{"entity":{"id":"atm","kind":"target","name":"ATM","aka":["ATM serine/threonine kinase","Serine-protein kinase ATM","TEL1","TELO1"],"tldr":"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.","summary":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:795","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:795"},{"label":"UniProt Q13315","url":"https://www.uniprot.org/uniprotkb/Q13315/entry"},{"label":"NCBI Gene 472","url":"https://www.ncbi.nlm.nih.gov/gene/472"},{"label":"Ensembl ENSG00000149311","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000149311"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["breast-cancer","colorectal","non-hodgkin-lymphoma","prostate","leukaemia","gastric","urothelial","ovarian","pancreatic","gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","p53-cell-cycle","p53-mdm2-axis","synthetic-lethality-map"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018","paper-shindo-germline-sporadic-pancreatic-jco-2017","paper-biankin-pancreatic-exomes-axon-guidance-nature-2012","paper-caps-consortium-surveillance-recommendations-gut-2020","paper-park-hrd-pancreatic-platinum-ccr-2020","paper-erices-chilean-gallbladder-landscape-front-oncol-2025","paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021"],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 14 therapies; IntOGen calls it an activating (Act) driver in 14 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 36 cohorts; CIViC holds 61 clinical evidence items on its variants; UniProt keyword \"DNA damage\". Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Haematologic Cancer.","Pancreatic ductal adenocarcinoma: germline variants in 1.2 to 2.3% with an odds ratio of 5.71, the second commonest pancreatic risk gene after BRCA2 (Hu 2018, Shindo 2017); somatic or germline ATM mutations appear in 3 to 5% of tumours (cBioPortal). ATM is a non-core homologous recombination gene, so platinum benefit is less clear than for BRCA1, BRCA2 and PALB2 (Park 2020), but ATM carriers with one affected first-degree relative are eligible for surveillance (Goggins 2020)."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"ATM","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker","dna-repair"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:795","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:795","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q13315","url":"https://www.uniprot.org/uniprotkb/Q13315/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene ATM","url":"https://civicdb.org/features/69","note":"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)"},{"label":"Open Targets ENSG00000149311","url":"https://platform.opentargets.org/target/ENSG00000149311/associations","note":"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)"},{"label":"IntOGen ATM","url":"https://www.intogen.org/search?gene=ATM","note":"driver in 50 cohorts (Act 14, LoF 36); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"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.)","specificitySources":[{"label":"UniProt Q13315","url":"https://www.uniprot.org/uniprotkb/Q13315/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene ATM","url":"https://civicdb.org/features/69","note":"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)"},{"label":"IntOGen ATM","url":"https://www.intogen.org/search?gene=ATM","note":"driver in 50 cohorts (Act 14, LoF 36); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas ATM tissue","url":"https://www.proteinatlas.org/ENSG00000149311-ATM/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000149311 associations","url":"https://platform.opentargets.org/target/ENSG00000149311/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:795","ensembl":"ENSG00000149311","uniprot":"Q13315","entrez":"472","firstDescribed":1995,"firstDescribedBasis":"sequence","firstDescribedNote":"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\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8589678/","biology":"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).","whereFound":["Breast cancer: Open Targets association 0.84 with breast cancer (MONDO_0007254); IntOGen driver in 2 cohorts (BRCA)","Colorectal cancer: Open Targets association 0.78 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease","Non-Hodgkin lymphoma: Open Targets association 0.78 with non-Hodgkin lymphoma (MONDO_0018908); CIViC evidence names this disease","Prostate cancer: Open Targets association 0.76 with prostate cancer (MONDO_0008315); CIViC evidence names this disease","Leukaemia: Open Targets association 0.75 with leukaemia (MONDO_0005059)","Gastric & gastro-oesophageal junction cancer: Open Targets association 0.74 with gastric cancer (MONDO_0001056); CIViC evidence names this disease","Pancreatic ductal adenocarcinoma: germline pathogenic variant (somatic in a further 3 to 4%) 1.2-2.3%","Gallbladder cancer: mutation 7-16%","Prostate cancer: inactivating mutation, germline or somatic 3-11% depending on disease state"],"targetClass":"kinase","prevalence":[{"cancerId":"pancreatic","pct":"1.2-2.3","measure":"Germline pathogenic variant (somatic in a further 3 to 4%)","source":"https://doi.org/10.1001/jama.2018.6228","note":"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)."},{"cancerId":"gallbladder","pct":"7-16","measure":"Mutation","source":"https://www.cbioportal.org/study/summary?id=gbc_mskcc_2022","note":"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)."},{"cancerId":"prostate","pct":"3-11","measure":"Inactivating mutation, germline or somatic","source":"https://www.cbioportal.org/study/summary?id=prad_tcga_pan_can_atlas_2018","note":"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)."