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TGM5 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

TGM5 gene

The TGM5 gene encodes the enzyme transglutaminase 5, which is critical for skin stability; mutations in this gene lead to peeling skin syndrome 2.

Normal Function

The TGM5 gene provides instructions for making an enzyme called transglutaminase 5. While found in many tissues, it plays a key role in the epidermis. In the epidermis, transglutaminase 5 is involved in the formation of the cornified cell envelope, which surrounds epidermal cells and helps the skin form a protective barrier. The enzyme forms strong bonds, called cross-links, between structural proteins, providing strength and stability to the epidermis.

Health Conditions Related to Genetic Changes

Peeling skin syndrome 2

Several variants (mutations) in the TGM5 gene have been found to cause peeling skin syndrome 2, a condition characterized by the painless peeling of the top layer of skin, most notably on the hands and feet.

  • Most variants change single amino acids in transglutaminase 5.
  • The most common variant in people of European ancestry (Gly113Cys) replaces the amino acid glycine with cysteine.
  • These variants reduce the activity of transglutaminase 5 or prevent the production of the enzyme entirely.
  • A shortage of transglutaminase 5 function 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.

Frequently Asked Questions

Patients with peeling skin syndrome 2 should use gentle, fragrance-free emollients immediately after bathing to lock in moisture and support the compromised skin barrier. It is crucial to avoid harsh soaps, hot water, and physical exfoliants, as these can strip natural oils and exacerbate the separation of the outer skin layers. Wearing soft, breathable cotton clothing and protective gloves during household chores can also minimize friction and mechanical stress on the hands and feet.
There is currently no specific dietary intervention or supplement that can replace the function of the missing or defective transglutaminase 5 enzyme. While general skin health is supported by adequate hydration and a balanced diet rich in essential fatty acids and vitamins, these measures do not correct the underlying genetic defect in the cornified cell envelope. Management remains focused on external skin care and protecting the skin from environmental irritants rather than internal nutritional changes.
While the hands and feet are the most commonly and severely affected areas due to high mechanical stress, peeling can occasionally occur on other parts of the body, such as the face, trunk, or extremities. The severity and distribution of peeling can vary significantly between individuals, even within the same family. In some cases, the peeling may be limited to the palms and soles, while in others, it may be more widespread, though it typically remains painless.
Peeling skin syndrome 2 is an autosomal recessive condition, meaning an individual must inherit two mutated copies of the TGM5 gene, one from each parent, to develop the disorder. If both parents are carriers, there is a 25 percent chance with each pregnancy that the child will be affected, a 50 percent chance the child will be a carrier, and a 25 percent chance the child will not inherit the mutation. Genetic counseling is recommended for families with a history of the condition to assess risks and discuss testing options.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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