ATR |
- 1
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- ATR (HGNC:882) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- ATR serine/threonine kinase
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- No previous names found
- Alias symbols
- FRP1, SCKL, SCKL1, MEC1
- %HI
- 8.61(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0(Read more about gnomAD pLI score)
- LOEUF
- 0.4(Read more about gnomAD LOEUF score)
- Cytoband
- 3q23
- Genomic Coordinates
-
GRCh37/hg19: chr3:142168077-142297575 NCBI Ensembl UCSC GRCh38/hg38: chr3:142449235-142578733 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001184.4 ENST00000350721.9 (Read more about MANE Select)
- 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:10608806, PubMed:10859164, PubMed:11721054, PubMed:12791985, PubMed:12814551, PubMed:14657349, PubMed:14729973, PubMed:14742437, PubMed:15210935, PubMed:15496423, PubMed:16260606, PubMed:21144835, PubMed:27723717, PubMed:27723720, PubMed:33848395, PubMed:942... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-25974
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency
(1)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
06/05/2020
Haploinsufficiency (HI) Score Details
HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- Familial cutaneous telangiectasia and cancer syndrome Monarch
HI Evidence:
-
PUBMED:
30159786
de Souza Timoteo AR et al (2018) detected a nonsense variant in ATR (c.3043C>T) in the exon 14 using NGS (targeted capture sequencing) in an individual with bilateral breast cancer (age of diagnosis: 46 and 52 years old) and bone metastasis. Her daughter was negative for this variant by Sanger sequencing. No other family history.
-
PUBMED:
26556299
Schrader KA et al (2016) reported a germline partial deletion of ATR in a breast cancer patient, and a frame-shift variant (c.4915_4918dupGATA, p.T1640fs*21) in a patient with bladder/urinary tract cancer. No family information.
-
PUBMED:
29439820
Antonarakis ES et al (2018) reported a germline splicing variant (c.2634-1G>A) in ATR in a patient with metatatic castration-resistant prostate cancer patient using whole exome sequencing. No family information. 0.2?
HI Evidence Comments:
ATR is one of the main regulators of the DNA damage response. Biallelic loss-of-function variants of ATR are associated with Seckel syndrome (OMIM 210600), a rare autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic ‘bird-headed’ facial appearance.
Germline heterozygous mutations in ATR have been reported in individuals with variety of cancers, and an increased risk for cancer has been proposed for carriers. Other germline heterozygous deleterious variants (nonsense, frameshift, splicing and partial deletion) have also been reported in different patients with a variety of cancers (breast cancer, ovarian cancer, prostate cancer, gastric cancer, etc). They are c.5342T>A p.L1781* in a breast cancer (26822949), c.3889delG p.V1297fs in breast cancer (30262796), c.4957C>T p.Arg1653X in prostate cancer (27084275), 3 frameshift variants in ovarian cancer (28541631), and c.6075A→T p.Tyr2025X in gastric cancer (29706558).
Tanaka A et al (2012) (PMID: 22341969) reported a heterozygous missense variant (c.6431A>G; p.Gln2144Arg) in a large 4-generation family with 24 affected individuals. All had telangiectases that appeared during infancy (before 18 months of age), thinning of the lateral eyebrows and patchy alopecia in areas of skin with prominent telangiectases. In addition, 10 of the 24 cases developed oropharyngeal cancer, typically in the third decade of life or later. Other reported malignancies included nonmelanoma skin cancer (basal cell carcinoma, squamous cell carcinoma, and sebaceous carcinoma) in 3 individuals, breast cancer in 1, and cervical cancer in 1. The variant segregated with the disease and was not found in 220 ethnically matched control chromosomes. The mutation occurs within the important FAT (FRAP, ATM, and TRRAP) domain (which can activate p53) of ATR. The mutation did not lead to a reduction in ATR expression, but cultured fibroblasts showed lower p53 levels after activation of ATR with hydroxyurea than did normal control fibroblasts.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
no evidence for triplosensitivity
Genomic View
Select assembly:
(NC_000003.11)
(NC_000003.12)