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. Activity of this protein is modulated by binding to the Wnt co-receptor and the co-factor kremen 2. [provided by RefSeq, Jul 2008] See more...

Aliases for DKK4 Gene

Aliases for DKK4 Gene

  • Dickkopf WNT Signaling Pathway Inhibitor 4 2 3 5
  • Dickkopf-Related Protein 4 3 4
  • Dickkopf-4 3 4
  • HDkk-4 3 4
  • Dickkopf (Xenopus Laevis) Homolog 4 2
  • Dickkopf Homolog 4 (Xenopus Laevis) 2
  • DKK-4 3
  • Dkk-4 4

External Ids for DKK4 Gene

Previous GeneCards Identifiers for DKK4 Gene

  • GC08P041716
  • GC08M042257
  • GC08M041972
  • GC08M042248
  • GC08M042350
  • GC08M040754

Summaries for DKK4 Gene

Entrez Gene Summary for DKK4 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. Activity of this protein is modulated by binding to the Wnt co-receptor and the co-factor kremen 2. [provided by RefSeq, Jul 2008]

GeneCards Summary for DKK4 Gene

DKK4 (Dickkopf WNT Signaling Pathway Inhibitor 4) is a Protein Coding gene. Diseases associated with DKK4 include Cone-Rod Dystrophy 2. Among its related pathways are Signaling by Wnt and Negative regulation of TCF-dependent signaling by WNT ligand antagonists.

UniProtKB/Swiss-Prot Summary for DKK4 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).

Additional gene information for DKK4 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DKK4 Gene

Genomics for DKK4 Gene

GeneHancer (GH) Regulatory Elements for DKK4 Gene

Promoters and enhancers for DKK4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around DKK4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for DKK4

Top Transcription factor binding sites by QIAGEN in the DKK4 gene promoter:
  • AML1a
  • AREB6
  • NF-kappaB
  • NF-kappaB1
  • Nkx3-1
  • Nkx3-1 v1
  • Nkx3-1 v2
  • NRSF form 1
  • NRSF form 2
  • RelA

Genomic Locations for DKK4 Gene

Genomic Locations for DKK4 Gene
chr8:42,373,194-42,391,754
(GRCh38/hg38)
Size:
18,561 bases
Orientation:
Minus strand
chr8:42,231,586-42,234,750
(GRCh37/hg19)
Size:
3,165 bases
Orientation:
Minus strand

Genomic View for DKK4 Gene

Genes around DKK4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DKK4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DKK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DKK4 Gene

Proteins for DKK4 Gene

  • Protein details for DKK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UBT3-DKK4_HUMAN
    Recommended name:
    Dickkopf-related protein 4
    Protein Accession:
    Q9UBT3
    Secondary Accessions:
    • Q3KNX0
    • Q9Y4C3

    Protein attributes for DKK4 Gene

    Size:
    224 amino acids
    Molecular mass:
    24876 Da
    Quaternary structure:
    • Interacts with LRP5 and LRP6.

    Three dimensional structures from OCA and Proteopedia for DKK4 Gene

neXtProt entry for DKK4 Gene

Post-translational modifications for DKK4 Gene

Other Protein References for DKK4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for DKK4 Gene

Domains & Families for DKK4 Gene

Gene Families for DKK4 Gene

Human Protein Atlas (HPA):
  • Predicted secreted proteins

Protein Domains for DKK4 Gene

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

Suggested Antigen Peptide Sequences for DKK4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ56584, highly similar to Dickkopf-related protein 4 (B4DWN3_HUMAN)
  • Dickkopf-related protein 4 (DKK4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UBT3

UniProtKB/Swiss-Prot:

DKK4_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 DKK4: view

Function for DKK4 Gene

Molecular function for DKK4 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).

LifeMap Function Summary for DKK4 Gene

During embryonic development, DKK4 as signaling molecule is secreted from the following cells

Phenotypes From GWAS Catalog for DKK4 Gene

Gene Ontology (GO) - Molecular Function for DKK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003674 molecular_function ND --
GO:0039706 co-receptor binding IBA 21873635
GO:0048019 receptor antagonist activity IBA 21873635
genes like me logo Genes that share ontologies with DKK4: view
genes like me logo Genes that share phenotypes with DKK4: view

Animal Models for DKK4 Gene

MGI Knock Outs for DKK4:
  • Dkk4 Dkk4<tm1.1(KOMP)Vlcg>

Animal Model Products

  • Taconic Biosciences Mouse Models for DKK4

miRNA for DKK4 Gene

miRTarBase miRNAs that target DKK4

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for DKK4 Gene

Localization for DKK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DKK4 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 DKK4 gene
Compartment Confidence
extracellular 5
plasma membrane 2
nucleus 2
cytoskeleton 1
endoplasmic reticulum 1
endosome 1
cytosol 1

Gene Ontology (GO) - Cellular Components for DKK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005575 cellular_component ND --
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IBA 21873635
genes like me logo Genes that share ontologies with DKK4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for DKK4 Gene

