Huang Haisheng, Wang Yumeng, Chen Fuying, Zhao Anqi, He Wei, Li Ming
Anhui University of Science and Technology First Affiliated Hospital, Anhui, 232001, China.
Department of Dermatology, The Children's Hospital of Fudan University, Shanghai, 201102, China.
Funct Integr Genomics. 2025 Aug 29;25(1):178. doi: 10.1007/s10142-025-01694-y.
The MBTPS1 gene, which is located on chromosome 16q24, encodes the membrane-bound transcription factor protease site-1 (MBTPS1), commonly referred to as site-1 protease (S1P). S1P can process a variety of substrates independently or in conjunction with membrane-bound transcription factor protease site-2 (MBTPS2, also known as S2P), including sterol regulatory element binding proteins (SREBPs), activating transcription factor 6 (ATF6) and cyclic-AMP responsive element‑binding protein 3 (CREB3). Variants in the MBTPS1 gene can lead to multiple clinically distinct disorders with different phenotypes, including spondyloepiphyseal dysplasia of Kondo-Fu type (SEDKF), Cataract, alopecia, oral mucosal disorder, and psoriasis-like (CAOP) syndrome, and Silver-Russell-like syndrome (SRS). This review presents the structural and functional characteristics of S1P, enumerates the relevant substrates and elucidates the spectrum of associated disorders resulting from pathogenic variants of MBTPS1, and discusses the correlations investigates the genotype-phenotype correlations underlying these distinct clinical manifestations.
MBTPS1基因位于16号染色体q24上，编码膜结合转录因子蛋白酶位点1（MBTPS1），通常称为位点1蛋白酶（S1P）。S1P可以独立或与膜结合转录因子蛋白酶位点2（MBTPS2，也称为S2P）一起处理多种底物，包括固醇调节元件结合蛋白（SREBPs）、激活转录因子6（ATF6）和环磷酸腺苷反应元件结合蛋白3（CREB3）。MBTPS1基因的变异可导致多种具有不同表型的临床不同疾病，包括近藤-富型脊椎骨骺发育不良（SEDKF）、白内障、脱发、口腔黏膜疾病和银屑病样（CAOP）综合征以及银-罗素样综合征（SRS）。本综述介绍了S1P的结构和功能特征，列举了相关底物，阐明了MBTPS1致病变异导致的相关疾病谱，并探讨了这些不同临床表现背后的基因型-表型相关性。
