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FZD5 (frizzled class receptor 5)

Written2018-06Ilaria Esposito
Department of Health Sciences, University of Milan, via A. Di Rudinò, 8 20142, Milan (Italy);ilaria.esposito1@studenti.unimi.it

Abstract The Wnt signalling pathways are ways of signalling that transduce signals into cells through cell surface receptors; they are three different type of pathways and all of these are activated by binding a Wnt-protein ligand to a Frizzled family receptor. Frizzled is a family of G-protein coupled receptor proteins that works as receptor in the Wnt signalling pathway; when activated, Frizzled works activating the Dishevelled protein inside the cell, to transduce the signal. Frizzled-5 (FZD5) is part of this family and it is encoded by the FZD5 gene (located on the chr2, 2q33.3). Like all Frizzled members, FZD5 has an amino-terminal cysteine-rich domain (CRD) which allows the Wnt binding, seven-transmembrane domains and a cytoplasmic tail containing the PDZ domain binding motif at the carboxy-terminus. FZD5 shows an important role in development and it seems to be overexpressed in several types of cancer. FZD5 preferably binds WNT3A, WNT5A, WNT7A and WNT10B, activating both canonical and non-canonical pathways.

Keywords Wnt signalling pathway, FZD5, Frizzled, Coloboma

(Note : for Links provided by Atlas : click)

Identity

Alias_namesC2orf31
frizzled (Drosophila) homolog 5
chromosome 2 open reading frame 31
frizzled homolog 5 (Drosophila)
frizzled 5, seven transmembrane spanning receptor
frizzled family receptor 5
Alias_symbol (synonym)HFZ5
DKFZP434E2135
Other aliasC2orf31 (Chromosome 2 open reading frame 31)
Frizzled-5, seven transmembrane spanning receptor,
Fz-5
FzE5
HGNC (Hugo) FZD5
LocusID (NCBI) 7855
Atlas_Id 47614
Location 2q33.3 [link to chromosomal band 2q33.  [Link to chromosome band 2q33]
Location_base_pair Starts at 207762586 and ends at 207769419 bp from pter ( according to hg19-Feb_2009)  [Mapping FZD5.png]
 
  Figure 1: A) Location of FZD5 gene on chr2. B) Schematic representation of FZD5 gene, with exons 1 and 2. C) Protein structure and the subdivision into various domains.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

Note The FZD5 gene (6978 bp) contains a total of 2 exons and the FZD5 transcript is 6708 bp.
 
  Figure 2: Schematic representation of FZD5 gene.
Description Genomic size: 6978 bp. Exons count: 2, only one of which is coding. This gene has 1 transcript (splice variant), 66 orthologues, 12 paralogues.
Transcription 1 transcript variant has been found for this gene (font. www.ensembl.org). FZD5-201 ENST00000295417.3: mRNA 6708 bp, protein 585 aa.

Protein

 
  Figure 3: Schematic illustration of domains of FZD5 protein.
Description FZD5 protein, comprised of 585 aa with a mass of 64 kDa, is part of the frizzled gene family, 7-transmembrane domain proteins, which includes 10 members (FZD1 to FZD10). The FZD1-10 are bound and activated by the WNT family of lipoglycoproteins, inducing a network of signalling pathways: the WNT-FZD signalling system has a prevalent role in physiology during adulthood and dysfunction of this signalling leads to diseases, such as cancer and neurological and bone disorders. Wnt signals are transduced through at least three different pathways, including the canonical Wnt/β-catenin pathway, the Wnt/Ca2+ pathway, and the non-canonical planar cell polarity (PCP). The exclusive involvement of FZD5 in one of these three pathways is unclear, although some cases have been reported that WNT5A activate the canonical pathway in the presence of overexpressed FZD5 (He et al., 1997) and that WNT7A interacts with FZD5 to activate CTNNB1 (β-catenin)/canonical signalling (Carmon and Loose, 2008); however other evidences report that FZD5 can been associated with non-canonical Wnt signalling (Bischoff et al., 2015).
The secondary structure of FZD5 protein is composed by a large domain, the FZ domain, and two motifs, the Lys-Thr-X-X-X-Trp motif, and the PDZ-binding motif. The FZ domain (from aa 28 to aa 150) is an intracellular domain of about 120 amino acids, located close to the N-terminal end, first identified in the alpha-1 chain of mouse type XVIII collagen (Rehn and Pihlajaniemi, 1995). The FZ domain, also known as CRD (cysteine rich domain) contains 10 conserved cysteines, and its crystal structure shows predominance of α -helix with disulphide bonds. Its presence is widely demonstrated to be involved in Wnt signalling (Povelones et al., 2005). The C-terminal cytoplasmic Lys-Thr-X-X-X-Trp motif (from aa 525 to aa 530) is located two amino acids after the seventh TM and frizzled receptors with point mutations into this motif lose their capacity to activate Wnt/β-catenin signalling (Umbhauer et al., 2000). The PDZ domain (from aa 583 to aa 585) is a structural domain found in the signalling proteins and it plays a role in transport, ion channel signalling and transduction system, that typically recognize the extreme C-terminal end of the target proteins (Lee and Zheng, 2010).
 
