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): 1,180 total — 3 pathogenic (top 2% of genes corpus-wide)
• Regional missense constraint (gnomAD): 2 of 9 regions constrained (≈4% of expected missense variation)
• GTEx eGene: eQTL in 24 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 101
• Drug target: yes — 9 via a complex or family; 11 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• Approved drugs acting on a complex or family including it: 4 — Amsacrine, Dexrazoxane, Etoposide, +1 more (DNA topoisomerase II)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.33 (highly constrained)
• MANE Select transcript: NM_001330700
• Interaction hub: 3,105 STRING partners (top 2% of genes corpus-wide)

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: 43 — 19 protein_coding, 18 retained_intron, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000264331

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1, TSL 4: 2, TSL 5: 2

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, ENST00001035567, ENST00001035568, ENST00001035573, ENST00001035574, ENST00001035575, ENST00001035577, ENST00001035578, ENST00001058116, ENST00001058117, ENST00001058118, ENST00001058119, ENST00001128404, ENST00001139996

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.

Highest expression (Bgee): ganglionic eminence, cortical plate, ventricular zone, endothelial cell, calcaneal tendon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TOP2B is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 24 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 29 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	eqtl	6.3e-38	-0.89	3:25663941:GAA:G
Thyroid	eqtl	8.8e-10	-0.14	3:25668154:T:C
Nerve Tibial	eqtl	7.6e-08	-0.11	3:25681870:C:T
Cells Cultured fibroblasts	eqtl	1.3e-07	-0.10	3:25610620:A:G
Heart Left Ventricle	eqtl	1.1e-05	+0.10	3:25618603:G:GT
Whole Blood	eqtl	2.2e-05	-0.12	3:25655375:C:G
Cells EBV-transformed lymphocytes	sqtl	2.5e-05	-0.53	3:25644817:T:C
Brain Caudate basal ganglia	eqtl	2.6e-05	-0.19	3:25630287:C:T
Esophagus Mucosa	eqtl	8.3e-05	-0.12	3:25687424:A:T
Brain Cortex	eqtl	6.6e-04	-0.20	3:25631589:C:T
Adrenal Gland	eqtl	1.2e-03	-0.18	3:25603772:C:G
Brain Cerebellum	eqtl	1.2e-03	-0.12	3:25630287:C:T
Muscle Skeletal	eqtl	1.4e-03	+0.11	3:26113316:T:C
Stomach	sqtl	5.1e-03	-2.73	3:26040275:C:T
Artery Aorta	eqtl	5.3e-03	-0.12	3:25588575:G:A
Brain Nucleus accumbens basal ganglia	eqtl	9.4e-03	-0.32	3:24939085:C:T
Colon Transverse	eqtl	1.0e-02	-0.10	3:25610620:A:G
Esophagus Gastroesophageal Junction	sqtl	1.1e-02	+1.30	3:26280625:A:C
Brain Cerebellar Hemisphere	eqtl	1.3e-02	+0.45	3:25810113:T:A
Brain Anterior cingulate cortex BA24	eqtl	1.4e-02	-0.19	3:25611012:T:G

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 301 tissues 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
endocervix	UBERON:0000458	96.49	gold quality
caudate nucleus	UBERON:0001873	96.42	gold quality
bone marrow cell	CL:0002092	96.41	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.40	gold quality
right ovary	UBERON:0002118	96.33	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.33	gold quality
tibial nerve	UBERON:0001323	96.32	gold quality
lower esophagus	UBERON:0013473	96.32	gold quality
gingival epithelium	UBERON:0001949	96.31	gold quality
ectocervix	UBERON:0012249	96.26	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.26	gold quality
skin of leg	UBERON:0001511	96.24	gold quality
nucleus accumbens	UBERON:0001882	96.21	gold quality
tibial artery	UBERON:0007610	96.21	gold quality
popliteal artery	UBERON:0002250	96.20	gold quality
skin of hip	UBERON:0001554	96.19	gold quality
corpus callosum	UBERON:0002336	96.13	gold quality
descending thoracic aorta	UBERON:0002345	96.13	gold quality
globus pallidus	UBERON:0001875	96.11	gold quality
amygdala	UBERON:0001876	96.08	gold quality
left lobe of thyroid gland	UBERON:0001120	96.07	gold quality
right lung	UBERON:0002167	96.07	gold quality
artery	UBERON:0001637	96.05	gold quality
zone of skin	UBERON:0000014	96.03	gold quality
urinary bladder	UBERON:0001255	96.03	gold quality
vagina	UBERON:0000996	96.02	gold quality
metanephros cortex	UBERON:0010533	96.01	gold quality
putamen	UBERON:0001874	96.00	gold quality
thyroid gland	UBERON:0002046	95.95	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.93	gold quality
aorta	UBERON:0000947	95.91	gold quality
cingulate cortex	UBERON:0003027	95.91	gold quality
anterior cingulate cortex	UBERON:0009835	95.90	gold quality
adenohypophysis	UBERON:0002196	95.89	gold quality
sigmoid colon	UBERON:0001159	95.88	gold quality
uterus	UBERON:0000995	95.87	gold quality
ovary	UBERON:0000992	95.85	gold quality
prefrontal cortex	UBERON:0000451	95.84	gold quality
body of pancreas	UBERON:0001150	95.73	gold quality
right uterine tube	UBERON:0001302	95.69	gold quality
esophagus	UBERON:0001043	95.68	gold quality
right atrium auricular region	UBERON:0006631	95.68	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.68	gold quality
right coronary artery	UBERON:0001625	95.64	gold quality
trabecular bone tissue	UBERON:0002483	95.64	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.62	gold quality
granulocyte	CL:0000094	95.61	gold quality
lymph node	UBERON:0000029	95.61	gold quality
right lobe of thyroid gland	UBERON:0001119	95.60	gold quality
neocortex	UBERON:0001950	95.60	gold quality
cerebellar vermis	UBERON:0004720	95.60	gold quality
left uterine tube	UBERON:0001303	95.59	gold quality
epithelium of nasopharynx	UBERON:0001951	95.59	gold quality
amniotic fluid	UBERON:0000173	95.57	gold quality
thoracic aorta	UBERON:0001515	95.57	gold quality
prostate gland	UBERON:0002367	95.57	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.57	gold quality
female reproductive system	UBERON:0000474	95.56	gold quality
brain	UBERON:0000955	95.53	gold quality
ascending aorta	UBERON:0001496	95.53	gold quality
central nervous system	UBERON:0001017	95.52	gold quality
vermiform appendix	UBERON:0001154	95.51	gold quality
upper leg skin	UBERON:0004262	95.49	gold quality
tendon	UBERON:0000043	95.46	gold quality
minor salivary gland	UBERON:0001830	95.46	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.44	gold quality
occipital lobe	UBERON:0002021	95.43	gold quality
blood vessel layer	UBERON:0004797	95.43	gold quality
body of stomach	UBERON:0001161	95.42	gold quality
telencephalon	UBERON:0001893	95.42	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Retina	tissue	65.3
Thymus	tissue	63.4
Nucleus accumbens	tissue	48.2
Cerebellum	tissue	47.5	high
Hippocampus	tissue	44.4	high
Midbrain	tissue	44.0
Thalamus	tissue	43.2
Putamen	tissue	43.0
Olfactory bulb	tissue	42.9
Postcentral gyrus	tissue	42.6
Parathyroid gland	tissue	42.2	medium
Choroid plexus	tissue	41.4
Corpus callosum	tissue	41.1
Superior colliculi	tissue	40.5
Cerebral cortex	tissue	39.9	high
Somatosensory cortex	tissue	39.9
Occipital cortex	tissue	39.7
Pons	tissue	39.5
Hippocampal formation	tissue	39.1
Entorhinal cortex	tissue	39.1
Substantia nigra	tissue	39.0
Motor cortex	tissue	38.9
Tonsil	tissue	38.7	high
Prefrontal cortex	tissue	38.4
Medulla oblongata	tissue	38.3
Spinal cord	tissue	37.7
Locus coeruleus	tissue	37.2
Hypothalamus	tissue	37.1
Lymph node	tissue	36.9	high
Ventral forebrain	tissue	36.8
Temporal cortex	tissue	36.4
Retrosplenial and cingulate cortex	tissue	36.3
Periaqueductal gray	tissue	36.3
Thyroid gland	tissue	36.2	medium
Septum	tissue	35.9
Retrosplenial cortex	tissue	35.2
Urinary bladder	tissue	34.4	high
Endometrium 1	tissue	34.3	medium
Basal ganglia	tissue	33.3	high
Amygdala	tissue	32.6
Insular cortex	tissue	32.1
Appendix	tissue	31.7	high
Heart muscle	tissue	31.0	high
Cervix	tissue	29.9	high
Prostate	tissue	29.7	medium
Tongue	tissue	29.3
Ovary	tissue	29.0	medium
Smooth muscle	tissue	28.9	medium
Spleen	tissue	27.7	medium
Esophagus	tissue	27.5	high
Placenta	tissue	27.5	high
Rectum	tissue	27.2	high
Seminal vesicle	tissue	26.6	medium
Stomach 1	tissue	26.0	high
Kidney	tissue	25.7	high
Fallopian tube	tissue	25.4	high
Frontal cortex	tissue	25.2
Breast	tissue	24.6	medium
Bone marrow	tissue	24.2	high
Colon	tissue	23.9	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Corpus callosum, genu (white matter) (61.6), Cerebellar cortex (58.3), Vermis (55.5), Corpus callosum, splenium (white matter) (54.9), Flocculonodular lobe (52.2).

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)

Targeting TOP2B by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 61 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.328, missense Z 3.7 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000264331 splits into 9 regions with different missense tolerance; 2 are missense-constrained (≈4% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
3:25,598,310–25,618,424	556 / 584.2	0.95	no
3:25,618,425–25,628,951	379 / 615.1	0.62	no
3:25,628,952–25,630,038	7 / 48.8	0.14	yes (p 2.2e-09)
3:25,630,039–25,630,915	66 / 153.3	0.43	no
3:25,630,916–25,638,189	222 / 306.6	0.72	no
3:25,638,190–25,638,284	9 / 36.6	0.25	yes (p 5.1e-06)
3:25,638,285–25,642,357	21 / 19.6	1.07	no
3:25,642,358–25,645,393	35 / 85.8	0.41	no
3:25,645,394–25,664,297	83 / 59.3	1.40	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98791) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 46 distinct phenotype terms.

Mouse phenotype (MP)	Records
respiratory failure	2
neonatal lethality, complete penetrance	2
cleft palate	1
kyphosis	1
abnormal craniofacial morphology	1
abnormal spleen morphology	1
small spleen	1
paralysis	1
decreased brain size	1
abnormal cerebral cortex morphology	1
abnormal cerebral cortex lamination	1
abnormal hippocampus morphology	1
abnormal telencephalon development	1
abnormal motor neuron innervation pattern	1
abnormal retina rod cell morphology	1
abnormal retina cone cell morphology	1
abnormal innervation pattern to muscle	1
atelectasis	1
decreased body size	1
persistence of hyaloid vascular system	1
decreased embryo size	1
abnormal placenta morphology	1
edema	1
abnormal motor capabilities/coordination/movement	1
abnormal eye morphology	1

