TISIDB

Summary
Symbol	FZD4
Name	frizzled class receptor 4
Aliases	CD344; frizzled (Drosophila) homolog 4; frizzled homolog 4 (Drosophila); frizzled 4, seven transmembrane spa ......
Chromosomal Location	11q14-q21
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	Membrane; Multi-pass membrane protein. Cell membrane Multi-pass membrane protein
Domain	PF01534 Frizzled/Smoothened family membrane region PF01392 Fz domain
Function	Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). In retina, it can be both activated by Wnt protein-binding, but also by a Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues.

> Gene Ontology [ TOP ]
Biological Process	GO:0001101 response to acid chemical GO:0001553 luteinization GO:0001570 vasculogenesis GO:0001654 eye development GO:0001736 establishment of planar polarity GO:0001738 morphogenesis of a polarized epithelium GO:0006869 lipid transport GO:0007162 negative regulation of cell adhesion GO:0007164 establishment of tissue polarity GO:0007223 Wnt signaling pathway, calcium modulating pathway GO:0007254 JNK cascade GO:0007423 sensory organ development GO:0007548 sex differentiation GO:0007605 sensory perception of sound GO:0007626 locomotory behavior GO:0008406 gonad development GO:0008585 female gonad development GO:0009914 hormone transport GO:0010810 regulation of cell-substrate adhesion GO:0010812 negative regulation of cell-substrate adhesion GO:0010817 regulation of hormone levels GO:0010876 lipid localization GO:0016055 Wnt signaling pathway GO:0021549 cerebellum development GO:0022037 metencephalon development GO:0022412 cellular process involved in reproduction in multicellular organism GO:0022602 ovulation cycle process GO:0023061 signal release GO:0030902 hindbrain development GO:0030947 regulation of vascular endothelial growth factor receptor signaling pathway GO:0031098 stress-activated protein kinase signaling cascade GO:0031589 cell-substrate adhesion GO:0031987 locomotion involved in locomotory behavior GO:0032526 response to retinoic acid GO:0032872 regulation of stress-activated MAPK cascade GO:0032874 positive regulation of stress-activated MAPK cascade GO:0033674 positive regulation of kinase activity GO:0034446 substrate adhesion-dependent cell spreading GO:0035426 extracellular matrix-cell signaling GO:0035567 non-canonical Wnt signaling pathway GO:0035929 steroid hormone secretion GO:0042698 ovulation cycle GO:0042701 progesterone secretion GO:0043010 camera-type eye development GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0043506 regulation of JUN kinase activity GO:0043507 positive regulation of JUN kinase activity GO:0045137 development of primary sexual characteristics GO:0045860 positive regulation of protein kinase activity GO:0046328 regulation of JNK cascade GO:0046330 positive regulation of JNK cascade GO:0046545 development of primary female sexual characteristics GO:0046660 female sex differentiation GO:0046879 hormone secretion GO:0048010 vascular endothelial growth factor receptor signaling pathway GO:0048511 rhythmic process GO:0048514 blood vessel morphogenesis GO:0048608 reproductive structure development GO:0050886 endocrine process GO:0050954 sensory perception of mechanical stimulus GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0051403 stress-activated MAPK cascade GO:0060041 retina development in camera-type eye GO:0060070 canonical Wnt signaling pathway GO:0060071 Wnt signaling pathway, planar cell polarity pathway GO:0060986 endocrine hormone secretion GO:0061298 retina vasculature development in camera-type eye GO:0061299 retina vasculature morphogenesis in camera-type eye GO:0061300 cerebellum vasculature development GO:0061301 cerebellum vasculature morphogenesis GO:0061304 retinal blood vessel morphogenesis GO:0061458 reproductive system development GO:0070302 regulation of stress-activated protein kinase signaling cascade GO:0070304 positive regulation of stress-activated protein kinase signaling cascade GO:0071229 cellular response to acid chemical GO:0071300 cellular response to retinoic acid GO:0071396 cellular response to lipid GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0090175 regulation of establishment of planar polarity GO:0090287 regulation of cellular response to growth factor stimulus GO:0198738 cell-cell signaling by wnt GO:1905330 regulation of morphogenesis of an epithelium GO:2000027 regulation of organ morphogenesis
Molecular Function	GO:0017147 Wnt-protein binding GO:0019955 cytokine binding GO:0030165 PDZ domain binding GO:0031625 ubiquitin protein ligase binding GO:0042813 Wnt-activated receptor activity GO:0044389 ubiquitin-like protein ligase binding GO:0046982 protein heterodimerization activity
Cellular Component	GO:0030135 coated vesicle GO:0030136 clathrin-coated vesicle GO:0030139 endocytic vesicle GO:0030659 cytoplasmic vesicle membrane GO:0030662 coated vesicle membrane GO:0030665 clathrin-coated vesicle membrane GO:0030666 endocytic vesicle membrane GO:0030669 clathrin-coated endocytic vesicle membrane GO:0045334 clathrin-coated endocytic vesicle