  Figure 4: Visualization of WNT10B-FZD5 interaction in MCF-7 adherent cells (Lazzaroni et al., 2016).
Expression Ishikawa et al. (2001) first isolated and characterized this novel mouse frizzled gene Fzd5. Its mRNA was expressed in the yolk sac, eyes and lung bud at 9.5 days post coitum, demonstrating its essential role in development. In Xenopus embryos, after determining synergistic interactions between Wnts and frizzleds, misexpression, disruption or depletion of these components of Wnt pathway can inhibit the dorsal axis formation: these results suggest that the frizzled proteins work as receptors for Wnt ligands. To confirm that, Ishikawa et al. presents the evidence that the homozygous Fzd5 knockout mice are embryonically lethal, due to the defects they develop in the yolk sac vasculogenesis. Fzd5 is expressed in the developing retina in zebrafish, Xenopus Laevis, chick and mouse. Later, human FZD5 was mapped on chromosome 2q33.3-q34 (Saitoh et al., 2001) and one of its ligand, WNT7A, activate Wnt/β-catenin signalling pathway and cell motility/invasion in metastatic melanoma, endometrial and ovarian cancer cell lines (Carmon and Loose, 2008, Ueno et al., 2013).
Localisation FZD5 is localized at the plasma membrane and it is also found at the Golgi apparatus membrane. (UniProt FZD5)
Function FZD5 is part of the 7-transmembrane domain proteins, receptors for Wnt signalling proteins. When the Wnt signalling pathway is activated, FZD receptors are internalized in response to their Wnt ligands: internalization of FZD5 is induced by WNT3A, complexed with LRP6 (Yamamoto et al., 2006). A recent study (Terabayashi et al., 2009) demonstrated that FZD5 is internalized in response to WNT3A stimulation via the clathrin-dependent pathway to activate downstream signalling pathways. Terabayashi et al., found that the expression of SCYL2 (CVAK104), a coated vesicle-associated kinase of 104 kDa which is part of the endocytic process, induces intracellular accumulation of FZD5 and the latter is internalized and degraded by a lysosomal pathway, suggesting a model for regulating the turnover of specific subclass of FZD receptors. FZD5 protein is believed to be the receptor for the WNT5A ligand, in some contexts such as the induction of Tissue Factor (TF) expression for angiogenesis in monocytes (Arderiu et al., 2014), or in the pancreatic cancer context. This interaction between WNT5A and FZD5 results in activation of the Wnt/β-catenin canonical pathway, therefore FZD5 can be considered as a receptor for WNT5A (He et al., 1997). Other evidences of interaction of FZD5 with WNT5A have been provided by Ishikawa et al., investigating the presence of WNT5A and WNT10B in the yolk sac and inducing the formation of secondary axes in Xenopus. The synergy between WNT10B and FDZ5 has been proved by Lazzaroni et al., (2016), confirming an autocrine mechanism for Wnt signalling activation in a breast cellular model (MCF7). Moreover, FZD5 conjugated with LRP6 can interact and transduce a WNT7A signal for the activation of Wnt/β-catenin canonical signalling pathway and for the induction of proliferation in endometrial cancer cells (Carmon and Loose, 2008). WNT2 is also a FZD5 ligand, and WNT2 deficient embryos show placental defects, suggesting their role in vascular growth during the developmental stage (Ishikawa et al., 2001). FZD5 seems to have also an important role in the early stage of the eye development; this function may be species-dependent (Carole et al., 2008). Other findings have discovered a FZD5's role in neuronal development and polarity. Starting from the evidence that WNT3A is essential for neuronal differentiation of hNP cells, Bengoa-Vergniory et al., (2016) has performed the silencing of its receptors FZD4, FZD5, ROR1 and LRP6 and has shown a trend for reducing neuronal differentiation and gene expression. Instead, Slater et al., (2013) suggests a role for FZD5, in cell culture of hippocampal neurons of rat, in the establishment of neuronal polarity and in its morphogenesis, through the non-canonical Wnt mechanism.
Homology The FZD5 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish. The characteristic domain Fz, also known as CRD domain, is conserved in all the members of the Frizzled family

