TOP1

Summary

TOP1 (DNA topoisomerase I, HGNC:11986) is a protein-coding gene on chromosome 20q12, encoding DNA topoisomerase 1 (P11387). Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. In precision oncology, TOP1 Amplification confers sensitivity to Cetuximab + FOLFIRI Regimen in Colorectal Cancer (CIViC Level B); 3 further curated variant–drug associations are listed below. It is a common-essential gene (DepMap: required in 93.0% of cancer cell lines).

This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus altering the topology of DNA. This gene is localized to chromosome 20 and has pseudogenes which reside on chromosomes 1 and 22.

Source: NCBI Gene 7150 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 31 total
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 4 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• Cancer dependency (DepMap): dependent in 93.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_003286

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11986
Approved symbol	TOP1
Name	DNA topoisomerase I
Location	20q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198900
Ensembl biotype	protein_coding
OMIM	126420
Entrez	7150

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 retained_intron, 2 protein_coding, 1 nonsense_mediated_decay

ENST00000361337, ENST00000680945, ENST00000681058, ENST00000681113, ENST00000681392, ENST00000681884

RefSeq mRNA: 1 — MANE Select: NM_003286 NM_003286

CCDS: CCDS13312

Canonical transcript exons

ENST00000361337 — 21 exons

Exon	Start	End
ENSE00000844695	41077582	41077637
ENSE00000844696	41080085	41080180
ENSE00000844697	41081165	41081240
ENSE00000844698	41084462	41084568
ENSE00000844699	41092472	41092587
ENSE00000844700	41097220	41097341
ENSE00000844701	41098215	41098337
ENSE00000844702	41100056	41100243
ENSE00000844703	41101209	41101353
ENSE00000844704	41112782	41112925
ENSE00000844706	41113970	41114155
ENSE00000844709	41115371	41115439
ENSE00000844711	41116278	41116392
ENSE00000844712	41118169	41118296
ENSE00000844716	41121696	41121790
ENSE00000844717	41122006	41122155
ENSE00001037776	41076171	41076294
ENSE00001159738	41123195	41124487
ENSE00001159739	41061394	41061490
ENSE00001174139	41029431	41029455
ENSE00001174143	41028822	41029100

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 121.3635 / max 2619.5462, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184619	88.3409	1825
184620	23.7300	1811
184621	9.2925	1703

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.27	gold quality
ventricular zone	UBERON:0003053	97.06	gold quality
secondary oocyte	CL:0000655	96.77	gold quality
ganglionic eminence	UBERON:0004023	96.77	gold quality
cortical plate	UBERON:0005343	96.09	gold quality
cervix squamous epithelium	UBERON:0006922	95.53	gold quality
pericardium	UBERON:0002407	95.09	gold quality
pylorus	UBERON:0001166	94.39	gold quality
vena cava	UBERON:0004087	94.38	gold quality
pancreatic ductal cell	CL:0002079	94.34	gold quality
superior surface of tongue	UBERON:0007371	94.20	gold quality
monocyte	CL:0000576	94.13	gold quality
pharyngeal mucosa	UBERON:0000355	94.12	gold quality
lymph node	UBERON:0000029	94.11	gold quality
islet of Langerhans	UBERON:0000006	94.02	gold quality
mononuclear cell	CL:0000842	93.95	gold quality
rectum	UBERON:0001052	93.80	gold quality
leukocyte	CL:0000738	93.76	gold quality
cardia of stomach	UBERON:0001162	93.51	gold quality
mammary duct	UBERON:0001765	93.10	gold quality
embryo	UBERON:0000922	92.85	gold quality
upper lobe of left lung	UBERON:0008952	92.80	gold quality
colonic epithelium	UBERON:0000397	92.62	gold quality
epithelium of mammary gland	UBERON:0003244	92.62	gold quality
upper lobe of lung	UBERON:0008948	92.61	gold quality
gall bladder	UBERON:0002110	92.59	gold quality
right lung	UBERON:0002167	92.49	gold quality
stromal cell of endometrium	CL:0002255	92.35	gold quality
tongue	UBERON:0001723	92.27	gold quality
tonsil	UBERON:0002372	92.09	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8530	yes	763.90
E-CURD-114	yes	6.81
E-HCAD-9	yes	6.54
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, E2F1, E2F4, MYC

miRNA regulators (miRDB)

