Details for: WIF1

Gene ID: 11197

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: WIF1

Ensembl ID: ENSG00000156076

Description: WNT inhibitory factor 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • Mueller cell CL0000636
    CSI 40.77
    rCSI 93.04%
    PRS 92.95
  • skin fibroblast CL0002620
    CSI 24.01
    rCSI 20.7%
    PRS 96.48
  • enteric smooth muscle cell CL0002504
    CSI 17.64
    rCSI 25.17%
    PRS 96.86
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 9.96
    rCSI 17.58%
    PRS 89.63
  • pulmonary alveolar type 2 cell CL0002063
    CSI 8.26
    rCSI 12.81%
    PRS 96.51
  • sst GABAergic cortical interneuron CL4023017
    CSI 7.15
    rCSI 9.22%
    PRS 90.64
  • myoepithelial cell CL0000185
    CSI 6.57
    rCSI 16.62%
    PRS 97.5
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 6.5
    rCSI 8.08%
    PRS 88.31
  • inhibitory interneuron CL0000498
    CSI 6.04
    rCSI 13.95%
    PRS 91.28
  • lung ciliated cell CL1000271
    CSI 5.07
    rCSI 5.87%
    PRS 93.07
  • ON-bipolar cell CL0000749
    CSI 4.33
    rCSI 6.44%
    PRS 95.28
  • epithelial cell of lower respiratory tract CL0002632
    CSI 4.18
    rCSI 3.24%
    PRS 97.83
  • sncg GABAergic cortical interneuron CL4023015
    CSI 3.55
    rCSI 5.7%
    PRS 90.44
  • multi-ciliated epithelial cell CL0005012
    CSI 3.41
    rCSI 3.4%
    PRS 92.95
  • chondrocyte CL0000138
    CSI 3.36
    rCSI 5.34%
    PRS 93.97
  • basal cell CL0000646
    CSI 3.09
    rCSI 4.13%
    PRS 94.61
  • retinal bipolar neuron CL0000748
    CSI 2.63
    rCSI 4.93%
    PRS 91.8
  • retina horizontal cell CL0000745
    CSI 2.59
    rCSI 3.94%
    PRS 94.56
  • basal cell of prostate epithelium CL0002341
    CSI 2.55
    rCSI 7.38%
    PRS 97.14
  • rod bipolar cell CL0000751
    CSI 2.53
    rCSI 4.55%
    PRS 93.56
  • OFF-bipolar cell CL0000750
    CSI 2.28
    rCSI 3.11%
    PRS 94.67
  • Bergmann glial cell CL0000644
    CSI 2.24
    rCSI 3.07%
    PRS 92.12
  • glycinergic amacrine cell CL4030028
    CSI 1.87
    rCSI 4.88%
    PRS 91.94
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.87
    rCSI 4.19%
    PRS 90.21
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.77
    rCSI 2.98%
    PRS 89.98
  • retinal cone cell CL0000573
    CSI 1.69
    rCSI 2.72%
    PRS 91.48
  • pulmonary alveolar type 1 cell CL0002062
    CSI 1.61
    rCSI 9.28%
    PRS 94.67
  • odontoblast CL0000060
    CSI 1.59
    rCSI 35.96%
    PRS 98.65
  • amacrine cell CL0000561
    CSI 1.47
    rCSI 4.25%
    PRS 91.4
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.19
    rCSI 3.71%
    PRS 91.71
  • mesenchymal cell CL0008019
    CSI 1.17
    rCSI 2.98%
    PRS 94.81
  • starburst amacrine cell CL0004232
    CSI 0.75
    rCSI 6.28%
    PRS 86.57