Mutations

 
  Figure 5: Overview of major types of mutations occurring in FZD5.
Germinal Liu et al., (2016) reports an ultra-rare heterozygous frameshift mutation in FZD5 (p. Ala219Glufs*49) responsible of autosomal dominant non-syndromic coloboma. This frameshift variant is not a canonical substrate for nonsense-mediated decay, so the result is the production of a truncated protein, that lacks the transmembrane domain. The truncated protein is secreted from cells and becomes a dominant-negative FZD5 receptor, so it antagonises both canonical and non-canonical WNT signalling.
Somatic Wang et al., (2014) has observed 2 mutations in FZD5 that led to loss of functional pathway activation. The first one (p. Y46*) is a nonsense mutation that results in a premature truncation of the protein, generating a new protein (MT1) that led to a loss of Wnt-activating function. The second one (p. V290I) is a missense mutation that produces the protein named MT2. MT2, in contrast to MT1, did not change Wnt pathway activity. Some somatic mutations have been identified and described by COSMIC (Catalogue of Somatic Mutation In Cancer) and most are listed as nonsense, missense and synonymous substitutions; nevertheless, their role in disease has not yet been clarified.

Implicated in

  
Entity Pancreatic ductal adenocarcinoma
Note Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas. One of the most mutated gene in this type of cancer is RNF43, ubiquitin E3 ligase ring finger 43, suggested as a negative regulator of Wnt signalling. RNF43 inhibits Wnt/β-catenin signalling by reducing Frizzled levels on the membranes (Jiang et al., 2013). Considering this evident role of frizzled receptors in RNF43-mutant PDAC, has been discovered a unique requirement of Wnt/Fzd signalling: FZD5. As results, knockout of FZD5 led to robust growth inhibition in RNF43-mutant cells, and moreover they develop an anti-FZD5 antibody that inhibits the growth of RNF43-mutant PDAC through cell-cycle arrest. (Steinhart et al., 2017).
  
  
Entity Colorectal cancer
Note One of the most common mutation in colorectal cancers (CRC) is RNF43, like PDAC. Like for PDAC, so for CRC using anti-FZD5 antibody has been proved that the FZD5 dependency may exist also in this type of cancer. As result, anti-FZD5 antibody inhibits survival of RNF46-mutant CRC organoids. (Steinhart et al., 2017).
  
  
Entity Prostate cancer
Note Prostate cancer (PCa) is the most common malignancy in men. Because WNT5A expression was significantly higher in PC3 cells, two common WNT5A receptors (FZD5 and ROR2) were investigated and as result, FZD5 was expressed 70-fold higher in advanced PCa, while ROR2 was not significantly increased (Thiele et al., 2011).
  
  
Entity Gastric cancer
Note FZD5 has a high overexpression in gastric cancer samples, due to the overexpression of its ligand, WNT5A, highly expressed in advanced stages of gastric cancer and correlated with poor prognosis (Bizama et al., 2014).
  
  
Entity Renal cell carcinoma
Note FDZ5 is increased in RCC when compared to the normal kidney tissue, this can suggest a biomarker role in RCC. Moreover, its repression overcomes the chemo-resistance mediated by P-glycoprotein in RCC (Long et al., 2013).
  
  
Entity Type I endometrial carcinoma
Note FZD5 is downregulated in type I endometrial adenocarcinoma, concordant with the downregulation of FZD5, and its ligand WNT5A, regulated by an estrogen receptor agonist and estradiol (Menezes Mde et al., 2011). Moreover, WNT7A also shows an upregulation correlated with a worse prognosis, by a signalling involving FZD5 (Ford et al., 2015).
  
  
Entity Breast cancer
Note Recently, has been suggested a role in the autocrine activation of Wnt signalling guided by the interaction between WNT10B and FZD5; this interaction has been proved in the breast cancer MCF7 cells, through PLA analysis (Lazzaroni et al., 2016).
  
