Details for: WNT3

Gene ID: 7473

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: WNT3

Ensembl ID: ENSG00000108379

Description: Wnt family member 3

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • keratinocyte CL0000312
    CSI 10.33
    rCSI 8.66%
    PRS 97.91
  • radial glial cell CL0000681
    CSI 2.86
    rCSI 3.97%
    PRS 98.56
  • Bergmann glial cell CL0000644
    CSI 2.8
    rCSI 3.83%
    PRS 95.91
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.78
    rCSI 3.21%
    PRS 96.37
  • melanocyte of skin CL1000458
    CSI 2.52
    rCSI 3.43%
    PRS 85.01
  • basal cell of epidermis CL0002187
    CSI 2.15
    rCSI 3.81%
    PRS 83.84
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.07
    rCSI 3.66%
    PRS 95.53
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.22
    rCSI 1.48%
    PRS 88.33

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [WNT3](/details-gene/7473) is a protein-coding gene that encodes a member of the Wnt family of secreted signaling proteins. As a proto-oncogene, it is a critical player in the [canonical Wnt signaling pathway](/details-go/GO:0060070), which is fundamental to numerous developmental processes, including [anterior/posterior axis specification](/details-go/GO:0009948), [cell fate commitment](/details-go/GO:0045165), and organogenesis ([Link](https://doi.org/10.1006/geno.1993.1412)). Functioning as a [cytokine](/details-go/GO:0005125) and [receptor ligand](/details-go/GO:0048018), [WNT3](/details-gene/7473) binds to Frizzled family receptors to initiate intracellular signaling cascades. Its expression is most significant in epidermal cells, particularly [keratinocytes](/details-cell/CL0000312), and in various neurodevelopmental cell types, such as [radial glial cells](/details-cell/CL0000681). Clinically, homozygous mutations in [WNT3](/details-gene/7473) are associated with tetra-amelia, a severe congenital disorder characterized by the absence of all four limbs ([OMIM](/details-omim/273395); [Link](https://doi.org/10.1086/382196)). ## Cellular Roles and Expression Landscape The expression profile of [WNT3](/details-gene/7473) highlights its specialized roles in epithelial tissues and the developing nervous system. **Overall**, the gene shows its highest significance in [keratinocytes](/details-cell/CL0000312) (CSI: 10.33), suggesting a primary function in the establishment and maintenance of the epidermis. This is further supported by notable expression in other epidermal lineage cells, including [melanocytes of skin](/details-cell/CL1000458) and [basal cells of the epidermis](/details-cell/CL0002187). A second major site of [WNT3](/details-gene/7473) activity is within the developing central nervous system. It is a significant marker for progenitor and glial cell types, including [radial glial cells](/details-cell/CL0000681), [Bergmann glial cells](/details-cell/CL0000644), and [neuroblasts](/details-cell/CL0000338). This expression pattern is consistent with its established role in guiding neurogenesis and axon development. Additionally, a lower but notable significance is observed in a subset of adaptive immune cells, specifically [CD8-positive, alpha-beta memory T cells, CD45RO-positive](/details-cell/CL0001203), which may indicate a contextual role in T cell biology. ## Pathways and Molecular Function [WNT3](/details-gene/7473) functions as a secreted ligand that initiates the [Signaling by Wnt](/details-reactome/R-HSA-195721) pathway. Its molecular function is defined by its ability to bind [Frizzled receptors](/details-go/GO:0005109) on the surface of target cells, leading to the activation of [TCF dependent signaling in response to Wnt](/details-reactome/R-HSA-201681). As a secreted protein, it is processed through the [endoplasmic reticulum](/details-go/GO:0005788) and [Golgi](/details-go/GO:0005796) and is found in the [extracellular space](/details-go/GO:0005615) and [extracellular exosomes](/details-go/GO:0070062), where it can be maintained in a soluble, active form by serum glycoproteins ([Link](https://doi.org/10.7554/elife.11621)). The biological processes associated with [WNT3](/details-gene/7473) are predominantly related to embryonic development and cellular differentiation. Its involvement in [anterior/posterior axis specification](/details-go/GO:0009948), [limb bud formation](/details-go/GO:0060174), and [mesoderm formation](/details-go/GO:0001707) underscores its critical role in establishing the body plan. The high expression in neural progenitors is directly linked to its function in regulating [neuron differentiation](/details-go/GO:0030182), [neurogenesis](/details-go/GO:0050767), and [axon guidance](/details-go/GO:0007411). Furthermore, its role in promoting [stem cell proliferation](/details-go/GO:0072089) and [positive regulation of osteoblast differentiation](/details-go/GO:0045669) highlights its importance in tissue homeostasis and repair beyond embryogenesis. ## Research Directions Given the proto-oncogenic nature of [WNT3](/details-gene/7473) and its tight regulation during development, its dysregulation is a strong candidate for driving pathological processes in adult tissues, particularly in cancers of epithelial origin. ### Testable Hypotheses 1. **Role in Skin Carcinogenesis:** Based on its exceptionally high significance in [keratinocytes](/details-cell/CL0000312), we hypothesize that aberrant overexpression or reactivation of [WNT3](/details-gene/7473) in adult epidermal cells is a key event in the initiation or progression of non-melanoma skin cancers, such as basal cell carcinoma or squamous cell carcinoma, by promoting uncontrolled proliferation. 2. **Modulation of Anti-Tumor Immunity:** The expression of [WNT3](/details-gene/7473) in [CD8-positive, alpha-beta memory T cells, CD45RO-positive](/details-cell/CL0001203) suggests a potential immunomodulatory role. We hypothesize that secretion of [WNT3](/details-gene/7473) within the tumor microenvironment could influence the survival, persistence, or effector function of memory T cells, thereby shaping the efficacy of anti-tumor immune responses. 3. **Involvement in Neurodegenerative Repair:** Considering its function in [neuron differentiation](/details-go/GO:0030182) and regulation of glial cells, we hypothesize that therapeutic administration of [WNT3](/details-gene/7473) or modulation of its pathway could promote neuronal repair or regeneration in the context of neurodegenerative diseases or brain injury. ### Proposed Key Experiment To test the hypothesis that [WNT3](/details-gene/7473) drives skin carcinogenesis (Hypothesis 1), a powerful approach would be to use a genetically engineered mouse model. A conditional-on allele for *Wnt3* (e.g., Lox-Stop-Lox-Wnt3) could be crossed with a keratinocyte-specific, tamoxifen-inducible Cre-recombinase driver (e.g., KRT14-CreERT2). Upon topical tamoxifen application to the skin of adult mice, [WNT3](/details-gene/7473) expression would be induced specifically in keratinocytes. The mice would be monitored for the development of skin lesions, and tissues would be analyzed by histology, immunohistochemistry (for proliferation markers like Ki-67 and Wnt pathway targets like beta-catenin), and RNA-sequencing to confirm pathway activation and characterize the resulting tumors. ### Therapeutic Potential As a secreted proto-oncogene, [WNT3](/details-gene/7473) represents an attractive therapeutic target for **inhibition**, particularly in cancers driven by its overexpression. Its extracellular location makes it highly amenable to targeting by biologic drugs, such as neutralizing monoclonal antibodies that can block its interaction with Frizzled receptors. Small molecule inhibitors targeting downstream components of the Wnt pathway are also in development. Such a strategy would be aimed at suppressing tumor cell proliferation and promoting differentiation, and could be most effective in stratified patient populations where [WNT3](/details-gene/7473) is identified as a key oncogenic driver.

