ATM

Summary

ATM (ATM serine/threonine kinase, HGNC:795) is a protein-coding gene on chromosome 11q22.3, encoding Serine-protein kinase ATM (Q13315). Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. In precision oncology, ATM Mutation confers sensitivity to Olaparib in Castration-resistant Prostate Carcinoma (CIViC Level A); 28 further curated variant–drug associations are listed below. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder.

Source: NCBI Gene 472 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ataxia telangiectasia (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 33
• Clinical variants (ClinVar): 18,501 total — 2543 pathogenic, 659 likely-pathogenic
• Phenotypes (HPO): 138
• Druggable target: yes — 35 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 29 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 24 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 27 downstream targets (CollecTRI)
• MANE Select transcript: NM_000051

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:795
Approved symbol	ATM
Name	ATM serine/threonine kinase
Location	11q22.3
Locus type	gene with protein product
Status	Approved
Aliases	TEL1, TELO1
Ensembl gene	ENSG00000149311
Ensembl biotype	protein_coding
OMIM	607585
Entrez	472

Gene structure

Transcript identifiers

Ensembl transcripts: 64 — 22 protein_coding, 19 retained_intron, 12 protein_coding_CDS_not_defined, 11 nonsense_mediated_decay

ENST00000278616, ENST00000419286, ENST00000452508, ENST00000524792, ENST00000525012, ENST00000525056, ENST00000525178, ENST00000525537, ENST00000526567, ENST00000527181, ENST00000527389, ENST00000527805, ENST00000529588, ENST00000530958, ENST00000531525, ENST00000532765, ENST00000532931, ENST00000533526, ENST00000533690, ENST00000533733, ENST00000533979, ENST00000601453, ENST00000638443, ENST00000638786, ENST00000639240, ENST00000639953, ENST00000640388, ENST00000675595, ENST00000675843, ENST00000682147, ENST00000682286, ENST00000682289, ENST00000682302, ENST00000682430, ENST00000682465, ENST00000682516, ENST00000682569, ENST00000682956, ENST00000683100, ENST00000683150, ENST00000683174, ENST00000683468, ENST00000683488, ENST00000683524, ENST00000683605, ENST00000683914, ENST00000684029, ENST00000684037, ENST00000684061, ENST00000684152, ENST00000684179, ENST00000684180, ENST00000684447, ENST00000713593, ENST00000713840, ENST00000713841, ENST00000713842, ENST00000713843, ENST00000713844, ENST00000713845, ENST00000713846, ENST00000713847, ENST00000923922, ENST00000971291

RefSeq mRNA: 4 — MANE Select: NM_000051 NM_000051, NM_001351834, NM_001351835, NM_001351836

CCDS: CCDS31669, CCDS86245

Canonical transcript exons

ENST00000675843 — 63 exons

Exon	Start	End
ENSE00003129472	108235670	108235834
ENSE00003725082	108227776	108227888
ENSE00003742933	108227595	108227696
ENSE00003744805	108229178	108229323
ENSE00004021445	108316011	108316113
ENSE00004021446	108315823	108315911
ENSE00004021447	108365082	108365218
ENSE00004021448	108329021	108329238
ENSE00004021449	108256215	108256340
ENSE00004021450	108284227	108284473
ENSE00004021451	108294927	108295059
ENSE00004021452	108310160	108310315
ENSE00004021453	108365325	108369102
ENSE00004021454	108244788	108245026
ENSE00004021455	108343222	108343371
ENSE00004021456	108331879	108332037
ENSE00004021457	108246964	108247127
ENSE00004021458	108332762	108332900
ENSE00004021459	108307897	108307984
ENSE00004021460	108319954	108320058
ENSE00004021461	108335845	108335961
ENSE00004021462	108271064	108271146
ENSE00004021463	108279491	108279608
ENSE00004021464	108289602	108289801
ENSE00004021465	108325310	108325544
ENSE00004021466	108272532	108272607
ENSE00004021467	108280995	108281168
ENSE00004021468	108330214	108330421
ENSE00004021469	108243953	108244118
ENSE00004021470	108333886	108333968
ENSE00004021471	108347279	108347365
ENSE00004021472	108282710	108282879
ENSE00004021473	108248933	108249102
ENSE00004021474	108223067	108223186
ENSE00004021475	108252817	108252912
ENSE00004021476	108327645	108327758
ENSE00004021477	108293313	108293477
ENSE00004021478	108253814	108254039
ENSE00004021479	108297287	108297382
ENSE00004021480	108299714	108299885
ENSE00004021481	108345743	108345908
ENSE00004021482	108287600	108287715
ENSE00004021483	108258986	108259075
ENSE00004021484	108257481	108257606
ENSE00004021485	108302853	108303029
ENSE00004021486	108317373	108317521
ENSE00004021487	108321301	108321420
ENSE00004021488	108271251	108271406
ENSE00004021489	108292619	108292793
ENSE00004021490	108288977	108289103
ENSE00004021491	108326058	108326225
ENSE00004021492	108331444	108331557
ENSE00004021493	108250701	108251072
ENSE00004021494	108267171	108267342
ENSE00004021495	108301648	108301789
ENSE00004021496	108304675	108304852
ENSE00004021497	108251837	108252031
ENSE00004021498	108268410	108268609
ENSE00004021499	108353766	108353880
ENSE00004021500	108272722	108272852
ENSE00004021501	108334969	108335109
ENSE00004021502	108354811	108354874
ENSE00004021503	108312411	108312498

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.8631 / max 648.4987, expressed in 1785 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116523	17.0357	1773
116531	2.3205	187
116525	2.0985	1050
116527	1.0873	454
116524	0.4146	170
116529	0.4115	86
116528	0.1575	55
116526	0.1555	68
116532	0.0997	48
116530	0.0423	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.33	gold quality
colonic epithelium	UBERON:0000397	97.24	gold quality
corpus callosum	UBERON:0002336	96.41	gold quality
lymph node	UBERON:0000029	96.36	gold quality
bone marrow cell	CL:0002092	96.26	gold quality
body of pancreas	UBERON:0001150	95.70	gold quality
adrenal tissue	UBERON:0018303	95.39	gold quality
sural nerve	UBERON:0015488	95.28	gold quality
tonsil	UBERON:0002372	95.10	gold quality
tendon	UBERON:0000043	94.86	gold quality
superficial temporal artery	UBERON:0001614	94.55	gold quality
ventricular zone	UBERON:0003053	94.50	gold quality
buccal mucosa cell	CL:0002336	94.38	gold quality
leukocyte	CL:0000738	94.37	gold quality
spleen	UBERON:0002106	94.31	gold quality
monocyte	CL:0000576	94.26	gold quality
mononuclear cell	CL:0000842	94.26	gold quality
granulocyte	CL:0000094	94.24	gold quality
left ovary	UBERON:0002119	93.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.75	gold quality
right ovary	UBERON:0002118	93.70	gold quality
pituitary gland	UBERON:0000007	93.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.01	gold quality
epithelium of nasopharynx	UBERON:0001951	92.81	gold quality
nasopharynx	UBERON:0001728	92.79	gold quality
trigeminal ganglion	UBERON:0001675	92.74	gold quality
ganglionic eminence	UBERON:0004023	92.73	gold quality
bone marrow	UBERON:0002371	92.60	gold quality
blood	UBERON:0000178	92.52	gold quality
vermiform appendix	UBERON:0001154	92.50	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-76312	yes	175.40
E-HCAD-4	yes	92.05
E-HCAD-1	yes	30.19
E-CURD-122	yes	26.93
E-ANND-3	yes	13.89
E-MTAB-6678	yes	11.40
E-CURD-112	yes	7.74
E-CURD-119	yes	5.26
E-MTAB-9067	yes	4.76
E-GEOD-150728	no	1811.22
E-MTAB-8911	no	459.53
E-MTAB-6142	no	67.23

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

27 targets.

Target	Regulation
APLF	Unknown
BAX	Activation
BCL2	Repression
CDKN1A	Unknown
CFLAR	Activation
COL3A1	Activation
DUSP1	Activation
E2F1	Activation
FAS	Activation
FOXM1	Activation
GADD45A	Activation
IGF1R	Unknown
ITGA8	Activation
KLRK1	Activation
MCL1	Activation
MTF1	Unknown
PBK	Unknown
PCNA	Unknown
PDGFRB	Activation
PMAIP1	Repression
PVR	Activation
SLC2A1	Repression
SP1	Repression
TERF1	Repression
TNFRSF10B	Repression
VEGFA	Repression
ZFHX3	Activation

Upstream regulators (CollecTRI, top): AHR, AP1, AR, BRCA1, BTF3, DMAP1, E2F1, E2F3, FOXO3, GLI3, GRHL3, KMT2A, MEF2D, MYC, NFAT5, NFATC2, NR2C2, RBBP8, RBPJ, RELA, SP1, TFCP2, TP63, TWIST1, TWIST2, ZNF148

miRNA regulators (miRDB)

