DKK3 Gene

Name	dickkopf WNT signaling pathway inhibitor 3
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Dickkopf‐3 (DKK3) is a secreted modulator of canonical Wnt signaling that plays diverse roles in development and tumor suppression. In multiple cancer types—including osteosarcoma, melanoma, hepatocellular carcinoma, lung, cervical, and prostate cancers—DKK3 is frequently downregulated or silenced (often by promoter hypermethylation), which is associated with enhanced tumor cell proliferation, reduced apoptosis, diminished cell–cell adhesion, increased migration, and overall tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": " Conversely, restoration or ectopic expression of DKK3 in these tumor cells has been shown to inhibit β‐catenin nuclear translocation, reactivate adhesion molecules (such as E‐cadherin), reduce invasive behavior, and ultimately suppress tumor growth."}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its tumor cell–intrinsic effects, DKK3 also functions in the tumor microenvironment. Specifically, stromal expression of DKK3 has been linked to the modulation of pro‐tumorigenic signaling pathways, including the activation of YAP/TAZ through canonical Wnt components, an effect correlated with increased aggressiveness in breast, colorectal, and ovarian cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In developmental processes, DKK3 is expressed in distinct spatial‐temporal patterns. For example, during ocular and limb development DKK3 is part of a regulatory network—including interactions with transcription factors such as PAX6—that helps dictate the balance between retinal formation and pigment epithelium differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Clinically, aberrant methylation of the DKK3 promoter has been detected in several tumors, including gastric, colorectal, and breast cancers, and these epigenetic alterations are emerging as potential diagnostic and prognostic biomarkers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, microRNA‐mediated suppression of DKK3 contributes to constitutive activation of Wnt/β‐catenin signaling and the promotion of cancer stem cell traits"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", while differential DKK3 expression has been associated with lymph node metastasis in cervical cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies underscore DKK3’s role as a critical negative regulator of Wnt-driven signaling whose loss contributes to tumor progression and metastasis, and they highlight its potential as both a therapeutic target and a biomarker across a spectrum of human malignancies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ruth Scherz-Shouval, Sandro Santagata, Marc L Mendillo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The reprogramming of tumor stroma by HSF1 is a potent enabler of malignancy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2014.05.045"}], "href": "https://doi.org/10.1016/j.cell.2014.05.045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25083868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25083868"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "S Kuphal, S Lodermeyer, F Bataille, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of Dickkopf genes is strongly reduced in malignant melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1209508"}], "href": "https://doi.org/10.1038/sj.onc.1209508"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16568085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16568085"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sen-Yung Hsieh, Pei-Shan Hsieh, Cheng-Tang Chiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dickkopf-3/REIC functions as a suppressor gene of tumor growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1208138"}], "href": "https://doi.org/10.1038/sj.onc.1208138"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15516983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15516983"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Wen Yue, Quanhong Sun, Sanja Dacic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of Dkk3 activates beta-catenin/TCF-4 signaling in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgm267"}], "href": "https://doi.org/10.1093/carcin/bgm267"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18048388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18048388"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Eun-Ju Lee, Minwha Jo, Seung Bae Rho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dkk3, downregulated in cervical cancer, functions as a negative regulator of beta-catenin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.23913"}], "href": "https://doi.org/10.1002/ijc.23913"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19003969"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19003969"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Y Kawano, M Kitaoka, Y Hamada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of prostate cell growth and morphogenesis by Dickkopf-3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1209661"}], "href": "https://doi.org/10.1038/sj.onc.1209661"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16751809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16751809"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Nicola Ferrari, Romana Ranftl, Ievgeniia Chicherova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dickkopf-3 links HSF1 and YAP/TAZ signalling to control aggressive behaviours in cancer-associated fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-07987-0"}], "href": "https://doi.org/10.1038/s41467-018-07987-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30631061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30631061"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Kapil Bharti, Melanie Gasper, Jingxing Ou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A regulatory loop involving PAX6, MITF, and WNT signaling controls retinal pigment epithelium development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1002757"}], "href": "https://doi.org/10.1371/journal.pgen.1002757"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22792072"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22792072"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jun Yu, Qian Tao, Yuen Y Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Promoter methylation of the Wnt/beta-catenin signaling antagonist Dkk-3 is associated with poor survival in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cncr.23989"}], "href": "https://doi.org/10.1002/cncr.23989"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19051296"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19051296"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Vera Kloten, Birte Becker, Kirsten Winner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Promoter hypermethylation of the tumor-suppressor genes ITIH5, DKK3, and RASSF1A as novel biomarkers for blood-based breast cancer screening."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/bcr3375"}], "href": "https://doi.org/10.1186/bcr3375"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23320751"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23320751"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Lishan Fang, Junchao Cai, Baixue Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aberrantly expressed miR-582-3p maintains lung cancer stem cell-like traits by activating Wnt/β-catenin signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms9640"}], "href": "https://doi.org/10.1038/ncomms9640"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26468775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26468775"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Maartje G Noordhuis, Rudolf S N Fehrmann, G Bea A Wisman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of the TGF-beta and beta-catenin pathways in pelvic lymph node metastasis in early-stage cervical cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-10-2320"}], "href": "https://doi.org/10.1158/1078-0432.CCR-10-2320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21385933"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21385933"}]}]}]}
Synonyms	REIC
Proteins	DKK3_HUMAN
NCBI Gene ID	27122
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DKK3 has 10,775 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 114 datasets.

Click the + buttons to view associations for DKK3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DKK3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by DKK3 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of DKK3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of DKK3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of DKK3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of DKK3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of DKK3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of DKK3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of DKK3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of DKK3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DKK3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of DKK3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DKK3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DKK3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DKK3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DKK3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of DKK3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of DKK3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DKK3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing DKK3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing DKK3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DKK3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with DKK3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of DKK3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DKK3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DKK3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DKK3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by DKK3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with DKK3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with DKK3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with DKK3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with DKK3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with DKK3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DKK3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at DKK3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DKK3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DKK3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing DKK3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with DKK3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with DKK3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of DKK3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.