ATM
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
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.
External identifiers
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)
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).
- 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
Notes
top- 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.
Latest papers
topQuery 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.
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