TDP2

Chr 6AR

tyrosyl-DNA phosphodiesterase 2

ENSG00000111802UniProt: O95551OMIM: 605764

This protein is a DNA repair enzyme that removes covalent adducts from DNA by hydrolyzing 5'-phosphodiester bonds, particularly repairing topoisomerase 2-induced DNA breaks and protecting genes involved in neurological development. Mutations cause spinocerebellar ataxia with axonal neuropathy-2 (SCAN2), an autosomal recessive disorder characterized by progressive ataxia, peripheral neuropathy, and intellectual disability with childhood to adolescent onset. The gene is highly constrained against loss-of-function mutations (LOEUF 1.13), indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismARLOEUF 1.131 OMIM phenotype
Clinical Summary— TDP2
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Gene-Disease Validity (ClinGen)
spinocerebellar ataxia, autosomal recessive 23 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 56 VUS of 100 total submissions
Explore recent and relevant literature in Research Assistant →
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.000
Z-score 1.10
OE 0.74 (0.49–1.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.11Z-score
OE missense 0.98 (0.86–1.10)
183 obs / 187.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.74 (0.49–1.13)
0≤0.351.4
Missense OE0.98 (0.86–1.10)
0≤0.61.4
Synonymous OE1.37
0≤1.21.6
LoF obs/exp: 15 / 20.4Missense obs/exp: 183 / 187.4Syn Z: -2.37

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic2
VUS56
Likely Benign16
Benign4
9
Pathogenic
2
Likely Pathogenic
56
VUS
16
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
0
0
9
Likely Pathogenic
1
0
1
0
2
VUS
0
53
2
1
56
Likely Benign
0
5
2
9
16
Benign
0
2
0
2
4
Total106051287

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TDP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
TDP2 drives immune evasion and metastatic progression in prostate cancer.
Cao H et al.·PLoS One
2026Open Access
Spinocerebellar ataxia, autosomal recessive type 23 (SCAR23) with compound TDP2 variants: clinical, molecular, and quantitative follow-up.
Colona VL et al.·Neurol Sci
2025Natural history
Indole diketopiperazine-based hybrids with dual TDP1 and TDP2 inhibitory activities from marine fungus aspergillus sp. EGF 15-0-3.
Wei X et al.·Fitoterapia
2026
The effect of dimeric bisbenzimidazoles on the activity of DNA repair enzymes TDP1, TDP2, PARP1 and PARP2.
Dyrkheeva NS et al.·Vavilovskii Zhurnal Genet Selektsii
2025Open Access
Validation of Prognostic Circulating Cell-Free RNA Biomarkers HPGD, PACS1, and TDP2 in Colorectal Cancer Through TaqMan qPCR and Correlation Analysis.
Kan CM et al.·Curr Issues Mol Biol
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients