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TGM3 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

TGM3 gene

The TGM3 gene encodes the enzyme transglutaminase 3, which is responsible for providing strength and structure to skin and hair cells.

Normal Function

The TGM3 gene provides instructions for making an enzyme called transglutaminase 3. This enzyme is found in skin cells (keratinocytes and corneocytes) and in the roots and shafts of scalp hair.

Transglutaminase 3 helps bind proteins together at their glutamine and lysine amino acids. This process creates stabilizing cross-links between proteins, which provide necessary strength and structure to skin and hair.

Health Conditions Related to Genetic Changes

Uncombable hair syndrome

Mutations in the TGM3 gene have been found to cause uncombable hair syndrome, a condition characterized by dry, frizzy, blond hair that cannot be combed flat. While the condition often improves by adolescence, the underlying genetic cause involves a premature stop signal in the instructions for transglutaminase 3, resulting in an abnormally short and inactive enzyme.

A deficiency of this enzyme impairs the cross-linking of proteins, such as trichohyalin and keratin intermediate filaments. Because these proteins cannot properly bind to form the cylindrical shape of the hair shaft, the shaft becomes triangular, heart-shaped, or flat. These angular shapes result in the frizzy, uncombable texture associated with the syndrome.

Frequently Asked Questions

There is no cure, but regular conditioning with protein‑rich masks, gentle detangling, and avoiding heat styling can reduce brittleness. Some families report modest improvement with topical minoxidil or biotin supplements, but evidence is limited; the condition often improves naturally during adolescence.
If the hair is blonde or light‑colored, stands up in a triangular or heart‑shaped shaft, and is difficult to comb despite gentle brushing, uncombable hair syndrome is a possibility. A dermatologist can confirm the diagnosis with a scalp examination and, if needed, a hair shaft microscopy; genetic testing for TGM3 mutations may be offered for confirmation.
Testing is optional but helpful for confirming the diagnosis, especially if the family is considering future family planning. A simple blood or saliva sample sent for targeted TGM3 sequencing can identify pathogenic variants; results also aid in counseling about the typically benign course of the condition.
Uncombable hair syndrome caused by TGM3 mutations is usually isolated to the hair shaft and does not affect skin integrity, immune function, or other organ systems. Routine pediatric care is sufficient; however, monitor for secondary skin irritation from frequent scratching or harsh hair products.
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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