DKK2 (dickkopf Wnt signaling pathway inhibitor 2)

Gene

• Entrez ID: 27123
• Gene name: Dickkopf Wnt signaling pathway inhibitor 2
• Gene symbol: DKK2
• Synonyms (NCBI Gene): DKK-2
• Chromosome: 4
• Chromosome location: 4q25
• Summary: 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. It can act as either an agonist

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT007048	hsa-miR-218-5p	Luciferase reporter assay	23060446
MIRT018639	hsa-miR-335-5p	Microarray	18185580
MIRT003362	hsa-miR-221-3p	Reporter assay;Microarray	20018759
MIRT053325	hsa-miR-222-3p	Luciferase reporter assay, qRT-PCR, Western blot	23587485
MIRT053327	hsa-miR-1260b	Luciferase reporter assay, qRT-PCR, Western blot	23591200
MIRT007048	hsa-miR-218-5p	Luciferase reporter assay, qRT-PCR, Western blot	24091133
MIRT731607	hsa-miR-27a-3p	Luciferase reporter assay, qRT-PCR, Western blot	26656471
MIRT731607	hsa-miR-27a-3p	Luciferase reporter assay, qRT-PCR, Western blot	26656471
MIRT003362	hsa-miR-221-3p	Luciferase reporter assay, qRT-PCR, Western blot	27501171
MIRT736035	hsa-miR-203a-3p	Luciferase reporter assay, Western blotting	31489578
MIRT937664	hsa-miR-141	CLIP-seq
MIRT937665	hsa-miR-200a	CLIP-seq
MIRT937666	hsa-miR-204	CLIP-seq
MIRT937667	hsa-miR-211	CLIP-seq
MIRT937668	hsa-miR-2113	CLIP-seq
MIRT937669	hsa-miR-217	CLIP-seq
MIRT937670	hsa-miR-298	CLIP-seq
MIRT937671	hsa-miR-3064-5p	CLIP-seq
MIRT937672	hsa-miR-3187-3p	CLIP-seq
MIRT937673	hsa-miR-3678-3p	CLIP-seq
MIRT937674	hsa-miR-3688-3p	CLIP-seq
MIRT937675	hsa-miR-369-3p	CLIP-seq
MIRT937676	hsa-miR-374a	CLIP-seq
MIRT937677	hsa-miR-374b	CLIP-seq
MIRT937678	hsa-miR-4261	CLIP-seq
MIRT937679	hsa-miR-4287	CLIP-seq
MIRT937680	hsa-miR-4469	CLIP-seq
MIRT937681	hsa-miR-450b-5p	CLIP-seq
MIRT937682	hsa-miR-4529-5p	CLIP-seq
MIRT937683	hsa-miR-4685-3p	CLIP-seq
MIRT937684	hsa-miR-4793-3p	CLIP-seq
MIRT937685	hsa-miR-507	CLIP-seq
MIRT937686	hsa-miR-557	CLIP-seq
MIRT937687	hsa-miR-604	CLIP-seq
MIRT937688	hsa-miR-647	CLIP-seq
MIRT937689	hsa-miR-758	CLIP-seq
MIRT937690	hsa-miR-892b	CLIP-seq
MIRT937691	hsa-miR-944	CLIP-seq
MIRT1977560	hsa-miR-1252	CLIP-seq
MIRT1977561	hsa-miR-4496	CLIP-seq
MIRT1977562	hsa-miR-4652-3p	CLIP-seq
MIRT1977563	hsa-miR-545	CLIP-seq
MIRT937666	hsa-miR-204	CLIP-seq
MIRT937667	hsa-miR-211	CLIP-seq
MIRT937668	hsa-miR-2113	CLIP-seq
MIRT2212831	hsa-miR-3194-3p	CLIP-seq
MIRT2212832	hsa-miR-3647-3p	CLIP-seq
MIRT937674	hsa-miR-3688-3p	CLIP-seq
MIRT937678	hsa-miR-4261	CLIP-seq
MIRT937679	hsa-miR-4287	CLIP-seq
MIRT937680	hsa-miR-4469	CLIP-seq
MIRT937683	hsa-miR-4685-3p	CLIP-seq
MIRT2212833	hsa-miR-4713-5p	CLIP-seq
MIRT937689	hsa-miR-758	CLIP-seq
MIRT2212834	hsa-miR-767-3p	CLIP-seq
MIRT2516665	hsa-miR-1206	CLIP-seq
MIRT2516666	hsa-miR-153	CLIP-seq
MIRT937666	hsa-miR-204	CLIP-seq
MIRT937667	hsa-miR-211	CLIP-seq
MIRT2516667	hsa-miR-342-3p	CLIP-seq
MIRT2516668	hsa-miR-3618	CLIP-seq
MIRT2516669	hsa-miR-4277	CLIP-seq
MIRT937679	hsa-miR-4287	CLIP-seq
MIRT2516670	hsa-miR-4307	CLIP-seq
MIRT2516671	hsa-miR-4452	CLIP-seq
MIRT937680	hsa-miR-4469	CLIP-seq
MIRT2516672	hsa-miR-4680-3p	CLIP-seq
MIRT937683	hsa-miR-4685-3p	CLIP-seq
MIRT2516673	hsa-miR-4700-3p	CLIP-seq
MIRT2212833	hsa-miR-4713-5p	CLIP-seq
MIRT2516674	hsa-miR-4760-3p	CLIP-seq
MIRT2516675	hsa-miR-548p	CLIP-seq
MIRT2516676	hsa-miR-576-5p	CLIP-seq
MIRT2516677	hsa-miR-656	CLIP-seq
MIRT2516678	hsa-miR-660	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	21944579, 32296183, 33961781
GO:0005576	Component	Extracellular region	IEA
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IDA	11742004
GO:0005615	Component	Extracellular space	TAS	10570958
GO:0016055	Process	Wnt signaling pathway	IEA
GO:0030178	Process	Negative regulation of Wnt signaling pathway	IEA
GO:0039706	Function	Co-receptor binding	IBA
GO:0039706	Function	Co-receptor binding	IEA
GO:0048019	Function	Receptor antagonist activity	IBA
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IBA
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IDA	11742004
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	NAS	24431302
GO:0090263	Process	Positive regulation of canonical Wnt signaling pathway	IDA	12857724
GO:0090263	Process	Positive regulation of canonical Wnt signaling pathway	NAS	24431302