+21 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Cricetulus longicaudatus	Q64399	98.6%	Diamond
Cricetulus griseus	P41515	92.7%	Diamond
Sus scrofa	O46374	91.3%	Diamond
Caenorhabditis elegans	Q23670	89.5%	Diamond
Gallus gallus	O42131	88.7%	Diamond
Leishmania chagasi	O61078	84.6%	Diamond
Crithidia fasciculata	P27570	84.6%	Diamond
Trypanosoma brucei brucei	P12531	78.0%	Diamond
Trypanosoma cruzi	P30190	78.0%	Diamond
Candida albicans	P87078	72.6%	Diamond
Meyerozyma guilliermondii ATCC 6260	Q01879	72.6%	Diamond
Saccharomyces cerevisiae S288C	P06786	72.0%	Diamond
Nakaseomyces glabratus CBS 138	O93794	71.9%	Diamond
Drosophila melanogaster	P15348	68.6%	Diamond
Bombyx mori	O16140	64.3%	Diamond
Lathyrus oleraceus	O24308	57.5%	Diamond
Arabidopsis thaliana	P30182	57.4%	Diamond
Penicillium chrysogenum	Q9Y8G8	56.7%	Diamond
Schizosaccharomyces pombe 972h-	P08096	56.4%	Diamond
Plasmodium falciparum K1	P41001	48.9%	Diamond
Dictyostelium discoideum	Q55BP5	48.3%	Diamond
Invertebrate iridescent virus 3	Q196X4	41.2%	Diamond
Invertebrate iridescent virus 6	Q9QSK1	41.0%	Diamond
Acanthamoeba polyphaga mimivirus	Q5UQE6	40.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
NGLY1	protein-coding	55768
RARB	protein-coding	5915
MIR4442	ncRNA	100616477
RARB-AS1	ncRNA	105376997
OXSM	protein-coding	54995

Protein

Protein identifiers

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

Alternative names: DNA topoisomerase II, beta isozyme

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

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 (236 total): helix 62, strand 45, modified residue 35, cross-link 34, turn 10, 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)

21 structures by resolution:

PDB	Title	Method	Resolution (Å)
9BQ8	Human Topoisomerase 2 Beta ATPase domain bound to non-hydrolyzable ATP analog AMPPNP	X-RAY DIFFRACTION	1.25
9BQC	Human Topoisomerase 2 Beta ATPase domain bound to obex 5c and non-hydrolyzable ATP analog …	X-RAY DIFFRACTION	1.45
9BQD	Human Topoisomerase 2 Beta ATPase domain bound to topobexin and non-hydrolyzable ATP …	X-RAY DIFFRACTION	1.5
7QFO	Human Topoisomerase II Beta ATPase AMPPNP	X-RAY DIFFRACTION	1.9
9BQA	Human Topoisomerase 2 Beta ATPase domain bound to BNS22 and non-hydrolyzable ATP analog …	X-RAY DIFFRACTION	1.9
3QX3	Human topoisomerase IIbeta in complex with DNA and etoposide	X-RAY DIFFRACTION	2.16
4J3N	Human Topoisomerase Iibeta in complex with DNA	X-RAY DIFFRACTION	2.3
5ZRF	Crystal structure of human topoisomerase II beta in complex with …	X-RAY DIFFRACTION	2.3
7ZBG	Human Topoisomerase II Beta ATPase ADP	X-RAY DIFFRACTION	2.3
5ZAD	Human topoisomerase II beta in complex with DNA	X-RAY DIFFRACTION	2.54
4G0V	Human topoisomerase iibeta in complex with DNA and mitoxantrone	X-RAY DIFFRACTION	2.55
5GWJ	Structure of a Human topoisomerase IIbeta fragment in complex with DNA and E7873S	X-RAY DIFFRACTION	2.57
7QFN	Human Topoisomerase II Beta ATPase ADP	X-RAY DIFFRACTION	2.62
4G0W	Human topoisomerase iibeta in complex with DNA and ametantrone	X-RAY DIFFRACTION	2.7
4G0U	Human topoisomerase IIbeta in complex with DNA and amsacrine	X-RAY DIFFRACTION	2.7
5GWI	Structure of a Human topoisomerase IIbeta fragment in complex with DNA and E7873R	X-RAY DIFFRACTION	2.74
5ZEN	Crystal structure of human topoisomerase II beta in complex with DNA: a new quaternary …	X-RAY DIFFRACTION	2.75
8KE7	Crystal structure of DNA binding and cleavage core of human topoisomerase 2-beta in a DNA …	X-RAY DIFFRACTION	2.8
25EC	Crystal Structure of a Human Topoisomerase II Beta-DNA Cleavage Complex Trapped in N-gate …	X-RAY DIFFRACTION	2.9
5ZQF	Crystal structure of human topoisomerase II beta in complex with …	X-RAY DIFFRACTION	3.87
7YQ8	Cryo-EM structure of human topoisomerase II beta in complex with DNA and etoposide	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Isomerase, Predicted intracellular proteins, Plasma proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH supported · IF enhanced

