TDP1

Chr 14AR

tyrosyl-DNA phosphodiesterase 1

TDP1 encodes a DNA repair enzyme that removes covalent adducts from DNA by hydrolyzing 3'-phosphodiester bonds, including repair of stalled topoisomerase I-DNA complexes and radiation-induced DNA breaks. Biallelic mutations cause spinocerebellar ataxia with axonal neuropathy 1 (SCAN1), an autosomal recessive disorder affecting both the cerebellum and peripheral nerves. The gene is not highly constrained against loss-of-function variants (LOEUF 1.107), consistent with its recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 1.111 OMIM phenotype
Clinical SummaryTDP1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — TDP1
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.11LOEUF
pLI 0.000
Z-score 1.03
OE 0.82 (0.611.11)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.60Z-score
OE missense 0.91 (0.831.00)
303 obs / 333.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.82 (0.611.11)
00.351.4
Missense OE0.91 (0.831.00)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 30 / 36.8Missense obs/exp: 303 / 333.8Syn Z: 0.48

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TDP1 · 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

No active trials found for this gene.

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Clinical Literature
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