Members of the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) family mediate membrane fusion processes associated with vesicular trafficking and autophagy. SNAREs mediate core membrane fusion processes essential for all cells, but some SNAREs serve cell/tissue type‐specific exocytic/endocytic functions, and are therefore critical for various aspects of embryonic development. Mutations or variants of their encoding genes could give rise to developmental disorders, such as those affecting the nervous system and immune system in humans. Mutations to components in the canonical synaptic vesicle fusion SNARE complex (VAMP2, STX1A/B, and SNAP25) and a key regulator of SNARE complex formation MUNC18‐1, produce variant phenotypes of autism, intellectual disability, movement disorders, and epilepsy. STX11 and MUNC18‐2 mutations underlie 2 subtypes of familial hemophagocytic lymphohistiocytosis. STX3 mutations contribute to variant microvillus inclusion disease. Chromosomal microdeletions involving STX16 play a role in pseudohypoparathyroidism type IB associated with abnormal imprinting of the GNAS complex locus. In this short review, I discuss these and other SNARE gene mutations and variants that are known to be associated with a variety developmental disorders, with a focus on their underlying cellular and molecular pathological basis deciphered through disease modeling. Possible pathogenic potentials of other SNAREs whose variants could be disease predisposing are also speculated upon.

中文翻译：

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圈套和发育障碍

可溶性N 的成员-乙基马来酰亚胺 - 敏感因子附着蛋白受体 (SNARE) 家族介导与囊泡运输和自噬相关的膜融合过程。SNAREs 介导所有细胞必不可少的核心膜融合过程，但一些 SNAREs 服务于细胞/组织类型特异性的胞吐/内吞功能，因此对胚胎发育的各个方面至关重要。其编码基因的突变或变异可能会导致发育障碍，例如影响人类神经系统和免疫系统的发育障碍。经典突触囊泡融合 SNARE 复合体（VAMP2、STX1A/B 和 SNAP25）和 SNARE 复合体形成的关键调节因子 MUNC18-1 中成分的突变会产生自闭症、智力障碍、运动障碍和癫痫的变异表型。STX11和MUNC18-2突变是家族性噬血细胞性淋巴组织细胞增生症2 种亚型的基础。STX3突变导致变异微绒毛包涵体病。涉及STX16 的染色体微缺失在与GNAS复合位点异常印记相关的 IB 型假性甲状旁腺功能减退症中起作用。在这篇简短的评论中，我讨论了这些和其他已知与多种发育障碍相关的 SNARE 基因突变和变体，重点是通过疾病模型破译的潜在细胞和分子病理基础。还推测其他 SNARE 的可能致病潜力，其变异可能是疾病易感性。