This gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Frizzled-4 is the only representative of frizzled family members that binds strongly an additional ligand Norrin that is functionally similar but structurally different from Wingless type proteins.[8] FZD4 signaling induced by Norrin regulates vascular development of vertebrate retina and controls important blood vessels in the ear. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This protein may play a role as a positive regulator of the Wingless type MMTV integration site signaling pathway. A transcript variant retaining intronic sequence and encoding a shorter isoform has been described, however, its expression is not supported by other experimental evidence.[7]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Kirikoshi H, Sagara N, Koike J, Tanaka K, Sekihara H, Hirai M, Katoh M (Nov 1999). "Molecular cloning and characterization of human Frizzled-4 on chromosome 11q14-q21". Biochemical and Biophysical Research Communications. 264 (3): 955–61. doi:10.1006/bbrc.1999.1612. PMID10544037.
Li Y, Fuhrmann C, Schwinger E, Gal A, Laqua H (Jun 1992). "The gene for autosomal dominant familial exudative vitreoretinopathy (Criswick-Schepens) on the long arm of chromosome 11". American Journal of Ophthalmology. 113 (6): 712–3. doi:10.1016/s0002-9394(14)74800-7. PMID1598965.
Sagara N, Kirikoshi H, Terasaki H, Yasuhiko Y, Toda G, Shiokawa K, Katoh M (Apr 2001). "FZD4S, a splicing variant of frizzled-4, encodes a soluble-type positive regulator of the WNT signaling pathway". Biochemical and Biophysical Research Communications. 282 (3): 750–6. doi:10.1006/bbrc.2001.4634. PMID11401527.
Omoto S, Hayashi T, Kitahara K, Takeuchi T, Ueoka Y (Jun 2004). "Autosomal dominant familial exudative vitreoretinopathy in two Japanese families with FZD4 mutations (H69Y and C181R)". Ophthalmic Genetics. 25 (2): 81–90. doi:10.1080/13816810490514270. PMID15370539. S2CID32817238.
Yoshida S, Arita R, Yoshida A, Tada H, Emori A, Noda Y, Nakao S, Fujisawa K, Ishibashi T (Oct 2004). "Novel mutation in FZD4 gene in a Japanese pedigree with familial exudative vitreoretinopathy". American Journal of Ophthalmology. 138 (4): 670–1. doi:10.1016/j.ajo.2004.05.001. PMID15488808.
Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H (Aug 2005). "Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes". Human Mutation. 26 (2): 104–12. doi:10.1002/humu.20191. PMID15981244. S2CID20271372.
Nallathambi J, Shukla D, Rajendran A, Namperumalsamy P, Muthulakshmi R, Sundaresan P (2006). "Identification of novel FZD4 mutations in Indian patients with familial exudative vitreoretinopathy". Molecular Vision. 12: 1086–92. PMID17093393.