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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®


Reviewed July 2014

What is the official name of the WNT4 gene?

The official name of this gene is “wingless-type MMTV integration site family member 4.”

WNT4 is the gene's official symbol. The WNT4 gene is also known by other names, listed below.

What is the normal function of the WNT4 gene?

The WNT4 gene belongs to a family of WNT genes that play critical roles in development before birth. WNT genes provide instructions for making proteins that participate in chemical signaling pathways in the body. These pathways control the activity of certain genes and regulate the interactions between cells during embryonic development.

The WNT4 gene provides instructions for producing a protein that is important for the formation of the female reproductive system, the kidneys, and several hormone-producing glands. During the development of the female reproductive system, the WNT4 protein regulates the formation of the Müllerian ducts, which are structures in the embryo that develop into the uterus, fallopian tubes, cervix, and the upper part of the vagina. This protein is also involved in development of the ovaries, from before birth through adulthood, and is important for development and maintenance of egg cells (oocytes) in the ovaries. In addition, the WNT4 protein regulates the production of male sex hormones (androgens).

Does the WNT4 gene share characteristics with other genes?

The WNT4 gene belongs to a family of genes called endogenous ligands (endogenous ligands). It also belongs to a family of genes called WNT (wingless-type MMTV integration sites).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? ( in the Handbook.

How are changes in the WNT4 gene related to health conditions?

Müllerian aplasia and hyperandrogenism - caused by mutations in the WNT4 gene

At least three mutations in the WNT4 gene have been found to cause Müllerian aplasia and hyperandrogenism, a condition that affects the reproductive system in females. Girls and women with this condition typically have an underdeveloped or absent uterus and do not menstruate. They may also have abnormally high levels of androgens, which can cause acne and excessive facial hair.

WNT4 gene mutations involved in Müllerian aplasia and hyperandrogenism change single protein building blocks (amino acids) in the WNT4 protein. Researchers suspect that the altered protein cannot be released from cells as it normally would be; the trapped protein is unable to perform its usual functions. Loss of regulation by WNT4 likely disrupts development of the female reproductive system and induces abnormal production of androgens, leading to the features of Müllerian aplasia and hyperandrogenism.

other disorders - caused by mutations in the WNT4 gene

A mutation in the WNT4 gene has been found to cause a severe condition called SERKAL (SEx Reversal and abnormal development of Kidneys, Adrenals, and Lungs) syndrome. In this condition, male sex development may occur despite the chromosome pattern typical of females. SERKAL syndrome has been reported in only one family and likely is not compatible with life. The mutation that causes SERKAL syndrome replaces the protein building block (amino acid) alanine with the amino acid valine at position 114 in the WNT4 protein (written as Ala114Val or A114V). This mutation is present in both copies of the WNT4 gene in each cell and likely eliminates the function of the WNT4 protein. The absence of WNT4 protein results in the wide variety of developmental abnormalities seen in SERKAL syndrome.

A duplication of genetic material in a specific region of chromosome 1 can result in an extra copy of the WNT4 gene. Having an additional copy of this gene leads to the production of extra WNT4 protein. People with this duplication may develop some female features despite having the chromosome pattern typical of males. These individuals can have an underdeveloped uterus and nonfunctional testes.

Where is the WNT4 gene located?

Cytogenetic Location: 1p36.23-p35.1

Molecular Location on chromosome 1: base pairs 22,117,305 to 22,143,981

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (

The WNT4 gene is located on the short (p) arm of chromosome 1 between positions 36.23 and 35.1.

The WNT4 gene is located on the short (p) arm of chromosome 1 between positions 36.23 and 35.1.

More precisely, the WNT4 gene is located from base pair 22,117,305 to base pair 22,143,981 on chromosome 1.

See How do geneticists indicate the location of a gene? ( in the Handbook.

Where can I find additional information about WNT4?

You and your healthcare professional may find the following resources about WNT4 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the WNT4 gene or gene products?

  • wingless-type MMTV integration site family, member 4
  • WNT-4
  • WNT-4 protein

See How are genetic conditions and genes named? ( in the Handbook.

