Reviewed November 2009
What is the official name of the YWHAE gene?
The official name of this gene is “tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon.”
YWHAE is the gene's official symbol. The YWHAE gene is also known by other names, listed below.
What is the normal function of the YWHAE gene?
The YWHAE gene provides instructions for making the 14-3-3 epsilon (ε) protein, which is part of the large 14-3-3 protein family. Proteins in this family attach (bind) to other proteins involved in cell signaling. 14-3-3 proteins either turn on (activate) or turn off (inactivate) these other proteins. The 14-3-3ε protein helps to regulate a variety of processes including cell division and sensitivity to insulin, a hormone that helps control blood sugar levels.
The 14-3-3ε protein is active in tissues throughout the body, although its function is sometimes unclear. In the brain, this protein is involved in directing the movement of nerve cells (neuronal migration) by binding to other proteins involved in this process. It is thought that the 14-3-3ε protein is critical for proper neuronal migration and normal brain development.
How are changes in the YWHAE gene related to health conditions?
- Miller-Dieker syndrome - associated with the YWHAE gene
The characteristic signs and symptoms of Miller-Dieker syndrome are caused by a deletion of genetic material near the end of the short (p) arm of chromosome 17. The chromosomal region that is typically deleted contains multiple genes, including the YWHAE gene. As a result of the deletion, people with this condition have only one copy of the YWHAE gene in each cell instead of the usual two copies.
A deletion of one copy of the YWHAE gene in each cell reduces the amount of 14-3-3ε protein by about half. A shortage of 14-3-3ε protein increases the severity of lissencephaly (a problem with brain development in which the surface of the brain is abnormally smooth) in people with Miller-Dieker syndrome.
- other disorders - caused by mutations in the YWHAE gene
A deletion that only involves the YWHAE gene can also cause health problems. People with a YWHAE gene deletion are missing one copy of the gene in each cell, which reduces the amount of 14-3-3ε protein that is produced by about half. A deficiency (shortage) of this protein is thought to cause short stature; intellectual disability; and distinctive facial features including a prominent forehead, wide nasal bridge, and small jaw. People with a YWHAE gene deletion do not have lissencephaly but tend to have other brain abnormalities.
Where is the YWHAE gene located?
Cytogenetic Location: 17p13.3
Molecular Location on chromosome 17: base pairs 1,344,540 to 1,400,375
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/7531))
The YWHAE gene is located on the short (p) arm of chromosome 17 at position 13.3.
More precisely, the YWHAE gene is located from base pair 1,344,540 to base pair 1,400,375 on chromosome 17.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about YWHAE?
You and your healthcare professional may find the following resources about YWHAE helpful.
Educational resources - Information pages
- Madame Curie Bioscience Database: 14-3-3 Proteins (http://www.ncbi.nlm.nih.gov/books/NBK5962/)
- Neuroscience (second edition, 2001): Neuronal Migration (http://www.ncbi.nlm.nih.gov/books/NBK10831/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for YWHAE (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=7531%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28YWHAE%5BTIAB%5D%29%20OR%20%28%2814-3-3E%5BTIAB%5D%29%20OR%20%2814-3-3%20epsilon%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20720%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/605066)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_YWHAE.html)
- HGNC Gene Family: 14-3-3 phospho-serine/phospho-threonine binding proteins (http://www.genenames.org/cgi-bin/genefamilies/set/1053)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=12851)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7531)
What other names do people use for the YWHAE gene or gene products?
- 14-3-3 epsilon
- mitochondrial import stimulation factor L subunit
- protein kinase C inhibitor protein-1
- tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide
- tyrosine 3/tryptophan 5 -monooxygenase activation protein, epsilon polypeptide
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding YWHAE?
cell division ;
gene deletion ;
neuronal migration ;
short stature ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Jin DY, Lyu MS, Kozak CA, Jeang KT. Function of 14-3-3 proteins. Nature. 1996 Jul 25;382(6589):308. (http://www.ncbi.nlm.nih.gov/pubmed/8684458?dopt=Abstract)
- Mignon-Ravix C, Cacciagli P, El-Waly B, Moncla A, Milh M, Girard N, Chabrol B, Philip N, Villard L. Deletion of YWHAE in a patient with periventricular heterotopias and pronounced corpus callosum hypoplasia. J Med Genet. 2010 Feb;47(2):132-6. doi: 10.1136/jmg.2009.069112. Epub 2009 Jul 26. (http://www.ncbi.nlm.nih.gov/pubmed/19635726?dopt=Abstract)
- Nagamani SC, Zhang F, Shchelochkov OA, Bi W, Ou Z, Scaglia F, Probst FJ, Shinawi M, Eng C, Hunter JV, Sparagana S, Lagoe E, Fong CT, Pearson M, Doco-Fenzy M, Landais E, Mozelle M, Chinault AC, Patel A, Bacino CA, Sahoo T, Kang SH, Cheung SW, Lupski JR, Stankiewicz P. Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment. J Med Genet. 2009 Dec;46(12):825-33. doi: 10.1136/jmg.2009.067637. Epub 2009 Jul 6. (http://www.ncbi.nlm.nih.gov/pubmed/19584063?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7531)
- Ogihara T, Isobe T, Ichimura T, Taoka M, Funaki M, Sakoda H, Onishi Y, Inukai K, Anai M, Fukushima Y, Kikuchi M, Yazaki Y, Oka Y, Asano T. 14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain. J Biol Chem. 1997 Oct 3;272(40):25267-74. (http://www.ncbi.nlm.nih.gov/pubmed/9312143?dopt=Abstract)
- Tak H, Jang E, Kim SB, Park J, Suk J, Yoon YS, Ahn JK, Lee JH, Joe CO. 14-3-3epsilon inhibits MK5-mediated cell migration by disrupting F-actin polymerization. Cell Signal. 2007 Nov;19(11):2379-87. Epub 2007 Jul 31. (http://www.ncbi.nlm.nih.gov/pubmed/17728103?dopt=Abstract)
- Toyo-oka K, Shionoya A, Gambello MJ, Cardoso C, Leventer R, Ward HL, Ayala R, Tsai LH, Dobyns W, Ledbetter D, Hirotsune S, Wynshaw-Boris A. 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome. Nat Genet. 2003 Jul;34(3):274-85. (http://www.ncbi.nlm.nih.gov/pubmed/12796778?dopt=Abstract)
- OMIM: TYROSINE 3-MONOOXYGENASE/TRYPTOPHAN 5-MONOOXYGENASE ACTIVATION PROTEIN, EPSILON ISOFORM (http://omim.org/entry/605066)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.