FZD8 Gene (Protein Coding)

Frizzled Class Receptor 8

GC10M035638
GIFtS:
42
This intronless 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. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This gene is highly expressed in two human cancer cell lines, indicating t... See more...

Aliases for FZD8 Gene

Aliases for FZD8 Gene

  • Frizzled Class Receptor 8 2 3 5
  • Frizzled 8, Seven Transmembrane Spanning Receptor 2 3
  • Frizzled Family Receptor 8 2 3
  • Frizzled-8 3 4
  • Frizzled (Drosophila) Homolog 8 2
  • Frizzled Homolog 8 (Drosophila) 2
  • Frizzled Homolog 8 3
  • FZ-8 3
  • HFZ8 3
  • Fz-8 4
  • HFz8 4

External Ids for FZD8 Gene

Previous GeneCards Identifiers for FZD8 Gene

  • GC10M035674
  • GC10M036077
  • GC10M035931
  • GC10M035967
  • GC10M035927

Summaries for FZD8 Gene

Entrez Gene Summary for FZD8 Gene

  • This intronless 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. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This gene is highly expressed in two human cancer cell lines, indicating that it may play a role in several types of cancer. The crystal structure of the extracellular cysteine-rich domain of a similar mouse protein has been determined. [provided by RefSeq, Jul 2008]

GeneCards Summary for FZD8 Gene

FZD8 (Frizzled Class Receptor 8) is a Protein Coding gene. Diseases associated with FZD8 include Interstitial Cystitis and Cystitis. Among its related pathways are Transcription Androgen Receptor nuclear signaling and Wnt Signaling Pathway and Pluripotency. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and transmembrane signaling receptor activity. An important paralog of this gene is FZD5.

UniProtKB/Swiss-Prot Summary for FZD8 Gene

  • Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes. The beta-catenin canonical signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Coreceptor along with RYK of Wnt proteins, such as WNT1.

Gene Wiki entry for FZD8 Gene

Additional gene information for FZD8 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FZD8 Gene

Genomics for FZD8 Gene

GeneHancer (GH) Regulatory Elements for FZD8 Gene

Promoters and enhancers for FZD8 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH10J035636 Promoter/Enhancer 2.3 VISTA FANTOM5 Ensembl ENCODE CraniofacialAtlas 752.8 +1.7 1651 8.3 ZBTB40 CTCF ZBTB6 POLR2A NFYC ZNF701 L3MBTL2 RAD21 ZNF121 POU5F1 FZD8 ENSG00000287528 MIR4683 piR-46029 ENSG00000271335 PRDX2P2 LOC105376494 HSALNG0077286 ENSG00000273312
GH10J035683 Enhancer 1.1 VISTA Ensembl 16.1 -43.2 -43206 3 MIXL1 HLF ZNF121 RERE SP1 SP7 ZNF680 HNF1A ZNF404 ZNF560 FZD8 ENSG00000271335 piR-41525-062 RPL7P37
GH10J035889 Enhancer 1 Ensembl ENCODE 14.5 -248.1 -248123 2 CTBP1 ZNF133 HLF ZNF121 BCL6B SP7 PKNOX1 ZIC2 RXRA ZBTB8A FZD8 LINC02630 piR-59769-055
GH10J035668 Enhancer 0.7 Ensembl ENCODE 16.2 -27.2 -27174 1.3 ZNF121 MNT ZSCAN4 OSR2 WT1 MAX FZD8 HSALNG0077287 piR-41525-062
GH10J035663 Enhancer 0.4 Ensembl 16.6 -22.3 -22323 1.6 PRDM10 WT1 FOXA1 FZD8 HSALNG0077287 piR-41525-062 HSALNG0077286
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FZD8 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the FZD8 gene promoter:
  • AREB6
  • C/EBPalpha
  • CHOP-10
  • E2F
  • E2F-1
  • ER-alpha
  • GR
  • GR-alpha
  • IRF-1
  • TBP

Genomic Locations for FZD8 Gene

Genomic Locations for FZD8 Gene
chr10:35,638,249-35,642,278
(GRCh38/hg38)
Size:
4,030 bases
Orientation:
Minus strand
chr10:35,927,177-35,930,362
(GRCh37/hg19)
Size:
3,186 bases
Orientation:
Minus strand

Genomic View for FZD8 Gene

Genes around FZD8 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FZD8 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FZD8 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for FZD8 Gene

Proteins for FZD8 Gene

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  • Protein details for FZD8 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H461-FZD8_HUMAN
    Recommended name:
    Frizzled-8
    Protein Accession:
    Q9H461

    Protein attributes for FZD8 Gene

    Size:
    694 amino acids
    Molecular mass:
    73300 Da
    Quaternary structure:
    • Component of a Wnt-signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly with LRP5 or LRP6; the interaction is promoted by Wnt-binding and signaling and inhibited by DKK1. Interacts with GPOC, RSPO1 and RSPO3 (By similarity). Interacts with glypican GPC3 (PubMed:24496449).