What glossary definitions help with understanding WNT4?

acids ; acne ; alanine ; amino acid ; androgens ; cell ; chromosome ; duplication ; egg ; embryo ; embryonic ; gene ; hormone ; mutation ; protein ; syndrome ; testes ; valine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Bernard P, Harley VR. Wnt4 action in gonadal development and sex determination. Int J Biochem Cell Biol. 2007;39(1):31-43. Epub 2006 Jul 5. Review. (
  • Biason-Lauber A, De Filippo G, Konrad D, Scarano G, Nazzaro A, Schoenle EJ. WNT4 deficiency--a clinical phenotype distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome: a case report. Hum Reprod. 2007 Jan;22(1):224-9. Epub 2006 Sep 7. (
  • Biason-Lauber A, Konrad D, Navratil F, Schoenle EJ. A WNT4 mutation associated with Müllerian-duct regression and virilization in a 46,XX woman. N Engl J Med. 2004 Aug 19;351(8):792-8. (
  • Biason-Lauber A, Konrad D. WNT4 and sex development. Sex Dev. 2008;2(4-5):210-8. doi: 10.1159/000152037. Epub 2008 Nov 5. Review. (
  • Biason-Lauber A. WNT4, RSPO1, and FOXL2 in sex development. Semin Reprod Med. 2012 Oct;30(5):387-95. doi: 10.1055/s-0032-1324722. Epub 2012 Oct 8. Review. (
  • Clément-Ziza M, Khen N, Gonzales J, Crétolle-Vastel C, Picard JY, Tullio-Pelet A, Besmond C, Munnich A, Lyonnet S, Nihoul-Fékété C. Exclusion of WNT4 as a major gene in Rokitansky-Küster-Hauser anomaly. Am J Med Genet A. 2005 Aug 15;137(1):98-9. (
  • Jääskeläinen M, Prunskaite-Hyyryläinen R, Naillat F, Parviainen H, Anttonen M, Heikinheimo M, Liakka A, Ola R, Vainio S, Vaskivuo TE, Tapanainen JS. WNT4 is expressed in human fetal and adult ovaries and its signaling contributes to ovarian cell survival. Mol Cell Endocrinol. 2010 Apr 12;317(1-2):106-11. doi: 10.1016/j.mce.2009.11.013. Epub 2009 Dec 3. (
  • Jordan BK, Mohammed M, Ching ST, Délot E, Chen XN, Dewing P, Swain A, Rao PN, Elejalde BR, Vilain E. Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans. Am J Hum Genet. 2001 May;68(5):1102-9. Epub 2001 Mar 29. (
  • Mandel H, Shemer R, Borochowitz ZU, Okopnik M, Knopf C, Indelman M, Drugan A, Tiosano D, Gershoni-Baruch R, Choder M, Sprecher E. SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4. Am J Hum Genet. 2008 Jan;82(1):39-47. doi: 10.1016/j.ajhg.2007.08.005. (
  • NCBI Gene (
  • Philibert P, Biason-Lauber A, Rouzier R, Pienkowski C, Paris F, Konrad D, Schoenle E, Sultan C. Identification and functional analysis of a new WNT4 gene mutation among 28 adolescent girls with primary amenorrhea and müllerian duct abnormalities: a French collaborative study. J Clin Endocrinol Metab. 2008 Mar;93(3):895-900. doi: 10.1210/jc.2007-2023. Epub 2008 Jan 8. (
  • Prunskaite-Hyyryläinen R, Shan J, Railo A, Heinonen KM, Miinalainen I, Yan W, Shen B, Perreault C, Vainio SJ. Wnt4, a pleiotropic signal for controlling cell polarity, basement membrane integrity, and antimüllerian hormone expression during oocyte maturation in the female follicle. FASEB J. 2014 Apr;28(4):1568-81. doi: 10.1096/fj.13-233247. Epub 2013 Dec 26. (


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 healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: July 2014
Published: February 8, 2016