ADAMTS13 变体 VWF 切割缺陷
中文名称
通路描述
在正常生理条件下，ADAMTS13 通过剪切 VWF A2 域中酪氨酸 1605 和甲硫氨酸 1606 之间的肽键，以剪切依赖性方式下调 VWF 促凝血活性。ADAMTS13 活性缺陷导致血浆中超大 VWF 多聚体切割缺陷，并与血小板减少性紫癜 (TTP) 患者微血管中过度血栓形成的关联相关 (Zheng XL 2015; Sukumar S 等。2021)。TTP 是由 ADAMTS13 基因中的遗传突变或针对 ADAMTS13 蛋白的获得性抑制性自身抗体引起的。该 Reactome 事件描述了由 TTP 引起的 ADAMTS13 功能丧失变体 VWF 切割缺陷，包括 A250V、P475S 和 Q449*，这些变体显示出正常或轻微减少的分泌 (Kokame K 等，2002; Uchida T 等，2004; Markham-Lee Z 等，2022)。
英文描述
Defective VWF cleavage by ADAMTS13 variant Under normal physiological conditions, a disintegrin and metalloproteinase with thrombospondin type 1 repeats 13 (ADAMTS13) downregulates VWF procoagulant activity by cleaving the peptide bond between Tyr1605 and Met1606 within the A2 domain of VWF in a shear-dependent manner. Deficiencies in ADAMTS13 activity results in defective cleavage of ultra large VWF multimer in the plasma and are associated with excessive thrombi formation in the microvasculature in patients with thrombotic thrombocytopenic purpura (TTP) (Zheng XL 2015; Sukumar S et al. 2021). TTP is caused either by inherited mutations in the ADAMTS13 gene or by acquired inhibitory autoantibodies directed against the ADAMTS13 protein. This Reactome event describes defective cleavage of VWF by TTP-causing loss-of-function ADAMTS13 variants, A250V, P475S, Q449*, which showed normal or slightly reduced secretion (Kokame K et al., 2002; Uchida T et al., 2004; Markham-Lee Z et al., 2022).
所含基因
3 个基因