Details for: WFDC1

Gene ID: 58189

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: WFDC1

Ensembl ID: ENSG00000103175

Description: WAP four-disulfide core domain 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • OFF-bipolar cell CL0000750
    CSI 27.18
    rCSI 37.17%
    PRS 95.78
  • retinal pigment epithelial cell CL0002586
    CSI 18.03
    rCSI 35.8%
    PRS 95.43
  • myofibroblast cell CL0000186
    CSI 17.04
    rCSI 23.6%
    PRS 95.87
  • ON-bipolar cell CL0000749
    CSI 11.97
    rCSI 17.79%
    PRS 96.11
  • enteric smooth muscle cell CL0002504
    CSI 10.53
    rCSI 15.03%
    PRS 97.78
  • invaginating midget bipolar cell CL4033034
    CSI 8.61
    rCSI 50.87%
    PRS 91.53
  • microcirculation associated smooth muscle cell CL0008035
    CSI 8.29
    rCSI 24%
    PRS 96.85
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 7.31
    rCSI 13.29%
    PRS 94.05
  • tracheobronchial smooth muscle cell CL0019019
    CSI 7.02
    rCSI 12.38%
    PRS 98.2
  • neural progenitor cell CL0011020
    CSI 6.86
    rCSI 30.19%
    PRS 90.54
  • fibroblast of lung CL0002553
    CSI 6.6
    rCSI 6.14%
    PRS 98.25
  • rod bipolar cell CL0000751
    CSI 6.57
    rCSI 11.81%
    PRS 94.71
  • renal interstitial pericyte CL1001318
    CSI 6.26
    rCSI 17.27%
    PRS 96.68
  • bronchus fibroblast of lung CL2000093
    CSI 6.2
    rCSI 5.03%
    PRS 97.43
  • Bergmann glial cell CL0000644
    CSI 5.88
    rCSI 8.05%
    PRS 93.53
  • retinal bipolar neuron CL0000748
    CSI 5.83
    rCSI 10.91%
    PRS 93.24
  • flat midget bipolar cell CL4033033
    CSI 5.68
    rCSI 40.59%
    PRS 91.17
  • diffuse bipolar 3a cell CL4033029
    CSI 5.67
    rCSI 38.59%
    PRS 91.82
  • lung pericyte CL0009089
    CSI 5.03
    rCSI 13.28%
    PRS 98.73
  • smooth muscle cell CL0000192
    CSI 4.96
    rCSI 11.82%
    PRS 94.79
  • hepatic stellate cell CL0000632
    CSI 4.91
    rCSI 18.4%
    PRS 96.04
  • vascular associated smooth muscle cell CL0000359
    CSI 4.82
    rCSI 15.63%
    PRS 96.97
  • alveolar type 1 fibroblast cell CL4028004
    CSI 4.57
    rCSI 5.01%
    PRS 98.13
  • glioblast CL0000030
    CSI 4.55
    rCSI 7.25%
    PRS 93.58
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 4.45
    rCSI 16.81%
    PRS 91.83
  • mesenchymal cell CL0008019
    CSI 3.92
    rCSI 9.95%
    PRS 96
  • perivascular cell CL4033054
    CSI 3.75
    rCSI 5.13%
    PRS 98.56
  • diffuse bipolar 6 cell CL4033032
    CSI 3.51
    rCSI 18.44%
    PRS 90.81
  • cerebral cortex endothelial cell CL1001602
    CSI 3.31
    rCSI 5.73%
    PRS 95.3
  • stromal cell CL0000499
    CSI 3.2
    rCSI 9.01%
    PRS 95.91
  • myoepithelial cell CL0000185
    CSI 3.11
    rCSI 7.87%
    PRS 98.15
  • diffuse bipolar 4 cell CL4033031
    CSI 3.04
    rCSI 34.81%
    PRS 87.77
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 2.87
    rCSI 10.34%
    PRS 90.74
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 2.86
    rCSI 16.82%
    PRS 92.01
  • bronchiolar smooth muscle cell CL4033017
    CSI 2.71
    rCSI 40.61%
    PRS 98.81
  • cone retinal bipolar cell CL0000752
    CSI 2.47
    rCSI 32.2%
    PRS 93.9
  • OFFx cell CL4033036
    CSI 1.89
    rCSI 8.9%
    PRS 90.36
  • smooth muscle cell of the pulmonary artery CL0002591
    CSI 1.36
    rCSI 10.41%
    PRS 97.68
  • blood vessel smooth muscle cell CL0019018
    CSI 1.18
    rCSI 9.58%
    PRS 96.84
  • diffuse bipolar 1 cell CL4033027
    CSI 1.15
    rCSI 8.62%
    PRS 90.21
  • smooth muscle cell of prostate CL1000487
    CSI 1.07
    rCSI 6.28%
    PRS 98.32

