ATR (ATR checkpoint kinase)

Gene

• Entrez ID: 545
• Gene name: ATR checkpoint kinase
• Gene symbol: ATR
• Synonyms (NCBI Gene): FCTCS, FRP1, MEC1, SCKL, SCKL1
• Chromosome: 3
• Chromosome location: 3q23
• Summary: 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 replicat

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28910273	A>C	Likely-benign, conflicting-interpretations-of-pathogenicity	Non coding transcript variant, genic downstream transcript variant, missense variant, downstream transcript variant, coding sequence variant
rs77208665	T>C	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, non coding transcript variant
rs141783863	A>G	Conflicting-interpretations-of-pathogenicity, uncertain-significance, likely-benign	Missense variant, non coding transcript variant, coding sequence variant
rs147895945	A>G	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, non coding transcript variant
rs150008448	T>C	Risk-factor, conflicting-interpretations-of-pathogenicity, likely-benign	Missense variant, coding sequence variant, non coding transcript variant
rs199731535	C>A,T	Likely-pathogenic	Splice donor variant
rs387906797	T>C	Pathogenic	Non coding transcript variant, downstream transcript variant, missense variant, coding sequence variant, genic downstream transcript variant
rs387907327	C>A	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant, intron variant
rs587776690	T>C	Pathogenic	Coding sequence variant, non coding transcript variant, synonymous variant
rs587777851	C>A	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs587777852	G>C	Pathogenic	Intron variant, genic downstream transcript variant
rs797045403	C>A	Pathogenic	Splice donor variant
rs1481733213	T>C	Likely-pathogenic	Intron variant
rs1553760567	C>T	Likely-pathogenic	Splice donor variant
rs1553761113	C>A	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1577488520	A>G	Likely-pathogenic	Splice donor variant, genic downstream transcript variant
rs1577513795	A>G	Likely-pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT051394	hsa-let-7f-5p	CLASH	23622248
MIRT053599	hsa-miR-185-5p	Flow, Microarray, qRT-PCR, Western blot	23807228
MIRT053599	hsa-miR-185-5p	Flow, Microarray, qRT-PCR, Western blot	23807228
MIRT441143	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT441143	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT810375	hsa-miR-132	CLIP-seq
MIRT810376	hsa-miR-212	CLIP-seq
MIRT810377	hsa-miR-383	CLIP-seq
MIRT810378	hsa-miR-3919	CLIP-seq
MIRT810379	hsa-miR-4756-3p	CLIP-seq
MIRT810380	hsa-miR-4772-5p	CLIP-seq
MIRT810381	hsa-miR-539	CLIP-seq
MIRT1939461	hsa-miR-3143	CLIP-seq
MIRT1939462	hsa-miR-4477a	CLIP-seq
MIRT1939463	hsa-miR-4760-5p	CLIP-seq
MIRT1939464	hsa-miR-4803	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000077	Process	DNA damage checkpoint signaling	IBA
GO:0000077	Process	DNA damage checkpoint signaling	IDA	14657349, 21705319, 21777809
GO:0000077	Process	DNA damage checkpoint signaling	IEA
GO:0000086	Process	G2/M transition of mitotic cell cycle	IDA	19160488, 30139873
GO:0000166	Function	Nucleotide binding	IEA
GO:0000723	Process	Telomere maintenance	IBA
GO:0000781	Component	Chromosome, telomeric region	IC	26586433
GO:0003677	Function	DNA binding	IEA
GO:0004672	Function	Protein kinase activity	IDA	14657349
GO:0004672	Function	Protein kinase activity	IEA
GO:0004672	Function	Protein kinase activity	TAS	8610130
GO:0004674	Function	Protein serine/threonine kinase activity	IBA
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	9733515, 9925639, 11390642, 21705319, 21777809, 23273981, 25083873, 27723717, 27723720, 30139873, 37788673, 37832547