Other IDs

• MIM: 605415
• HGNC: 2892
• e!Ensembl: ENSG00000155011

Protein

• UniProt ID: Q9UBU2
• Protein name: Dickkopf-related protein 2 (Dickkopf-2) (Dkk-2) (hDkk-2)
• Protein 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,
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04706	Dickkopf_N	77 → 128	Dickkopf N-terminal cysteine-rich region	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in heart, brain, skeletal muscle and lung.
• Sequence:

  MAALMRSKDSSCCLLLLAAVLMVESSQIGSSRAKLNSIKSSLGGETPGQAANRSAGMYQG
  LAFGGSKKGKNLGQAYPCSSDKECEVGRYCHSPHQGSSACMVCRRKKKRCHRDGMCCPST
  RCNNGICIPVTESILTPHIPALDGTRHRDRNHGHYSNHDLGWQNLGRPHTKMSHIKGHEG
  DPCLRSSDCIEGFCCARHFWTKICKPVLHQGEVCTKQRKKGSHGLEIFQRCDCAKGLSCK
  VWKDATYSSKARLHVCQKI

• Sequence length: 259

Pathways

KEGG:

Wnt signaling pathway
Alzheimer disease
Pathways of neurodegeneration - multiple diseases

Reactome:

Negative regulation of TCF-dependent signaling by WNT ligand antagonists
Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANDROGENETIC ALOPECIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLOR VISION DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LARGE ARTERY STROKE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute lymphocytic leukemia	Lymphocytic Leukemia	BEFREE	27296949		★☆☆☆☆ Found in Text Mining only
Adenocarcinoma of lung (disorder)	Lung adenocarcinoma	BEFREE	31537378		★☆☆☆☆ Found in Text Mining only
Adenoid Cystic Carcinoma	Adenocarcinoma	BEFREE	21598248		★☆☆☆☆ Found in Text Mining only
Adenoma	Adenoma	BEFREE	25432628		★☆☆☆☆ Found in Text Mining only
Alopecia	Alopecia	GWASCAT_DG	28196072		★☆☆☆☆ Found in Text Mining only
Alopecia, Androgenetic, 1	Androgenetic Alopecia	GWASCAT_DG	27182965		★☆☆☆☆ Found in Text Mining only
Alopecia, Androgenetic, 2	Androgenetic Alopecia	GWASCAT_DG	27182965		★☆☆☆☆ Found in Text Mining only
Alopecia, Androgenetic, 3	Androgenetic Alopecia	GWASCAT_DG	27182965		★☆☆☆☆ Found in Text Mining only
Alopecia, Male Pattern	Alopecia, Male Pattern	GWASCAT_DG	27182965		★☆☆☆☆ Found in Text Mining only
Alopecia, Male Pattern	Alopecia, Male Pattern	BEFREE	28272467		★☆☆☆☆ Found in Text Mining only
Androgenetic Alopecia	Androgenetic Alopecia	GWASCAT_DG	27182965		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANOPHTHALMIA AND PULMONARY HYPOPLASIA	Syndromic microphthalmia	BEFREE	31583260		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety disorder	Pubtator	37029353	Associate	★☆☆☆☆ Found in Text Mining only
Aortic Dissection	Aortic dissection	Pubtator	36959563	Associate	★☆☆☆☆ Found in Text Mining only
Benign Neoplasm	Benign Neoplasm	BEFREE	22964660		★☆☆☆☆ Found in Text Mining only
Beta ketothiolase deficiency	Beta-ketothiolase deficiency	Pubtator	33909798	Associate	★☆☆☆☆ Found in Text Mining only
Bone Diseases Metabolic	Bone disease	Pubtator	24584697	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	28467796, 30320375		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	30320375	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	27203079	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	27203079	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	27640551, 29749862		★☆☆☆☆ Found in Text Mining only
Carcinoma Ovarian Epithelial	Epithelial ovarian carcinoma	Pubtator	33679613	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	31583260	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	33679613	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	22964660		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	28365691		★☆☆☆☆ Found in Text Mining only
Colonic Diseases	Colonic disease	Pubtator	15858124	Associate	★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic Neoplasms	BEFREE	28365691		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	28365691, 30867812		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	19659606, 29945573, 30867812, 33909798	Associate	★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	19562778, 19755393		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	25312721, 29257293		★☆☆☆☆ Found in Text Mining only
Diabetes Gestational	Gestational diabetes	Pubtator	35721735	Associate	★☆☆☆☆ Found in Text Mining only
