BLM

Summary

BLM (BLM RecQ like helicase, HGNC:1058) is a protein-coding gene on chromosome 15q26.1, encoding RecQ-like DNA helicase BLM (P54132). ATP-dependent DNA helicase that unwinds double-stranded (ds)DNA in a 3’-5’ direction.

The Bloom syndrome is an autosomal recessive disorder characterized by growth deficiency, microcephaly and immunodeficiency among others. It is caused by homozygous or compound heterozygous mutation in the gene encoding DNA helicase RecQ protein on chromosome 15q26. This Bloom-associated helicase unwinds a variety of DNA substrates including Holliday junction, and is involved in several pathways contributing to the maintenance of genome stability. Identification of pathogenic Bloom variants is required for heterozygote testing in at-risk families.

Source: NCBI Gene 641 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Bloom syndrome (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 5,268 total — 351 pathogenic, 172 likely-pathogenic
• Phenotypes (HPO): 99
• Druggable target: yes — 284 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000057

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1058
Approved symbol	BLM
Name	BLM RecQ like helicase
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	BS, RECQL3, RECQ2
Ensembl gene	ENSG00000197299
Ensembl biotype	protein_coding
OMIM	604610
Entrez	641

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 17 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000355112, ENST00000558599, ENST00000558825, ENST00000559282, ENST00000559426, ENST00000559724, ENST00000560136, ENST00000560509, ENST00000560559, ENST00000560821, ENST00000648453, ENST00000680772, ENST00000681142, ENST00000891949, ENST00000936445, ENST00000936446, ENST00000936447, ENST00000936448, ENST00000936449, ENST00000936450, ENST00000936451, ENST00000936452, ENST00000936453, ENST00000936454, ENST00000936455

RefSeq mRNA: 4 — MANE Select: NM_000057 NM_000057, NM_001287246, NM_001287247, NM_001287248

CCDS: CCDS10363, CCDS73782

Canonical transcript exons

ENST00000355112 — 22 exons

Exon	Start	End
ENSE00001294214	90747389	90747490
ENSE00001310444	90815102	90816166
ENSE00001316594	90749367	90750067
ENSE00001322880	90760147	90760279
ENSE00001376121	90717346	90717440
ENSE00003474567	90811205	90811406
ENSE00003482664	90766910	90767023
ENSE00003491150	90760594	90761255
ENSE00003496273	90803521	90803720
ENSE00003506653	90794167	90794357
ENSE00003521971	90798190	90798337
ENSE00003535610	90762966	90763157
ENSE00003539502	90790649	90790844
ENSE00003544672	90769438	90769586
ENSE00003559872	90809137	90809259
ENSE00003609890	90751787	90751946
ENSE00003636417	90765296	90765414
ENSE00003659505	90784921	90785081
ENSE00003677528	90782822	90782928
ENSE00003680170	90754811	90754938
ENSE00003686858	90804167	90804359
ENSE00003690666	90769133	90769231

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 98.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.3665 / max 146.1200, expressed in 1294 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148473	7.9772	1206
148475	0.1399	74
148478	0.1292	38
148476	0.1202	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	98.72	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.37	gold quality
secondary oocyte	CL:0000655	87.62	gold quality
oocyte	CL:0000023	86.68	gold quality
ventricular zone	UBERON:0003053	85.87	gold quality
ganglionic eminence	UBERON:0004023	84.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.18	gold quality
tonsil	UBERON:0002372	83.88	gold quality
embryo	UBERON:0000922	82.75	gold quality
apex of heart	UBERON:0002098	81.78	gold quality
trabecular bone tissue	UBERON:0002483	81.78	gold quality
right atrium auricular region	UBERON:0006631	81.63	gold quality
bone marrow	UBERON:0002371	81.24	gold quality
epithelium of nasopharynx	UBERON:0001951	80.54	silver quality
heart left ventricle	UBERON:0002084	80.50	gold quality
cardiac atrium	UBERON:0002081	80.43	gold quality
cardiac ventricle	UBERON:0002082	79.96	gold quality
bone marrow cell	CL:0002092	78.84	gold quality
buccal mucosa cell	CL:0002336	78.23	gold quality
granulocyte	CL:0000094	77.96	gold quality
mucosa of transverse colon	UBERON:0004991	77.65	gold quality
heart	UBERON:0000948	77.36	gold quality
lymph node	UBERON:0000029	76.77	gold quality
amygdala	UBERON:0001876	76.47	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.39	gold quality
leukocyte	CL:0000738	76.27	gold quality
mononuclear cell	CL:0000842	75.97	gold quality
monocyte	CL:0000576	75.92	gold quality
cerebellar cortex	UBERON:0002129	75.79	gold quality
cerebellar hemisphere	UBERON:0002245	75.75	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.41

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

19 targeting BLM, 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-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-1182	96.41	64.89	336

