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FZD4 (frizzled class receptor 4)

Written2017-11Alessandro Beghini, Adriana Cassaro
Department of Health Sciences, University of Milan, via A. Di Rudini', 8 20142, Milan (Italy); alessandro.beghini@unimi.it; adriana.cassaro87@gmail.com

Abstract Fzd4 is a receptor for Wnt proteins, belonging to the frizzled receptors family. Its stimulation can activate both Wnt/β-catenin canonical and Wnt/Ca2+ non canonical pathways. This receptor plays an important role in the development processes, in particular in the retinal vascularization: it binds the Norrin ligand, a Wnt-unrelated growth factor, and activates β-catenin signalling pathway. Mutations of FZD4 gene are associated with Familial Exudative Vitreoretinopathy (FEVR). Recently dysregulation of FZD4 expression has been reported in different type of cancers, but FZD4 contribution in tumor pathogenesis and progression is still not entirely elucidated.

Keywords Frizzled 4, WNT, Wnt/β-catenin signaling

(Note : for Links provided by Atlas : click)

Identity

Alias_namesEVR1
frizzled (Drosophila) homolog 4
exudative vitreoretinopathy 1
frizzled homolog 4 (Drosophila)
frizzled 4, seven transmembrane spanning receptor
frizzled family receptor 4
Alias_symbol (synonym)CD344
Other aliasFrizzled 4, Seven Transmembrane Spanning Receptor
Frizzled (Drosophila) homology 4
Frizzled homolog 4 (Drosophila)
CD344 Antigen
FEVR
Fz-4
FZD4
Wnt receptor Frizzled -4
hFz4
HGNC (Hugo) FZD4
LocusID (NCBI) 8322
Atlas_Id 40655
Location 11q14.2  [Link to chromosome band 11q14]
Location_base_pair Starts at 86945675 and ends at 86955398 bp from pter ( according to hg19-Feb_2009)  [Mapping FZD4.png]
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

 
  Figure 1: Schematic representation of FZD4 gene that contains a total of two exons and FZD4 transcript.
Description DNA size: 9.71kb encoding two exons. This gene has one transcript (splice variant), 82 orthologues, 12 paralogues (www.emsable.org). Sagara et al., reported a splice variant of FZD4 gene which they called FZD4SA, it retains intronic sequence and encodes shorter isoform of only 125 aa. However, its expression is not supported by other experimental evidences.
Transcription The FZD4 mRNA transcript is 7383 bp. FZD4-001 ENST00000531380.1: mRNA7383 bp, protein 537 aa.

Protein

Description The gene FZD4 encodes a 537 aa protein with a molecular weight of 59 kDa. FZD4 is a member of the seven transmembrane receptor family consist of 10 receptors that are activated by Wnt family of lipo-glycoproteins. The Wnt/ FZD signaling is involved in a variety of biological processes and its dysregulation have been implicated in cancer development. FZD4 protein contains the N-terminal signal peptide (aa 1-36) that assurances proper membrane insertion of the protein, an extracellular cysteine rich domain (CRD; aa 40-161), which creates the binding site for WNT ligands, a seven-pass transmembrane domain (aa 161-221) that gives rise to three intracellular loops, three extracellular loops and a C- terminal domain (aa 221-537). The CRD domain is necessary to bind WNT ligands or Norrin ligand leading to initiation of distinct downstream signaling pathways. (Schulte G., 2010).
 
Expression In human, FZD4 is a ubiquitous protein. It is expressed in brain, ovary, liver, pancreas, brain, colon, heart, skeletal muscle, endothelial cells, endometrium, bone marrow, prostate, spleen, breast (www.ncbi.nlm.nih.gov).
 
  Figure 2: Visualization of FZD4/WNT10B interaction in MCF7 adherent (top) and tumorsphere (bottom) by proximity ligation assay (Lazzaroni et al.,2016).
Localisation FZD4 is localized on the plasma membrane surface. It can be internalized through both constitutive and agonist dependent endocytosis in response to Wnt5a stimulation (Chen W. et al., 2003).
 
