TOP2B

Summary

TOP2B (DNA topoisomerase II beta, HGNC:11990) is a protein-coding gene on chromosome 3p24.2, encoding DNA topoisomerase 2-beta (Q02880). Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand.

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.

Source: NCBI Gene 7155 — RefSeq curated summary.

At a glance

• Gene–disease (curated): B-cell immunodeficiency, distal limb anomalies, and urogenital malformations (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 1,159 total — 4 pathogenic
• Druggable target: yes — 11 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001330700

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11990
Approved symbol	TOP2B
Name	DNA topoisomerase II beta
Location	3p24.2
Locus type	gene with protein product
Status	Approved
Aliases	top2beta, TOPIIB
Ensembl gene	ENSG00000077097
Ensembl biotype	protein_coding
OMIM	126431
Entrez	7155

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 18 retained_intron, 9 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000264331, ENST00000413971, ENST00000424225, ENST00000435706, ENST00000470132, ENST00000475717, ENST00000491510, ENST00000699028, ENST00000699029, ENST00000699030, ENST00000699031, ENST00000699032, ENST00000699033, ENST00000699034, ENST00000699035, ENST00000699036, ENST00000699038, ENST00000699039, ENST00000699040, ENST00000699041, ENST00000699042, ENST00000699043, ENST00000699044, ENST00000699045, ENST00000699046, ENST00000854207, ENST00000854208, ENST00000957358, ENST00000957359, ENST00000957360

RefSeq mRNA: 2 — MANE Select: NM_001330700 NM_001068, NM_001330700

CCDS: CCDS46776, CCDS82746

Canonical transcript exons

ENST00000264331 — 36 exons

Exon	Start	End
ENSE00000581630	25635936	25636148
ENSE00000581636	25630312	25630469
ENSE00000581643	25624682	25624803
ENSE00000581645	25623515	25623746
ENSE00000757645	25624297	25624445
ENSE00000757647	25626560	25626674
ENSE00000757648	25626772	25626864
ENSE00000757660	25630801	25630939
ENSE00000757662	25632446	25632583
ENSE00000757668	25633841	25634014
ENSE00000757672	25637215	25637312
ENSE00000757675	25638165	25638310
ENSE00000997555	25664229	25664907
ENSE00000997560	25618418	25618509
ENSE00000997564	25619862	25620062
ENSE00000997569	25642322	25642385
ENSE00000997571	25620682	25620816
ENSE00001133532	25632693	25632794
ENSE00001154487	25597984	25598477
ENSE00001649661	25645300	25645470
ENSE00001673966	25643694	25643784
ENSE00001688151	25630029	25630154
ENSE00001698838	25627187	25627296
ENSE00003459496	25606043	25606122
ENSE00003474282	25599435	25599529
ENSE00003491541	25628847	25628952
ENSE00003557336	25615205	25615288
ENSE00003572286	25609183	25609344
ENSE00003579863	25629035	25629145
ENSE00003593334	25607171	25607375
ENSE00003604124	25601100	25601225
ENSE00003617488	25615431	25615586
ENSE00003619156	25618654	25618849
ENSE00003632037	25604760	25604870
ENSE00003643062	25609568	25609712
ENSE00003689111	25612515	25612709

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.4911 / max 880.1026, expressed in 1816 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41504	43.4911	1816
41500	0.3776	156

Top tissues by expression

301 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.48	gold quality
cortical plate	UBERON:0005343	99.41	gold quality
ventricular zone	UBERON:0003053	99.36	gold quality
endothelial cell	CL:0000115	98.86	gold quality
calcaneal tendon	UBERON:0003701	98.52	gold quality
embryo	UBERON:0000922	98.37	gold quality
cerebellar cortex	UBERON:0002129	98.03	gold quality
cerebellar hemisphere	UBERON:0002245	98.02	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.84	gold quality
cerebellum	UBERON:0002037	97.47	gold quality
pigmented layer of retina	UBERON:0001782	97.45	gold quality
retina	UBERON:0000966	97.43	gold quality
colonic epithelium	UBERON:0000397	97.36	gold quality
adrenal tissue	UBERON:0018303	97.34	gold quality
rectum	UBERON:0001052	97.30	gold quality
tonsil	UBERON:0002372	97.26	gold quality
mucosa of stomach	UBERON:0001199	97.15	gold quality
germinal epithelium of ovary	UBERON:0001304	97.04	gold quality
corpus epididymis	UBERON:0004359	96.97	gold quality
endometrium	UBERON:0001295	96.87	gold quality
body of uterus	UBERON:0009853	96.82	gold quality
medial globus pallidus	UBERON:0002477	96.76	gold quality
left ovary	UBERON:0002119	96.74	gold quality
bone marrow	UBERON:0002371	96.74	gold quality
primary visual cortex	UBERON:0002436	96.68	gold quality
caput epididymis	UBERON:0004358	96.68	gold quality
right frontal lobe	UBERON:0002810	96.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.60	gold quality
skin of abdomen	UBERON:0001416	96.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.54	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	52.90
E-CURD-112	yes	50.82
E-HCAD-6	yes	43.24
E-MTAB-9067	yes	18.28
E-CURD-122	yes	5.53
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
CDH13	Activation
DAB1	Activation
EPHA7	Activation
PBX3	Activation
RELN	Activation
RUNX1	Activation
SST	Activation

Upstream regulators (CollecTRI, top): CUX1, NONO, NOTO, PARP1, SFPQ, SP1, TFDP1

miRNA regulators (miRDB)

61 targeting TOP2B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-607	99.97	73.62	5593
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-4524A-3P	99.72	66.85	2406

Literature-anchored findings (GeneRIF, showing 40)

