Formins are a conserved family of proteins that primarily act to form linear polymers of actin. Despite their importance to the normal functioning of the cytoskeleton, for a long time, the only two formin genes known to be a genetic cause of human disorders were DIAPH1 and DIAPH3, whose mutation causes two distinct forms of hereditary deafness. In the last 10 years, however, the formin INF2 has emerged as an important target of mutations responsible for the appearance of focal segmental glomerulosclerosis, which are histological lesions associated with glomerulus degeneration that often leads to end-stage renal disease. In some rare cases, focal segmental glomerulosclerosis concurs with Charcot–Marie–Tooth disease, which is a degenerative neurological disorder affecting peripheral nerves. All known INF2 gene mutations causing disease map to the exons encoding the amino-terminal domain. In this review, we summarize the structure, biochemical features and functions of INF2, conduct a systematic and comprehensive analysis of the pathogenic INF2 mutations, including a detailed study exon-by-exon of patient cases and mutations, address the impact of the pathogenic mutations on the structure, regulation and known functions of INF2, draw a series of conclusions that could be useful for INF2-related disease diagnosis, and suggest lines of research for future work on the molecular mechanisms by which INF2 causes disease.

福尔明是一个保守的蛋白质家族，主要作用是形成肌动蛋白的线性聚合物。尽管福明基因对细胞骨架的正常功能很重要，但长期以来，已知的唯一两个导致人类疾病的遗传原因是DIAPH1和DIAPH3 ，它们的突变导致两种不同形式的遗传性耳聋。然而，在过去 10 年中，formin INF2 已成为导致局灶节段性肾小球硬化出现的重要突变靶标，局灶节段性肾小球硬化是与肾小球变性相关的组织学病变，通常导致终末期肾病。在一些罕见的病例中，局灶节段性肾小球硬化症与夏科-玛丽-图思病同时发生，这是一种影响周围神经的退行性神经系统疾病。所有已知的导致疾病的INF2基因突变都映射到编码氨基末端结构域的外显子。在这篇综述中，我们总结了INF2的结构、生化特征和功能，对INF2的致病突变进行了系统、全面的分析，包括对患者病例和突变的逐个外显子进行详细研究，解决致病突变的影响研究人员对 INF2 的结构、调控和已知功能进行了研究，得出了一系列可能有助于 INF2 相关疾病诊断的结论，并为未来 INF2 引起疾病的分子机制的研究方向提出了建议。