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MIM.603490 1p35

Thursday 22 December 2005

Wnt-4 is a member of the Wnt family (WNTs) of locally acting secreted growth factors.

Wnt-4 is the first signaling molecule shown to influence the sex-determination cascade. In mice, a targeted deletion of Wnt-4 causes the masculinization of XX pups.

Therefore, WNT-4, the human homologue of murine Wnt-4, is a strong candidate gene for sex-reversal phenotypes in humans.

In testicular Sertoli and Leydig cells, Wnt-4 up-regulates Dax1, a gene known to antagonize the testis-determining factor, Sry.


- WNT4 germline mutations in mullerian agenesis (Rokitansky-Kuster-Hauser syndrome)

- XY sex reversal associated with a 1p31-p35 duplication including WNT-4.

  • Overexpression of WNT-4 leads to up-regulation of DAX1, which results in an XY female phenotype.
  • WNT-4 and DAX1 play a concerted role in both the control of female development and the prevention of testes formation.
  • The mammalian sex determination is sensitive to dosage.

See also

- WNTs


- Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans. Jordan BK, Mohammed M, Ching ST, Délot E, Chen XN, Dewing P, Swain A, Rao PN, Elejalde BR, Vilain E. Am J Hum Genet. 2001 May;68(5):1102-9. PMID: 11283799 (Free)