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)

Position	Role
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)

Position	Role
112	ATP
141	ATP
169–171	ATP
182–189	ATP
397–399	ATP
482	Mg(2+)
562	Mg(2+)
564	Mg(2+)

Post-translational modifications (69)

Type	Positions
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	1440, 1456, 1490, 28, 29, 33, 34, 177, 178, 228, 299, 367, 373, 437, 439, 446, 600, 605, 635, 643, 646, 676, 712, 1092, 1214, 1217, 1226, 1227, 1250, 1262, 1271, 1323, 1327, 1398
N-acetylalanine	2
N6-acetyllysine	3
Phosphoserine	1236, 1336, 1340, 1342, 1344, 1358, 1375, 1400, 1413, 1424, 1441, 1452, 1454, 1461, 1466, 1473, 1476, 1522, 1524, 1526, 1550, 1552, 1576, 1581, 1596, 1613
Phosphothreonine	1292, 1403, 1575, 1592
Phosphotyrosine	1370, 1421, 1609

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 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-4615885	SUMOylation of DNA replication proteins	curated
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins	—
R-HSA-2990846	SUMOylation	—

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 (10): resolution of meiotic recombination intermediates (GO:0000712), sister chromatid segregation (GO:0000819), DNA topological change (GO:0006265), B cell differentiation (GO:0030183), 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 (10): 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), isomerase activity (GO:0016853)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), ribonucleoprotein complex (GO:1990904), heterochromatin (GO:0000792), chromosome (GO:0005694)

Reactome top-level categories

4 top-level categories:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1

GO top-level categories

45 GO namespaces:

Category	Terms
binding	2
nuclear lumen	2
cellular anatomical structure	2
intracellular membraneless organelle	2
reciprocal meiotic recombination	1
meiosis I cell cycle process	1
chromosome organization	1
nuclear chromosome segregation	1
DNA metabolic process	1
DNA conformation change	1
lymphocyte differentiation	1
B cell activation	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
anion binding	1
protein-containing complex binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
DNA binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on DNA	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
protein-containing complex	1
chromatin	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
B cell differentiation	BP	mutant phenotype
DNA topological change	BP	direct assay
positive regulation of single stranded viral RNA replication via double stranded DNA intermediate	BP	mutant phenotype
cytosol	CC	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	MF	direct assay
chromatin binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,105 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOP2B	TOP1MT	Q969P6	919
TOP2B	TOP1	P11387	853
TOP2B	TDP2	O95551	680
TOP2B	TOP3B	O95985	646
TOP2B	ILF2	Q12905	640
TOP2B	TOP3A	Q13472	625
TOP2B	TOPBP1	Q92547	609
TOP2B	XPC	Q01831	592
TOP2B	ILF3	Q12906	577
TOP2B	TDP1	Q9NUW8	565
TOP2B	AFF1	P51825	535
TOP2B	MLLT3	P42568	527
TOP2B	GAS7	O60861	524
TOP2B	SPO11	Q9Y5K1	521
TOP2B	H1-0	P07305	488

IntAct

Human interaction partners of TOP2B in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
PIAS4	physical association	0.500	1
MED15	physical association	0.400	1
MED24	physical association	0.400	1
VAMP4	physical association	0.400	1