  Figure 3. Schematic illustrating the activation of βcatenin via the FZD4 receptor.
Function FZD4 is a member of Frizzled gene family involved in neuronal, follicle, cardiomyocyte and retinal vascular development, likewise its dysregulated expression lead to cancer and other diseases. Depending on the cellular contest, FZD4 interacts with different WNT ligands, leading to the activation of Wnt/β catenin signaling and sometimes non canonical Wnt/Ca2+ signaling. Wnt/β catenin signaling is activated when WNT ligands bind CDR FZD/Low-density lipoprotein receptor-related protein5/6 ( LRP5/ LRP6) complex, in this case CTNNB1 (β-catenin) degradation complex becomes inactivated, resulting in stabilization of β-catenin that can translocate in the nucleus, where it interacts with LEF1 (TCF/LEF) transcription factor, inducing the transcription of target genes (Clevers H., 2006). Recently, WNT10B/FZD4 interaction in the MCF7 breast cancer cell line suggests an autocrine activation of Wnt signalling in this cell line model (Lazzaroni F. et al, 2016). In melanoma FZD4 binds WNT5A and stimulates tumor invasion through activation of βcatenin signaling (Grossman A. et al., 2013), while in acute myeloid leukemia the interaction between WNT3A and FZD4 induce higher resistance against apoptosis (Tickenbrock L. et al., 2008). WNT2, WNT5A/ WNT5B and WNT11 via FZD4 and FZD6 induced non canonical Wnt signaling activation that regulates cardiomyocite differentiation (Mazzotta S. et al., 2016)
FZD4 is also the only FZD family member that binds selectively a growth factor called NDP (Norrin) and regulates endothelial cells growth during retinal vascular development. In retina, the binding of Norrin with FZD4 conjugated with LRP5 co-receptor and protein TSPAN12 (Tetraspanin-12), results in activation of βcatenin signalling (Schulte G., 2010), alteration in one of this gene is associated with Familial Exudative Vitreoretinopathy.
Homology The FZD4 gene is conserved in chimpanzee, mouse, Rhesus monkey, dog, cow, rat, chicken, zebrafish and frog.

Mutations

Germinal Several types of mutations (missense, nonsense, small deletions) have been reported for the human FZD4 gene and are related to the familial exudative vitreoretinopathy (FEVR). Among these mutations, different heterozygous substitutions have been reported: M342V, W335C, R417, I256V, P33S, G36N, H69Y, M105T, M105V, C181R, C204R, C204Y, C45Y, Y58C, W226X, and G488D (Zhang K. et al., 2011; Kondo H. et al. 2003; Quin et al., 2005) It has also been described a loss of function mutation of FZD4 with nucleotides 1479-1484 deletion in two cases of FEVR, resulting in the lacking of met493 and trp494 that leads to a frameshift and creates a stop codon at residue 533 (Robitaille J. et al.,2002).

Implicated in

  
Entity Familial Exudative Vitreoretinopathy (FEVR)
Note Familial Exudative Vitreoretinopathy (FEVR) is a hereditary ocular disorder characterized by incomplete development of the retinal vasculature.
It is possible to distinguish two forms of FEVR: one with dominant autosomal inheritance and one with X-linked recessive inheritance (Gilmour DF., 2015).
Autosomal inheritance has been associated with mutation of FZD4, LRP5 or Tetraspanin 12 (TSPAN12) genes, while X-linked recessive inheritance is due to mutation of Norrin gene (NPD) that it is also involved in other ocular disease.
Several FZD4 mutations were connected with FEVR, many of which were found in the extracellular portion of the protein. Kaykas et al., have shown how some FZD4 mutations in FEVR lead to the retention of mutated protein within the endoplasmic reticulum (ER), where it is recognized by endoplasmic-reticulum-associated protein degradation (ERAD) and degraded, not allowing its exposure on the plasma membrane. They also demonstrated that oligomerization of mutants and wild-type FZD4 in the ER reduces the FZD4 function by preventing a sufficient amount of FZD4 from reaching the cell membrane and inhibits its signaling. This dominant-negative effect can partly explain the pathological mechanism that causes the disease phenotype, in patients with heterozygous FZD4 mutations. Mutations that do not cause retention in ER of mutated protein, induce a conformational modification of the CRD FZD4 that doesn't permit the biding to its ligands or downstream targets.
  
