FZD8 Gene

HGNC Family	G protein-coupled receptors
Name	frizzled class receptor 8
Description	This intronless gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This gene is highly expressed in two human cancer cell lines, indicating that it may play a role in several types of cancer. The crystal structure of the extracellular cysteine-rich domain of a similar mouse protein has been determined. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Frizzled‐8 (FZD8) functions as a critical receptor modulating Wnt signaling in multiple biological contexts. In neural development, a soluble form of the FZD8 cysteine‐rich domain antagonizes endogenous Wnt ligands such as Wnt‑1 and Wnt‑5a, thereby regulating the proliferation and differentiation of dopaminergic precursors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " FZD8 also serves as a receptor target for members of the R‑spondin family, which bind FZD8 together with LRP6 to promote canonical Wnt/β‑catenin signaling, stabilize β‑catenin and activate downstream gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In the hematopoietic stem cell niche, FZD8 is expressed along with Flamingo to mediate noncanonical Wnt signals that help maintain long‐term quiescence by suppressing the Ca²⁺–NFAT–IFNγ pathway and antagonizing canonical signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, functional studies in cancer models indicate that targeting FZD8 with specific antibodies can inhibit the growth of RNF43‑mutant pancreatic ductal adenocarcinoma cells, underscoring its context‑dependent role in tumor cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, modulation of FZD8 expression is linked to oncogenic Ras signaling, where reduced FZD8 correlates with enhanced noncanonical Wnt/Ca²⁺ pathway activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In bone biology, FZD8 is important for regulating osteoclastogenesis, as Fzd8‑deficient mice develop osteopenia due to increased bone resorption, independently of osteoblast‐mediated mechanisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, in airway smooth muscle cells FZD8 participates in noncanonical Wnt‑5A signaling that links TGF‑β responses to extracellular matrix deposition, a process relevant to tissue remodeling in chronic lung diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, in head and neck cancer stem‐like cells, FZD8 is upregulated in response to c‑Met signaling via an ERK/c‑Fos cascade, and its expression is essential for maintaining the Wnt/β‑catenin pathway activity that supports tumor initiation and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gonçalo Castelo-Branco, Joseph Wagner, Francisco J Rodriguez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1534900100"}], "href": "https://doi.org/10.1073/pnas.1534900100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14557550"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14557550"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ju-Suk Nam, Taryn J Turcotte, Peter F Smith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M508324200"}], "href": "https://doi.org/10.1074/jbc.M508324200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16543246"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16543246"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ryohichi Sugimura, Xi C He, Aparna Venkatraman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2012.05.041"}], "href": "https://doi.org/10.1016/j.cell.2012.05.041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22817897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22817897"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zachary Steinhart, Zvezdan Pavlovic, Megha Chandrashekhar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.4219"}], "href": "https://doi.org/10.1038/nm.4219"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27869803"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27869803"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Man-Tzu Wang, Matthew Holderfield, Jacqueline Galeas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "K-Ras Promotes Tumorigenicity through Suppression of Non-canonical Wnt Signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2015.10.041"}], "href": "https://doi.org/10.1016/j.cell.2015.10.041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26590425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26590425"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Joachim Albers, Johannes Keller, Anke Baranowsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201207142"}], "href": "https://doi.org/10.1083/jcb.201207142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23401003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23401003"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kuldeep Kumawat, Mark H Menzen, I Sophie T Bos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Noncanonical WNT-5A signaling regulates TGF-β-induced extracellular matrix production by airway smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.12-217539"}], "href": "https://doi.org/10.1096/fj.12-217539"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23254341"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23254341"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Shuyang Sun, Suling Liu, Sheng Zhong Duan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting the c-Met/FZD8 signaling axis eliminates patient-derived cancer stem-like cells in head and neck squamous carcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-14-0826"}], "href": "https://doi.org/10.1158/0008-5472.CAN-14-0826"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25320014"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25320014"}]}]}]}
Synonyms	FZ-8, HFZ8
Proteins	FZD8_HUMAN
NCBI Gene ID	8325
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

FZD8 has 6,021 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 112 datasets.

Click the + buttons to view associations for FZD8 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

FZD8 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 FZD8 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 FZD8 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 FZD8 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of FZD8 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of FZD8 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 FZD8 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 FZD8 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 FZD8 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 FZD8 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 FZD8 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of FZD8 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of FZD8 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 FZD8 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with FZD8 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 FZD8 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of FZD8 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 FZD8 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 FZD8 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing FZD8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with FZD8 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 FZD8 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing FZD8 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of FZD8 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with FZD8 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with FZD8 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with FZD8 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by FZD8 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with FZD8 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with FZD8 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 FZD8 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 FZD8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with FZD8 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 FZD8 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 FZD8 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of FZD8 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 FZD8 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with FZD8 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with FZD8 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 FZD8 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with FZD8 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.