This gene encodes a protein that is a member of the dickkopf family. The secreted protein contains two cysteine rich regions and is involved in embryonic development through its interactions with the Wnt signaling pathway. The expression of this gene is decreased in a variety of cancer cell lines and it may function as a tumor suppressor gene. Alternative splicing results in mu... See more...

Aliases for DKK3 Gene

Aliases for DKK3 Gene

  • Dickkopf WNT Signaling Pathway Inhibitor 3 2 3 5
  • Dickkopf-Related Protein 3 3 4
  • Regulated In Glioma 2 3
  • Dickkopf-3 3 4
  • HDkk-3 3 4
  • Dkk-3 3 4
  • REIC 3 4
  • Dickkopf (Xenopus Laevis) Homolog 3 2
  • Dickkopf 3 Homolog (Xenopus Laevis) 2
  • Dickkopf 3 Homolog 3
  • Dickkopf Homolog 3 3
  • RIG-Like 5-6 3
  • RIG-Like 7-1 3
  • RIG 3

External Ids for DKK3 Gene

Previous GeneCards Identifiers for DKK3 Gene

  • GC11M013255
  • GC11M012554
  • GC11M012023
  • GC11M011948
  • GC11M011941
  • GC11M011660
  • GC11M011984

Summaries for DKK3 Gene

Entrez Gene Summary for DKK3 Gene

  • This gene encodes a protein that is a member of the dickkopf family. The secreted protein contains two cysteine rich regions and is involved in embryonic development through its interactions with the Wnt signaling pathway. The expression of this gene is decreased in a variety of cancer cell lines and it may function as a tumor suppressor gene. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

GeneCards Summary for DKK3 Gene

DKK3 (Dickkopf WNT Signaling Pathway Inhibitor 3) is a Protein Coding gene. Diseases associated with DKK3 include Alzheimer Disease and Lung Cancer. Among its related pathways are CDK-mediated phosphorylation and removal of Cdc6 and Regulation of Wnt/B-catenin Signaling by Small Molecule Compounds.

UniProtKB/Swiss-Prot Summary for DKK3 Gene

  • Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease (By similarity).

Gene Wiki entry for DKK3 Gene

Additional gene information for DKK3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DKK3 Gene

Genomics for DKK3 Gene

GeneHancer (GH) Regulatory Elements for DKK3 Gene

Promoters and enhancers for DKK3 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
GH11J012004 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 508.4 +2.8 2842 5.9 REST ZBTB26 POLR2A CEBPB ZNF777 STAT3 FOS ZNF335 CTCF EZH2 DKK3 lnc-DKK3-4 lnc-GALNT18-7 lnc-USP47-4
GH11J012016 Enhancer 1.2 Ensembl ENCODE CraniofacialAtlas dbSUPER 31.2 -9.1 -9084 4.9 CTBP1 MEF2A CTCF ZNF316 GABPA FOS PBX2 GATA3 HDAC2 RAD21 DKK3 MICALCL MICAL2 LINC02547
GH11J012028 Enhancer 1 Ensembl ENCODE dbSUPER 25.5 -19.4 -19424 3.2 FOS JUN NR2F2 NFE2 FOSL1 JUND NR2F1 FOSL2 RAD21 RFX5 LINC02547 DKK3 MICALCL
GH11J011972 Promoter/Enhancer 1.7 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 12.4 +31.4 31413 11.6 TCF12 JUND FOS ZIC2 REST RBM25 GABPA POLR2A FOSL2 YY1 lnc-GALNT18-6 DKK3 MICALCL MICAL2 USP47 GALNT18 lnc-DKK3-4 piR-44883-002
GH11J012041 Enhancer 1.3 FANTOM5 ENCODE dbSUPER 13.5 -33.8 -33790 4 CTCF TCF12 JUND FOS ZNF639 REST CLOCK AFF1 TRIM28 MYC DKK3 piR-32539-004 LINC02547 RF00017-865
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around DKK3 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for DKK3

Top Transcription factor binding sites by QIAGEN in the DKK3 gene promoter:
  • AP-1
  • ATF-2

Genomic Locations for DKK3 Gene

Genomic Locations for DKK3 Gene
chr11:11,956,207-12,009,769
(GRCh38/hg38)
Size:
53,563 bases
Orientation:
Minus strand
chr11:11,984,543-12,031,316
(GRCh37/hg19)
Size:
46,774 bases
Orientation:
Minus strand

Genomic View for DKK3 Gene

Genes around DKK3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DKK3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DKK3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DKK3 Gene

Proteins for DKK3 Gene

  • Protein details for DKK3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UBP4-DKK3_HUMAN
    Recommended name:
    Dickkopf-related protein 3
    Protein Accession:
    Q9UBP4
    Secondary Accessions:
    • A8K1I2
    • D3DQW1
    • Q9ULB7

