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Gene Review

FZD5  -  frizzled class receptor 5

Homo sapiens

Synonyms: C2orf31, DKFZP434E2135, Frizzled-5, Fz-5, FzE5, ...
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Disease relevance of FZD5


High impact information on FZD5

  • Wnt-5A induced axis duplication and an ectopic Spemann organizer in the presence of hFz5, a member of the Frizzled family of seven-transmembrane receptors [6].
  • We show that human peripheral-blood mononuclear cells express the WNT5A receptor Frizzled-5 (FZD5) [2].
  • Furthermore, among the three known Wnt pathways, Fz5/8 appears to signal via the planar cell polarity pathway [7].
  • During development, Fz5/8 displays restricted expression, beginning at the 60-cell stage in the animal domain and then from mesenchyme blastula stage, in both the animal domain and a subset of secondary mesenchyme cells (SMCs) [7].
  • GSK-3beta is a component of the wnt signaling pathway, and EC express wnt-5a and T cells express frizzled-5, a wnt-5a receptor [8].

Biological context of FZD5


Anatomical context of FZD5

  • Functional studies showed that WNT5A and FZD5 regulate the microbially induced interleukin-12 response of antigen-presenting cells and interferon-gamma production by mycobacterial antigen-stimulated T cells [2].
  • FZD5 was highly expressed in fetal liver and adult pancreas, and moderately expressed in fetal lung, kidney and adult liver [3].
  • Previously, we found that these FLS expressed high levels of both Wnt-5A and Frizzled 5 (Fz5), a receptor-ligand pair implicated in both limb bud and bone marrow stem cell development [9].

Other interactions of FZD5

  • Among human FZD family, FZD8 was most homologous to FZD5 (total amino-acid identity 69.1%) [10].
  • For FZD5, we did not observe a segregating variant, however, for PTHR2, a missense variant (A225S) cosegregated with FOA in one family [11].
  • Wnt-independent activation of beta-catenin mediated by a Dkk1-Fz5 fusion protein [12].

Analytical, diagnostic and therapeutic context of FZD5

  • Western blot analysis of crude membrane fractions revealed that Fzd5 protein expression in the matched tumor/normal kidney samples correlated with the observed mRNA level [5].


  1. Conserved POU-binding site linked to SP1-binding site within FZD5 promoter: Transcriptional mechanisms of FZD5 in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and diffuse-type gastric cancer. Katoh, Y., Katoh, M. Int. J. Oncol. (2007) [Pubmed]
  2. The Wingless homolog WNT5A and its receptor Frizzled-5 regulate inflammatory responses of human mononuclear cells induced by microbial stimulation. Blumenthal, A., Ehlers, S., Lauber, J., Buer, J., Lange, C., Goldmann, T., Heine, H., Brandt, E., Reiling, N. Blood (2006) [Pubmed]
  3. Molecular cloning and characterization of human Frizzled-5 gene on chromosome 2q33.3-q34 region. Saitoh, T., Hirai, M., Katoh, M. Int. J. Oncol. (2001) [Pubmed]
  4. A formylated hexapeptide ligand mimics the ability of Wnt-5a to impair migration of human breast epithelial cells. Säfholm, A., Leandersson, K., Dejmek, J., Nielsen, C.K., Villoutreix, B.O., Andersson, T. J. Biol. Chem. (2006) [Pubmed]
  5. Alteration of frizzled expression in renal cell carcinoma. Janssens, N., Andries, L., Janicot, M., Perera, T., Bakker, A. Tumour Biol. (2004) [Pubmed]
  6. A member of the Frizzled protein family mediating axis induction by Wnt-5A. He, X., Saint-Jeannet, J.P., Wang, Y., Nathans, J., Dawid, I., Varmus, H. Science (1997) [Pubmed]
  7. Frizzled5/8 is required in secondary mesenchyme cells to initiate archenteron invagination during sea urchin development. Croce, J., Duloquin, L., Lhomond, G., McClay, D.R., Gache, C. Development (2006) [Pubmed]
  8. Endothelial cells stimulate T cell NFAT nuclear translocation in the presence of cyclosporin A: involvement of the wnt/glycogen synthase kinase-3 beta pathway. Murphy, L.L., Hughes, C.C. J. Immunol. (2002) [Pubmed]
  9. Blockade of Wnt-5A/frizzled 5 signaling inhibits rheumatoid synoviocyte activation. Sen, M., Chamorro, M., Reifert, J., Corr, M., Carson, D.A. Arthritis Rheum. (2001) [Pubmed]
  10. Molecular cloning and characterization of human Frizzled-8 gene on chromosome 10p11.2. Saitoh, T., Hirai, M., Katoh, M. Int. J. Oncol. (2001) [Pubmed]
  11. Strong linkage on 2q33.3 to familial early-onset generalized osteoarthritis and a consideration of two positional candidate genes. Meulenbelt, I., Min, J.L., van Duijn, C.M., Kloppenburg, M., Breedveld, F.C., Slagboom, P.E. Eur. J. Hum. Genet. (2006) [Pubmed]
  12. Wnt-independent activation of beta-catenin mediated by a Dkk1-Fz5 fusion protein. Holmen, S.L., Robertson, S.A., Zylstra, C.R., Williams, B.O. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
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