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04150 mTOR signaling pathway hsa04310 Wnt signaling pathway hsa04390 Hippo signaling pathway hsa04550 Signaling pathways regulating pluripotency of stem cells hsa04916 Melanogenesis
Reactome	R-HSA-4608870: Asymmetric localization of PCP proteins R-HSA-3858494: Beta-catenin independent WNT signaling R-HSA-4086398: Ca2+ pathway R-HSA-8856825: Cargo recognition for clathrin-mediated endocytosis R-HSA-373080: Class B/2 (Secretin family receptors) R-HSA-8856828: Clathrin-mediated endocytosis R-HSA-1643685: Disease R-HSA-5663202: Diseases of signal transduction R-HSA-500792: GPCR ligand binding R-HSA-199991: Membrane Trafficking R-HSA-4086400: PCP/CE pathway R-HSA-5340588: RNF mutants show enhanced WNT signaling and proliferation R-HSA-4641263: Regulation of FZD by ubiquitination R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR R-HSA-4791275: Signaling by WNT in cancer R-HSA-195721: Signaling by Wnt R-HSA-201681: TCF dependent signaling in response to WNT R-HSA-5653656: Vesicle-mediated transport R-HSA-5099900: WNT5A-dependent internalization of FZD4

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04150 mTOR signaling pathway
hsa04310 Wnt signaling pathway
hsa04390 Hippo signaling pathway
hsa04550 Signaling pathways regulating pluripotency of stem cells
hsa04916 Melanogenesis

Reactome

R-HSA-4608870: Asymmetric localization of PCP proteins
R-HSA-3858494: Beta-catenin independent WNT signaling
R-HSA-4086398: Ca2+ pathway
R-HSA-8856825: Cargo recognition for clathrin-mediated endocytosis
R-HSA-373080: Class B/2 (Secretin family receptors)
R-HSA-8856828: Clathrin-mediated endocytosis
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-500792: GPCR ligand binding
R-HSA-199991: Membrane Trafficking
R-HSA-4086400: PCP/CE pathway
R-HSA-5340588: RNF mutants show enhanced WNT signaling and proliferation
R-HSA-4641263: Regulation of FZD by ubiquitination
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
R-HSA-4791275: Signaling by WNT in cancer
R-HSA-195721: Signaling by Wnt
R-HSA-201681: TCF dependent signaling in response to WNT
R-HSA-5653656: Vesicle-mediated transport
R-HSA-5099900: WNT5A-dependent internalization of FZD4

Summary
Symbol	FZD4
Name	frizzled class receptor 4
Aliases	CD344; frizzled (Drosophila) homolog 4; frizzled homolog 4 (Drosophila); frizzled 4, seven transmembrane spa ......
Chromosomal Location	11q14-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between FZD4 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 ]
There is no record.

Summary
Symbol	FZD4
Name	frizzled class receptor 4
Aliases	CD344; frizzled (Drosophila) homolog 4; frizzled homolog 4 (Drosophila); frizzled 4, seven transmembrane spa ......
Chromosomal Location	11q14-q21
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 FZD4 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	Second most enriched score: 0.52	Sensitive to T cell-mediated killing
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	FZD4
Name	frizzled class receptor 4
Aliases	CD344; frizzled (Drosophila) homolog 4; frizzled homolog 4 (Drosophila); frizzled 4, seven transmembrane spa ......
Chromosomal Location	11q14-q21
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 FZD4 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	-0.508	0.0659
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.56	0.615
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.472	0.584
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.476	0.195
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.342	0.831
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.64	0.734
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.228	0.546
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.333	0.806
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.087	0.955
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.846	0.596
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	1.888	0.382
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.318	0.0113

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of FZD4 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	3.7	0	3.7	0.27
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	3.7	0	3.7	0.314
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	0	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	7.7	-7.7	0.371
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	FZD4
Name	frizzled class receptor 4
Aliases	CD344; frizzled (Drosophila) homolog 4; frizzled homolog 4 (Drosophila); frizzled 4, seven transmembrane spa ......
Chromosomal Location	11q14-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FZD4. 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	FZD4
Name	frizzled class receptor 4
Aliases	CD344; frizzled (Drosophila) homolog 4; frizzled homolog 4 (Drosophila); frizzled 4, seven transmembrane spa ......
Chromosomal Location	11q14-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FZD4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FZD4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	FZD4
Name	frizzled class receptor 4
Aliases	CD344; frizzled (Drosophila) homolog 4; frizzled homolog 4 (Drosophila); frizzled 4, seven transmembrane spa ......
Chromosomal Location	11q14-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FZD4. 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	FZD4
Name	frizzled class receptor 4
Aliases	CD344; frizzled (Drosophila) homolog 4; frizzled homolog 4 (Drosophila); frizzled 4, seven transmembrane spa ......
Chromosomal Location	11q14-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of FZD4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	FZD4
Name	frizzled class receptor 4
Aliases	CD344; frizzled (Drosophila) homolog 4; frizzled homolog 4 (Drosophila); frizzled 4, seven transmembrane spa ......
Chromosomal Location	11q14-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between FZD4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	FZD4
Name	frizzled class receptor 4
Aliases	CD344; frizzled (Drosophila) homolog 4; frizzled homolog 4 (Drosophila); frizzled 4, seven transmembrane spa ......
Chromosomal Location	11q14-q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting FZD4 collected from DrugBank database.

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

Browse FZD4