ATR, ATR serine/threonine kinase, 545

N. diseases: 321; N. variants: 38
Source: ALL
Disease Score gda Association Type Type Original DB Sentence supporting the association PMID PMID Year
CUI: C0265202
Disease: Seckel syndrome
Seckel syndrome 		0.800 GeneticVariation disease BEFREE Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. 23516378 2013
CUI: C0265202
Disease: Seckel syndrome
Seckel syndrome 		0.800 GeneticVariation disease BEFREE While NBS shares overlapping characteristics with ataxia telangiectasia, it also has features overlapping with ATR-Seckel (ATR: ataxia-telangiectasia and Rad3-related protein) syndrome, a subclass of Seckel syndrome mutated in ATR. 15616588 2005
CUI: C0265202
Disease: Seckel syndrome
Seckel syndrome 		0.800 GeneticVariation disease BEFREE Although primary microcephaly can be caused by mutations in microcephalin (MCPH1), cells from patients with Seckel syndrome and MOPD II harbor mutations in ataxia telangiectasia and Rad3 related (ATR) or pericentrin (PCNT), leading to disturbed ATR signaling. 19546241 2009
CUI: C0265202
Disease: Seckel syndrome
Seckel syndrome 		0.800 GeneticVariation disease BEFREE Altogether these data elucidate the molecular mechanisms of the ATR c.2101A>G mutation and identify two potential complementary RNA-based therapies for Seckel syndrome. 27639833 2017
CUI: C0265202
Disease: Seckel syndrome
Seckel syndrome 		0.800 GeneticVariation disease BEFREE Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. 18157127 2008
CUI: C0265202
Disease: Seckel syndrome
Seckel syndrome 		0.800 GeneticVariation disease BEFREE However, the only human genetic ATR defect reported so far is a hypomorphic splicing mutation identified in five related individuals with Seckel syndrome. 23111928 2013
CUI: C0265202
Disease: Seckel syndrome
Seckel syndrome 		0.800 GeneticVariation disease BEFREE Analysis of novel missense ATR mutations reveals new splicing defects underlying Seckel syndrome. 30199583 2018
CUI: C0265202
Disease: Seckel syndrome
Seckel syndrome 		0.800 GeneticVariation disease BEFREE Previously, autosomal-recessive loss-of-function mutations in ATR have been demonstrated in Seckel syndrome, a developmental disorder. 22341969 2012
CUI: C0265202
Disease: Seckel syndrome
Seckel syndrome 		0.800 GeneticVariation disease BEFREE Recently, more sophisticated mouse models have been published including a conditional ATR-knockdown system and by modelling the human ATR-Seckel syndrome-causative mutation. 19782648 2009
CUI: C3281203
Disease: CUTANEOUS TELANGIECTASIA AND CANCER SYNDROME, FAMILIAL
CUTANEOUS TELANGIECTASIA AND CANCER SYNDROME, FAMILIAL 		0.700 GeneticVariation disease UNIPROT Germline mutation in ATR in autosomal- dominant oropharyngeal cancer syndrome. 22341969 2012
CUI: C4551474
Disease: Seckel syndrome 1
Seckel syndrome 1 		0.610 GeneticVariation disease CLINVAR
CUI: C0006826
Disease: Malignant Neoplasms
Malignant Neoplasms 		0.400 GeneticVariation group BEFREE Taken together, our results provide a functional rationale to profile human tumors for disabling <i>ATM</i> mutations, particularly given their impact on PARP1 and ATR inhibitors.<i>Cancer Res; 77(11); 3040-56.©2017 AACR</i>. 28363999 2017
CUI: C0006826
Disease: Malignant Neoplasms
Malignant Neoplasms 		0.400 GeneticVariation group BEFREE Mutations in p53, critical for G1 checkpoint control, are common in cancer and predicted to confer vulnerability to ATR inhibitors. 30127241 2018
CUI: C0006826
Disease: Malignant Neoplasms
Malignant Neoplasms 		0.400 GeneticVariation group BEFREE MEC1 is a homolog of ATM, mutations in which cause ataxia telangiectasia (A-T), a disease characterized by various neurologic and immunologic abnormalities, a predisposition for cancer, and a cellular defect in repair of DSBs. 10367890 1999
CUI: C0006826
Disease: Malignant Neoplasms
Malignant Neoplasms 		0.400 GeneticVariation group BEFREE Clinical data has recently shown the presence of heterozygous mutations in ATR and Chk1 in human cancers that exhibit MSI, suggesting that those mutations may contribute to tumorigenesis. 19570909 2009
CUI: C0006826
Disease: Malignant Neoplasms
Malignant Neoplasms 		0.400 GeneticVariation group BEFREE The genes involved include the ATM, ATR, FA-associated genes, NBS1 and the cancer susceptibility genes BRCA1 and BRCA2. 16002101 2005
CUI: C0006826
Disease: Malignant Neoplasms
Malignant Neoplasms 		0.400 GeneticVariation group BEFREE ATR is an attractive target in cancer therapy because it signals replication stress and DNA lesions for repair and to S/G2 checkpoints. 26486089 2015
CUI: C0006826
Disease: Malignant Neoplasms
Malignant Neoplasms 		0.400 GeneticVariation group BEFREE Collectively, the clinicopathological and molecular findings point to a cancer syndrome and provide evidence implicating a germline mutation in ATR and susceptibility to malignancy in humans. 22341969 2012
CUI: C0006826
Disease: Malignant Neoplasms
Malignant Neoplasms 		0.400 GeneticVariation group BEFREE Taken together, our results demonstrate that ATR may represent a novel therapeutic target in patients with MDS carrying the U2AF1(S34F) mutation and potentially other malignancies harboring spliceosome mutations.<b>Significance:</b> This study provides preclinical evidence that patients with MDS or other myeloid malignancies driven by spliceosome mutations may benefit from ATR inhibition to exploit the R loop-associated vulnerability induced by perturbations in splicing.<i>Cancer Res; 78(18); 5363-74.©2018 AACR</i>. 30054334 2018
CUI: C0006826
Disease: Malignant Neoplasms
Malignant Neoplasms 		0.400 GeneticVariation group BEFREE Overall, our results offered a preclinical mechanistic rationale for the use of PARP and ATR inhibitors to improve treatment of ATM-mutant PDAC.<i>Cancer Res; 77(20); 5576-90.©2017 AACR</i>. 28790064 2017
CUI: C0024623
Disease: Malignant neoplasm of stomach
Malignant neoplasm of stomach 		0.320 GeneticVariation disease BEFREE These findings imply that ATR mutations play an important role in the development and clinical behavior of a subset of microsatellite instability-positive endometrial, colon, and stomach cancers. 16103057 2005
CUI: C0152013
Disease: Adenocarcinoma of lung (disorder)
Adenocarcinoma of lung (disorder) 		0.320 GeneticVariation disease UNIPROT
CUI: C0919267
Disease: ovarian neoplasm
ovarian neoplasm 		0.320 GeneticVariation disease BEFREE The present study does not support a major role for ATR mutations in hereditary susceptibility to breast and ovarian cancer. 15987455 2005
CUI: C1140680
Disease: Malignant neoplasm of ovary
Malignant neoplasm of ovary 		0.320 GeneticVariation disease BEFREE The present study does not support a major role for ATR mutations in hereditary susceptibility to breast and ovarian cancer. 15987455 2005
CUI: C0149782
Disease: Squamous cell carcinoma of lung
Squamous cell carcinoma of lung 		0.300 GeneticVariation disease UNIPROT