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Genetics Home Reference: your guide to understanding genetic conditions
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WNT4

Reviewed February 2009

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 duct, a structure present in the embryo that develops into the uterus, fallopian tubes, cervix, and the upper part of the vagina. This protein also regulates the production of male sex hormones (androgens) and the development and maintenance of egg cells (oocytes).

Does the WNT4 gene share characteristics with other genes?

The WNT4 gene belongs to a family of genes called WNT (wingless-type MMTV integration site family).

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? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

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

WNT4 Müllerian aplasia and ovarian dysfunction - caused by mutations in the WNT4 gene

At least three mutations in the WNT4 gene have been found to cause WNT4 Müllerian aplasia and ovarian dysfunction. These mutations change single protein building blocks (amino acids) in the WNT4 protein. Researchers suspect that the altered protein cannot be secreted, which would leave it trapped within cells and unable to perform its usual functions. It remains unclear how mutations in the WNT4 gene lead to the signs and symptoms of WNT4 Müllerian aplasia and ovarian dysfunction.

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 non-functional testes.

Where is the WNT4 gene located?

Cytogenetic Location: 1p36.23-p35.1

Molecular Location on chromosome 1: base pairs 22,443,797 to 22,469,518

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 22,443,797 to base pair 22,469,518 on chromosome 1.

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 WNT4?

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

  • Educational resources - Information pages
    Developmental Biology (sixth edition, 2000): Wnt4: a potential ovary-determining gene on an autosome (http://www.ncbi.nlm.nih.gov/books/NBK9967/)
  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1547/)

  • Genetic Testing Registry - Repository of genetic test information

    • GTR: Genetic tests for WNT4 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=54361%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=(WNT4%5BTIAB%5D)%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)

  • OMIM - Genetic disorder catalog

    • 46,XX SEX REVERSAL WITH DYSGENESIS OF KIDNEYS, ADRENALS, AND LUNGS (http://omim.org/entry/611812)
    • WINGLESS-TYPE MMTV INTEGRATION SITE FAMILY, MEMBER 4 (http://omim.org/entry/603490)

  • Research Resources - Tools for researchers

    • Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_WNT4.html)
    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/54361)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=54361)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=12783)

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

  • WNT-4
  • WNT4_HUMAN
  • WNT-4 protein

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 WNT4?

acids ; amino acid ; androgens ; cell ; chromosome ; duct ; duplication ; egg ; embryo ; embryonic ; gene ; hormone ; mutation ; ovarian ; protein ; syndrome ; testes

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/16905353?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/16959810?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/15317892?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18987495?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/16007613?dopt=Abstract)
  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/54361)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/11283799?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18179883?dopt=Abstract)
  • OMIM: 46,XX SEX REVERSAL WITH DYSGENESIS OF KIDNEYS, ADRENALS, AND LUNGS (http://omim.org/entry/611812)
  • OMIM: WINGLESS-TYPE MMTV INTEGRATION SITE FAMILY, MEMBER 4 (http://omim.org/entry/603490)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18182450?dopt=Abstract)

 

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? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2009
Published: May 20, 2013