}]},"route":"/targets/atm/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"pathway":[{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"},{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"},{"id":"synthetic-lethality-map","kind":"pathway","name":"Synthetic lethality: paired dependencies","route":"/pathways/synthetic-lethality-map/"},{"id":"p53-mdm2-axis","kind":"pathway","name":"The p53 network (guardian of the genome)","route":"/pathways/p53-mdm2-axis/"}],"paper":[{"id":"paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018","kind":"paper","name":"Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer","route":"/key-papers/paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018/"},{"id":"paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021","kind":"paper","name":"Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference","route":"/key-papers/paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021/"},{"id":"paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018","kind":"paper","name":"Circulating tumour DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer","route":"/key-papers/paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018/"},{"id":"paper-shindo-germline-sporadic-pancreatic-jco-2017","kind":"paper","name":"Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma","route":"/key-papers/paper-shindo-germline-sporadic-pancreatic-jco-2017/"},{"id":"paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021","kind":"paper","name":"Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms","route":"/key-papers/paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021/"},{"id":"paper-park-hrd-pancreatic-platinum-ccr-2020","kind":"paper","name":"Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection","route":"/key-papers/paper-park-hrd-pancreatic-platinum-ccr-2020/"},{"id":"paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020","kind":"paper","name":"Genomics of lethal prostate cancer at diagnosis and castration resistance","route":"/key-papers/paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020/"},{"id":"paper-yurgelun-germline-second-hits-resected-pancreatic-genet-med-2019","kind":"paper","name":"Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer","route":"/key-papers/paper-yurgelun-germline-second-hits-resected-pancreatic-genet-med-2019/"},{"id":"paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","kind":"paper","name":"Inherited DNA-repair gene mutations in men with metastatic prostate cancer","route":"/key-papers/paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016/"},{"id":"paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018","kind":"paper","name":"Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer","route":"/key-papers/paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018/"},{"id":"paper-caps-consortium-surveillance-recommendations-gut-2020","kind":"paper","name":"Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium","route":"/key-papers/paper-caps-consortium-surveillance-recommendations-gut-2020/"},{"id":"paper-biankin-pancreatic-exomes-axon-guidance-nature-2012","kind":"paper","name":"Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes","route":"/key-papers/paper-biankin-pancreatic-exomes-axon-guidance-nature-2012/"},{"id":"paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019","kind":"paper","name":"Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines","route":"/key-papers/paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019/"},{"id":"paper-profound-nejm-2020","kind":"paper","name":"PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations","route":"/key-papers/paper-profound-nejm-2020/"},{"id":"paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018","kind":"paper","name":"Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms","route":"/key-papers/paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018/"},{"id":"paper-seshagiri-rspo-fusions-colon-nature-2012","kind":"paper","name":"Recurrent R-spondin fusions in colon cancer","route":"/key-papers/paper-seshagiri-rspo-fusions-colon-nature-2012/"},{"id":"paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","kind":"paper","name":"SU2C-PCF: integrative clinical genomics of advanced prostate cancer","route":"/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/"},{"id":"paper-kumar-interindividual-genomic-diversity-metastatic-prostate-nat-med-2016","kind":"paper","name":"Substantial interindividual and limited intraindividual genomic diversity among tumours from men with metastatic prostate cancer","route":"/key-papers/paper-kumar-interindividual-genomic-diversity-metastatic-prostate-nat-med-2016/"},{"id":"paper-erices-chilean-gallbladder-landscape-front-oncol-2025","kind":"paper","name":"The mutational landscape and actionable targets of gallbladder cancer: an ancestry-informed and comparative analysis of a Chilean population","route":"/key-papers/paper-erices-chilean-gallbladder-landscape-front-oncol-2025/"},{"id":"paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015","kind":"paper","name":"TOPARP-A: DNA-repair defects and olaparib in metastatic prostate cancer","route":"/key-papers/paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015/"},{"id":"paper-fizazi-triton3-rucaparib-nejm-2023","kind":"paper","name":"TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer","route":"/key-papers/paper-fizazi-triton3-rucaparib-nejm-2023/"},{"id":"paper-roberts-familial-pancreatic-whole-genome-cancer-discov-2016","kind":"paper","name":"Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer","route":"/key-papers/paper-roberts-familial-pancreatic-whole-genome-cancer-discov-2016/"}],"term":[{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"},{"id":"familial-pancreatic-cancer","kind":"term","name":"Familial pancreatic cancer and inherited risk (who qualifies for surveillance)","route":"/terms/familial-pancreatic-cancer/"},{"id":"genome-wide-loss-of-heterozygosity","kind":"term","name":"Genome-wide loss of heterozygosity (gLOH)","route":"/terms/genome-wide-loss-of-heterozygosity/"},{"id":"cyclin-d1-t11-14","kind":"term","name":"t(11;14), cyclin D1 and SOX11","route":"/terms/cyclin-d1-t11-14/"},{"id":"prostate-hrr-eligibility","kind":"term","name":"Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters","route":"/terms/prostate-hrr-eligibility/"}],"idea":[{"id":"idea-prostate-hrr-testing-at-metastatic-diagnosis","kind":"idea","name":"Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later","route":"/ideas/idea-prostate-hrr-testing-at-metastatic-diagnosis/"}],"trial":[{"id":"triton3","kind":"trial","name":"TRITON3","route":"/trials/triton3/"}],"biomarker":[{"id":"ctdna-tumour-fraction","kind":"biomarker","name":"Circulating tumour DNA fraction (and what a negative plasma result means)","route":"/biomarkers/ctdna-tumour-fraction/"},{"id":"hrr-gene-mutation","kind":"biomarker","name":"Homologous recombination repair gene mutation in prostate cancer","route":"/biomarkers/hrr-gene-mutation/"}]}}