128 targeting TOP1, 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-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
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-3912-5P	99.95	66.11	925
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 93.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• CPT-11 may provide therapeutic efficacy for esophageal squamous cell cancer and the effects correlate with the level of DNA topoisomerase I protein. (PMID:11749700)
• active site of a type I DNA topoisomerase from the kinetoplastid protozoan Leishmania donovani, compared to human structure (PMID:11809893)
• Different effects on human topoisomerase I by minor groove and intercalated deoxyguanosine adducts derived from two polycyclic aromatic hydrocarbon diol epoxides at or near a normal cleavage site. (PMID:11832494)
• Point mutations in the topoisomerase I gene in patients with non-small cell lung cancer treated with irinotecan (PMID:11844605)
• The origin recognition complex (ORC) marks a replication origin in the promoter (PMID:12004060)
• ATP and Topoisomerase I activity found indispensable for cDNA synthesis in the HIV-1 replication process. Mutant enzyme lacking activity inhibited HIV-1 infectivity (PMID:12051740)
• role of N-terminal domain in nucleolar localization of human DNA topoisomerase I (PMID:12119295)
• TOP1 delocalizes from the nucleolus to the nucleoplasm when sumoylated by camptothecin (PMID:12149243)
• binds to DNA first in an inactive conformation and then rearranges its active site for catalysis (PMID:12209008)
• DNA binding induces conformational transition within this enzyme in solution (PMID:12209444)
• presence of dna topoisomerase I in different testicular tumor types (PMID:12237772)
• Binding and dissociation of human emzyme with hairpin-loop RNAs: implications for the regulation of HIV-1 replication (PMID:12270136)
• RNA splicing factor ASF/SF2 inhibits human topoisomerase I mediated DNA relaxation (PMID:12270705)
• The x-ray crystal structure of human topoisomerase I covalently joined to double-stranded DNA & bound to Topotecan shows that Topotecan mimics a DNA base pair & binds at the DNA cleavage site, intercalating between the upstream & downstream base pairs. (PMID:12426403)
• proteins indentified binding to the N-terminal domain of human topoisomerase I (PMID:12549820)
• DNA is unwound bidirectionally by a ternary complex of T antigen, nucleolin and this enzyme. (PMID:12634843)
• The exon 2 region was required for physical binding of p14(ARF) to Topo I & stimulatory activity. p14(ARF) (R71A) was more efficient than wild-type to activate Topo I. Nucleolar location is linked the biological function of the ARF-Topo I complex. (PMID:12673200)
• The contributions of strong and week nonspecific electrostatic, van der Waals’s, and hydrophobic interactions, and hydrogen bonding of the enzymes to the complex formation with the single- and double-stranded DNAs were determined. (PMID:12708316)
• DNA relaxation by this enzyme occurs in the closed clamp conformation of the protein. (PMID:12711735)
• Factors affecting the specific recognition of topologically stressed DNA were analyzed on the basis of the thermodynamic and kinetic data on the Topo-DNA interaction and the X-ray data on human Topo (PMID:12723479)
• Human topoisomerase I plays an important role in HIV-1 replication and infectivity, and differences in the species specificity of HIV-1 infection can at least in part be attributed to differences in topoisomerase I activities. (PMID:12829794)
• a single mutation in the linker domain confers protein flexibility and camptothecin resistance to human topoisomerase I (PMID:12904303)
• Topo I activity is now shown to be involved in DNA damage/repair pathway in vivo (PMID:13679149)
• Lys(532) functions as a general acid during cleavage to protonate the leaving 5’-oxygen (PMID:14594810)
• topo I truncated up to position 210 is not stabilized by camptothecin in covalent DNA-complexes inside a living cell, whereas in vitro it retains full DNA-relaxation activity, and is targeted by camptothecin in the usual manner (PMID:14654701)
• topoisomerase I-mediated DNA damage and cell death is induced by hydrogen peroxide (PMID:14688260)
• human topoisomerase I exclusively dissociated HIV-1 reverse transcriptase, which strongly binds to structural RNAs (PMID:14706652)
• DNA damage at telomeric repeats by topoisomerase I is a prominent feature of camptothecin-induced apoptosis (PMID:14729676)
• Data describe the specific functions of individual N-terminal regions of topoisomerase I by characterizing mutants lacking amino acid residues 1-202 or 191-206 or having tryptophane-205 substituted by glycine. (PMID:14741206)
• p53 disruption has a dramatic effect on how glioblastoma cells process topoisomerase I inhibitor-mediated DNA damage. (PMID:14961077)
• topoisomerase I cleavage complexes correlate with apoptosis, however, at low UV doses the cleavage complex level was very low and the complexes were repaired (PMID:15010314)
• nucleolar/nucleoplasmic partitioning of topoisomerase I is regulated by interactions with RNA polymerase I and DNA but not by sumoylation (PMID:15014084)
• expression of human NUP98-TOP1 in murine bone marrow confers a potent in vitro growth advantage and a block in differentiation in hematopoietic precursors (PMID:15100157)
• Data report the synthesis of a number of oligonucleotides containing methylphosphonates at single positions for the purpose of investigating the hydrogen-bonding contacts necessary for human topoisomerase I function. (PMID:15147201)
• propose that arsenic trioxide induces topoisomerase I-DNA complexes that participate in chromatin fragmentation and programmed cell death during apoptosis (PMID:15178684)
• function for the automodification reaction is to regulate the interaction between PARP-1 and Topo I, and consequently, the Topo I activity, in response to DNA damage. (PMID:15247263)
• An essential component of this Top1/DNA active site model is the rotated +1 deoxyguanosine, and in vitro experiments and molecular modeling studies supported rotation of the +1 deoxyguanosine out of the helix (PMID:15351405)
• This is the first report that conjugated PUFA such as cEPA act as inhibitors of pols and topos. (PMID:15680922)
• The complexities of the relaxation reaction, the cellular roles, and the pathways that must exist to repair topoisomerase I-mediated DNA damage highlight the importance of continued study of this essential enzyme. (review) (PMID:15830206)
• Identification of 36 nuclear proteins that were associated with topoisomerase I. (PMID:15848144)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	top1a	ENSDARG00000070545
danio_rerio	top1b	ENSDARG00000086775
mus_musculus	Top1	ENSMUSG00000070544
rattus_norvegicus	Top1	ENSRNOG00000047611

Paralogs (1): TOP1MT (ENSG00000184428)

Protein

Protein identifiers

DNA topoisomerase 1 — P11387 (reviewed: P11387)

Alternative names: DNA topoisomerase I

All UniProt accessions (3): P11387, A0A7P0T852, A0A7P0T9R7

UniProt curated annotations — full annotation on UniProt →

Function. Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3’-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5’-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5’-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the BMAL1 promoter.

