TDP1 Gene (Tyrosyl-DNA Phosphodiesterase 1)
Key player in DNA repair and neurodegenerative disease genetics
Gene Information Card
| Symbol | TDP1 |
|---|---|
| Full Name | Tyrosyl-DNA Phosphodiesterase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.2 |
| NCBI Gene ID | 55775 ncbi.nlm.nih.gov/gene/55775 |
| Ensembl ID | ENSG00000100804 |
| UniProt ID | Q9NUW8 |
| OMIM ID | 607198 |
| HGNC ID | 11690 |
| Aliases | TDP1, SCAN1 |
Description
The TDP1 gene encodes tyrosyl-DNA phosphodiesterase 1, a DNA repair enzyme that hydrolyzes the phosphodiester bond between a tyrosine residue and the 3'-phosphate of DNA. It is essential for repairing topoisomerase I (TOP1)-DNA covalent complexes and other 3'-end DNA lesions. Mutations in TDP1 cause spinocerebellar ataxia with axonal neuropathy (SCAN1), an autosomal recessive neurodegenerative disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinocerebellar ataxia with axonal neuropathy (SCAN1) | Loss-of-function mutations impair removal of TOP1-DNA adducts, leading to accumulation of DNA damage and neuronal death. | OMIM #607250; ClinVar; PMID: 15696165 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebellum | 12.5 | Medium |
| Cerebral cortex | 10.2 | Medium |
| Testis | 8.9 | Low |
| Liver | 6.3 | Low |
| Heart | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.3 | High expression |
| HeLa | 11.7 | Medium expression |
| SH-SY5Y | 9.8 | Medium expression |
| HepG2 | 7.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1478A>G (p.His493Arg) | Missense | Homozygous in SCAN1 families | Loss of catalytic activity; impaired DNA repair |
| c.1492C>T (p.Arg498Trp) | Missense | Rare | Reduced enzyme activity |
| c.1105C>T (p.Arg369*) | Nonsense | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations (e.g., p.His493Arg, p.Arg369*) reduce or abolish TDP1 catalytic activity, leading to defective repair of TOP1-DNA complexes and SCAN1.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; SCAN1 is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • DNA repair | • phosphodiesterase activity |
| • hydrolase activity | • topoisomerase I binding |
| • nucleus | • cytoplasm |
Pathways
• DNA damage repair (TOP1-mediated)
• Tyrosyl-DNA phosphodiesterase pathway
• Base excision repair
Protein Summary
TDP1 is a 608-amino acid protein with a conserved catalytic domain that hydrolyzes 3'-phosphotyrosyl bonds. It plays a critical role in resolving stalled topoisomerase I cleavage complexes and repairing oxidative DNA damage. The protein is ubiquitously expressed, with highest levels in the brain and testis. Defects in TDP1 lead to SCAN1, characterized by cerebellar ataxia, axonal neuropathy, and elevated sensitivity to DNA damaging agents.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TDP1 Knockout HEK293 Cell Line | EDJ-KQ15672 | Human | 55775 | Details Get a Quote |
| TDP1 Knockout A-549 Cell Line | EDJ-KQ46576 | Human | 55775 | Details Get a Quote |
| TDP1 Knockout HCT 116 Cell Line | EDJ-KQ46577 | Human | 55775 | Details Get a Quote |
| TDP1 Knockout HeLa Cell Line | EDJ-KQ46578 | Human | 55775 | Details Get a Quote |
