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FZD9

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Target not currently curated in GtoImmuPdb

Target id: 237

Nomenclature: FZD9

Family: Class Frizzled GPCRs

Gene and Protein Information Click here for help
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 75.08 cM Fzd9 frizzled class receptor 9
Rat 7 592 12q12 Fzd9 frizzled class receptor 9
Previous and Unofficial Names Click here for help
CD349 | FZD3 | frizzled family receptor 9 | FZD9
Database Links Click here for help
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
Wnt
Agonist Comments
Wnt-2 activates FZD9-dependent TCF transcription [4]. Wnt-7a interacts with FZD9 and activates the JNK pathway [9].
Immuno Process Associations
Immuno Process:  Tissue repair
GO Annotations:  Associated to 1 GO processes
GO:1990523 bone regeneration ISS
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:0030183 B cell differentiation IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:0030183 B cell differentiation IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:0030183 B cell differentiation IEA
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family
References:  5
Tissue Distribution Click here for help
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 Click here for help

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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 Click here for help
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 Click here for help
FZD9 siRNA reduced cell proliferation and motility
Species:  Human
Tissue:  HB and HCC cells
References:  2
Physiological Consequences of Altering Gene Expression Click here for help
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 Click here for help 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]

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