TISIDB

Summary
Symbol	DKK2
Name	dickkopf WNT signaling pathway inhibitor 2
Aliases	dickkopf (Xenopus laevis) homolog 2; dickkopf 2 homolog (Xenopus laevis); DKK-2; dickkopf 2 homolog; dickkop ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Secreted.
Domain	PF04706 Dickkopf N-terminal cysteine-rich region
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).

> Gene Ontology [ TOP ]
Biological Process	GO:0016055 Wnt signaling pathway GO:0030111 regulation of Wnt signaling pathway GO:0030177 positive regulation of Wnt signaling pathway GO:0030178 negative regulation of Wnt signaling pathway GO:0060070 canonical Wnt signaling pathway GO:0060828 regulation of canonical Wnt signaling pathway GO:0090090 negative regulation of canonical Wnt signaling pathway GO:0090263 positive regulation of canonical Wnt signaling pathway GO:0198738 cell-cell signaling by wnt
Molecular Function	GO:0039706 co-receptor binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04310 Wnt signaling pathway
Reactome	R-HSA-1643685: Disease R-HSA-5663202: Diseases of signal transduction R-HSA-5339717: Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling R-HSA-3772470: Negative regulation of TCF-dependent signaling by WNT ligand antagonists R-HSA-162582: Signal Transduction R-HSA-4791275: Signaling by WNT in cancer R-HSA-195721: Signaling by Wnt R-HSA-201681: TCF dependent signaling in response to WNT

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04310 Wnt signaling pathway

Reactome

R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-5339717: Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling
R-HSA-3772470: Negative regulation of TCF-dependent signaling by WNT ligand antagonists
R-HSA-162582: Signal Transduction
R-HSA-4791275: Signaling by WNT in cancer
R-HSA-195721: Signaling by Wnt
R-HSA-201681: TCF dependent signaling in response to WNT

Summary
Symbol	DKK2
Name	dickkopf WNT signaling pathway inhibitor 2
Aliases	dickkopf (Xenopus laevis) homolog 2; dickkopf 2 homolog (Xenopus laevis); DKK-2; dickkopf 2 homolog; dickkop ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between DKK2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

[ TOP ]

Literatures describing the relation between DKK2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29431745	Colorectal Carcinoma; Melanoma	Inhibit immunity; Resistant to immunotherapy	DKK2 secreted by tumor cells acts on cytotoxic lymphocytes, inhibiting STAT5 signaling by impeding STAT5 nuclear localization via LRP5, but independently of LRP6 and the Wnt-β-catenin pathway. Genetic or antibody-mediated ablation of DKK2 activates natural killer (NK) cells and CD8+T cells in tumors, impedes tumor progression, and enhances the effects of PD-1 blockade.

Summary
Symbol	DKK2
Name	dickkopf WNT signaling pathway inhibitor 2
Aliases	dickkopf (Xenopus laevis) homolog 2; dickkopf 2 homolog (Xenopus laevis); DKK-2; dickkopf 2 homolog; dickkop ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

[ TOP ]

Statistical results of DKK2 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	DKK2
Name	dickkopf WNT signaling pathway inhibitor 2
Aliases	dickkopf (Xenopus laevis) homolog 2; dickkopf 2 homolog (Xenopus laevis); DKK-2; dickkopf 2 homolog; dickkop ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the expression difference of DKK2 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.93	0.0431
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.762	0.334
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-1.049	0.106
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.505	0.493
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.177	0.878
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.915	0.476
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.091	0.894
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.154	0.875
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.22	0.835
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.942	0.175
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.809	0.0383
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.446	0.0648

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of DKK2 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	2.7	-2.7	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	7.9	0	7.9	0.26
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	13.6	0	13.6	0.279
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	DKK2
Name	dickkopf WNT signaling pathway inhibitor 2
Aliases	dickkopf (Xenopus laevis) homolog 2; dickkopf 2 homolog (Xenopus laevis); DKK-2; dickkopf 2 homolog; dickkop ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DKK2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	DKK2
Name	dickkopf WNT signaling pathway inhibitor 2
Aliases	dickkopf (Xenopus laevis) homolog 2; dickkopf 2 homolog (Xenopus laevis); DKK-2; dickkopf 2 homolog; dickkop ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DKK2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DKK2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	DKK2
Name	dickkopf WNT signaling pathway inhibitor 2
Aliases	dickkopf (Xenopus laevis) homolog 2; dickkopf 2 homolog (Xenopus laevis); DKK-2; dickkopf 2 homolog; dickkop ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DKK2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	DKK2
Name	dickkopf WNT signaling pathway inhibitor 2
Aliases	dickkopf (Xenopus laevis) homolog 2; dickkopf 2 homolog (Xenopus laevis); DKK-2; dickkopf 2 homolog; dickkop ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of DKK2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	DKK2
Name	dickkopf WNT signaling pathway inhibitor 2
Aliases	dickkopf (Xenopus laevis) homolog 2; dickkopf 2 homolog (Xenopus laevis); DKK-2; dickkopf 2 homolog; dickkop ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between DKK2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	DKK2
Name	dickkopf WNT signaling pathway inhibitor 2
Aliases	dickkopf (Xenopus laevis) homolog 2; dickkopf 2 homolog (Xenopus laevis); DKK-2; dickkopf 2 homolog; dickkop ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting DKK2 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse DKK2