Subunit / interactions. Monomer. Interacts with ERCC6. Interacts with TPRN; TPRN interacts with a number of DNA damage response proteins, is recruited to sites of DNA damage and may play a role in DNA damage repair. (Microbial infection) Interacts with SV40 Large T antigen; this interactions allows viral DNA replication.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm.

Tissue specificity. Endothelial cells.

Post-translational modifications. Sumoylated. Lys-117 is the main site of sumoylation. Sumoylation plays a role in partitioning TOP1 between nucleoli and nucleoplasm. Levels are dramatically increased on camptothecin (CPT) treatment. Phosphorylation at Ser-506 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin.

Disease relevance. A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98.

Activity regulation. Specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity.

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 IB topoisomerase family.

RefSeq proteins (1): NP_003277* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001631	TopoI	Family
IPR008336	TopoI_DNA-bd_euk	Domain
IPR011010	DNA_brk_join_enz	Homologous_superfamily
IPR013030	DNA_topo_DNA_db_N_dom2	Homologous_superfamily
IPR013034	DNA_topo_DNA_db_N_dom1	Homologous_superfamily
IPR013499	TopoI_euk	Domain
IPR013500	TopoI_cat_euk	Domain
IPR014711	TopoI_cat_a-hlx-sub_euk	Homologous_superfamily
IPR014727	TopoI_cat_a/b-sub_euk	Homologous_superfamily
IPR018521	TopoIB_AS	Active_site
IPR025834	TopoI_C_dom	Domain
IPR036202	TopoI_DNA-bd_euk_N_sf	Homologous_superfamily
IPR048045	Topoisomer_I_DNA-bd	Domain
IPR051062	Topoisomerase_IB	Family

Pfam: PF01028, PF02919, PF14370

Enzyme classification (BRENDA):

• EC 5.6.2.1 — DNA topoisomerase (BRENDA: 73 organisms, 262 substrates, 1102 inhibitors, 6 Km, 1 kcat entries)
• EC 5.99.1.2 — DNA topoisomerase (BRENDA: 0 organisms, 0 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NEGATIVELY SUPERCOILED PLASMID PXXZ06 DNA	—	1

UniProt features (115 total): helix 25, strand 20, cross-link 19, site 9, turn 8, modified residue 8, sequence variant 6, mutagenesis site 6, compositionally biased region 5, region of interest 4, initiator methionine 1, chain 1, active site 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
1A31	X-RAY DIFFRACTION	2.1
1K4T	X-RAY DIFFRACTION	2.1
1RRJ	X-RAY DIFFRACTION	2.3
1A35	X-RAY DIFFRACTION	2.5
1EJ9	X-RAY DIFFRACTION	2.6
1RR8	X-RAY DIFFRACTION	2.6
1A36	X-RAY DIFFRACTION	2.8
1SC7	X-RAY DIFFRACTION	3
1SEU	X-RAY DIFFRACTION	3
1T8I	X-RAY DIFFRACTION	3
1NH3	X-RAY DIFFRACTION	3.1
1TL8	X-RAY DIFFRACTION	3.1
1R49	X-RAY DIFFRACTION	3.13
1LPQ	X-RAY DIFFRACTION	3.14
1K4S	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11387-F1	80.25	0.70

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): 723 (o-(3’-phospho-dna)-tyrosine intermediate); 316 (interaction with dna); 364 (interaction with dna); 412 (interaction with dna); 443 (interaction with dna); 501 (interaction with dna); 532 (interaction with dna); 574 (interaction with dna); 632 (interaction with dna); 650 (interaction with dna)

Post-translational modifications (27): 2, 2, 10, 57, 112, 172, 280, 506, 101, 103, 103, 117, 117, 117, 134, 148, 153, 153, 158, 164 …

Mutagenesis-validated functional residues (6):

Position	Phenotype
103	localizes in both nucleoplasm and nucleoli; when associated with r-117 or r-153. almost complete loss of sumoylation, co
117	5-fold decrease in sumoylation. localizes in both nucleoplasm and nucleoli; when associated with or without r-103 or r-1
153	localizes in both nucleoplasm and nucleoli; when associated with r-103 or r-117. almost complete loss of sumoylation, co
532	almost abolishes enzyme activity.
532	strongly reduced enzyme activity.
723	no change in cpt-induced clearing from nuclei.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 414 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_CIRCADIAN_RHYTHM, GOBP_CHROMOSOME_ORGANIZATION, E2F_Q4_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_RESPONSE_TO_IONIZING_RADIATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, MORF_UBE2I, GEORGES_CELL_CYCLE_MIR192_TARGETS, GOBP_REGENERATION, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, FOXO4_01, KAUFFMANN_DNA_REPAIR_GENES

GO Biological Process (17): DNA replication (GO:0006260), DNA topological change (GO:0006265), chromatin remodeling (GO:0006338), chromosome segregation (GO:0007059), circadian rhythm (GO:0007623), response to temperature stimulus (GO:0009266), rRNA transcription (GO:0009303), response to xenobiotic stimulus (GO:0009410), response to gamma radiation (GO:0010332), programmed cell death (GO:0012501), animal organ regeneration (GO:0031100), circadian regulation of gene expression (GO:0032922), embryonic cleavage (GO:0040016), response to cAMP (GO:0051591), cellular response to luteinizing hormone stimulus (GO:0071373), peptidyl-serine phosphorylation (GO:0018105), rhythmic process (GO:0048511)

