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); 34 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 (top 4% of genes corpus-wide)
• Clinical variants (ClinVar): 19,051 total — 2621 pathogenic, 675 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 26 tissues, sQTL in 8 (q < 0.05)
• Phenotypes (HPO): 138
• ChEMBL bioactivity: 35 clinical-phase molecules tested; no curated mechanism-of-action drug
• Precision-oncology evidence (CIViC): 35 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 24 cancer types (inferred from mutation patterns)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.85 (unconstrained)
• Transcription factor: yes — 27 downstream targets (CollecTRI)
• MANE Select transcript: NM_000051
• Interaction hub: 5,734 STRING partners (top 1% of genes corpus-wide)

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: 73 — 29 protein_coding, 19 retained_intron, 13 nonsense_mediated_decay, 12 protein_coding_CDS_not_defined

MANE Select: ENST00000675843

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 8, TSL 2: 3, TSL 3: 4, TSL 4: 3, TSL 5: 9

ENST00000675843, 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, 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, ENST00001003555, ENST00001003556, ENST00001078762, ENST00001078763, ENST00001078764, ENST00001078765, ENST00001096341, ENST00001109966, ENST00001143982

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.

Highest expression (Bgee): calcaneal tendon, colonic epithelium, corpus callosum, lymph node, bone marrow cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ATM is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 26 tissues and its splicing (sQTL) in 8 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 34 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	4.8e-27	-0.17	11:108180573:A:G
Esophagus Muscularis	eqtl	2.4e-18	-0.22	11:108188273:T:C
Cells Cultured fibroblasts	sqtl	1.3e-17	-0.57	11:108303464:C:T
Cells Cultured fibroblasts	eqtl	7.9e-17	-0.17	11:108363212:T:A
Esophagus Gastroesophageal Junction	eqtl	2.2e-14	-0.24	11:108194208:A:G
Artery Aorta	eqtl	1.1e-08	-0.16	11:108188273:T:C
Nerve Tibial	sqtl	1.7e-07	-0.43	11:108196507:ATAAT:A
Artery Tibial	eqtl	2.7e-07	-0.10	11:108402731:T:TCC
Muscle Skeletal	eqtl	1.5e-05	-0.13	11:108481726:CA:C
Prostate	eqtl	2.8e-05	-0.18	11:108375510:A:G
Cells EBV-transformed lymphocytes	sqtl	5.6e-04	-0.63	11:108391670:C:T
Pancreas	sqtl	6.1e-04	-0.36	11:108377161:A:G
Thyroid	eqtl	6.5e-04	+0.10	11:108361630:T:C
Esophagus Mucosa	eqtl	8.1e-04	-0.08	11:108194208:A:G
Heart Atrial Appendage	eqtl	1.4e-03	-0.11	11:108374194:TCCCTGAC:T
Cells EBV-transformed lymphocytes	eqtl	1.6e-03	+0.11	11:108339382:A:G
Lung	sqtl	1.7e-03	-3.74	11:107768996:G:A
Minor Salivary Gland	eqtl	1.9e-03	-0.50	11:107257182:T:C
Colon Sigmoid	eqtl	4.1e-03	-0.14	11:108362811:C:T
Adipose Visceral Omentum	sqtl	4.2e-03	-0.29	11:108223106:G:A

FANTOM5 promoters

showing 10 of 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

showing 100 of 297 tissues 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
ovary	UBERON:0000992	92.48	gold quality
stromal cell of endometrium	CL:0002255	92.39	gold quality
adenohypophysis	UBERON:0002196	92.30	gold quality
caecum	UBERON:0001153	92.25	gold quality
spinal cord	UBERON:0002240	92.22	gold quality
cerebellar hemisphere	UBERON:0002245	92.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.12	gold quality
inferior vagus X ganglion	UBERON:0005363	92.09	gold quality
cerebellar cortex	UBERON:0002129	92.06	gold quality
pylorus	UBERON:0001166	92.04	gold quality
germinal epithelium of ovary	UBERON:0001304	91.86	gold quality
pancreas	UBERON:0001264	91.81	gold quality
cardia of stomach	UBERON:0001162	91.49	gold quality
tibial nerve	UBERON:0001323	91.44	gold quality
cerebellum	UBERON:0002037	91.34	gold quality
body of uterus	UBERON:0009853	91.20	gold quality
tendon of biceps brachii	UBERON:0008188	91.16	gold quality
renal medulla	UBERON:0000362	91.09	gold quality
superior surface of tongue	UBERON:0007371	91.04	gold quality
subthalamic nucleus	UBERON:0001906	90.86	gold quality
endocervix	UBERON:0000458	90.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.84	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.66	gold quality
dorsal root ganglion	UBERON:0000044	90.62	gold quality
nipple	UBERON:0002030	90.62	gold quality
medulla oblongata	UBERON:0001896	90.51	gold quality
right adrenal gland cortex	UBERON:0035827	90.38	gold quality
pericardium	UBERON:0002407	90.26	gold quality
ventral tegmental area	UBERON:0002691	90.21	gold quality
superior vestibular nucleus	UBERON:0007227	90.17	gold quality
right adrenal gland	UBERON:0001233	90.07	gold quality
right lung	UBERON:0002167	89.99	gold quality
trabecular bone tissue	UBERON:0002483	89.96	gold quality
adrenal gland	UBERON:0002369	89.93	gold quality
right coronary artery	UBERON:0001625	89.81	gold quality
adrenal cortex	UBERON:0001235	89.78	gold quality
fundus of stomach	UBERON:0001160	89.74	gold quality
embryo	UBERON:0000922	89.66	gold quality
tibia	UBERON:0000979	89.65	gold quality
left adrenal gland	UBERON:0001234	89.63	gold quality
cortical plate	UBERON:0005343	89.61	gold quality
endometrium	UBERON:0001295	89.60	gold quality
left adrenal gland cortex	UBERON:0035825	89.48	gold quality
right uterine tube	UBERON:0001302	89.43	gold quality
right lobe of thyroid gland	UBERON:0001119	89.34	gold quality
right atrium auricular region	UBERON:0006631	89.26	gold quality
uterus	UBERON:0000995	89.24	gold quality
small intestine	UBERON:0002108	89.23	gold quality
saliva-secreting gland	UBERON:0001044	89.19	gold quality
thyroid gland	UBERON:0002046	89.16	gold quality
upper lobe of left lung	UBERON:0008952	89.13	gold quality
urethra	UBERON:0000057	89.12	gold quality
female reproductive system	UBERON:0000474	89.11	gold quality
minor salivary gland	UBERON:0001830	89.10	gold quality
descending thoracic aorta	UBERON:0002345	89.10	gold quality
left lobe of thyroid gland	UBERON:0001120	89.07	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	89.02	gold quality
stomach	UBERON:0000945	88.85	gold quality
mucosa of stomach	UBERON:0001199	88.74	gold quality
upper lobe of lung	UBERON:0008948	88.69	gold quality
left uterine tube	UBERON:0001303	88.65	gold quality
peritoneum	UBERON:0002358	88.64	gold quality
omental fat pad	UBERON:0010414	88.64	gold quality
thoracic aorta	UBERON:0001515	88.61	gold quality
ascending aorta	UBERON:0001496	88.60	gold quality
cardiac atrium	UBERON:0002081	88.52	gold quality
metanephros cortex	UBERON:0010533	88.52	gold quality
right lobe of liver	UBERON:0001114	88.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.44	gold quality
ectocervix	UBERON:0012249	88.43	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Corpus callosum	tissue	69.0
Choroid plexus	tissue	46.8
Cerebellum	tissue	44.7	medium
Putamen	tissue	42.0
Ventral forebrain	tissue	40.0
Olfactory bulb	tissue	39.4
Cerebral cortex	tissue	38.1	medium
Retrosplenial cortex	tissue	38.1
Substantia nigra	tissue	37.7
Periaqueductal gray	tissue	37.7
Midbrain	tissue	37.5
Medulla oblongata	tissue	36.9
Amygdala	tissue	36.7
Insular cortex	tissue	36.4
Septum	tissue	35.9
Hippocampal formation	tissue	35.8
Retrosplenial and cingulate cortex	tissue	35.7
Spinal cord	tissue	35.4
Occipital cortex	tissue	34.3
Nucleus accumbens	tissue	34.2
Thalamus	tissue	33.5
Temporal cortex	tissue	33.5
Motor cortex	tissue	33.4
Entorhinal cortex	tissue	33.3
Basal ganglia	tissue	33.0	low
Prefrontal cortex	tissue	32.5
Hypothalamus	tissue	32.5
Somatosensory cortex	tissue	32.4
Superior colliculi	tissue	31.4
Pons	tissue	30.7
Hippocampus	tissue	29.5	medium
Locus coeruleus	tissue	29.0
Lymph node	tissue	25.8	high
Postcentral gyrus	tissue	21.8
Tonsil	tissue	20.0	high
Spleen	tissue	17.7	high
Retina	tissue	16.4
Thymus	tissue	14.3
Appendix	tissue	13.7	high
Bone marrow	tissue	11.7	high
Ovary	tissue	8.9	low
Epididymis	tissue	8.4	high
Salivary gland	tissue	7.9	medium
Parathyroid gland	tissue	7.7	high
Endometrium 1	tissue	7.5	high
Thyroid gland	tissue	7.3	high
Breast	tissue	7.0	high
Pancreas	tissue	6.8	high
Cervix	tissue	6.7	high
Stomach 1	tissue	6.5	high
Adrenal gland	tissue	6.5	high
Liver	tissue	6.4	medium
Gallbladder	tissue	6.3	high
Placenta	tissue	6.2	high
Urinary bladder	tissue	6.1	high
Skin 1	tissue	6.0	high
Lung	tissue	6.0	high
Adipose tissue	tissue	5.6	medium
Colon	tissue	5.6	high
Heart muscle	tissue	5.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (69.0), Parieto-temporal junction (white matter) (60.8), Temporal white matter (56.6), Corpus callosum, genu (white matter) (55.0), Corpus callosum, splenium (white matter) (55.0).