Genular Protein ID: 3108330587

Symbol: WNT3_HUMAN

Name: Proto-oncogene Wnt-3

UniProtKB Accession Codes:

P56703 Q2M237 Q9H1J9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 3 GO 40 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11604997

Title: Molecular cloning and characterization of human WNT3.

PubMed ID: 11604997

DOI: 10.3892/ijo.19.5.977

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8244403

Title: Molecular cloning and chromosomal localization to 17q21 of the human WNT3 gene.

PubMed ID: 8244403

DOI: 10.1006/geno.1993.1412

PubMed ID: 14872406

Title: Homozygous WNT3 mutation causes tetra-amelia in a large consanguineous family.

PubMed ID: 14872406

DOI: 10.1086/382196

PubMed ID: 26902720

Title: Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/alpha-albumin.

PubMed ID: 26902720

DOI: 10.7554/elife.11621

Sequence Information:

  • Length: 355
  • Mass: 39645
  • Checksum: 85D15F2C7884A64F
  • Sequence:
    • MEPHLLGLLL GLLLGGTRVL AGYPIWWSLA LGQQYTSLGS QPLLCGSIPG LVPKQLRFCR 
NYIEIMPSVA EGVKLGIQEC QHQFRGRRWN CTTIDDSLAI FGPVLDKATR ESAFVHAIAS 
AGVAFAVTRS CAEGTSTICG CDSHHKGPPG EGWKWGGCSE DADFGVLVSR EFADARENRP 
DARSAMNKHN NEAGRTTILD HMHLKCKCHG LSGSCEVKTC WWAQPDFRAI GDFLKDKYDS 
ASEMVVEKHR ESRGWVETLR AKYSLFKPPT ERDLVYYENS PNFCEPNPET GSFGTRDRTC 
NVTSHGIDGC DLLCCGRGHN TRTEKRKEKC HCIFHWCCYV SCQECIRIYD VHTCK