• topo II is not an immobile, structural component of the chromosomal scaffold or the interphase karyoskeleton, but rather a dynamic interaction partner of such structures. (PMID:11927602)
• shows for the first time that topoisomerase II beta is a substrate for PKC zeta, and that PKC zeta may significantly influence topoisomerase II inhibitor-induced cytotoxicity by altering topoisomerase II beta activity through its kinase function (PMID:12105221)
• analysis of binding sites for NF-Y and Sp1, which are critical for TOP2B transcription (PMID:12197834)
• proteasomal degradation of TOP2beta induced by the TOP2-DNA covalent complex or the TOP2 circular clamp is due to transcriptional arrest but not DNA damage (PMID:12629207)
• topoisomerase II is actively exported from the nuclease and is mediated by a CRM1-dependent pathway (PMID:12821127)
• demonstrated that neither A or B isoform has any preference for a specific DNA conformation as substrate under the conditions used in these experiments (PMID:14596941)
• Topoisomerase II is a potential target for new antilesishmanial drug development. (PMID:14723357)
• When both topo IIalpha and topo IIbeta were removed, the segregation of chromosomes was severely arrested, suggesting that topo IIbeta could partially substitute for topo IIalpha. (PMID:14996935)
• UVA-modified DNA is preferentially targeted and processed by topoisomerase IIalpha and IIbeta. (PMID:15044480)
• This is the first report that conjugated PUFA such as cEPA act as inhibitors of pols and topos. (PMID:15680922)
• Further analysis of purified virus showed that HIV-1 virion contained topoisomerase II isoform-specific kinase activities, which were partially isolated (PMID:16091284)
• TOP2A may have a role in response to doxorubicin-based chemotherapy (PMID:16502015)
• Topoisomerase II alpha and beta isoforms are present in the pre-integration complexes, suggesting their significant role in HIV-1 replication. (PMID:16712776)
• reported that signal-dependent activation of gene transcription by nuclear receptors and other classes of transcription factors requires DNA topoisomerase IIbeta-dependent, transient, site-specific dsDNA break formation (PMID:16794079)
• Reduced expression of topo IIbeta induces apoptosis in part by impairing the anti-oxidant capacity of the cell owing to downregulation of PRDX2. (PMID:16932348)
• EGF may have a role in drug resistance in cultured tumor cells through the downregulation of topoII (PMID:16969495)
• We conclude that topo II alpha and beta nuclear export is inhibited in proliferating cells so that these proteins do not shuttle. (PMID:17182034)
• directed mutation of TOP2B demonstrated missense mutations selected for acridine resistance varied with acridine structure (PMID:17209120)
• Topo IIalpha and beta mRNA expression, but not the Topo IIalpha labeling index, might be a useful marker for sensitivity to etoposide in human malignant neuroepithelial tumors. (PMID:17361331)
• The C-terminal region of human topoisomerase II beta determines its isoform-specific functions in proliferating cells. (PMID:17526531)
• TopoIIbeta binds a retinoic acid response element. Inhibition causes hyperacetylation of histone 3 at lysine 9 & transcription activation.Increased levels of & association with TopoIIbeta cause resistance to RA in acute promyelocytic leukemia cell lines. (PMID:18212063)
• NRF-1 can also directly interact with poly(ADP-ribose) polymerase 1 (PARP-1) and co-purify the PARP-1.DNA-PK.Ku80.Ku70.topoisomerase IIbeta-containing protein complex. (PMID:19181665)
• Data show a difference in metal ion utilization during DNA cleavage mediated by human topoisomerase IIalpha and IIbeta. (PMID:19222228)
• Data show significant associations between SNPs in RARA, RARB, TOP2B and RARG, RXRA, TLR3, TRIM5 and RIG-I genes and rubella virus-specific cytokine immune responses. (PMID:19902255)
• [review] Accumulating studies show the significant role of Top IIbeta in neuronal development through regulating expression of certain genes in cells committed to the neuronal fate after the final division. (PMID:20882068)
• Tyrosine 656 in topoisomerase II beta is important for the catalytic activity of the enzyme. (PMID:21280220)
• Overexpression of Lewis(y) antigen confers cell adhesion-mediated drug resistance to apoptosis in ovarian cancer cells by the upregulation of Topo-I and Topo-II beta. (PMID:21542140)
• results suggest that the low expression of TOPOIIbeta in patients with tongue carcinoma indicates that intrinsic drug resistance may exist in tongue carcinoma, and is associated with tumor differentiation and cisplatin resistance in tongue carcinoma. (PMID:21793937)
• Downregulating topoisomerase IIbeta confers resistance specifically to mitoxantrone. (PMID:23696245)
• Top2beta-DNA cleavage complexes arrest transcription elongation and induce a proteasomal degradation of Top2beta on DNA. (PMID:23938298)
• There is an association between chemosensitivity and Pgp, GST-pi and Topo II expression in gastric cancer. (PMID:24326092)
• These results are consistent with the hypothesis that etoposide quinone contributes to etoposide-related leukemogenesis through an interaction with topoisomerase IIbeta. (PMID:24766193)
• This study demonstrated that top IIbeta overexpression is necessary for RA-induced neuronal differentiation. (PMID:24801450)
• Proteolytic degradation of Top2 enables the processing of Top2.DNA and Top2.RNA covalent complexes by TDP2. (PMID:24808172)
• Human cytomegalovirus IE1 exon 4 interacts with Topoisomerase IIbeta (TOPOIIbeta), whose activity is required for viral genome persistence and maintenance via binding to a cis-acting viral maintenance element. (PMID:25011107)
• Data suggest that DNA topoisomerase IIbeta (topoIIbeta) silencing can significantly alter the gene expression pattern of genes involved in variety of biological processes and signal transduction pathways. (PMID:25217229)
• Cinobufacini inhibited the proliferation of the HepG-2 cells induced apoptosis in a dose- and time-dependent manner and downregulated the mRNA and protein expression levels of TOPO I and TOPO II (PMID:25815590)
• A direct interaction between Ku70/86 and BRG1 brings together SWI/SNF remodeling capabilities and TOP2beta activity to enhance the transcriptional response to hormone stimulation. (PMID:26055322)
• during early development, TOP2A is likely to have a role in cell proliferation, whereas TOP2B is expressed in post-mitotic cells and may be important in controlling expression of long genes even at this early stage. (PMID:26612825)
• TopoIIbeta is involved in the cascade of coactivator complexes that are recruited to LTR for regulation of HIV-1 transcription. (PMID:26876283)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	top2b	ENSDARG00000034195
mus_musculus	Top2b	ENSMUSG00000017485
rattus_norvegicus	Top2b	ENSRNOG00000048795

Paralogs (1): TOP2A (ENSG00000131747)

Protein

Protein identifiers

DNA topoisomerase 2-beta — Q02880 (reviewed: Q02880)

Alternative names: DNA topoisomerase II, beta isozyme

All UniProt accessions (5): Q02880, A0A8V8TN33, A0A8V8TPE3, E9PCY5, H7BZ82

UniProt curated annotations — full annotation on UniProt →

Function. Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand. Plays a role in B-cell differentiation.

