Alt. symbols: ATA | ATDC | ATC | ATD | TEL1 | TELO1

Approved name: ATM serine/threonine kinase
Alt. names: ataxia telangiectasia mutated (includes complementation groups A, C and D), ataxia telangiectasia mutated | TEL1, telomere maintenance 1, homolog (S. cerevisiae)

Location: 11q22.3: 108222804 - 108369102 (+)
Gene type: protein_coding, 62 transcripts.

Scores: LoFtool: 0.782000 | pLI: 0.00000000 | LOEUF: 0.710

HGNC: 795

NCBI: 472, RefSeq: NG_009830.1

Ensembl: ENSG00000149311.22

LRG_135 | Status: public

OMIM: 607585

Expression | ProteinAtlas

The ATM gene encodes an evolutionarily ancient and important Ser/Thr PI3/PI4-kinase. ATM is an important cell cycle checkpoint that acts as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1 - located primarily in the nucleus of cells - where it helps control the rate at which cells grow and divide. ATM also plays an important role in the normal development and activity of several body systems, including the nervous system and the immune system. Additionally, the ATM protein assists cells in recognizing damaged or broken DNA strands. ATM coordinates DNA repair by activating enzymes that fix the broken strands.

Bi-allelic splice site, frameshift, nonsense, missense and intronic mutations in ATM have been associated with autosomal recessive (AR) ataxia telangiectasia (A-T) [OMIM:208900], though a second variant may not always be identifiable for patients with a clinical diagnosis of A-T. A-T is a multi-system disease known for its broad spectrum of neurological and immune phenotypes, but also affecting other organs such as the liver. However, mono-allelic germline heterozygous variants may be associated with increased risk for certain malignancies, especially breast cancer in female carriers [MIM:114480]. Somatic mutations in ATM have also been associated with T-cell prolymphocytic leukemia, mantle cell lymphoma, and B-cell non-Hodgkin lymphoma. Selective IgA deficiency (sIgAD) is the main immunological problem detected in nearly half of A-T patients (PMID: 27266541). A review of the literature by Albohassani et al. (2016) noted 30 unique patients with confirmed ATM mutations who were found to be IgA deficient, while some siblings with the same ATM mutation(s) were immunologically normal or had either sIgAD or CVID (PMID: 11068401, 11981817, 15196260, 15880721, 23807571, 19705055, 22006793, 25614872). [Load More]