A2M

Chr 12

alpha-2-macroglobulin

Also known as: A2MD, CPAMD5, FWP007, S863-7

NCBI Gene: 2 ENSG00000175899 UniProt: P01023 OMIM: 103950

Alpha-2-macroglobulin functions as a protease inhibitor that uses a unique "bait-and-trap" mechanism to inhibit multiple classes of proteinases and also serves as a cytokine transporter to disrupt inflammatory cascades. Mutations cause alpha-2-macroglobulin deficiency with autosomal recessive inheritance. This gene is extremely intolerant to loss-of-function variation (pLI near 1.0, LOEUF 0.544), indicating that heterozygous loss-of-function mutations are likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a protease inhibitor and cytokine transporter. It uses a bait-and-trap mechanism to inhibit a broad spectrum of proteases, including trypsin, thrombin and collagenase. It can also inhibit inflammatory cytokines, and it thus disrupts inflammatory cascades. Mutations in this gene are a cause of alpha-2-macroglobulin deficiency. This gene is implicated in Alzheimer's disease (AD) due to its ability to mediate the clearance and degradation of A-beta, the major component of beta-amyloid deposits. A related pseudogene, which is also located on the p arm of chromosome 12, has been identified. [provided by RefSeq, Nov 2016]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.54

LOEUF

Mechanism· predicted