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)

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

showing 30 of 154 miRNAs:

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

gnomAD constraint: pLI 1.48e-69, LOEUF 0.847, missense Z 2.54 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000675843 splits into 4 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
11:108,227,625–108,293,379	1791 / 1804.5	0.99	no
11:108,293,380–108,353,872	1405 / 1604.4	0.88	no
11:108,353,873–108,365,145	21 / 51.6	0.41	no
11:108,365,146–108,365,505	95 / 100.3	0.95	no
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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:107202) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 133 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased T cell derived lymphoma incidence	9
premature death	7
decreased T cell number	7
decreased body weight	6
decreased CD4-positive, alpha-beta T cell number	5
decreased thymocyte number	4
male infertility	4
abnormal T cell differentiation	4
abnormal cell cycle checkpoint function	4
small thymus	3
decreased body size	3
increased mortality induced by gamma-irradiation	3
postnatal growth retardation	3
female infertility	3
increased cellular sensitivity to gamma-irradiation induced cell death	3
increased double-positive T cell number	3
decreased single-positive T cell number	3
abnormal Purkinje cell morphology	2
small testis	2
decreased locomotor activity	2
abnormal gametogenesis	2
increased tumor incidence	2
absent ovarian follicles	2
abnormal cell cycle	2
abnormal chromosome morphology	2

+108 more (showing top 25).

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Sus scrofa	Q6PQD5	88.4%	Diamond
Xenopus laevis	Q9DE14	72.6%	Diamond
Saccharomyces cerevisiae S288C	P32600	68.5%	Diamond
Aspergillus nidulans FGSC A4	Q5BHE2	62.0%	Diamond
Eremothecium gossypii ATCC 10895	Q75DB8	56.3%	Diamond
Dictyostelium discoideum	P54677	54.3%	Diamond
Nakaseomyces glabratus CBS 138	Q6FX42	54.1%	Diamond
Drosophila melanogaster	Q9VK45	53.8%	Diamond
Schizosaccharomyces pombe 972h-	O14356	52.1%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CT34	50.6%	Diamond
Caenorhabditis elegans	Q95Q95	43.5%	Diamond
Yarrowia lipolytica CLIB122	Q6CAD2	42.3%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SSE7	34.8%	Diamond

Genomic neighbors (locus context)

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

Symbol	Type	Entrez
POGLUT3	protein-coding	143888
C11orf65	protein-coding	160140
DDX10	protein-coding	1662
EXPH5	protein-coding	23086
NPAT	protein-coding	4863
ACAT1	protein-coding	38
CUL5	protein-coding	8065

Protein

Protein identifiers

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

Alternative names: Ataxia telangiectasia mutated

All UniProt accessions (15): A0A087X0E9, A0A6Q8PH76, A0A804HL86, A0AAA9YI03, A0AAQ5BH05, A0AAQ5BH14, A0AAQ5BH18, A0AAQ5BH23, A0AAQ5BH37, E9PIN0, Q13315, 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, UCHL3 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)

• 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 (484 total): sequence variant 188, helix 179, strand 42, turn 26, 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 by resolution:

PDB	Title	Method	Resolution (Å)
8OXQ	ATM(Q2971A) dimeric C-terminal region in complex with Mg AMP-PNP	ELECTRON MICROSCOPY	2.5
7SIC	Human ATM Dimer	ELECTRON MICROSCOPY	2.51
7SID	Human ATM Dimer Bound to Nbs1	ELECTRON MICROSCOPY	2.53
8OXP	ATM(Q2971A) in complex with Mg AMP-PNP	ELECTRON MICROSCOPY	2.6
7NI5	Human ATM kinase with bound inhibitor KU-55933	ELECTRON MICROSCOPY	2.78
7NI6	Human ATM kinase with bound ATPyS	ELECTRON MICROSCOPY	2.8
7NI4	Human ATM kinase domain with bound M4076 inhibitor	ELECTRON MICROSCOPY	3
8OXO	ATM(Q2971A) dimeric C-terminal region activated by oxidative stress in complex with Mg …	ELECTRON MICROSCOPY	3
8OXM	ATM(Q2971A) activated by oxidative stress in complex with Mg AMP-PNP and p53 peptide	ELECTRON MICROSCOPY	3.3
6K9L	4.27 Angstrom resolution cryo-EM structure of human dimeric ATM kinase	ELECTRON MICROSCOPY	4.27
5NP0	Closed dimer of human ATM (Ataxia telangiectasia mutated)	ELECTRON MICROSCOPY	5.7
5NP1	Open protomer of human ATM (Ataxia telangiectasia mutated)	ELECTRON MICROSCOPY	5.7
6K9K	Monomeric human ATM (Ataxia telangiectasia mutated) kinase	ELECTRON MICROSCOPY	7.82
6HKA	The solution structure of the micelle-associated FATC domain of the human protein kinase …	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Atypical kinases, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Mutated cancer genes, Mutational cancer driver genes, Disease related genes, Potential drug targets, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; vesicles; golgi apparatus

