ATM是抑癌基因，编码一种丝氨酸/苏氨酸蛋白激酶，ATM作为肿瘤抑制因子在DNA双链断裂（DSBs）积累或者其他形式的细胞应激积累后启动DNA损伤检查点信号传导。活化的ATM可以磷酸化上百种底物以达到启动和扩大DNA损伤反应（导致DNA修复，细胞周期停滞和/或细胞凋亡）。当DNA双链发生断裂时，ATM的激酶活性迅速增加。ATM涉及DNA修复、细胞凋亡、G1/S期、S检查点和G2/M检查点、基因调控、翻译起始和端粒维持。因此，ATM缺陷会对某些类型的DNA损伤修复机制造成严重影响，不正确的DNA修复积累引发癌症。ATM胚系致病变异常导致常染色体隐性遗传性共济失调性毛细血管扩张症（A-T）的发生，A-T常表现出多种神经病症，肺和皮肤病和免疫缺陷。另外，A-T的患者也易患多种癌症，尤其是儿童期淋巴瘤和白血病以及乳腺癌。 已经在淋巴恶性肿瘤和妇科肿瘤/肺癌等癌种中鉴定了ATM中的体细胞突变。

ATM is a member of the protein superfamily of phosphatidylinositol 3-kinase related serine/threonine kinases (PIKKs). ATM functions as a tumor suppressor that initiates DNA damage checkpoint signaling after accumulation of DNA double-strand breaks (DSBs) or after accumulation of other forms of cellular stress. Activated ATM can phosphorylate hundreds of substrates in order to initiate and amplify the DNA damage response resulting in DNA repair, cell cycle arrest and/or apoptosis. Germline loss-of-function mutations in ATM have been identified in the autosomal recessive disorder Ataxia telangiectasia (A-T), a disorder that presents with a variety of neurologic conditions, lung and skin disorders and immunodeficiency. Patients with A-T are also predisposed to a wide variety of cancers, particularly childhood lymphomas and leukemia as well as breast cancer. Somatic mutations in ATM have been identified in lymphoid malignancies and a selection of solid tumors. 

GeneCards OncoKB My Cancer Genome