TOP3B: DNA Topoisomerase III Beta
A key regulator of genome stability and RNA metabolism
Gene Information Card
| Symbol | TOP3B |
|---|---|
| Full Name | DNA topoisomerase III beta |
| Gene Type | Protein coding |
| Chromosomal Location | 22q11.22 |
| NCBI Gene ID | 8940 ncbi.nlm.nih.gov/gene/8940 |
| Ensembl ID | ENSG00000100038 |
| UniProt ID | O95985 |
| OMIM ID | 603582 |
| HGNC ID | 11993 |
| Aliases | TOP3B1, TOP3B2, MGC138237 |
Description
TOP3B encodes DNA topoisomerase III beta, a type IA topoisomerase that regulates DNA topology by relaxing supercoiled DNA and resolving recombination intermediates. It also functions in RNA metabolism, including mRNA splicing and translation. TOP3B is essential for genome stability and neurodevelopment.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal dominant 26 (MRD26) | Loss-of-function mutations impair topoisomerase activity, leading to defective RNA processing and synaptic dysfunction. | OMIM #617862; ClinVar |
| Schizophrenia (susceptibility) | TOP3B deletions or missense variants disrupt RNA topoisomerase function, altering expression of synaptic genes. | PMID: 23994610; NCBI |
| Breast cancer | Somatic mutations and copy-number alterations in TOP3B may contribute to genomic instability. | COSMIC; PMID: 26689913 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Testis | 9.8 | Medium |
| Heart | 6.2 | Low |
| Liver | 3.1 | Low |
| Kidney | 4.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Embryonic kidney; high expression |
| SH-SY5Y | 11.0 | Neuroblastoma; relevant to neuronal function |
| HeLa | 8.7 | Cervical carcinoma; moderate expression |
| MCF7 | 6.3 | Breast cancer; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1315C>T (p.Arg439*) | Nonsense | Rare | Loss of function; associated with MRD26 |
| c.2023G>A (p.Gly675Arg) | Missense | Rare | Impaired RNA topoisomerase activity; schizophrenia risk |
| c.1685_1686del (p.Lys562fs) | Frameshift | Rare | Loss of function; intellectual disability |
| c.2740C>T (p.Arg914Trp) | Missense | Somatic (0.1% in COSMIC) | Unknown functional effect; observed in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg439*, p.Lys562fs) cause premature truncation, abolishing topoisomerase activity and leading to intellectual disability.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported for TOP3B.
Dominant Negative (DN)
Missense variants (e.g., p.Gly675Arg) may act dominant-negative by disrupting RNA topoisomerase complexes, contributing to schizophrenia susceptibility.
View complete mutation data：
Gene Ontology (GO)
| • DNA topoisomerase type I (single strand cut, ATP-independent) activity | • RNA topoisomerase activity |
| • DNA binding | • RNA binding |
| • chromosome segregation | • DNA recombination |
| • mRNA splicing | • via spliceosome |
| • negative regulation of DNA recombination |
Pathways
• Homologous recombination
• Resolution of D-loop structures
• mRNA splicing (minor spliceosome)
• Telomere maintenance
Protein Summary
TOP3B is a 862-amino acid protein containing a topoisomerase/primase domain and a zinc-finger motif. It catalyzes the transient breakage and rejoining of single-stranded DNA and RNA, relaxing supercoils and resolving recombination intermediates. Unlike TOP3A, TOP3B also acts on RNA, influencing splicing and translation. It interacts with TDRD3 and other RNA-binding proteins to form a functional complex in the nucleus and cytoplasm.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TOP3B Knockout HEK293 Cell Line | EDJ-KQ6410 | Human | 8940 | Details Get a Quote |
| TOP3B Knockout A-549 Cell Line | EDJ-KQ29118 | Human | 8940 | Details Get a Quote |
| TOP3B Knockout HCT 116 Cell Line | EDJ-KQ30450 | Human | 8940 | Details Get a Quote |
| TOP3B Knockout HeLa Cell Line | EDJ-KQ30451 | Human | 8940 | Details Get a Quote |
