ATM
Chr 11ADSomaticARATM serine/threonine kinase
Also known as: AT1, ATA, ATC, ATD, ATDC, ATE, TEL1, TELO1
The ATM protein is a cell cycle checkpoint kinase that phosphorylates key downstream proteins including p53, BRCA1, and CHK2 to control DNA damage response and maintain genome stability. Biallelic mutations cause ataxia-telangiectasia, an autosomal recessive disorder, while heterozygous mutations confer dominant susceptibility to breast cancer. The pathogenic mechanism involves dominant-negative effects for cancer predisposition and loss of function for ataxia-telangiectasia.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ATM · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Phase 1/1B Study of ST-01156, a Small Molecule RBM39 Degrader, in Patients With Advanced Solid Malignancies
RECRUITINGComprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO
ACTIVE NOT RECRUITINGA Study of RP-3500 in Combination With Standard Radiation Therapy in People With Solid Tumor Cancer
ACTIVE NOT RECRUITINGA Prospective Registry for Patients at High-Risk for Pancreatic Cancer
RECRUITINGHigh Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers
RECRUITINGCombination Therapy in Cancers With Mutations in DNA Repair Genes
RECRUITINGPROMISE Registry: A Prostate Cancer Registry of Outcomes and Germline Mutations for Improved Survival and Treatment Effectiveness
RECRUITINGKPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II
RECRUITINGLow Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion
ACTIVE NOT RECRUITINGPrevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History
NOT YET RECRUITINGNordicTrip, a Translational Study of Preoperative Chemotherapy in TNBC
ACTIVE NOT RECRUITINGPancreatic Cancer Registry: For Any Person With a Personal or Family History
RECRUITINGExternal Resources
Links to major genomics databases and tools