The TGM5 gene provides instructions for making an enzyme called transglutaminase 5. This enzyme is found in many of the body's tissues, although it seems to play a particularly important role in the outer layer of skin (the epidermis). In the epidermis, transglutaminase 5 is involved in the formation of the cornified cell envelope, which is a structure that surrounds cells and helps the skin form a protective barrier between the body and its environment. Specifically, transglutaminase 5 forms strong bonds, called cross-links, between the structural proteins that make up the cornified cell envelope. This cross-linking provides strength and stability to the epidermis.
At least 22 mutations in the TGM5 gene have been found to cause acral peeling skin syndrome. This condition is characterized by painless peeling of the top layer of skin that is most apparent on the hands and feet but can also affect the arms and legs. Most of the mutations change single protein building blocks (amino acids) in transglutaminase 5, including the most common mutation in people of European ancestry, which replaces the amino acid glycine with the amino acid cysteine at position 113 (written as Gly113Cys or G113C). TGM5 gene mutations reduce the amount of transglutaminase 5 that is produced or prevent cells from making any of this enzyme. A shortage of transglutaminase 5 impairs protein cross-linking, which weakens the cornified cell envelope and allows the outermost cells of the epidermis to separate easily from the underlying skin and peel off. This peeling is most noticeable on the hands and feet probably because those areas tend to be heavily exposed to moisture and friction.
- protein-glutamine gamma-glutamyltransferase 5
- protein-glutamine gamma-glutamyltransferase 5 isoform 1
- protein-glutamine gamma-glutamyltransferase 5 isoform 2
- TGase X
- transglutaminase V
- transglutaminase X