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 [WFDC1](/details-gene/58189) (WAP four-disulfide core domain 1) is a protein-coding gene located on chromosome 16q24.1. It encodes a secreted protein that functions as a [serine-type endopeptidase inhibitor](/details-go/GO:0004867). This molecular activity is associated with several key biological processes, including the negative regulation of cell growth ([GO:0030308](https://www.ebi.ac.uk/QuickGO/term/GO:0030308)), inflammatory responses ([GO:0050728](https://www.ebi.ac.uk/QuickGO/term/GO:0050728)), and wound healing ([GO:0061045](https://www.ebi.ac.uk/QuickGO/term/GO:0061045)). Expression data highlights its significant role in specialized cells of the retina, such as [OFF-bipolar cells](/details-cell/CL0000750) and [retinal pigment epithelial cells](/details-cell/CL0002586), as well as in various mesenchymal cell types, including [myofibroblast cells](/details-cell/CL0000186) and smooth muscle cells. The gene's location in a chromosomal region frequently associated with loss of heterozygosity in multiple cancers suggests a potential role as a tumor suppressor ([Link](https://doi.org/10.1007/s003350010135)). ## Cellular Roles and Expression Landscape The **Overall** expression profile of [WFDC1](/details-gene/58189) indicates a highly specific but functionally diverse cellular landscape. Its most significant expression is observed in the eye, where it is a top marker for [OFF-bipolar cells](/details-cell/CL0000750) (CSI: 27.18), [retinal pigment epithelial cells](/details-cell/CL0002586) (CSI: 18.03), and [ON-bipolar cells](/details-cell/CL0000749) (CSI: 11.97), suggesting a crucial role in retinal homeostasis and neural signal processing. Beyond the retina, [WFDC1](/details-gene/58189) is also a significant marker in a broad range of mesenchymal and stromal cell populations. These include [myofibroblast cells](/details-cell/CL0000186) (CSI: 17.04), various smooth muscle cells such as [enteric smooth muscle cells](/details-cell/CL0002504) (CSI: 10.53), and fibroblasts like [fibroblasts of the lung](/details-cell/CL0002553) (CSI: 6.60). This expression pattern in cells responsible for generating and remodeling connective tissue is consistent with its annotated role in regulating the extracellular environment and wound healing. The gene's presence in [neural progenitor cells](/details-cell/CL0011020) and [Bergmann glial cells](/details-cell/CL0000644) further points to a potential involvement in nervous system development and maintenance. ## Pathways and Molecular Function Functionally, [WFDC1](/details-gene/58189) is primarily characterized as a secreted [serine-type endopeptidase inhibitor](/details-go/GO:0004867). This inhibitory function is believed to be the primary mechanism through which it exerts its biological effects. Its presence in the [extracellular space](/details-go/GO:0005615) allows it to modulate the activity of proteases involved in tissue remodeling, cell signaling, and inflammation. The Gene Ontology (GO) annotations for biological processes align well with this molecular function. [WFDC1](/details-gene/58189) is implicated in the negative regulation of several key physiological events: * **Negative regulation of cell growth** ([GO:0030308](https://www.ebi.ac.uk/QuickGO/term/GO:0030308)): By inhibiting proteases that may be required for cell proliferation or invasion, [WFDC1](/details-gene/58189) may act as a brake on cell division. * **Negative regulation of inflammatory response** ([GO:0050728](https://www.ebi.ac.uk/QuickGO/term/GO:0050728)): It