  
Entity Acute myeloid leukemia (AML)
Note It was demonstrated that FZD4 represents one of the mechanism of canonical or non canonical Wnt signaling activation in the pathogenesis of AML. Recently microarray analysis confirmed a higher expression of FZD4 in primary AML blast cells. (Beghini A. et al., 2012).
Tickenbrock, A. et al, also showed FZD4 overexpression in primary AML blasts, both in the presence or absence of FLT3 mutations. They also showed a canonical Wnt pathway activation due at specific WNT3A/FZD4 interaction, that leads to the stabilization of β-catenin and induces higher resistance against apoptosis. It was observed an involvement of FZD4 in differentiation of AML cell line mediated by 6-benzylthioinosine (6-BT) treatment. 6-BT treatment results in downregulation of canonical Wnt molecules and up-regulation of transcriptional level of the non canonical Wnt ligand Wnt5a and receptors FZD2, FZD4, FZD5, resulting in activation of Wnt/Ca2+ pathway ( Zang S. et al., 2014).
  
  
Entity Non small cell lung cancer (NSCLC)
Note Recently several studies have reported that single nucleotide polymorphisms (SNPs) of FZD4 gene can influence recurrence and survival of early stage NSCLC patients treated with only surgery or in combination with chemotherapy.
miR-related SNP (rs713065) in the 3?UTR region of FZD4 gene is associated with decreased risk of death in early stage NSCLC patients treated with only surgery, while it is related to increased risk of death in patients treated with surgery plus chemotherapy (Pu X. et al., 2013). This FZD4-miR-SNP specifically interacts with MIR204 which acts as a tumor suppressor and inhibits the expression of FZD4 and transduction of Wnt/βcatenin signalling (Lin J. et al, 2017).) This FZD4-miR-SNP specifically interacts with miR-204 which acts as a tumor suppressor and inhibits the expression of FZD4 and transduction of Wnt/βcatenin signalling (Lin J. et al, 2017).
Coscio A. et al, demonstrated that miR-SNP (rs10898564) of FZD4 is most significantly associated with increased recurrence and death risk in NSCLC patients treated with only surgery but not in patients treated with surgery and chemotherapy. These reports suggest a potential role of FZD4-SNPs as predictive biomarkers for both recurrence and survival in early stage NSCLC patients.
  
  
Entity Prostate cancer
Note In prostate cancer cells have been shown activation of Wnt signalling through FZD4 leading to epithelial-to-mesenchymal transition (EMT) and loss of cell adhesion (Gupta S. et al., 2010; Acevedo VD et al., 2007).
  
  
Entity Breast cancer
Note Recently Lazzaroni F. et al. evidenced an autocrine activation of Wnt signalling in breast cancer cell line model. In MCF7 cell line model they identified the WNT10B/FZD4 interacting complex using the in situ proximity ligation assay and a dose dependent reduction of WNT10B/FZD4 complex after the treatment with pharmacological inhibitor of porcupine, a membrane-bound acyltransferase that is essential to the production of Wnt proteins.
  
  
Entity Liver cancer
Note It was revealed that Let7b microRNA inhibit Wnt/β-catenin signaling pathway via downregulation of FZD4 in liver cancer cell, resulting in a reduction of proliferation, invasion, migration of liver cancer cells and reduction in the amount of cancer stem cells in liver (Cai H.et al 2017).
  
  
Entity Glioblastoma
Note Microarray analysis in U87R4 invasive glioblastoma cell line reported an overexpression of FZD4, which actives Wnt/β catenin signalling pathway and promotes stemness and invasiveness of glioblastoma cells. (Jin X. et al. 2011).
  