Subunit / interactions. Homodimer. Interacts with KIAA1210. Interacts with PLSCR1.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm.

Tissue specificity. Expressed in the tonsil, spleen, lymph node, thymus, skin, pancreas, testis, colon, kidney, liver, brain and lung. Also found in breast, colon and lung carcinomas, Hodgkin’s disease, large-cell non-Hodgkin’s lymphoma, lymphocytic lymphomas and seminomas.

Post-translational modifications. (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1; leading to stabilized SUMOylated TOP2A trapped in cleavage complexes, which halts the DNA damage response to TOP2A-induced double-strand DNA breaks. SUMOylated.

Disease relevance. Defects in TOP2B may be involved in global developmental delay with autism spectrum disorder (ASD). B-cell immunodeficiency, distal limb anomalies, and urogenital malformations (BILU) [MIM:609296] An autosomal dominant disorder characterized by humoral immunodeficiency with undetectable B cells, distal limb anomalies, dysmorphic facial features, and urogenital malformations. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds two Mg(2+) per subunit. The magnesium ions form salt bridges with both the protein and the DNA. Can also accept other divalent metal cations, such as Mn(2+) or Ca(2+).

Miscellaneous. Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.

Similarity. Belongs to the type II topoisomerase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q02880-1	Beta-2	yes
Q02880-2	Beta-1

RefSeq proteins (2): NP_001059, NP_001317629* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001154	TopoII_euk	Family
IPR001241	Topo_IIA	Family
IPR002205	Topo_IIA_dom_A	Domain
IPR003594	HATPase_dom	Domain
IPR006171	TOPRIM_dom	Domain
IPR012542	DTHCT	Domain
IPR013506	Topo_IIA_bsu_dom2	Domain
IPR013757	Topo_IIA_A_a_sf	Homologous_superfamily
IPR013758	Topo_IIA_A/C_ab	Homologous_superfamily
IPR013759	Topo_IIA_B_C	Homologous_superfamily
IPR013760	Topo_IIA-like_dom_sf	Homologous_superfamily
IPR014721	Ribsml_uS5_D2-typ_fold_subgr	Homologous_superfamily
IPR018522	TopoIIA_CS	Conserved_site
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR031660	TOPRIM_C	Domain
IPR034157	TOPRIM_TopoII	Domain
IPR036890	HATPase_C_sf	Homologous_superfamily
IPR050634	DNA_Topoisomerase_II	Family

Pfam: PF00204, PF00521, PF01751, PF02518, PF08070, PF16898

Enzyme classification (BRENDA):

• EC 5.6.2.2 — DNA topoisomerase (ATP-hydrolysing) (BRENDA: 99 organisms, 409 substrates, 1698 inhibitors, 38 Km, 31 kcat entries)
• EC 5.99.1.3 — DNA topoisomerase (ATP-hydrolysing) (BRENDA: 0 organisms, 0 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0771–1.5	22
DNA	0.21–0.94	6
DATP	0.5–0.63	2
SUPERCOILED DNA	—	1

UniProt features (227 total): helix 52, strand 45, modified residue 35, cross-link 34, turn 11, binding site 9, site 9, compositionally biased region 7, sequence variant 5, mutagenesis site 5, region of interest 5, sequence conflict 3, domain 2, initiator methionine 1, chain 1, splice variant 1, active site 1, short sequence motif 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
9BQ8	X-RAY DIFFRACTION	1.25
9BQC	X-RAY DIFFRACTION	1.45
9BQD	X-RAY DIFFRACTION	1.5
7QFO	X-RAY DIFFRACTION	1.9
9BQA	X-RAY DIFFRACTION	1.9
3QX3	X-RAY DIFFRACTION	2.16
4J3N	X-RAY DIFFRACTION	2.3
5ZRF	X-RAY DIFFRACTION	2.3
7ZBG	X-RAY DIFFRACTION	2.3
5ZAD	X-RAY DIFFRACTION	2.54
4G0V	X-RAY DIFFRACTION	2.55
5GWJ	X-RAY DIFFRACTION	2.57
7QFN	X-RAY DIFFRACTION	2.62
4G0W	X-RAY DIFFRACTION	2.7
4G0U	X-RAY DIFFRACTION	2.7
5GWI	X-RAY DIFFRACTION	2.74
5ZEN	X-RAY DIFFRACTION	2.75
8KE7	X-RAY DIFFRACTION	2.8
5ZQF	X-RAY DIFFRACTION	3.87
7YQ8	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02880-F1	74.09	0.45

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (10): 826 (o-(5’-phospho-dna)-tyrosine intermediate); 510 (interaction with dna); 513 (interaction with dna); 682 (interaction with dna); 683 (interaction with dna); 744 (interaction with dna); 778 (interaction with dna); 825 (transition state stabilizer); 877 (important for dna bending; intercalates between base pairs of target dna); 952 (interaction with dna)

Ligand- & substrate-binding residues (9): 112; 141; 169–171; 182–189; 397–399; 482; 562; 562; 564

Post-translational modifications (69): 1440, 1456, 1490, 28, 29, 2, 3, 1236, 1292, 1336, 1340, 1342, 1344, 1358, 1370, 1375, 1400, 1403, 1413, 1421 …

Mutagenesis-validated functional residues (5):

Position	Phenotype
482	strongly reduced enzyme activity.
485	slightly reduced enzyme activity.
508	slightly reduced enzyme activity.
510	strongly reduced enzyme activity.
515	slightly reduced enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-4615885	SUMOylation of DNA replication proteins

MSigDB gene sets: 276 (showing top): WENDT_COHESIN_TARGETS_UP, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_B_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION, GOBP_NEUROGENESIS, GOBP_CELLULAR_SENESCENCE, KAUFFMANN_DNA_REPAIR_GENES, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_ATP, GOBP_DNA_CONFORMATION_CHANGE, GOBP_ORGANELLE_FISSION