    Protein attributes for DKK3 Gene

    Size:
    350 amino acids
    Molecular mass:
    38390 Da
    Quaternary structure:
    • Interacts with LRP5 and LRP6.

neXtProt entry for DKK3 Gene

Post-translational modifications for DKK3 Gene

  • N- and O-glycosylated.
  • Glycosylation at Thr26, Thr28, Asn96, Asn106, Asn121, and Asn204
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • DKK3_HUMAN (822)

No data available for DME Specific Peptides for DKK3 Gene

Domains & Families for DKK3 Gene

Gene Families for DKK3 Gene

Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted secreted proteins

Protein Domains for DKK3 Gene

Blocks:
  • Dickkopf, N-terminal cysteine-rich
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for DKK3 Gene

GenScript: Design optimal peptide antigens:
  • Dickkopf homolog 3 (Xenopus laevis), isoform CRA_a (D3DQW3_HUMAN)
  • Dickkopf-related protein 3 (DKK3_HUMAN)
  • Putative tumor suppressor Dkk-3/REIC (Q6PQ81_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UBP4

UniProtKB/Swiss-Prot:

DKK3_HUMAN :
  • The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6.
  • Belongs to the dickkopf family.
Domain:
  • The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6.
Family:
  • Belongs to the dickkopf family.
genes like me logo Genes that share domains with DKK3: view

Function for DKK3 Gene

Molecular function for DKK3 Gene

UniProtKB/Swiss-Prot Function:
Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease (By similarity).

Phenotypes From GWAS Catalog for DKK3 Gene

Gene Ontology (GO) - Molecular Function for DKK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0039706 co-receptor binding IBA 21873635
GO:0048019 receptor antagonist activity IBA 21873635
genes like me logo Genes that share ontologies with DKK3: view
genes like me logo Genes that share phenotypes with DKK3: view

Animal Models for DKK3 Gene

MGI Knock Outs for DKK3:

Animal Model Products

  • Taconic Biosciences Mouse Models for DKK3

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DKK3

Clone Products

  • Addgene plasmids for DKK3

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for DKK3 Gene

Localization for DKK3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DKK3 Gene

Secreted.

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 DKK3 gene
Compartment Confidence
extracellular 5
plasma membrane 3
cytosol 3
cytoskeleton 2
nucleus 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Vesicles (3)
  • Cytosol (1)
  • Nuclear bodies (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for DKK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IBA,TAS 21873635
genes like me logo Genes that share ontologies with DKK3: view

Pathways & Interactions for DKK3 Gene

genes like me logo Genes that share pathways with DKK3: view

Pathways by source for DKK3 Gene

1 Sino Biological pathway for DKK3 Gene
1 GeneTex pathway for DKK3 Gene

Gene Ontology (GO) - Biological Process for DKK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007275 multicellular organism development IEA --
GO:0009653 anatomical structure morphogenesis TAS 10570958
GO:0016055 Wnt signaling pathway IEA --
GO:0017015 regulation of transforming growth factor beta receptor signaling pathway NAS 24431302
GO:0030178 negative regulation of Wnt signaling pathway IEA --
genes like me logo Genes that share ontologies with DKK3: view

No data available for SIGNOR curated interactions for DKK3 Gene

Drugs & Compounds for DKK3 Gene

No Compound Related Data Available

Transcripts for DKK3 Gene

mRNA/cDNA for DKK3 Gene

4 REFSEQ mRNAs :
24 NCBI additional mRNA sequence :
16 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 DKK3

Clone Products

  • Addgene plasmids for DKK3

Alternative Splicing Database (ASD) splice patterns (SP) for DKK3 Gene

ExUns: 1 ^ 2a · 2b ^ 3a · 3b · 3c · 3d ^ 4a · 4b · 4c ^ 5 ^ 6a · 6b · 6c · 6d · 6e ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12a · 12b · 12c ^ 13a ·
SP1: - - - - - - - - - - - - -
SP2: - - - - - - - - -
SP3: - - - - - - - - - -
SP4: - - - - - - -
SP5: - -
SP6: - - - - - - - - - -
SP7: - - - - - - -
SP8: - - - - - - - - - - -
SP9: -
SP10: - - - - - - - -
SP11: - - - - - - - - - - - -
SP12: - - - - - - - - - - - - -
SP13: - - - - - -
SP14:
SP15:
SP16: - - - - - - - - - - - - - - -
SP17: - - -

ExUns: 13b · 13c ^ 14a · 14b · 14c · 14d · 14e ^ 15a · 15b ^ 16
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11: - - -
SP12:
SP13:
SP14:
SP15:
SP16: - - - - - - - - -
SP17:

Relevant External Links for DKK3 Gene

GeneLoc Exon Structure for
DKK3

Expression for DKK3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for DKK3 Gene

mRNA differential expression in normal tissues according to GTEx for DKK3 Gene

This gene is overexpressed in Heart - Atrial Appendage (x8.6).