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The C-terminal domain of the Bloom syndrome DNA helicase is essential for genomic stability as measured by the sister chromatid exchange assay. (PMID:11472631)
• Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype (PMID:11532193)
• binds human mismatch repair protein MLH1; nuclear localization (PMID:11691925)
• mutation results in bloom syndrome (PMID:11741924)
• The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control (PMID:11781842)
• is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest. (PMID:11916980)
• Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins (PMID:11919194)
• Bloom’s syndrome protein response to ultraviolet-C radiation and hydroxyurea-mediated DNA synthesis inhibition. (PMID:11960380)
• ATM and BLM function together in recognizing abnormal DNA structures by direct interaction and that these phosphorylation sites in BLM are important for radiosensitivity status but not for SCE frequency. (PMID:12034743)
• recombinant p53 binds to BLM and WRN helicases and attenuates their ability to unwind synthetic Holliday junctions in vitro (PMID:12080066)
• binding by and stimulation of by telomere-binding proteing TRF2 (PMID:12181313)
• data show that carriers of a BLM mutation have an increased risk for colorectal cancer (PMID:12242432)
• The Bloom’s syndrome helicase stimulates the activity of topoisomerase IIIalpha (PMID:12433984)
• Immunofluorescence studies show that BLM helicase co-localizes with telomeric foci in approximately 70% of cells in asynchronous cultures of ALT human cell lines. (PMID:12444098)
• These results indicate that p53 and BLM functionally interact during resolution of stalled DNA replication forks and provide insight into the mechanism of genomic fidelity maintenance by these nuclear proteins. (PMID:12606585)
• these data define a minimal helicase domain of BLM and demonstrate its ability to act as a suppressor of illegitimate recombination (PMID:12818200)
• Human BLM interacts with both scDna2 and scFEN1. It may participate in the same steps of DNA replication or repair as scFEN1 & scDna2, acting as a molecular matchmaker at a crossroad between replication & repair. (PMID:12826610)
• hMSH6, a component of the heterodimeric mismatch recognition complex hMSH2/hMSH6 (hMutS(alpha)), interacts with the BLM protein both in vivo and in vitro (PMID:12974384)
• BLM co-operates with RAD51 paralogs during the late stages of homologous recombination processes that serve to restore productive DNA replication at sites of damaged or stalled replication forks (PMID:12975363)
• BLM is essential for timely BRCA1/NBS1 function (PMID:14517203)
• NHEJ (non-homologous DNA end joining) activation mediates BLM dissociation from DNA, whereas, under conditions where homologous recombination is favored, e.g. at the replication fork, BLM exhibits an anti-recombinogenic role (PMID:14576316)
• BLM and hTOPO IIIalpha together effect the resolution of a recombination intermediate containing a double Holliday junction (PMID:14685245)
• the Bloom’s syndrome protein has a role in stimulating flap endonuclease-1 (PMID:14688284)
• hMSH2/6 formed a complex with BLM-p53-RAD51 in response to the damaged DNA forks during double-stranded break repair. (PMID:15064730)
• BLM functions in recombination-mediated telomere lengthening. (PMID:15229185)
• Fanconi anaemia core complex is necessary for BLM phosphorylation (PMID:15257300)
• Common mutations in the BLM gene were studied in 4 Japanese Bloom Syndrome kindreds. (PMID:15289897)
• interactions between BLM and DNA ligase IV play a role in DNA repair in human cells (PMID:15509577)
• Thus, optimal repair of damaged replication fork lesions likely requires both ATR and ATM. BLM recruits 53BP1 to these lesions independent of its helicase activity, and optimal activation of ATM requires both p53 and BLM helicase activities. (PMID:15539948)
• results suggest that BLM suppresses genome instability by aiding FEN1 cleavage of structure-containing flaps (PMID:15579905)
• SCE in the fancc/blm mutant was similar to that in blm cells, indicating functional linkage between FANCC and BLM (PMID:15616572)
• BLM collaborates with RAD51 to facilitate recombination repair and promotes the resistance of BCR/ABL-positive leukemia cells to DNA-damaging agents. (PMID:15750625)
• Data suggest a new function of BLM in cooperating with Mus81 during processing and restoration of stalled replication forks. (PMID:15805243)
• WRN, BLM, and dmRecQ5b have a novel strand pairing capability that, when coordinated with the well established helicase activity, endows these RecQ helicases with a strand exchange function (PMID:15845538)
• physical interaction between RPA and WRN or BLM helicases plays an important role in the mechanism for RPA stimulation of helicase-catalyzed DNA unwinding. (PMID:15965237)
• Dissolution is highly specific for BLM among human RecQ helicases and critically depends upon a functional HRDC domain in BLM. (PMID:15990871)
• POT1 and RecQ helicases WRN and BLM have cooperative roles in resolving DNA structures at telomeric ends, in a manner that protects the telomeric 3’ tail as it is exposed during unwinding (PMID:16030011)
• BLM appears to dissociate from Top3alpha and PML following its phosphorylation and facilitates H2AX phosphorylation in response to replication double-strand breaks induced by Top1. (PMID:16199871)
• if a DNA oligomer complementary to one strand of the DNA substrate to be unwound is added during the helicase reaction, both WRN and BLM unwinding is enhanced, presumably by preventing protein-mediated re-annealing (PMID:16412221)
• a component of the BLM/TOPO IIIalpha complex, BLAP75/RMI1, promotes dissolution catalyzed by TOPO IIIalpha (PMID:16537486)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	blm	ENSDARG00000077089
mus_musculus	Blm	ENSMUSG00000030528
rattus_norvegicus	Blm	ENSRNOG00000011213
drosophila_melanogaster	Blm	FBGN0002906
caenorhabditis_elegans		WBGENE00001865

Paralogs (4): RECQL (ENSG00000004700), RECQL5 (ENSG00000108469), RECQL4 (ENSG00000160957), WRN (ENSG00000165392)

Protein

Protein identifiers

RecQ-like DNA helicase BLM — P54132 (reviewed: P54132)

Alternative names: Bloom syndrome protein, DNA 3’-5’ helicase BLM, DNA helicase, RecQ-like type 2, RecQ protein-like 3

All UniProt accessions (5): A0A3B3IT82, A0A7P0TBM9, P54132, H0YLV8, H0YNU5

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent DNA helicase that unwinds double-stranded (ds)DNA in a 3’-5’ direction. Participates in DNA replication and repair. Involved in 5’-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5’-ssDNA. Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution. Binds single-stranded DNA (ssDNA), forked duplex DNA and Holliday junction DNA. Unwinds G-quadruplex DNA; unwinding occurs in the 3’-5’ direction and requires a 3’ single-stranded end of at least 7 nucleotides. Helicase activity is higher on G-quadruplex substrates than on duplex DNA substrates. Telomeres, immunoglobulin heavy chain switch regions and rDNA are notably G-rich; formation of G-quadruplex DNA would block DNA replication and transcription. Negatively regulates sister chromatid exchange (SCE). Recruited by the KHDC3L-OOEP scaffold to DNA replication forks where it is retained by TRIM25 ubiquitination, it thereby promotes the restart of stalled replication forks. (Microbial infection) Eliminates nuclear HIV-1 cDNA, thereby suppressing immune sensing and proviral hyper-integration.

Subunit / interactions. Monomer. Homodimer (via N-terminus). Homotetramer (via N-terminus); dimer of dimers. Homohexamer (via N-terminus). Self-association negatively regulates DNA unwinding amplitude and rate. Oligomeric complexes dissociate into monomer in presence of ATP. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with RMI complex. Interacts directly with RMI1 (via N-terminal region) component of RMI complex. Found in a complex, at least composed of BLM, RAD51 and SPIDR; the complex formation is mediated by SPIDR. Interacts with the KHDC3L/FILIA-OOEP/FLOPED scaffold complex and TRIM25 at DNA replication forks. Interacts with ubiquitinated FANCD2. Interacts with SUPV3L1. Interacts with TOP3A (via N-terminal region). Interacts with SPIDR (via C-terminal region); the interaction is direct and required to target BLM to sites of DNA damage.

Subcellular location. Nucleus.

Post-translational modifications. Poly-ubiquitinated by TRIM25 at Lys-259. Deubiquitinated by USP37; leading to stabilization in order to sustain the DNA damage response. Phosphorylated in response to DNA damage. Phosphorylation requires the FANCA-FANCC-FANCE-FANCF-FANCG protein complex, as well as the presence of RMI1. (Microbial infection) Sumoylation of BLM is decreased by HIV-1 Vpu protein, unleashing end degradation of viral cDNA.

Disease relevance. Bloom syndrome (BLM) [MIM:210900] An autosomal recessive disorder. It is characterized by proportionate pre- and postnatal growth deficiency, sun-sensitive telangiectatic hypo- and hyperpigmented skin, predisposition to malignancy, and chromosomal instability. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Helicase activity on forked duplex DNA is not inhibited by telomestatin (TMS); TMS does inhibit helicase activity on G-quadruplex DNA.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The N-terminal region mediates dimerization and homooligomerization. Both the helicase ATP-binding domain and the helicase C-terminal domain form intramolecular interactions with the HRDC domain in a ATP-dependent manner. The HRDC domain is required for single-stranded DNA (ssDNA) and DNA Holliday junction binding.

Similarity. Belongs to the helicase family. RecQ subfamily.