GO Molecular Function (18): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA binding (GO:0003677), chromatin binding (GO:0003682), double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), DNA topoisomerase type I (single strand cut, ATP-independent) activity (GO:0003917), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), DNA binding, bending (GO:0008301), protein domain specific binding (GO:0019904), chromatin DNA binding (GO:0031490), protein-containing complex binding (GO:0044877), supercoiled DNA binding (GO:0097100), molecular condensate scaffold activity (GO:0140693), DNA topoisomerase activity (GO:0003916), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (12): P-body (GO:0000932), fibrillar center (GO:0001650), dense fibrillar component (GO:0001651), male germ cell nucleus (GO:0001673), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), protein-DNA complex (GO:0032993), perikaryon (GO:0043204), nuclear chromosome (GO:0000228), cytoplasm (GO:0005737)

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
DNA binding	5
cellular anatomical structure	5
binding	3
nuclear lumen	3
DNA metabolic process	2
nucleic acid binding	2
nucleolus	2
intracellular membraneless organelle	2
DNA biosynthetic process	1
DNA conformation change	1
chromatin organization	1
cell cycle process	1
rhythmic process	1
response to abiotic stimulus	1
DNA-templated transcription	1
rRNA metabolic process	1
response to chemical	1
response to ionizing radiation	1
signal transduction	1
cell death	1
regeneration	1
animal organ development	1
circadian rhythm	1
regulation of gene expression	1
embryo development	1
cell division	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
response to luteinizing hormone	1
cellular response to gonadotropin stimulus	1
cellular response to peptide hormone stimulus	1
protein phosphorylation	1
peptidyl-serine modification	1
biological_process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
DNA topoisomerase activity	1
protein kinase activity	1
adenyl ribonucleotide binding	1

Protein interactions and networks

STRING

3410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOP1	TDP1	Q9NUW8	978
TOP1	TOP2A	P11388	960
TOP1	ALYREF	Q86V81	902
TOP1	RBMX	P38159	888
TOP1	TOP2B	Q02880	876
TOP1	TP53	P04637	860
TOP1	PARP1	P09874	832
TOP1	BTBD1	Q9H0C5	823
TOP1	TOPORS	Q9NS56	820
TOP1	TOP3A	Q13472	815
TOP1	BTBD2	Q9BX70	811
TOP1	DDX4	Q9NQI0	770
TOP1	DDX3Y	O15523	767
TOP1	PPP1CC	P36873	766
TOP1	H2AX	P16104	762

IntAct

213 interactions, top by confidence:

A	B	Type	Score
XRCC5	PARP1	psi-mi:“MI:0915”(physical association)	0.880
APLF	PARP1	psi-mi:“MI:0914”(association)	0.870
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
	TOP1	psi-mi:“MI:0407”(direct interaction)	0.730
TOP1		psi-mi:“MI:0407”(direct interaction)	0.730
NKX3-1	TOP1	psi-mi:“MI:0915”(physical association)	0.630
TOP1	NKX3-1	psi-mi:“MI:0915”(physical association)	0.630
NKX3-1	TOP1	psi-mi:“MI:0407”(direct interaction)	0.630
TOP1	ABL1	psi-mi:“MI:0915”(physical association)	0.600
ABL1	TOP1	psi-mi:“MI:0915”(physical association)	0.600
TOP1	ABL1	psi-mi:“MI:0407”(direct interaction)	0.600
ABL1	TOP1	psi-mi:“MI:0407”(direct interaction)	0.600
Pawr	HSPA5	psi-mi:“MI:0914”(association)	0.580
WAS	TOP1	psi-mi:“MI:0914”(association)	0.560
TOP1	WAS	psi-mi:“MI:0915”(physical association)	0.560
H2AC11	PARP1	psi-mi:“MI:0914”(association)	0.530
PRICKLE3	SIAH2	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530

BioGRID (912): TOP1 (Affinity Capture-MS), TOP1 (Affinity Capture-MS), TOP1 (Affinity Capture-MS), TOP1 (Affinity Capture-MS), TP53 (Affinity Capture-Western), TOP1 (Affinity Capture-MS), TOP1 (Affinity Capture-MS), TOP1 (Affinity Capture-MS), TOP1 (Affinity Capture-MS), RBM25 (Co-fractionation), TOP1 (Co-fractionation), TOP1 (Co-fractionation), TOP1 (Co-fractionation), TOP1 (Co-fractionation), TOP1 (Co-fractionation)

ESM2 similar proteins: A0A0L0P4F8, A3KN83, A8XEA2, A9Q1D5, A9UL78, B2GUV7, G5EDG2, O17966, O36966, O95251, P04786, P07799, P0CL88, P0CL89, P11387, P30181, P30189, P41511, P41512, P93119, Q00313, Q04750, Q05D44, Q06698, Q07050, Q09475, Q23243, Q23541, Q27746, Q4IEV4, Q4P3S3, Q54RC3, Q54UU6, Q5BJL5, Q5F1R6, Q5F371, Q5SVQ0, Q5UQH6, Q61T02, Q689Z5

