Multiple sequence alignment, AF3 structures, and Origin plots of human NOTCH3 with 113 mammals using CLUSTAL-Omega.

NOTCH3 is a highly conserved transmembrane receptor implicated in CADASIL, a hereditary small vessel disease driven by mutations in its extracellular EGF-like repeats. The mechanism by which these mutations cause pathology remains unclear. We present the first large-scale comparative bioinformatic analysis of NOTCH3 across 113 mammalian species, uncovering three novel insights.

Notch受体3（NOTCH3）是一种高度保守的跨膜受体，与伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）密切相关——该疾病是一类由其细胞外表皮生长因子样重复序列（EGF-like repeats）突变驱动的遗传性小血管病。此类突变引发病理改变的具体机制目前仍不明晰。本研究首次针对113种哺乳动物的NOTCH3开展大规模比较生物信息学分析，揭示了三项全新的研究发现。