BioGRID (365 interactions; top human partners by supporting records): PARP1 (Proximity Label-MS; 5 records), PIAS4 (Affinity Capture-MS; 5 records), TOP2A (Reconstituted Complex; 5 records), HDAC1 (Affinity Capture-Western; 4 records), UBE2I (Two-hybrid; 4 records), CUL5 (Affinity Capture-MS; 3 records), NPM1 (Affinity Capture-MS; 3 records), SMARCA4 (Co-fractionation; 3 records), SMARCB1 (Co-fractionation; 3 records), TP53 (Affinity Capture-Western; 3 records), ASB3 (Affinity Capture-MS; 2 records), BRCA1 (Co-localization; 2 records), BRD4 (Affinity Capture-MS; 2 records), BTRC (Affinity Capture-Western; 2 records), CD3E (Affinity Capture-Western; 2 records)

SIGNOR signaling

15 signaling 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

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
★ TLE1 corepressor complex	10	HSPA4, NCL, NPM1, RAD50, TOP2B, ACTB, MYH10, NONO, PARP1, TLE1
★ TLE1 corepressor complex	8	NCL, NONO, NPM1, PARP1, RAD50, TLE1, TOP2B, HSPA4
★ TOP2A-TOP2B complex	2	TOP2A, TOP2B
★ TOP2B homodimer	1	TOP2B

Disease & clinical

Genetic variants

Variant evidence for TOP2B: 1,180 ClinVar records (3 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

1,180 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	562
Likely benign	488
Benign	35

Top pathogenic / likely-pathogenic (3)

Showing all 3 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1319985	NM_001330700.2(TOP2B):c.1468G>C (p.Ala490Pro)	Pathogenic	criteria provided, single submitter	2
1319982	NM_001330700.2(TOP2B):c.1776_1778del (p.Glu593del)	Pathogenic	no assertion criteria provided	1
1319983	NM_001330700.2(TOP2B):c.1463C>T (p.Ser488Leu)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore TOP2B’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 2,956):

Position(s)	Effect	Δscore	Sites
3:25604758–25604759	donor_loss	1.0000	5
3:25607169–25607170	donor_loss	1.0000	3
3:25607376–25607377	acceptor_loss	1.0000	6
3:25609181–25609182	donor_loss	1.0000	3
3:25609192	donor_gain	1.0000
3:25609345–25609346	acceptor_loss	1.0000	5
3:25609352	acceptor_gain	1.0000
3:25609566–25609567	donor_loss	1.0000	5
3:25609713	acceptor_gain	1.0000
3:25609714	acceptor_loss	1.0000	3

AlphaMissense

5,501 missense substitutions predicted likely pathogenic (of 10,821 scored), across 1,134 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M560	9	0.984	1.000
M123	9	0.960	0.995
M690	9	0.946	0.998
M219	9	0.942	0.998
M558	9	0.929	0.999
M1149	9	0.895	0.989
M786	9	0.861	0.995
M1021	9	0.850	0.973
D562	8	1.000	1.000
D564	8	1.000	1.000
D566	8	1.000	1.000
H569	8	0.999	1.000
F674	8	0.999	1.000
D741	8	0.999	1.000
H63	8	0.998	1.000
D115	8	0.998	1.000
F649	8	0.998	1.000
D731	8	0.998	1.000
H779	8	0.998	1.000
H780	8	0.998	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.56e-05
Rectum Adenocarcinoma (TCGA)	favorable	9.51e-05

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
B-cell immunodeficiency, distal limb anomalies, and urogenital malformations	Strong	Autosomal dominant	5
neurodevelopmental disorder	Limited	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
COVID-19 research	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green
Monogenic hearing loss	amber
Paediatric disorders	amber

Mondo (2): B-cell immunodeficiency, distal limb anomalies, and urogenital malformations (MONDO:0012243), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): B-cell immunodeficiency-limb anomaly-urogenital malformation syndrome (Orphanet:567502)

