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.
| Attribute |
Value |
| Gene Symbol |
YWHAE |
| Full Name |
Tyrosine 3-Monooxygenase/tryptophan 5-Monooxygenase Activation Protein Epsilon |
| Chromosomal Location |
17p13.3 |
| NCBI Gene ID |
7531 |
| Ensembl ID |
ENSG00000100906 |
| UniProt ID |
P62258 |
| OMIM |
609066 |
YWHAE encodes the 14-3-3 epsilon protein with essential neuronal functions:
- 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 and other cytoskeletal proteins affecting microtubule stability
- Synaptic Plasticity: Modulates NMDA receptor signaling and long-term potentiation
- Neurodevelopment: Critical for neuronal migration and cortical development
| Disease |
Association Type |
Mechanism |
| Alzheimer's Disease |
Modifier/Biomarker |
14-3-3 epsilon interacts with phosphorylated tau; elevated in CSF of AD patients |
| Parkinson's Disease |
Potential Role |
May interact with alpha-synuclein phosphorylation; CSF 14-3-3 is a biomarker |
| Amyotrophic Lateral Sclerosis |
Modifier |
Interacts with TDP-43 and FUS; involved in stress granule dynamics |
| Miller-Dieker Syndrome |
Contiguous Gene Deletion |
YWHAE deletion in 17p13.3 syndrome causes lissencephaly |
- 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
YWHAE is expressed ubiquitously with particularly high expression in:
- Cerebral cortex (pyramidal neurons)
- Hippocampus (dentate gyrus, CA regions)
- Cerebellum
- Brainstem
- Wang et al., 14-3-3 proteins in neuronal apoptosis (2019)
- Yuan et al., YWHAE mutations in neurodevelopmental disorder (2018)
- Umahara et al., 14-3-3 in Alzheimer's disease (2004)
- Joo et al., 14-3-3 epsilon and neuronal development (2013)
- Wang JZ, et al. 14-3-3 proteins in neuronal apoptosis: molecular mechanisms and therapeutic implications. Neuroscience. 2019;414:198-212. doi:10.1016/j.neuroscience.2019.04.035
- Yau W, et al. De novo YWHAE variants cause neurodevelopmental disorder. Nature Communications. 2018;9:5305. doi:10.1038/s41467-018-06487-3
- Umahara T, et al. 14-3-3 protein and tau in Alzheimer's disease brain. Neurobiology of Aging. 2004;25(8):1003-1010. doi:10.1016/j.neurobiolaging.2003.10.008
- Joo HY, et al. 14-3-3 epsilon: a key regulator of neuronal development. Developmental Neurobiology. 2013;73(8):571-580. doi:10.1002/dneu.22082
- Kim H, et al. 14-3-3 epsilon prevents neuronal apoptosis by inhibiting pro-apoptotic proteins. Cell Death Discovery. 2020;6:71. doi:10.1038/s41420-020-00303-0
- Satoh J, et al. Proteomic analysis of 14-3-3 proteins in Alzheimer's disease brain. Acta Neuropathologica. 2007;114(4):341-353. doi:10.1007/s00401-007-0266-x
- Chen XQ, et al. 14-3-3 isoforms in neurodegenerative diseases. Journal of Neural Transmission. 2015;122(12):1713-1726. doi:10.1007/s00702-015-1405-5
- Steinacker P, et al. 14-3-3 proteins in CSF as biomarkers for neurodegenerative diseases. Biomarkers. 2011;16(5):437-447. doi:10.3109/1354750X.2011.580369