GO Biological Process (13): resolution of meiotic recombination intermediates (GO:0000712), sister chromatid segregation (GO:0000819), neuron migration (GO:0001764), DNA topological change (GO:0006265), axonogenesis (GO:0007409), B cell differentiation (GO:0030183), forebrain development (GO:0030900), positive regulation of single stranded viral RNA replication via double stranded DNA intermediate (GO:0045870), cellular response to hydrogen peroxide (GO:0070301), cellular response to ATP (GO:0071318), cellular senescence (GO:0090398), positive regulation of double-strand break repair via nonhomologous end joining (GO:2001034), DNA metabolic process (GO:0006259)

GO Molecular Function (11): DNA binding (GO:0003677), chromatin binding (GO:0003682), DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity (GO:0003918), ATP binding (GO:0005524), ribonucleoprotein complex binding (GO:0043021), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), DNA topoisomerase activity (GO:0003916), protein binding (GO:0005515), ATP-dependent activity, acting on DNA (GO:0008094), isomerase activity (GO:0016853)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), ribonucleoprotein complex (GO:1990904), heterochromatin (GO:0000792)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
catalytic activity, acting on DNA	2
nuclear lumen	2
cellular anatomical structure	2
reciprocal meiotic recombination	1
meiosis I cell cycle process	1
chromosome organization	1
nuclear chromosome segregation	1
cell migration	1
generation of neurons	1
DNA metabolic process	1
DNA conformation change	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
lymphocyte differentiation	1
B cell activation	1
brain development	1
anatomical structure development	1
single stranded viral RNA replication via double stranded DNA intermediate	1
positive regulation of viral genome replication	1
regulation of single stranded viral RNA replication via double stranded DNA intermediate	1
positive regulation of RNA biosynthetic process	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
response to ATP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
cellular process	1
cellular response to stress	1
double-strand break repair via nonhomologous end joining	1
positive regulation of double-strand break repair	1
regulation of double-strand break repair via nonhomologous end joining	1
nucleic acid metabolic process	1
nucleic acid binding	1
DNA topoisomerase activity	1
ATP-dependent activity, acting on DNA	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein-containing complex binding	1

Protein interactions and networks

STRING

4831 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOP2B	TOPBP1	Q92547	937
TOP2B	TOP1MT	Q969P6	929
TOP2B	TOP1	P11387	876
TOP2B	TDP2	O95551	818
TOP2B	AR	P10275	771
TOP2B	TOP3A	Q13472	646
TOP2B	ILF2	Q12905	625
TOP2B	TOP3B	O95985	617
TOP2B	RARG	P13631	611
TOP2B	TDP1	Q9NUW8	606
TOP2B	CTCF	P49711	598
TOP2B	ACTB	P02570	590
TOP2B	XPC	Q01831	589
TOP2B	ILF3	Q12906	570
TOP2B	PGK1	P00558	562

IntAct

109 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PRKCD	TOP2A	psi-mi:“MI:0914”(association)	0.680
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
CUL5	SOCS7	psi-mi:“MI:0914”(association)	0.640
USF1	PARP1	psi-mi:“MI:0914”(association)	0.560
USF1	PARP1	psi-mi:“MI:0915”(physical association)	0.560
NAPA	NBAS	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
MED27	POLR2D	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
HSD3B2	NARS1	psi-mi:“MI:0914”(association)	0.530
PTGES3	AIP	psi-mi:“MI:0914”(association)	0.530
PIAS4	TOP2B	psi-mi:“MI:0915”(physical association)	0.500
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
NOTCH1	PRKDC	psi-mi:“MI:0914”(association)	0.460
ESR1		psi-mi:“MI:0914”(association)	0.460
VAMP4	TOP2B	psi-mi:“MI:0915”(physical association)	0.400
Top2b		psi-mi:“MI:0915”(physical association)	0.400
MED15	TOP2B	psi-mi:“MI:0915”(physical association)	0.400
MED24	TOP2B	psi-mi:“MI:0915”(physical association)	0.400
FOXD3	MYL12B	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
NP	HNRNPCL1	psi-mi:“MI:0914”(association)	0.350
NP	KPNA4	psi-mi:“MI:0914”(association)	0.350
NP	IPO5	psi-mi:“MI:0914”(association)	0.350

BioGRID (358): TOP2B (Affinity Capture-MS), TOP2B (Affinity Capture-MS), UBE2I (Two-hybrid), TOP2B (Reconstituted Complex), TOP2B (Affinity Capture-Western), TOP2B (Biochemical Activity), TOP2B (Reconstituted Complex), TOP2B (Affinity Capture-Western), TOP2B (Two-hybrid), TOP2B (Affinity Capture-RNA), GLYR1 (Co-fractionation), POLE3 (Co-fractionation), SUPT16H (Co-fractionation), TOP1 (Co-fractionation), TOP2B (Affinity Capture-MS)

ESM2 similar proteins: A1CRW7, A1D4S4, A2Q8L1, A3GFA2, A4R1J7, A5DA00, A5E7S3, A7SDW5, C7ZA26, F4JWP9, O74873, O94316, O94672, P0CR38, P0CR39, P0CR40, P0CR41, P15303, P26659, P34567, P48612, P50444, Q02880, Q0CUU1, Q0US25, Q0V3J4, Q1DY01, Q2HB00, Q2URM9, Q4P9K4, Q4PE39, Q4WK80, Q54T59, Q5A455, Q5BGR9, Q6BQT6, Q6C2T4, Q6C5L5, Q6CPH3, Q6FSI6

Diamond homologs: A0A0G2Q9F8, A1SCM2, B8GXQ0, C1CVF4, C5C7X9, C5CHA8, G5ECQ8, O16140, O24308, O42130, O42131, O46374, O51859, O61078, O67137, O84192, O93794, P06786, P08096, P0A2I3, P0A2I4, P0AES4, P0AES5, P0AES6, P0AES7, P0AES8, P0CAX1, P11388, P12531, P13364, P14829, P15348, P22118, P22447, P27570, P29435, P30182, P30190, P34030, P34031

