以提前终止密码子为特征的无义变异在人类遗传疾病以及癌症易感性中发挥着重要作用。尽管其患病率很高，但针对提前终止密码子的有效治疗策略仍然是一个挑战。为了理解和探索所涉及的复杂机制，我们开发了 StopKB，这是一个综合知识库，汇集了来自多个来源的无义变异、相关基因、疾病和表型的数据。 StopKB 识别出 637~317 个独特的无义变异，分布在 18~022 个人类基因中，与 3206 种疾病和 7765 个表型相关。值得注意的是，其中约 32% 的变异被归类为无义介导的 mRNA 衰变不敏感，可能代表无义抑制疗法的合适靶点。我们还提供交互式网络界面，以促进高效、直观的数据探索，使研究人员和临床医生能够驾驭无意义变化的复杂景观。 StopKB 代表了推进精准医学研究的宝贵资源，更具体地说，是开发针对与无意义变异相关的遗传疾病的靶向治疗干预措施。数据库网址：https://lbgi.fr/stopkb/。© 作者 2024。由牛津大学出版社出版。

Nonsense variations, characterized by premature termination codons, play a major role in human genetic diseases as well as in cancer susceptibility. Despite their high prevalence, effective therapeutic strategies targeting premature termination codons remain a challenge. To understand and explore the intricate mechanisms involved, we developed StopKB, a comprehensive knowledgebase aggregating data from multiple sources on nonsense variations, associated genes, diseases, and phenotypes. StopKB identifies 637 317 unique nonsense variations, distributed across 18 022 human genes and linked to 3206 diseases and 7765 phenotypes. Notably, ∼32% of these variations are classified as nonsense-mediated mRNA decay-insensitive, potentially representing suitable targets for nonsense suppression therapies. We also provide an interactive web interface to facilitate efficient and intuitive data exploration, enabling researchers and clinicians to navigate the complex landscape of nonsense variations. StopKB represents a valuable resource for advancing research in precision medicine and more specifically, the development of targeted therapeutic interventions for genetic diseases associated with nonsense variations. Database URL: https://lbgi.fr/stopkb/.© The Author(s) 2024. Published by Oxford University Press.