ATR Gene

Name	ATR serine/threonine kinase
Description	The protein encoded by this gene is a serine/threonine kinase and DNA damage sensor, activating cell cycle checkpoint signaling upon DNA stress. The encoded protein can phosphorylate and activate several proteins involved in the inhibition of DNA replication and mitosis, and can promote DNA repair, recombination, and apoptosis. This protein is also important for fragile site stability and centrosome duplication. Defects in this gene are a cause of Seckel syndrome 1. [provided by RefSeq, Aug 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The ataxia‐telangiectasia and Rad3‐related (ATR) kinase is a master regulator of the cellular response to replication stress and DNA damage. Activated primarily by stretches of single‐stranded DNA that become coated with replication protein A, ATR is recruited to stalled replication forks and other damage sites through a network of sensor and adaptor proteins—including TopBP1, RHINO in complex with the 9–1–1 clamp, and ETAA1—that serve to amplify its signaling output."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Once activated, ATR phosphorylates several key substrates such as CHK1, SMARCAL1, and components of the replisome including MCM2, thereby enforcing cell cycle checkpoints, stabilizing replication forks, and preventing deleterious fork collapse."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition to safeguarding replication, ATR contributes to the repair of DNA double‐strand breaks generated during replication by promoting extensive end resection and facilitating homologous recombination in S and G2 phases—a process that involves CtIP‐dependent recruitment of ATR to damage sites."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " ATR’s influence extends to telomere biology, where it becomes activated upon telomere deprotection when normal capping by shelterin components is compromised (for example, when POT1 function is lost), thus integrating telomere integrity into the broader DNA damage response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " During meiosis, ATR is essential for phosphorylating H2AX within the sex body, ensuring proper chromosomal silencing and segregation in the absence of ATM function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, ATR signaling can modulate immunomodulatory processes by regulating factors such as PD-L1 following DNA double-strand break induction"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and it plays a noncanonical role at the nuclear envelope where its activation in response to mechanical forces helps maintain nuclear integrity and proper chromatin dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Finally, pharmacological inhibition of ATR has been shown to be synthetically lethal in tumor cells deficient in ATM or p53, underscoring its critical function in sustaining genomic stability under replicative stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jacob Falck, Julia Coates, Stephen P Jackson "}, {"type": "b", "children": [{"type": "t", "text": "Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature03442"}], "href": "https://doi.org/10.1038/nature03442"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15758953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15758953"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Joshua C Saldivar, David Cortez, Karlene A Cimprich "}, {"type": "b", "children": [{"type": "t", "text": "The essential kinase ATR: ensuring faithful duplication of a challenging genome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Mol Cell Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nrm.2017.67"}], "href": "https://doi.org/10.1038/nrm.2017.67"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28811666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28811666"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Cecilia Cotta-Ramusino, E Robert McDonald, Kristen Hurov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1203430"}], "href": "https://doi.org/10.1126/science.1203430"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21659603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21659603"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Frank B Couch, Carol E Bansbach, Robert Driscoll, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATR phosphorylates SMARCAL1 to prevent replication fork collapse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.214080.113"}], "href": "https://doi.org/10.1101/gad.214080.113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23873943"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23873943"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Alessia Montagnoli, Barbara Valsasina, Deborah Brotherton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of Mcm2 phosphorylation sites by S-phase-regulating kinases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M512921200"}], "href": "https://doi.org/10.1074/jbc.M512921200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16446360"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16446360"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Alessandro A Sartori, Claudia Lukas, Julia Coates, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human CtIP promotes DNA end resection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06337"}], "href": "https://doi.org/10.1038/nature06337"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17965729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17965729"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Eros Lazzerini Denchi, Titia de Lange "}, {"type": "b", "children": [{"type": "t", "text": "Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06065"}], "href": "https://doi.org/10.1038/nature06065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17687332"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17687332"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Rachel Litman Flynn, Richard C Centore, Roderick J O'Sullivan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09772"}], "href": "https://doi.org/10.1038/nature09772"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21399625"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21399625"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Simone Difilippantonio, Arkady Celeste, Oscar Fernandez-Capetillo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of Nbs1 in the activation of the Atm kinase revealed in humanized mouse models."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1270"}], "href": "https://doi.org/10.1038/ncb1270"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15965469"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15965469"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Marina A Bellani, Peter J Romanienko, Damian A Cairatti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPO11 is required for sex-body formation, and Spo11 heterozygosity rescues the prophase arrest of Atm-/- spermatocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.02466"}], "href": "https://doi.org/10.1242/jcs.02466"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15998665"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15998665"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Hiro Sato, Atsuko Niimi, Takaaki Yasuhara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-017-01883-9"}], "href": "https://doi.org/10.1038/s41467-017-01883-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29170499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29170499"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Amit Kumar, Michele Mazzanti, Martin Mistrik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATR mediates a checkpoint at the nuclear envelope in response to mechanical stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2014.05.046"}], "href": "https://doi.org/10.1016/j.cell.2014.05.046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25083873"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25083873"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Marwan Kwok, Nicholas Davies, Angelo Agathanggelou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATR inhibition induces synthetic lethality and overcomes chemoresistance in TP53- or ATM-defective chronic lymphocytic leukemia cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2015-05-644872"}], "href": "https://doi.org/10.1182/blood-2015-05-644872"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26563132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26563132"}]}]}]}
Synonyms	FCTCS, MEC1, FRP1, SCKL, SCKL1
Proteins	ATR_HUMAN
NCBI Gene ID	545
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ATR has 11,577 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 119 datasets.

Click the + buttons to view associations for ATR from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ATR Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by ATR gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ATR gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of ATR gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ATR gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of ATR gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ATR gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving ATR protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ATR gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ATR gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ATR gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of ATR gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with ATR gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ATR protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ATR gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ATR gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ATR gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of ATR gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with ATR gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of ATR gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ATR gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ATR protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ATR protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	CORUM Protein Complexes	protein complexs containing ATR protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of ATR gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ATR gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ATR gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ATR gene/protein from the curated CTD Gene-Disease Associations dataset.
	DGIdb Drug Targets 2026	interacting drugs for ATR protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ATR gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ATR gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with ATR gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with ATR gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ATR gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ATR gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ATR gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ATR gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing ATR from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ATR gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with ATR gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of ATR gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.