RefSeq proteins (4): NP_000048, NP_001274175, NP_001274176, NP_001274177 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001650	Helicase_C-like	Domain
IPR002121	HRDC_dom	Domain
IPR002464	DNA/RNA_helicase_DEAH_CS	Conserved_site
IPR004589	DNA_helicase_ATP-dep_RecQ	Family
IPR010997	HRDC-like_sf	Homologous_superfamily
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR012532	BDHCT	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR018982	RQC_domain	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032284	RecQ_Zn-bd	Domain
IPR032437	BLM_N	Domain
IPR032439	BDHCT_assoc	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR044876	HRDC_dom_sf	Homologous_superfamily

Pfam: PF00270, PF00271, PF00570, PF08072, PF09382, PF16124, PF16202, PF16204

Enzyme classification (BRENDA):

• EC 3.6.4.12 — DNA helicase (BRENDA: 0 organisms, 0 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (190 total): helix 38, cross-link 32, strand 22, modified residue 20, sequence variant 17, region of interest 14, mutagenesis site 13, binding site 8, turn 7, compositionally biased region 7, site 6, domain 3, short sequence motif 2, chain 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
7XV0	X-RAY DIFFRACTION	1.5
7AUC	X-RAY DIFFRACTION	1.53
7XUW	X-RAY DIFFRACTION	1.8
5LUP	X-RAY DIFFRACTION	2.03
5MK5	X-RAY DIFFRACTION	2.16
4O3M	X-RAY DIFFRACTION	2.3
5U6K	X-RAY DIFFRACTION	2.6
3WE2	X-RAY DIFFRACTION	2.7
4CDG	X-RAY DIFFRACTION	2.79
3WE3	X-RAY DIFFRACTION	2.9
7AUD	X-RAY DIFFRACTION	2.96
4CGZ	X-RAY DIFFRACTION	3.2
2KV2	SOLUTION NMR
2MH9	SOLUTION NMR
2RRD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54132-F1	61.10	0.30

Antibody-complex structures (SAbDab): 1 — 4CDG

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 (6): 717 (3’ overhang dna-binding); 808 (3’ overhang dna-binding); 920 (3’ overhang dna-binding; via amide nitrogen); 946 (3’ overhang dna-binding); 968 (3’ overhang dna-binding); 1110 (3’ overhang dna-binding)

Ligand- & substrate-binding residues (8): 668–672; 692–696; 982; 1036; 1055; 1063; 1066; 1242

Post-translational modifications (52): 28, 48, 57, 114, 168, 171, 328, 338, 358, 419, 422, 426, 464, 499, 508, 863, 1197, 1295, 1296, 1310 …

Mutagenesis-validated functional residues (13):

Position	Phenotype
666	reduced intramolecular association between both the helicase atp-binding domain and the helicase c-terminal domain with
729	reduced intramolecular interaction between both the helicase atp-binding domain and the helicase c-terminal domain with
1094–1103	decreased dna holliday junction binding.
1121	decreased slightly dna holliday junction binding.
1125	decreased dna holliday junction binding.
1139	decreased strongly dna holliday junction binding.
1164	reduced strongly dna helicase activity.
1227	reduced ssdna binding. no change in dna holliday junction binding.
1237	no change in ssdna binding. increased dna holliday junction binding.
1239	reduced ssdna binding. no change in dna holliday junction binding.
1243	no change in ssdna binding. decreased dna holliday junction binding.
1244	reduced ssdna binding. increased dna holliday junction binding.
1270	reduced intramolecular interaction between both the helicase atp-binding domain and the helicase c-terminal domain with

Function

Pathways and Gene Ontology

Reactome pathways

45 pathways

ID	Pathway
R-HSA-174414	Processive synthesis on the C-strand of the telomere
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5693554	Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693579	Homologous DNA Pairing and Strand Exchange
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-912446	Meiotic recombination
R-HSA-9701192	Defective homologous recombination repair (HRR) due to BRCA1 loss of function
R-HSA-9704331	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function
R-HSA-9704646	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function
R-HSA-9709570	Impaired BRCA2 binding to RAD51
R-HSA-9709603	Impaired BRCA2 binding to PALB2
R-HSA-1474165	Reproduction
R-HSA-1500620	Meiosis
R-HSA-157579	Telomere Maintenance
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-174417	Telomere C-strand (Lagging Strand) Synthesis
R-HSA-180786	Extension of Telomeres
R-HSA-212436	Generic Transcription Pathway
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-392499	Metabolism of proteins
R-HSA-5633007	Regulation of TP53 Activity

MSigDB gene sets: 622 (showing top): PID_FANCONI_PATHWAY, GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, REACTOME_MEIOTIC_RECOMBINATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_RESPONSE_TO_IONIZING_RADIATION, PID_TELOMERASE_PATHWAY, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DIVISION, GOBP_CELL_CYCLE_DNA_REPLICATION, FISCHER_G1_S_CELL_CYCLE, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, GOBP_CELL_CYCLE_PHASE_TRANSITION

GO Biological Process (24): regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079), telomere maintenance (GO:0000723), double-strand break repair via homologous recombination (GO:0000724), DNA double-strand break processing (GO:0000729), DNA replication (GO:0006260), DNA repair (GO:0006281), DNA recombination (GO:0006310), DNA damage response (GO:0006974), mitotic G2 DNA damage checkpoint signaling (GO:0007095), response to X-ray (GO:0010165), replication fork processing (GO:0031297), telomere maintenance via semi-conservative replication (GO:0032201), DNA geometric change (GO:0032392), positive regulation of DNA-templated transcription (GO:0045893), negative regulation of DNA recombination (GO:0045910), protein complex oligomerization (GO:0051259), protein homooligomerization (GO:0051260), negative regulation of cell division (GO:0051782), telomeric D-loop disassembly (GO:0061820), resolution of DNA recombination intermediates (GO:0071139), cellular response to ionizing radiation (GO:0071479), cellular response to hydroxyurea (GO:0072711), cellular response to camptothecin (GO:0072757), t-circle formation (GO:0090656)

GO Molecular Function (29): four-way junction DNA binding (GO:0000400), Y-form DNA binding (GO:0000403), bubble DNA binding (GO:0000405), p53 binding (GO:0002039), DNA binding (GO:0003677), DNA helicase activity (GO:0003678), single-stranded DNA binding (GO:0003697), helicase activity (GO:0004386), ATP binding (GO:0005524), ATP-dependent activity, acting on DNA (GO:0008094), zinc ion binding (GO:0008270), four-way junction helicase activity (GO:0009378), ATP hydrolysis activity (GO:0016887), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), 3’-5’ DNA helicase activity (GO:0043138), G-quadruplex DNA binding (GO:0051880), forked DNA-dependent helicase activity (GO:0061749), telomeric D-loop binding (GO:0061821), telomeric G-quadruplex DNA binding (GO:0061849), 8-hydroxy-2’-deoxyguanosine DNA binding (GO:1905773), DNA/DNA annealing activity (GO:1990814), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides (GO:0016818), isomerase activity (GO:0016853), metal ion binding (GO:0046872)

