TDP2

Chr 6

tyrosyl-DNA phosphodiesterase 2

Also known as: AD022, EAP2, EAPII, TTRAP, dJ30M3.3, hTDP2

NCBI Gene: 51567 ENSG00000111802 UniProt: O95551

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of a superfamily of divalent cation-dependent phosphodiesterases. The encoded protein associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor associated factors (TRAFs), and inhibits nuclear factor-kappa-B activation. This protein has sequence and structural similarities with APE1 endonuclease, which is involved in both DNA repair and the activation of transcription factors. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpinocerebellar ataxia, autosomal recessive, 23

Clinical highlights

Gene-disease validity (ClinGen)

spinocerebellar ataxia, autosomal recessive 23 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

1.13

LOEUF

LOF

Mechanism· G2P

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