Understanding the functions of disease-associated noncoding variants is essential for understanding the molecular mechanisms driving diseases with a genetic cause and for identifying therapeutic targets. Combined computational and experimental analyses have demonstrated that IRF5 is hyperactivated by a pathogenic allele of TNPO3 through long-distance chromatin looping. This finding identifies a molecular mechanism contributing to the polygenic autoimmune diseases of systemic lupus erythematosus and systemic sclerosis.

中文翻译：

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非编码变体作为自身免疫性疾病发病机理的遗传因素。

理解与疾病相关的非编码变体的功能对于理解驱动遗传原因的疾病的分子机制以及确定治疗靶点至关重要。组合的计算和实验分析表明，IRPO5被TNPO3的致病等位基因通过长距离染色质环超活化。该发现确定了导致系统性红斑狼疮和系统性硬化的多基因自身免疫疾病的分子机制。