Human Gene FZD6 (ENST00000522566.5) from GENCODE V44
  Description: Homo sapiens frizzled class receptor 6 (FZD6), transcript variant 2, mRNA. (from RefSeq NM_001164615)
RefSeq Summary (NM_001164615): This gene represents a member of the 'frizzled' gene family, which encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The protein encoded by this family member contains a signal peptide, a cysteine-rich domain in the N-terminal extracellular region, and seven transmembrane domains, but unlike other family members, this protein does not contain a C-terminal PDZ domain-binding motif. This protein functions as a negative regulator of the canonical Wnt/beta-catenin signaling cascade, thereby inhibiting the processes that trigger oncogenic transformation, cell proliferation, and inhibition of apoptosis. Alternative splicing results in multiple transcript variants, some of which do not encode a protein with a predicted signal peptide.[provided by RefSeq, Aug 2011].
Gencode Transcript: ENST00000522566.5
Gencode Gene: ENSG00000164930.12
Transcript (Including UTRs)
   Position: hg38 chr8:103,298,433-103,332,817 Size: 34,385 Total Exon Count: 7 Strand: +
Coding Region
   Position: hg38 chr8:103,300,108-103,331,509 Size: 31,402 Coding Exon Count: 6 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr8:103,298,433-103,332,817)mRNA (may differ from genome)Protein (706 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCLynxMalacardsMGIneXtProtOMIM
PubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: FZD6_HUMAN
DESCRIPTION: RecName: Full=Frizzled-6; Short=Fz-6; Short=hFz6; Flags: Precursor;
FUNCTION: Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which 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.
SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein (By similarity).
TISSUE SPECIFICITY: Detected in adult heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, thymus, prostate, testis, ovary, small intestine and colon. In the fetus, expressed in brain, lung, liver and kidney.
DOMAIN: Lys-Thr-X-X-X-Trp motif interacts with the PDZ doman of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway (By similarity).
DOMAIN: The FZ domain is involved in binding with Wnt ligands (By similarity).
PTM: Ubiquitinated by ZNRF3, leading to its degradation by the proteasome (By similarity).
DISEASE: Defects in FZD6 are the cause of nail disorder non- syndromic congenital type 10 (NDNC10) [MIM:614157]. NDNC10 is a nail disorder characterized by a variable degree of onychauxis (thick nails), hyponychia, and onycholysis of all nails, with claw-shaped fingernails in some individuals. No other anomalies of ectodermal tissues, including hair, teeth, sweat glands, or skin, are noted, and individuals with dysplastic nails have normal hearing and normal psychomotor development.
DISEASE: Note=Rare non-synonymous variants in FZD6 may contribute to neural tube defects, congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy.
SIMILARITY: Belongs to the G-protein coupled receptor Fz/Smo family.
SIMILARITY: Contains 1 FZ (frizzled) domain.

-  Primer design for this transcript
 

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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: FZD6
Diseases sorted by gene-association score: nail disorder, nonsyndromic congenital, 10,* (1550), nail disease* (416), nail disorder, nonsyndromic congenital, 1 (17), neural tube defects (8), exudative vitreoretinopathy (7), colorectal cancer (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 15.69 RPKM in Cells - Cultured fibroblasts
Total median expression: 306.43 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -80.80290-0.279 Picture PostScript Text
3' UTR -249.001308-0.190 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000539 - Frizzled
IPR015526 - Frizzled/SFRP
IPR020067 - Frizzled_dom
IPR026543 - FZD6
IPR017981 - GPCR_2-like

Pfam Domains:
PF01534 - Frizzled/Smoothened family membrane region
PF01392 - Fz domain

ModBase Predicted Comparative 3D Structure on O60353
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004871 signal transducer activity
GO:0004888 transmembrane signaling receptor activity
GO:0004930 G-protein coupled receptor activity
GO:0005515 protein binding
GO:0017147 Wnt-protein binding
GO:0031625 ubiquitin protein ligase binding
GO:0042813 Wnt-activated receptor activity
GO:0001540 beta-amyloid binding

Biological Process:
GO:0001736 establishment of planar polarity
GO:0001843 neural tube closure
GO:0001942 hair follicle development
GO:0007165 signal transduction
GO:0007166 cell surface receptor signaling pathway
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007223 Wnt signaling pathway, calcium modulating pathway
GO:0007275 multicellular organism development
GO:0016055 Wnt signaling pathway
GO:0030168 platelet activation
GO:0030901 midbrain development
GO:0033278 cell proliferation in midbrain
GO:0035567 non-canonical Wnt signaling pathway
GO:0035880 embryonic nail plate morphogenesis
GO:0042472 inner ear morphogenesis
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0048105 establishment of body hair planar orientation
GO:0060071 Wnt signaling pathway, planar cell polarity pathway
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:1904693 midbrain morphogenesis

Cellular Component:
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016324 apical plasma membrane
GO:0016327 apicolateral plasma membrane
GO:0030659 cytoplasmic vesicle membrane
GO:0031410 cytoplasmic vesicle
GO:0045177 apical part of cell


