TDG (Thymine DNA Glycosylase)
A key enzyme in base excision repair and epigenetic regulation
Gene Information Card
| Symbol | TDG |
|---|---|
| Full Name | Thymine DNA Glycosylase |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.11 |
| NCBI Gene ID | 6996 ncbi.nlm.nih.gov/gene/6996 |
| Ensembl ID | ENSG00000139352 |
| UniProt ID | Q13569 |
| OMIM ID | 601423 |
| HGNC ID | 11700 |
| Aliases | hTDG, MBD4L, TDG1 |
Description
The TDG gene encodes thymine DNA glycosylase, an enzyme that initiates base excision repair by removing thymine or uracil from G:T and G:U mismatches. It also plays a role in epigenetic regulation by excising 5-formylcytosine and 5-carboxylcytosine, intermediates in active DNA demethylation. TDG is essential for embryonic development and genomic stability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Loss of TDG function leads to increased mutation frequency and genomic instability | PMID: 23222409; COSMIC |
| Gastric cancer | TDG downregulation associated with microsatellite instability | PMID: 25670082 |
| Lung cancer | Somatic mutations in TDG impair DNA repair capacity | PMID: 27527242; COSMIC |
| Hereditary nonpolyposis colorectal cancer (Lynch syndrome) | TDG variants may modify mismatch repair deficiency phenotype | PMID: 23334667 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 45.2 | High |
| Thyroid | 38.1 | High |
| Adrenal gland | 32.5 | Medium |
| Brain | 28.7 | Medium |
| Liver | 22.3 | Medium |
| Heart | 18.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 35.6 | Cervical carcinoma |
| A549 | 30.2 | Lung carcinoma |
| HCT116 | 28.4 | Colorectal carcinoma |
| MCF7 | 25.1 | Breast carcinoma |
| HEK293 | 22.8 | Embryonic kidney |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Gly199Ser | Missense | <0.1% (COSMIC) | Reduced glycosylase activity |
| p.Arg275Trp | Missense | <0.1% (COSMIC) | Impaired substrate binding |
| p.Thr72Ala | Missense | <0.1% (COSMIC) | Decreased catalytic efficiency |
| c.1-?_*_del | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Gly199Ser, p.Arg275Trp) reduce or abolish glycosylase activity, impairing base excision repair and promoting genomic instability.
Gain of Function (GOF)
No gain-of-function mutations reported in TDG.
Dominant Negative (DN)
No dominant-negative mutations reported in TDG.
View complete mutation data：
Gene Ontology (GO)
| • damaged DNA binding (GO:0003684) | • DNA N-glycosylase activity (GO:0003913) |
| • base-excision repair (GO:0006284) | • DNA dealkylation involved in DNA repair (GO:0006307) |
| • oxidative DNA demethylase activity (GO:0035511) | • ATP-dependent chromatin remodeling (GO:0043044) |
Pathways
• Base excision repair (BER) - Reactome R-HSA-73884
• Active DNA demethylation - Reactome R-HSA-212300
• DNA repair - KEGG hsa03410
Protein Summary
Thymine DNA glycosylase (TDG) is a 410-amino acid protein that localizes to the nucleus. It recognizes and excises thymine or uracil mispaired with guanine in double-stranded DNA, initiating the base excision repair pathway. TDG also processes 5-formylcytosine and 5-carboxylcytosine, key intermediates in active DNA demethylation, linking DNA repair to epigenetic regulation. The protein interacts with transcription factors and chromatin modifiers, influencing gene expression. Structural studies reveal a conserved catalytic domain with a helix-hairpin-helix motif.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TDG Knockout HEK293 Cell Line | EDJ-KQ50682 | Human | 6996 | Details Get a Quote |
| TDG Knockout HeLa Cell Line | EDJ-KQ54636 | Human | 6996 | Details Get a Quote |
| TDG Knockout A-549 Cell Line | EDJ-KQ63118 | Human | 6996 | Details Get a Quote |
| TDG Knockout HCT 116 Cell Line | EDJ-KQ71589 | Human | 6996 | Details Get a Quote |