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
TOP2B	“up-regulates quantity by expression”	RELN	“transcriptional regulation”
TOP2B	“up-regulates quantity by expression”	DAB1	“transcriptional regulation”
TOP2B	“up-regulates quantity by expression”	CDH13	“transcriptional regulation”
TOP2B	“up-regulates quantity by expression”	SST	“transcriptional regulation”
TOP2B	“up-regulates quantity by expression”	PBX3	“transcriptional regulation”
TOP2B	“up-regulates quantity by expression”	EPHA7	“transcriptional regulation”
TOP2B	down-regulates	Survival
“Daunorubicin hydrochloride”	“down-regulates activity”	TOP2B	“chemical inhibition”
etoposide	“down-regulates activity”	TOP2B	“chemical inhibition”
idarubicin	“down-regulates activity”	TOP2B	“chemical inhibition”
teniposide	“down-regulates activity”	TOP2B	“chemical inhibition”
valrubicin	“down-regulates activity”	TOP2B	“chemical inhibition”
CSNK1D	“down-regulates quantity by destabilization”	TOP2B	phosphorylation
ATM	“down-regulates quantity by destabilization”	TOP2B	phosphorylation
SCF-betaTRCP	“down-regulates quantity by destabilization”	TOP2B	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Influenza Infection	6	10.3×	5e-03
SUMOylation of DNA damage response and repair proteins	6	8.6×	8e-03
Estrogen-dependent gene expression	8	5.9×	8e-03
Viral Infection Pathways	16	4.8×	5e-05
Infectious disease	18	4.4×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	6	14.7×	9e-04
double-strand break repair	7	11.6×	9e-04
RNA polymerase II preinitiation complex assembly	5	11.1×	1e-02
cytoplasmic translation	6	9.0×	8e-03
chromosome segregation	6	8.5×	1e-02
chromatin remodeling	10	5.9×	2e-03
DNA damage response	12	5.2×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1159 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	555
Likely benign	479
Benign	58

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1319982	NM_001330700.2(TOP2B):c.1776_1778del (p.Glu593del)	Pathogenic
1319983	NM_001330700.2(TOP2B):c.1463C>T (p.Ser488Leu)	Pathogenic
1319985	NM_001330700.2(TOP2B):c.1468G>C (p.Ala490Pro)	Pathogenic
265791	NM_001330700.2(TOP2B):c.187C>T (p.His63Tyr)	Pathogenic

SpliceAI

5324 predictions. Top by Δscore:

Variant	Effect	Δscore
3:25604754:ACAT:A	donor_loss	1.0000
3:25604755:CAT:C	donor_loss	1.0000
3:25604756:ATAC:A	donor_loss	1.0000
3:25604757:TACC:T	donor_loss	1.0000
3:25604758:A:AC	donor_gain	1.0000
3:25604758:A:T	donor_loss	1.0000
3:25604758:AC:A	donor_gain	1.0000
3:25604759:C:CC	donor_gain	1.0000
3:25604759:C:CG	donor_loss	1.0000
3:25604759:CC:C	donor_gain	1.0000
3:25604775:CCGTT:C	donor_gain	1.0000
3:25604785:TGGA:T	donor_gain	1.0000
3:25604871:C:CC	acceptor_gain	1.0000
3:25606123:C:CC	acceptor_gain	1.0000
3:25606126:T:TC	acceptor_gain	1.0000
3:25607166:CTTA:C	donor_gain	1.0000
3:25607167:TTACT:T	donor_loss	1.0000
3:25607168:TA:T	donor_loss	1.0000
3:25607169:A:AC	donor_gain	1.0000
3:25607169:ACT:A	donor_gain	1.0000
3:25607170:C:CT	donor_gain	1.0000
3:25607170:CT:C	donor_gain	1.0000
3:25607170:CTC:C	donor_gain	1.0000
3:25607170:CTCT:C	donor_gain	1.0000
3:25607170:CTCTG:C	donor_gain	1.0000
3:25607371:TTCGG:T	acceptor_gain	1.0000
3:25607372:TCGG:T	acceptor_gain	1.0000
3:25607373:CGG:C	acceptor_gain	1.0000
3:25607373:CGGC:C	acceptor_gain	1.0000
3:25607374:GG:G	acceptor_gain	1.0000

AlphaMissense

10821 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:25615477:A:G	L1154P	1.000
3:25618476:A:G	L1098S	1.000
3:25618688:G:C	F1075L	1.000
3:25618688:G:T	F1075L	1.000
3:25618689:A:G	F1075S	1.000
3:25618690:A:G	F1075L	1.000
3:25618692:C:G	R1074P	1.000
3:25618696:C:G	A1073P	1.000
3:25618752:C:G	R1054P	1.000
3:25618841:A:C	F1024L	1.000
3:25618841:A:T	F1024L	1.000
3:25618843:A:G	F1024L	1.000
3:25619890:A:G	L1012P	1.000
3:25619959:A:G	F989S	1.000
3:25620001:A:T	I975N	1.000
3:25620054:T:A	K957N	1.000
3:25620054:T:G	K957N	1.000
3:25620056:T:C	K957E	1.000
3:25620059:A:C	Y956D	1.000
3:25620690:A:G	W952R	1.000
3:25620690:A:T	W952R	1.000
3:25620704:A:G	L947P	1.000
3:25620704:A:T	L947H	1.000
3:25620713:A:C	I944S	1.000
3:25620713:A:T	I944N	1.000
3:25620749:C:T	G932D	1.000
3:25623599:C:A	W881C	1.000
3:25623599:C:G	W881C	1.000
3:25623601:A:G	W881R	1.000
3:25623601:A:T	W881R	1.000

dbSNP variants (sampled 300 via entrez): RS1000116519 (3:25631089 C>G), RS1000123392 (3:25661813 G>C), RS1000145774 (3:25665923 G>T), RS1000172258 (3:25616252 A>G), RS1000291125 (3:25633849 T>C), RS1000326412 (3:25623868 A>C), RS1000334414 (3:25640183 T>C), RS1000398137 (3:25654511 A>C), RS1000433774 (3:25616599 G>C), RS1000452369 (3:25633523 C>T), RS1000465565 (3:25660404 C>T), RS1000569810 (3:25603706 A>G), RS1000572425 (3:25624097 G>A), RS1000635614 (3:25642271 G>A), RS1000637086 (3:25654744 G>C)

Disease associations

OMIM: gene MIM:126431 | disease phenotypes: MIM:609296

GenCC curated gene-disease

Disease	Classification	Inheritance
B-cell immunodeficiency, distal limb anomalies, and urogenital malformations	Strong	Autosomal dominant
neurodevelopmental disorder	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
B-cell immunodeficiency, distal limb anomalies, and urogenital malformations	Moderate	AD

