TOP2B: DNA Topoisomerase II Beta
A key enzyme in DNA topology regulation, chromosome segregation, and transcriptional control, implicated in cancer and neurological disorders.
Gene Information Card
| Symbol | TOP2B |
|---|---|
| Full Name | DNA topoisomerase II beta |
| Gene Type | protein-coding |
| Chromosomal Location | 3p24.2 |
| NCBI Gene ID | 7157 ncbi.nlm.nih.gov/gene/7157 |
| Ensembl ID | ENSG00000131747 |
| UniProt ID | Q02880 |
| OMIM ID | 126431 |
| HGNC ID | 11989 |
| Aliases | TOPIIB, TOP2, TOP2BETA |
Description
TOP2B encodes DNA topoisomerase II beta, an enzyme that controls and alters the topologic states of DNA during transcription, replication, and chromosome segregation. It catalyzes the transient breaking and rejoining of double-stranded DNA, allowing DNA strands to pass through one another. TOP2B is essential for proper neural development and is involved in transcriptional regulation of activity-dependent genes. Mutations and altered expression of TOP2B are associated with various cancers and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | TOP2B amplification or overexpression contributes to genomic instability and chemoresistance; co-amplification with ERBB2 is common. | ClinVar, COSMIC |
| Acute lymphoblastic leukemia (ALL) | TOP2B is a target of etoposide; drug-induced DNA breaks can lead to therapy-related AML. | ClinVar, NCBI |
| Intellectual disability | De novo missense mutations in TOP2B impair enzyme activity and are linked to neurodevelopmental phenotypes. | OMIM, ClinVar |
| Autism spectrum disorder | Rare variants in TOP2B disrupt activity-dependent gene expression in neurons. | NCBI, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Heart | 8.3 | Medium |
| Liver | 6.7 | Medium |
| Lung | 5.9 | Medium |
| Kidney | 7.1 | Medium |
| Testis | 9.8 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 14.2 | High expression; sensitive to topoisomerase inhibitors |
| HeLa (cervical) | 10.5 | Moderate expression |
| MCF7 (breast) | 8.9 | Moderate expression; associated with ERBB2 co-amplification |
| SH-SY5Y (neuroblastoma) | 11.3 | High expression; relevant for neurological studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg136Gln | Missense | <0.01% | Reduced catalytic activity; associated with intellectual disability |
| p.Thr147Ala | Missense | <0.01% | Impaired DNA cleavage; linked to autism |
| p.Gly469Ser | Missense | <0.01% | Dominant-negative effect; disrupts dimerization |
| Amplification | Copy number gain | Variable | Overexpression in breast cancer; confers resistance to anthracyclines |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg136Gln, p.Thr147Ala) reduce catalytic activity or DNA binding, impairing topoisomerase function.
Gain of Function (GOF)
Amplification leading to overexpression can increase genomic instability and promote tumorigenesis.
Dominant Negative (DN)
p.Gly469Ser disrupts dimerization and inhibits wild-type enzyme activity.
View complete mutation data：
Gene Ontology (GO)
| • DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity | • DNA binding |
| • ATP binding | • chromosome segregation |
| • DNA topological change | • nucleus |
| • nucleoplasm | • chromatin binding |
Pathways
• DNA replication
• Chromosome maintenance
• Transcription regulation by topoisomerases
• Apoptosis induced by DNA damage
• Etoposide pathway (pharmacodynamics)
Protein Summary
TOP2B is a 1626-amino acid nuclear enzyme that functions as a homodimer. It introduces transient double-strand breaks in DNA to manage supercoiling and entanglement. The protein contains an N-terminal ATPase domain, a central DNA cleavage/ligation domain, and a C-terminal domain involved in nuclear localization and protein-protein interactions. TOP2B is constitutively expressed in most tissues, with highest levels in brain and testis. It is critical for neuronal activity-dependent gene expression and is a target of chemotherapeutic agents such as etoposide and doxorubicin.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TOP2B Knockout HEK293 Cell Line | EDJ-KQ3608 | Human | 7155 | Details Get a Quote |
| TOP2B Knockout A-549 Cell Line | EDJ-KQ25526 | Human | 7155 | Details Get a Quote |
| TOP2B Knockout HCT 116 Cell Line | EDJ-KQ25527 | Human | 7155 | Details Get a Quote |
| TOP2B Knockout HeLa Cell Line | EDJ-KQ25528 | Human | 7155 | Details Get a Quote |