  
Entity Medulloblastoma
Note Recently evidences showed an involvement of Norrin/FZD4 signaling pathway in the cerebellar tumor medulloblastoma (MB) initiation. In this tumor, Norrin/FZD4 pathway acts as anti-tumor signal in the preneoplastic niche, in fact loss of function of Norrin/FZD4 signaling in the endothelian cells promotes the formation of preneoplastic lesion of MB and their progression to malignancies (Bassett E. et al., 2016).
  
  
Entity Bladder cancer
Note FZD4 is a target of miR-493 in the bladder cancer. It was observed a down-regulated expression of miR-493 in the bladder cancer tissue in comparison with normal bladder tissue. MIR493 transfection in the T24 or J82 bladder cancer cell line inhibits FZD4 and Rho4 expression, resulting in the inhibition of cell motility and migration
These results, suggested that miR-493 represent a new tumor suppressor in the bladder cancer (Ueno K. et al., 2012).
  
  
Entity Melanoma
Note It was reported that in melanoma cells Wnt signalling activation through FZD4 promotes tumor cell invasion and metastasis. WNT5a binds FZD4/LRP6 receptor complex and actives the guanosine triphosphatase adenosine diphosphate ribosylation factor 6 ( ARF6), leading to the disruption of N-cadherin-βcatenin complex and accumulation of nuclear βcatenin, which increases the transcription of its target genes and stimulates melanoma invasion (Grossman A. et al., 2013)
  
  
Entity Chronic Myeloid Leukemia
Note Agarwal P. et al., revealed a role of FZD4 in Wnt-mediated regulation of CML progenitor growth and their resistance to tyrosine kinase inhibitor (TKI) treatment. Silencing of FZD4 expression in combination with Nilotinib (NIL) treatment reduces Wnt signalling activation and the colony forming capacity of CML cells.
  
  
Entity Colorectal cancer
Note Expression of FZD4 in colorectal cancer and its binding with the Norrin ligand, produced by the same cells and endothelial tumor cells, activates β-catenin signalling and regulates angiogenesis in the colorectal cancer microenvironment (K. Platinus et al. 2014).
  

Bibliography

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Citation

This paper should be referenced as such :
Beghini A, Cassaro A
FZD4 (frizzled class receptor 4);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/FZD4ID40655ch11q14.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(11;11)(q13;q14) FZD4/LAMTOR1