    Three dimensional structures from OCA and Proteopedia for FZD8 Gene

neXtProt entry for FZD8 Gene

Protein Expression for FZD8 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for FZD8 Gene

  • Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.
  • Glycosylation at Asn49, Asn152, and Asn475
  • Modification sites at PhosphoSitePlus

Other Protein References for FZD8 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for FZD8 Gene

Domains & Families for FZD8 Gene

Gene Families for FZD8 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • G-protein coupled receptors
  • Plasma proteins
  • Predicted membrane proteins

Protein Domains for FZD8 Gene

Blocks:
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for FZD8 Gene

GenScript: Design optimal peptide antigens:
  • Frizzled-8 (FZD8_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9H461

UniProtKB/Swiss-Prot:

FZD8_HUMAN :
  • The PDZ-binding motif mediates interaction with GOPC.
  • Belongs to the G-protein coupled receptor Fz/Smo family.
Domain:
  • The PDZ-binding motif mediates interaction with GOPC.
  • Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.
  • The FZ domain is involved in binding with Wnt ligands.
Family:
  • Belongs to the G-protein coupled receptor Fz/Smo family.
genes like me logo Genes that share domains with FZD8: view

Function for FZD8 Gene

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Molecular function for FZD8 Gene

UniProtKB/Swiss-Prot Function:
Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes. The beta-catenin canonical signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Coreceptor along with RYK of Wnt proteins, such as WNT1.

Phenotypes From GWAS Catalog for FZD8 Gene

Gene Ontology (GO) - Molecular Function for FZD8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004888 transmembrane signaling receptor activity IEA --
GO:0004930 G protein-coupled receptor activity IEA --
GO:0005102 signaling receptor binding IEA --
GO:0005515 protein binding IPI 22682250
GO:0017147 Wnt-protein binding IBA,IEA 21873635
genes like me logo Genes that share ontologies with FZD8: view
genes like me logo Genes that share phenotypes with FZD8: view

Animal Models for FZD8 Gene

MGI Knock Outs for FZD8:

Animal Model Products

  • Taconic Biosciences Mouse Models for FZD8

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FZD8

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for FZD8 Gene

Localization for FZD8 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FZD8 Gene

Membrane; Multi-pass membrane protein. Golgi apparatus. Cell membrane; Multi-pass membrane protein. Note=Colocalizes with GOPC at the Golgi apparatus. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for FZD8 gene
Compartment Confidence
plasma membrane 4
golgi apparatus 3
extracellular 1
cytoskeleton 1
nucleus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endoplasmic reticulum (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for FZD8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005794 Golgi apparatus IEA --
GO:0005886 plasma membrane IBA 21873635
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane TAS 11295046
GO:1990851 Wnt-Frizzled-LRP5/6 complex IEA --
genes like me logo Genes that share ontologies with FZD8: view

Pathways & Interactions for FZD8 Gene

genes like me logo Genes that share pathways with FZD8: view

Pathways by source for FZD8 Gene

11 Qiagen pathways for FZD8 Gene
  • Colorectal Cancer Metastasis
  • Factors Promoting Cardiogenesis in Vertebrates
  • G12-G13 in Cellular Signaling
  • Glioblastoma Multiforme
  • GSK3 Signaling
2 GeneTex pathways for FZD8 Gene

SIGNOR curated interactions for FZD8 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for FZD8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA --
GO:0001525 angiogenesis IEA --
GO:0001934 positive regulation of protein phosphorylation IEA --
GO:0007165 signal transduction IEA --
GO:0007166 cell surface receptor signaling pathway IEA --
genes like me logo Genes that share ontologies with FZD8: view

Drugs & Compounds for FZD8 Gene

Products:

  1. Drug

(1) Drugs for FZD8 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium Approved Nutra 7773
genes like me logo Genes that share compounds with FZD8: view

Transcripts for FZD8 Gene

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mRNA/cDNA for FZD8 Gene

(1) REFSEQ mRNAs :
(2) Additional mRNA sequences :
(65) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FZD8

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for FZD8 Gene

No ASD Table

Relevant External Links for FZD8 Gene

GeneLoc Exon Structure for
FZD8
ECgene alternative splicing isoforms for
FZD8

Expression for FZD8 Gene

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  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for FZD8 Gene

mRNA expression in normal human tissues for FZD8 Gene
mRNA expression by GTEx for FZD8 GenemRNA expression by BioGPS for FZD8 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for FZD8 Gene

This gene is overexpressed in Cervix (37.2) and Lung (26.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for FZD8 Gene



Protein tissue co-expression partners for FZD8 Gene

NURSA nuclear receptor signaling pathways regulating expression of FZD8 Gene:

FZD8

SOURCE GeneReport for Unigene cluster for FZD8 Gene:

Hs.302634

mRNA Expression by UniProt/SwissProt for FZD8 Gene:

Q9H461-FZD8_HUMAN
Tissue specificity: Most abundant in fetal kidney, followed by brain and lung. In adult tissues, expressed in kidney, heart, pancreas and skeletal muscle.
genes like me logo Genes that share expression patterns with FZD8: view

No data available for mRNA differential expression in normal tissues , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for FZD8 Gene

Orthologs for FZD8 Gene

This gene was present in the common ancestor of animals.

