receptor-mediated clearance. A2M is involved in coagulation, inflammation, and immune modulation. Variants in A2M have been associated with Alzheimer disease and other neurodegenerative conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer Disease | A2M variants may alter protease inhibition and amyloid-beta clearance, contributing to neurodegeneration. | OMIM #104300; multiple case-control studies |
| Alpha-2-Macroglobulin Deficiency | Loss-of-function mutations lead to reduced protease inhibitor activity, potentially increasing susceptibility to inflammatory disorders. | OMIM #103950; rare case reports |
| Chronic Obstructive Pulmonary Disease (COPD) | A2M polymorphisms associated with altered protease-antiprotease balance in lung tissue. | NCBI Gene; GWAS studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 123.4 | High |
| Plasma | N/A | High (secreted) |
| Lung | 12.1 | Low |
| Brain | 8.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 145.2 | Hepatocyte cell line, high expression |
| A549 | 9.8 | Lung carcinoma cell line, low expression |
| SH-SY5Y | 6.3 | Neuroblastoma cell line, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3832852 (5-bp deletion in exon 18) | Deletion | Allele frequency ~0.12 in European populations | Associated with altered A2M function and Alzheimer disease risk |
| rs669 (Ile1000Val) | Missense | Allele frequency ~0.35 | May affect protease binding; conflicting association data |
| rs1800433 (Ala1000Thr) | Missense | Rare | Potential impact on protein stability |
Mutation functional classification
Loss of Function (LOF)
Deletions or nonsense mutations that reduce A2M protein levels or protease inhibitory activity.
Gain of Function (GOF)
Not well documented for A2M.
Dominant Negative (DN)
Not reported for A2M.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004866 - endopeptidase inhibitor activity | • GO:0005615 - extracellular space |
| • GO:0030162 - regulation of proteolysis | • GO:0006953 - acute-phase response |
| • GO:0002020 - protease binding |
Pathways
• Complement and coagulation cascades (KEGG: hsa04610)
• Alzheimer disease (KEGG: hsa05010)
• Proteolysis and endocytosis
Protein Summary
Alpha-2-macroglobulin (P01023) is a 720 kDa homotetrameric glycoprotein synthesized primarily in the liver and secreted into plasma. It functions as a universal protease inhibitor by trapping proteases within a cage-like structure, which is then recognized by the LRP1 receptor for clearance. A2M also binds and transports cytokines and growth factors, modulating inflammatory and immune responses. Its structure includes a thiol ester bond critical for conformational change upon protease cleavage.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| A2M Knockout HEK293 Cell Line | EDJ-KQ3329 | Human | 2 | Details Get a Quote |
| A2ML1 Knockout HEK293 Cell Line | EDJ-KQ10423 | Human | 144568 | Details Get a Quote |
| A2M Knockout HeLa Cell Line | EDJ-KQ26299 | Human | 2 | Details Get a Quote |
| A2ML1 Knockout HeLa Cell Line | EDJ-KQ58511 | Human | 144568 | Details Get a Quote |
| A2M Knockout A-549 Cell Line | EDJ-KQ61010 | Human | 2 | Details Get a Quote |
| A2ML1 Knockout A-549 Cell Line | EDJ-KQ66999 | Human | 144568 | Details Get a Quote |
| A2M Knockout HCT 116 Cell Line | EDJ-KQ69483 | Human | 2 | Details Get a Quote |
| A2ML1 Knockout HCT 116 Cell Line | EDJ-KQ75400 | Human | 144568 | Details Get a Quote |
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