TGM3: Transglutaminase 3 – Key Player in Epidermal Differentiation and Barrier Function
Comprehensive genomic, functional, and clinical overview of TGM3, a member of the transglutaminase family involved in cornified envelope formation and associated with skin disorders and cancer.
Gene Information Card
| Symbol | TGM3 |
|---|---|
| Full Name | Transglutaminase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 20p13 |
| NCBI Gene ID | 7053 ncbi.nlm.nih.gov/gene/7053 |
| Ensembl ID | ENSG00000125787 |
| UniProt ID | Q08188 |
| OMIM ID | 600238 |
| HGNC ID | 11779 |
| Aliases | TGE, TGase-3, TG3, transglutaminase E3 |
Description
TGM3 encodes transglutaminase 3 (TGase-3), a calcium-dependent enzyme that catalyzes cross-linking of proteins such as loricrin, involucrin, and small proline-rich proteins to form the cornified cell envelope. This process is critical for terminal differentiation of keratinocytes and maintenance of the epidermal barrier. TGM3 is predominantly expressed in stratified squamous epithelia, including skin, esophagus, and oral mucosa. Mutations in TGM3 are associated with autosomal recessive congenital ichthyosis, and altered expression is observed in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive congenital ichthyosis (ARCI) | Loss-of-function mutations in TGM3 impair cross-linking of cornified envelope proteins, leading to defective skin barrier and scaling. | ClinVar; OMIM #600238 |
| Esophageal squamous cell carcinoma | Downregulation of TGM3 contributes to loss of differentiation and increased invasiveness; promoter hypermethylation is observed. | COSMIC; PubMed studies |
| Head and neck squamous cell carcinoma | Reduced TGM3 expression correlates with poor differentiation and worse prognosis. | NCBI Gene; PubMed |
| Lung cancer | Altered TGM3 expression reported in squamous cell carcinoma subtypes. | COSMIC; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 126.4 | High |
| Esophagus | 78.2 | High |
| Oral mucosa | 55.1 | High |
| Cervix | 12.3 | Medium |
| Vagina | 9.8 | Medium |
| Lung | 2.1 | Low |
| Breast | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 85.3 | High expression; used as model for epidermal differentiation |
| A431 (epidermoid carcinoma) | 62.1 | Moderate expression; reduced compared to normal keratinocytes |
| KYSE-30 (esophageal squamous) | 15.4 | Low expression; associated with promoter methylation |
| SCC-25 (oral squamous) | 8.2 | Low expression; correlates with invasive phenotype |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.337C>T (p.Arg113*) | Nonsense | Rare | Loss of function; associated with ARCI |
| c.1048G>A (p.Gly350Arg) | Missense | Rare | Impaired enzyme activity; reported in ARCI |
| c.1520T>C (p.Leu507Pro) | Missense | Rare | Reduced stability and activity; ARCI |
| c.1966G>A (p.Gly656Arg) | Missense | Rare | Likely pathogenic; ARCI |
| c.1118_1119del (p.Glu373Glyfs*12) | Frameshift | Rare | Loss of function; ARCI |
Mutation functional classification
Loss of Function (LOF)
Most TGM3 mutations in ARCI are loss-of-function (nonsense, frameshift, missense with reduced activity), leading to defective cornified envelope formation.
Gain of Function (GOF)
No gain-of-function mutations reported for TGM3.
Dominant Negative (DN)
No dominant-negative mutations reported; ARCI is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Keratinocyte differentiation (Reactome: R-HSA-6809371)
• Formation of the cornified envelope (Reactome: R-HSA-6809371)
• Transglutaminase-mediated cross-linking (Reactome: R-HSA-6809371)
Protein Summary
Transglutaminase 3 (TGase-3) is a 692-amino acid protein (UniProt Q08188) with a molecular weight of ~77 kDa. It contains a catalytic domain with an active-site cysteine (Cys277) essential for transamidation activity. TGase-3 is synthesized as a zymogen and activated by proteolytic cleavage. It cross-links structural proteins (loricrin, involucrin, SPRRs) via ε-(γ-glutamyl)lysine isopeptide bonds, contributing to the mechanical integrity of the cornified envelope. The protein is localized in the cytoplasm and plasma membrane of differentiated keratinocytes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TGM3 Knockout HEK293 Cell Line | EDJ-KQ50685 | Human | 7053 | Details Get a Quote |
| TGM3 Knockout HeLa Cell Line | EDJ-KQ54651 | Human | 7053 | Details Get a Quote |
| TGM3 Knockout A-549 Cell Line | EDJ-KQ63132 | Human | 7053 | Details Get a Quote |
| TGM3 Knockout HCT 116 Cell Line | EDJ-KQ71605 | Human | 7053 | Details Get a Quote |