  
Entity Ovarian cancer
Note A high number of malignant ovarian specimens are FZD5-positive than normal ovary. FZD5 is highly expressed in ovarian cancer cell lines, associated with poor prognosis, such as its ligand WNT5a, and it is upregulated by ARID3B (the DNA-binding protein AT-rich interactive domain 3B, a protein involved in chromatin remodelling and regulation of gene expression). This upregulation leads to increased adhesion to ECM components, such as fibronectin and collagen IV. Previously, it was demonstrated that FZD5 with its ligand WNT7A increases adhesion in ovarian cancer. As expected, knockdown of FZD5 in ovarian cancer cells leads to decreased adhesion (Bobbs et al., 2015).
  
  
Entity Coloboma
Note Ocular coloboma is an eye malformation, resulting from incomplete fusion of the optic fissure during development. The classical description in medical literature is of a key-hole shaped defect in one or both the structures of the eye, in post-embryonic life. Coloboma is often associated with microphthalmia and/or contralateral anophthalmia, and together they represent the 10-15% of pediatric blindness.
The Wnt receptor FZD5 mediates both canonical and non-canonical signalling in the development of the eye, depending on the organism. Recently, has been reported an ultra-rare frameshift mutation in FZD5, in zebrafish, that creates the A219Xfs*49 mutant transcript as result of a truncated FZD5 protein without the seven-transmembrane domain. This mutation converts FZD5 from a membrane-bound receptor to a secreted FZD antagonist that give dominant-negative effect to the WNT signalling. As result, retinal neuroblasts exhibit apical junction defects, leading to microphthalmia and coloboma. Liu et al., also shows that the effects on the eye were similar when both FZD5-wt and FZD5-mut were overexpressed, suggesting a key role of dosage in ocular development (Liu et al., 2016).
  
  
Entity Alcoholic liver disease
Note Alcoholic liver disease (ALD) consists of a spectrum of disease that has the potentiality of progressing to hepatocellular carcinoma. Through microarray analysis has been found that FZD5 was the second key gene in the network of gene-modulating ALD. Its value in alcoholic hepatitis and cirrhosis was downregulated, leading to decreased gene activity and reduced synthesis of multi-transmembrane transport protein. This may reduce the binding between FZD5 and Wnt protein, as well as the number of β-catenin in the cytoplasm, leading to hepatocyte apoptosis (Liu et al., 2013).
  
  
Entity Amyotrophic lateral sclerosis
Note FZD5 receptor is involved in the pathophysiology of ALS and in the response of neuronal cells against neurodegeneration. FZD5 shows changes in expression pattern during the progression of the disease, founding an increase immunoreactivity of this receptor (González-Fernández et al., 2016).
  
  
Entity Psoriasis Lesion
Note WNT5a and FZD5 are mainly expressed in inflammatory and endothelial cells; moreover, they are expressed in healthy skin and overexpressed in psoriasis lesions (Zhang et al., 2015).
  

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Citation

This paper should be referenced as such :
Esposito I
FZD5 (frizzled class receptor 5);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/FZD5ID47614ch2q33.html