-  Descriptions from all associated GenBank mRNAs
  LF212602 - JP 2014500723-A/20105: Polycomb-Associated Non-Coding RNAs.
MA448179 - JP 2018138019-A/20105: Polycomb-Associated Non-Coding RNAs.
LF210258 - JP 2014500723-A/17761: Polycomb-Associated Non-Coding RNAs.
MA445835 - JP 2018138019-A/17761: Polycomb-Associated Non-Coding RNAs.
BX640609 - Homo sapiens mRNA; cDNA DKFZp686I13174 (from clone DKFZp686I13174).
AK313789 - Homo sapiens cDNA, FLJ94402, highly similar to Homo sapiens frizzled homolog 6 (Drosophila) (FZD6), mRNA.
AK299341 - Homo sapiens cDNA FLJ50183 complete cds, highly similar to Frizzled-6 precursor.
AK296824 - Homo sapiens cDNA FLJ57315 complete cds, highly similar to Frizzled-6 precursor.
BC060836 - Homo sapiens frizzled homolog 6 (Drosophila), mRNA (cDNA clone MGC:71723 IMAGE:30340365), complete cds.
BC036106 - Homo sapiens frizzled homolog 6 (Drosophila), mRNA (cDNA clone IMAGE:5276005), containing frame-shift errors.
AB012911 - Homo sapiens Hfz6 mRNA for Frizzled-6, complete cds.
AK304092 - Homo sapiens cDNA FLJ51187 complete cds, highly similar to Frizzled-6 precursor.
AK316544 - Homo sapiens cDNA, FLJ79443 complete cds, highly similar to Frizzled-6 precursor.
AF072873 - Homo sapiens frizzled 6 mRNA, complete cds.
LF213364 - JP 2014500723-A/20867: Polycomb-Associated Non-Coding RNAs.
MA448941 - JP 2018138019-A/20867: Polycomb-Associated Non-Coding RNAs.
JD133587 - Sequence 114611 from Patent EP1572962.
LF336209 - JP 2014500723-A/143712: Polycomb-Associated Non-Coding RNAs.
MA571786 - JP 2018138019-A/143712: Polycomb-Associated Non-Coding RNAs.
KJ897827 - Synthetic construct Homo sapiens clone ccsbBroadEn_07221 FZD6 gene, encodes complete protein.
LF336210 - JP 2014500723-A/143713: Polycomb-Associated Non-Coding RNAs.
MA571787 - JP 2018138019-A/143713: Polycomb-Associated Non-Coding RNAs.
AB209734 - Homo sapiens mRNA for Putative G-protein coupled receptor variant protein.
LF336223 - JP 2014500723-A/143726: Polycomb-Associated Non-Coding RNAs.
MA571800 - JP 2018138019-A/143726: Polycomb-Associated Non-Coding RNAs.
LF336224 - JP 2014500723-A/143727: Polycomb-Associated Non-Coding RNAs.
MA571801 - JP 2018138019-A/143727: Polycomb-Associated Non-Coding RNAs.
LF336225 - JP 2014500723-A/143728: Polycomb-Associated Non-Coding RNAs.
MA571802 - JP 2018138019-A/143728: Polycomb-Associated Non-Coding RNAs.
LF336226 - JP 2014500723-A/143729: Polycomb-Associated Non-Coding RNAs.
MA571803 - JP 2018138019-A/143729: Polycomb-Associated Non-Coding RNAs.
LF336227 - JP 2014500723-A/143730: Polycomb-Associated Non-Coding RNAs.
MA571804 - JP 2018138019-A/143730: Polycomb-Associated Non-Coding RNAs.
JD065489 - Sequence 46513 from Patent EP1572962.
JD048348 - Sequence 29372 from Patent EP1572962.
JD378367 - Sequence 359391 from Patent EP1572962.
JD354547 - Sequence 335571 from Patent EP1572962.
JD538822 - Sequence 519846 from Patent EP1572962.
JD553199 - Sequence 534223 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04310 - Wnt signaling pathway
hsa04916 - Melanogenesis
hsa05200 - Pathways in cancer
hsa05217 - Basal cell carcinoma

Reactome (by CSHL, EBI, and GO)

Protein O60353 (Reactome details) participates in the following event(s):

R-HSA-3965446 WNT5A and WNT11 bind FZD receptors to initiate Ca2+ signaling
R-HSA-201708 Frizzled receptors bind Wnts
R-HSA-3858491 WNTs bind the FZD receptor to initiate PCP pathway
R-HSA-3965441 FZD recruits trimeric G-proteins
R-HSA-3965447 G-protein subunits dissociate from WNT:FZD complex
R-HSA-3858482 DVL is recruited to the receptor
R-HSA-3858480 WNT-dependent phosphorylation of DVL
R-HSA-4641249 ZNRF3,RNF43 binds the FZD:LRP5/6 receptor complex
R-HSA-4641236 USP8 deubiquitinates FZD to potentiate WNT signaling
R-HSA-4641253 ZNRF3 ubiquitinates FZD to promote its downregulation
R-HSA-3965444 WNT:FZD complex promotes G-protein nucleotide exchange
R-HSA-4086398 Ca2+ pathway
R-HSA-373080 Class B/2 (Secretin family receptors)
R-HSA-4086400 PCP/CE pathway
R-HSA-3858494 Beta-catenin independent WNT signaling
R-HSA-500792 GPCR ligand binding
R-HSA-4641263 Regulation of FZD by ubiquitination
R-HSA-5340588 RNF mutants show enhanced WNT signaling and proliferation
R-HSA-195721 Signaling by WNT
R-HSA-372790 Signaling by GPCR
R-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-4791275 Signaling by WNT in cancer
R-HSA-162582 Signal Transduction
R-HSA-5663202 Diseases of signal transduction
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: B4DRN0, ENST00000522566.1, ENST00000522566.2, ENST00000522566.3, ENST00000522566.4, FZD6_HUMAN, NM_001164615, O60353, Q6N0A5, Q6P9C3, Q8WXR9, uc003ylh.1, uc003ylh.2, uc003ylh.3, uc003ylh.4
UCSC ID: ENST00000522566.5
RefSeq Accession: NM_001164615
Protein: O60353 (aka FZD6_HUMAN)
CCDS: CCDS55268.1, CCDS6298.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.