GO Cellular Component (14): nuclear chromosome (GO:0000228), lateral element (GO:0000800), nucleus (GO:0005634), nucleoplasm (GO:0005654), replication fork (GO:0005657), chromosome (GO:0005694), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear matrix (GO:0016363), PML body (GO:0016605), RecQ family helicase-topoisomerase III complex (GO:0031422), protein-containing complex (GO:0032991), chromosome, telomeric region (GO:0000781)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	3
Resolution of D-Loop Structures	2
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	2
Telomere C-strand (Lagging Strand) Synthesis	1
SUMO E3 ligases SUMOylate target proteins	1
HDR through Homologous Recombination (HRR)	1
Homologous DNA Pairing and Strand Exchange	1
Regulation of TP53 Activity	1
G2/M Checkpoints	1
Meiosis	1
Diseases of DNA Double-Strand Break Repair	1
Reproduction	1
Cell Cycle	1
Chromosome Maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	6
cellular anatomical structure	6
nuclear lumen	4
DNA secondary structure binding	3
ATP-dependent activity	3
DNA helicase activity	3
chromosome	3
double-strand break repair	2
DNA recombination	2
protein binding	2
DNA binding	2
intracellular membraneless organelle	2
cyclin-dependent protein serine/threonine kinase activity	1
regulation of protein serine/threonine kinase activity	1
telomere organization	1
recombinational repair	1
5’-3’ DNA exonuclease activity	1
DNA biosynthetic process	1
DNA damage response	1
cellular response to stress	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
response to ionizing radiation	1
DNA-templated DNA replication maintenance of fidelity	1
telomere maintenance	1
cell cycle process	1
nuclear DNA replication	1
DNA conformation change	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of DNA recombination	1
negative regulation of DNA metabolic process	1
protein-containing complex assembly	1
protein complex oligomerization	1
negative regulation of cellular process	1
cell division	1
regulation of cell division	1
telomeric loop disassembly	1

Protein interactions and networks

STRING

2263 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BLM	RMI1	Q9H9A7	993
BLM	TOP3A	Q13472	952
BLM	DNA2	P51530	919
BLM	EXO1	Q9UQ84	915
BLM	RAD51	Q06609	892
BLM	MSH6	P52701	884
BLM	RMI2	Q96E14	881
BLM	ATM	Q13315	847
BLM	FANCM	Q8IYD8	839
BLM	FANCA	O15360	835
BLM	FANCC	Q00597	825
BLM	FANCF	Q9NPI8	822
BLM	FANCG	O15287	809
BLM	MLH1	P40692	808
BLM	FANCE	Q9HB96	806

IntAct

226 interactions, top by confidence:

A	B	Type	Score
BRIP1	BRCA1	psi-mi:“MI:0914”(association)	0.980
RPA2	RPA1	psi-mi:“MI:0914”(association)	0.960
RPA3	RPA2	psi-mi:“MI:0914”(association)	0.930
RMI1	BLM	psi-mi:“MI:0914”(association)	0.930
RMI1	BLM	psi-mi:“MI:0915”(physical association)	0.930
BLM	RMI1	psi-mi:“MI:0915”(physical association)	0.930
RMI1	BLM	psi-mi:“MI:0403”(colocalization)	0.930
BLM	TOP3A	psi-mi:“MI:0914”(association)	0.890
TOP3A	BLM	psi-mi:“MI:0915”(physical association)	0.890
BLM	TOP3A	psi-mi:“MI:0403”(colocalization)	0.890
RMI2	BLM	psi-mi:“MI:0914”(association)	0.830
ERCC6L	PLK1	psi-mi:“MI:0914”(association)	0.790
RIF1	BLM	psi-mi:“MI:0914”(association)	0.740
BLM	RIF1	psi-mi:“MI:0403”(colocalization)	0.740
BLM	TERF2	psi-mi:“MI:0407”(direct interaction)	0.690
TERF2	BLM	psi-mi:“MI:0915”(physical association)	0.690
BLM	TERF2	psi-mi:“MI:0403”(colocalization)	0.690
RPA1	BLM	psi-mi:“MI:0915”(physical association)	0.670
BLM	RPA1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (521): BLM (Affinity Capture-MS), BLM (Affinity Capture-Western), BLM (Affinity Capture-Western), BLM (Affinity Capture-MS), FAN1 (Affinity Capture-Western), FANCD2 (Affinity Capture-Western), RPA1 (Affinity Capture-Western), BLM (Affinity Capture-MS), BLM (Reconstituted Complex), BLM (Reconstituted Complex), BLM (Biochemical Activity), BLM (Affinity Capture-MS), BLM (Affinity Capture-MS), BLM (Affinity Capture-MS), BLM (Affinity Capture-Western)

ESM2 similar proteins: A0A0G2L7I0, A0A0R4IWG9, A0JMK9, A5D979, B0BLU1, D3ZVU1, F6UH96, G3X912, O70445, O88700, P54132, P59110, Q03111, Q0VBD2, Q1LVK9, Q22557, Q24558, Q24595, Q28E45, Q5EAW4, Q5I2W8, Q5R1T0, Q5SPR8, Q5XI59, Q6A037, Q6DJS0, Q6INS5, Q6P2L6, Q6XV80, Q6ZPI0, Q71M44, Q7KW09, Q7L590, Q7T308, Q7ZVP1, Q7ZXG4, Q801E2, Q803U7, Q80Z32, Q8AXF4

Diamond homologs: A2XVF7, A3AVH5, A4RK80, A8WK63, D4ACP5, G2TRN7, O09053, O18017, O34748, O88700, O93530, O94761, O94762, P0CQ88, P0CQ89, P15043, P35187, P40724, P46063, P50729, P54132, P71359, P73421, Q09811, Q0WVW7, Q14191, Q19546, Q5RF63, Q5UPX0, Q6AYJ1, Q75NR7, Q7RZH4, Q8L840, Q8VID5, Q9CL21, Q9DEY9, Q9FT70, Q9FT72, Q9FT73, Q9FT74

SIGNOR signaling

20 interactions.

A	Effect	B	Mechanism
MSH2	up-regulates	BLM	binding
MSH6	up-regulates	BLM	binding
CHEK1	up-regulates	BLM	phosphorylation
MSH2/MSH6	up-regulates	BLM	binding
BRIP1	“up-regulates quantity by stabilization”	BLM	binding
BLM	up-regulates	DNA_repair
RNF168	“up-regulates activity”	BLM	ubiquitination
RNF8	“up-regulates activity”	BLM	ubiquitination
BLM	“up-regulates activity”	UIMC1	binding
GSK3B	“down-regulates quantity by destabilization”	BLM	phosphorylation
CyclinA2/CDK2	“down-regulates quantity by destabilization”	BLM	phosphorylation
CHEK2	“down-regulates quantity by destabilization”	BLM	phosphorylation
CHEK1	“down-regulates quantity by destabilization”	BLM	phosphorylation
SCF-FBW7	“down-regulates quantity by destabilization”	BLM	ubiquitination
MIB1	“down-regulates quantity by destabilization”	BLM	ubiquitination
ATR	“up-regulates activity”	BLM	phosphorylation
TTK	“up-regulates activity”	BLM	phosphorylation
ATM	up-regulates	BLM	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 185 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Removal of the Flap Intermediate from the C-strand	7	35.0×	2e-08
Impaired BRCA2 binding to PALB2	8	28.8×	1e-08
Impaired BRCA2 binding to RAD51	11	26.7×	9e-11
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	8	26.6×	1e-08
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	8	26.6×	1e-08
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	8	26.6×	1e-08
HDR through Single Strand Annealing (SSA)	11	25.4×	9e-11
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	8	24.8×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of double-strand break repair via homologous recombination	6	22.8×	2e-05
mismatch repair	5	19.8×	4e-04
cellular response to gamma radiation	5	18.4×	5e-04
mitophagy	8	15.5×	6e-06
ribosomal small subunit biogenesis	10	13.9×	5e-07
cytoplasmic translation	12	13.6×	4e-08
double-strand break repair via homologous recombination	14	13.3×	3e-09
telomere maintenance	8	13.1×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