External links

Nomenclature
HGNC (Hugo)FZD4   4042
Cards
AtlasFZD4ID40655ch11q14
Entrez_Gene (NCBI)FZD4  8322  frizzled class receptor 4
AliasesCD344; EVR1; FEVR; FZD4S; 
Fz-4; Fz4; FzE4; GPCR; hFz4
GeneCards (Weizmann)FZD4
Ensembl hg19 (Hinxton)ENSG00000174804 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000174804 [Gene_View]  ENSG00000174804 [Sequence]  chr11:86945675-86955398 [Contig_View]  FZD4 [Vega]
ICGC DataPortalENSG00000174804
TCGA cBioPortalFZD4
AceView (NCBI)FZD4
Genatlas (Paris)FZD4
WikiGenes8322
SOURCE (Princeton)FZD4
Genetics Home Reference (NIH)FZD4
Genomic and cartography
GoldenPath hg38 (UCSC)FZD4  -     chr11:86945675-86955398 -  11q14.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)FZD4  -     11q14.2   [Description]    (hg19-Feb_2009)
EnsemblFZD4 - 11q14.2 [CytoView hg19]  FZD4 - 11q14.2 [CytoView hg38]
Mapping of homologs : NCBIFZD4 [Mapview hg19]  FZD4 [Mapview hg38]
OMIM133780   604579   
Gene and transcription
Genbank (Entrez)AB032417 AB054881 AK025516 AK025791 AK292768
RefSeq transcript (Entrez)NM_012193
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)FZD4
Cluster EST : UnigeneHs.591968 [ NCBI ]
CGAP (NCI)Hs.591968
Alternative Splicing GalleryENSG00000174804
Gene ExpressionFZD4 [ NCBI-GEO ]   FZD4 [ EBI - ARRAY_EXPRESS ]   FZD4 [ SEEK ]   FZD4 [ MEM ]
Gene Expression Viewer (FireBrowse)FZD4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)8322
GTEX Portal (Tissue expression)FZD4
Human Protein AtlasENSG00000174804-FZD4 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9ULV1   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9ULV1  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9ULV1
Splice isoforms : SwissVarQ9ULV1
PhosPhoSitePlusQ9ULV1
Domaine pattern : Prosite (Expaxy)FZ (PS50038)    G_PROTEIN_RECEP_F2_4 (PS50261)   
Domains : Interpro (EBI)Frizzled    Frizzled/SFRP    Frizzled_dom    FZD4    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)FZD4
DMDM Disease mutations8322
Blocks (Seattle)FZD4
PDB (SRS)5BPB    5BPQ    5BQC    5BQE    5CL1    5CM4   
PDB (PDBSum)5BPB    5BPQ    5BQC    5BQE    5CL1    5CM4   
PDB (IMB)5BPB    5BPQ    5BQC    5BQE    5CL1    5CM4   
PDB (RSDB)5BPB    5BPQ    5BQC    5BQE    5CL1    5CM4   
Structural Biology KnowledgeBase5BPB    5BPQ    5BQC    5BQE    5CL1    5CM4   
SCOP (Structural Classification of Proteins)5BPB    5BPQ    5BQC    5BQE    5CL1    5CM4   
CATH (Classification of proteins structures)5BPB    5BPQ    5BQC    5BQE    5CL1    5CM4   
SuperfamilyQ9ULV1
Human Protein Atlas [tissue]ENSG00000174804-FZD4 [tissue]
Peptide AtlasQ9ULV1
HPRD05203
IPIIPI00387029   IPI00977659   
Protein Interaction databases
DIP (DOE-UCLA)Q9ULV1
IntAct (EBI)Q9ULV1
FunCoupENSG00000174804
BioGRIDFZD4
STRING (EMBL)FZD4
ZODIACFZD4
Ontologies - Pathways
QuickGOQ9ULV1
Ontology : AmiGOamyloid-beta binding  vasculogenesis  G-protein coupled receptor activity  protein binding  plasma membrane  plasma membrane  integral component of plasma membrane  cell-cell junction  G-protein coupled receptor signaling pathway  Wnt signaling pathway, calcium modulating pathway  Wnt signaling pathway, calcium modulating pathway  sensory perception of sound  cell surface  negative regulation of cell-substrate adhesion  integral component of membrane  Wnt signaling pathway  Wnt signaling pathway  Wnt-protein binding  Wnt-protein binding  cytokine binding  PDZ domain binding  PDZ domain binding  neuron differentiation  dendrite  clathrin-coated vesicle membrane  clathrin-coated endocytic vesicle membrane  regulation of vascular endothelial growth factor receptor signaling pathway  ubiquitin protein ligase binding  locomotion involved in locomotory behavior  substrate adhesion-dependent cell spreading  extracellular matrix-cell signaling  non-canonical Wnt signaling pathway  signaling receptor activity  progesterone secretion  protein homodimerization activity  Wnt-activated receptor activity  positive regulation of JUN kinase activity  positive regulation of transcription, DNA-templated  protein heterodimerization activity  positive regulation of DNA binding transcription factor activity  canonical Wnt signaling pathway  canonical Wnt signaling pathway  Wnt signaling pathway, planar cell polarity pathway  membrane organization  retina vasculature morphogenesis in camera-type eye  cerebellum vasculature morphogenesis  retinal blood vessel morphogenesis  extracellular exosome  cellular response to retinoic acid  amyloid-beta complex  positive regulation of neuron projection arborization  cellular response to leukemia inhibitory factor  