GO:0004674	Function	Protein serine/threonine kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	TAS
GO:0005515	Function	Protein binding	IPI	9733515, 14657349, 17686975, 18583959, 19633697, 19889979, 20616048, 20810650, 20864032, 20930849, 23144622, 27723717, 27723720, 33961781, 35849344
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	NAS	11721054
GO:0005635	Component	Nuclear envelope	IDA	25083873, 37788673, 37832547
GO:0005635	Component	Nuclear envelope	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005694	Component	Chromosome	IBA
GO:0005694	Component	Chromosome	IEA
GO:0005694	Component	Chromosome	ISS
GO:0005794	Component	Golgi apparatus	IDA
GO:0006139	Process	Nucleobase-containing compound metabolic process	NAS	28036033
GO:0006260	Process	DNA replication	IEA
GO:0006260	Process	DNA replication	TAS
GO:0006281	Process	DNA repair	IBA
GO:0006281	Process	DNA repair	IEA
GO:0006281	Process	DNA repair	TAS	8610130
GO:0006302	Process	Double-strand break repair	IDA	11390642
GO:0006338	Process	Chromatin remodeling	IEA
GO:0006974	Process	DNA damage response	IDA	30898438
GO:0006974	Process	DNA damage response	IDA	11673449, 27723717, 27723720, 37788673, 37832547
GO:0006974	Process	DNA damage response	IEA
GO:0006974	Process	DNA damage response	TAS	15538388
GO:0006998	Process	Nuclear envelope organization	IDA	2188730
GO:0008156	Process	Negative regulation of DNA replication	IMP	14657349
GO:0009410	Process	Response to xenobiotic stimulus	IEA
GO:0009612	Process	Response to mechanical stimulus	IDA	25083873
GO:0016301	Function	Kinase activity	IEA
GO:0016605	Component	PML body	IDA	12814551
GO:0016740	Function	Transferase activity	IEA
GO:0031297	Process	Replication fork processing	ISS
GO:0032212	Process	Positive regulation of telomere maintenance via telomerase	ISS
GO:0032405	Function	MutLalpha complex binding	IDA	16713580
GO:0032407	Function	MutSalpha complex binding	IDA	16713580
GO:0034644	Process	Cellular response to UV	IMP	9925639
GO:0035979	Function	Histone H2AXS139 kinase activity	IDA	11673449
GO:0036297	Process	Interstrand cross-link repair	TAS
GO:0043517	Process	Positive regulation of DNA damage response, signal transduction by p53 class mediator	IDA	9733515
GO:0043517	Process	Positive regulation of DNA damage response, signal transduction by p53 class mediator	IMP	9925639
GO:0044818	Process	Mitotic G2/M transition checkpoint	IDA	30139873
GO:0046685	Process	Response to arsenic-containing substance	IEA
GO:0051081	Process	Nuclear membrane disassembly	IDA	37788673, 37832547
GO:0070198	Process	Protein localization to chromosome, telomeric region	IMP	21829167
GO:0070310	Component	ATR-ATRIP complex	IEA
GO:0070310	Component	ATR-ATRIP complex	IPI	11721054
GO:0071480	Process	Cellular response to gamma radiation	IDA	9925639
GO:0080135	Process	Regulation of cellular response to stress	IEA
GO:0090399	Process	Replicative senescence	IMP	15149599
GO:0090734	Component	Site of DNA damage	IDA	21777809
GO:0097694	Process	Establishment of RNA localization to telomere	IMP	26586433
GO:0097695	Process	Establishment of protein-containing complex localization to telomere	IC	26586433
GO:0106310	Function	Protein serine kinase activity	IEA
GO:0110025	Process	DNA strand resection involved in replication fork processing	IDA	27814491, 27889449, 29670289, 30612738
GO:1900034	Process	Regulation of cellular response to heat	TAS
GO:1904884	Process	Positive regulation of telomerase catalytic core complex assembly	IMP	26586433
GO:1990166	Process	Protein localization to site of double-strand break	IDA	12419185, 24534091, 27814491, 27889449, 30898438, 37674080
GO:2000779	Process	Regulation of double-strand break repair	NAS	11721054