5268 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	351
Likely pathogenic	172
Uncertain significance	2716
Likely benign	1535
Benign	73

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068907	NM_000057.4(BLM):c.2592C>G (p.Tyr864Ter)	Pathogenic
1069141	NM_000057.4(BLM):c.3616del (p.Ala1206fs)	Pathogenic
1069515	NM_000057.4(BLM):c.1176dup (p.Leu393fs)	Pathogenic
1069614	NM_000057.4(BLM):c.3869del (p.Ser1290fs)	Pathogenic
1069959	NM_000057.4(BLM):c.1641_1642insAGAAAGAGAAACCCGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAGATCGAGACCATCCTGGCTAACACAGTGAAACCCCGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAA (p.Gln548delinsArgLysArgAsnProAlaGlyArgGlyGlySerArgLeuTer)	Pathogenic
1070009	NC_000015.9:g.(?91341410)(91341577_?)del	Pathogenic
1070833	NM_000057.4(BLM):c.3634G>T (p.Glu1212Ter)	Pathogenic
1071254	NM_000057.4(BLM):c.3860_3863del (p.Glu1287fs)	Pathogenic
1072379	NM_000057.4(BLM):c.2292T>G (p.Tyr764Ter)	Pathogenic
1073712	NM_000057.4(BLM):c.589C>T (p.Gln197Ter)	Pathogenic
1073777	NM_000057.4(BLM):c.1991_1992insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAGGAGATCGAGACCATCNNNNNNNNNNACGGGTCGCTGGCGTTGAGCCGCTTTTGCCCCACTCACGTCCGCCGTCCCCCCGGGGCTACACAGCCATAAACCTACAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAATTTGG (p.Leu665fs)	Pathogenic
1074060	NM_000057.4(BLM):c.2917del (p.Tyr973fs)	Pathogenic
1074816	NM_000057.4(BLM):c.572_573del (p.Arg191fs)	Pathogenic
1075178	NM_000057.4(BLM):c.227del (p.Pro76fs)	Pathogenic
1075440	NM_000057.4(BLM):c.2281_2291del (p.Lys761fs)	Pathogenic
1075675	NM_000057.4(BLM):c.826del (p.Glu276fs)	Pathogenic
1076010	NM_000057.4(BLM):c.1628T>G (p.Leu543Ter)	Pathogenic
1076035	NC_000015.9:g.(?91290623)(91298188_?)del	Pathogenic
1076386	NM_000057.4(BLM):c.3011_3012del (p.Leu1004fs)	Pathogenic
1177404	NM_000057.4(BLM):c.175_176del (p.Val59fs)	Pathogenic
127478	NM_000057.4(BLM):c.1642C>T (p.Gln548Ter)	Pathogenic
127491	NM_000057.4(BLM):c.2695C>T (p.Arg899Ter)	Pathogenic
1324491	NM_000057.4(BLM):c.1341del (p.Asn448fs)	Pathogenic
1324525	NM_000057.4(BLM):c.397dup (p.Asp133fs)	Pathogenic
1339538	NM_000057.4(BLM):c.1535dup (p.Asn515fs)	Pathogenic
1350415	NM_000057.4(BLM):c.919G>T (p.Glu307Ter)	Pathogenic
1359680	NM_000057.4(BLM):c.2131_2132del (p.Val711fs)	Pathogenic
1361379	NM_000057.4(BLM):c.700_710del (p.Asp234fs)	Pathogenic
1364586	NM_000057.4(BLM):c.583A>T (p.Lys195Ter)	Pathogenic
1366642	NM_000057.4(BLM):c.1489C>T (p.Gln497Ter)	Pathogenic

SpliceAI

3964 predictions. Top by Δscore:

Variant	Effect	Δscore
15:90717441:G:GG	donor_gain	1.0000
15:90747465:T:G	donor_gain	1.0000
15:90747465:T:TG	donor_gain	1.0000
15:90747491:G:GG	donor_gain	1.0000
15:90749365:A:AG	acceptor_gain	1.0000
15:90749366:G:GG	acceptor_gain	1.0000
15:90749366:GA:G	acceptor_gain	1.0000
15:90750029:A:T	donor_gain	1.0000
15:90750065:G:GT	donor_gain	1.0000
15:90750065:GAG:G	donor_gain	1.0000
15:90751786:GATA:G	acceptor_gain	1.0000
15:90751940:GCCT:G	donor_gain	1.0000
15:90751943:TTAGG:T	donor_loss	1.0000
15:90751944:TAGGT:T	donor_loss	1.0000
15:90751945:AGGT:A	donor_loss	1.0000
15:90751946:GGT:G	donor_loss	1.0000
15:90751947:G:C	donor_loss	1.0000
15:90751948:T:A	donor_loss	1.0000
15:90751956:C:G	donor_gain	1.0000
15:90754809:A:AG	acceptor_gain	1.0000
15:90754809:AGTAC:A	acceptor_gain	1.0000
15:90754810:G:GA	acceptor_gain	1.0000
15:90754810:GT:G	acceptor_gain	1.0000
15:90754810:GTAC:G	acceptor_gain	1.0000
15:90754810:GTACG:G	acceptor_gain	1.0000
15:90765290:TTTCA:T	acceptor_loss	1.0000
15:90765292:TCA:T	acceptor_loss	1.0000
15:90765293:CAGGA:C	acceptor_loss	1.0000
15:90765294:A:C	acceptor_loss	1.0000
15:90765295:GGA:G	acceptor_gain	1.0000

AlphaMissense

9423 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:90765307:A:C	S696R	1.000
15:90765309:T:A	S696R	1.000
15:90765309:T:G	S696R	1.000
15:90765356:T:A	V712D	1.000
15:90765377:T:C	L719P	1.000
15:90765401:T:C	L727P	1.000
15:90766926:T:C	L737P	1.000
15:90767004:T:C	L763P	1.000
15:90769212:A:C	E796A	1.000
15:90769212:A:T	E796V	1.000
15:90769222:T:G	C799W	1.000
15:90769226:A:C	S801R	1.000
15:90769228:T:A	S801R	1.000
15:90769228:T:G	S801R	1.000
15:90769438:T:A	W803R	1.000
15:90769438:T:C	W803R	1.000
15:90769440:G:C	W803C	1.000
15:90769440:G:T	W803C	1.000
15:90769450:T:C	F807L	1.000
15:90769452:T:A	F807L	1.000
15:90769452:T:G	F807L	1.000
15:90769523:C:A	A831D	1.000
15:90785058:T:A	W934R	1.000
15:90785058:T:C	W934R	1.000
15:90790659:C:A	A945D	1.000
15:90790670:T:C	F949L	1.000
15:90790672:T:A	F949L	1.000
15:90790672:T:G	F949L	1.000
15:90790677:T:C	M951T	1.000
15:90790679:G:A	G952R	1.000

dbSNP variants (sampled 300 via entrez): RS1000028199 (15:90814662 T>A), RS1000099001 (15:90796635 A>G), RS1000140269 (15:90726732 A>C), RS1000142009 (15:90737180 T>C,G), RS1000188825 (15:90730972 G>A), RS1000222584 (15:90732468 A>G), RS1000287414 (15:90773590 T>G), RS1000338549 (15:90738215 T>G), RS1000353906 (15:90812512 C>A,G), RS1000412570 (15:90720712 G>A,C), RS1000448138 (15:90796444 C>T), RS1000458869 (15:90762574 A>C), RS1000468830 (15:90737167 T>C,G), RS1000473158 (15:90802772 C>T), RS1000501461 (15:90727431 T>C)