Eccrine dermal cylindroma	Cylindromatosis	BEFREE	21598248		★☆☆☆☆ Found in Text Mining only
Epithelial ovarian cancer	Ovarian cancer	BEFREE	22964660		★☆☆☆☆ Found in Text Mining only
Erectile dysfunction	Erectile Dysfunction	BEFREE	29559443		★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophageal neoplasm	Pubtator	30990378	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	30990378	Associate	★☆☆☆☆ Found in Text Mining only
Ewings sarcoma	Ewing sarcoma	BEFREE	23204234		★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	BEFREE	21763422		★☆☆☆☆ Found in Text Mining only
Gallbladder Carcinoma	Gallbladder cancer	BEFREE	26715268		★☆☆☆☆ Found in Text Mining only
Gallbladder Neoplasms	Gallbladder neoplasm	Pubtator	26715268	Associate	★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	25312721	Stimulate	★☆☆☆☆ Found in Text Mining only
Intestinal Neoplasms	Intestinal neoplasm	Pubtator	29431745	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Neoplasms	Kidney neoplasm	Pubtator	23591200	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	24809435, 27203079, 30453289		★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	BEFREE	25826080		★☆☆☆☆ Found in Text Mining only
Lung Diseases Interstitial	Lung disease	Pubtator	37587067	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	28467796, 30320375		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of gallbladder	Gallbladder cancer	BEFREE	26715268		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of kidney	Kidney Cancer	BEFREE	19755393		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	25826080		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	27640551, 29749862		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	23204234, 27640551, 31212691		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	28467796		★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	Pubtator	23567267	Associate	★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	LHGDN	16568085		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	29431745	Associate	★☆☆☆☆ Found in Text Mining only
Mouth Neoplasms	Mouth neoplasm	Pubtator	23999978	Associate	★☆☆☆☆ Found in Text Mining only
Muscular Dystrophy Duchenne	Duchenne muscular dystrophy	Pubtator	18021006	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	21598248, 24091497, 25479246, 25826080, 27203079, 28365691, 28467796, 29431745, 30997579, 31583260		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	Pubtator	21909813	Associate	★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	29259207		★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	25312721, 29257293	Stimulate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	29806631	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	33679613	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	39972314	Stimulate	★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	19711349		★☆☆☆☆ Found in Text Mining only
Pancreatic Ductal Adenocarcinoma	Pancreatic adenocarcinoma	BEFREE	31583260		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	22344199	Associate	★☆☆☆☆ Found in Text Mining only
Precursor Cell Lymphoblastic Leukemia Lymphoma	Lymphoblastic Leukemia	BEFREE	27296949		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	33488078	Associate	★☆☆☆☆ Found in Text Mining only
Renal carcinoma	Renal Carcinoma	BEFREE	19755393		★☆☆☆☆ Found in Text Mining only
Renal Cell Carcinoma	Renal Carcinoma	BEFREE	19562778, 19755393		★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	23546988		★☆☆☆☆ Found in Text Mining only
Sarcoma Ewing	Sarcoma	Pubtator	19247449	Associate	★☆☆☆☆ Found in Text Mining only
Scleroderma Diffuse	Scleroderma	Pubtator	22328118	Inhibit	★☆☆☆☆ Found in Text Mining only
Scleroderma Systemic	Systemic sclerosis	Pubtator	37587067	Associate	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	23999978	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	23942619, 28152305	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	30053090		★☆☆☆☆ Found in Text Mining only
Vascular Diseases	Vascular Diseases	BEFREE	29259207		★☆☆☆☆ Found in Text Mining only