Antibody reliability (HPA): IH supported · IF supported

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)

Type	Positions
N-acetylserine	2
Phosphoserine	367, 1893, 1981, 1983, 2996
N6-acetyllysine	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 activity. no effect on …
1807	decreased phosphorylation of target proteins.
1893	loss of ir-induced s-1893 autophosphorylation. reduced correction of cell cycle checkpoint defects and dna-repair activity. no effect on …
1941	decreased phosphorylation of target proteins.
1981	loss of ir-induced s-1981 autophosphorylation. reduced correction of cell cycle checkpoint defects and dna-repair activity. no effect on …
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 response.
3016	loss of dna damage-inducible acetylation. retains constitutive kinase activity, but blocks dna damage-induced kinase activation. disrupts …
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

27 curated (TAS) of 61; 10 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 61 pathways:

ID	Pathway	Evidence
R-HSA-9704331	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function ⚕	curated
R-HSA-9704646	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function ⚕	curated
R-HSA-9701192	Defective homologous recombination repair (HRR) due to BRCA1 loss of function ⚕	curated
R-HSA-9709603	Impaired BRCA2 binding to PALB2 ⚕	curated
R-HSA-9709570	Impaired BRCA2 binding to RAD51 ⚕	curated
R-HSA-349425	Autodegradation of the E3 ubiquitin ligase COP1	curated
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence	curated
R-HSA-69473	G2/M DNA damage checkpoint	curated
R-HSA-5685942	HDR through Homologous Recombination (HRR)	curated
R-HSA-5685938	HDR through Single Strand Annealing (SSA)	curated
R-HSA-5693579	Homologous DNA Pairing and Strand Exchange	curated
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)	curated
R-HSA-9664873	Pexophagy	curated
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange	curated
R-HSA-5693607	Processing of DNA double-strand break ends	curated
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	curated
R-HSA-3371453	Regulation of HSF1-mediated heat shock response	curated
R-HSA-6804760	Regulation of TP53 Activity through Methylation	curated
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation	curated
R-HSA-6804757	Regulation of TP53 Degradation	curated
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates	curated
R-HSA-5693554	Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	curated
R-HSA-5693548	Sensing of DNA Double Strand Breaks	curated
R-HSA-69541	Stabilization of p53	curated
R-HSA-6803207	TP53 Regulates Transcription of Caspase Activators and Caspases	curated
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes	curated
R-HSA-6803204	TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	curated
R-HSA-9701190	Defective homologous recombination repair (HRR) due to BRCA2 loss of function ⚕	—
R-HSA-9701193	Defective homologous recombination repair (HRR) due to PALB2 loss of function ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-9675136	Diseases of DNA Double-Strand Break Repair ⚕	—
R-HSA-9675135	Diseases of DNA repair ⚕	—
R-HSA-9612973	Autophagy	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69620	Cell Cycle Checkpoints	—
R-HSA-2559583	Cellular Senescence	—
R-HSA-3371556	Cellular response to heat stress	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-5693606	DNA Double Strand Break Response	—
R-HSA-5693532	DNA Double-Strand Break Repair	—
R-HSA-73894	DNA Repair	—
R-HSA-69615	G1/S DNA Damage Checkpoints	—
R-HSA-69481	G2/M Checkpoints	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	—
R-HSA-5693538	Homology Directed Repair	—
R-HSA-1632852	Macroautophagy	—
R-HSA-1500620	Meiosis	—
R-HSA-912446	Meiotic recombination	electronic
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-5633007	Regulation of TP53 Activity	—
R-HSA-6806003	Regulation of TP53 Expression and Degradation	—
R-HSA-1474165	Reproduction	—
R-HSA-5693537	Resolution of D-Loop Structures	—
R-HSA-9663891	Selective autophagy	—
R-HSA-5633008	TP53 Regulates Transcription of Cell Death Genes	—
R-HSA-3700989	Transcriptional Regulation by TP53	—
R-HSA-69563	p53-Dependent G1 DNA Damage Response	—

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 (59): 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), pre-B cell allelic exclusion (GO:0002331), double-strand break repair (GO:0006302), double-strand break repair via nonhomologous end joining (GO:0006303), 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), signal transduction (GO:0007165), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), 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), cellular response to stress (GO:0033554), cellular response to reactive oxygen species (GO:0034614), peptidyl-serine autophosphorylation (GO:0036289), signal transduction in response to DNA damage (GO:0042770), regulation of apoptotic process (GO:0042981), positive regulation of apoptotic process (GO:0043065), positive regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043517), positive regulation of cell adhesion (GO:0045785), positive regulation of transcription by RNA polymerase II (GO:0045944), protein autophosphorylation (GO:0046777), protein stabilization (GO:0050821), regulation of cell cycle (GO:0051726), histone mRNA catabolic process (GO:0071044), cellular response to retinoic acid (GO:0071300), cellular response to gamma radiation (GO:0071480), cellular response to X-ray (GO:0071481), cellular response to nitrosative stress (GO:0071500), cellular senescence (GO:0090398), replicative senescence (GO:0090399), establishment of RNA localization to telomere (GO:0097694), establishment of protein-containing complex localization to telomere (GO:0097695), regulation of cellular response to heat (GO:1900034), regulation of signal transduction by p53 class mediator (GO:1901796), negative regulation of TORC1 signaling (GO:1904262), negative regulation of telomere capping (GO:1904354), positive regulation of telomere maintenance via telomere lengthening (GO:1904358), positive regulation of telomerase catalytic core complex assembly (GO:1904884), positive regulation of double-strand break repair (GO:2000781), regulation of autophagosome assembly (GO:2000785), DNA repair (GO:0006281), chromatin remodeling (GO:0006338), meiosis I (GO:0007127), regulation of gene expression (GO:0010468), positive regulation of macromolecule biosynthetic process (GO:0010557), phosphatidylinositol-3-phosphate biosynthetic process (GO:0036092), regulation of cellular response to stress (GO:0080135), cellular response to oxygen-containing compound (GO:1901701)

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 (14): 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), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

14 top-level categories:

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

showing 60 of 78 GO namespaces:

Category	Terms
double-strand break repair	3
cellular anatomical structure	3
intracellular membraneless organelle	3
signal transduction in response to DNA damage	2
DNA metabolic process	2
regulation of gene expression	2
protein kinase activity	2
protein serine/threonine kinase activity	2
binding	2
nuclear lumen	2
cytoplasm	2
DNA integrity checkpoint signaling	1
macroautophagy	1
autophagy of peroxisome	1
telomere organization	1
recombinational repair	1
5’-3’ DNA exonuclease activity	1
pre-B cell differentiation	1
DNA repair	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
reciprocal homologous recombination	1
meiotic cell cycle process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
response to radiation	1
autophagy	1
regulation of catabolic process	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
signal transduction by p53 class mediator	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
regulation of B cell proliferation	1
B cell proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of B cell activation	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
phosphatidylinositol-3-phosphate biosynthetic process	1
phosphatidylinositol kinase activity	1
histone H2AX kinase activity	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 46 of 87 annotations. The rest are phylogenetic / computational / electronic (IEA).

