Details for: TOP3B

Gene ID: 8940

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: TOP3B

Ensembl ID: ENSG00000100038

Description: DNA topoisomerase III beta

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • double-positive, alpha-beta thymocyte CL0000809
    CSI 3.33
    rCSI 3.39%
    PRS 99.35
  • extravillous trophoblast CL0008036
    CSI 2.61
    rCSI 3.23%
    PRS 98.27
  • ependymal cell CL0000065
    CSI 2.47
    rCSI 5.01%
    PRS 93.69
  • intestinal tuft cell CL0019032
    CSI 2.22
    rCSI 3.4%
    PRS 98.63
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.99
    rCSI 3.34%
    PRS 96.66
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.89
    rCSI 4.23%
    PRS 96.44

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [TOP3B](/details-gene/8940) (DNA Topoisomerase III Beta) is a protein-coding gene that encodes a type I topoisomerase essential for maintaining genome integrity. Its primary function involves altering DNA topology to facilitate critical cellular processes such as [DNA recombination](/details-gene/GO:0006310), [DNA repair](/details-gene/GO:0006281), and [chromosome segregation](/details-gene/GO:0007059). Uniquely, [TOP3B](/details-gene/8940) also exhibits [RNA topoisomerase activity](/details-gene/GO:0140226), suggesting a role in resolving complex RNA structures or DNA:RNA hybrids. Reflecting its fundamental role in genomic maintenance, the gene shows significant expression in a diverse range of highly active cell types, including developing immune cells like [double-positive, alpha-beta thymocytes](/details-cell/CL0000809), placental [extravillous trophoblasts](/details-cell/CL0008036), and various cells of the central nervous system, such as [ependymal cells](/details-cell/CL0000065). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [TOP3B](/details-gene/8940) highlights its importance in cells undergoing significant genomic activity, such as proliferation, differentiation, or high levels of transcription. Its highest significance is observed in [double-positive, alpha-beta thymocytes](/details-cell/CL0000809), a stage of T-cell development characterized by V(D)J recombination of T-cell receptor genes. This cellular context is consistent with the gene's established role in managing DNA topological stress during recombination events. High significance in [extravillous trophoblasts](/details-cell/CL0008036), which are highly proliferative and invasive cells essential for placenta formation, further underscores its role in supporting rapid cell division and maintaining genomic stability. Furthermore, [TOP3B](/details-gene/8940) shows notable significance in several cell types within the central nervous system, including [ependymal cells](/details-cell/CL0000065), [lamp5 GABAergic cortical interneurons](/details-cell/CL4023011), and [astrocytes of the cerebral cortex](/details-cell/CL0002605). Its activity in these often long-lived and metabolically active cells may point to a crucial housekeeping role in repairing DNA damage and resolving transcriptional stress that accumulates over time. ## Pathways and Molecular Function [TOP3B](/details-gene/8940) functions as a type IA topoisomerase, which relaxes DNA supercoiling by introducing a transient single-strand break ([GO:0003917](https://www.ebi.ac.uk/QuickGO/term/GO:0003917)). This core molecular function is integral to several high-order biological processes. Its involvement in [DNA recombination](/details-gene/GO:0006310) is well-supported, and it is known to interact with RecQ family helicases to resolve Holliday junction intermediates during