TGM5 Gene - Transglutaminase 5
Genetic and Functional Insights into TGM5
Gene Information Card
| Symbol | TGM5 |
|---|---|
| Full Name | Transglutaminase 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q15.2 |
| NCBI Gene ID | 9337 ncbi.nlm.nih.gov/gene/9337 |
| Ensembl ID | ENSG00000104047 |
| UniProt ID | O43548 |
| OMIM ID | 603805 |
| HGNC ID | 11781 |
| Aliases | TGX, TGMX, transglutaminase X |
Description
TGM5 encodes transglutaminase 5, a member of the transglutaminase family that catalyzes cross-linking of proteins via epsilon-(gamma-glutamyl) lysine isopeptide bonds. This enzyme is primarily expressed in the epidermis and plays a critical role in keratinocyte differentiation and skin barrier formation. Mutations in TGM5 are associated with acral peeling skin syndrome (APSS), a rare autosomal recessive disorder characterized by painless peeling of the skin on the hands and feet.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acral peeling skin syndrome (APSS) | Loss-of-function mutations in TGM5 impair transglutaminase activity, leading to defective cornification and adhesion of the stratum corneum, resulting in skin peeling. | ClinVar, OMIM |
| Lamellar ichthyosis (possible modifier) | Reduced TGM5 activity may contribute to abnormal epidermal differentiation, though direct causal evidence is limited. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 15.2 | Medium |
| Esophagus | 8.1 | Low |
| Oral mucosa | 6.5 | Low |
| Vagina | 4.3 | Low |
| Prostate | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 12.5 | High expression in keratinocyte cell line |
| A431 (epidermoid carcinoma) | 9.8 | Moderate expression |
| HEK293 (embryonic kidney) | 0.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.337G>T (p.Gly113Cys) | Missense | Common in APSS | Loss of transglutaminase activity |
| c.1130T>C (p.Leu377Pro) | Missense | Rare | Reduced enzyme stability |
| c.1528G>A (p.Gly510Arg) | Missense | Rare | Impaired cross-linking function |
Mutation functional classification
Loss of Function (LOF)
Most TGM5 mutations in acral peeling skin syndrome are loss-of-function, reducing or abolishing transglutaminase activity.
Gain of Function (GOF)
No gain-of-function mutations reported for TGM5.
Dominant Negative (DN)
No dominant-negative effects documented; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Transglutaminase-mediated cross-linking of proteins (Reactome: R-HSA-6809371)
• Keratinization (Reactome: R-HSA-6805567)
Protein Summary
Transglutaminase 5 is a 811-amino acid protein (UniProt O43548) that catalyzes calcium-dependent cross-linking of structural proteins in the epidermis. It is essential for the formation of the cornified cell envelope during terminal differentiation of keratinocytes. The protein contains a transglutaminase catalytic domain and four beta-sandwich domains. Defects in TGM5 lead to compromised skin barrier integrity, manifesting as acral peeling skin syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TGM5 Knockout HEK293 Cell Line | EDJ-KQ6550 | Human | 9333 | Details Get a Quote |
| TGM5 Knockout HeLa Cell Line | EDJ-KQ55131 | Human | 9333 | Details Get a Quote |
| TGM5 Knockout A-549 Cell Line | EDJ-KQ63609 | Human | 9333 | Details Get a Quote |
| TGM5 Knockout HCT 116 Cell Line | EDJ-KQ72074 | Human | 9333 | Details Get a Quote |