External links

Nomenclature
HGNC (Hugo)FZD5   4043
Cards
AtlasFZD5ID47614ch2q33.txt
Entrez_Gene (NCBI)FZD5  7855  frizzled class receptor 5
AliasesC2orf31; HFZ5
GeneCards (Weizmann)FZD5
Ensembl hg19 (Hinxton)ENSG00000163251 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000163251 [Gene_View]  ENSG00000163251 [Sequence]  chr2:207762586-207769419 [Contig_View]  FZD5 [Vega]
ICGC DataPortalENSG00000163251
TCGA cBioPortalFZD5
AceView (NCBI)FZD5
Genatlas (Paris)FZD5
WikiGenes7855
SOURCE (Princeton)FZD5
Genetics Home Reference (NIH)FZD5
Genomic and cartography
GoldenPath hg38 (UCSC)FZD5  -     chr2:207762586-207769419 -  2q33.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)FZD5  -     2q33.3   [Description]    (hg19-Feb_2009)
EnsemblFZD5 - 2q33.3 [CytoView hg19]  FZD5 - 2q33.3 [CytoView hg38]
Mapping of homologs : NCBIFZD5 [Mapview hg19]  FZD5 [Mapview hg38]
OMIM601723   
Gene and transcription
Genbank (Entrez)AB043702 AK000125 AK024850 AK315338 AL136852
RefSeq transcript (Entrez)NM_003468 NM_030804
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)FZD5
Cluster EST : UnigeneHs.17631 [ NCBI ]
CGAP (NCI)Hs.17631
Alternative Splicing GalleryENSG00000163251
Gene ExpressionFZD5 [ NCBI-GEO ]   FZD5 [ EBI - ARRAY_EXPRESS ]   FZD5 [ SEEK ]   FZD5 [ MEM ]
Gene Expression Viewer (FireBrowse)FZD5 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7855
GTEX Portal (Tissue expression)FZD5
Human Protein AtlasENSG00000163251-FZD5 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13467   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ13467  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13467
Splice isoforms : SwissVarQ13467
PhosPhoSitePlusQ13467
Domaine pattern : Prosite (Expaxy)FZ (PS50038)    G_PROTEIN_RECEP_F2_4 (PS50261)   
Domains : Interpro (EBI)Frizzled/SFRP    Frizzled/Smoothened_TM    Frizzled_dom    Frizzled_dom_sf    FZ5_CRD    GPCR_2-like   
Domain families : Pfam (Sanger)Frizzled (PF01534)    Fz (PF01392)   
Domain families : Pfam (NCBI)pfam01534    pfam01392   
Domain families : Smart (EMBL)FRI (SM00063)  Frizzled (SM01330)  
Conserved Domain (NCBI)FZD5
DMDM Disease mutations7855
Blocks (Seattle)FZD5
PDB (SRS)5URY    5URZ   
PDB (PDBSum)5URY    5URZ   
PDB (IMB)5URY    5URZ   
PDB (RSDB)5URY    5URZ   
Structural Biology KnowledgeBase5URY    5URZ   
SCOP (Structural Classification of Proteins)5URY    5URZ   
CATH (Classification of proteins structures)5URY    5URZ   
SuperfamilyQ13467
Human Protein Atlas [tissue]ENSG00000163251-FZD5 [tissue]
Peptide AtlasQ13467
HPRD03427
IPIIPI00298743   
Protein Interaction databases
DIP (DOE-UCLA)Q13467
IntAct (EBI)Q13467
FunCoupENSG00000163251
BioGRIDFZD5
STRING (EMBL)FZD5
ZODIACFZD5
Ontologies - Pathways
QuickGOQ13467
Ontology : AmiGOGolgi membrane  embryonic axis specification  angiogenesis  amyloid-beta binding  amyloid-beta binding  positive regulation of T cell cytokine production  G protein-coupled receptor activity  protein binding  plasma membrane  plasma membrane  integral component of plasma membrane  bicellular tight junction  G protein-coupled receptor signaling pathway  Wnt signaling pathway, calcium modulating pathway  synapse assembly  negative regulation of cell proliferation  lipid binding  anterior/posterior axis specification, embryo  cell surface  Wnt-protein binding  Wnt-protein binding  Wnt-protein binding  protein kinase binding  neuron differentiation  axon  dendrite  clathrin-coated endocytic vesicle membrane  post-embryonic camera-type eye development  ubiquitin protein ligase binding  early endosome membrane  positive regulation of interferon-gamma production  T cell differentiation in thymus  non-canonical Wnt signaling pathway  Wnt-activated receptor activity  Wnt-activated receptor activity  Wnt-activated receptor activity  Wnt-activated receptor activity  perikaryon  positive regulation of JUN kinase activity  protein-containing complex binding  synapse  positive regulation of transcription by RNA polymerase II  positive regulation of transcription by RNA polymerase II  cell maturation  perinuclear region of cytoplasm  embryonic camera-type eye morphogenesis  positive regulation of interleukin-1 beta secretion  Spemann organizer formation  canonical Wnt signaling pathway  canonical Wnt signaling pathway  canonical Wnt signaling pathway  Wnt signaling pathway, planar cell polarity pathway  apoptotic process involved in morphogenesis  branching involved in labyrinthine layer morphogenesis  syncytiotrophoblast cell differentiation involved in labyrinthine layer development  labyrinthine layer blood vessel development  chorionic trophoblast cell differentiation  cellular response to molecule of bacterial origin  regulation of chorionic trophoblast cell proliferation  regulation of autophagy of mitochondrion  positive regulation of protein targeting to mitochondrion  positive regulation of tumor necrosis factor secretion  beta-catenin destruction complex disassembly  regulation of bicellular tight junction assembly  