Diamond homologs: A0A0L0P4F8, A9Q1D5, O17966, P04786, P07799, P11387, P30181, P30189, P41511, P41512, P93119, Q00313, Q04750, Q07050, Q54RC3, Q6IM78, Q7YR26, Q8R4U6, Q969P6, Q9FJ79, Q9WUL0

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
irinotecan	“down-regulates activity”	TOP1	“chemical inhibition”
topotecan	“down-regulates activity”	TOP1	“chemical inhibition”
ABL1	“up-regulates activity”	TOP1	phosphorylation
PRKDC	“down-regulates quantity by destabilization”	TOP1	phosphorylation
BRCA1	“down-regulates quantity by destabilization”	TOP1	ubiquitination
NONO	up-regulates	TOP1	binding
SFPQ	up-regulates	TOP1	binding
TOP1	“down-regulates quantity by repression”	ARNTL	“transcriptional regulation”
PRKCA	“up-regulates activity”	TOP1	phosphorylation
CSNK2A1	“up-regulates activity”	TOP1	phosphorylation
CDK1	“up-regulates activity”	TOP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 183 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.

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair via nonhomologous end joining	6	15.3×	8e-04
positive regulation of fibroblast proliferation	7	12.5×	6e-04
positive regulation of miRNA transcription	6	10.6×	5e-03
DNA damage response	13	4.2×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — BCC, HCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2562 predictions. Top by Δscore:

Variant	Effect	Δscore
20:41029096:CCCAG:C	donor_loss	1.0000
20:41029100:GGTAC:G	donor_loss	1.0000
20:41029101:GTAC:G	donor_loss	1.0000
20:41029102:T:A	donor_loss	1.0000
20:41061385:T:TA	acceptor_gain	1.0000
20:41061389:TGCA:T	acceptor_loss	1.0000
20:41061390:GCA:G	acceptor_loss	1.0000
20:41061391:CAG:C	acceptor_loss	1.0000
20:41061392:A:AG	acceptor_gain	1.0000
20:41061393:G:C	acceptor_loss	1.0000
20:41061393:G:GG	acceptor_gain	1.0000
20:41061487:ACAGG:A	donor_loss	1.0000
20:41061488:CAGGT:C	donor_loss	1.0000
20:41061489:AGGTA:A	donor_loss	1.0000
20:41061492:T:G	donor_loss	1.0000
20:41076166:TACA:T	acceptor_loss	1.0000
20:41076169:A:AG	acceptor_gain	1.0000
20:41076169:A:T	acceptor_loss	1.0000
20:41076169:AGT:A	acceptor_gain	1.0000
20:41076170:G:GA	acceptor_gain	1.0000
20:41076170:GT:G	acceptor_gain	1.0000
20:41076170:GTG:G	acceptor_gain	1.0000
20:41076170:GTGA:G	acceptor_gain	1.0000
20:41076170:GTGAA:G	acceptor_gain	1.0000
20:41076290:A:T	donor_gain	1.0000
20:41076290:AAAAG:A	donor_loss	1.0000
20:41076291:AAAGG:A	donor_loss	1.0000
20:41076292:AAGG:A	donor_loss	1.0000
20:41076293:AG:A	donor_loss	1.0000
20:41076294:GG:G	donor_loss	1.0000

AlphaMissense

5182 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:41092473:T:A	W206R	1.000
20:41092473:T:C	W206R	1.000
20:41092475:G:C	W206C	1.000
20:41092475:G:T	W206C	1.000
20:41092506:T:A	W217R	1.000
20:41092506:T:C	W217R	1.000
20:41092508:G:C	W217C	1.000
20:41092508:G:T	W217C	1.000
20:41100101:T:C	C341R	1.000
20:41100103:T:G	C341W	1.000
20:41100161:T:C	F361L	1.000
20:41100163:C:A	F361L	1.000
20:41100163:C:G	F361L	1.000
20:41100167:G:C	G363R	1.000
20:41100168:G:A	G363D	1.000
20:41100170:C:A	R364S	1.000
20:41100180:A:G	H367R	1.000
20:41100181:C:A	H367Q	1.000
20:41100181:C:G	H367Q	1.000
20:41100191:G:C	G371R	1.000
20:41100191:G:T	G371C	1.000
20:41100192:G:A	G371D	1.000
20:41100192:G:T	G371V	1.000
20:41100200:A:G	K374E	1.000
20:41100202:G:C	K374N	1.000
20:41100202:G:T	K374N	1.000
20:41100235:C:A	N385K	1.000
20:41100235:C:G	N385K	1.000
20:41101246:T:A	W401R	1.000
20:41101246:T:C	W401R	1.000

dbSNP variants (sampled 300 via entrez): RS1000019429 (20:41076959 A>G), RS1000049948 (20:41062026 C>T), RS1000050169 (20:41095208 A>G), RS1000108066 (20:41057306 C>T), RS1000168987 (20:41037022 G>A), RS1000191089 (20:41117297 C>T), RS1000192635 (20:41027104 G>A,T), RS1000197995 (20:41036675 A>G), RS1000213763 (20:41088924 A>G), RS1000236391 (20:41079927 T>C), RS1000312548 (20:41082405 A>C), RS1000314568 (20:41095503 C>A,T), RS1000339917 (20:41056107 A>T), RS1000351296 (20:41063654 C>T), RS1000458855 (20:41092330 G>A)