Other IDs

• MIM: 601215
• HGNC: 882
• e!Ensembl: ENSG00000175054

Protein

• UniProt ID: Q13535
• Protein name: Serine/threonine-protein kinase ATR (EC 2.7.11.1) (Ataxia telangiectasia and Rad3-related protein) (FRAP-related protein 1)
• Protein function: Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor (PubMed:10597277, PubMed:106
• PDB: 5YZ0
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08064	UME	1122 → 1223	UME (NUC010) domain	Domain
  PF02259	FAT	1771 → 2092	FAT domain	Family
  PF00454	PI3_PI4_kinase	2322 → 2567	Phosphatidylinositol 3- and 4-kinase	Family
  PF02260	FATC	2613 → 2644	FATC domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitous, with highest expression in testis. {ECO:0000269|PubMed:11470508, ECO:0000269|PubMed:8610130, ECO:0000269|PubMed:8843195}.; TISSUE SPECIFICITY: [Isoform 2]: Isoform 2 is found in pancreas, placenta and liver but not in heart
• Sequence:

  MGEHGLELASMIPALRELGSATPEEYNTVVQKPRQILCQFIDRILTDVNVVAVELVKKTD
  SQPTSVMLLDFIQHIMKSSPLMFVNVSGSHEAKGSCIEFSNWIITRLLRIAATPSCHLLH
  KKICEVICSLLFLFKSKSPAIFGVLTKELLQLFEDLVYLHRRNVMGHAVEWPVVMSRFLS
  QLDEHMGYLQSAPLQLMSMQNLEFIEVTLLMVLTRIIAIVFFRRQELLLWQIGCVLLEYG
  SPKIKSLAISFLTELFQLGGLPAQPASTFFSSFLELLKHLVEMDTDQLKLYEEPLSKLIK
  TLFPFEAEAYRNIEPVYLNMLLEKLCVMFEDGVLMRLKSDLLKAALCHLLQYFLKFVPAG
  YESALQVRKVYVRNICKALLDVLGIEVDAEYLLGPLYAALKMESMEIIEEIQCQTQQENL
  SSNSDGISPKRRRLSSSLNPSKRAPKQTEEIKHVDMNQKSILWSALKQKAESLQISLEYS
  GLKNPVIEMLEGIAVVLQLTALCTVHCSHQNMNCRTFKDCQHKSKKKPSVVITWMSLDFY
  TKVLKSCRSLLESVQKLDLEATIDKVVKIYDALIYMQVNSSFEDHILEDLCGMLSLPWIY
  SHSDDGCLKLTTFAANLLTLSCRISDSYSPQAQSRCVFLLTLFPRRIFLEWRTAVYNWAL
  QSSHEVIRASCVSGFFILLQQQNSCNRVPKILIDKVKDDSDIVKKEFASILGQLVCTLHG
  MFYLTSSLTEPFSEHGHVDLFCRNLKATSQHECSSSQLKASVCKPFLFLLKKKIPSPVKL
  AFIDNLHHLCKHLDFREDETDVKAVLGTLLNLMEDPDKDVRVAFSGNIKHILESLDSEDG
  FIKELFVLRMKEAYTHAQISRNNELKDTLILTTGDIGRAAKGDLVPFALLHLLHCLLSKS
  ASVSGAAYTEIRALVAAKSVKLQSFFSQYKKPICQFLVESLHSSQMTALPNTPCQNADVR
  KQDVAHQREMALNTLSEIANVFDFPDLNRFLTRTLQVLLPDLAAKASPAASALIRTLGKQ
  LNVNRREILINNFKYIFSHLVCSCSKDELERALHYLKNETEIELGSLLRQDFQGLHNELL
  LRIGEHYQQVFNGLSILASFASSDDPYQGPRDIISPELMADYLQPKLLGILAFFNMQLLS
  SSVGIEDKKMALNSLMSLMKLMGPKHVSSVRVKMMTTLRTGLRFKDDFPELCCRAWDCFV
  RCLDHACLGSLLSHVIVALLPLIHIQPKETAAIFHYLIIENRDAVQDFLHEIYFLPDHPE
  LKKIKAVLQEYRKETSESTDLQTTLQLSMKAIQHENVDVRIHALTSLKETLYKNQEKLIK
  YATDSETVEPIISQLVTVLLKGCQDANSQARLLCGECLGELGAIDPGRLDFSTTETQGKD
  FTFVTGVEDSSFAYGLLMELTRAYLAYADNSRAQDSAAYAIQELLSIYDCREMETNGPGH
  QLWRRFPEHVREILEPHLNTRYKSSQKSTDWSGVKKPIYLSKLGSNFAEWSASWAGYLIT
  KVRHDLASKIFTCCSIMMKHDFKVTIYLLPHILVYVLLGCNQEDQQEVYAEIMAVLKHDD
  QHTINTQDIASDLCQLSTQTVFSMLDHLTQWARHKFQALKAEKCPHSKSNRNKVDSMVST
  VDYEDYQSVTRFLDLIPQDTLAVASFRSKAYTRAVMHFESFITEKKQNIQEHLGFLQKLY
  AAMHEPDGVAGVSAIRKAEPSLKEQILEHESLGLLRDATACYDRAIQLEPDQIIHYHGVV
  KSMLGLGQLSTVITQVNGVHANRSEWTDELNTYRVEAAWKLSQWDLVENYLAADGKSTTW
  SVRLGQLLLSAKKRDITAFYDSLKLVRAEQIVPLSAASFERGSYQRGYEYIVRLHMLCEL
  EHSIKPLFQHSPGDSSQEDSLNWVARLEMTQNSYRAKEPILALRRALLSLNKRPDYNEMV
  GECWLQSARVARKAGHHQTAYNALLNAGESRLAELYVERAKWLWSKGDVHQALIVLQKGV
  ELCFPENETPPEGKNMLIHGRAMLLVGRFMEETANFESNAIMKKYKDVTACLPEWEDGHF
  YLAKYYDKLMPMVTDNKMEKQGDLIRYIVLHFGRSLQYGNQFIYQSMPRMLTLWLDYGTK
  AYEWEKAGRSDRVQMRNDLGKINKVITEHTNYLAPYQFLTAFSQLISRICHSHDEVFVVL
  MEIIAKVFLAYPQQAMWMMTAVSKSSYPMRVNRCKEILNKAIHMKKSLEKFVGDATRLTD
  KLLELCNKPVDGSSSTLSMSTHFKMLKKLVEEATFSEILIPLQSVMIPTLPSILGTHANH
  ASHEPFPGHWAYIAGFDDMVEILASLQKPKKISLKGSDGKFYIMMCKPKDDLRKDCRLME
  FNSLINKCLRKDAESRRRELHIRTYAVIPLNDECGIIEWVNNTAGLRPILTKLYKEKGVY
  MTGKELRQCMLPKSAALSEKLKVFREFLLPRHPPIFHEWFLRTFPDPTSWYSSRSAYCRS
  TAVMSMVGYILGLGDRHGENILFDSLTGECVHVDFNCLFNKGETFEVPEIVPFRLTHNMV
  NGMGPMGTEGLFRRACEVTMRLMRDQREPLMSVLKTFLHDPLVEWSKPVKGHSKAPLNET
  GEVVNEKAKTHVLDIEQRLQGVIKTRNRVTGLPLSIEGHVHYLIQEATDENLLCQMYLGW
  TPYM