46 experimentally-supported GO terms:

GO term	NS	Evidence
DNA damage checkpoint signaling	BP	direct assay
DNA damage response	BP	direct assay
DNA double-strand break processing	BP	direct assay
cellular response to X-ray	BP	direct assay
cellular response to gamma radiation	BP	direct assay
cellular response to nitrosative stress	BP	direct assay
cellular response to reactive oxygen species	BP	direct assay
cellular response to stress	BP	direct assay
double-strand break repair	BP	direct assay
double-strand break repair via homologous recombination	BP	direct assay
establishment of RNA localization to telomere	BP	mutant phenotype
establishment of protein-containing complex localization to telomere	BP	mutant phenotype
histone mRNA catabolic process	BP	direct assay
mitotic G2 DNA damage checkpoint signaling	BP	mutant phenotype
mitotic spindle assembly checkpoint signaling	BP	mutant phenotype
negative regulation of B cell proliferation	BP	mutant phenotype
negative regulation of TORC1 signaling	BP	mutant phenotype
negative regulation of telomere capping	BP	mutant phenotype
peptidyl-serine autophosphorylation	BP	mutant phenotype
pexophagy	BP	direct assay
positive regulation of DNA damage response, signal transduction by p53 class mediator	BP	mutant phenotype
positive regulation of apoptotic process	BP	mutant phenotype
positive regulation of cell migration	BP	mutant phenotype
positive regulation of double-strand break repair	BP	mutant phenotype
positive regulation of gene expression	BP	mutant phenotype
positive regulation of telomerase catalytic core complex assembly	BP	mutant phenotype
positive regulation of telomere maintenance via telomere lengthening	BP	mutant phenotype
protein autophosphorylation	BP	mutant phenotype
protein stabilization	BP	direct assay
regulation of autophagy	BP	mutant phenotype
regulation of cell cycle	BP	mutant phenotype
regulation of telomere maintenance via telomerase	BP	genetic interaction
replicative senescence	BP	mutant phenotype
response to ionizing radiation	BP	direct assay
signal transduction in response to DNA damage	BP	direct assay
DNA repair complex	CC	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
peroxisomal matrix	CC	direct assay
site of double-strand break	CC	direct assay
1-phosphatidylinositol-3-kinase activity	MF	mutant phenotype
DNA-dependent protein kinase activity	MF	direct assay
identical protein binding	MF	physical interaction
protein serine/threonine kinase activity	MF	direct assay
protein-containing complex binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 5,734 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATM	CHEK2	O96017	980
ATM	CHEK1	O14757	969
ATM	BRCA1	P38398	969
ATM	RAD50	Q92878	967
ATM	TP53BP1	Q12888	956
ATM	TP53	P04637	954
ATM	H2AX	P16104	951
ATM	BRCA2	P51587	944
ATM	RAD51	Q06609	925
ATM	MSH6	P52701	915
ATM	MRE11	P49959	911
ATM	MDC1	Q14676	909
ATM	MSH2	P43246	906
ATM	MLH1	P40692	900
ATM	NBN	O60934	895

IntAct

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

showing 30 of 61 partners by confidence:

Partner	Interaction type	MIscore	Records
ABL1	physical association	0.700	4
TELO2	direct interaction	0.680	1
NOTCH1	physical association	0.660	7
TERF1	physical association	0.650	9
AKT1	physical association	0.640	4
TTI1	physical association	0.610	4
NABP2	physical association	0.600	4
MDC1	physical association	0.600	1
TP53BP1	phosphorylation reaction	0.570	1
ATMIN	physical association	0.560	5
ESRRG	physical association	0.560	3
AATF	physical association	0.540	3
FBXO31	phosphorylation reaction	0.540	2
TERF2	physical association	0.540	2
P2RY10	association	0.530	1
IKBKG	physical association	0.520	4
NSD3	physical association	0.510	3
IL24	physical association	0.510	2
NAT2	physical association	0.510	2
NBN	association	0.500	2
RRM2B	physical association	0.500	2
H2AX	colocalization	0.490	1
BRAT1	physical association	0.460	3
PPP2R5C	phosphorylation reaction	0.440	2
SIN3A	direct interaction	0.440	1
SMC1A	phosphorylation reaction	0.440	1
PEX5	physical association	0.400	2
GAPDHS	physical association	0.400	1
LMNB1	physical association	0.400	1
PRMT8	physical association	0.400	1

BioGRID (682 interactions; top human partners by supporting records in a sample of 600 records): TP53 (Biochemical Activity; 30 records), NBN (Affinity Capture-Western; 15 records), H2AFX (Affinity Capture-Western; 12 records), ABL1 (Biochemical Activity; 10 records), BRCA1 (Protein-peptide; 9 records), MDC1 (Co-localization; 8 records), TP53BP1 (Reconstituted Complex; 8 records), FOXO3 (Affinity Capture-Western; 6 records), IKBKG (Affinity Capture-Western; 6 records), KAT8 (Two-hybrid; 6 records), RBBP8 (Affinity Capture-Western; 6 records), BLM (Co-purification; 5 records), BSG (Affinity Capture-MS; 5 records), MRE11A (Protein-peptide; 5 records), PRKDC (Protein-peptide; 5 records)

SIGNOR signaling

showing 34 of 200 signaling 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
ATM	down-regulates	COP1	phosphorylation
ATM	“down-regulates quantity by destabilization”	MDM4	phosphorylation
ATR	“up-regulates activity”	ATM	phosphorylation
ATM	up-regulates	PRKDC	phosphorylation
ATM	up-regulates	TAOK1	phosphorylation
ATM	up-regulates	ZNF148	phosphorylation
ATM	unknown	RAD50	phosphorylation
ATM	up-regulates	H2AX	phosphorylation
ATM	down-regulates	AURKB
ATM	down-regulates	PPP1R2	phosphorylation
ATM	“down-regulates activity”	AKT1
ATM	up-regulates	RASSF1	phosphorylation
ATM	up-regulates	EXO1	phosphorylation
ATM	up-regulates	CHEK1	phosphorylation
ATM	up-regulates	EP300	phosphorylation
ATM	up-regulates	HIF1A	phosphorylation

Protein complexes (CORUM) (5)

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

5 complexes by size:

Complex	Subunits	Members
BASC complex (BRCA1-associated genome surveillance complex)	12	MRE11, MSH2, MSH6, NBN, RFC1, ATM, RAD50, RFC2, RFC4, BLM, BRCA1, MLH1
MDC1-MRN-ATM-FANCD2 complex	6	MRE11, NBN, RAD50, ATM, FANCD2, MDC1
BASC (Ab 81) complex (BRCA1-associated genome surveillance complex)	6	RFC4, ATM, BRCA1, MLH1, RFC1, RFC2
ATM-NBN complex	2	ATM, NBN
ATM homodimer	1	ATM

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 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
Meiosis	5	31.0×	5e-05
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	7	22.3×	5e-06
Nonhomologous End-Joining (NHEJ)	6	21.9×	4e-05
DNA Damage/Telomere Stress Induced Senescence	6	21.3×	4e-05
G2/M DNA damage checkpoint	8	20.9×	1e-06
Reproduction	5	20.7×	2e-04
G2/M Checkpoints	6	17.5×	9e-05
Meiotic synapsis	5	15.3×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of G2/M transition of mitotic cell cycle	5	50.1×	2e-05
response to ionizing radiation	5	34.2×	8e-05
double-strand break repair	5	16.9×	2e-03
DNA damage response	12	10.7×	9e-07
DNA repair	7	7.5×	3e-03
protein stabilization	6	6.7×	8e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	7	6.1×	6e-03

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).

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for ATM: 19,051 ClinVar records (3,296 pathogenic / likely pathogenic); 154 ClinGen expert-panel interpretations; 19 CIViC cancer variants; 2 PharmGKB clinical annotations; 33 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

19,051 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2621
Likely pathogenic	675
Uncertain significance	6100
Likely benign	3567
Benign	408

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 3,296 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
127340	NM_000051.4(ATM):c.1564_1565del (p.Glu522fs)	Pathogenic	reviewed by expert panel	45
127374	NM_000051.4(ATM):c.3802del (p.Glu1267_Val1268insTer)	Pathogenic	reviewed by expert panel	45
3023	NM_000051.4(ATM):c.7271T>G (p.Val2424Gly)	Pathogenic	reviewed by expert panel	39
140889	NM_000051.4(ATM):c.1402_1403del (p.Lys468fs)	Pathogenic	reviewed by expert panel	32
3035	NM_000051.4(ATM):c.3576G>A (p.Lys1192=)	Pathogenic	reviewed by expert panel	31
186242	NM_000051.4(ATM):c.8395_8404del (p.Phe2799fs)	Pathogenic	reviewed by expert panel	29
135780	NM_000051.4(ATM):c.8266A>T (p.Lys2756Ter)	Pathogenic	reviewed by expert panel	27
3029	NM_000051.4(ATM):c.9139C>T (p.Arg3047Ter)	Pathogenic	reviewed by expert panel	22
3033	NM_000051.4(ATM):c.3245_3247delinsTGAT (p.His1082fs)	Pathogenic	reviewed by expert panel	22
216021	NM_000051.4(ATM):c.2413C>T (p.Arg805Ter)	Pathogenic	reviewed by expert panel	22
127463	NM_000051.4(ATM):c.8786+1G>A	Pathogenic	reviewed by expert panel	21
127405	NM_000051.4(ATM):c.5290del (p.Leu1764fs)	Pathogenic	reviewed by expert panel	20
141742	NM_000051.4(ATM):c.790del (p.Tyr264fs)	Pathogenic	reviewed by expert panel	20
216024	NM_000051.4(ATM):c.748C>T (p.Arg250Ter)	Pathogenic	reviewed by expert panel	20
232248	NM_000051.4(ATM):c.67C>T (p.Arg23Ter)	Pathogenic	reviewed by expert panel	19

Per-variant reference — Sugi Variant

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

ClinGen expert-panel interpretations (154)

Expert ACMG interpretations from Hereditary Breast, Ovarian and Pancreatic Cancer VCEP for ATM-related cancer predisposition — a higher-authority tier than individual ClinVar submissions.

Assertion	Variants
Pathogenic	79
Likely Pathogenic	29
Uncertain Significance	27
Likely Benign	8
Benign	11

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 18 predictions of 6,110):

Position(s)	Effect	Δscore	Sites
11:108224054	donor_gain	1.0000
11:108224058	donor_gain	1.0000
11:108227769	acceptor_gain	1.0000
11:108227859	donor_gain	1.0000
11:108227875	donor_gain	1.0000
11:108227889–108227890	donor_loss	1.0000	4
11:108243951	acceptor_gain	1.0000
11:108249047	donor_gain	1.0000
11:108250814	donor_gain	1.0000
11:108252815–108252816	acceptor_loss	1.0000	6

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Chromophobe (TCGA)	unfavorable	0.000116
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000446
Rectum Adenocarcinoma (TCGA)	favorable	0.000718

Disease associations

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

GenCC curated gene-disease

7 curated gene-disease records:

Disease	Classification	Inheritance	Records
hereditary breast carcinoma	Definitive	Autosomal dominant	2
ataxia telangiectasia	Definitive	Autosomal recessive	9
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

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

2 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (28 panels, 27 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

28 panels:

Panel	Rating
Adult solid tumours cancer susceptibility	green
Adult solid tumours for rare disease	green
Adult-onset neurological disorders	green
Ataxia and cerebellar anomalies - childhood onset	green
Ataxia telangiectasia - mutation testing	green
Brain cancer pertinent cancer susceptibility	green
COVID-19 research	green
Childhood solid tumours	green
Childhood solid tumours cancer susceptibility	green
DDG2P	green
Dystonia, chorea or related movement disorder, adult onset	green
Dystonia, chorea or related movement disorder, childhood onset	green
Early onset dystonia	green
Familial breast cancer	green
Haematological malignancies cancer susceptibility	green
Haematological malignancies for rare disease	green
Hereditary ataxia	green
Hereditary ataxia and cerebellar anomalies, childhood onset	green
Hereditary ataxia, adult onset	green
Hereditary neuropathy	green
Hereditary neuropathy or pain disorder	green
Inherited breast cancer and ovarian cancer	green
Inherited pancreatic cancer	green
Inherited prostate cancer	green
Paediatric disorders	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green
Vascular skin disorders	green
Sarcoma susceptibility	amber

Mondo (46): 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), breast carcinoma (MONDO:0004989), malignant colon neoplasm (MONDO:0021063), breast-ovarian cancer, familial, susceptibility to, 1 (MONDO:0011450), familial pancreatic carcinoma (MONDO:0015278), malignant glioma (MONDO:0100342), urinary bladder cancer (MONDO:0001187), endometrial carcinoma (MONDO:0002447), cardiac valvular dysplasia, X-linked (MONDO:0010753), hereditary breast ovarian cancer syndrome (MONDO:0003582), uterine corpus cancer (MONDO:0006003), prostate cancer, hereditary (MONDO:0700275), exocrine pancreatic carcinoma (MONDO:0005192), Lynch syndrome 1 (MONDO:0007356), colon carcinoma (MONDO:0002032), adenocarcinoma (MONDO:0004970), Koolen-de Vries syndrome (MONDO:0012496), ovarian carcinoma (MONDO:0005140), ovarian cancer (MONDO:0008170), T-cell prolymphocytic leukemia (MONDO:0019468), breast neoplasm (MONDO:0021100), ataxia - telangiectasia variant (MONDO:0018266), BAP1-related tumor predisposition syndrome (MONDO:0013692), malignant pancreatic neoplasm (MONDO:0009831), mantle cell lymphoma (MONDO:0018876), cerebellar ataxia (MONDO:0000437), immunodeficiency disease (MONDO:0021094), ovarian cancer, susceptibility to, 1 (MONDO:0011931), neoplasm (MONDO:0005070), colonic neoplasm (MONDO:0005401), plasma cell myeloma (MONDO:0009693), gastric carcinoma (MONDO:0004950), prostate cancer (MONDO:0008315), hereditary nonpolyposis colon cancer (MONDO:0018630), sarcoma (MONDO:0005089)

Orphanet (26): 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), Familial pancreatic carcinoma (Orphanet:1333), 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), Koolen-De Vries syndrome (Orphanet:96169), Rare ovarian cancer (Orphanet:213500), T-cell prolymphocytic leukemia (Orphanet:86871), Ataxia-telangiectasia variant (Orphanet:370109), BAP1-related tumor predisposition syndrome (Orphanet:289539), Hereditary papillary renal cell carcinoma (Orphanet:47044), Mantle cell lymphoma (Orphanet:52416), Rare ataxia (Orphanet:102002), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443), OBSOLETE: Familial ovarian cancer (Orphanet:213517), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667), NON RARE IN EUROPE: Bladder cancer (Orphanet:157980)

HPO phenotypes

showing 60 of 138 phenotypes (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
HP:0001288	Gait disturbance
HP:0001315	Diminished deep tendon reflex
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001350	Slurred speech
HP:0001371	Flexion contracture
HP:0001402	Hepatocellular carcinoma
HP:0001442	Typified by somatic mosaicism
HP:0001508	Failure to thrive
HP:0001595	Abnormal hair morphology
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001888	Decreased total lymphocyte count
HP:0001909	Leukemia
HP:0001945	Fever
HP:0001952	Glucose intolerance
HP:0002017	Nausea and vomiting
HP:0002019	Constipation
HP:0002024	Malabsorption
HP:0002027	Abdominal pain
HP:0002028	Chronic diarrhea
HP:0002039	Anorexia
HP:0002073	Progressive cerebellar ataxia
HP:0002075	Dysdiadochokinesis
HP:0002076	Migraine
HP:0002080	Intention tremor
HP:0002110	Bronchiectasis
HP:0002167	Abnormal speech pattern
HP:0002205	Recurrent respiratory infections

GWAS associations

showing 30 of 33 associations:

Study	Trait	p-value
GCST90002381_344	Eosinophil count	3e-29
GCST010304_40	Cutaneous malignant melanoma	2e-21
GCST010303_13	Nevus count or cutaneous melanoma	4e-21
GCST90002382_319	Eosinophil percentage of white cells	8e-21
GCST010002_200	Refractive error	4e-19
GCST004624_192	Sum eosinophil basophil counts	6e-14
GCST004606_207	Eosinophil count	3e-13
GCST006462_12	Uterine fibroids	3e-12
GCST008366_17	Leukocyte telomere length	7e-12
GCST005996_55	Red blood cell count	1e-11
GCST006462_51	Uterine fibroids	3e-11
GCST007505_27	Nevus count or cutaneous melanoma	8e-11
GCST008366_9	Leukocyte telomere length	2e-10
GCST90000032_12	Myeloproliferative neoplasms	2e-10
GCST90002388_187	Lymphocyte count	6e-10
GCST000927_1	Response to metformin in type 2 diabetes (glycemic)	3e-9
GCST001267_4	Melanoma	3e-9
GCST004142_8	Melanoma	3e-9
GCST90002396_553	Mean reticulocyte volume	3e-9
GCST004600_26	Eosinophil percentage of white cells	6e-9
GCST006085_14	Prostate cancer	8e-9
GCST004710_7	Renal cell carcinoma	9e-9
GCST002318_141	Rheumatoid arthritis	1e-8
GCST002318_81	Rheumatoid arthritis	1e-8
GCST009856_33	Leukocyte telomere length	1e-8
GCST006462_52	Uterine fibroids	7e-8
GCST002990_4	Gastric adenocarcinoma (histologically verified)	2e-7
GCST007250_11	Nonunion in individuals with fractures	3e-7
GCST006959_99	Rheumatoid arthritis	4e-7
GCST002992_5	Gastric cancer	6e-7

EFO canonical traits (from GWAS)

10 canonical traits:

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

20 disease descriptors:

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
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
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
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
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
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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 451,324 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

35 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1083993	AMIODARONE HYDROCHLORIDE	4	3,298
CHEMBL1200964	AMITRIPTYLINE HYDROCHLORIDE	4	9,435
CHEMBL932	DIPYRIDAMOLE	4	52,091
CHEMBL421701	DITHIAZANINE IODIDE	4	3,409
CHEMBL249856	ENOXIMONE	4	5,236
CHEMBL1200430	ESTRADIOL ACETATE	4	1,127
CHEMBL1511	ESTRADIOL VALERATE	4	7,361
CHEMBL456	ETHACRYNIC ACID	4	20,123
CHEMBL672	FENOFIBRATE	4	42,938
CHEMBL1409	FLUVOXAMINE MALEATE	4	4,012
CHEMBL1103	FURAZOLIDONE	4	14,641
CHEMBL590	MENADIONE	4	21,230
CHEMBL405110	METHYLENE BLUE ANHYDROUS	4	114,909
CHEMBL1200938	METHYSERGIDE MALEATE	4	4
CHEMBL1670	MITOTANE	4	84,824
CHEMBL1200493	NAFTIFINE HYDROCHLORIDE	4	1,515
CHEMBL1525	PERMETHRIN	4	47,700
CHEMBL498847	SECNIDAZOLE	4	1,876
CHEMBL1717	TICLOPIDINE HYDROCHLORIDE	4	12,929
CHEMBL1256400	XYLOMETAZOLINE HYDROCHLORIDE	4	2,666
CHEMBL1879463	DACTOLISIB	3
CHEMBL599870	ALTHIAZIDE	2
CHEMBL3989870	BERZOSERTIB	2
CHEMBL1256686	CALCIMYCIN	2
CHEMBL6246	ELLAGIC ACID	2
CHEMBL1327821	ENPIROLINE	2
CHEMBL282575	ESTRADIOL BENZOATE	2
CHEMBL5314413	LARTESERTIB	2
CHEMBL8659	OLEIC ACID	2
CHEMBL1407356	OXACEPROL	2
CHEMBL11417	STREPTONIGRIN	2
CHEMBL1790006	TOLONIUM CHLORIDE	2
CHEMBL4594429	AZD-1390	1
CHEMBL4439259	AZD-7648	1
CHEMBL4647810	ELIMUSERTIB	1

Clinical evidence (CIViC)

Drug × variant × indication, from 37 curated evidence items; also 4 prognostic, 1 oncogenic. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

showing 30 of 35 predictive associations by evidence level:

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 Mutation	Talazoparib + Enzalutamide	Castration-resistant Prostate Carcinoma	Sensitivity/Response	CIViC B	EID11736
ATM Mutation	Olaparib	Solid Tumor	Sensitivity/Response	CIViC B	EID13081
ATM Mutation	Olaparib	Colorectal Cancer	Sensitivity/Response	CIViC B	EID13082
ATM Mutation	Olaparib	Pancreatic Cancer	Sensitivity/Response	CIViC B	EID13083
ATM Mutation	Olaparib	Lung Cancer	Sensitivity/Response	CIViC B	EID13084
ATM Mutation	Rucaparib	Castration-resistant Prostate Carcinoma	Sensitivity/Response	CIViC B	EID13268
ATM Underexpression	Olaparib + Paclitaxel	Stomach Cancer	Sensitivity/Response	CIViC B	EID5215
ATM Underexpression	Paclitaxel + Olaparib	Stomach Cancer	Sensitivity/Response	CIViC B	EID7708
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

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

CIViC curated variants (19)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

K293* (stop gained), F1025L (missense variant), D1930V (missense variant), E2187* (stop gained), L2427P (missense variant), F2732V (missense variant), K468FS (frameshift variant), D1682H (missense variant), A2062V (missense variant), C2488Y (missense variant), Mutation (transcription variant,loss of function variant), Underexpression, S2289* (frameshift truncation), N2875H (missense variant), c.902-1G>T, c.7089+1del, c.7515+1_2del, T2666A (missense variant), R3008C (missense variant).

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

2 annotations by evidence level (1 strongest → 4):

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

PharmGKB variants

2 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

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

6 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs1801516	cyclophosphamide, doxorubicin, fluorouracil	Toxicity	Genotypes AA + AG are associated with increased risk of Nausea when treated with cyclophosphamide, doxorubicin and fluorouracil in women with Breast Neoplasms as compared to genotype GG.	PMID:29507678
rs1801516	cyclophosphamide, doxorubicin, fluorouracil	Toxicity	Genotype AA is associated with increased risk of Vomiting when treated with cyclophosphamide, doxorubicin and fluorouracil in women with Breast Neoplasms as compared to genotypes AG + GG.	PMID:29507678
rs620815	Iodine (131I) compounds, radiotherapy	Toxicity	Genotype TT is associated with increased likelihood of gastrointestinal toxicity when treated with Iodine (131I) compounds and radiotherapy in people with Thyroid Neoplasms as compared to genotype CC.	PMID:30430914
rs11212570	Iodine (131I) compounds, radiotherapy	Toxicity	Genotypes AA + AG is associated with increased likelihood of Pain when treated with Iodine (131I) compounds and radiotherapy in people with Thyroid Neoplasms as compared to genotype GG.	PMID:30430914
rs11212617	metformin	Efficacy	Genotype AC is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to genotypes AA + CC.	PMID:34545025
rs11212570	Iodine (131I) compounds, radiotherapy	Toxicity	Genotype AG is associated with decreased likelihood of Fatigue when treated with Iodine (131I) compounds and radiotherapy in people with Thyroid Neoplasms as compared to genotype GG.	PMID:37708952

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
elrelesertib	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)

932 measured of 1309 human assays (1313 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
US20240294545, Compound A-33	IC50	0.08 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-176	IC50	0.17 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
3-[3-[4-[dideuterio(methylamino)methyl]phenyl]isoxazol-5-yl]-5-(4-isopropylsulfonylphenyl)pyrazin-2-amine	IC50	0.2 nM
8-(1,3-Dimethylpyrazol-4- yl)-1-[3-fluoro-5-(trideuterio- methoxy)-4-pyridyl]-7- methoxy-3-methyl-imidazo- [4,5-c]quinolin-2-one	IC50	0.2 nM
US20240294545, Compound A-9	IC50	0.2 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-166	IC50	0.21 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-187	IC50	0.22 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-202	IC50	0.23 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-183	IC50	0.23 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-177	IC50	0.25 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-178	IC50	0.25 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-179	IC50	0.25 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-184	IC50	0.25 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-180	IC50	0.26 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-67	IC50	0.26 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-30	IC50	0.27 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-27	IC50	0.28 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-28	IC50	0.28 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-208	IC50	0.29 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
CHEMBL5191923	IC50	0.32 nM
US20240294545, Compound A-161	IC50	0.32 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-167	IC50	0.33 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-211	IC50	0.33 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-162	IC50	0.36 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-6	IC50	0.37 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-165	IC50	0.37 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-68	IC50	0.37 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-212	IC50	0.37 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-186	IC50	0.38 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-189	IC50	0.38 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-188	IC50	0.4 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-13	IC50	0.4 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
CHEMBL5408388	IC50	0.41 nM
US20240294545, Compound A-195	IC50	0.41 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-14	IC50	0.42 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-23	IC50	0.42 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-171	IC50	0.42 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-160	IC50	0.43 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-198	IC50	0.44 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-207	IC50	0.44 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
CHEMBL6171509	IC50	0.45 nM
US20240294545, Compound A-194	IC50	0.45 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
US20240294545, Compound A-182	IC50	0.46 nM	US-20240294545: A CLASS OF FUSED RING COMPOUNDS, AND PREPARATION AND USE THEREOF
CHEMBL5429597	IC50	0.48 nM
CHEMBL4210045	IC50	0.5 nM
CHEMBL4763842	IC50	0.5 nM
CHEMBL4792191	IC50	0.5 nM
CHEMBL4763108	IC50	0.5 nM
CHEMBL4748079	IC50	0.5 nM

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

645 with measured affinity, of 1118 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
9-methoxy-3-methyl-10-(1-methylpyrazol-4-yl)-12-oxa-1,3,6-triazapentacyclo[9.7.2.04,19.07,20.013,18]icosa-4(19),5,7,9,11(20),13,15,17-octaen-2-one	2253801: Inhibition of ATM (unknown origin)	ic50	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
3-fluoro-4-[7-methoxy-3-methyl-8-(1-methylpyrazol-4-yl)-2-oxoimidazo[4,5-c]quinolin-1-yl]benzonitrile	2253562: Inhibition of ATM (unknown origin) by TR-FRET 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
9-fluoro-3-methyl-10-[6-(3-piperidin-1-ylpropoxy)-3-pyridinyl]-12-oxa-1,3,6-triazapentacyclo[9.7.2.04,19.07,20.013,18]icosa-4(19),5,7,9,11(20),13,15,17-octaen-2-one	2253801: Inhibition of ATM (unknown origin)	ic50	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
(5R)-5-ethyl-10-fluoro-2-methyl-9-[6-(3-piperidin-1-ylpropoxy)-3-pyridinyl]-7-oxa-2,4,13-triazatetracyclo[6.6.2.04,15.012,16]hexadeca-1(15),8(16),9,11,13-pentaen-3-one	2253801: Inhibition of ATM (unknown origin)	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
10-fluoro-2,5,5-trimethyl-9-[6-(3-piperidin-1-ylpropoxy)-3-pyridinyl]-2,4,7,13-tetrazatetracyclo[6.6.2.04,15.012,16]hexadeca-1(15),8(16),9,11,13-pentaen-3-one	2253801: Inhibition of ATM (unknown origin)	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

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	decreases expression, decreases reaction, increases expression, increases phosphorylation, increases reaction (+3 more)	12
Caffeine	affects cotreatment, decreases response to substance, decreases phosphorylation, decreases reaction, increases phosphorylation (+2 more)	12
Doxorubicin	decreases activity, increases phosphorylation, increases reaction, decreases expression, decreases reaction (+5 more)	9
Hydrogen Peroxide	affects reaction, affects localization, decreases reaction, increases phosphorylation, affects expression (+6 more)	8
bisphenol A	decreases expression, increases expression, increases methylation, increases phosphorylation, decreases reaction (+2 more)	7
Resveratrol	decreases reaction, increases phosphorylation, affects cotreatment, increases acetylation, increases reaction (+3 more)	7
Benzo(a)pyrene	affects response to substance, affects methylation, affects localization, affects cotreatment, increases expression (+4 more)	7
Cisplatin	affects reaction, increases expression, increases activity, affects binding, increases reaction (+6 more)	7
Arsenic Trioxide	increases reaction, affects cotreatment, increases phosphorylation, decreases expression, decreases phosphorylation (+1 more)	6
Acetylcysteine	increases phosphorylation, decreases reaction, increases expression, increases activity, increases reaction	6
sodium arsenite	increases expression, increases response to substance, increases reaction, decreases expression, affects cotreatment (+5 more)	5
Decitabine	affects reaction, increases expression, affects response to substance, affects localization, affects methylation (+3 more)	4
Arsenic	affects cotreatment, decreases expression, decreases phosphorylation, affects reaction, affects response to substance (+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	increases abundance, affects reaction, increases expression, increases ubiquitination, affects response to substance (+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 reaction, increases phosphorylation, increases expression, decreases activity	3
Copper	affects cotreatment, decreases phosphorylation, increases abundance, increases phosphorylation, increases response to substance (+2 more)	3
Estradiol	decreases expression, increases expression	3
Valproic Acid	decreases expression, decreases methylation	3
Nanotubes, Carbon	decreases methylation, increases expression, decreases expression	3
lasiocarpine	decreases expression, increases metabolic processing	2
trichostatin A	decreases expression, increases expression, affects cotreatment	2
zinc chromate	affects expression, affects phosphorylation, increases 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

336 cell lines: 143 transformed cell line, 117 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)

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

showing 60 of 598 trials:

NCT	Phase	Status	Title
NCT00365508	Phase 4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	Phase 4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	Phase 4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00666978	Phase 4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT01038154	Phase 4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01234272	Phase 4	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	Phase 4	TERMINATED	A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer
NCT01271582	Phase 4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01401075	Phase 4	COMPLETED	RCT With Adjuvant Mistletoe Treatment in Gastric Cancer Patients
NCT01471756	Phase 4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01766765	Phase 4	UNKNOWN	Early Jejunostomy Nutrition Minimizes Time to Chemotherapy
NCT01910948	Phase 4	UNKNOWN	Perioperative Application of Omega-3 Polyunsaturated Fatty Acids in Gastric Cancer Patients
NCT01927328	Phase 4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	Phase 4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT01962376	Phase 4	UNKNOWN	Preoperative Chemotherapy With Bevacizumab For Potentially Resectable Gastric Cancer With Liver Metastasis
NCT02047994	Phase 4	RECRUITING	Multicentric Randomized Study of H. Pylori Eradication and Pepsinogen Testing for Prevention of Gastric Cancer Mortality
NCT02366819	Phase 4	SUSPENDED	Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
NCT02401971	Phase 4	UNKNOWN	Irinotecan Plus Thalidomide in Second Line Advanced Gastric Cancer
NCT02458573	Phase 4	COMPLETED	Comparison of the Effects of Continuous Epidural Analgesia and Continuous Intravenous Analgesia on Postoperative Bowel Movement in Patients Undergoing Laparoscopic Gastrectomy
NCT02638584	Phase 4	COMPLETED	Effects of Ilaprazole on Ulcer Healing Rate and Prevention of Gastrointestinal Bleeding in the Patients Undergone ESD.
NCT02776527	Phase 4	UNKNOWN	A Clinical Trial of Maintenance Treatment of Apatinib in Advanced Gastric Cancer Patients Have Completed Postoprative Adjuvant Chemotherapy
NCT03384511	Phase 4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03550482	Phase 4	COMPLETED	Oncoxin® and Quality of Life in Cancer Patients
NCT03609892	Phase 4	COMPLETED	Helicobacter Rescue Therapy With Berberine Plus Amoxicillin Quadruple Therapy Versus Tetracycline Plus Furazolidone Quadruple Therapy
NCT03642093	Phase 4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03733639	Phase 4	UNKNOWN	Tisseel® as a Reinforcement of Esophagojejunal Anastomoses
NCT04168346	Phase 4	NOT_YET_RECRUITING	Preoperative Intravenous Iron Therapy in Patients With Gastric Cancer
NCT04209933	Phase 4	COMPLETED	Helicobacter Pylori Eradication With Different Bismuth Quadruple Therapies
NCT04591028	Phase 4	WITHDRAWN	A Study to Evaluate Indocyanine Green Lymphangiography to Improve Lymphadenectomy in Gastric Cancer Patients
NCT04607057	Phase 4	UNKNOWN	Supplemental Parenteral Nutrition During Postgastrectomy in Nutritionally at Risk Patient
NCT04660123	Phase 4	COMPLETED	A Real World Study of Bismuth Colloidal Pectin Granules Quadruple Therapy for H. Pylori Eradication
NCT04678492	Phase 4	COMPLETED	Helicobacter Rescue Therapy With High-dose Esomeprazole and Amoxicillin Dual Therapy Versus Bismuth-containing Quadruple Therapy
NCT04697186	Phase 4	COMPLETED	Helicobacter Pylori Eradication With Berberine Plus Amoxicillin Triple Therapy Versus Bismuth-containing Quadruple Therapy
NCT05029453	Phase 4	UNKNOWN	Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy
NCT05183126	Phase 4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT05229809	Phase 4	UNKNOWN	Clinical Trial of Yiqi Wenyang Jiedu Prescription in the Prevention and Treatment of Postoperative Metastasis and Recurrence of Gastric Cancer
NCT05354856	Phase 4	TERMINATED	The Effect of Chemoradiotherapy on Gastric Perfusion in Patients With Gastric Cancer.
NCT05410535	Phase 4	COMPLETED	To Evaluate Efficacy of Ursodeoxycholic Acid (UDCA) for the Prevention of Gallstone Formation After Gasterectomy
NCT05498766	Phase 4	NOT_YET_RECRUITING	Effect and Safety of Huaier Granule Versus SOX Regimen in Gastric Cancer Patients
NCT05518929	Phase 4	COMPLETED	Hypoxia During Gastroenterological Endoscope Procedures Sedated With Ciprofol In Overweight Or Obesity Patients
NCT05742568	Phase 4	COMPLETED	Effects of High-dose Dual Therapy and Bismuth Quadruple Therapy for Helicobacter Pylori Eradication on Intestinal Microecology
NCT06169410	Phase 4	UNKNOWN	Ramucirumab Combined With Nab-paclitaxel, Lobaplatin, and S-1 in Neoadjuvant Transformation Therapy for Advanced Gastric Cancer
NCT06499610	Phase 4	NOT_YET_RECRUITING	Clinical Study of Irinotecan Liposome Combination Therapy for Advanced Gastric Cancer
NCT07124351	Phase 4	RECRUITING	Intraoperative Imaging of Gastrointestinal Malignancies Using Pafolacianine (CYTALUX™)
NCT07139366	Phase 4	RECRUITING	Saccharomyces Boulardii Combined With Bismuth Quadruple Therapy for Helicobacter Pylori Rescue Treatment
NCT07224035	Phase 4	ACTIVE_NOT_RECRUITING	Helicobacter Pylori Screening and Treatment in the At-risk South Florida Community- AIM 1
NCT07224048	Phase 4	ACTIVE_NOT_RECRUITING	Helicobacter Pylori Screening and Treatment in the At-risk South Florida Community-AIM 2
NCT07467174	Phase 4	NOT_YET_RECRUITING	RCT Comparing Reduced-port Robotic and Conventional Laparoscopic Subtotal Gastrectomy
NCT07502027	Phase 4	NOT_YET_RECRUITING	A Clinical Study of Iparomlimab and Tuvonralimab Combined With SOX Following Heterogeneous Radiotherapy as First-line Treatment for Unresectable Locally Advanced or Metastatic HER2-negative Gastric or Gastroesophageal Junction Adenocarcinoma
NCT07772453	Phase 4	NOT_YET_RECRUITING	Ferric Carboxymaltose Versus Iron Sucrose for Iron Deficiency Anemia After Radical Gastrectomy for Gastric Cancer
NCT01052623	Phase 4	UNKNOWN	Status of Growth Hormone/ Insulin-like Growth Factor-1 (GH/IGF-1) Axis and Growth Failure in Ataxia Telangiectasia (AT)
NCT02733679	Phase 4	COMPLETED	Response of Individuals With Ataxia-Telangiectasia to Metformin and Pioglitazone
NCT00014638	Phase 4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	Phase 4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	Phase 4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	Phase 4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	Phase 4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	Phase 4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	Phase 4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)

Predicted chemistry — Sugi Predict

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