Ontology : EGO-EBIamyloid-beta binding  vasculogenesis  G-protein coupled receptor activity  protein binding  plasma membrane  plasma membrane  integral component of plasma membrane  cell-cell junction  G-protein coupled receptor signaling pathway  Wnt signaling pathway, calcium modulating pathway  Wnt signaling pathway, calcium modulating pathway  sensory perception of sound  cell surface  negative regulation of cell-substrate adhesion  integral component of membrane  Wnt signaling pathway  Wnt signaling pathway  Wnt-protein binding  Wnt-protein binding  cytokine binding  PDZ domain binding  PDZ domain binding  neuron differentiation  dendrite  clathrin-coated vesicle membrane  clathrin-coated endocytic vesicle membrane  regulation of vascular endothelial growth factor receptor signaling pathway  ubiquitin protein ligase binding  locomotion involved in locomotory behavior  substrate adhesion-dependent cell spreading  extracellular matrix-cell signaling  non-canonical Wnt signaling pathway  signaling receptor activity  progesterone secretion  protein homodimerization activity  Wnt-activated receptor activity  positive regulation of JUN kinase activity  positive regulation of transcription, DNA-templated  protein heterodimerization activity  positive regulation of DNA binding transcription factor activity  canonical Wnt signaling pathway  canonical Wnt signaling pathway  Wnt signaling pathway, planar cell polarity pathway  membrane organization  retina vasculature morphogenesis in camera-type eye  cerebellum vasculature morphogenesis  retinal blood vessel morphogenesis  extracellular exosome  cellular response to retinoic acid  amyloid-beta complex  positive regulation of neuron projection arborization  cellular response to leukemia inhibitory factor  
Pathways : KEGGColorectal cancer    Wnt signaling pathway   
REACTOMEQ9ULV1 [protein]
REACTOME PathwaysR-HSA-8856828 [pathway]   
NDEx NetworkFZD4
Atlas of Cancer Signalling NetworkFZD4
Wikipedia pathwaysFZD4
Orthology - Evolution
OrthoDB8322
GeneTree (enSembl)ENSG00000174804
Phylogenetic Trees/Animal Genes : TreeFamFZD4
HOVERGENQ9ULV1
HOGENOMQ9ULV1
Homologs : HomoloGeneFZD4
Homology/Alignments : Family Browser (UCSC)FZD4
Gene fusions - Rearrangements
Fusion : MitelmanFZD4/LAMTOR1 [11q14.2/11q13.4]  
Fusion PortalFZD4 11q14.2 LAMTOR1 11q13.4 BRCA
Fusion PortalFZD4 11q14.2 RP11-115C10.1 PRAD
Fusion : QuiverFZD4
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerFZD4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)FZD4
dbVarFZD4
ClinVarFZD4
1000_GenomesFZD4 
Exome Variant ServerFZD4
ExAC (Exome Aggregation Consortium)ENSG00000174804
GNOMAD BrowserENSG00000174804
Genetic variants : HAPMAP8322
Genomic Variants (DGV)FZD4 [DGVbeta]
DECIPHERFZD4 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisFZD4 
Mutations
ICGC Data PortalFZD4 
TCGA Data PortalFZD4 
Broad Tumor PortalFZD4
OASIS PortalFZD4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICFZD4  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDFZD4
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Mendelian genes
LOVD (Leiden Open Variation Database)Eye diseases - LOVD
BioMutasearch FZD4
DgiDB (Drug Gene Interaction Database)FZD4
DoCM (Curated mutations)FZD4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)FZD4 (select a term)
intoGenFZD4
NCG5 (London)FZD4
Cancer3DFZD4(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM133780    604579   
Orphanet7036    11941    12154   
DisGeNETFZD4
MedgenFZD4
Genetic Testing Registry FZD4
NextProtQ9ULV1 [Medical]
TSGene8322
GENETestsFZD4
Target ValidationFZD4
Huge Navigator FZD4 [HugePedia]
snp3D : Map Gene to Disease8322
BioCentury BCIQFZD4
ClinGenFZD4 (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD8322
Chemical/Pharm GKB GenePA28459
Clinical trialFZD4
Miscellaneous
canSAR (ICR)FZD4 (select the gene name)
Probes
Litterature
PubMed74 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineFZD4
EVEXFZD4
GoPubMedFZD4
iHOPFZD4
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Jun 22 17:07:37 CEST 2018

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