The YWHAE gene (Tyrosine 3-Monooxygenase/tryptophan 5-Monooxygenase Activation Protein Epsilon) encodes the epsilon isoform of 14-3-3 proteins. The 14-3-3 family consists of highly conserved adaptor proteins that regulate diverse cellular processes by binding to phosphorylated serine/threonine motifs on target proteins. YWHAE is widely expressed and plays critical roles in neuronal development and function. [@joo2013]
Gene Information
Function
YWHAE encodes the 14-3-3 epsilon protein with essential neuronal functions:
[Apoptosis](/entities/apoptosis) Regulation: Binds to and sequesters pro-apoptotic proteins including BAD, BAX, and FOXO transcription factors
Signal Transduction: Regulates MAPK/ERK, PI3K/Akt, and other kinase signaling pathways
Cytoskeletal Dynamics: Interacts with [tau](/proteins/tau) and other cytoskeletal proteins affecting microtubule stability
Synaptic Plasticity: Modulates [NMDA receptor](/entities/nmda-receptor) signaling and [long-term potentiation](/mechanisms/long-term-potentiation)
Neurodevelopment: Critical for neuronal migration and cortical development
Disease Associations
Neurodegenerative Diseases
Neurodevelopmental Disorders
Epilepsy: YWHAE mutations associated with early-onset seizure disorders
Intellectual Disability: YWHAE variants cause neurodevelopmental delay
Autism Spectrum Disorder: 14-3-3 epsilon dysregulation reported in ASD
Expression
YWHAE is expressed ubiquitously with particularly high expression in:
[Wang JZ, et al, 14-3-3 proteins in neuronal apoptosis: molecular mechanisms and therapeutic implications (2019)](https://doi.org/10.1016/j.neuroscience.2019.04.035)
[Yau W, et al, De novo YWHAE variants cause neurodevelopmental disorder (2018)](https://doi.org/10.1038/s41467-018-06487-3)
[Umahara T, et al, 14-3-3 protein and tau in Alzheimer's disease brain (2004)](https://doi.org/10.1016/j.neurobiolaging.2003.10.008)
[Joo HY, et al, 14-3-3 epsilon: a key regulator of neuronal development (2013)](https://doi.org/10.1002/dneu.22082)
[Kim H, et al, 14-3-3 epsilon prevents neuronal apoptosis by inhibiting pro-apoptotic proteins (2020)](https://doi.org/10.1038/s41420-020-00303-0)
[Satoh J, et al, Proteomic analysis of 14-3-3 proteins in Alzheimer's disease brain (2007)](https://doi.org/10.1007/s00401-007-0266-x)
[Chen XQ, et al, 14-3-3 isoforms in neurodegenerative diseases (2015)](https://doi.org/10.1007/s00702-015-1405-5)
[Steinacker P, et al, 14-3-3 proteins in CSF as biomarkers for neurodegenerative diseases (2011)](https://doi.org/10.3109/1354750X.2011.580369)