FZD<sub>9</sub> | Class Frizzled GPCRs | IUPHAR/BPS Guide to PHARMACOLOGY

FZD9

Target id: 237

Nomenclature: FZD9

Family: Class Frizzled GPCRs

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for FZD9 in GtoImmuPdb

Gene and Protein Information
Frizzled family G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 591 7q11.23 FZD9 frizzled class receptor 9
Mouse 7 592 5 G2 Fzd9 frizzled class receptor 9
Rat 7 592 12q12 Fzd9 frizzled class receptor 9
Previous and Unofficial Names
CD349 | FZD3 | frizzled family receptor 9 | FZD9
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
Wnt
Agonist Comments
Wnt-2 activates FZD9-dependent TCF transcription [4]. Wnt-7a interacts with FZD9 and activates the JNK pathway [9].
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
References:  5
Tissue Distribution
Neural tube, trunk skeletal muscle precursors (myotomes), limb skeletal anlagen, craniofacial regions, nephric ducts in embryos
Species:  Mouse
Technique:  In situ hybridisation
References:  8
Heart, brain, testis, and skeletal muscle in adults
Species:  Mouse
Technique:  Northern blot
References:  8
Medial cortical wall
Species:  Mouse
Technique:  Immunohistochemistry
References:  11
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Wnt-2 activates Fzd9 in T cell factor (TCF)-dependent transcription
Species:  Rat
Tissue:  HEK293T cells
Response measured:  TCF activation
References:  4
Wnt-7a and Fzd9 signaling through activation of the JNK pathway induces cadherin proteins and the receptor tyrosine kinase inhibitor Sprouty-4
Species:  Mouse
Tissue:  NSCLC cells
Response measured:  JNK pathway activation
References:  9
FZD9 is present in a locus which is aberantly methylated in myelodysplastic syndromes
Species:  Human
Tissue:  Bone marrow
Response measured:  Correlation with survival prognosis
References:  3
Physiological Functions
FZD9 siRNA reduced cell proliferation and motility
Species:  Human
Tissue:  HB and HCC cells
References:  2
Physiological Consequences of Altering Gene Expression
Increased apoptotic cell death and increased precursor proliferation during hippocampal development and severe defects in learning and memory deficits in null mutants
Species:  Mouse
Tissue:  Brain
Technique:  Gene knockouts
References:  10
Depletion of developing B cells in the bone marrow and reduced life expectancy of mice with receptor knockout
Species:  Mouse
Tissue:  Bone marrow
Technique:  Gene knockouts
References:  6
Mice with receptor knockout display low bone mass caused by impaired bone formation
Species:  Mouse
Tissue:  Bone
Technique:  Gene knockouts
References:  1
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Fzd9tm1Lex Fzd9tm1Lex/Fzd9tm1Lex
involves: 129S5/SvEvBrd * C57BL/6J
MGI:1313278  MP:0003795 abnormal bone structure
Fzd9tm1Sjp Fzd9tm1Sjp/Fzd9tm1Sjp
involves: C57BL/6J
MGI:1313278  MP:0000812 abnormal dentate gyrus morphology PMID: 15930120 
Fzd9+|Fzd9tm1Sjp Fzd9tm1Sjp/Fzd9+
involves: C57BL/6J
MGI:1313278  MP:0000812 abnormal dentate gyrus morphology PMID: 15930120 
Fzd9tm1Sjp Fzd9tm1Sjp/Fzd9tm1Sjp
involves: C57BL/6J
MGI:1313278  MP:0003232 abnormal forebrain development PMID: 15930120 
Fzd9+|Fzd9tm1Sjp Fzd9tm1Sjp/Fzd9+
involves: C57BL/6J
MGI:1313278  MP:0003232 abnormal forebrain development PMID: 15930120 
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0002339 abnormal lymph node morphology PMID: 15572594 
Fzd9tm1Sjp Fzd9tm1Sjp/Fzd9tm1Sjp
involves: C57BL/6J
MGI:1313278  MP:0001463 abnormal spatial learning PMID: 15930120 
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0002362 abnormal spleen marginal zone morphology PMID: 15572594 
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0002356 abnormal spleen red pulp morphology PMID: 15572594 
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0005017 decreased B cell number PMID: 15572594 
Fzd9tm1Lex Fzd9tm1Lex/Fzd9tm1Lex
involves: 129S5/SvEvBrd * C57BL/6J
MGI:1313278  MP:0001258 decreased body length
Fzd9tm1Lex Fzd9tm1Lex/Fzd9tm1Lex
involves: 129S5/SvEvBrd * C57BL/6J
MGI:1313278  MP:0001262 decreased body weight
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0008209 decreased pre-B cell number PMID: 15572594 
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0008208 decreased pro-B cell number PMID: 15572594 
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0000702 enlarged lymph nodes PMID: 15572594 
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0000691 enlarged spleen PMID: 15572594 
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0005011 increased eosinophil cell number PMID: 15572594 
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0000218 increased leukocyte cell number PMID: 15572594 
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0000220 increased monocyte cell number PMID: 15572594 
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0000219 increased neutrophil cell number PMID: 15572594 
Fzd9tm1Sjp Fzd9tm1Sjp/Fzd9tm1Sjp
involves: C57BL/6J
MGI:1313278  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 15930120 
Fzd9tm1Lex Fzd9tm1Lex/Fzd9tm1Lex
involves: 129S5/SvEvBrd * C57BL/6J
MGI:1313278  MP:0001732 postnatal growth retardation
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0002083 premature death PMID: 15572594 
Fzd9tm1Uta Fzd9tm1Uta/Fzd9tm1Uta
involves: 129S6/SvEvTac * 129X1/SvJ
MGI:1313278  MP:0003644 thymus atrophy PMID: 15572594 
Clinically-Relevant Mutations and Pathophysiology Comments
FZD9 is located in 7q11.23, the same locus, where the deletion causing Williams syndrome occurs [7].

