TGM6 (Transglutaminase 6)
Gene encoding transglutaminase 6, implicated in spinocerebellar ataxia and neuronal function
Gene Information Card
| Symbol | TGM6 |
|---|---|
| Full Name | Transglutaminase 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 20p13 |
| NCBI Gene ID | 343641 ncbi.nlm.nih.gov/gene/343641 |
| Ensembl ID | ENSG00000101210 |
| UniProt ID | Q6ZYX8 |
| OMIM ID | 613900 |
| HGNC ID | 16259 |
| Aliases | TG6, TGM3L, TGM6L, bA554I22.1 |
Description
TGM6 encodes transglutaminase 6 (TG6), a member of the transglutaminase family that catalyzes cross-linking of proteins via epsilon-(gamma-glutamyl) lysine isopeptide bonds. TG6 is predominantly expressed in the central nervous system, particularly in the cerebellum, and plays a role in neuronal development and function. Mutations in TGM6 are associated with spinocerebellar ataxia type 35 (SCA35), an autosomal dominant neurodegenerative disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinocerebellar ataxia 35 (SCA35) | Missense mutations in TGM6 lead to altered transglutaminase activity, impaired protein cross-linking, and neuronal dysfunction in the cerebellum. | OMIM #613908; ClinVar; multiple case reports (e.g., Wang et al., 2010) |
| Gluten-sensitive enteropathy (celiac disease) | TG6 is a target of autoantibodies in celiac disease, particularly in patients with neurological involvement. | NCBI Gene; PMID: 20427749 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebellum | 12.5 | Medium |
| Cerebral cortex | 5.2 | Low |
| Spinal cord | 3.8 | Low |
| Testis | 2.1 | Low |
| Heart | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.9 | Neuronal model |
| U-87 MG (glioblastoma) | 6.3 | Glial model |
| HEK293 (embryonic kidney) | 1.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1550T>C (p.Leu517Pro) | Missense | <0.01% | Alters catalytic domain; associated with SCA35 |
| c.1528G>C (p.Asp510His) | Missense | <0.01% | Reduced transglutaminase activity; SCA35 |
| c.1468C>T (p.Arg490Trp) | Missense | <0.01% | Impaired protein stability; SCA35 |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Leu517Pro, p.Asp510His) reduce enzymatic activity, leading to loss of normal cross-linking function in neurons.
Gain of Function (GOF)
Not reported for TGM6.
Dominant Negative (DN)
Proposed mechanism for SCA35: mutant TG6 interferes with wild-type TG6 or other transglutaminases, disrupting neuronal homeostasis.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Transglutaminase activation and cross-linking (Reactome: R-HSA-6805567)
• Spinocerebellar ataxia pathway (KEGG: hsa05017)
Protein Summary
Transglutaminase 6 (TG6) is a 706-amino acid protein with a molecular weight of ~80 kDa. It contains a transglutaminase catalytic domain (residues 1-580) and a C-terminal beta-barrel domain. TG6 is calcium-dependent and catalyzes protein cross-linking, contributing to neuronal stability and synaptic function. In the cerebellum, TG6 is enriched in Purkinje cells, and its dysfunction leads to progressive ataxia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TGM6 Knockout HEK293 Cell Line | EDJ-KQ15712 | Human | 343641 | Details Get a Quote |
| TGM6 Knockout HeLa Cell Line | EDJ-KQ59762 | Human | 343641 | Details Get a Quote |
| TGM6 Knockout A-549 Cell Line | EDJ-KQ68231 | Human | 343641 | Details Get a Quote |
| TGM6 Knockout HCT 116 Cell Line | EDJ-KQ76606 | Human | 343641 | Details Get a Quote |