HPO phenotypes

showing 60 of 101 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000020	Urinary incontinence
HP:0000039	Epispadias
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000064	Hypoplastic labia minora
HP:0000066	Labial hypoplasia
HP:0000076	Vesicoureteral reflux
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000160	Narrow mouth
HP:0000188	Short upper lip
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000430	Underdeveloped nasal alae
HP:0000954	Single transverse palmar crease
HP:0000960	Sacral dimple
HP:0000979	Purpura
HP:0001159	Syndactyly
HP:0001199	Triphalangeal thumb
HP:0001245	Small thenar eminence
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001287	Meningitis
HP:0001371	Flexion contracture
HP:0001508	Failure to thrive
HP:0001545	Anteriorly placed anus
HP:0001762	Talipes equinovarus
HP:0001840	Metatarsus adductus
HP:0001845	Overlapping toe
HP:0001945	Fever
HP:0001973	Autoimmune thrombocytopenia
HP:0002205	Recurrent respiratory infections
HP:0002315	Headache
HP:0002342	Moderate intellectual disability
HP:0002353	EEG abnormality
HP:0002553	Highly arched eyebrow
HP:0002561	Absent nipple
HP:0002572	Episodic vomiting
HP:0002719	Recurrent infections
HP:0002720	Decreased circulating IgA concentration
HP:0002721	Immunodeficiency
HP:0002783	Recurrent lower respiratory tract infections
HP:0002788	Recurrent upper respiratory tract infections
HP:0002850	Decreased circulating IgM concentration
HP:0002958	Immune dysregulation
HP:0003196	Short nose
HP:0003577	Congenital onset
HP:0004209	Clinodactyly of the 5th finger
HP:0004283	Narrow palm
HP:0004315	Decreased circulating IgG concentration

GWAS associations

1 associations:

Study	Trait	p-value
GCST007692_64	Chronic obstructive pulmonary disease	1e-6

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
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)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes TOP2B — the drug acts on the assembly or class, not necessarily on this subunit alone.

9 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
AMSACRINE	DNA topoisomerase II	2	4
DEXRAZOXANE	DNA topoisomerase II	2	4
ETOPOSIDE	DNA topoisomerase II	2	4
TENIPOSIDE	DNA topoisomerase II	2	4
BECATECARIN	DNA topoisomerase II	2	3
PAZUFLOXACIN	DNA topoisomerase II	2	3
VOSAROXIN	DNA topoisomerase II	2	3
BERUBICIN HYDROCHLORIDE	DNA topoisomerase II	2	2
C-1311	DNA topoisomerase II	2	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,047,187 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

11 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL43	AMSACRINE	4	83,286
CHEMBL8	CIPROFLOXACIN	4	98,734
CHEMBL1738	DEXRAZOXANE	4	34,543
CHEMBL53463	DOXORUBICIN	4	317,622
CHEMBL44657	ETOPOSIDE	4	228,302
CHEMBL452231	TENIPOSIDE	4	137,895
CHEMBL84	TOPOTECAN	4	143,303
CHEMBL49442	AMETANTRONE	2	58
CHEMBL3039513	DECERNOTINIB	2	1,509
CHEMBL2140408	AMG-900	1	708
CHEMBL3408248	AZD-8186	1	1,227