may temper inflammation by inhibiting proteases that activate pro-inflammatory mediators. * **Negative regulation of wound healing** ([GO:0061045](https://www.ebi.ac.uk/QuickGO/term/GO:0061045)): Its high expression in myofibroblasts and fibroblasts suggests a role in controlling the extent of tissue remodeling and preventing excessive fibrosis during the healing process. ## Research Directions The functional annotations and expression profile of [WFDC1](/details-gene/58189), particularly its potential role as a tumor suppressor located in a region of frequent LOH in cancer ([Link](https://doi.org/10.1007/s003350010135)), provide a basis for several testable hypotheses. 1. **Hypothesis 1:** In retinal tissue, [WFDC1](/details-gene/58189) secreted by bipolar and pigment epithelial cells is essential for maintaining the integrity of the extracellular matrix and modulating synaptic signaling. Its dysregulation could contribute to retinal degenerative diseases by permitting uncontrolled proteolytic activity. 2. **Hypothesis 2:** The loss of [WFDC1](/details-gene/58189) expression in stromal cells like myofibroblasts and fibroblasts creates a pro-tumorigenic microenvironment. This loss would lead to disinhibition of extracellular peptidases, promoting extracellular matrix degradation, tumor cell invasion, and aberrant growth signaling. * **Proposed Experiment to Test Hypothesis 2:** To investigate the role of [WFDC1](/details-gene/58189) in the tumor microenvironment, CRISPR-Cas9 could be used to knock out the gene in primary human lung fibroblasts. These engineered fibroblasts could then be co-cultured with a non-small cell lung cancer (NSCLC) cell line in a 3D spheroid or organoid model. The impact on tumor cell invasion and proliferation could be quantified using confocal microscopy and proliferation assays. Furthermore, secretome analysis via mass spectrometry could identify the specific proteases that become hyperactive and the downstream signaling pathways that are altered in the absence of [WFDC1](/details-gene/58189). * **Therapeutic Potential:** As a secreted protein with tumor-suppressive functions (negative regulation of cell growth), [WFDC1](/details-gene/58189) presents a compelling candidate for therapeutic *activation* or protein replacement therapy. For cancers characterized by LOH at the 16q24.1 locus, systemic or local delivery of a stable, recombinant WFDC1 protein could potentially restore its inhibitory functions on the tumor microenvironment. This approach could help suppress tumor growth and metastasis by re-establishing normal control over extracellular protease activity.

Genular Protein ID: 1104857632

Symbol: WFDC1_HUMAN

Name: WAP four-disulfide core domain protein 1

UniProtKB Accession Codes:

Q9HC57 D3DUL7 Q8NC27 Q9HAU1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 6 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 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 RefSeq 3 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10967136

Title: The WFDC1 gene encoding ps20 localizes to 16q24, a region of LOH in multiple cancers.

PubMed ID: 10967136

DOI: 10.1007/s003350010135

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 220
  • Mass: 23977
  • Checksum: 8098EB9379F88CBD
  • Sequence:
    • MPLTGVGPGS CRRQIIRALC LLLLLLHAGS AKNIWKRALP ARLAEKSRAE EAGAPGGPRQ 
PRADRCPPPP RTLPPGACQA ARCQADSECP RHRRCCYNGC AYACLEAVPP PPVLDWLVQP 
KPRWLGGNGW LLDGPEEVLQ AEACSTTEDG AEPLLCPSGY ECHILSPGDV AEGIPNRGQC 
VKQRRQADGR ILRHKLYKEY PEGDSKNVAE PGRGQQKHFQ