Ontology : EGO-EBIGolgi membrane  embryonic axis specification  angiogenesis  amyloid-beta binding  amyloid-beta binding  positive regulation of T cell cytokine production  G protein-coupled receptor activity  protein binding  plasma membrane  plasma membrane  integral component of plasma membrane  bicellular tight junction  G protein-coupled receptor signaling pathway  Wnt signaling pathway, calcium modulating pathway  synapse assembly  negative regulation of cell proliferation  lipid binding  anterior/posterior axis specification, embryo  cell surface  Wnt-protein binding  Wnt-protein binding  Wnt-protein binding  protein kinase binding  neuron differentiation  axon  dendrite  clathrin-coated endocytic vesicle membrane  post-embryonic camera-type eye development  ubiquitin protein ligase binding  early endosome membrane  positive regulation of interferon-gamma production  T cell differentiation in thymus  non-canonical Wnt signaling pathway  Wnt-activated receptor activity  Wnt-activated receptor activity  Wnt-activated receptor activity  Wnt-activated receptor activity  perikaryon  positive regulation of JUN kinase activity  protein-containing complex binding  synapse  positive regulation of transcription by RNA polymerase II  positive regulation of transcription by RNA polymerase II  cell maturation  perinuclear region of cytoplasm  embryonic camera-type eye morphogenesis  positive regulation of interleukin-1 beta secretion  Spemann organizer formation  canonical Wnt signaling pathway  canonical Wnt signaling pathway  canonical Wnt signaling pathway  Wnt signaling pathway, planar cell polarity pathway  apoptotic process involved in morphogenesis  branching involved in labyrinthine layer morphogenesis  syncytiotrophoblast cell differentiation involved in labyrinthine layer development  labyrinthine layer blood vessel development  chorionic trophoblast cell differentiation  cellular response to molecule of bacterial origin  regulation of chorionic trophoblast cell proliferation  regulation of autophagy of mitochondrion  positive regulation of protein targeting to mitochondrion  positive regulation of tumor necrosis factor secretion  beta-catenin destruction complex disassembly  regulation of bicellular tight junction assembly  
Pathways : KEGGWnt signaling pathway    Hippo signaling pathway    Melanogenesis    HTLV-I infection    Pathways in cancer    Proteoglycans in cancer    Basal cell carcinoma   
REACTOMEQ13467 [protein]
REACTOME PathwaysR-HSA-5340588 [pathway]   
NDEx NetworkFZD5
Atlas of Cancer Signalling NetworkFZD5
Wikipedia pathwaysFZD5
Orthology - Evolution
OrthoDB7855
GeneTree (enSembl)ENSG00000163251
Phylogenetic Trees/Animal Genes : TreeFamFZD5
HOVERGENQ13467
HOGENOMQ13467
Homologs : HomoloGeneFZD5
Homology/Alignments : Family Browser (UCSC)FZD5
Gene fusions - Rearrangements
Fusion : QuiverFZD5
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerFZD5 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)FZD5
dbVarFZD5
ClinVarFZD5
1000_GenomesFZD5 
Exome Variant ServerFZD5
ExAC (Exome Aggregation Consortium)ENSG00000163251
GNOMAD BrowserENSG00000163251
Varsome BrowserFZD5
Genetic variants : HAPMAP7855
Genomic Variants (DGV)FZD5 [DGVbeta]
DECIPHERFZD5 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisFZD5 
Mutations
ICGC Data PortalFZD5 
TCGA Data PortalFZD5 
Broad Tumor PortalFZD5
OASIS PortalFZD5 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICFZD5  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDFZD5
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch FZD5
DgiDB (Drug Gene Interaction Database)FZD5
DoCM (Curated mutations)FZD5 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)FZD5 (select a term)
intoGenFZD5
NCG5 (London)FZD5
Cancer3DFZD5(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM601723   
Orphanet13959    13964    13962    13963    13960    13961   
DisGeNETFZD5
MedgenFZD5
Genetic Testing Registry FZD5
NextProtQ13467 [Medical]
TSGene7855
GENETestsFZD5
Target ValidationFZD5
Huge Navigator FZD5 [HugePedia]
snp3D : Map Gene to Disease7855
BioCentury BCIQFZD5
ClinGenFZD5
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7855
Chemical/Pharm GKB GenePA28460
Clinical trialFZD5
Miscellaneous
canSAR (ICR)FZD5 (select the gene name)
Probes
Litterature
PubMed56 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineFZD5
EVEXFZD5
GoPubMedFZD5
iHOPFZD5
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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