Protein differential expression in normal tissues from HIPED for DKK3 Gene

This gene is overexpressed in Vitreous humor (34.5), Cerebrospinal fluid (16.6), and Amniocyte (15.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for DKK3 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for DKK3

SOURCE GeneReport for Unigene cluster for DKK3 Gene:

Hs.292156

mRNA Expression by UniProt/SwissProt for DKK3 Gene:

Q9UBP4-DKK3_HUMAN
Tissue specificity: Highest expression in heart, brain, and spinal cord.

Evidence on tissue expression from TISSUES for DKK3 Gene

  • Nervous system(5)
  • Kidney(4.6)
  • Pancreas(4.4)
  • Lung(3.7)
  • Skin(3.7)
  • Heart(3.2)
  • Eye(2.8)
  • Muscle(2.8)
  • Adrenal gland(2.3)
  • Intestine(2.1)
genes like me logo Genes that share expression patterns with DKK3: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for DKK3 Gene

Orthologs for DKK3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for DKK3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia DKK3 31 30
  • 99.05 (n)
OneToOne
cow
(Bos Taurus)
Mammalia DKK3 31 30
  • 88.83 (n)
OneToOne
dog
(Canis familiaris)
Mammalia DKK3 31 30
  • 88.09 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Dkk3 17 31 30
  • 84.81 (n)
rat
(Rattus norvegicus)
Mammalia Dkk3 30
  • 83.18 (n)
oppossum
(Monodelphis domestica)
Mammalia DKK3 31
  • 61 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia DKK3 31
  • 55 (a)
OneToOne
chicken
(Gallus gallus)
Aves DKK3 31 30
  • 66.56 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia DKK3 31
  • 48 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii dkk3 30
  • 54.01 (n)
dkk3b 31
  • 42 (a)
OneToMany
dkk3a 31
  • 37 (a)
OneToMany
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.13938 30
sea squirt
(Ciona savignyi)
Ascidiacea CSA.181 31
  • 18 (a)
OneToOne
Species where no ortholog for DKK3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • fruit fly (Drosophila melanogaster)
  • 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)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for DKK3 Gene

ENSEMBL:
Gene Tree for DKK3 (if available)
TreeFam:
Gene Tree for DKK3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for DKK3: view image

Paralogs for DKK3 Gene

No data available for Paralogs for DKK3 Gene

Variants for DKK3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for DKK3 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
689683 Uncertain Significance: Marfanoid habitus and intellectual disability 11,968,418(-) G/T MISSENSE_VARIANT
711543 Benign: not provided 12,002,374(-) T/C MISSENSE_VARIANT
768428 Benign: not provided 11,964,597(-) T/C MISSENSE_VARIANT
rs11544816 - p.Glu49Asp
rs3206824 - p.Arg335Gly

Additional dbSNP identifiers (rs#s) for DKK3 Gene

Structural Variations from Database of Genomic Variants (DGV) for DKK3 Gene

Variant ID Type Subtype PubMed ID
esv3625384 CNV gain 21293372
esv3625386 CNV gain 21293372
nsv483000 CNV loss 15286789
nsv515847 CNV gain+loss 19592680
nsv524257 CNV loss 19592680
nsv526144 CNV loss 19592680
nsv553544 CNV gain 21841781
nsv832067 CNV gain 17160897

Variation tolerance for DKK3 Gene

Residual Variation Intolerance Score: 42.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.39; 54.21% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DKK3 Gene

Human Gene Mutation Database (HGMD)
DKK3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
DKK3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for DKK3 Gene

Disorders for DKK3 Gene

MalaCards: The human disease database

(4) MalaCards diseases for DKK3 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
alzheimer disease
  • ad
lung cancer
  • adenocarcinoma of lung
gastric cancer
  • gastric cancer, somatic
cone-rod dystrophy 2
  • cord2
- elite association - COSMIC cancer census association via MalaCards
Search DKK3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for DKK3

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 DKK3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for DKK3 Gene

Publications for DKK3 Gene

  1. Wnt antagonist gene polymorphisms and renal cancer. (PMID: 19562778) Hirata H … Dahiya R (Cancer 2009) 3 23 41 54
  2. Reduced expression of the REIC/Dkk-3 gene by promoter-hypermethylation in human tumor cells. (PMID: 11814687) Kobayashi K … Shimizu K (Gene 2002) 3 4 23 54
  3. A REIC gene shows down-regulation in human immortalized cells and human tumor-derived cell lines. (PMID: 10652205) Tsuji T … Namba M (Biochemical and biophysical research communications 2000) 3 4 23 54
  4. Functional and structural diversity of the human Dickkopf gene family. (PMID: 10570958) Krupnik VE … McCarthy SA (Gene 1999) 2 3 4 54
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54

Products for DKK3 Gene

Sources for DKK3 Gene