Orthologs for FZD8 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia FZD8 33 32
  • 97.97 (n)
 OneToOne
oppossum
(Monodelphis domestica)
 Mammalia FZD8 33
  • 93 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia FZD8 33 32
  • 91.96 (n)
 OneToOne
cow
(Bos Taurus)
 Mammalia FZD8 33 32
  • 91.46 (n)
 OneToOne
rat
(Rattus norvegicus)
 Mammalia LOC100909849 32
  • 87.26 (n)
mouse
(Mus musculus)
 Mammalia Fzd8 17 33 32
  • 86.33 (n)
chicken
(Gallus gallus)
 Aves FZD8 33
  • 94 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia FZD8 33
  • 82 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia fzd8 32
  • 78.38 (n)
Str.10842 32
African clawed frog
(Xenopus laevis)
 Amphibia Xl.412 32
zebrafish
(Danio rerio)
 Actinopterygii fzd8a 33 32 32
  • 77.2 (n)
 OneToMany
fzd8b 33
  • 73 (a)
 OneToMany
fruit fly
(Drosophila melanogaster)
 Insecta fz2 33
  • 48 (a)
 OneToMany
worm
(Caenorhabditis elegans)
 Secernentea cfz-2 32
  • 53.99 (n)
sea squirt
(Ciona savignyi)
 Ascidiacea -- 33
  • 35 (a)
 OneToMany
Species where no ortholog for FZD8 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for FZD8 Gene

ENSEMBL:
Gene Tree for FZD8 (if available)
TreeFam:
Gene Tree for FZD8 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FZD8: view image

Paralogs for FZD8 Gene

Paralogs for FZD8 Gene

(8) SIMAP similar genes for FZD8 Gene using alignment to 1 proteins:

  • FZD8_HUMAN
genes like me logo Genes that share paralogs with FZD8: view

Variants for FZD8 Gene

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Sequence variations from dbSNP and Humsavar for FZD8 Gene

SNP ID Clin Chr 10 pos Variation AA Info Type
rs1000117060 -- 35,642,727(-) C/G upstream_transcript_variant
rs1000524802 -- 35,641,881(-) G/A upstream_transcript_variant
rs1000551106 -- 35,642,482(-) T/G upstream_transcript_variant
rs1001282277 -- 35,643,070(-) C/G upstream_transcript_variant
rs1001514046 -- 35,641,853(-) G/A upstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for FZD8 Gene

Variant ID Type Subtype PubMed ID
dgv1034n54 CNV loss 21841781
dgv1035n54 CNV loss 21841781
dgv1036n54 CNV loss 21841781
dgv144n67 CNV gain 20364138
esv22469 CNV loss 19812545
nsv1068298 CNV deletion 25765185
nsv466871 CNV loss 19166990
nsv521143 CNV loss 19592680
nsv550413 CNV loss 21841781
nsv550415 CNV loss 21841781
nsv550416 CNV gain 21841781
nsv825337 CNV gain 20364138
nsv825340 CNV gain 20364138
nsv825341 CNV gain 20364138

Variation tolerance for FZD8 Gene

Residual Variation Intolerance Score: 6.35% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.13; 22.95% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FZD8 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
FZD8

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FZD8 Gene

Disorders for FZD8 Gene

MalaCards: The human disease database

(4) MalaCards diseases for FZD8 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
interstitial cystitis
  • pbs
cystitis
  • infective cystitis
split-hand/foot malformation 6
  • shfm6
exudative vitreoretinopathy
  • exudative vitreoretinopathy 1
- elite association - COSMIC cancer census association via MalaCards
Search FZD8 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for FZD8

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with FZD8: view

No data available for UniProtKB/Swiss-Prot and Genatlas for FZD8 Gene

Publications for FZD8 Gene

  1. Molecular cloning and characterization of human Frizzled-8 gene on chromosome 10p11.2. (PMID: 11295046) Saitoh T … Katoh M (International journal of oncology 2001) 2 3 4 23 56
  2. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. (PMID: 22575959) Hao HX … Cong F (Nature 2012) 3 4 56
  3. Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia. (PMID: 20634891) Jugessur A … Murray JC (PloS one 2010) 3 43 56
  4. A genome-wide association study identifies protein quantitative trait loci (pQTLs). (PMID: 18464913) Melzer D … Ferrucci L (PLoS genetics 2008) 3 43 56
  5. The DNA sequence and comparative analysis of human chromosome 10. (PMID: 15164054) Deloukas P … Rogers J (Nature 2004) 3 4 56

ExternalLinks

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