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URL of this page: https://medlineplus.gov/genetics/gene/ywhae/

YWHAE gene

tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon

Normal Function

The YWHAE gene provides instructions for making the 14-3-3 epsilon protein, which is part of the large 14-3-3 protein family. Proteins in this family attach (bind) to other proteins that are involved in cell signaling. Proteins in the 14-3-3 family either turn on (activate) or turn off (inactivate) these other proteins. The 14-3-3 proteins are also involved in processes such as the self-destruction of cells when they are no longer needed (apoptosis), the production of energy within cells, and the movement (transport) of proteins within cells.  

The 14-3-3 epsilon protein is active in tissues throughout the body, although research has focused on its role in the brain. In the brain, this protein helps direct the movement of nerve cells (neuronal migration) by binding to other proteins. It is thought that the 14-3-3 epsilon protein is critical for proper neuronal migration and normal brain development.

Health Conditions Related to Genetic Changes

Miller-Dieker syndrome

A deletion of genetic material near the end of the short (p) arm of chromosome 17 causes Miller-Dieker syndrome. This region contains numerous genes, including the YWHAE gene. Miller-Dieker syndrome is characterized by intellectual disabilities and developmental delays that are caused by an abnormally smooth brain that does not have the normal folds and grooves (lissencephaly).

As a result of the deletion, people with Miller-Dieker syndrome 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 available 14-3-3 epsilon protein. In people with Miller-Dieker syndrome, a shortage of 14-3-3 epsilon protein contributes to severe lissencephaly.

Other deleted genes in the same region of chromosome 17 likely contribute to the other features of Miller-Dieker syndrome.

More About This Health Condition

Schizophrenia

MedlinePlus Genetics provides information about Schizophrenia

More About This Health Condition

Other disorders

Variants that only affect the YWHAE gene have been reported in a few families. Some of these variants disrupt the way the gene's instructions are used to make the 14-3-3 epsilon protein, while others delete some or all of the YWHAE gene. These variants have been associated with weak muscle tone (hypotonia), developmental delays, delayed speech, seizures, and brain abnormalities.

Other Names for This Gene

  • 14-3-3 epsilon
  • 14-3-3E
  • HEL2
  • KCIP-1
  • MDCR

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Baker EK, Brewer CJ, Ferreira L, Schapiro M, Tenney J, Wied HM, Kline-Fath BM, Smolarek TA, Weaver KN, Hopkin RJ. Further expansion and confirmation of phenotype in rare loss of YWHAE gene distinct from Miller-Dieker syndrome. Am J Med Genet A. 2023 Feb;191(2):526-539. doi: 10.1002/ajmg.a.63057. Epub 2022 Nov 25. Citation on PubMed
  • Denomme-Pichon AS, Collins SC, Bruel AL, Mikhaleva A, Wagner C, Vancollie VE, Thomas Q, Chevarin M, Weber M, Prada CE, Overs A, Palomares-Bralo M, Santos-Simarro F, Pacio-Miguez M, Busa T, Legius E, Bacino CA, Rosenfeld JA, Le Guyader G, Egloff M, Le Guillou X, Mencarelli MA, Renieri A, Grosso S, Levy J, Dozieres B, Desguerre I, Vitobello A, Duffourd Y, Lelliott CJ, Thauvin-Robinet C, Philippe C, Faivre L, Yalcin B. YWHAE loss of function causes a rare neurodevelopmental disease with brain abnormalities in human and mouse. Genet Med. 2023 Jul;25(7):100835. doi: 10.1016/j.gim.2023.100835. Epub 2023 Mar 28. Citation on PubMed
  • Jin DY, Lyu MS, Kozak CA, Jeang KT. Function of 14-3-3 proteins. Nature. 1996 Jul 25;382(6589):308. doi: 10.1038/382308a0. No abstract available. Citation on PubMed
  • 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. Citation on PubMed
  • Noor A, Bogatan S, Watkins N, Meschino WS, Stavropoulos DJ. Disruption of YWHAE gene at 17p13.3 causes learning disabilities and brain abnormalities. Clin Genet. 2018 Feb;93(2):365-367. doi: 10.1111/cge.13056. Epub 2017 Aug 31. Citation on PubMed
  • Obsilova V, Obsil T. Structural insights into the functional roles of 14-3-3 proteins. Front Mol Biosci. 2022 Sep 16;9:1016071. doi: 10.3389/fmolb.2022.1016071. eCollection 2022. Citation on PubMed
  • 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. doi: 10.1074/jbc.272.40.25267. Citation on PubMed
  • 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. doi: 10.1016/j.cellsig.2007.07.016. Epub 2007 Jul 31. Citation on PubMed
  • 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. doi: 10.1038/ng1169. Citation on PubMed

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