References

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1. Albers J, Schulze J, Beil FT, Gebauer M, Baranowsky A, Keller J, Marshall RP, Wintges K, Friedrich FW, Priemel M et al.. (2011) Control of bone formation by the serpentine receptor Frizzled-9. J. Cell Biol., 192 (6): 1057-72. [PMID:21402791]

2. Fujimoto T, Tomizawa M, Yokosuka O. (2009) SiRNA of frizzled-9 suppresses proliferation and motility of hepatoma cells. Int. J. Oncol., 35 (4): 861-6. [PMID:19724923]

3. Jiang Y, Dunbar A, Gondek LP, Mohan S, Rataul M, O'Keefe C, Sekeres M, Saunthararajah Y, Maciejewski JP. (2009) Aberrant DNA methylation is a dominant mechanism in MDS progression to AML. Blood, 113 (6): 1315-25. [PMID:18832655]

4. Karasawa T, Yokokura H, Kitajewski J, Lombroso PJ. (2002) Frizzled-9 is activated by Wnt-2 and functions in Wnt/beta -catenin signaling. J. Biol. Chem., 277 (40): 37479-86. [PMID:12138115]

5. Ramírez VT, Ramos-Fernández E, Henríquez JP, Lorenzo A, Inestrosa NC. (2016) Wnt-5a/Frizzled9 Receptor Signaling through the Gαo-Gβγ Complex Regulates Dendritic Spine Formation. J. Biol. Chem., 291 (36): 19092-107. [PMID:27402827]

6. Ranheim EA, Kwan HC, Reya T, Wang YK, Weissman IL, Francke U. (2005) Frizzled 9 knock-out mice have abnormal B-cell development. Blood, 105 (6): 2487-94. [PMID:15572594]

7. Wang YK, Samos CH, Peoples R, Pérez-Jurado LA, Nusse R, Francke U. (1997) A novel human homologue of the Drosophila frizzled wnt receptor gene binds wingless protein and is in the Williams syndrome deletion at 7q11.23. Hum. Mol. Genet., 6 (3): 465-72. [PMID:9147651]

8. Wang YK, Spörle R, Paperna T, Schughart K, Francke U. (1999) Characterization and expression pattern of the frizzled gene Fzd9, the mouse homolog of FZD9 which is deleted in Williams-Beuren syndrome. Genomics, 57 (2): 235-48. [PMID:10198163]

9. Winn RA, Marek L, Han SY, Rodriguez K, Rodriguez N, Hammond M, Van Scoyk M, Acosta H, Mirus J, Barry N et al.. (2005) Restoration of Wnt-7a expression reverses non-small cell lung cancer cellular transformation through frizzled-9-mediated growth inhibition and promotion of cell differentiation. J. Biol. Chem., 280 (20): 19625-34. [PMID:15705594]

10. Zhao C, Avilés C, Abel RA, Almli CR, McQuillen P, Pleasure SJ. (2005) Hippocampal and visuospatial learning defects in mice with a deletion of frizzled 9, a gene in the Williams syndrome deletion interval. Development, 132 (12): 2917-27. [PMID:15930120]

11. Zhao C, Pleasure SJ. (2005) Frizzled9 protein is regionally expressed in the developing medial cortical wall and the cells derived from this region. Brain Res. Dev. Brain Res., 157 (1): 93-7. [PMID:15939089]

Contributors

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How to cite this page

Gunnar Schulte, Jacomijn Dijksterhuis, Julian Petersen, Elisa Arthofer, Belma Hot, Katerina Strakova, Shane Wright, Jana Valnohova, Matthias Lauth.
Class Frizzled GPCRs: FZD9. Last modified on 22/02/2017. Accessed on 19/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=237.