Mondo (4): B-cell immunodeficiency, distal limb anomalies, and urogenital malformations (MONDO:0012243), neurodevelopmental disorder (MONDO:0700092), autism spectrum disorder (MONDO:0005258), intellectual disability (MONDO:0001071)

Orphanet (3): B-cell immunodeficiency-limb anomaly-urogenital malformation syndrome (Orphanet:567502), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007692_14	Chronic obstructive pulmonary disease	1.000000e-06

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C563745	B-Cell Immunodeficiency, Distal Limb Anomalies, And Urogenital Malformations (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2094255 (PROTEIN FAMILY), CHEMBL3396 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

11 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,035,956 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL43	AMSACRINE	4	82,326
CHEMBL44657	ETOPOSIDE	4	226,069
CHEMBL452231	TENIPOSIDE	4	136,487
CHEMBL53463	DOXORUBICIN	4	314,282
CHEMBL8	CIPROFLOXACIN	4	97,708
CHEMBL84	TOPOTECAN	4	141,586
CHEMBL1738	DEXRAZOXANE	4	34,186
CHEMBL3039513	DECERNOTINIB	2	1,418
CHEMBL49442	AMETANTRONE	2	58
CHEMBL2140408	AMG-900	1	675
CHEMBL3408248	AZD-8186	1	1,161

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10865801	RARB, TOP2B		0.00	0

ChEMBL bioactivities

173 potent at pChembl≥5 of 319 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.16	IC50	6.85	nM	CHEMBL4161876
8.05	IC50	9	nM	CHEMBL47027
7.90	IC50	12.6	nM	CHEMBL4174756
7.70	IC50	20	nM	CHEMBL108283
7.59	IC50	25.8	nM	CHEMBL5266387
7.52	IC50	30	nM	AMETANTRONE
7.52	EC50	30	nM	CIPROFLOXACIN
7.50	IC50	31.68	nM	CHEMBL4160802
7.35	IC50	45	nM	CHEMBL326664
7.27	IC50	54	nM	CHEMBL322325
7.20	IC50	63	nM	CHEMBL325543
7.16	IC50	69.8	nM	ETOPOSIDE
7.09	IC50	81.42	nM	CHEMBL4172196
7.02	EC50	96	nM	CHEMBL440642
7.01	EC50	98	nM	CHEMBL428339
6.96	IC50	110.5	nM	CHEMBL4169404
6.94	IC50	116	nM	CHEMBL108404
6.89	IC50	130	nM	CHEMBL4751362
6.83	Kd	148	nM	DECERNOTINIB
6.82	IC50	150	nM	CHEMBL47885
6.80	EC50	160	nM	CHEMBL7877
6.80	EC50	160	nM	CHEMBL269139
6.66	IC50	220	nM	CHEMBL47526
6.65	IC50	226	nM	CHEMBL325588
6.64	IC50	230	nM	CHEMBL4469453
6.62	IC50	240	nM	CHEMBL135778
6.48	EC50	330	nM	CHEMBL27233
6.48	EC50	330	nM	CHEMBL268458
6.44	EC50	360	nM	CHEMBL7690
6.38	IC50	420	nM	CHEMBL137098
6.36	IC50	440	nM	CHEMBL4470431
6.36	IC50	440	nM	CHEMBL337526
6.32	IC50	480	nM	TOPOTECAN
6.31	IC50	490	nM	CHEMBL335700
6.30	EC50	500	nM	CHEMBL132098
6.30	EC50	500	nM	CHEMBL121666
6.30	IC50	500	nM	CHEMBL173975
6.30	IC50	500	nM	CHEMBL367883
6.29	IC50	510	nM	CHEMBL101299
6.26	IC50	550	nM	CHEMBL5408150
6.26	EC50	550	nM	CHEMBL30104
6.26	IC50	550	nM	CHEMBL334497
6.24	IC50	580	nM	CHEMBL4213218
6.19	IC50	640	nM	CHEMBL337205
6.14	EC50	720	nM	AMSACRINE
6.14	IC50	730	nM	TOPOTECAN
6.14	IC50	727	nM	DOXORUBICIN
6.14	IC50	720	nM	CHEMBL335387
6.12	IC50	752	nM	CHEMBL5271017
6.11	IC50	776	nM	CHEMBL5275333

