# ATM

Source: https://onco.cc/targets/atm/  
OnCo record `atm` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: ATM serine/threonine kinase; Serine-protein kinase ATM; TEL1; TELO1
- Tags: cancer-genes-wave
- Symbol: ATM
- Class: kinase
- 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).
- Where found: 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

## 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).

## Sources

- HGNC HGNC:795: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:795
- UniProt Q13315: https://www.uniprot.org/uniprotkb/Q13315/entry
- NCBI Gene 472: https://www.ncbi.nlm.nih.gov/gene/472
- Ensembl ENSG00000149311: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000149311

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Mantle cell lymphoma](https://onco.cc/cancers/mantle-cell-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- pathways: [Double-strand break repair: HR versus end joining](https://onco.cc/pathways/homologous-recombination-repair/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [Synthetic lethality: paired dependencies](https://onco.cc/pathways/synthetic-lethality-map/), [The p53 network (guardian of the genome)](https://onco.cc/pathways/p53-mdm2-axis/)
- key papers: [Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer](https://onco.cc/key-papers/paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018/), [Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference](https://onco.cc/key-papers/paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021/), [Circulating tumour DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer](https://onco.cc/key-papers/paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018/), [Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-shindo-germline-sporadic-pancreatic-jco-2017/), [Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms](https://onco.cc/key-papers/paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021/), [Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection](https://onco.cc/key-papers/paper-park-hrd-pancreatic-platinum-ccr-2020/), [Genomics of lethal prostate cancer at diagnosis and castration resistance](https://onco.cc/key-papers/paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020/), [Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer](https://onco.cc/key-papers/paper-yurgelun-germline-second-hits-resected-pancreatic-genet-med-2019/), [Inherited DNA-repair gene mutations in men with metastatic prostate cancer](https://onco.cc/key-papers/paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016/), [Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer](https://onco.cc/key-papers/paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018/), [Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium](https://onco.cc/key-papers/paper-caps-consortium-surveillance-recommendations-gut-2020/), [Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes](https://onco.cc/key-papers/paper-biankin-pancreatic-exomes-axon-guidance-nature-2012/), [Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines](https://onco.cc/key-papers/paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019/), [PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations](https://onco.cc/key-papers/paper-profound-nejm-2020/), [Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms](https://onco.cc/key-papers/paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018/), [Recurrent R-spondin fusions in colon cancer](https://onco.cc/key-papers/paper-seshagiri-rspo-fusions-colon-nature-2012/), [SU2C-PCF: integrative clinical genomics of advanced prostate cancer](https://onco.cc/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/), [Substantial interindividual and limited intraindividual genomic diversity among tumours from men with metastatic prostate cancer](https://onco.cc/key-papers/paper-kumar-interindividual-genomic-diversity-metastatic-prostate-nat-med-2016/), [The mutational landscape and actionable targets of gallbladder cancer: an ancestry-informed and comparative analysis of a Chilean population](https://onco.cc/key-papers/paper-erices-chilean-gallbladder-landscape-front-oncol-2025/), [TOPARP-A: DNA-repair defects and olaparib in metastatic prostate cancer](https://onco.cc/key-papers/paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015/), [TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-fizazi-triton3-rucaparib-nejm-2023/), [Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer](https://onco.cc/key-papers/paper-roberts-familial-pancreatic-whole-genome-cancer-discov-2016/)
- terms: [Checkpoint (two meanings)](https://onco.cc/terms/checkpoint/), [Familial pancreatic cancer and inherited risk (who qualifies for surveillance)](https://onco.cc/terms/familial-pancreatic-cancer/), [Genome-wide loss of heterozygosity (gLOH)](https://onco.cc/terms/genome-wide-loss-of-heterozygosity/), [t(11;14), cyclin D1 and SOX11](https://onco.cc/terms/cyclin-d1-t11-14/), [Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters](https://onco.cc/terms/prostate-hrr-eligibility/)
- ideas: [Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later](https://onco.cc/ideas/idea-prostate-hrr-testing-at-metastatic-diagnosis/)
- trials: [TRITON3](https://onco.cc/trials/triton3/)
- biomarkers: [Circulating tumour DNA fraction (and what a negative plasma result means)](https://onco.cc/biomarkers/ctdna-tumour-fraction/), [Homologous recombination repair gene mutation in prostate cancer](https://onco.cc/biomarkers/hrr-gene-mutation/)

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JSON: https://onco.cc/api/v1/entities/atm.json