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

282 measured of 352 human assays (359 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4161876	IC50	6.9 nM
NB-506 Analogue	EC50	8 nM
CHEMBL4174756	IC50	13 nM
CHEMBL6189613	IC50	16 nM
NB-506 Analogue	EC50	17 nM
NB-506 Analogue	EC50	20 nM
CHEMBL108283	IC50	20 nM
NB-506 Analogue	EC50	25 nM
NB-506 Analogue	EC50	26 nM
CHEMBL5266387	IC50	26 nM
NB-506 Analogue	EC50	30 nM
Ametantrone	IC50	30 nM
NB-506 Analogue	EC50	32 nM
CHEMBL4160802	IC50	32 nM
NB-506 Analogue	EC50	42 nM
CHEMBL326664	IC50	45 nM
Edotecarin	EC50	51 nM
CHEMBL322325	IC50	54 nM
CHEMBL325543	IC50	63 nM
1,4-Dihydroxyanthrachinon	IC50	65 nM
2-[1,11-dihydroxy-5,7-dioxo-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-6-ylamino]ethyl cyanide	EC50	70 nM
NB-506 Analogue	EC50	80 nM
CHEMBL4172196	IC50	81 nM
1,11-dihydroxy-5,7-dioxo-6-(2-pyridylcarboxamido)-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole	EC50	90 nM
CHEMBL440642	EC50	96 nM
CHEMBL428339	EC50	98 nM
NB-506 Analogue	EC50	100 nM
CHEMBL4169404	IC50	110 nM
CHEMBL108404	IC50	116 nM
NB-506 Analogue	EC50	130 nM
NB-506 Analogue	EC50	140 nM
4-[1,11-dihydroxy-5,7-dioxo-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-6-ylamino]benzoic acid	EC50	160 nM
CHEMBL7877	EC50	160 nM
CHEMBL269139	EC50	160 nM
CHEMBL4751362	IC50	171 nM
5,8-Dihydroxy-2-(1-hydroxy-4-methyl-pent-3-enyl)-[1,4]naphthoquinone	IC50	190 nM
CHEMBL325588	IC50	226 nM
NB-506 Analogue	EC50	230 nM
CHEMBL4469453	IC50	230 nM
NB-506 Analogue	EC50	240 nM
CHEMBL135778	IC50	240 nM
6-amino-1,11-dihydroxy-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	EC50	270 nM
1,11-dihydroxy-6-(4-methylphenylsulfonamido)-5,7-dioxo-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole	EC50	270 nM
1,11-dihydroxy-6-(3-hydroxybenzylamino)-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	EC50	300 nM
NB-506 Analogue	EC50	300 nM
CHEMBL268458	EC50	330 nM
CHEMBL27233	EC50	330 nM
1,11-dihydroxy-6-methylamino-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	EC50	350 nM

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 2093 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	decreases expression, affects expression, decreases methylation, affects cotreatment	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	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	Phase 4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	Phase 4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	Phase 4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	Phase 4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	Phase 4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	Phase 4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	Phase 4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	Phase 4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	Phase 4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	Phase 4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	Phase 4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	Phase 4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	Phase 4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	Phase 4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	Phase 4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	Phase 4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	Phase 4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	Phase 4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	Phase 4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	Phase 4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	Phase 4	RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT07770152	Phase 4	NOT_YET_RECRUITING	Semaglutide in Youth With Autism Spectrum Disorder
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT01302964	Phase 3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	Phase 3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	Phase 3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	Phase 3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	Phase 3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	Phase 3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	Phase 3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	Phase 3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	Phase 3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	Phase 3	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	Phase 3	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	Phase 3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	Phase 3	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
NCT04623398	Phase 3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	Phase 3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	Phase 3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	Phase 3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	Phase 3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	Phase 3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder
NCT06333964	Phase 3	COMPLETED	A Study to Evaluate the Efficacy and Safety of AST-001 in ASD Children
NCT07257939	Phase 3	NOT_YET_RECRUITING	NTI164 in Autism Spectrum Disorder
NCT07655115	Phase 3	RECRUITING	Single Dose Double-blind, Placebo-controlled Cross-over (SDDBPCCO) Shiftability Study, Will be Followed by a 10-week Open-label Study With Arbaclofen (4 Weeks of Titration and Then 6 Weeks of Active/Stable Treatment). The Effects of Arbaclofen on Target EEG and ERG Metrics Will be Associated With th
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00251303	Phase 2	COMPLETED	Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders
NCT00614198	Phase 2	COMPLETED	ScanBrit Dietary Intervention in Autism
NCT00619190	Phase 2	COMPLETED	Study of Aripiprazole to Treat Children and Adolescents With Autism
NCT00709202	Phase 2	COMPLETED	Efficacy and Tolerability Study of Betahistine to Ameliorate Antipsychotic Associated Weight Gain
NCT00846547	Phase 2	COMPLETED	Open-Label Study of the Safety and Tolerability of STX209 in Subjects With Autism Spectrum Disorders
NCT01064973	Phase 2	TERMINATED	An Open Label Extension Study of STX209 in Subjects With Autism Spectrum Disorders
NCT01170325	Phase 2	WITHDRAWN	A Study of Divalproex Sodium in Children With ASD and Epileptiform EEG

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TOP2B across ~30M SureChEMBL compounds — explore on Sugi Predict.