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

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • 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 [WIF1](/details-gene/11197) (WNT inhibitory factor 1) is a protein-coding gene located on chromosome 12q14.3. It encodes a secreted protein that functions as a key antagonist of the Wnt signaling pathway. [WIF1](/details-gene/11197) binds directly to Wnt proteins in the extracellular space, preventing them from interacting with their cell-surface receptors and thereby inhibiting downstream signal transduction [Link](https://doi.org/10.1038/18899). This regulatory role is critical for numerous developmental processes, including embryonic patterning and organogenesis. Expression data indicates that **Overall**, [WIF1](/details-gene/11197) shows highly significant and specific expression in a diverse range of cell types, most notably in retinal [Mueller cell](/details-cell/CL0000636)s, as well as in mesenchymal cells like [skin fibroblast](/details-cell/CL0002620)s and [enteric smooth muscle cell](/details-cell/CL0002504)s, highlighting its importance in tissue homeostasis and development across multiple organ systems. ## Cellular Roles and Expression Landscape The expression profile of [WIF1](/details-gene/11197) underscores its specialized roles in neural, mesenchymal, and epithelial tissues. **Overall**, the gene's significance is exceptionally high in [Mueller cell](/details-cell/CL0000636)s of the retina (CSI: 40.77), suggesting it is a primary regulator of Wnt signaling in the context of retinal development and maintenance. Its role extends to various structural and stromal cell populations. High significance is observed in [skin fibroblast](/details-cell/CL0002620)s (CSI: 24.01), [enteric smooth muscle cell](/details-cell/CL0002504)s (CSI: 17.64), and [chondrocyte](/details-cell/CL0000138)s (CSI: 3.36), which is consistent with the Wnt pathway's established function in regulating cell fate, proliferation, and differentiation in mesenchymal lineages. Furthermore, [WIF1](/details-gene/11197) is significantly expressed in specific neuronal subtypes, including various GABAergic cortical interneurons and [ON-bipolar cell](/details-cell/CL0000749)s. It also shows notable significance in specialized epithelial cells, such as [pulmonary alveolar type 2 cell](/details-cell/CL0002063)s, [lung ciliated cell](/details-cell/CL1000271)s, and [myoepithelial cell](/details-cell/CL0000185)s. This broad but specific expression pattern points to a role for [WIF1](/details-gene/11197) as a secreted, local modulator of Wnt signaling that maintains tissue architecture and cellular quiescence in a variety of contexts. ## Pathways and Molecular Function [WIF1](/details-gene/11197) is a well-characterized antagonist of the Wnt signaling pathway. Its primary molecular function is direct [Wnt-protein binding](/details-go/GO:0017147) within the [extracellular region](/details-go/GO:0005576). This interaction is central to its role in the [negative regulation of wnt signaling pathway](/details-go/GO:0030178) and, more specifically, the [negative regulation of tcf-dependent signaling by wnt ligand antagonists](/details-reactome/R-HSA-3772470). This fundamental inhibitory function underpins its involvement in a wide array of biological processes. Functional annotation links [WIF1](/details-gene/11197) to critical developmental events such as [anterior/posterior pattern specification](/details-go/GO:0009952), [heart development](/details-go/GO:0007507), and [blood vessel development](/details-go/GO:0001568). Its involvement in these processes is consistent with its expression in developmental tissues and its ability to create precise gradients of Wnt activity. The gene is also implicated in the [nodal signaling pathway](/details-go/GO:0038092), suggesting crosstalk between major developmental signaling cascades. The structural basis for its inhibitory activity has been explored through NMR studies of its WIF domain [Link](https://doi.org/10.1016/j.jmb.2006.01.047). ## Research Directions Given that [WIF1](/details-gene/11197) acts as a natural brake on the Wnt signaling pathway, which is frequently dysregulated in disease, several research avenues are pertinent. **Proposed Hypotheses:** 1. Given its exceptionally high significance in [Mueller cell](/details-cell/CL0000636)s, dysregulation or downregulation of [WIF1](/details-gene/11197) may contribute to the pathogenesis of retinal diseases characterized by aberrant glial activation and neuronal degeneration, such as diabetic retinopathy or glaucoma. 2. The high expression of [WIF1](/details-gene/11197) in [skin fibroblast](/details-cell/CL0002620)s suggests that it is a key regulator of fibroblast homeostasis. Its epigenetic silencing or downregulation during tissue injury could be a permissive step for the development of pathological fibrosis by allowing for unchecked Wnt-driven fibroblast-to-myofibroblast differentiation. **Key Experimental Approach:** To test the second hypothesis regarding its role in fibrosis, a multi-pronged approach could be employed. Initially, primary human dermal fibroblasts could be cultured *in vitro* and treated with pro-fibrotic stimuli like TGF-β. [WIF1](/details-gene/11197) expression would be silenced using siRNA or CRISPR-Cas9 gene editing. The impact on myofibroblast differentiation could then be quantified by measuring alpha-smooth muscle actin (α-SMA) expression via western blot and immunofluorescence, alongside assessing collagen production. Subsequently, these findings could be validated *in vivo* using a conditional knockout mouse model where *Wif1* is specifically deleted in fibroblasts. These mice would be subjected to a skin wounding model, and outcomes such as wound closure rate, scar size, and collagen deposition would be compared to wild-type controls. **Therapeutic Potential:** The Wnt pathway is a well-established oncogenic driver in many cancers, and [WIF1](/details-gene/11197) is frequently silenced via promoter hypermethylation in tumors. Consequently, [WIF1](/details-gene/11197) represents a potential tumor suppressor whose function could be restored therapeutically. Instead of inhibition, a therapeutic strategy would likely involve **activation** or re-introduction. This could be achieved through the development of demethylating agents to reactivate endogenous gene expression or through the systemic administration of a stable, recombinant [WIF1](/details-gene/11197) protein. Such an approach could selectively inhibit Wnt-dependent tumor growth while potentially having minimal effects on healthy tissues where Wnt signaling is already appropriately regulated.

Genular Protein ID: 2712160998

Symbol: WIF1_HUMAN

Name: Wnt inhibitory factor 1

UniProtKB Accession Codes:

Q9Y5W5 Q6UXI1 Q8WVG4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 14 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 5 PDBsum 5 PIR 1 PRINTS 1 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SignaLink 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10201374

Title: A new secreted protein that binds to Wnt proteins and inhibits their activities.

PubMed ID: 10201374

DOI: 10.1038/18899

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

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: 19188438

Title: Myocilin is a modulator of Wnt signaling.

PubMed ID: 19188438

DOI: 10.1128/mcb.01274-08

PubMed ID: 16476441

Title: NMR structure of the WIF domain of the human Wnt-inhibitory factor-1.

PubMed ID: 16476441

DOI: 10.1016/j.jmb.2006.01.047

Sequence Information:

  • Length: 379
  • Mass: 41528
  • Checksum: 32ADFA6644833E9D
  • Sequence:
    • MARRSAFPAA ALWLWSILLC LLALRAEAGP PQEESLYLWI DAHQARVLIG FEEDILIVSE 
GKMAPFTHDF RKAQQRMPAI PVNIHSMNFT WQAAGQAEYF YEFLSLRSLD KGIMADPTVN 
VPLLGTVPHK ASVVQVGFPC LGKQDGVAAF EVDVIVMNSE GNTILQTPQN AIFFKTCQQA 
ECPGGCRNGG FCNERRICEC PDGFHGPHCE KALCTPRCMN GGLCVTPGFC ICPPGFYGVN 
CDKANCSTTC FNGGTCFYPG KCICPPGLEG EQCEISKCPQ PCRNGGKCIG KSKCKCSKGY 
QGDLCSKPVC EPGCGAHGTC HEPNKCQCQE GWHGRHCNKR YEASLIHALR PAGAQLRQHT 
PSLKKAEERR DPPESNYIW