TDP2 (Tyrosyl-DNA Phosphodiesterase 2)
A key enzyme in DNA repair, resolving topoisomerase II-mediated DNA damage and maintaining genomic stability.
Gene Information Card
| Symbol | TDP2 |
|---|---|
| Full Name | Tyrosyl-DNA Phosphodiesterase 2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 6p22.3 |
| NCBI Gene ID | 51567 ncbi.nlm.nih.gov/gene/51567 |
| Ensembl ID | ENSG00000111846 |
| UniProt ID | O95551 |
| OMIM ID | 605764 |
| HGNC ID | 17768 |
| Aliases | TTRAP, EAP2, dJ30M3.3 |
Description
TDP2 (tyrosyl-DNA phosphodiesterase 2) encodes a DNA repair enzyme that specifically hydrolyzes 5'-phosphotyrosyl bonds, resolving topoisomerase II (TOP2)-DNA covalent complexes. This activity is critical for repairing TOP2-induced DNA double-strand breaks and maintaining genomic integrity. TDP2 also participates in non-homologous end joining (NHEJ) and is implicated in cellular responses to chemotherapeutic agents such as etoposide.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy (SCAN1) | Loss-of-function mutations in TDP2 impair resolution of TOP2-DNA adducts, leading to accumulation of DNA damage in neurons. | OMIM #607250; ClinVar |
| Breast cancer | TDP2 overexpression may confer resistance to TOP2-targeting chemotherapies (e.g., etoposide, doxorubicin) by enhancing repair of drug-induced DNA damage. | COSMIC; PubMed studies |
| Glioblastoma | Altered TDP2 expression levels correlate with tumor progression and response to topoisomerase inhibitors. | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Brain (cerebellum) | 8.7 | Medium |
| Heart | 6.5 | Low |
| Liver | 4.2 | Low |
| Lung | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 9.8 | Embryonic kidney; high TDP2 activity |
| HeLa | 7.4 | Cervical carcinoma; moderate expression |
| MCF7 | 5.6 | Breast cancer; variable expression |
| U2OS | 6.2 | Osteosarcoma; used in DNA repair studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.118C>T (p.Arg40*) | Nonsense | Rare (0.0001) | Loss of function; truncated protein; associated with SCAN1 |
| c.449G>A (p.Arg150His) | Missense | Rare (0.0002) | Reduced catalytic activity; impaired DNA repair |
| c.832C>T (p.Arg278Trp) | Missense | Rare (0.0001) | Decreased phosphodiesterase activity; linked to neurological phenotypes |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg40*, p.Arg150His) that reduce or abolish TDP2 enzymatic activity, leading to accumulation of TOP2-DNA adducts and genomic instability.
Gain of Function (GOF)
Not well-documented; overexpression in certain cancers may enhance repair of TOP2-mediated damage, potentially conferring chemoresistance.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported; TDP2 functions as a monomer, and heterozygous loss-of-function may contribute to disease via haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Non-homologous end joining (NHEJ) - Reactome R-HSA-5693571
• Resolution of TOP2-DNA complexes - Reactome R-HSA-5693567
• DNA double-strand break repair - KEGG hsa03450
Protein Summary
TDP2 is a 362-amino acid protein (UniProt O95551) belonging to the phosphodiesterase family. It contains a conserved catalytic domain that hydrolyzes 5'-phosphotyrosyl bonds, specifically removing TOP2 adducts from DNA ends. The protein localizes to the nucleus and cytoplasm, and its activity is essential for repairing TOP2-induced DNA damage, particularly in post-mitotic neurons. TDP2 interacts with components of the NHEJ machinery and is regulated by post-translational modifications.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TDP2 Knockout HEK293 Cell Line | EDJ-KQ2148 | Human | 51567 | Details Get a Quote |
| TDP2 Knockout A-549 Cell Line | EDJ-KQ22332 | Human | 51567 | Details Get a Quote |
| TDP2 Knockout HCT 116 Cell Line | EDJ-KQ22333 | Human | 51567 | Details Get a Quote |
| TDP2 Knockout HeLa Cell Line | EDJ-KQ22334 | Human | 51567 | Details Get a Quote |
