TOP2B

Chr 3

DNA topoisomerase II beta

Also known as: BILU, TOPIIB, top2beta

NCBI Gene: 7155 ENSG00000077097 UniProt: Q02880

This gene encodes DNA topoisomerase II beta, which alters DNA topology by creating transient double-strand breaks to allow DNA strands to pass through each other during transcription and replication, and specifically functions as a key decatenating enzyme important for B-cell differentiation. Mutations cause autosomal dominant B-cell immunodeficiency with distal limb anomalies and urogenital malformations. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be severely deleterious.

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 nuclear enzyme is involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another, thus altering the topology of DNA. Two forms of this enzyme exist as likely products of a gene duplication event. The gene encoding this form, beta, is localized to chromosome 3 and the alpha form is localized to chromosome 17. The gene encoding this enzyme functions as the target for several anticancer agents and a variety of mutations in this gene have been associated with the development of drug resistance. Reduced activity of this enzyme may also play a role in ataxia-telangiectasia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtB-cell immunodeficiency, distal limb anomalies, and urogenital malformations

Clinical highlights

Gene-disease validity (ClinGen)

B-cell immunodeficiency, distal limb anomalies, and urogenital malformations · ADModerateconsider for supplementary testing

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

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