Pathways & Interactions for DKK4 Gene

genes like me logo Genes that share pathways with DKK4: view

Pathways by source for DKK4 Gene

2 Qiagen pathways for DKK4 Gene
  • Reelin Pathway (Cajal-Retzius cells)
  • WNT Signaling
1 GeneTex pathway for DKK4 Gene

Gene Ontology (GO) - Biological Process for DKK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007275 multicellular organism development IEA --
GO:0016055 Wnt signaling pathway IEA --
GO:0030178 negative regulation of Wnt signaling pathway NAS 10570958
GO:0061170 negative regulation of hair follicle placode formation IEA --
GO:0090090 negative regulation of canonical Wnt signaling pathway NAS 24431302
genes like me logo Genes that share ontologies with DKK4: view

No data available for SIGNOR curated interactions for DKK4 Gene

Drugs & Compounds for DKK4 Gene

(1) Drugs for DKK4 Gene - From: ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
KY 02111 Pharma WNT signaling inhibitor 0

(1) ApexBio Compounds for DKK4 Gene

Compound Action Cas Number
KY 02111 WNT signaling inhibitor 1118807-13-8
genes like me logo Genes that share compounds with DKK4: view

Drug Products

Transcripts for DKK4 Gene

mRNA/cDNA for DKK4 Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for DKK4 Gene

No ASD Table

Relevant External Links for DKK4 Gene

GeneLoc Exon Structure for
DKK4

Expression for DKK4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for DKK4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for DKK4 Gene

This gene is overexpressed in Brain - Cerebellar Hemisphere (x6.8), Esophagus - Mucosa (x5.9), Brain - Cerebellum (x5.6), and Vagina (x5.5).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for DKK4

SOURCE GeneReport for Unigene cluster for DKK4 Gene:

Hs.159311

mRNA Expression by UniProt/SwissProt for DKK4 Gene:

Q9UBT3-DKK4_HUMAN
Tissue specificity: Expressed in cerebellum, T-cells, esophagus and lung.
genes like me logo Genes that share expression patterns with DKK4: view

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for DKK4 Gene

Orthologs for DKK4 Gene

This gene was present in the common ancestor of mammals.

Orthologs for DKK4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia DKK4 31 30
  • 99.55 (n)
OneToOne
dog
(Canis familiaris)
Mammalia DKK4 31 30
  • 84.25 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Dkk4 17 31 30
  • 75.72 (n)
rat
(Rattus norvegicus)
Mammalia Dkk4 30
  • 75.11 (n)
oppossum
(Monodelphis domestica)
Mammalia DKK4 31
  • 75 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 72 (a)
OneToMany
-- 31
  • 60 (a)
OneToMany
cow
(Bos Taurus)
Mammalia DKK4 31
  • 55 (a)
OneToOne
Species where no ortholog for DKK4 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)
  • chicken (Gallus gallus)
  • 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)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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)
  • zebrafish (Danio rerio)

Evolution for DKK4 Gene

ENSEMBL:
Gene Tree for DKK4 (if available)
TreeFam:
Gene Tree for DKK4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for DKK4: view image

Paralogs for DKK4 Gene

(2) SIMAP similar genes for DKK4 Gene using alignment to 1 proteins:

  • DKK4_HUMAN
genes like me logo Genes that share paralogs with DKK4: view

No data available for Paralogs for DKK4 Gene

Variants for DKK4 Gene

Additional dbSNP identifiers (rs#s) for DKK4 Gene

Structural Variations from Database of Genomic Variants (DGV) for DKK4 Gene

Variant ID Type Subtype PubMed ID
nsv831301 CNV loss 17160897

Variation tolerance for DKK4 Gene

Residual Variation Intolerance Score: 39.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.69; 14.73% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DKK4 Gene

Human Gene Mutation Database (HGMD)
DKK4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
DKK4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for DKK4 Gene

Disorders for DKK4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for DKK4 Gene - From: DISEASES

Disorder Aliases PubMed IDs
cone-rod dystrophy 2
  • cord2
- elite association - COSMIC cancer census association via MalaCards
Search DKK4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for DKK4

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 DKK4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for DKK4 Gene

Publications for DKK4 Gene

  1. Functional and structural diversity of the human Dickkopf gene family. (PMID: 10570958) Krupnik VE … McCarthy SA (Gene 1999) 2 3 4 23 54
  2. Wnt antagonist gene polymorphisms and renal cancer. (PMID: 19562778) Hirata H … Dahiya R (Cancer 2009) 3 23 41 54
  3. Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity. (PMID: 19773279) Hosgood HD … Lan Q (Occupational and environmental medicine 2009) 3 41 54
  4. High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men. (PMID: 19453261) Yerges LM … MrOS Research Group (Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2009) 3 41 54
  5. DICKKOPF-4 is induced by TCF/beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1alpha,25-dihydroxyvitamin D3. (PMID: 18408752) Pendás-Franco N … González-Sancho JM (Oncogene 2008) 3 23 54

Products for DKK4 Gene

Sources for DKK4 Gene