Disease associations

OMIM: gene MIM:126420 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000759_18	LDL cholesterol	3.000000e-19
GCST000760_34	Cholesterol, total	3.000000e-17
GCST002221_42	Cholesterol, total	1.000000e-16
GCST002222_10	LDL cholesterol	5.000000e-18
GCST004233_38	LDL cholesterol levels	2.000000e-34
GCST004233_65	LDL cholesterol levels	3.000000e-06
GCST004235_1	Total cholesterol levels	1.000000e-06
GCST004235_27	Total cholesterol levels	5.000000e-29
GCST004253_8	Accelerated cognitive decline after conversion of mild cognitive impairment to Alzheimer’s disease (Alzhiemer’s diagnosis trajectory interaction)	4.000000e-06
GCST006661_160	Male-pattern baldness	2.000000e-15
GCST008972_4	Urate levels	4.000000e-10
GCST009302_14	Antipsychotic drug-induced weight gain in schizophrenia	4.000000e-06
GCST009365_37	LDL cholesterol levels x short total sleep time interaction (2df test)	8.000000e-19
GCST009366_5	LDL cholesterol levels x long total sleep time interaction (2df test)	2.000000e-15
GCST009391_1997	Metabolite levels	8.000000e-06
GCST010002_67	Refractive error	7.000000e-10
GCST010320_57	PR interval	5.000000e-08
GCST010321_155	PR interval	2.000000e-08
GCST010703_20	Brain morphology (MOSTest)	1.000000e-09
GCST90002384_472	Hemoglobin	2.000000e-10
GCST90002403_318	Red blood cell count	4.000000e-09
GCST90013407_129	Liver enzyme levels (gamma-glutamyl transferase)	2.000000e-42
GCST90020025_1664	Waist-to-hip ratio adjusted for BMI	4.000000e-08
GCST90020027_336	Waist-hip index	3.000000e-08
GCST90020028_1569	Hip circumference adjusted for BMI	3.000000e-09

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0007710	cognitive decline measurement
EFO:0004531	urate measurement
EFO:0004567	antipsychotic drug related weight gain
EFO:0010542	ureidopropionic acid measurement
EFO:0004462	PR interval
EFO:0004346	neuroimaging measurement
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1781 (SINGLE PROTEIN), CHEMBL4106174 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,440,992 (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
CHEMBL1607	TOPOTECAN HYDROCHLORIDE	4	56,379
CHEMBL1643	RIBAVIRIN	4	78,049
CHEMBL43	AMSACRINE	4	82,326
CHEMBL53463	DOXORUBICIN	4	314,282
CHEMBL84	TOPOTECAN	4	141,586
CHEMBL15245	YOHIMBINE	3	11,917
CHEMBL273862	HYDROXYCAMPTOTHECIN	3	11,312
CHEMBL435191	EDOTECARIN	3	1,181
CHEMBL11252	STALLIMYCIN	2	1,910
CHEMBL274070	9-AMINOCAMPTOTHECIN	2	16,073
CHEMBL837	7-ETHYL-10-HYDROXYCAMPTOTHECIN	2	12,139
CHEMBL8659	OLEIC ACID	2	713,838

Clinical evidence (CIViC)

Drug × variant × indication: 4 predictive associations from 4 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
TOP1 Amplification	Cetuximab + FOLFIRI Regimen	Colorectal Cancer	Sensitivity/Response	CIViC B	EID12143
TOP1 Amplification	Irinotecan	Colorectal Cancer	Sensitivity/Response	CIViC B	EID888
TOP1 EXPRESSION	Carboplatin + Cyclophosphamide + Topotecan	Ovarian Cancer	Sensitivity/Response	CIViC B	EID910
TOP1 EXPRESSION	Irinotecan	Colorectal Cancer	Sensitivity/Response	CIViC B	EID912

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6072262	Toxicity	3	irinotecan

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6072262	TOP1	3	2.00	1	irinotecan

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — DNA topoisomerases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 5z [PMID: 8410981]	Inhibition	7.57	pIC50
compound 19 [PMID: 7707314]	Inhibition	7.55	pIC50