154 targeting ATM, 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-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• In ataxia telangiectasia-mutated (ATM)-deficient cells the amount of nuclear PP2A heterotrimer relative to heterodimer was not We conclude a novel ATM-dependent mechanism is regulating association of B55 subunits with nuclear PP2A in response to IR (PMID:11723136)
• Missense mutations but not allelic variants alter the function of ATM by dominant interference in patients with breast cancer. (PMID:11805335)
• role in breast cancer (PMID:11830600)
• at least two ATM mutations are associated with a sufficiently high risk of breast cancer to be found in multiple-case breast cancer families; genetic susceptibility for breast cancer (PMID:11830610)
• ATM: from phenotype to functional genomics–and back (PMID:11859564)
• mediates phosphorylation at multiple p53 sites in response to ionizing radiation (PMID:11875057)
• A new type of mutation causes a splicing defect in ATM (PMID:11889466)
• ATM mutations in Finnish breast cancer patients. (PMID:11897822)
• lack of role in cellular response to DNA strand-scission enediyne C-1027 (PMID:11927575)
• risk of developing BC is 3.6-fold higher among ATM heterozygous women (PMID:11992555)
• The data are compatible with certain missense mutations in ATM predisposing to breast cancer. (PMID:11996792)
• Aberrant methylation of the ATM promoter correlates with increased radiosensitivity in a human colorectal tumor cell line. (PMID:12032824)
• 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)
• Roles of DNA-dependent protein kinase and ATM in cell-cycle-dependent radiation sensitivity in human cells. (PMID:12065055)
• dominant negative mutations in breast cancer families (PMID:12072552)
• ATM mutations are rare in familial chronic lymphocytic leukemia. (PMID:12091354)
• ATM mutations contribute to the development of diffuse large B-cell lymphoma (PMID:12149228)
• These findings indicate that ATM activation is not limited to the ionizing radiation-induced response and potentially plays an important role in response to DNA alkylation. (PMID:12151394)
• These observations provide the first link between ATM and LKB1 and suggest that ATM could regulate LKB1 (PMID:12234250)
• Subtle constitutional alterations of ATM may impart an increased risk of developing breast cancer and therefore act as a low penetrance, high prevalence gene in the general population. (PMID:12362033)
• deficiency in the repair of UV-induced DNA damage in human skin fibroblasts compromised for the gene (PMID:12376469)
• Data suggest that a novel AMPK family member, ARK5, is the tumor cell survival factor activated by Akt and acts as an ATM kinase under the conditions of nutrient starvation. (PMID:12409306)
• ATM kinase has a role in orchestrating the coordinated induction and transcriptional cooperation of IRF-1 and p53 to regulate p21 expression. (PMID:12420214)
• ATM kinase is not required for signaling when chromatid decatenation is blocked (PMID:12429935)
• A dominant-negative germline missense ATM mutation (8921C>T; Pro2974Leu), located in the PI-3-kinase domain was found in a childhood ALL patient with MLL rearrangement. Altered ATM function plays some pathogenic role in the development of MLL+ leukemia. (PMID:12511424)
• ATM protein plays a critical role in the signal transduction of cell cycle checkpoint, the repair of damaged DNA and the apoptosis. (PMID:12513844)
• ATM has a critical role in the response of hypoxia and reperfusion in solid tumors. (PMID:12519769)
• ATM does not have a critical role in regulating chromosomal fragile site stability (PMID:12526805)
• our data suggest that ATM may mediate cell response to mitogenic factors by tightly regulating the set point of the CaR and thereby modulating the crosstalk between this metabotropic receptor and growth factor receptors (PMID:12545170)
• Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity (PMID:12556884)
• Review. DNA double-strand breaks activate ATM. ATM modulates many signalling pathways. ATM mutations cause the cancer-prone disorder ataxia-telangiectasia. Understanding ATM’s action clarifies the relation of defective responses to DNA damage & cancer. (PMID:12612651)
• ATM functions upstream of protein kinase c-delta. (PMID:12628935)
• ATM is a major signal initiator for genotoxin-induced apoptosis but, paradoxically, also contributes to maintenance of cell survival by facilitating recovery/escape from terminal growth arrest (PMID:12637545)
• ATM is activated by ATP in a mechanism involving autophosphorylation (PMID:12645530)
• ATM seems dispensable in the somatic hypermutation and Ig heavy chain variable-diversity- joining recombination processes but is clearly involved in the end joining-repair machinery in class switch recombination. (PMID:12646636)
• In conclusion, effective and prompt IR-induced Rad51 focus formation is cell cycle-regulated and requires both ATM and c-Abl. (PMID:12650908)
• targets tousled like kinasese via DNA damage checkpoint (PMID:12660173)
• ataxia telangiectasia mutated (ATM) gene mutation/deletion is Associated with rhabdomyosarcoma (PMID:12673126)
• ATM is the transducer of the S phase checkpoint and presumably propagates the signal through downstream effector kinases. (PMID:12676583)
• BRCA1 facilitates the ability of ATM and ATR to phosphorylate downstream substrates that directly influence cell cycle checkpoint arrest and apoptosis (PMID:12773400)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	atm	ENSDARG00000002385
mus_musculus	Atm	ENSMUSG00000034218
rattus_norvegicus	Atm	ENSRNOG00000029773

Paralogs (5): SMG1 (ENSG00000157106), ATR (ENSG00000175054), TRRAP (ENSG00000196367), MTOR (ENSG00000198793), PRKDC (ENSG00000253729)

Protein

Protein identifiers

Serine-protein kinase ATM — Q13315 (reviewed: Q13315)

Alternative names: Ataxia telangiectasia mutated

All UniProt accessions (15): Q13315, A0A087X0E9, A0A6Q8PH76, A0A804HL86, A0AAA9YI03, A0AAQ5BH05, A0AAQ5BH14, A0AAQ5BH18, A0AAQ5BH23, A0AAQ5BH37, E9PIN0, H0YDU7, H0YEC6, M0QXY8, Q6P7P1

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates ‘Ser-139’ of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FBXW7, FANCD2, NFKBIA, BRCA1, CREBBP/CBP, RBBP8/CTIP, FBXO46, MRE11, nibrin (NBN), RAD50, RAD17, PELI1, TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C. May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response. Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks. Phosphorylates TTC5/STRAP at ‘Ser-203’ in the cytoplasm in response to DNA damage, which promotes TTC5/STRAP nuclear localization. Also involved in pexophagy by mediating phosphorylation of PEX5: translocated to peroxisomes in response to reactive oxygen species (ROS), and catalyzes phosphorylation of PEX5, promoting PEX5 ubiquitination and induction of pexophagy.

Subunit / interactions. Homodimer. Dimers or tetramers in inactive state. On DNA damage, autophosphorylation dissociates ATM into monomers rendering them catalytically active. Binds p53/TP53, ABL1, BRCA1 and TERF1. Interacts with NBN (via FxF/Y motif). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBN protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with RAD17; DNA damage promotes the association. Interacts with EEF1E1; the interaction, induced on DNA damage, up-regulates TP53. Interacts with KAT8, NABP2, ATMIN and CEP164. Interacts with AP2B1 and AP3B2; the interaction occurs in cytoplasmic vesicles. Interacts with TELO2 and TTI1. Interacts with DDX1. Interacts with BRAT1. Interacts with CYREN (via XLF motif). Interacts (via microbody targeting signal) with PEX5; promoting translocation to peroxisomes in response to reactive oxygen species (ROS).

Subcellular location. Nucleus. Cytoplasmic vesicle. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Peroxisome matrix.

Tissue specificity. Found in pancreas, kidney, skeletal muscle, liver, lung, placenta, brain, heart, spleen, thymus, testis, ovary, small intestine, colon and leukocytes.

Post-translational modifications. Phosphorylated by NUAK1/ARK5. Autophosphorylation on Ser-367, Ser-1893, Ser-1981 correlates with DNA damage-mediated activation of the kinase. During the late stages of DNA damage response, dephosphorylated following deacetylation by SIRT7, leading to ATM deactivation. Acetylation, on DNA damage, is required for activation of the kinase activity, dimer-monomer transition, and subsequent autophosphorylation on Ser-1981. Acetylated in vitro by KAT5/TIP60. Deacetylated by SIRT7 during the late stages of DNA damage response, promoting ATM dephosphorylation and subsequent deactivation.

Disease relevance. Ataxia telangiectasia (AT) [MIM:208900] A rare recessive disorder characterized by progressive cerebellar ataxia, dilation of the blood vessels in the conjunctiva and eyeballs, immunodeficiency, growth retardation and sexual immaturity. Patients have a strong predisposition to cancer; about 30% of patients develop tumors, particularly lymphomas and leukemias. Cells from affected individuals are highly sensitive to damage by ionizing radiation and resistant to inhibition of DNA synthesis following irradiation. The disease is caused by variants affecting the gene represented in this entry. Defects in ATM may contribute to T-cell acute lymphoblastic leukemia (TALL) and T-prolymphocytic leukemia (TPLL). TPLL is characterized by a high white blood cell count, with a predominance of prolymphocytes, marked splenomegaly, lymphadenopathy, skin lesions and serous effusion. The clinical course is highly aggressive, with poor response to chemotherapy and short survival time. TPLL occurs both in adults as a sporadic disease and in younger AT patients. Defects in ATM may contribute to B-cell non-Hodgkin lymphomas (BNHL), including mantle cell lymphoma (MCL). Defects in ATM may contribute to B-cell chronic lymphocytic leukemia (BCLL). BCLL is the commonest form of leukemia in the elderly. It is characterized by the accumulation of mature CD5+ B-lymphocytes, lymphadenopathy, immunodeficiency and bone marrow failure.

Activity regulation. Activated by the MRN (MRE11-RAD50-NBS1) complex in response to DNA double strand breaks (DSBs), which recruits ATM to DSBs and promotes its activation. Inhibited by wortmannin.

Domain organisation. The FATC domain is required for interaction with KAT5.

Induction. By ionizing radiation.

Similarity. Belongs to the PI3/PI4-kinase family. ATM subfamily.

RefSeq proteins (4): NP_000042, NP_001338763, NP_001338764, NP_001338765 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000403	PI3/4_kinase_cat_dom	Domain
IPR003151	PIK-rel_kinase_FAT	Domain
IPR003152	FATC_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR014009	PIK_FAT	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR018936	PI3/4_kinase_CS	Conserved_site
IPR021668	TAN	Domain
IPR036940	PI3/4_kinase_cat_sf	Homologous_superfamily
IPR038980	ATM_plant	Family
IPR044107	PIKKc_ATM	Domain

Pfam: PF00454, PF02259, PF02260, PF11640

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (469 total): sequence variant 188, helix 163, strand 42, turn 27, mutagenesis site 21, sequence conflict 11, modified residue 7, region of interest 4, domain 3, initiator methionine 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
8OXQ	ELECTRON MICROSCOPY	2.5
7SIC	ELECTRON MICROSCOPY	2.51
7SID	ELECTRON MICROSCOPY	2.53
8OXP	ELECTRON MICROSCOPY	2.6
7NI5	ELECTRON MICROSCOPY	2.78
7NI6	ELECTRON MICROSCOPY	2.8
7NI4	ELECTRON MICROSCOPY	3
8OXO	ELECTRON MICROSCOPY	3
8OXM	ELECTRON MICROSCOPY	3.3
6K9L	ELECTRON MICROSCOPY	4.27
5NP0	ELECTRON MICROSCOPY	5.7
5NP1	ELECTRON MICROSCOPY	5.7
6K9K	ELECTRON MICROSCOPY	7.82
6HKA	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for Q13315 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Post-translational modifications (7): 2, 367, 1893, 1981, 1983, 2996, 3016

Mutagenesis-validated functional residues (21):

Position	Phenotype
367	loss of ir-induced s-367 autophosphorylation. reduced correction of cell cycle checkpoint defects and dna-repair activit
1807	decreased phosphorylation of target proteins.
1893	loss of ir-induced s-1893 autophosphorylation. reduced correction of cell cycle checkpoint defects and dna-repair activi
1941	decreased phosphorylation of target proteins.
1981	loss of ir-induced s-1981 autophosphorylation. reduced correction of cell cycle checkpoint defects and dna-repair activi
1981	disrupts the dimer.
2019	loss of phosphorylation of target proteins.
2039	decreased phosphorylation of target proteins.
2338	loss of phosphorylation of target proteins.
2394	loss of phosphorylation of target proteins.
2452	loss of phosphorylation of target proteins.
2685	no effect on phosphorylation of target proteins.
2699	loss of phosphorylation of target proteins.
2708	decreased phosphorylation of target proteins.
2730	loss of phosphorylation of target proteins.
2870	loss of kinase activity.
2875	loss of kinase activity.
3016	mimics acetylation, preventing dephosphorylation and subsequent atm deactivation during the late stage of dna damage res
3016	loss of dna damage-inducible acetylation. retains constitutive kinase activity, but blocks dna damage-induced kinase act
3018	retains dna damage-inducible acetylation and s-1981 autophosphorylation.
3047	abolished interaction with pex5 and translocation to peroxisomes in response to reactive oxygen species (ros).

Function

Pathways and Gene Ontology

Reactome pathways

61 pathways

ID	Pathway
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-349425	Autodegradation of the E3 ubiquitin ligase COP1
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5693548	Sensing of DNA Double Strand Breaks
R-HSA-5693554	Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)
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-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-6803204	TP53 Regulates Transcription of Genes Involved in Cytochrome C Release
R-HSA-6803207	TP53 Regulates Transcription of Caspase Activators and Caspases
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-6804757	Regulation of TP53 Degradation
R-HSA-6804760	Regulation of TP53 Activity through Methylation
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-69541	Stabilization of p53
R-HSA-912446	Meiotic recombination
R-HSA-9664873	Pexophagy
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

MSigDB gene sets: 920 (showing top): PID_FANCONI_PATHWAY, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_MEIOTIC_RECOMBINATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_EPITHELIUM_DEVELOPMENT, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_DNA_DAMAGE_RESPONSE_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR

GO Biological Process (93): DNA damage checkpoint signaling (GO:0000077), pexophagy (GO:0000425), telomere maintenance (GO:0000723), double-strand break repair via homologous recombination (GO:0000724), DNA double-strand break processing (GO:0000729), ovarian follicle development (GO:0001541), somitogenesis (GO:0001756), pre-B cell allelic exclusion (GO:0002331), double-strand break repair (GO:0006302), double-strand break repair via nonhomologous end joining (GO:0006303), protein phosphorylation (GO:0006468), DNA damage response (GO:0006974), mitotic spindle assembly checkpoint signaling (GO:0007094), mitotic G2 DNA damage checkpoint signaling (GO:0007095), reciprocal meiotic recombination (GO:0007131), male meiotic nuclear division (GO:0007140), female meiotic nuclear division (GO:0007143), signal transduction (GO:0007165), brain development (GO:0007420), heart development (GO:0007507), determination of adult lifespan (GO:0008340), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), post-embryonic development (GO:0009791), response to ionizing radiation (GO:0010212), regulation of autophagy (GO:0010506), positive regulation of gene expression (GO:0010628), DNA damage response, signal transduction by p53 class mediator (GO:0030330), positive regulation of cell migration (GO:0030335), negative regulation of B cell proliferation (GO:0030889), regulation of telomere maintenance via telomerase (GO:0032210), positive regulation of telomere maintenance via telomerase (GO:0032212), V(D)J recombination (GO:0033151), cellular response to stress (GO:0033554), cellular response to reactive oxygen species (GO:0034614), multicellular organism growth (GO:0035264), peptidyl-serine autophosphorylation (GO:0036289), lipoprotein catabolic process (GO:0042159), signal transduction in response to DNA damage (GO:0042770), regulation of apoptotic process (GO:0042981), positive regulation of apoptotic process (GO:0043065)

GO Molecular Function (14): DNA binding (GO:0003677), protein serine/threonine kinase activity (GO:0004674), DNA-dependent protein kinase activity (GO:0004677), ATP binding (GO:0005524), 1-phosphatidylinositol-3-kinase activity (GO:0016303), histone H2AXS139 kinase activity (GO:0035979), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (16): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), cytoplasm (GO:0005737), peroxisomal matrix (GO:0005782), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), site of double-strand break (GO:0035861), extrinsic component of synaptic vesicle membrane (GO:0098850), DNA repair complex (GO:1990391), chromosome, telomeric region (GO:0000781), peroxisome (GO:0005777), cytoskeleton (GO:0005856), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	3
DNA Double Strand Break Response	2
Resolution of D-Loop Structures	2
TP53 Regulates Transcription of Cell Death Genes	2
Regulation of TP53 Activity	2
Cellular Senescence	1
Cellular response to heat stress	1
Stabilization of p53	1
DNA Double-Strand Break Repair	1
HDR through Homologous Recombination (HRR)	1
Homologous DNA Pairing and Strand Exchange	1
Transcriptional Regulation by TP53	1
Regulation of TP53 Expression and Degradation	1
G2/M Checkpoints	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	4
double-strand break repair	3
cellular anatomical structure	3
DNA metabolic process	2
meiotic cell cycle	2
meiotic nuclear division	2
animal organ development	2
protein kinase activity	2
protein serine/threonine kinase activity	2
binding	2
nuclear lumen	2
cytoplasm	2
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
macroautophagy	1
autophagy of peroxisome	1
telomere organization	1
recombinational repair	1
5’-3’ DNA exonuclease activity	1
female gonad development	1
anatomical structure development	1
anterior/posterior pattern specification	1
segmentation	1
chordate embryonic development	1
anatomical structure formation involved in morphogenesis	1
somite development	1
pre-B cell differentiation	1
regulation of gene expression	1
DNA repair	1
phosphorylation	1
protein modification process	1
cellular response to stress	1
mitotic cell cycle	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
meiosis I	1

Protein interactions and networks

STRING

6446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATM	CHEK2	O96017	999
ATM	BRCA1	P38398	999
ATM	MDC1	Q14676	997
ATM	TP53BP1	Q12888	996
ATM	MSH2	P43246	995
ATM	ATRIP	Q8WXE1	995
ATM	MSH6	P52701	994
ATM	MLH1	P40692	992
ATM	H2AX	P16104	984
ATM	TP53	P04637	975
ATM	CHEK1	O14757	975
ATM	BRCA2	P51587	972
ATM	FANCD2	Q9BXW9	968
ATM	XRCC5	P13010	964
ATM	ATMIN	O43313	961

IntAct

264 interactions, top by confidence:

A	B	Type	Score
MDC1	NBN	psi-mi:“MI:0914”(association)	0.970
SNX6	SNX2	psi-mi:“MI:0914”(association)	0.800
TELO2	TTI1	psi-mi:“MI:0914”(association)	0.760
ABL1	ATM	psi-mi:“MI:0915”(physical association)	0.700
ATM	ABL1	psi-mi:“MI:0915”(physical association)	0.700
ABL1	ATM	psi-mi:“MI:0407”(direct interaction)	0.700
ATM	ABL1	psi-mi:“MI:0407”(direct interaction)	0.700
TTI2	TTI1	psi-mi:“MI:0914”(association)	0.690
ATM	TELO2	psi-mi:“MI:0407”(direct interaction)	0.680
NOTCH1	ATM	psi-mi:“MI:0915”(physical association)	0.660
NOTCH1	ATM	psi-mi:“MI:0407”(direct interaction)	0.660
ATM	TERF1	psi-mi:“MI:0915”(physical association)	0.650
TERF1	ATM	psi-mi:“MI:0407”(direct interaction)	0.650
ATM	TERF1	psi-mi:“MI:0414”(enzymatic reaction)	0.650
TERF1	ATM	psi-mi:“MI:0414”(enzymatic reaction)	0.650
ATM	AKT1	psi-mi:“MI:0915”(physical association)	0.640
ATM	TERF1	psi-mi:“MI:0915”(physical association)	0.610
ATM	TERF1	psi-mi:“MI:0407”(direct interaction)	0.610
TTI1	ATM	psi-mi:“MI:0915”(physical association)	0.610
ATM	TTI1	psi-mi:“MI:0915”(physical association)	0.610
TTI1	ATM	psi-mi:“MI:0914”(association)	0.610

BioGRID (673): HIF1A (Biochemical Activity), ATM (Affinity Capture-Western), ABL1 (Biochemical Activity), POLR2A (Biochemical Activity), ATM (Affinity Capture-Western), CREB1 (Biochemical Activity), ATM (Affinity Capture-Western), ZEB1 (Biochemical Activity), TP53 (Biochemical Activity), ATM (Affinity Capture-Western), TTI1 (Affinity Capture-Western), ATM (Affinity Capture-MS), ATM (Affinity Capture-MS), ATM (Affinity Capture-MS), ATM (Affinity Capture-MS)

ESM2 similar proteins: A0JM49, A2AKG8, B0V0U5, B1AUR6, C5J7W8, E1BGH8, E1C231, E1C2Z0, E7FGT5, E7FH61, E9Q3L2, F6S215, O08662, O60287, O94822, P42356, P57678, P78527, P97313, Q13315, Q13535, Q14146, Q1RLU1, Q2TAW0, Q3TQQ9, Q3URQ0, Q571H0, Q5RDK1, Q5VW36, Q5WNI9, Q5XI94, Q5ZM41, Q62388, Q6A009, Q6DFV1, Q6PQD5, Q6ZRQ5, Q7SY48, Q86XI2, Q8BKX6

Diamond homologs: A2YH41, C5J7W8, O01510, O74630, P38110, P38111, P54676, Q02099, Q13315, Q13535, Q2U639, Q4IB89, Q4WVM7, Q54ER4, Q59LR2, Q5ABX0, Q5BHE2, Q5EAK6, Q5Z987, Q61CW2, Q62388, Q6BV76, Q6CAD2, Q6CP76, Q6FRZ9, Q6FX42, Q6P435, Q6PQD5, Q751J3, Q75DB8, Q7RZT9, Q86C65, Q8BKX6, Q8SQY7, Q96Q15, Q9DE14, Q9FKS4, Q9JKK8, Q9M3G7, Q9TXI7

SIGNOR signaling

200 interactions.

A	Effect	B	Mechanism
ATM	unknown	TP53BP1	phosphorylation
ATM	“up-regulates activity”	RAD9A	phosphorylation
ATM	“down-regulates activity”	MDM2	phosphorylation
ATM	“up-regulates activity”	TERF1	phosphorylation
ATM	“up-regulates quantity by stabilization”	TP53	phosphorylation
ATM	up-regulates	SMC1A	phosphorylation
ATM	up-regulates	RPA2	phosphorylation
ATM	unknown	RPA2	phosphorylation
ATM	“down-regulates activity”	CREB1	phosphorylation
ATM	down-regulates	CREB1	phosphorylation
ATM	up-regulates	NFAT5	phosphorylation
ATM	unknown	MCM3	phosphorylation
2-(4-morpholinyl)-6-(1-thianthrenyl)-4-pyranone	down-regulates	ATM	“chemical inhibition”
NBN	up-regulates	ATM	binding
ATM	up-regulates	ATF2	phosphorylation
ATM	down-regulates	MDM4	phosphorylation
ATM	“down-regulates activity”	IKBKG	phosphorylation
ATM	up-regulates	DCLRE1C	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 184 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
DNA Double Strand Break Response	5	19.5×	7e-04
Meiosis	6	14.0×	6e-04
Homology Directed Repair	5	12.7×	3e-03
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	5	12.7×	3e-03
DNA Double-Strand Break Repair	5	10.2×	6e-03
G2/M Checkpoints	9	9.9×	1e-04
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	8	9.6×	4e-04
Reproduction	6	9.4×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
response to ionizing radiation	6	15.1×	8e-04
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	7	14.5×	2e-04
positive regulation of DNA repair	6	13.2×	1e-03
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	7	9.4×	2e-03
positive regulation of cytosolic calcium ion concentration	11	7.9×	2e-04
DNA damage response	15	4.9×	2e-04
cell surface receptor signaling pathway	11	4.3×	8e-03
G protein-coupled receptor signaling pathway	18	4.0×	2e-04

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

Ataxia-telangiectasia (A-T) is a recessive disorder resulting from germline mutation of the A-T mutated (ATM) gene on chromosome 11q. Upon sensing double-stranded breaks (DSB), the wild-type kinase encoded by ATM initiates the DNA-damage response by phosphorylating histone H2AX and, subsequently, various other proteins, such as BRCA1 and the MRE11–RAD50–NBS1 (MRN) complex, which are recruited to the damaged site. Additionally, ATM phosphorylates p53, resulting in expression of the cyclin-dependent kinase inhibitor p21 and leading to senescence or apoptosis. Somatic variants can result in inhibition or loss of these functions and can cause resistance to therapies that rely on inducing apoptosis via DSBs. Germline variants in A-T patients result in a predisposition to cancer, most frequently hematologic or breast. PARP inhibition has been studied for its potential in treating ATM mutated breast cancer patients.

