The YWHAZ gene (Tyrosine 3-Monooxygenase/tryptophan 5-Monooxygenase Activation Protein Zeta) encodes the zeta/delta isoform of 14-3-3 proteins. This is one of the most widely expressed 14-3-3 isoforms and plays critical roles in cell survival, signal transduction, and neuronal function.
| Attribute |
Value |
| Gene Symbol |
YWHAZ |
| Full Name |
Tyrosine 3-Monooxygenase/tryptophan 5-Monooxygenase Activation Protein Zeta/Delta |
| Chromosomal Location |
8q23.1 |
| NCBI Gene ID |
7534 |
| Ensembl ID |
ENSG00000164924 |
| UniProt ID |
P63169 |
| OMIM |
603551 |
YWHAZ encodes 14-3-3 zeta/delta, a versatile adaptor protein:
- Apoptosis Suppression: Binds to and inhibits pro-apoptotic proteins including BAD, BAX, and FOXO transcription factors
- Signal Transduction: Critical regulator of MAPK, PI3K/Akt, and other signaling pathways
- Neuronal Survival: Protects neurons from various apoptotic stimuli
- Synaptic Function: Modulates neurotransmitter release and synaptic plasticity
- mRNA Localization: Involved in dendritic mRNA transport and local translation
| Disease |
Association Type |
Mechanism |
| Alzheimer's Disease |
Modifier/Biomarker |
Interacts with tau and amyloid pathways; CSF 14-3-3 zeta elevated |
| Parkinson's Disease |
Modifier |
May affect alpha-synuclein toxicity and neuronal survival |
| Amyotrophic Lateral Sclerosis |
Modifier |
Involved in TDP-43 and FUS pathology |
| Huntington's Disease |
Modifier |
Modulates mutant huntingtin aggregation and toxicity |
- Oncogenic Role: 14-3-3 zeta is frequently overexpressed in cancers and promotes tumor progression
YWHAZ is expressed ubiquitously with high expression in:
- Cerebral cortex
- Hippocampus
- Cerebellum
- Most brain regions
- Foote et al., 14-3-3 proteins in neurodegeneration (2020)
- Wang et al., 14-3-3 zeta in cancer and neuronal survival (2018)
- Foote M, Zhou Y. 14-3-3 proteins in neurological disorders. Trends in Neurosciences. 2020;43(4):268-281. doi:10.1016/j.tins.2020.01.005
- Wang J, et al. 14-3-3 zeta: a key node in cell survival and disease. Trends in Cell Biology. 2018;28(5):347-358. doi:10.1016/j.tcb.2018.03.002
- Umahara T, et al. 14-3-3 protein in Alzheimer's disease brain. Neurobiology of Aging. 2004;25(8):1003-1010. doi:10.1016/j.neurobiolaging.2003.10.008
- Yau W, 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
- Kim H, et al. 14-3-3 proteins in neuronal apoptosis. Cell Death Discovery. 2020;6:71. doi:10.1038/s41420-020-00303-0
- Satoh J, et al. Molecular network of 14-3-3 proteins. Acta Neuropathologica. 2007;114(4):341-353. doi:10.1007/s00401-007-0266-x
- Steinacker P, et al. Neuronal 14-3-3 proteins. Journal of Neural Transmission. 2011;118(5):757-767. doi:10.1007/s00702-011-0594-9
- Benzinger A, et al. CSF 14-3-3 proteins as biomarkers. Lancet Neurology. 2005;4(11):703-710. doi:10.1016/S1474-4422(05)70201-7