TOP3A

Chr 17AR

DNA topoisomerase III alpha

Also known as: MGRISCE2, PEOB5, TOP3, ZGRF7

NCBI Gene: 7156 ENSG00000177302 UniProt: Q13472 OMIM: 601243

The protein functions as a DNA topoisomerase that relieves supercoiling tension during DNA replication and transcription by transiently cleaving and rejoining single DNA strands, and is essential for mitochondrial DNA decatenation and segregation. Biallelic mutations cause autosomal recessive disorders including microcephaly with growth restriction and increased sister chromatid exchange, as well as progressive external ophthalmoplegia with mitochondrial DNA deletions. This gene is highly constrained against loss-of-function mutations (pLI near 1.0), indicating intolerance to protein truncation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus reducing the number of supercoils and altering the topology of DNA. This enzyme forms a complex with BLM which functions in the regulation of recombination in somatic cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Microcephaly, growth restriction, and increased sister chromatid exchange 2MIM #618097

Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5MIM #618098

Clinical highlights

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

0.68

LOEUF

LOF

Mechanism· G2P

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GeneReview available — TOP3A