Cryptic mutations of PLC family members in brain disorders: recent discoveries and a deep learning-based approach.

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Abstract

Phospholipase C is an essential isozyme involved in the phosphoinositide signaling pathway, which maintains cellular homeostasis. Gain-of-function and loss-of-function mutations in phospholipase C impact enzymatic activity and are therefore associated with several disorders. Alternative splicing variants of phospholipase C can interfere with complex signaling networks associated with oncogenic transformation and other diseases, including brain disorders. Cells and tissues with various mutations in phospholipase C contribute different phosphoinositide signaling pathways and disease progression; however, identifying cryptic mutations in phospholipase C remains challenging. Herein, we review both the mechanisms underlying phospholipase C regulation of the phosphoinositide signaling pathway and the genetic variation of phospholipase C in several brain disorders. In addition, we discuss the present challenges associated with the potential of deep-learning-based analysis for the identification of phospholipase C mutations in brain disorders.© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.