Disease associations

OMIM: gene MIM:604610 | disease phenotypes: MIM:210900, MIM:167000, MIM:114500, MIM:114480

GenCC curated gene-disease

Disease	Classification	Inheritance
Bloom syndrome	Definitive	Autosomal recessive
osteosarcoma	Moderate	Autosomal recessive
colorectal cancer	Limited	Autosomal dominant
breast cancer	Disputed Evidence	Autosomal dominant
hereditary nonpolyposis colon cancer	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
colorectal cancer	Limited	AD
Bloom syndrome	Definitive	AR

Mondo (12): Bloom syndrome (MONDO:0008876), hereditary neoplastic syndrome (MONDO:0015356), ovarian cancer (MONDO:0008170), colorectal cancer (MONDO:0005575), microcephaly (MONDO:0001149), hereditary breast ovarian cancer syndrome (MONDO:0003582), endometrial carcinoma (MONDO:0002447), hereditary breast carcinoma (MONDO:0016419), hereditary disease (MONDO:0003847), breast cancer (MONDO:0007254), hereditary nonpolyposis colon cancer (MONDO:0018630), osteosarcoma (MONDO:0009807)

Orphanet (6): Bloom syndrome (Orphanet:125), Inherited cancer-predisposing syndrome (Orphanet:140162), Rare ovarian cancer (Orphanet:213500), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Hereditary breast cancer (Orphanet:227535), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

99 total (30 of 99 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000272	Malar flattening
HP:0000275	Narrow face
HP:0000278	Retrognathia
HP:0000347	Micrognathia
HP:0000388	Otitis media
HP:0000411	Protruding ear
HP:0000448	Prominent nose
HP:0000488	Retinopathy
HP:0000554	Uveitis
HP:0000653	Sparse eyelashes
HP:0000690	Agenesis of maxillary lateral incisor
HP:0000798	Oligozoospermia
HP:0000819	Diabetes mellitus
HP:0000855	Insulin resistance
HP:0000868	Decreased fertility in females
HP:0000957	Cafe-au-lait spot
HP:0000988	Skin rash
HP:0000992	Cutaneous photosensitivity
HP:0000998	Hypertrichosis
HP:0001009	Telangiectasia
HP:0001010	Hypopigmentation of the skin
HP:0001029	Poikiloderma
HP:0001041	Facial erythema
HP:0001159	Syndactyly

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003518_37	Daytime sleep phenotypes	9.000000e-06
GCST010479_39	Coronary artery disease	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D001816	Bloom Syndrome	C16.131.077.137; C16.320.798.313; C18.452.284.100; C20.673.795.313
D030342	Genetic Diseases, Inborn	C16.320
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D012516	Osteosarcoma	C04.557.450.565.575.650; C04.557.450.795.620
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293237 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

284 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 881,478 (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
CHEMBL1006	AMIFOSTINE	4	34,963
CHEMBL1023	BEXAROTENE	4	40,951
CHEMBL1034	DICLOFENAC SODIUM	4	45,460
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1057	FLUORESCEIN	4	329,940
CHEMBL1068	OXCARBAZEPINE	4	16,118
CHEMBL1072	BUMETANIDE	4	22,087
CHEMBL1073	GLIPIZIDE	4	42,268
CHEMBL1082607	SALMETEROL XINAFOATE	4	15,201
CHEMBL1083993	AMIODARONE HYDROCHLORIDE	4	3,265
CHEMBL1091250	INDIGOTINDISULFONATE	4	340
CHEMBL1092	TRIHEXYPHENIDYL HYDROCHLORIDE	4	7,793
CHEMBL1116	RALOXIFENE HYDROCHLORIDE	4	28,574
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL1128	EDROPHONIUM CHLORIDE	4	20,117
CHEMBL1159	PINACIDIL ANHYDROUS	4	6,303
CHEMBL1185568	DITHIAZANINE	4	123
CHEMBL119	TRIMETREXATE	4	57,002
CHEMBL1200326	NICARDIPINE HYDROCHLORIDE	4	3,903
CHEMBL1200330	PILOCARPINE HYDROCHLORIDE	4	14,680
CHEMBL1200339	PHENYLEPHRINE HYDROCHLORIDE	4
CHEMBL1200379	APRACLONIDINE HYDROCHLORIDE	4
CHEMBL1200392	DOXYLAMINE SUCCINATE	4
CHEMBL1200411	ROPINIROLE HYDROCHLORIDE	4
CHEMBL1200413	TETRAHYDROZOLINE HYDROCHLORIDE	4
CHEMBL1200419	MOLINDONE HYDROCHLORIDE	4
CHEMBL1200425	PARGYLINE HYDROCHLORIDE	4
CHEMBL1200494	GUANFACINE HYDROCHLORIDE	4
CHEMBL1200503	BROMOCRIPTINE MESYLATE	4
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 3.6.4.12 RecQ helicases family

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
compound 9h [PMID: 32697083]	Inhibition	6.12	pKd
ML216	Inhibition	5.74	pIC50
compound 2 [PMID: 33647232]	Inhibition	5.66	pIC50
compound 21 [PMID: 36459756]	Inhibition	5.64	pIC50
AO/854	Inhibition	5.0	pIC50

