TISIDB

Summary
Symbol	DKK3
Name	dickkopf WNT signaling pathway inhibitor 3
Aliases	REIC; regulated in glioma; dickkopf (Xenopus laevis) homolog 3; dickkopf 3 homolog (Xenopus laevis); RIG-lik ......
Chromosomal Location	11p15.3
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:0006081 cellular aldehyde metabolic process GO:0006694 steroid biosynthetic process GO:0006700 C21-steroid hormone biosynthetic process GO:0006704 glucocorticoid biosynthetic process GO:0006705 mineralocorticoid biosynthetic process GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007179 transforming growth factor beta receptor signaling pathway GO:0008202 steroid metabolic process GO:0008207 C21-steroid hormone metabolic process GO:0008211 glucocorticoid metabolic process GO:0008212 mineralocorticoid metabolic process GO:0010565 regulation of cellular ketone metabolic process GO:0010566 regulation of ketone biosynthetic process GO:0010817 regulation of hormone levels GO:0010894 negative regulation of steroid biosynthetic process GO:0016055 Wnt signaling pathway GO:0017015 regulation of transforming growth factor beta receptor signaling pathway GO:0019216 regulation of lipid metabolic process GO:0019218 regulation of steroid metabolic process GO:0030111 regulation of Wnt signaling pathway GO:0030178 negative regulation of Wnt signaling pathway GO:0030325 adrenal gland development GO:0031943 regulation of glucocorticoid metabolic process GO:0031944 negative regulation of glucocorticoid metabolic process GO:0031946 regulation of glucocorticoid biosynthetic process GO:0031947 negative regulation of glucocorticoid biosynthetic process GO:0032341 aldosterone metabolic process GO:0032342 aldosterone biosynthetic process GO:0032344 regulation of aldosterone metabolic process GO:0032345 negative regulation of aldosterone metabolic process GO:0032347 regulation of aldosterone biosynthetic process GO:0032348 negative regulation of aldosterone biosynthetic process GO:0032350 regulation of hormone metabolic process GO:0032351 negative regulation of hormone metabolic process GO:0032353 negative regulation of hormone biosynthetic process GO:0034650 cortisol metabolic process GO:0034651 cortisol biosynthetic process GO:0034754 cellular hormone metabolic process GO:0035270 endocrine system development GO:0042180 cellular ketone metabolic process GO:0042181 ketone biosynthetic process GO:0042445 hormone metabolic process GO:0042446 hormone biosynthetic process GO:0044283 small molecule biosynthetic process GO:0045833 negative regulation of lipid metabolic process GO:0045939 negative regulation of steroid metabolic process GO:0046184 aldehyde biosynthetic process GO:0046885 regulation of hormone biosynthetic process GO:0046890 regulation of lipid biosynthetic process GO:0048732 gland development GO:0050810 regulation of steroid biosynthetic process GO:0051055 negative regulation of lipid biosynthetic process GO:0060070 canonical Wnt signaling pathway GO:0060828 regulation of canonical Wnt signaling pathway GO:0071559 response to transforming growth factor beta GO:0071560 cellular response to transforming growth factor beta stimulus GO:0090030 regulation of steroid hormone biosynthetic process GO:0090032 negative regulation of steroid hormone biosynthetic process GO:0090090 negative regulation of canonical Wnt signaling pathway GO:0090092 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway GO:0090287 regulation of cellular response to growth factor stimulus GO:0198738 cell-cell signaling by wnt GO:1901615 organic hydroxy compound metabolic process GO:1901617 organic hydroxy compound biosynthetic process GO:1902612 regulation of anti-Mullerian hormone signaling pathway GO:1902613 negative regulation of anti-Mullerian hormone signaling pathway GO:1903844 regulation of cellular response to transforming growth factor beta stimulus GO:1990262 anti-Mullerian hormone signaling pathway GO:2000064 regulation of cortisol biosynthetic process GO:2000065 negative regulation of cortisol biosynthetic process
Molecular Function	-
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	DKK3
Name	dickkopf WNT signaling pathway inhibitor 3
Aliases	REIC; regulated in glioma; dickkopf (Xenopus laevis) homolog 3; dickkopf 3 homolog (Xenopus laevis); RIG-lik ......
Chromosomal Location	11p15.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between DKK3 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 DKK3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26734010	Melanoma	Inhibit immunity (infiltration)	Increased CD8(+) T cell and reduced M2-type macrophages infiltration was observed in tumors inoculated together with DKK3-deficient MSCs.

Summary
Symbol	DKK3
Name	dickkopf WNT signaling pathway inhibitor 3
Aliases	REIC; regulated in glioma; dickkopf (Xenopus laevis) homolog 3; dickkopf 3 homolog (Xenopus laevis); RIG-lik ......
Chromosomal Location	11p15.3
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 DKK3 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	DKK3
Name	dickkopf WNT signaling pathway inhibitor 3
Aliases	REIC; regulated in glioma; dickkopf (Xenopus laevis) homolog 3; dickkopf 3 homolog (Xenopus laevis); RIG-lik ......
Chromosomal Location	11p15.3
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

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Points in the above scatter plot represent the expression difference of DKK3 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	-1.865	0.00473
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-2.509	0.194
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-1.382	0.302
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.151	0.731
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.4	0.845
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.159	0.949
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.15	0.796
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.245	0.868
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.046	0.976
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.005	0.625
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	2.147	0.448
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.358	0.00809

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of DKK3 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	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	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	1.4	-1.4	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	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	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	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
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	DKK3
Name	dickkopf WNT signaling pathway inhibitor 3
Aliases	REIC; regulated in glioma; dickkopf (Xenopus laevis) homolog 3; dickkopf 3 homolog (Xenopus laevis); RIG-lik ......
Chromosomal Location	11p15.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DKK3. 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	DKK3
Name	dickkopf WNT signaling pathway inhibitor 3
Aliases	REIC; regulated in glioma; dickkopf (Xenopus laevis) homolog 3; dickkopf 3 homolog (Xenopus laevis); RIG-lik ......
Chromosomal Location	11p15.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DKK3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DKK3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	DKK3
Name	dickkopf WNT signaling pathway inhibitor 3
Aliases	REIC; regulated in glioma; dickkopf (Xenopus laevis) homolog 3; dickkopf 3 homolog (Xenopus laevis); RIG-lik ......
Chromosomal Location	11p15.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DKK3. 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	DKK3
Name	dickkopf WNT signaling pathway inhibitor 3
Aliases	REIC; regulated in glioma; dickkopf (Xenopus laevis) homolog 3; dickkopf 3 homolog (Xenopus laevis); RIG-lik ......
Chromosomal Location	11p15.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of DKK3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	DKK3
Name	dickkopf WNT signaling pathway inhibitor 3
Aliases	REIC; regulated in glioma; dickkopf (Xenopus laevis) homolog 3; dickkopf 3 homolog (Xenopus laevis); RIG-lik ......
Chromosomal Location	11p15.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between DKK3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	DKK3
Name	dickkopf WNT signaling pathway inhibitor 3
Aliases	REIC; regulated in glioma; dickkopf (Xenopus laevis) homolog 3; dickkopf 3 homolog (Xenopus laevis); RIG-lik ......
Chromosomal Location	11p15.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting DKK3 collected from DrugBank database.

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

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