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Genetics Home Reference: your guide to understanding genetic conditions
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FZD4

Reviewed February 2009

What is the official name of the FZD4 gene?

The official name of this gene is “frizzled class receptor 4.”

FZD4 is the gene's official symbol. The FZD4 gene is also known by other names, listed below.

What is the normal function of the FZD4 gene?

The FZD4 gene provides instructions for making a protein called frizzled-4. This protein is embedded in the outer membrane of many types of cells, where it is involved in transmitting chemical signals from outside the cell to the cell's nucleus. Specifically, frizzled-4 participates in the Wnt signaling pathway, a series of steps that affect the way cells and tissues develop. Wnt signaling is important for cell division (proliferation), attachment of cells to one another (adhesion), cell movement (migration), and many other cellular activities.

Studies suggest that, at the cell surface, the frizzled-4 protein interacts with a protein called norrin (produced from the NDP gene). The two proteins fit together like a key in a lock. Researchers suspect that when norrin attaches (binds) to frizzled-4, it initiates a multi-step process that regulates the activity of certain genes. During early development, signaling by norrin and frizzled-4 plays a critical role in the specialization of cells in the retina, which is the light-sensing tissue at the back of the eye. This signaling pathway is also involved in the establishment of a blood supply to the retina and the inner ear.

Does the FZD4 gene share characteristics with other genes?

The FZD4 gene belongs to a family of genes called CD (CD molecules). It also belongs to a family of genes called GPCRF (class F GPCRs, frizzled-type).

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 FZD4 gene related to health conditions?

familial exudative vitreoretinopathy - caused by mutations in the FZD4 gene

More than 20 mutations in the FZD4 gene have been identified in people with an eye disorder called familial exudative vitreoretinopathy. Some of these mutations change single protein building blocks (amino acids) in frizzled-4, while others insert or delete genetic material in the FZD4 gene. Most FZD4 mutations reduce the amount of frizzled-4 that is produced within cells. Other mutations are thought to result in the production of an unstable protein that cannot bind to norrin.

A reduction in the amount of frizzled-4 disrupts chemical signaling in the developing eye, which interferes with the formation of blood vessels at the edges of the retina. The resulting abnormal blood supply to this tissue leads to retinal damage and vision loss in some people with familial exudative vitreoretinopathy.

Where is the FZD4 gene located?

Cytogenetic Location: 11q14.2

Molecular Location on chromosome 11: base pairs 86,945,674 to 86,955,397

The FZD4 gene is located on the long (q) arm of chromosome 11 at position 14.2.

The FZD4 gene is located on the long (q) arm of chromosome 11 at position 14.2.

More precisely, the FZD4 gene is located from base pair 86,945,674 to base pair 86,955,397 on chromosome 11.

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 FZD4?

You and your healthcare professional may find the following resources about FZD4 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 FZD4 gene or gene products?

  • CD344
  • EVR1
  • FEVR
  • frizzled 4
  • frizzled family receptor 4
  • frizzled homolog 4 (Drosophila)
  • Fz-4
  • FZD4_HUMAN
  • FZD4S
  • FzE4
  • GPCR
  • MGC34390
  • WNT receptor frizzled-4

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 FZD4?

acids ; cell ; cell division ; class ; familial ; gene ; nucleus ; proliferation ; protein ; receptor ; retina ; tissue

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

References

  • Kondo H, Hayashi H, Oshima K, Tahira T, Hayashi K. Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity. Br J Ophthalmol. 2003 Oct;87(10):1291-5. (http://www.ncbi.nlm.nih.gov/pubmed/14507768?dopt=Abstract)
  • Nallathambi J, Shukla D, Rajendran A, Namperumalsamy P, Muthulakshmi R, Sundaresan P. Identification of novel FZD4 mutations in Indian patients with familial exudative vitreoretinopathy. Mol Vis. 2006 Sep 21;12:1086-92. (http://www.ncbi.nlm.nih.gov/pubmed/17093393?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/8322)
  • Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H. Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes. Hum Mutat. 2005 Aug;26(2):104-12. (http://www.ncbi.nlm.nih.gov/pubmed/15981244?dopt=Abstract)
  • Qin M, Kondo H, Tahira T, Hayashi K. Moderate reduction of Norrin signaling activity associated with the causative missense mutations identified in patients with familial exudative vitreoretinopathy. Hum Genet. 2008 Jan;122(6):615-23. Epub 2007 Oct 23. (http://www.ncbi.nlm.nih.gov/pubmed/17955262?dopt=Abstract)
  • Toomes C, Bottomley HM, Jackson RM, Towns KV, Scott S, Mackey DA, Craig JE, Jiang L, Yang Z, Trembath R, Woodruff G, Gregory-Evans CY, Gregory-Evans K, Parker MJ, Black GC, Downey LM, Zhang K, Inglehearn CF. Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. Am J Hum Genet. 2004 Apr;74(4):721-30. Epub 2004 Mar 11. (http://www.ncbi.nlm.nih.gov/pubmed/15024691?dopt=Abstract)
  • Toomes C, Bottomley HM, Scott S, Mackey DA, Craig JE, Appukuttan B, Stout JT, Flaxel CJ, Zhang K, Black GC, Fryer A, Downey LM, Inglehearn CF. Spectrum and frequency of FZD4 mutations in familial exudative vitreoretinopathy. Invest Ophthalmol Vis Sci. 2004 Jul;45(7):2083-90. (http://www.ncbi.nlm.nih.gov/pubmed/15223780?dopt=Abstract)
  • Warden SM, Andreoli CM, Mukai S. The Wnt signaling pathway in familial exudative vitreoretinopathy and Norrie disease. Semin Ophthalmol. 2007 Oct-Dec;22(4):211-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18097984?dopt=Abstract)
  • Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell. 2004 Mar 19;116(6):883-95. (http://www.ncbi.nlm.nih.gov/pubmed/15035989?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: March 30, 2015