this process [Link](https://doi.org/10.1093/nar/27.4.993). This activity is critical for both meiotic recombination and the repair of double-strand breaks. A distinguishing feature of [TOP3B](/details-gene/8940) is its dual substrate specificity, as evidenced by its annotated roles in both [DNA binding](/details-gene/GO:0003677) and [RNA binding](/details-gene/GO:0003723). The enzyme possesses [RNA topoisomerase activity](/details-gene/GO:0140226), suggesting it can resolve topological constraints in RNA molecules or R-loops (stable DNA:RNA hybrids). This function may be particularly important for preventing transcriptional stalling and associated DNA damage. Consistent with its roles in managing the genome, [TOP3B](/details-gene/8940) is localized to the [nucleus](/details-gene/GO:0005634) and is associated with [condensed chromosomes](/details-gene/GO:0000793). ## Research Directions The diverse expression pattern and dual enzymatic activity of [TOP3B](/details-gene/8940) suggest several avenues for future investigation. **Testable Hypotheses:** 1. Given its peak significance in [double-positive, alpha-beta thymocytes](/details-cell/CL0000809), the primary role of [TOP3B](/details-gene/8940) in the thymus is to facilitate the successful completion of V(D)J recombination by resolving complex DNA structures that arise during the process, and its deficiency would lead to impaired T-cell development. 2. The [RNA topoisomerase activity](/details-gene/GO:0140226) of [TOP3B](/details-gene/8940) is critical for preventing the accumulation of transcription-associated R-loops in long-lived, post-mitotic cells like [neurons](/details-cell/CL4023011). Loss of this function may contribute to the genomic instability observed in certain neurodegenerative diseases. **Proposed Experiment:** To test the second hypothesis regarding its role in R-loop resolution in neurons, a compelling experiment would be to use a human iPSC-derived neuronal model. - **Methodology:** [TOP3B](/details-gene/8940) would be depleted in a neuronal cell line (e.g., [lamp5 GABAergic cortical interneurons](/details-cell/CL4023011)) using CRISPR interference (CRISPRi). The impact on R-loop formation would be quantified genome-wide using DNA:RNA Immunoprecipitation followed by sequencing (DRIP-seq). Concurrently, downstream effects on genomic stability would be assessed by measuring DNA damage markers (e.g., γH2AX foci) and analyzing transcriptional changes via RNA-seq. - **Expected Outcome:** Depletion of [TOP3B](/details-gene/8940) would be expected to cause a significant increase in R-loop abundance at highly transcribed gene loci, correlated with an increase in DNA damage markers and altered gene expression profiles, thereby establishing a direct mechanistic link. **Therapeutic Potential:** As a fundamental component of the DNA repair and maintenance machinery, [TOP3B](/details-gene/8940) presents a complex therapeutic profile. Direct inhibition is likely to cause significant toxicity in healthy, highly proliferative tissues (e.g., hematopoietic stem cells, gut epithelium), limiting its utility as a broad-spectrum anticancer agent. However, it may hold potential as a target in specific contexts, such as in synthetic lethality approaches. Cancers that have deficiencies in other DNA repair pathways (e.g., BRCA1/2 mutations) might develop a heightened dependency on [TOP3B](/details-gene/8940) for survival. In such cases, targeted inhibition of [TOP3B](/details-gene/8940) could selectively eliminate cancer cells while sparing healthy tissue, a strategy that warrants further investigation.