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 24 cancer types — BLCA, BRCA, CCRCC, CHOL, CLLSLL, COAD, COADREAD, ESCA, HCC, LUAD, LUSC, MEL…(+12 more).

Clinical variants and AI predictions

ClinVar

18501 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2543
Likely pathogenic	659
Uncertain significance	6100
Likely benign	3462
Benign	410

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027442	NM_000051.4(ATM):c.2152dup (p.Cys718fs)	Pathogenic
1049940	NM_000051.4(ATM):c.3403-1_3577-680del	Pathogenic
1050010	NM_000051.4(ATM):c.4674_4695del (p.Ile1559fs)	Pathogenic
1062106	NM_000051.4(ATM):c.5217_5231del (p.Asn1739_Thr1743del)	Pathogenic
1067957	NM_000051.4(ATM):c.1802+1G>T	Pathogenic
1068261	NM_000051.4(ATM):c.7788+1G>A	Pathogenic
1068534	NM_000051.4(ATM):c.6242T>A (p.Leu2081Ter)	Pathogenic
1068555	NM_000051.4(ATM):c.3216del (p.Val1073fs)	Pathogenic
1068579	NM_000051.4(ATM):c.8785A>T (p.Arg2929Ter)	Pathogenic
1068697	NM_000051.4(ATM):c.1276del (p.Ser426fs)	Pathogenic
1068740	NM_000051.4(ATM):c.935_936insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTNNNATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCCTTT (p.Leu312fs)	Pathogenic
1068798	NM_000051.4(ATM):c.6080T>G (p.Leu2027Ter)	Pathogenic
1068838	NM_000051.4(ATM):c.6295del (p.His2099fs)	Pathogenic
1069119	NM_000051.4(ATM):c.3105_3106del (p.Phe1036fs)	Pathogenic
1069197	NM_000051.4(ATM):c.1179G>A (p.Trp393Ter)	Pathogenic
1069441	NM_000051.4(ATM):c.1262C>G (p.Ser421Ter)	Pathogenic
1069467	NM_000051.4(ATM):c.3076del (p.Trp1026fs)	Pathogenic
1069556	NC_000011.9:g.(?108178614)(108178721_?)del	Pathogenic
1069557	NC_000011.9:g.(?108190675)(108190791_?)del	Pathogenic
1069558	NC_000011.9:g.(?108196027)(108196281_?)del	Pathogenic
1069559	NC_000011.9:g.(?108204603)(108204705_?)del	Pathogenic
1069594	NM_000051.4(ATM):c.6616C>T (p.Gln2206Ter)	Pathogenic
1069643	NM_000051.4(ATM):c.1966del (p.Thr656fs)	Pathogenic
1069650	NM_000051.4(ATM):c.3145_3146del (p.Leu1049fs)	Pathogenic
1069663	NM_000051.4(ATM):c.5737_5743del (p.Val1913fs)	Pathogenic
1069668	NC_000011.9:g.(?108151710)(108160538_?)del	Pathogenic
1069669	NC_000011.9:g.(?108153427)(108160538_?)del	Pathogenic
1069814	NM_000051.4(ATM):c.2626C>T (p.Gln876Ter)	Pathogenic
1069824	NM_000051.4(ATM):c.4668T>A (p.Tyr1556Ter)	Pathogenic
1069826	NC_000011.9:g.(?108213939)(108218102_?)del	Pathogenic

SpliceAI

11573 predictions. Top by Δscore:

Variant	Effect	Δscore
11:108224054:G:GT	donor_gain	1.0000
11:108224054:G:T	donor_gain	1.0000
11:108224058:T:G	donor_gain	1.0000
11:108227768:A:AG	acceptor_gain	1.0000
11:108227769:T:G	acceptor_gain	1.0000
11:108227772:TCA:T	acceptor_loss	1.0000
11:108227773:CAG:C	acceptor_loss	1.0000
11:108227774:A:AG	acceptor_gain	1.0000
11:108227775:G:GG	acceptor_gain	1.0000
11:108227775:GA:G	acceptor_gain	1.0000
11:108227775:GAA:G	acceptor_gain	1.0000
11:108227775:GAAA:G	acceptor_gain	1.0000
11:108227858:G:GT	donor_gain	1.0000
11:108227859:A:T	donor_gain	1.0000
11:108227875:G:GT	donor_gain	1.0000
11:108227875:G:T	donor_gain	1.0000
11:108227881:GTTTT:G	donor_gain	1.0000
11:108227882:TTTTT:T	donor_gain	1.0000
11:108227885:TTAG:T	donor_loss	1.0000
11:108227886:TAGGT:T	donor_loss	1.0000
11:108227889:GTATT:G	donor_loss	1.0000
11:108227890:T:A	donor_loss	1.0000
11:108229319:CAGAA:C	donor_gain	1.0000
11:108229321:GAA:G	donor_gain	1.0000
11:108229324:G:GG	donor_gain	1.0000
11:108243950:A:AG	acceptor_gain	1.0000
11:108243951:A:AG	acceptor_gain	1.0000
11:108243952:G:GG	acceptor_gain	1.0000
11:108243952:GAATT:G	acceptor_gain	1.0000
11:108247128:GTACA:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000005768 (11:108222901 C>G,T), RS1000007177 (11:108309111 G>A), RS1000032847 (11:108316037 T>A,C), RS1000035874 (11:108227072 T>A,C), RS1000040365 (11:108285420 C>A,T), RS1000049119 (11:108263449 C>G,T), RS1000055863 (11:108240493 A>G), RS1000098120 (11:108360262 T>C), RS1000129752 (11:108339269 G>A), RS1000143433 (11:108292445 A>G), RS1000166148 (11:108268200 T>C), RS1000188035 (11:108310000 A>G), RS1000220936 (11:108313457 C>A), RS1000228433 (11:108344001 A>C,G), RS1000231270 (11:108274739 A>G)

Disease associations

OMIM: gene MIM:607585 | disease phenotypes: MIM:208900, MIM:114480, MIM:613659, MIM:263300, MIM:114500, MIM:167000, MIM:612555, MIM:604370, MIM:260350, MIM:109800, MIM:314400, MIM:176807, MIM:120435, MIM:610443, MIM:608812, MIM:131100, MIM:614327, MIM:300755, MIM:607893, MIM:211980, MIM:254500

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary breast carcinoma	Definitive	Autosomal dominant
ataxia telangiectasia	Definitive	Autosomal recessive
ATM-related cancer predisposition	Definitive	Autosomal dominant
prostate cancer	Moderate	Autosomal dominant
sarcoma	Moderate	Autosomal dominant
gastric carcinoma	Limited	Autosomal dominant
hereditary nonpolyposis colon cancer	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
ataxia telangiectasia	Definitive	AR
ATM-related cancer predisposition	Definitive	AD

Mondo (64): ataxia telangiectasia (MONDO:0008840), hereditary neoplastic syndrome (MONDO:0015356), hereditary breast carcinoma (MONDO:0016419), ATM-related cancer predisposition (MONDO:0700270), breast cancer (MONDO:0007254), familial ovarian cancer (MONDO:0016248), gastric cancer (MONDO:0001056), familial colorectal cancer type X (MONDO:0018604), endometrial serous adenocarcinoma (MONDO:0006196), acquired polycythemia vera (MONDO:0009891), ovarian neoplasm (MONDO:0021068), colorectal cancer (MONDO:0005575), hereditary breast ovarian cancer syndrome (MONDO:0003582), breast carcinoma (MONDO:0004989), malignant colon neoplasm (MONDO:0021063)

Orphanet (32): Ataxia-telangiectasia (Orphanet:100), Inherited cancer-predisposing syndrome (Orphanet:140162), Hereditary breast cancer (Orphanet:227535), Familial colorectal cancer Type X (Orphanet:440437), Polycythemia vera (Orphanet:729), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Rare ovarian cancer (Orphanet:213500), Familial pancreatic carcinoma (Orphanet:1333), Hepatoblastoma (Orphanet:449), OBSOLETE: Congenital valvular dysplasia (Orphanet:1864), FLNA-related X-linked myxomatous valvular dysplasia (Orphanet:555877), X-linked Ehlers-Danlos syndrome (Orphanet:75497), Familial prostate cancer (Orphanet:1331), Rare carcinoma of pancreas (Orphanet:217074), Lynch syndrome (Orphanet:144)

HPO phenotypes

138 total (30 of 138 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000035	Abnormal testis morphology
HP:0000134	Female hypogonadism
HP:0000147	Polycystic ovaries
HP:0000246	Sinusitis
HP:0000252	Microcephaly
HP:0000486	Strabismus
HP:0000496	Abnormality of eye movement
HP:0000505	Visual impairment
HP:0000524	Conjunctival telangiectasia
HP:0000639	Nystagmus
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000778	Hypoplasia of the thymus
HP:0000819	Diabetes mellitus
HP:0000823	Delayed puberty
HP:0000957	Cafe-au-lait spot
HP:0001123	Visual field defect
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001266	Choreoathetosis
HP:0001276	Hypertonia

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST000927_1	Response to metformin in type 2 diabetes (glycemic)	3.000000e-09
GCST001267_4	Melanoma	3.000000e-09
GCST002318_137	Rheumatoid arthritis	1.000000e-08
GCST002318_43	Rheumatoid arthritis	1.000000e-08
GCST002990_4	Gastric adenocarcinoma (histologically verified)	2.000000e-07
GCST002990_5	Gastric adenocarcinoma (histologically verified)	1.000000e-06
GCST002992_5	Gastric cancer	6.000000e-07
GCST002992_6	Gastric cancer	3.000000e-06
GCST004142_8	Melanoma	3.000000e-09
GCST004600_100	Eosinophil percentage of white cells	6.000000e-09
GCST004606_207	Eosinophil count	3.000000e-13
GCST004624_192	Sum eosinophil basophil counts	6.000000e-14
GCST004710_7	Renal cell carcinoma	9.000000e-09
GCST005549_16	Alzheimer’s disease (late onset)	6.000000e-07
GCST005996_35	Red blood cell count	1.000000e-11
GCST006085_51	Prostate cancer	8.000000e-09
GCST006462_37	Uterine fibroids	3.000000e-12
GCST006462_51	Uterine fibroids	3.000000e-11
GCST006462_52	Uterine fibroids	7.000000e-08
GCST006959_76	Rheumatoid arthritis	4.000000e-07
GCST007250_11	Nonunion in individuals with fractures	3.000000e-07
GCST007505_27	Nevus count or cutaneous melanoma	8.000000e-11
GCST008366_17	Leukocyte telomere length	7.000000e-12
GCST008366_9	Leukocyte telomere length	2.000000e-10
GCST009856_8	Leukocyte telomere length	1.000000e-08
GCST010002_248	Refractive error	4.000000e-19
GCST010303_13	Nevus count or cutaneous melanoma	4.000000e-21
GCST010304_40	Cutaneous malignant melanoma	2.000000e-21
GCST90000032_12	Myeloproliferative neoplasms	2.000000e-10
GCST90002381_520	Eosinophil count	3.000000e-29