PubChem BioAssay actives

97 with measured affinity, of 2068 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[2,4-dibromo-6-[(Z)-[6-oxo-2-(5-phenyl-1,3-thiazol-2-yl)-3-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazin-5-ylidene]methyl]phenyl] acetate	1361532: Inhibition of human DNA topoisomerase 2beta after 2 hrs by ELISA	ic50	0.0069	uM
3,4,5-trihydroxy-N-[2-[(3,4,5-trihydroxybenzoyl)amino]phenyl]benzamide	57230: Inhibitory concentration against relaxation activity of DNA topoisomerase II by detecting the conversion of supercoiled pBR322 DNA to its relaxed form	ic50	0.0090	uM
[2,4-dibromo-6-[(Z)-[6-oxo-2-phenyl-3-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazin-5-ylidene]methyl]phenyl] acetate	1361532: Inhibition of human DNA topoisomerase 2beta after 2 hrs by ELISA	ic50	0.0126	uM
tert-butyl N-[3-(acridin-9-ylamino)-5-(methylcarbamoyloxymethyl)phenyl]carbamate	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	0.0200	uM
4-[4-[(3-benzyl-7-methyl-4-oxoquinazolin-2-yl)sulfanylmethyl]triazol-1-yl]benzoic acid	1925495: Inhibition of human DNA topoisomerase 2-beta	ic50	0.0258	uM
1,4-bis[2-(2-hydroxyethylamino)ethylamino]anthracene-9,10-dione	1584438: Poison activity at recombinant human topoisomerase 2beta using pBR322 plasmid as substrate after 30 mins by ethidium bromide staining based agarose gel electrophoresis	ic50	0.0300	uM
[2,4-dibromo-6-[(Z)-[2-carbamothioyl-6-oxo-3-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazin-5-ylidene]methyl]phenyl] acetate	1361532: Inhibition of human DNA topoisomerase 2beta after 2 hrs by ELISA	ic50	0.0317	uM
N-[3-(acridin-9-ylamino)-5-(hydroxymethyl)phenyl]methanesulfonamide	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	0.0450	uM
N-[3-(acridin-9-ylamino)-5-(hydroxymethyl)phenyl]-4-(dimethylamino)butanamide	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	0.0540	uM
[3-(acridin-9-ylamino)-5-(methanesulfonamido)phenyl]methyl acetate	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	0.0630	uM
Etoposide	1361532: Inhibition of human DNA topoisomerase 2beta after 2 hrs by ELISA	ic50	0.0698	uM
[2,4-dibromo-6-[(E)-3-(2-carbamothioylhydrazinyl)-3-oxo-2-[(3,4,5-trimethoxybenzoyl)amino]prop-1-enyl]phenyl] acetate	1361532: Inhibition of human DNA topoisomerase 2beta after 2 hrs by ELISA	ic50	0.0814	uM
[2,4-dibromo-6-[(Z)-[1-methyl-8-oxo-3-sulfanylidene-5-(3,4,5-trimethoxyphenyl)-[1,2,4]triazolo[1,2-a][1,2,4]triazin-7-ylidene]methyl]phenyl] acetate	1361532: Inhibition of human DNA topoisomerase 2beta after 2 hrs by ELISA	ic50	0.1105	uM
[3-(acridin-9-ylamino)-5-aminophenyl]methyl N-methylcarbamate	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	0.1160	uM
(5E)-5-(anthracen-9-ylmethylidene)-2-[(5-methyl-1,2-oxazol-3-yl)imino]-1,3-thiazolidin-4-one	1677850: Inhibition of Topoisomerase II beta (unknown origin) relative to control	ic50	0.1300	uM
(2R)-2-methyl-2-[[2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]-N-(2,2,2-trifluoroethyl)butanamide	1425203: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1480	uM
3,4,5-trihydroxy-N-[4-[(3,4,5-trihydroxybenzoyl)amino]phenyl]benzamide	57230: Inhibitory concentration against relaxation activity of DNA topoisomerase II by detecting the conversion of supercoiled pBR322 DNA to its relaxed form	ic50	0.1500	uM
3,4,5-trihydroxy-N-[3-[(3,4,5-trihydroxybenzoyl)amino]phenyl]benzamide	57230: Inhibitory concentration against relaxation activity of DNA topoisomerase II by detecting the conversion of supercoiled pBR322 DNA to its relaxed form	ic50	0.2200	uM
[3-(acridin-9-ylamino)phenyl]methanol	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	0.2260	uM
2-chloro-3-[(4-fluorophenyl)methoxy-thiophen-2-ylmethyl]quinoline	1600554: Inhibition of DNA topoisomerase 2 in human MCF7 cells incubated for 18 to 24 hrs by kinase assay	ic50	0.2300	uM
14-[(3R)-3-aminopyrrolidin-1-yl]-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.05,10.017,21]henicosa-2(11),3,5,7,9,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.2400	uM
methyl N-[[14-[2-(diethylamino)ethyl]-4-hydroxy-8-thia-14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2(7),3,5,9,11,13(16)-heptaen-10-yl]methyl]carbamate	211289: In vitro evaluation for inhibitor of human topoisomerase II from HeLa cells.	ec50	0.3300	uM
14-[(3R)-3-aminopyrrolidin-1-yl]-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.04,9.017,21]henicosa-2,4,6,8,10,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.4200	uM
2-chloro-3-[(4-chlorophenyl)methoxy-thiophen-2-ylmethyl]quinoline	1600554: Inhibition of DNA topoisomerase 2 in human MCF7 cells incubated for 18 to 24 hrs by kinase assay	ic50	0.4400	uM
14-[(3S)-3-aminopyrrolidin-1-yl]-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.04,9.017,21]henicosa-2,4,6,8,10,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.4400	uM
Topotecan	1600554: Inhibition of DNA topoisomerase 2 in human MCF7 cells incubated for 18 to 24 hrs by kinase assay	ic50	0.4800	uM
14-[(3S)-3-aminopyrrolidin-1-yl]-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.05,10.017,21]henicosa-2(11),3,5,7,9,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.4900	uM
2-[4-[5-[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenyl]furan-2-yl]phenyl]-1,4,5,6-tetrahydropyrimidine;dihydrochloride	57049: Inhibitory activity for 50% on topoisomerase II isolated from Giardia lamblia	ic50	0.5000	uM
N-[[1-[2-(diethylamino)ethylamino]-7-hydroxy-9-oxothioxanthen-4-yl]methyl]methanesulfonamide	211289: In vitro evaluation for inhibitor of human topoisomerase II from HeLa cells.	ec50	0.5000	uM
[amino-[4-[5-[4-[amino(azaniumylidene)methyl]phenyl]furan-2-yl]phenyl]methylidene]azanium dichloride	57048: Inhibitory activity for 50% on topoisomerase II isolated from Giardia lamblia	ic50	0.5000	uM
10-[(3S)-3-aminopyrrolidin-1-yl]-11-fluoro-14-oxo-8-oxa-1-azatetracyclo[7.7.1.02,7.013,17]heptadeca-2,4,6,9(17),10,12,15-heptaene-15-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.5100	uM
14-(3-aminopyrrolidin-1-yl)-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.05,10.017,21]henicosa-2(11),3,5,7,9,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.5500	uM
N-[[14-[2-(diethylamino)ethyl]-4-hydroxy-8-thia-14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2(7),3,5,9,11,13(16)-heptaen-10-yl]methyl]methanesulfonamide	211289: In vitro evaluation for inhibitor of human topoisomerase II from HeLa cells.	ec50	0.5500	uM
N-[2-[[4-(2-aminoethylcarbamoyl)phenyl]methoxy]-4-carbamoylphenyl]-3,4-dichloro-5-methyl-1H-pyrrole-2-carboxamide;dihydrochloride	1994666: Inhibition of human DNA topoisomerase 2 beta assessed as relaxation of supercoiled plasmid pBR322 DNA incubated for 30 mins by ethidium bromide staining based agarose gel electrophoresis	ic50	0.5500	uM
1-cyclopropyl-6-fluoro-7-[4-[2-[(2E)-2-[(2-hydroxyphenyl)methylidene]hydrazinyl]-2-oxoethyl]piperazin-1-yl]-4-oxoquinoline-3-carboxylic acid	1384115: Inhibition of human topoisomerase-2B after 2 hrs by ELISA	ic50	0.5800	uM
15-fluoro-18-oxo-14-piperazin-1-yl-12-oxa-1-azapentacyclo[11.7.1.02,11.04,9.017,21]henicosa-2,4,6,8,10,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.6400	uM
N-[4-(acridin-9-ylamino)-3-methoxyphenyl]methanesulfonamide	211292: Tested for inhibition of topoisomerase II isolated from HeLa cells by DNA-cleavage assay	ec50	0.7200	uM
14-[(3S)-3-aminopyrrolidin-1-yl]-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.03,8.017,21]henicosa-2(11),3,5,7,9,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.7200	uM
Doxorubicin	1677850: Inhibition of Topoisomerase II beta (unknown origin) relative to control	ic50	0.7270	uM
12-butan-2-yl-11-imino-9-(4-methoxyphenyl)-2-oxa-4,6,12,14-tetrazatricyclo[8.4.0.03,8]tetradeca-1(10),3(8),13-triene-5,7-dione	1939819: Inhibition of DNA topoisomerase 2 (unknown origin)	ic50	0.7520	uM
14-(3-aminopyrrolidin-1-yl)-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.03,8.017,21]henicosa-2(11),3,5,7,9,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.7700	uM
14-(3-aminopyrrolidin-1-yl)-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.04,9.017,21]henicosa-2,4,6,8,10,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.7700	uM
12-(2-hydroxyphenyl)-11-imino-9-(4-methoxyphenyl)-2-oxa-4,6,12,14-tetrazatricyclo[8.4.0.03,8]tetradeca-1(10),3(8),13-triene-5,7-dione	1939819: Inhibition of DNA topoisomerase 2 (unknown origin)	ic50	0.7760	uM
7-imino-9-(4-methoxyphenyl)-11,13-dioxo-N-phenyl-2-oxa-4,6,12,14-tetrazatricyclo[8.4.0.03,8]tetradeca-1(10),3(8),4-triene-6-carbothioamide	1939819: Inhibition of DNA topoisomerase 2 (unknown origin)	ic50	0.7910	uM
1-cyclopropyl-6-fluoro-7-[4-[2-[(2E)-2-(1H-indol-2-ylmethylidene)hydrazinyl]-2-oxoethyl]piperazin-1-yl]-4-oxoquinoline-3-carboxylic acid	1384115: Inhibition of human topoisomerase-2B after 2 hrs by ELISA	ic50	0.8600	uM
8-[(1R)-1-(3,5-difluoroanilino)ethyl]-N,N-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide	1425203: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.9360	uM
N-[4-(pyridin-2-ylsulfamoyl)phenyl]-2-([1,2,4]triazolo[4,3-a]quinoxalin-4-ylsulfanyl)acetamide	1942562: Inhibition of human Topoisomerase 2 incubated for 30 mins by ELISA assay	ic50	0.9700	uM
[3-(acridin-9-ylamino)-5-(4-oxopentanoylamino)phenyl]methyl 4-oxopentanoate	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	1.0000	uM
[3-(acridin-9-ylamino)-5-aminophenyl]methanol	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	1.0000	uM
N-[3-(acridin-9-ylamino)-5-(hydroxymethyl)phenyl]-4-oxopentanamide	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	1.0000	uM