• Sequence length: 2644

Pathways

KEGG:

Fanconi anemia pathway
Cell cycle
p53 signaling pathway
Cellular senescence
Human papillomavirus infection
Human T-cell leukemia virus 1 infection
Human immunodeficiency virus 1 infection

Reactome:

Activation of ATR in response to replication stress
Regulation of HSF1-mediated heat shock response
HDR through Single Strand Annealing (SSA)
Processing of DNA double-strand break ends
Presynaptic phase of homologous DNA pairing and strand exchange
Fanconi Anemia Pathway
TP53 Regulates Transcription of DNA Repair Genes
Regulation of TP53 Activity through Phosphorylation
G2/M DNA damage checkpoint

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
ATR-related disorder	Likely pathogenic; Pathogenic	rs587777852	RCV004751286	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Cornelia de Lange syndrome 1	Likely pathogenic; Pathogenic	rs1553760567	RCV005860090	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome	Likely pathogenic; Pathogenic	rs778813551, rs757500301	RCV005025342 RCV005027480 RCV005036463	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hereditary cancer-predisposing syndrome	Likely pathogenic; Pathogenic	rs778813551	RCV000210088	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Seckel syndrome 1	Pathogenic; Likely pathogenic	rs758234545, rs587777851, rs587777852, rs1196005889, rs797045403, rs778813551, rs2108266332, rs757500301, rs1553760567, rs387907327, rs1553761113, rs1481733213, rs1453839157	RCV005232302 RCV000144692 RCV000144693 RCV002308502 RCV000193414 RCV005025342 RCV004690423 RCV005027480 RCV000501635 RCV000034827 RCV000677226 RCV000677227 RCV003127681 RCV001255752	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Adrenocortical carcinoma, hereditary	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATR-X-related syndrome	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CUTANEOUS TELANGIECTASIA AND CANCER SYNDROME, FAMILIAL	—	CTD, HPO CTD, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL PROSTATE CARCINOMA	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of breast	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar GWAS catalog	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Seckel syndrome	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Thymoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
UROLOGIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Ataxia Telangiectasia	Ataxia telangiectasia	Pubtator	7545545	Associate	★☆☆☆☆ Found in Text Mining only