ChEMBL bioactivities

383 potent at pChembl≥5 of 545 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.53	Kd	0.296	nM	CHEMBL1813808
8.58	Kd	2.65	nM	CHEMBL1813809
8.48	EC50	3.3	nM	CHEMBL474561
8.19	Kd	6.526	nM	CHEMBL5653589
8.19	ED50	6.526	nM	CHEMBL5653589
8.10	EC50	8	nM	CHEMBL135492
7.96	IC50	11	nM	CHEMBL338843
7.92	EC50	12	nM	CHEMBL507686
7.82	IC50	15	nM	CHEMBL335455
7.80	EC50	16	nM	CHEMBL503051
7.77	EC50	17	nM	CHEMBL447826
7.77	EC50	17	nM	CHEMBL133209
7.77	EC50	17	nM	CHEMBL135491
7.72	EC50	19	nM	CHEMBL478720
7.70	EC50	20	nM	CHEMBL452445
7.70	EC50	20	nM	CHEMBL505815
7.70	EC50	20	nM	CHEMBL135881
7.68	IC50	21	nM	TOPOTECAN
7.66	EC50	22	nM	CHEMBL455328
7.66	EC50	22	nM	CHEMBL449831
7.66	EC50	22	nM	CHEMBL446276
7.64	EC50	23	nM	CHEMBL510006
7.62	IC50	24	nM	CHEMBL4791048
7.60	IC50	25	nM	CAMPTOTHECIN
7.60	EC50	25	nM	CHEMBL454734
7.60	EC50	25	nM	CHEMBL502679
7.60	EC50	25	nM	CHEMBL334337
7.58	EC50	26	nM	CHEMBL334869
7.58	EC50	26	nM	CHEMBL338966
7.58	Kd	26.5	nM	TOPOTECAN
7.57	EC50	27	nM	CHEMBL507295
7.57	IC50	27	nM	CHEMBL307794
7.55	IC50	28	nM	CHEMBL13935
7.54	IC50	29	nM	CHEMBL4454135
7.54	EC50	29	nM	CHEMBL509544
7.52	IC50	30	nM	CHEMBL286882
7.52	EC50	30	nM	CHEMBL500059
7.52	EC50	30	nM	CHEMBL503252
7.52	EC50	30	nM	CHEMBL475683
7.52	EC50	30	nM	CHEMBL450991
7.52	EC50	30	nM	CHEMBL448760
7.52	IC50	30	nM	CHEMBL307794
7.52	EC50	30	nM	CHEMBL135970
7.51	EC50	31	nM	CHEMBL507006
7.50	EC50	32	nM	CHEMBL132533
7.48	IC50	33	nM	CHEMBL13349
7.47	EC50	34	nM	CHEMBL117315
7.46	EC50	35	nM	CHEMBL506902
7.46	EC50	35	nM	CHEMBL508108
7.43	EC50	37	nM	CHEMBL323394

PubChem BioAssay actives

307 with measured affinity, of 6100 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
(19S)-19-ethyl-19-hydroxy-10-[(2-methylphenyl)iminomethyl]-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione	610760: Binding affinity to topoisomerase 1	kd	0.0003	uM
6,20-dihydroxy-13-[[6-(hydroxymethyl)-2-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0033	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149635: Binding affinity to human TOP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0065	uM
3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0080	uM
(18S)-2-(chloromethyl)-18-ethyl-18-hydroxy-6,9,20-trioxa-13,24-diazahexacyclo[12.11.0.03,12.05,10.015,24.017,22]pentacosa-1,3,5(10),11,13,15,17(22)-heptaene-19,23-dione	56570: Inhibition of topoisomerase I activity was determined in vitro by using the cleavable complex assay(calf thymus)	ic50	0.0110	uM
6,20-dihydroxy-13-[(4-hydroxyphenyl)methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0120	uM
(5S)-14-(chloromethyl)-5-ethyl-5-hydroxy-7,18,20-trioxa-11,24-diazahexacyclo[11.11.0.02,11.04,9.015,23.017,21]tetracosa-1(24),2,4(9),13,15,17(21),22-heptaene-6,10-dione	56570: Inhibition of topoisomerase I activity was determined in vitro by using the cleavable complex assay(calf thymus)	ic50	0.0150	uM
6,20-dihydroxy-13-[[2-(hydroxymethyl)phenyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0160	uM
3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0170	uM
3-[(2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0170	uM
6,20-dihydroxy-13-(quinolin-2-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0170	uM
6,20-dihydroxy-13-[[3-(hydroxymethyl)-2-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0190	uM
3-[(2R,3R,4S,5S)-5-(1,2-dihydroxyethyl)-3,4-dihydroxyoxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0200	uM
6,20-dihydroxy-13-(quinolin-4-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0200	uM
6,20-dihydroxy-13-[(3-hydroxyphenyl)methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0200	uM
6,20-dihydroxy-13-(pyridin-4-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0220	uM
6,20-dihydroxy-13-[[3-(hydroxymethyl)phenyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0220	uM
6,20-dihydroxy-13-[[4-(hydroxymethyl)-2-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0220	uM
6,20-dihydroxy-13-(pyridin-3-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0230	uM
6-(4-aminophenyl)-N-(3-imidazol-1-ylpropyl)-3-(1,3,4-oxadiazol-2-yl)quinolin-4-amine	1740932: Inhibition of recombinant human Top1 expressed in baculovirus infected sf9 insect cells using supercoiled pBS (SK+) DNA as substrate incubated for 30 mins by ethidium bromide staining based agarose gel electrophoresis analysis	ic50	0.0240	uM
13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0250	uM
(19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione	1544048: Poison activity at recombinant human TOP1 expressed in baculovirus infected Sf9 insect cells assessed as decrease in relaxed supercoiled pBS(SK+) DNA mobility measured after 30 mins by ethidium bromide staining based agarose gel electrophoresis	ic50	0.0250	uM
13-(benzylamino)-6,20-dihydroxy-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0250	uM
6,20-dihydroxy-13-[[4-(hydroxymethyl)-3-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0250	uM
13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0260	uM
13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3-[(2R,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0260	uM
6,20-dihydroxy-13-[[5-(hydroxymethyl)-2-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0270	uM
(19S)-7-bromo-19-ethyl-19-hydroxy-10-methyl-17-oxa-3,6,13-triazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione	56561: Inhibitory activity against DNA topoisomerase I	ic50	0.0280	uM
N-(3-imidazol-1-ylpropyl)-6-(4-methoxyphenyl)-3-(1,3,4-oxadiazol-2-yl)quinolin-4-amine	1544048: Poison activity at recombinant human TOP1 expressed in baculovirus infected Sf9 insect cells assessed as decrease in relaxed supercoiled pBS(SK+) DNA mobility measured after 30 mins by ethidium bromide staining based agarose gel electrophoresis	ic50	0.0290	uM
6,20-dihydroxy-13-[[3-(hydroxymethyl)-4-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0290	uM
3-[(2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0300	uM
6,20-dihydroxy-3-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	241607: Inhibition of topoisomerase I-DNA complex in trapping assay	ic50	0.0300	uM
13-(furan-3-ylmethylamino)-6,20-dihydroxy-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0300	uM
6,20-dihydroxy-13-(1H-pyrrol-2-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0300	uM
6,20-dihydroxy-13-(pyridin-2-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0300	uM
6,20-dihydroxy-13-(quinolin-3-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0300	uM
6,20-dihydroxy-13-[[6-(hydroxymethyl)-3-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0300	uM
6,20-dihydroxy-13-[[2-(hydroxymethyl)-4-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0310	uM
3-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0320	uM
(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,6,13-triazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-7-carboximidamide	56575: Minimum concentration that produced 50% fragmentation of DNA was measured in the presence of excess calf thymus topoisomerase.	ic50	0.0330	uM
6,20-dihydroxy-13-[[4-(hydroxymethyl)phenyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0340	uM
6,20-dihydroxy-13-(pyrazin-2-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0350	uM
6,20-dihydroxy-13-[[5-(hydroxymethyl)-3-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0350	uM
13-(1,3-dihydroxypropan-2-ylamino)-6,19-dihydroxy-3-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211098: In vitro inhibition of Topoisomerase I-mediated DNA cleavage using supercoiled pBR322 plasmid DNA.	ec50	0.0370	uM
(19S)-19-ethyl-19-hydroxy-8-methyl-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione	210946: Inhibition of Topoisomerase I by cleavage complex formation in human HL-60 cells	ic50	0.0380	uM
5-ethyl-5-hydroxy-7,18,20-trioxa-11,24-diazahexacyclo[11.11.0.02,11.04,9.015,23.017,21]tetracosa-1(13),2,4(9),14,16,21,23-heptaene-6,10-dione	210947: Inhibition of Topoisomerase I by cleavage complex formation in intact human HL-60 cells	ic50	0.0380	uM
13-(furan-2-ylmethylamino)-6,20-dihydroxy-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0380	uM
6,7,19,20-tetrafluoro-23-[5-fluoro-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]-3-thia-13,23-diazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaene-12,14-dione	240097: Topoisomerase I activity for single-strand breaks in the DNA substrate	ec50	0.0400	uM
3-[(2R,3R,4R)-3,4-dihydroxyoxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0400	uM
3-[(2R,3R,4S,5R)-5-(1,2-dihydroxyethyl)-3,4-dihydroxyoxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0420	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Camptothecin	decreases activity, affects cotreatment, decreases response to substance	6
Irinotecan	affects binding, decreases activity, affects response to substance	4
bisphenol A	affects expression, decreases expression	3
Estradiol	affects expression, increases expression	3
Cadmium Chloride	decreases methylation, increases expression	3
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Fluorouracil	decreases expression, affects response to substance	2
Menthol	decreases activity, decreases expression	2
Oleanolic Acid	decreases activity, decreases expression	2
Plant Extracts	decreases expression, affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Topotecan	decreases activity	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
graphene oxide	decreases expression	1
cyclocurcumin	affects binding, decreases activity	1
2,4,6-tribromophenol	increases expression	1
chloroacetaldehyde	decreases expression	1
palmatine	decreases activity	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	increases expression	1
trichostatin A	affects cotreatment, decreases expression	1
nitidine	decreases expression	1
tetrahydropalmatine	increases expression	1
afimoxifene	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
delphinidin	decreases activity	1
sodium arsenite	increases abundance, increases expression	1
tetrabromobisphenol A	increases expression	1

ChEMBL screening assays

1200 unique, capped per target: 1161 binding, 38 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000097	Binding	Inhibition of topoisomerase 1-mediated relaxation of supercoiled DNA assessed as DNA cleavage at 9 uM relative to control	Cytotoxic pyrroloiminoquinones from four new species of South African latrunculid sponges. — J Nat Prod
CHEMBL3266692	ADMET	Inhibition of human topoisomerase 1-mediated pHOT-1 DNA relaxation at 10 to 150 uM treated with pHOT-1 substrate for 15 mins prior to enzyme addition for 30 mins by agarose gel electrophoresis	Haloemodin as novel antibacterial agent inhibiting DNA gyrase and bacterial topoisomerase I. — J Med Chem
CHEMBL663638	Functional	Concentration that produces 50% DNA cleavage mediated by DNA topoisomerase I	Modification of the hydroxy lactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological activity. — J Med Chem

Cellosaurus cell lines

17 cell lines: 17 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2878	CPT-K5	Cancer cell line	Female
CVCL_A787	PC-7/CPT	Cancer cell line	Male
CVCL_AS75	DU145/RC0.1	Cancer cell line	Male
CVCL_B7PT	HCT116-s	Cancer cell line	Male
CVCL_B7PU	HCT116-A2	Cancer cell line	Male
CVCL_B7PV	HCT116-C8	Cancer cell line	Male
CVCL_B7PW	HCT116-G7	Cancer cell line	Male
CVCL_D639	DU145/RC1	Cancer cell line	Male
CVCL_HE09	NALM-6 TOP1(+/-)	Cancer cell line	Male
CVCL_M595	HONE-1/CPT30	Cancer cell line	Male

Clinical trials (associated diseases)

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