ChEMBL bioactivities

1196 potent at pChembl≥5 of 3498 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Potency	1	nM	CHEMBL1255662
9.00	Potency	1	nM	CHEMBL124267
9.00	Potency	1	nM	CHEMBL121915
9.00	Potency	1	nM	ETHAMIVAN
9.00	Potency	1	nM	KETOROLAC TROMETHAMINE
8.96	Potency	1.1	nM	ACETAMIDE
8.96	Potency	1.1	nM	NEBULARINE
8.96	Potency	1.1	nM	CHEMBL1608159
8.96	Potency	1.1	nM	SPIPERONE HYDROCHLORIDE
8.96	Potency	1.1	nM	CYCLOSERINE
8.96	Potency	1.1	nM	CHEMBL47529
8.89	Potency	1.3	nM	ENOXIMONE
8.89	Potency	1.3	nM	LOPERAMIDE HYDROCHLORIDE
8.89	Potency	1.3	nM	IDAZOXAN HYDROCHLORIDE
8.85	Potency	1.4	nM	7-NITROINDAZOLE
8.80	Potency	1.6	nM	FAMOTIDINE
8.80	Potency	1.6	nM	CYSTEAMINE HYDROCHLORIDE
8.80	Potency	1.6	nM	AZACITIDINE
8.80	Potency	1.6	nM	MELATONIN
8.80	Potency	1.6	nM	SULPIRIDE
8.80	Potency	1.6	nM	CHEMBL1256839
8.80	Potency	1.6	nM	BENZOQUINONE
8.74	Potency	1.8	nM	5-NITRO-2-PHENYLPROPYLAMINOBENZOIC ACID [NPPB]
8.70	Potency	2	nM	NOCODAZOLE
8.70	Potency	2	nM	CHEMBL1414236
8.70	Potency	2	nM	CHEMBL1256710
8.66	Potency	2.2	nM	CHELIDAMIC ACID
8.66	Potency	2.2	nM	SEPIAPTERIN
8.66	Potency	2.2	nM	PHENYTOIN
8.66	Potency	2.2	nM	CHEMBL1405759
8.60	Potency	2.5	nM	EDROPHONIUM CHLORIDE
8.60	Potency	2.5	nM	(D)-SERINE
8.60	Potency	2.5	nM	CHEMBL1394801
8.60	Potency	2.5	nM	CHEMBL113180
8.60	Potency	2.5	nM	CHEMBL26318
8.60	Potency	2.5	nM	DICLOFENAC SODIUM
8.60	Potency	2.5	nM	NEBOGLAMINE
8.60	Potency	2.5	nM	METHACHOLINE CHLORIDE
8.55	Potency	2.8	nM	FINASTERIDE
8.55	Potency	2.8	nM	CHEMBL1594626
8.55	Potency	2.8	nM	DEXIBUPROFEN
8.55	Potency	2.8	nM	CHEMBL1551643
8.55	Potency	2.8	nM	CHEMBL1556654
8.55	Potency	2.8	nM	PILOCARPINE HYDROCHLORIDE
8.55	Potency	2.8	nM	HYDROQUINONE
8.55	Potency	2.8	nM	5-AMINOPENTANOIC ACID HYDROCHLORIDE
8.55	Potency	2.8	nM	CORTODOXONE
8.55	Potency	2.8	nM	CHEMBL1255650
8.55	Potency	2.8	nM	VESAMICOL HYDROCHLORIDE
8.55	Potency	2.8	nM	DUBINIDINE

PubChem BioAssay actives

78 with measured affinity, of 279 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
1-(4-chloro-3-cyanophenyl)-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	0.1000	uM
1-(4-bromo-3-cyanophenyl)-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	0.1100	uM
1-(3-cyano-4-fluorophenyl)-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	0.3000	uM
3-(2-chloroethyl)-7-[3-(diethylamino)propylamino]-6-fluoro-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1665073: Binding affinity to wild-type His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells by isothermal calorimetric titration assay	kd	0.7600	uM
3-[(4-bromophenyl)methyl]-7-[3-(diethylamino)propylamino]-6-fluoro-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1979876: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5’-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay	ic50	0.8000	uM
1-(3-bromo-4-cyanophenyl)-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	0.9100	uM
(3E)-6-[3-(diethylamino)propylamino]-7-fluoro-3-[(4-propan-2-ylphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1524464: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as reduction in BLM helicase unwinding activity using 5’-biotin labeled forked-DNA as substrate after 1 hr by PAGE analysis	ic50	0.9500	uM
1-[3-cyano-4-(1H-pyrazol-4-yl)phenyl]-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	1.1000	uM
(3E)-6-[2-(diethylamino)ethylamino]-3-[(4-propan-2-ylphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	1.3000	uM
3-(3-chloropropyl)-7-[3-(diethylamino)propylamino]-6-fluoro-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1979876: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5’-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay	ic50	1.3000	uM
1-(4-chloro-3-nitrophenyl)-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	1.3000	uM
1-(3,4-dichlorophenyl)-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	1.4000	uM
(2,5-dioxopyrrol-1-yl)methyl propanoate	2139693: Inhibition of BLM (unknown origin) ATPase activity	ic50	1.6000	uM
1-(3-chloro-4-cyanophenyl)-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	1.6000	uM
(3E)-6-[4-(diethylamino)butylamino]-7-fluoro-3-[(4-propan-2-ylphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	1.8000	uM
1-[4-fluoro-3-(trifluoromethyl)phenyl]-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	1.8000	uM
1-[3-cyano-4-(1H-pyrrol-2-yl)phenyl]-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	1.8000	uM
(3E)-6-[2-(diethylamino)ethylamino]-7-fluoro-3-[(4-propan-2-ylphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	2.0000	uM
(3E)-6-[2-(diethylamino)ethylamino]-3-[[4-(diethylamino)-2-hydroxyphenyl]methylidene]-7-fluoro-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	2.1000	uM
1-(3,4-dibromophenyl)-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	2.1000	uM
7-[2-(diethylamino)ethylamino]-6-fluoro-3-methyl-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	2.2000	uM
3-[(3-bromophenyl)methyl]-7-[3-(diethylamino)propylamino]-6-fluoro-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1979876: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5’-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay	ic50	2.3000	uM
7-[3-(diethylamino)propylamino]-3-[2-(dimethylamino)ethyl]-6-fluoro-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1979876: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5’-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay	ic50	2.5000	uM
(3E)-3-[(4-tert-butylphenyl)methylidene]-6-[2-(diethylamino)ethylamino]-7-fluoro-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	2.7000	uM
(3E)-6-[2-(dimethylamino)ethylamino]-7-fluoro-3-[(4-propan-2-ylphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	2.8000	uM
7-[3-(diethylamino)propylamino]-3-ethyl-6-fluoro-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	2.8000	uM
3-[(2-bromophenyl)methyl]-7-[3-(diethylamino)propylamino]-6-fluoro-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1979876: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5’-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay	ic50	2.9000	uM
7-[2-(diethylamino)ethylamino]-6-fluoro-2-[(E)-2-(3-hydroxy-4-propan-2-ylphenyl)ethenyl]-3-methylquinazolin-4-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	3.0000	uM
(3E)-6-[2-(diethylamino)ethylamino]-7-fluoro-3-[[4-(2-methylpropyl)phenyl]methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	3.1000	uM
(3E)-6-[2-(diethylamino)ethylamino]-3-[(4-ethylphenyl)methylidene]-7-fluoro-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	3.2000	uM
1-(4-cyano-3-methylphenyl)-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	3.2000	uM
(3E)-6-[2-(diethylamino)ethylamino]-7-fluoro-3-[(4-propylphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	3.3000	uM
2-(3-hydroxy-5-sulfo-1H-indol-2-yl)-3-oxoindole-5-sulfonic acid	2139693: Inhibition of BLM (unknown origin) ATPase activity	ic50	3.3000	uM
1-(3,4-dichlorophenyl)-3-(5-pyridin-3-yl-1,3,4-thiadiazol-2-yl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	3.5000	uM
7-[3-(diethylamino)propylamino]-6-fluoro-3-(2-methylpropyl)-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	3.6000	uM
7-[3-(diethylamino)propylamino]-6-fluoro-3-pentyl-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1979876: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5’-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay	ic50	3.7000	uM
(3E)-6-[2-(diethylamino)ethylamino]-7-fluoro-3-[(2-hydroxy-4-propan-2-ylphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	4.0000	uM
7-[3-(diethylamino)propylamino]-6-fluoro-3-(2-phenylethyl)-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1979876: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5’-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay	ic50	4.0000	uM
1-(3,4-dichlorophenyl)-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)thiourea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	4.0000	uM
1-(3,4-dichlorophenyl)-3-(6-pyridin-4-yl-2-pyridinyl)urea	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	4.0000	uM
(3E)-6-[3-(diethylamino)propylamino]-7-fluoro-3-[(2-hydroxy-4-propan-2-ylphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	4.2000	uM
2-[7-[3-(diethylamino)propylamino]-6-fluoro-4-oxo-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-3-yl]acetonitrile	1979876: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5’-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay	ic50	4.3000	uM
3-(3,4-dichloroanilino)-4-[(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)amino]cyclobut-3-ene-1,2-dione	771544: Inhibition of BLM (unknown origin) by gel-based DNA unwinding assay	ic50	4.3000	uM
7-[3-(diethylamino)propylamino]-6-fluoro-3-methyl-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	4.7000	uM
7-[3-(diethylamino)propylamino]-6-fluoro-2-[(E)-2-[4-(2-methylpropyl)phenyl]ethenyl]-3H-quinazolin-4-one	1665070: Inhibition of His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA unwinding activity using 5’-biotin-labeled forked DNA as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by electrophoretic mobility shift assay	ic50	4.7000	uM
3-butyl-7-[3-(diethylamino)propylamino]-6-fluoro-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1979876: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5’-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay	ic50	4.8000	uM
7-[3-(diethylamino)propylamino]-6-fluoro-3-[(4-methoxyphenyl)methyl]-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1979876: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5’-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay	ic50	5.0000	uM
7-[3-(diethylamino)propylamino]-6-fluoro-3-(3-propan-2-yloxypropyl)-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1979876: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5’-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay	ic50	5.2000	uM
7-[3-(diethylamino)propylamino]-6-fluoro-3-[(2-fluorophenyl)methyl]-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]quinazolin-4-one	1979876: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5’-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay	ic50	5.2000	uM
7-[3-(diethylamino)propylamino]-6-fluoro-2-[(E)-2-(4-propan-2-ylphenyl)ethenyl]-3-[[2-(trifluoromethyl)phenyl]methyl]quinazolin-4-one	1979876: Inhibition of His-tagged BLM (unknown origin) expressed in Escherichia coli BL21 (DE3) using 5’-biotin-labeled duplex forked-DNA as substrate incubated for 10 mins followed by substrate addition measured after 30 mins in presence of ATP by electrophoretic mobility shift assay	ic50	5.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression, decreases reaction	4
Estradiol	decreases reaction, increases expression, affects cotreatment, decreases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Benzo(a)pyrene	decreases expression, increases expression	3
Tobacco Smoke Pollution	decreases expression, increases expression	3
lasiocarpine	decreases expression, increases metabolic processing, increases expression	2
Air Pollutants	increases expression, affects cotreatment, decreases expression, increases abundance	2
Arsenic	increases abundance, decreases expression, affects cotreatment	2
Cisplatin	decreases expression, increases expression	2
Doxorubicin	decreases expression	2
Hydroxyurea	decreases expression, increases expression	2
Methyl Methanesulfonate	decreases expression, increases expression	2
Valproic Acid	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
afuresertib	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
PF-06840003	decreases expression, decreases reaction	1
pradimicin-IRD	decreases expression, affects expression, affects response to substance	1
dicrotophos	decreases expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
propionaldehyde	decreases expression	1
4-biphenylamine	decreases expression, decreases reaction	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects response to substance, affects expression	1
VX-agent	increases expression	1
riddelliine	decreases expression, increases metabolic processing	1
arsenite	affects binding, decreases reaction	1

