TDP2

Chr 6p22.3

tyrosyl-DNA phosphodiesterase 2

MANE:: ENST00000378198.9

OMIM: 605764 ↗NCBI: 51567 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

TDP2 · O95551

v62025-08-01

Predicted Aligned Error matrix for TDP2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

85.1/ 100

Confident

362 residues

Confidence breakdown

Very high(≥ 90)71%
Confident(70–90)10%
Low(50–70)3%
Very low(< 50)17%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Ataxia and cerebellar anomalies - narrow panel
BIALLELIC, autosomal or pseudoautosomal
DDG2P
BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta
Skeletal dysplasia

Disease associations (Open Targets)

spinocerebellar ataxia, autosomal recessive 23
0.71
Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to TUD deficiency
0.71
neurodegenerative disease
0.54
hereditary disease
0.41
cerebellar ataxia
0.34
neoplasm
0.10
lung carcinoma
0.08
lung cancer
0.08
prostate cancer
0.08
prostate carcinoma
0.08

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Tyrosyl-DNA phosphodiesterase 2

DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DNA double-strand breaks/DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation (PubMed:27060144, PubMed:27099339). Thereby, protects the transcription of many genes involved in neurological development and maintenance from the abortive activity of TOP2. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DSBs due to DNA damage by radiation and free radicals. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. Acts as a regulator of ribosome biogenesis following stress. Also has 3'-tyrosyl DNA phosphodiesterase activity, but less efficiently and much slower than TDP1. Constitutes the major if not only 5'-tyrosyl-DNA phosphodiesterase in cells. Also acts as an adapter by participating in the specific activation of MAP3K7/TAK1 in response to TGF-beta: associates with components of the TGF-beta receptor-TRAF6-TAK1 signaling module and promotes their ubiquitination dependent complex formation. Involved in non-canonical TGF-beta induced signaling routes. May also act as a negative regulator of ETS1 and may inhibit NF-kappa-B activation