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:1001870	late-onset Alzheimers disease
EFO:0004305	erythrocyte count
EFO:0009707	fractures, ununited
EFO:0004632	nevus count
EFO:0004251	myeloproliferative disorder
EFO:0004587	lymphocyte count
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (27)

Descriptor	Name	Tree numbers
D000230	Adenocarcinoma	C04.557.470.200.025
D001260	Ataxia Telangiectasia	C10.228.140.252.190.530.060; C10.562.100; C10.597.350.090.500.530.060; C14.907.823.213; C16.320.080; C16.320.798.250; C18.452.284.060; C20.673.795.250
D001932	Brain Neoplasms	C04.588.614.250.195; C10.228.140.211; C10.551.240.250
D001943	Breast Neoplasms	C04.588.180; C17.800.090.500
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D003110	Colonic Neoplasms	C04.588.274.476.411.307.180; C06.301.371.411.307.180; C06.405.249.411.307.180; C06.405.469.158.356.180; C06.405.469.491.307.180
D005909	Glioblastoma	C04.557.465.625.600.380.080.335; C04.557.470.670.380.080.335; C04.557.580.625.600.380.080.335
D018197	Hepatoblastoma	C04.557.435.380
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
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D015461	Leukemia, Prolymphocytic, T-Cell	C04.557.337.428.565.750; C04.557.337.428.580.075; C15.378.508.428.565.750; C15.378.508.428.580.075; C15.604.515.560.550.750; C15.604.515.560.575.125; C20.683.515.528.565.750; C20.683.515.528.582.125
D020522	Lymphoma, Mantle-Cell	C04.557.386.480.525; C15.604.515.569.480.525; C20.683.515.761.480.525
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D018761	Multiple Endocrine Neoplasia Type 1	C04.588.322.400.500; C04.651.600.500; C04.700.630.500; C16.320.700.630.500; C19.344.400.500
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650
D009369	Neoplasms	C04
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
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
D011087	Polycythemia Vera	C04.588.448.200.500; C15.378.190.250.500; C15.378.190.636.753; C15.378.400.200.500
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D012509	Sarcoma	C04.557.450.795
D064726	Triple Negative Breast Neoplasms	C04.588.180.788; C17.800.090.500.788
C562840	Breast Cancer, Familial (supp.)
C535576	Cardiac valvular dysplasia, X-linked (supp.)
C537261	Lynch syndrome I (site-specific colonic cancer) (supp.)
C535837	Pancreatic carcinoma, familial (supp.)
C537243	Prostate cancer, familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3797 (SINGLE PROTEIN), CHEMBL3885635 (PROTEIN FAMILY), CHEMBL6066129 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

35 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 447,424 (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
CHEMBL1083993	AMIODARONE HYDROCHLORIDE	4	3,265
CHEMBL1103	FURAZOLIDONE	4	14,492
CHEMBL1200430	ESTRADIOL ACETATE	4	1,114
CHEMBL1200493	NAFTIFINE HYDROCHLORIDE	4	1,499
CHEMBL1200938	METHYSERGIDE MALEATE	4	4
CHEMBL1200964	AMITRIPTYLINE HYDROCHLORIDE	4	9,345
CHEMBL1256400	XYLOMETAZOLINE HYDROCHLORIDE	4	2,662
CHEMBL1409	FLUVOXAMINE MALEATE	4	3,999
CHEMBL1511	ESTRADIOL VALERATE	4	7,315
CHEMBL1525	PERMETHRIN	4	47,289
CHEMBL1670	MITOTANE	4	83,856
CHEMBL1717	TICLOPIDINE HYDROCHLORIDE	4	12,872
CHEMBL249856	ENOXIMONE	4	5,206
CHEMBL405110	METHYLENE BLUE ANHYDROUS	4	113,934
CHEMBL421701	DITHIAZANINE IODIDE	4	3,372
CHEMBL456	ETHACRYNIC ACID	4	20,004
CHEMBL498847	SECNIDAZOLE	4	1,851
CHEMBL590	MENADIONE	4	21,034
CHEMBL672	FENOFIBRATE	4	42,568
CHEMBL932	DIPYRIDAMOLE	4	51,743
CHEMBL1879463	DACTOLISIB	3
CHEMBL11417	STREPTONIGRIN	2
CHEMBL1256686	CALCIMYCIN	2
CHEMBL1327821	ENPIROLINE	2
CHEMBL1407356	OXACEPROL	2
CHEMBL1790006	TOLONIUM CHLORIDE	2
CHEMBL282575	ESTRADIOL BENZOATE	2
CHEMBL3989870	BERZOSERTIB	2
CHEMBL5314413	LARTESERTIB	2
CHEMBL599870	ALTHIAZIDE	2

Clinical evidence (CIViC)

Drug × variant × indication: 29 predictive associations from 32 curated evidence items; also 4 prognostic, 1 oncogenic.

Variant	Therapy	Indication	Effect	Level	CIViC
ATM Mutation	Olaparib	Castration-resistant Prostate Carcinoma	Sensitivity/Response	CIViC A	EID8505
ATM Mutation	Olaparib	Prostate Cancer	Sensitivity/Response	CIViC B	EID7458 +2
ATM Underexpression	Paclitaxel + Olaparib	Stomach Cancer	Sensitivity/Response	CIViC B	EID5215 +1
ATM Mutation	Enzalutamide + Talazoparib	Castration-resistant Prostate Carcinoma	Sensitivity/Response	CIViC B	EID11736
ATM N2875H	Olaparib	Prostate Cancer	Sensitivity/Response	CIViC C	EID648
ATM S2289*	Olaparib	Prostate Cancer	Sensitivity/Response	CIViC C	EID647
ATM Mutation	Camptothecin	Lymphoma	Sensitivity/Response	CIViC D	EID12758
ATM Mutation	Olaparib	Mantle Cell Lymphoma	Sensitivity/Response	CIViC D	EID1907
ATM Mutation	Temozolomide	Glioblastoma	Sensitivity/Response	CIViC D	EID452
ATM Mutation	Temozolomide	Melanoma	Sensitivity/Response	CIViC D	EID453
ATM Mutation	Olaparib	Hematologic Cancer	Sensitivity/Response	CIViC D	EID455
ATM Underexpression	NU7441 + KU-0060648	Cancer	Sensitivity/Response	CIViC D	EID454
ATM Underexpression	Olaparib	Gastric Adenocarcinoma	Sensitivity/Response	CIViC D	EID878
ATM A2062V	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2846
ATM C2488Y	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2849
ATM D1682H	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2845
ATM D1930V	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2837
ATM E2187*	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2839
ATM F1025L	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2835
ATM F2732V	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2841
ATM K293*	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2832
ATM K468FS	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2843
ATM L2427P	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2840
ATM Mutation	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2222
ATM R3008C	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2223
ATM T2666A	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2221
ATM c.7089+1del	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2830
ATM c.7515+1_2del	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2831
ATM c.902-1G>T	Doxorubicin	Chronic Lymphocytic Leukemia	Resistance	CIViC D	EID2224

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11212617	Efficacy	4	metformin	Diabetes Mellitus;Type 2
rs1801516	Toxicity	3	cyclophosphamide;doxorubicin;fluorouracil	Breast Neoplasms

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11212617	ATM, C11orf65	4	-2.00	1	metformin
rs1801516	ATM	3	5.50	1	cyclophosphamide;doxorubicin;fluorouracil
rs620815	ATM		0.00	0
rs11212570	ATM		0.00	0
rs1800058	ATM		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Other PIKK family kinases

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
AZD1390	Inhibition	10.11	pIC50
lartesertib	Inhibition	9.7	pIC50
AZD0156	Inhibition	9.24	pIC50
A011	Inhibition	9.0	pIC50
XRD-0394	Inhibition	8.61	pIC50
KU-60019	Inhibition	8.2	pIC50
KU-55933	Inhibition	7.89	pIC50
berzosertib	Inhibition	7.47	pKi
BAY-8400	Inhibition	4.71	pIC50

Binding affinities (BindingDB)

92 measured of 157 human assays (157 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
9-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	0.07 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-[6-[3-(dimethylamino)propoxy]-3-pyridinyl]-7-fluoro-1-[(1R,3R)-3-methoxycyclopentyl]-3-methylimidazo[4,5-c]quinolin-2-one	IC50	0.507 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
1-(3-methoxycyclobutyl)-8-[6-(3-pyrrolidin-1-ylpropoxy)-3-pyridinyl]-3H-imidazo[4,5-c]quinolin-2-one	IC50	0.589 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
9-(4-hydroxybicyclo[2.2.2]octan-1-yl)-7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	0.71 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-[6-[3-(dimethylamino)propoxy]-3-pyridinyl]-1-(3-methoxycyclobutyl)-3H-imidazo[4,5-c]quinolin-2-one	IC50	1.03 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
9-(3-fluorobicyclo[1.1.1]pentan-1-yl)-7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(3-fluorobicyclo[1.1.1]pentan-1-yl)-7-methyl-2-((7-methylquinoxalin-6-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
3-(7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-8-oxo-7,8-dihydro-9H-purin-9-yl) bicyclo[1.1.1]pentane-1-carbonitrile	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-9-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-9-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(3-(methoxymethyl)bicyclo[1.1.1]pentan-1-yl)-7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(3-(methoxymethyl)bicyclo[1.1.1]pentan-1-yl)-7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
2-(3-(7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-8-oxo-7,8-dihydro-9H-purin-9-yl)bicyclo[1.1.1]pentan-1-yl)acetonitrile	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
2-(3-(7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-8-oxo-7,8-dihydro-9H-purin-9-yl)bicyclo[1.1.1]pentan-1-yl)acetonitrile	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(4-methoxybicyclo[2.1.1]hexan-1-yl)-7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(4-methoxybicyclo[2.1.1]hexan-1-yl)-7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-7,9-dihydro-8H-purine-8-thione	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-7,9-dihydro-8H-purine-8-thione	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-7-methyl-2-((7-methylquinoxalin-6-yl)amino)-7,9-dihydro-8H-purine-8-thione	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
2-fluoro-4-((9-(4-methoxybicyclo[2.1.1]hexan-1-yl)-7-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl)amino)-5-methylbenzamide	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
2-((5-fluoro-2-methyl-4-(oxazol-5-yl)phenyl)amino)-9-(4-methoxybicyclo[2.1.1]hexan-1-yl)-7-methyl-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
1-(bicyclo[1.1.1]pentan-1-yl)-3-methyl-N-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
1-(bicyclo[1.1.1]pentan-1-yl)-3-methyl-N-(6-methylbenzo[d][1,3]dioxol-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-{4-Hydroxybicyclo[2.2.1]heptan-1-yl}-5-methyl-2-({7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}amino)-5,6,7,8-tetrahydropteridin-6-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-{3-Fluorobicyclo[1.1.1]pentan-1-yl}-5-methyl-2-({7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl}amino)-5,6,7,8-tetrahydropteridin-6-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-(3-fluorobicyclo[1.1.1]pentan-1-yl)-5-methyl-2-((7-methylquinolin-6-yl)amino)-7,8-dihydropteridin-6(5H)-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-(4-methoxybicyclo[2.2.1]heptan-1-yl)-5-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-7,8-dihydropteridin-6(5H)-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
7’-(3-fluorobicyclo[1.1.1]pentan-1-yl)-2’-((4-methyl-6-(oxazol-5-yl)pyridin-3-yl)amino)spiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidin]-6’(7’H)-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
7’-(3-fluorobicyclo[1.1.1]pentan-1-yl)-2’-((4-methyl-6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)spiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidin]-6’(7’H)-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
7’-(3-fluorobicyclo[1.1.1]pentan-1-yl)-2’-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)spiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidin]-6’(7’H)-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
N-[5-(1-cyclopropyl-3-methyl-2-oxoimidazo[4,5-c]quinolin-8-yl)-2-methoxy-3-pyridinyl]cyclopropanesulfonamide	IC50	13.1 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
9-(3-fluorobicyclo[1.1.1]pentan-1-yl)-7-methyl-2-((7-methyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	55 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
9-(3-fluorobicyclo[1.1.1]pentan-1-yl)-7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-7,9-dihydro-8H-purine-8-thione	IC50	55 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
2-((5-fluoro-2-methyl-4-(1-methyl-1H-pyrazol-4-yl)phenyl)amino)-9-(3-fluorobicyclo[1.1.1]pentan-1-yl)-7-methyl-7,9-dihydro-8H-purin-8-one	IC50	55 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
2-((5-fluoro-2-methyl-4-(1-methyl-1H-pyrazol-4-yl)phenyl)amino)-9-(4-methoxybicyclo[2.1.1]hexan-1-yl)-7-methyl-7,9-dihydro-8H-purin-8-one	IC50	55 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-{4-Hydroxybicyclo[2.2.1]heptan-1-yl}-5-methyl-2-[(6-methyl-2H-1,3-benzodioxol-5-yl)amino]-5,6,7,8-tetrahydropteridin-6-one	IC50	55 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-{3-Fluorobicyclo[1.1.1]pentan-1-yl}-5-methyl-2-[(6-methyl-2H-1,3-benzodioxol-5-yl)amino]-5,6,7,8-tetrahydropteridin-6-one	IC50	55 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
8-(2-aminopyrimidin-5-yl)-3-methyl-1-(oxan-4-yl)imidazo[4,5-c]quinolin-2-one	IC50	80.4 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
methyl 4-[8-(6-methoxy-3-pyridinyl)-3-methyl-2-oxoimidazo[4,5-c]quinolin-1-yl]piperidine-1-carboxylate	IC50	102 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
1-cyclopropyl-3-methyl-8-(1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[4,5-c]quinolin-2-one	IC50	149 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
1-(1-acetylpiperidin-4-yl)-8-(6-methoxy-3-pyridinyl)-3-methylimidazo[4,5-c]quinolin-2-one	IC50	153 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
3-methyl-8-[6-[3-(methylamino)propoxy]-3-pyridinyl]-1-[(3R)-oxan-3-yl]imidazo[4,5-c]quinolin-2-one	IC50	167 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
3-methyl-8-[6-[3-(methylamino)propoxy]-3-pyridinyl]-1-(oxan-4-yl)imidazo[4,5-c]quinolin-2-one	IC50	184 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
8-(6-methoxy-3-pyridinyl)-3-methyl-1-piperidin-4-ylimidazo[4,5-c]quinolin-2-one	IC50	188 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
8-(2-aminopyrimidin-5-yl)-1-cyclopropyl-3-methylimidazo[4,5-c]quinolin-2-one	IC50	247 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
8-[6-[3-(dimethylamino)propoxy]-3-pyridinyl]-3-methyl-1-[(3S)-oxolan-3-yl]imidazo[4,5-c]quinolin-2-one	IC50	260 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
3-methyl-1-[(3R)-oxan-3-yl]-8-[6-(3-pyrrolidin-1-ylpropoxy)-3-pyridinyl]imidazo[4,5-c]quinolin-2-one	IC50	264 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
3-methyl-8-[6-[3-(methylamino)propoxy]-3-pyridinyl]-1-[(3S)-oxan-3-yl]imidazo[4,5-c]quinolin-2-one	IC50	267 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
8-[6-[3-(dimethylamino)propoxy]-3-pyridinyl]-3-methyl-1-[(3R)-oxan-3-yl]imidazo[4,5-c]quinolin-2-one	IC50	311 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
1-(3-methoxycyclobutyl)-3-methyl-8-[6-[3-(methylamino)propoxy]-3-pyridinyl]imidazo[4,5-c]quinolin-2-one	IC50	321 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer

ChEMBL bioactivities

1929 potent at pChembl≥5 of 3942 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	IC50	0.04	nM	CHEMBL3960662
10.10	IC50	0.08	nM	CHEMBL6174896
10.05	IC50	0.09	nM	AZD-1390
10.00	Ki	0.1	nM	CHEMBL4850755
9.90	IC50	0.1259	nM	CHEMBL5573231
9.82	IC50	0.152	nM	CHEMBL3923182
9.77	IC50	0.17	nM	CHEMBL3936943
9.75	IC50	0.176	nM	CHEMBL3936943
9.70	IC50	0.2	nM	CHEMBL3960323
9.70	Ki	0.2	nM	CHEMBL4858310
9.70	IC50	0.2	nM	LARTESERTIB
9.68	IC50	0.208	nM	CHEMBL4115047
9.66	IC50	0.22	nM	CHEMBL3952396
9.66	IC50	0.22	nM	CHEMBL3960662
9.63	IC50	0.233	nM	CHEMBL4110135
9.62	IC50	0.24	nM	CHEMBL3889770
9.62	IC50	0.238	nM	CHEMBL3947316
9.60	IC50	0.249	nM	CHEMBL3936734
9.60	IC50	0.249	nM	CHEMBL3954517
9.60	IC50	0.25	nM	CHEMBL3936734
9.60	IC50	0.25	nM	CHEMBL3954517
9.60	IC50	0.2512	nM	CHEMBL5171429
9.60	IC50	0.2512	nM	CHEMBL5567522
9.60	IC50	0.2512	nM	CHEMBL5572255
9.60	IC50	0.25	nM	CHEMBL3672677
9.54	IC50	0.292	nM	CHEMBL3979811
9.54	IC50	0.29	nM	CHEMBL3979811
9.54	IC50	0.29	nM	CHEMBL4217549
9.52	IC50	0.301	nM	CHEMBL3927821
9.52	Ki	0.3	nM	CHEMBL4862803
9.51	IC50	0.31	nM	CHEMBL3890876
9.51	IC50	0.31	nM	CHEMBL3929864
9.51	Kd	0.31	nM	MEISOINDIGO
9.50	IC50	0.315	nM	CHEMBL4112870
9.49	IC50	0.324	nM	CHEMBL3898641
9.49	IC50	0.32	nM	CHEMBL5191923
9.48	IC50	0.329	nM	CHEMBL3890490
9.48	IC50	0.334	nM	CHEMBL3904625
9.48	IC50	0.33	nM	CHEMBL3890490
9.44	IC50	0.365	nM	CHEMBL3935033
9.40	Ki	0.4	nM	CHEMBL4852400
9.40	IC50	0.4	nM	CHEMBL3960662
9.40	IC50	0.3981	nM	CHEMBL5182423
9.40	Ki	0.4	nM	CHEMBL5597568
9.39	IC50	0.41	nM	CHEMBL5408388
9.38	IC50	0.418	nM	CHEMBL3895211
9.36	IC50	0.434	nM	CHEMBL3970378
9.35	IC50	0.447	nM	CHEMBL3898165
9.35	IC50	0.45	nM	CHEMBL6171509
9.32	IC50	0.48	nM	CHEMBL5429597

PubChem BioAssay actives

625 with measured affinity, of 1097 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
8-[6-[3-(dimethylamino)propoxy]-3-pyridinyl]-3-methyl-1-(oxan-4-yl)imidazo[4,5-c]quinolin-2-one	1358684: Inhibition of ATM (unknown origin) using p53 as substrate preincubated for 30 mins followed by substrate addition and measured after 2 hrs by HTRF assay	ic50	<0.0001	uM
7-fluoro-3-methyl-8-[6-(3-piperidin-1-ylpropoxy)-3-pyridinyl]-1-propan-2-ylimidazo[4,5-c]quinolin-2-one	1743716: Inhibition of ATM (unknown origin) assessed as ATM-dependent phosphorylation using GST-p53 ser15 as substrate	ic50	0.0001	uM
8-[6-[3-(4-fluoropiperidin-1-yl)propoxy]-3-pyridinyl]-3-methyl-1-propan-2-ylimidazo[4,5-c]quinolin-2-one	2088944: Inhibition of ATM in human HT-29 cells incubated for 2 hrs by Alexa Fluor 488/Hoeschst staining based plate reader assay	ic50	0.0001	uM
2-[(2R)-2-benzylazepan-1-yl]-4-morpholin-4-yl-1H-pyrimidin-6-one	1764610: Inhibition of full length recombinant FLAG-tagged human ATM assessed as decrease in p53 S15 phosphorylation using full length myc-tagged p53 as substrate incubated for 30 mins in presence of ATP by ELISA	ki	0.0001	uM
3-[[5-[3-(1-cyclopropylsulfonyl-2,3-dihydroindol-6-yl)imidazo[4,5-b]pyridin-5-yl]-2-pyridinyl]oxy]-N,N-dimethylpropan-1-amine	1990361: Inhibition of ATM kinase in human A549 cells in presence of etoposide by ICW assay	ic50	0.0001	uM
8-[6-[3-(dimethylamino)propoxy]-3-pyridinyl]-1-(3-hydroxycyclobutyl)-3-methylimidazo[4,5-c]quinolin-2-one	1358643: Inhibition of ATM autophosphorylation at Ser1981 in human HT29 cells preincubated for 1 hr followed by X ray irradiation and measured after 1 hr by Hoechst 33342 dye-based immunofluorescence assay	ic50	0.0002	uM
1-(3-methoxycyclobutyl)-3-methyl-8-[6-(3-pyrrolidin-1-ylpropoxy)-3-pyridinyl]imidazo[4,5-c]quinolin-2-one	1358643: Inhibition of ATM autophosphorylation at Ser1981 in human HT29 cells preincubated for 1 hr followed by X ray irradiation and measured after 1 hr by Hoechst 33342 dye-based immunofluorescence assay	ic50	0.0002	uM
1-(3-methoxycyclobutyl)-3-methyl-8-[6-(3-piperidin-1-ylpropoxy)-3-pyridinyl]imidazo[4,5-c]quinolin-2-one	1358643: Inhibition of ATM autophosphorylation at Ser1981 in human HT29 cells preincubated for 1 hr followed by X ray irradiation and measured after 1 hr by Hoechst 33342 dye-based immunofluorescence assay	ic50	0.0002	uM
8-(1,3-dimethylpyrazol-4-yl)-1-(3-fluoro-5-methoxy-4-pyridinyl)-7-methoxy-3-methylimidazo[4,5-c]quinolin-2-one	1997891: Inhibition of ATM (unknown origin)	ic50	0.0002	uM
2-[(1R,2S,5S)-2-benzyl-3-azabicyclo[3.1.0]hexan-3-yl]-4-morpholin-4-yl-1H-pyrimidin-6-one	1764610: Inhibition of full length recombinant FLAG-tagged human ATM assessed as decrease in p53 S15 phosphorylation using full length myc-tagged p53 as substrate incubated for 30 mins in presence of ATP by ELISA	ki	0.0002	uM
1-(3-methoxycyclobutyl)-3-methyl-8-[6-[3-(methylamino)propoxy]-3-pyridinyl]imidazo[4,5-c]quinolin-2-one	1358643: Inhibition of ATM autophosphorylation at Ser1981 in human HT29 cells preincubated for 1 hr followed by X ray irradiation and measured after 1 hr by Hoechst 33342 dye-based immunofluorescence assay	ic50	0.0003	uM
8-[6-[3-(dimethylamino)propoxy]-3-pyridinyl]-3-methyl-1-[(3S)-oxan-3-yl]imidazo[4,5-c]quinolin-2-one	1358643: Inhibition of ATM autophosphorylation at Ser1981 in human HT29 cells preincubated for 1 hr followed by X ray irradiation and measured after 1 hr by Hoechst 33342 dye-based immunofluorescence assay	ic50	0.0003	uM
8-[6-[3-(dimethylamino)propoxy]-3-pyridinyl]-1-(3-methoxycyclobutyl)-3-methylimidazo[4,5-c]quinolin-2-one	1358643: Inhibition of ATM autophosphorylation at Ser1981 in human HT29 cells preincubated for 1 hr followed by X ray irradiation and measured after 1 hr by Hoechst 33342 dye-based immunofluorescence assay	ic50	0.0003	uM
8-[6-[3-(azetidin-1-yl)propoxy]-3-pyridinyl]-1-(3-methoxycyclobutyl)-3-methylimidazo[4,5-c]quinolin-2-one	1358643: Inhibition of ATM autophosphorylation at Ser1981 in human HT29 cells preincubated for 1 hr followed by X ray irradiation and measured after 1 hr by Hoechst 33342 dye-based immunofluorescence assay	ic50	0.0003	uM
3-(2-hydroxy-1-methylindol-3-yl)indol-2-one	2070354: Binding affinity to recombinant ATM (unknown origin) assessed as dissociation constant by surface plasmon resonance assay	kd	0.0003	uM
3-methyl-1-propan-2-yl-8-[6-(3-pyrrolidin-1-ylpropoxy)-3-pyridinyl]imidazo[4,5-c]quinolin-2-one	2088944: Inhibition of ATM in human HT-29 cells incubated for 2 hrs by Alexa Fluor 488/Hoeschst staining based plate reader assay	ic50	0.0003	uM
3-methyl-8-[6-(3-piperidin-1-ylpropoxy)-3-pyridinyl]-1-propan-2-ylimidazo[4,5-c]quinolin-2-one	2088944: Inhibition of ATM in human HT-29 cells incubated for 2 hrs by Alexa Fluor 488/Hoeschst staining based plate reader assay	ic50	0.0003	uM
6-[6-[3-(dimethylamino)propoxy]-3-pyridinyl]-4-[[(1S)-1-(oxan-4-yl)ethyl]amino]cinnoline-3-carboxamide	1385779: Inhibition of ATM (unknown origin) using p53 as substrate pretreated for 30 mins followed by substrate addition and measured after 2 hrs by HTRF assay	ic50	0.0003	uM
6-[(1S,2S,5R)-2-benzyl-3-azabicyclo[3.1.0]hexan-3-yl]-4-morpholin-4-yl-1H-pyridin-2-one	1764610: Inhibition of full length recombinant FLAG-tagged human ATM assessed as decrease in p53 S15 phosphorylation using full length myc-tagged p53 as substrate incubated for 30 mins in presence of ATP by ELISA	ki	0.0003	uM
1-[2-(3-fluoroazetidin-1-yl)ethyl]-3-[4-[1-(2-methoxyethyl)-3-methyl-2-oxoimidazo[4,5-c]quinolin-8-yl]phenyl]urea	1905806: Inhibition of ATM in human A549 cells assessed as reduction in etoposide-stimulated KAP1 phosphorylation by In-Cell-Western assay	ic50	0.0003	uM
8-[6-[3-(dimethylamino)propoxy]-3-pyridinyl]-3-methyl-1-propan-2-ylimidazo[4,5-c]quinolin-2-one	2088944: Inhibition of ATM in human HT-29 cells incubated for 2 hrs by Alexa Fluor 488/Hoeschst staining based plate reader assay	ic50	0.0004	uM
2-[(2S,3R)-2-benzyl-3-methylpyrrolidin-1-yl]-4-morpholin-4-yl-1H-pyrimidin-6-one	1764610: Inhibition of full length recombinant FLAG-tagged human ATM assessed as decrease in p53 S15 phosphorylation using full length myc-tagged p53 as substrate incubated for 30 mins in presence of ATP by ELISA	ki	0.0004	uM
2-[(2R,3S)-2-benzyl-3-methylpyrrolidin-1-yl]-4-morpholin-4-yl-1H-pyrimidin-6-one	2122161: Binding affinity to ATM (unknown origin) assessed as inhibition constant	ki	0.0004	uM
8-[4-[3-(dimethylamino)propoxy]phenyl]-1-[(1S,3S)-3-methoxycyclopentyl]-3-methylimidazo[4,5-c]quinolin-2-one	2088944: Inhibition of ATM in human HT-29 cells incubated for 2 hrs by Alexa Fluor 488/Hoeschst staining based plate reader assay	ic50	0.0005	uM
8-[6-[3-[(3S)-3-fluoropyrrolidin-1-yl]propoxy]-3-pyridinyl]-3-methyl-1-propan-2-ylimidazo[4,5-c]quinolin-2-one	2088944: Inhibition of ATM in human HT-29 cells incubated for 2 hrs by Alexa Fluor 488/Hoeschst staining based plate reader assay	ic50	0.0005	uM
4-[[(1S)-1-(1,4-dimethylpyrazol-3-yl)ethyl]amino]-6-[6-(3-pyrrolidin-1-ylpropoxy)-3-pyridinyl]cinnoline-3-carboxamide	1385766: Inhibition of ATM autophosphorylation at Ser1981 residue in human HT-29 cells measured after 1 hr by Hoechst staining based fluorescence assay	ic50	0.0005	uM
2-(7-methoxy-9H-thioxanthen-4-yl)-6-morpholin-4-ylpyran-4-one	1764610: Inhibition of full length recombinant FLAG-tagged human ATM assessed as decrease in p53 S15 phosphorylation using full length myc-tagged p53 as substrate incubated for 30 mins in presence of ATP by ELISA	ki	0.0005	uM
2-[7-[2-(3,3-difluoropyrrolidin-1-yl)ethoxy]-9H-thioxanthen-4-yl]-6-morpholin-4-ylpyran-4-one	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0005	uM
2-morpholin-4-yl-6-[7-[2-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]ethoxy]-9H-thioxanthen-4-yl]pyran-4-one	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0005	uM
2-[7-[(3-methyloxetan-3-yl)methylamino]-9H-thioxanthen-4-yl]-6-morpholin-4-ylpyran-4-one	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0005	uM
2-morpholin-4-yl-6-[7-(oxan-4-ylmethoxy)-9H-thioxanthen-4-yl]pyran-4-one	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0005	uM
2-[7-[2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]ethoxy]-9H-thioxanthen-4-yl]-6-morpholin-4-ylpyran-4-one	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0005	uM
N,N-dimethyl-3-[[5-[3-(1-methylsulfonyl-2,3-dihydroindol-6-yl)imidazo[4,5-b]pyridin-5-yl]-2-pyridinyl]oxy]propan-1-amine	1990351: Inhibition of human ATM kinase using p53 as substrate by FRET assay	ic50	0.0005	uM
2-(7-hydroxy-9H-thioxanthen-4-yl)-6-morpholin-4-ylpyran-4-one	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0005	uM
7-fluoro-6-[6-(methoxymethyl)-3-pyridinyl]-4-[[(1S)-1-(1-methylpyrazol-3-yl)ethyl]amino]quinoline-3-carboxamide	1635523: Inhibition of ATM (unknown origin) using p53 as substrate incubated for 30 mins followed by substrate addition measured after 2 hrs in presence of ATP by HTRF method	ic50	0.0006	uM
2-morpholin-4-yl-6-[7-[(2R)-1-morpholin-4-ylpropan-2-yl]oxy-9H-thioxanthen-4-yl]pyran-4-one	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0006	uM
N-[5-(6-morpholin-4-yl-4-oxopyran-2-yl)-9H-thioxanthen-2-yl]acetamide	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0006	uM
2-[(1S,2S,5R)-2-benzyl-3-azabicyclo[3.1.0]hexan-3-yl]-4-morpholin-4-yl-1H-pyrimidin-6-one	1764610: Inhibition of full length recombinant FLAG-tagged human ATM assessed as decrease in p53 S15 phosphorylation using full length myc-tagged p53 as substrate incubated for 30 mins in presence of ATP by ELISA	ki	0.0006	uM
2-[7-[(2S)-2-hydroxypropoxy]-9H-thioxanthen-4-yl]-6-morpholin-4-ylpyran-4-one	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0006	uM
2-[7-[2-(3-fluoroazetidin-1-yl)ethoxy]-9H-thioxanthen-4-yl]-6-morpholin-4-ylpyran-4-one	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0006	uM
N-[5-(6-morpholin-4-yl-4-oxopyran-2-yl)-9H-thioxanthen-2-yl]cyclopropanecarboxamide	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0006	uM
1-[2-(dimethylamino)ethyl]-3-[3-fluoro-4-[1-(2-methoxyethyl)-3-methyl-2-oxoimidazo[4,5-c]quinolin-8-yl]phenyl]urea	1905806: Inhibition of ATM in human A549 cells assessed as reduction in etoposide-stimulated KAP1 phosphorylation by In-Cell-Western assay	ic50	0.0006	uM
1-[2-(dimethylamino)ethyl]-3-[4-[3-(1-methylsulfonyl-3,4-dihydro-2H-quinolin-7-yl)imidazo[4,5-b]pyridin-5-yl]phenyl]urea	1990351: Inhibition of human ATM kinase using p53 as substrate by FRET assay	ic50	0.0006	uM
3-(1-methylsulfonyl-2,3-dihydroindol-6-yl)-5-[6-(3-pyrrolidin-1-ylpropoxy)-3-pyridinyl]imidazo[4,5-b]pyridine	1990351: Inhibition of human ATM kinase using p53 as substrate by FRET assay	ic50	0.0006	uM
N,N-dimethyl-3-[[5-[3-(1-methylsulfonyl-3,4-dihydro-2H-quinolin-7-yl)imidazo[4,5-b]pyridin-5-yl]-2-pyridinyl]oxy]propan-1-amine	1990361: Inhibition of ATM kinase in human A549 cells in presence of etoposide by ICW assay	ic50	0.0006	uM
6-[6-[3-(dimethylamino)propoxy]-3-pyridinyl]-N-methyl-4-[[(1S)-1-(oxan-4-yl)ethyl]amino]cinnoline-3-carboxamide	1385779: Inhibition of ATM (unknown origin) using p53 as substrate pretreated for 30 mins followed by substrate addition and measured after 2 hrs by HTRF assay	ic50	0.0007	uM
2-[7-[2-(4-methylpiperazin-1-yl)ethoxy]-9H-thioxanthen-4-yl]-6-morpholin-4-ylpyran-4-one	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0007	uM
2-[7-[2-(4,4-difluoropiperidin-1-yl)ethoxy]-9H-thioxanthen-4-yl]-6-morpholin-4-ylpyran-4-one	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0007	uM
2-morpholin-4-yl-6-[7-[(2S)-2-morpholin-4-ylpropoxy]-9H-thioxanthen-4-yl]pyran-4-one	1687214: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA	ic50	0.0007	uM
1-[2-(dimethylamino)ethyl]-3-[2-fluoro-4-[1-(2-methoxyethyl)-3-methyl-2-oxoimidazo[4,5-c]quinolin-8-yl]phenyl]urea	1905806: Inhibition of ATM in human A549 cells assessed as reduction in etoposide-stimulated KAP1 phosphorylation by In-Cell-Western assay	ic50	0.0007	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one	increases activity, decreases activity, affects expression, decreases expression, decreases reaction (+3 more)	12
Caffeine	increases phosphorylation, increases activity, decreases activity, affects cotreatment, decreases response to substance (+2 more)	12
Doxorubicin	decreases reaction, increases expression, affects binding, affects expression, increases activity (+5 more)	9
Hydrogen Peroxide	decreases reaction, increases phosphorylation, increases reaction, affects expression, affects cotreatment (+6 more)	8
bisphenol A	increases methylation, increases phosphorylation, decreases reaction, increases reaction, affects cotreatment (+2 more)	7
Resveratrol	decreases phosphorylation, increases acetylation, decreases reaction, increases reaction, increases expression (+3 more)	7
Benzo(a)pyrene	affects cotreatment, affects response to substance, decreases expression, affects localization, decreases reaction (+4 more)	7
Cisplatin	decreases reaction, increases phosphorylation, affects reaction, increases expression, increases activity (+6 more)	7
Arsenic Trioxide	increases phosphorylation, decreases expression, decreases phosphorylation, increases expression, increases reaction (+1 more)	6
Acetylcysteine	decreases reaction, increases expression, increases activity, increases reaction, increases phosphorylation	6
sodium arsenite	increases response to substance, affects reaction, increases abundance, decreases phosphorylation, decreases reaction (+5 more)	5
Decitabine	affects methylation, affects cotreatment, decreases expression, decreases methylation, affects reaction (+3 more)	4
Arsenic	affects phosphorylation, affects methylation, affects reaction, affects response to substance, affects cotreatment (+3 more)	4
Quercetin	decreases expression, increases phosphorylation	4
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	4
Cadmium Chloride	decreases expression, increases abundance, increases phosphorylation, increases expression	4
Particulate Matter	decreases expression, increases abundance, affects reaction, increases expression, increases ubiquitination (+2 more)	4
2-(2,6-dimethylmorpholin-4-yl)-N-(5-(6-morpholin-4-yl-4-oxo-4H-pyran-2-yl)-9H-thioxanthen-2-yl)acetamide	decreases activity, decreases reaction, increases phosphorylation, increases expression	3
Copper	increases phosphorylation, increases response to substance, affects binding, increases expression, affects cotreatment (+2 more)	3
Estradiol	increases expression, decreases expression	3
Valproic Acid	decreases expression, decreases methylation	3
Nanotubes, Carbon	decreases expression, decreases methylation, increases expression	3
lasiocarpine	decreases expression, increases metabolic processing	2
trichostatin A	affects cotreatment, decreases expression, increases expression	2
zinc chromate	increases phosphorylation, affects expression, affects phosphorylation	2
manganese chloride	decreases expression, increases abundance, affects cotreatment	2
2-chloroethyl ethyl sulfide	increases phosphorylation, affects reaction	2
usnic acid	decreases reaction, increases phosphorylation, increases expression	2
Wortmannin	decreases reaction, increases phosphorylation, increases reaction	2
Vorinostat	increases expression, increases phosphorylation	2

ChEMBL screening assays

240 unique, capped per target: 233 binding, 5 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1049652	Binding	Inhibition of ATM	Identification and optimisation of novel and selective small molecular weight kinase inhibitors of mTOR. — Bioorg Med Chem Lett
CHEMBL1614153	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Identifying a Potential Treatment of Ataxia-Telangiectasia. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4670845	ADMET	Inhibition of ATM in human HCT116 cells assessed as decrease in Chk2 phosphorylation at Thr68 residue by measuring decrease in foci formation at 50 nM treated for 1 hr prior to UV-irradiation exposure and measured after 1 hr by immunofluore	Characterization of SPK 98, a Torin2 analog, as ATR and mTOR dual kinase inhibitor. — Bioorg Med Chem Lett

Cellosaurus cell lines

326 cell lines: 143 transformed cell line, 107 cancer cell line, 35 finite cell line, 27 induced pluripotent stem cell, 14 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0099	SNU-1	Cancer cell line	Male
CVCL_0134	A2780	Cancer cell line	Female
CVCL_0135	A2780/CP70	Cancer cell line	Female
CVCL_1053	8305C	Cancer cell line	Female
CVCL_1266	HCC2998	Cancer cell line	Sex unspecified
CVCL_1467	NCI-H1395	Cancer cell line	Female
CVCL_1476	NCI-H1568	Cancer cell line	Female
CVCL_1491	NCI-H1734	Cancer cell line	Female
CVCL_1499	NCI-H1838	Cancer cell line	Female
CVCL_1524	NCI-H2087	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01234272	PHASE4	COMPLETED	Comparison of the Analgesic Effect Between Intrathecal Morphine and IV-fentanyl Patient Controlled Analgesia (ITM-IVPCA) and Epidural PCA (PCEA) in Patients Undergoing Gastrectomy -Randomized Allocation Study-
NCT01260194	PHASE4	TERMINATED	A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01401075	PHASE4	COMPLETED	RCT With Adjuvant Mistletoe Treatment in Gastric Cancer Patients
NCT01471756	PHASE4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01766765	PHASE4	UNKNOWN	Early Jejunostomy Nutrition Minimizes Time to Chemotherapy
NCT01910948	PHASE4	UNKNOWN	Perioperative Application of Omega-3 Polyunsaturated Fatty Acids in Gastric Cancer Patients
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	PHASE4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT01962376	PHASE4	UNKNOWN	Preoperative Chemotherapy With Bevacizumab For Potentially Resectable Gastric Cancer With Liver Metastasis
NCT02047994	PHASE4	RECRUITING	Multicentric Randomized Study of H. Pylori Eradication and Pepsinogen Testing for Prevention of Gastric Cancer Mortality
NCT02366819	PHASE4	SUSPENDED	Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
NCT02401971	PHASE4	UNKNOWN	Irinotecan Plus Thalidomide in Second Line Advanced Gastric Cancer
NCT02458573	PHASE4	COMPLETED	Comparison of the Effects of Continuous Epidural Analgesia and Continuous Intravenous Analgesia on Postoperative Bowel Movement in Patients Undergoing Laparoscopic Gastrectomy
NCT02638584	PHASE4	COMPLETED	Effects of Ilaprazole on Ulcer Healing Rate and Prevention of Gastrointestinal Bleeding in the Patients Undergone ESD.
NCT02776527	PHASE4	UNKNOWN	A Clinical Trial of Maintenance Treatment of Apatinib in Advanced Gastric Cancer Patients Have Completed Postoprative Adjuvant Chemotherapy
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03550482	PHASE4	COMPLETED	Oncoxin® and Quality of Life in Cancer Patients
NCT03609892	PHASE4	COMPLETED	Helicobacter Rescue Therapy With Berberine Plus Amoxicillin Quadruple Therapy Versus Tetracycline Plus Furazolidone Quadruple Therapy
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03733639	PHASE4	UNKNOWN	Tisseel® as a Reinforcement of Esophagojejunal Anastomoses
NCT04168346	PHASE4	NOT_YET_RECRUITING	Preoperative Intravenous Iron Therapy in Patients With Gastric Cancer
NCT04209933	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Different Bismuth Quadruple Therapies
NCT04591028	PHASE4	WITHDRAWN	A Study to Evaluate Indocyanine Green Lymphangiography to Improve Lymphadenectomy in Gastric Cancer Patients
NCT04607057	PHASE4	UNKNOWN	Supplemental Parenteral Nutrition During Postgastrectomy in Nutritionally at Risk Patient
NCT04660123	PHASE4	COMPLETED	A Real World Study of Bismuth Colloidal Pectin Granules Quadruple Therapy for H. Pylori Eradication
NCT04678492	PHASE4	COMPLETED	Helicobacter Rescue Therapy With High-dose Esomeprazole and Amoxicillin Dual Therapy Versus Bismuth-containing Quadruple Therapy
NCT04697186	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Berberine Plus Amoxicillin Triple Therapy Versus Bismuth-containing Quadruple Therapy
NCT05029453	PHASE4	UNKNOWN	Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT05229809	PHASE4	UNKNOWN	Clinical Trial of Yiqi Wenyang Jiedu Prescription in the Prevention and Treatment of Postoperative Metastasis and Recurrence of Gastric Cancer
NCT05354856	PHASE4	TERMINATED	The Effect of Chemoradiotherapy on Gastric Perfusion in Patients With Gastric Cancer.
NCT05410535	PHASE4	COMPLETED	To Evaluate Efficacy of Ursodeoxycholic Acid (UDCA) for the Prevention of Gallstone Formation After Gasterectomy
NCT05498766	PHASE4	NOT_YET_RECRUITING	Effect and Safety of Huaier Granule Versus SOX Regimen in Gastric Cancer Patients
NCT05518929	PHASE4	COMPLETED	Hypoxia During Gastroenterological Endoscope Procedures Sedated With Ciprofol In Overweight Or Obesity Patients