CTD chemical–gene interactions

71 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	6
Etoposide	decreases activity, decreases response to substance, increases response to substance	4
Amsacrine	decreases response to substance	3
Doxorubicin	affects response to substance, decreases response to substance	3
ellipticine	decreases response to substance, increases response to substance	2
Curcumin	decreases expression, decreases reaction	2
Estradiol	increases expression	2
Menthol	decreases activity, increases expression	2
Quercetin	decreases expression, decreases phosphorylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
cyclocurcumin	affects binding, decreases activity	1
dicrotophos	decreases expression	1
quinone	affects activity	1
methylmercuric chloride	decreases expression	1
alternariol	decreases activity	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
afimoxifene	decreases expression	1
alternariol monomethyl ether	decreases activity	1
16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione	decreases expression	1
coumarin	decreases phosphorylation	1
1-nitropyrene	increases expression	1
1,4-naphthoquinone	affects activity	1
cryptotanshinone	decreases expression	1
1,2-naphthoquinone	affects activity	1
epigallocatechin gallate	increases expression	1
1,2-dihydroxynaphthalene	affects activity	1

ChEMBL screening assays

284 unique, capped per target: 247 binding, 36 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3607613	Binding	Interfacial poisoning activity at DNA-topoisomerase 2 (unknown origin) using catenated kDNA as substrate assessed as linear DNA formation at 1 to 100 uM after 30 mins by agarose gel electrophoresis	Design and synthesis of dithiocarbamate linked β-carboline derivatives: DNA topoisomerase II inhibition with DNA binding and apoptosis inducing ability. — Bioorg Med Chem
CHEMBL4358794	ADMET	Poison activity at topoisomerase-2 in human HL7702 cell lysate assessed as reduction in topoisomerase-2 band depletion at 50 uM after 3 hrs by Western blot analysis	Discovery of 4,6-O-Thenylidene-β-d-glucopyranoside-(2″-acetamido, 3″-acetyl-di-S-5-fluorobenzothizole/5-fluorobenzoxazole)-4’-demethylepipodophyllotoxin as Potential Less Toxic Antitumor Candidate Drugs by Reducing DNA Damage and Less Inhibition of PI3K. — J Med Chem
CHEMBL669735	Functional	TOP-2 mediated DNA cleavage measured as effective concentration relative to VM26	Diaza- and triazachrysenes: potent topoisomerase-targeting agents with exceptional antitumor activity against the human tumor xenograft, MDA-MB-435. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3JW	Abcam HEK293T TOP2B KO	Transformed cell line	Female
CVCL_HE10	NALM-6 TOP2B(-/-)	Cancer cell line	Male
CVCL_TT32	HAP1 TOP2B (-) 1	Cancer cell line	Male
CVCL_TT33	HAP1 TOP2B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder