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ATM is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
Serine/threonine protein kinase which activates checkpoint signalling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionising ultraviolet A light (UVA), thereby acting as a DNA damage sensor. Recognises the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism.
CIViC holds 61 clinical evidence items and 0 assertions across 38 variants, naming Doxorubicin, Olaparib, Temozolomide and Paclitaxel and others. Open Targets scores its association with cancer at 0.92 (direct and indirect evidence; datatypes genetic literature 0.85, affected pathway 0.93, literature 1.00, genetic association 0.95, somatic mutation 0.98, animal model 0.42). IntOGen calls it a driver in 50 cohorts (14 activating, 36 loss-of-function), covering Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Renal Clear Cell Carcinoma, Cholangiocarcinoma, Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma, Colon Adenocarcinoma and others.
In plain words · ATM is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
ATM is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
Serine/threonine protein kinase which activates checkpoint signalling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionising ultraviolet A light (UVA), thereby acting as a DNA damage sensor.
No product in this corpus aims at ATM yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA ATM: RNA low tissue specificity; high antibody staining in 31 normal tissues; highest cancer staining lymphoma (12 of 12 high). Distribution: 9 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Biliary tract cancer (all types), Breast cancer (all types), Colorectal cancer, Lymphoma, Prostate cancer, Leukaemia, Gastric & gastro-oesophageal junction cancer and more); Open Targets associates it with 26 specific cancer types at or above 0.5 (ataxia telangiectasia, breast cancer, breast carcinoma, hereditary breast carcinoma, ATM-related cancer predisposition, urinary bladder carcinoma and more). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt Q13315; CIViC gene ATM; IntOGen ATM; Human Protein Atlas ATM tissue; Open Targets ENSG00000149311 associations
First described 1995. Earliest sequence paper UniProt cites for the protein: Savitsky et al, Hum. Mol. Genet, 1995, "The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species". Source.
Sources: HGNC HGNC:795 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q13315 (protein name, function text, keywords and locations (REST API)); CIViC gene ATM (61 evidence items, 0 assertions, 38 variants; diseases: Chronic Lymphocytic Leukaemia, Prostate Cancer, Lymphoma, Castration-resistant Prostate Carcinoma, Lung Cancer and 15 more (GraphQL API, CC0)); Open Targets ENSG00000149311 (association with cancer (MONDO_0004992) 0.92; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.61, colorectal cancer 0.78, gastric cancer 0.74, prostate cancer 0.76, urinary bladder cancer 0.72, renal cell carcinoma 0.57 (GraphQL API, CC0)); IntOGen ATM (driver in 50 cohorts (Act 14, LoF 36); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Serine/threonine protein kinase which activates checkpoint signalling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionising ultraviolet A light (UVA), thereby acting as a DNA damage sensor. Recognises 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. Location: Nucleus; Cytoplasmic vesicle; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Peroxisome matrix (UniProt). Locus 11q22.3 (HGNC).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adipose tissue, Cerebellum, Cerebral cortex, Heart muscle, Hippocampus, Liver, Salivary gland, Skeletal muscle.
Medium only: liver cancer, lung cancer, melanoma, pancreatic cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Gallbladder cancer | 7-16% | Mutation | Mutation in 16 of 244 samples, 6.6%, in cBioPortal gbc_mskcc_2022 and 16 of 103, 15.5%, in gbc_msk_2018; among the actionable variants in the Chilean cohort (Erices 2025). | cBioPortal (TCGA) |
| Prostate cancer | 3-11% | Inactivating mutation, germline or somatic | cBioPortal mutation: 20 of 494, 4.0%, in prad_tcga_pan_can_atlas_2018; 8 of 477, 1.7%, in prad_cpcg_2017; 38 of 1,013, 3.8%, in prad_p1000; 24 of 424, 5.7%, in prad_mcspc_mskcc_2020; 96 of 2,260, 4.2%, in prostate_msk_2024; 27 of 444, 6.1%, in prad_su2c_2019; 16 of 141, 11.3%, in prad_fhcrc. Germline: 11 of 692 men with metastatic disease, 1.6% (Pritchard 2016). | cBioPortal (TCGA) |
| Pancreatic ductal adenocarcinoma | 1.2-2.3% | Germline pathogenic variant (somatic in a further 3 to 4%) | 2.3% of 3,030 against 0.37% of controls, odds ratio 5.71 (Hu 2018); 10 of 854, 1.2% (Shindo 2017); ATM among the new significantly mutated genes in 99 exomes (Biankin 2012). Tumour sequencing: 69 of 2,336, 3.0%, in pdac_msk_2024; 14 of 383, 3.7%, in paad_qcmg_uq_2016; 8 of 179, 4.5%, in paad_tcga_pan_can_atlas_2018 (cBioPortal). Germline ATM carriers with one affected first-degree relative became eligible for CAPS surveillance in 2020 (Goggins 2020). | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Chile has the world's highest gallbladder cancer mortality and until this paper almost no tumour genomics; the lower TP53 rate and high TSC2 and NOTCH1 hint at a different mutational grammar, but the panel and sample size mean the figures need replication.
The randomised proof for PARP inhibition in BRCA-altered prostate cancer, and the clearest evidence that the homologous recombination repair gene list should not be used as a single yes-or-no test. ATM-altered disease needs a different answer, and does not yet have one.
It identifies a way that a good test produces a wrong answer, and it names the fix. Any plasma repair-gene result used to decide on a PARP inhibitor should be run with a paired blood control, or an older man may be treated for a marrow clone rather than for his prostate cancer.
It established plasma profiling as a routine alternative to tissue for the BRCA question in advanced prostate cancer, with a sensible rule attached: if plasma finds nothing actionable, go back to tissue. It also documents at scale both the extra resistance information plasma gives and the clonal haematopoiesis noise that comes with it.
It defines who a homologous recombination result should send to platinum: core-gene and biallelic carriers, germline or somatic, rather than any repair-gene variant.
It splits the alterations into two groups with different practical meanings. The repair defects are present at diagnosis at close to their castration-resistant prevalence, so testing early is worthwhile; AR, TP53 and RB1 changes accumulate later, so a diagnostic sample does not answer questions about the disease in front of you at relapse.
The rulebook behind the CAPS cohorts and the UK EUROPAC programme; it is also the reason surveillance for carriers is not yet a routine NHS service, because the consortium itself asked for it to stay within research until benefit was shown.
Germline and tumour testing for homologous recombination repair genes is now standard in metastatic prostate cancer, and olaparib is approved for BRCA-mutated disease after a hormonal agent.
Query for this target: (TITLE:"ATM" OR ABSTRACT:"ATM" OR TITLE:"ATM serine/threonine kinase" OR ABSTRACT:"ATM serine/threonine kinase" OR TITLE:"Serine-protein kinase ATM" OR ABSTRACT:"Serine-protein kinase ATM" OR TITLE:"TEL1" OR ABSTRACT:"TEL1" OR TITLE:"TELO1" OR ABSTRACT:"TELO1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about ATM, not a curated reading list.
Shares Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference, Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines, Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms.
Shares Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer, Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms, Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma, Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection.
Shares Genomics of lethal prostate cancer at diagnosis and castration resistance, PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations, Genome-wide loss of heterozygosity (gLOH), Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later.
Shares Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer, Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer, Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma, Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.
Shares Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer, Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms, Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma, Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer.
Shares Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer, Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma, Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference.
Shares Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, TRITON3, Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters, PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations.
Shares PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations, TOPARP-A: DNA-repair defects and olaparib in metastatic prostate cancer, TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer, Genome-wide loss of heterozygosity (gLOH).