ChEMBL screening assays

82 unique, capped per target: 78 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1614067	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of Bloom’s syndrome helicase (BLM). (Class of assay: confirmatory) [Related pubchem assays: 593 (Fluorescein region spectral profiling screen), 2386 (Probe Development Summary for Inhibitors of Bl	PubChem BioAssay data set
CHEMBL2428102	Binding	Inhibition of BLM in human PSNF5 cells assessed as increase of sister chromatid exchange at 1 to 5 uM	Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase. — Bioorg Med Chem Lett

Cellosaurus cell lines

92 cell lines: 50 transformed cell line, 31 finite cell line, 9 cancer cell line, 1 induced pluripotent stem cell, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0378	KNS-42	Cancer cell line	Male
CVCL_2869	BSL2KA	Transformed cell line	Male
CVCL_7320	GM01492	Finite cell line	Male
CVCL_7408	GM04408	Transformed cell line	Male
CVCL_7488	GM08505	Transformed cell line	Female
CVCL_7651	GM16375	Transformed cell line	Male
CVCL_B7BK	GM3498B-HV1	Transformed cell line	Male
CVCL_B7BL	GM3498B-HV2	Transformed cell line	Male
CVCL_B8C1	Abcam HCT 116 BLM KO	Cancer cell line	Male
CVCL_B8SZ	Abcam MCF-7 BLM KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00014638	PHASE4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	PHASE4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	PHASE4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	PHASE4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	PHASE4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	PHASE4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	PHASE4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	PHASE4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	PHASE4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	PHASE4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	PHASE4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	PHASE4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	PHASE4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00237133	PHASE4	COMPLETED	Treatment of Locally Advanced Breast Cancer With Letrozole in Postmenopausal Women
NCT00237224	PHASE4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	PHASE4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	PHASE4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	PHASE4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	PHASE4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
NCT00413491	PHASE4	UNKNOWN	National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
NCT00484614	PHASE4	UNKNOWN	Study the Role of Positron Emission Mammography in Pre-surgical Planning for Breast Cancer
NCT00485953	PHASE4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00531973	PHASE4	UNKNOWN	A Study of Liposomal Doxorubicin in Women With Breast Cancer Exploiting Tissue Doppler Imaging
NCT00537771	PHASE4	COMPLETED	Liver Safety Under Upfront Arimidex vs Tamoxifen
NCT00544986	PHASE4	COMPLETED	A Prospective,Open-label Study of Anastrozole in Post-menopausal Women With Hormone Sensitive Advanced Breast Cancer
NCT00613275	PHASE4	COMPLETED	Patient Navigation in the Safety Net:CONNECTeDD
NCT00638599	PHASE4	COMPLETED	Comparison of Laryngeal Mask Airway (LMA®) and Tracheal Tube in Modified Radical Mastectomy on Breast Cancer
NCT00647075	PHASE4	UNKNOWN	Yunzhi as Dietary Supplement in Breast Cancer
NCT00688909	PHASE4	COMPLETED	Rheumatological Evaluation of Anastrozole and Letrozole as Adjuvant Treatment in Post-menopausal Women With Breast Cancer
NCT00699101	PHASE4	TERMINATED	Using the Conture® Multi-Lumen Balloon to Deliver Accelerated Partial Breast Brachytherapy
NCT00742222	PHASE4	COMPLETED	Electronic Xoft Intersociety Brachytherapy Trial: Electronic Brachytherapy (EBT) For Treatment of Early Stage Breast Cancer
NCT00754767	PHASE4	TERMINATED	L-Carnitine L-Tartrate in Preventing Peripheral Neuropathy Caused By Chemotherapy in Women With Metastatic Breast Cancer