Genular Protein ID: 3876072840

Symbol: TOP3B_HUMAN

Name: DNA topoisomerase 3-beta-1

UniProtKB Accession Codes:

O95985 A0M8Q3 Q9BUP5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DNASU 1 DisGeNET 1 EC 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 11 Gene3D 4 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 11 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 RefSeq 7 SMART 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9927731

Title: A new human topoisomerase III that interacts with SGS1 protein.

PubMed ID: 9927731

DOI: 10.1093/nar/27.4.993

PubMed ID: 9074928

Title: One-megabase sequence analysis of the human immunoglobulin lambda gene locus.

PubMed ID: 9074928

DOI: 10.1101/gr.7.3.250

PubMed ID: 15461802

Title: A genome annotation-driven approach to cloning the human ORFeome.

PubMed ID: 15461802

DOI: 10.1186/gb-2004-5-10-r84

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 862
  • Mass: 96662
  • Checksum: 75532827856CFF8F
  • Sequence:
    • MKTVLMVAEK PSLAQSIAKI LSRGSLSSHK GLNGACSVHE YTGTFAGQPV RFKMTSVCGH 
VMTLDFLGKY NKWDKVDPAE LFSQAPTEKK EANPKLNMVK FLQVEGRGCD YIVLWLDCDK 
EGENICFEVL DAVLPVMNKA HGGEKTVFRA RFSSITDTDI CNAMACLGEP DHNEALSVDA 
RQELDLRIGC AFTRFQTKYF QGKYGDLDSS LISFGPCQTP TLGFCVERHD KIQSFKPETY 
WVLQAKVNTD KDRSLLLDWD RVRVFDREIA QMFLNMTKLE KEAQVEATSR KEKAKQRPLA 
LNTVEMLRVA SSSLGMGPQH AMQTAERLYT QGYISYPRTE TTHYPENFDL KGSLRQQANH 
PYWADTVKRL LAEGINRPRK GHDAGDHPPI TPMKSATEAE LGGDAWRLYE YITRHFIATV 
SHDCKYLQST ISFRIGPELF TCSGKTVLSP GFTEVMPWQS VPLEESLPTC QRGDAFPVGE 
VKMLEKQTNP PDYLTEAELI TLMEKHGIGT DASIPVHINN ICQRNYVTVE SGRRLKPTNL 
GIVLVHGYYK IDAELVLPTI RSAVEKQLNL IAQGKADYRQ VLGHTLDVFK RKFHYFVDSI 
AGMDELMEVS FSPLAATGKP LSRCGKCHRF MKYIQAKPSR LHCSHCDETY TLPQNGTIKL 
YKELRCPLDD FELVLWSSGS RGKSYPLCPY CYNHPPFRDM KKGMGCNECT HPSCQHSLSM 
LGIGQCVECE SGVLVLDPTS GPKWKVACNK CNVVAHCFEN AHRVRVSADT CSVCEAALLD 
VDFNKAKSPL PGDETQHMGC VFCDPVFQEL VELKHAASCH PMHRGGPGRR QGRGRGRARR 
PPGKPNPRRP KDKMSALAAY FV

Genular Protein ID: 2521936526

Symbol: A8K4N2_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K4N2

Database IDs:

ARBA 6 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 2 CTD 1 DNASU 1 DisGeNET 1 EC 1 EMBL 2 GO 4 Gene3D 4 InterPro 11 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 3 PeptideAtlas 1 Pfam 2 RefSeq 1 RuleBase 1 SAM 1 SMART 3 SUPFAM 1

Sequence Information:

  • Length: 862
  • Mass: 96708
  • Checksum: 0F2F790BD7A8656E
  • Sequence:
    • MKTVLMVAEK PSLAQSIAKI LSRGSLSSHK GLNGACSVHE YTGTFAGQPV RFKMTSVCGH 
VMTLDFLGKY NKWDKVDPAE LFSQAPTEKK EANPKLNMVK FLQVEGRGCD YIVLWLDCDK 
EGENICFEVL DAVLPVMNKA HGGEKTVFRA RFSSITDTDI CNAMACLGEP DHNEALSVDA 
RQELDLRIGC AFTRFQTKYF QGKYGDLDSS LISFGPCQTP TLGFCVERHD KIQSFKPETY 
WVLQAKVNTD KDRSLLLDWD RVRVFDREIA QMFLNMTKLE KEAQVEATSR KEKAKQRPLA 
LNTVEMLRVA SSSLGMGPQH AMQTAERLYT QGYISYPRTE TTHYPENFDL KGSLRQQANH 
PYWADTVKRL LAEGINRPRK GHDAGDHPPI TPMKSATEAE LGGDAWRLYE YITRHFIATV 
SHDCKYLQST ISFRIGPELF TCSGKTVLSP GFTEVMPWQS VPLEESLPTC QRGDAFPVGE 
VKMLEKQTNP PDYLTEAELI TLMEKHGICT DASIPVHINN ICQRNYVTVE SGRRLKPTNL 
GIVLVHGYYK IDAELVLPTI RSAVEKQLNL IAQGKADYRQ VLGHTLDVFK RKFHYFVDSI 
AGMDELMEVS FSPLAATGKP LSRCGKCHRF MKYIQAKPSR LHCSHCDETY TLPQNGTIKL 
YKELRCPLDD FELVLWSSGS RGKSYPLCPY CYNHPPFRDM KKGMGCNECT HPSCQHSLSM 
LGIGQCVECE SGVLVLDPTS GPKWKVACNK CNVVAHCFEN AHRVRVSADT CSVCEAALLD 
VDFNKAKSPL PGDETQHMGC VFCDPVFQEL VELKHAASCH PMHRGGPGRR QGRGRGRARR 
PPGKPNPRRP KDKMSALAAY FV