Details for: WFDC3

Gene ID: 140686

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: WFDC3

Ensembl ID: ENSG00000124116

Description: WAP four-disulfide core domain 3

Cell Significance Landscape

Associated with

Significant Cells

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

  • epithelial cell of lung CL0000082
    CSI 5.03
    rCSI 4.17%
    PRS 99.41
  • ciliated epithelial cell CL0000067
    CSI 5.03
    rCSI 4.42%
    PRS 96.68
  • retinal rod cell CL0000604
    CSI 3.24
    rCSI 5.7%
    PRS 97.35
  • ependymal cell CL0000065
    CSI 3.03
    rCSI 6.14%
    PRS 93.6
  • retinal cone cell CL0000573
    CSI 1.79
    rCSI 2.88%
    PRS 96.55

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 [WFDC3](/details-gene/140686), or WAP four-disulfide core domain 3, is a protein-coding gene located on human chromosome 20q13.12 ([Link](https://doi.org/10.1038/414865a)). It encodes a secreted protein that functions as a serine-type endopeptidase inhibitor. Functional annotations suggest its involvement in the [innate immune response](/details-go/GO:0045087), particularly the [antibacterial humoral response](/details-go/GO:0019731). **Overall**, expression data indicates that [WFDC3](/details-gene/140686) is a highly specific marker for certain epithelial cell populations, with its most significant expression observed in the [epithelial cell of lung](/details-cell/CL0000082) and [ciliated epithelial cell](/details-cell/CL0000067), pointing towards a primary role in respiratory tract defense. ## Cellular Roles and Expression Landscape The expression profile of [WFDC3](/details-gene/140686) highlights its specialized function in specific barrier and sensory tissues. **Overall**, the gene shows its highest significance as a marker in the [epithelial cell of lung](/details-cell/CL0000082) (CSI: 5.03) and [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 5.03), suggesting a fundamental role in maintaining the function and innate immune defense of the airway epithelium. Beyond the respiratory system, [WFDC3](/details-gene/140686) is also significantly expressed in specialized neuro-epithelial cells. This includes notable expression in [retinal rod cell](/details-cell/CL0000604) (CSI: 3.24), [ependymal cell](/details-cell/CL0000065) (CSI: 3.03), and [retinal cone cell](/details-cell/CL0000573) (CSI: 1.79). This pattern suggests that in addition to its immune-related functions in the lung, [WFDC3](/details-gene/140686) may have distinct, tissue-specific roles in the central nervous system and the eye, possibly related to the regulation of the extracellular environment. ## Pathways and Molecular Function [WFDC3](/details-gene/140686) is part of a gene cluster on chromosome 20 that encodes proteins containing whey acidic protein (WAP) domains, which are known for their protease inhibitor activity ([Link](https://doi.org/10.1042/bj20020869)). The gene product is localized to the [extracellular space](/details-go/GO:0005615), consistent with a secreted protein involved in humoral responses. Its primary molecular function is defined as [serine-type endopeptidase inhibitor activity](/details-go/GO:0004867), which directly supports its biological role in the [negative regulation of peptidase activity](/details-go/GO:0010466). This function is integral to its participation in the [innate immune response](/details-go/GO:0045087) and [antibacterial humoral response](/details-go/GO:0019731). By inhibiting proteases, [WFDC3](/details-gene/140686) likely helps protect host tissues from damage caused by either pathogen-derived proteases or dysregulated host inflammatory proteases, a function particularly critical at mucosal surfaces like the lung epithelium. ## Research Directions The specific expression of [WFDC3](/details-gene/140686) in lung epithelial and retinal cells, combined with its function as a secreted protease inhibitor, suggests several avenues for future research. **Proposed Hypotheses:** 1. Given its high expression in [ciliated epithelial cell](/details-cell/CL0000067) and its role in the [innate immune response](/details-go/GO:0045087), [WFDC3](/details-gene/140686) may function as a key component of the lung's mucosal defense system by directly inhibiting microbial proteases or by modulating host inflammatory responses to prevent excessive tissue damage during infection. 2. The significant expression in [retinal rod cell](/details-cell/CL0000604) and [retinal cone cell](/details-cell/CL0000573) suggests a specialized, non-immunological function in the eye. [WFDC3](/details-gene/140686) may regulate extracellular matrix turnover or inhibit proteases involved in photoreceptor degradation, thereby contributing to retinal homeostasis and integrity. **Experimental Approach:** To test the first hypothesis regarding its role in respiratory defense, a robust experimental plan could be implemented. One could utilize an *in vitro* air-liquid interface (ALI) culture model of primary human bronchial epithelial cells. [WFDC3](/details-gene/140686) expression could be knocked down using siRNA or knocked out via CRISPR-Cas9. These modified cultures, along with wild-type controls, would then be challenged with a common respiratory pathogen such as *Pseudomonas aeruginosa* or influenza virus. The impact of [WFDC3](/details-gene/140686) loss could be assessed by measuring pathogen burden, epithelial barrier integrity (via transepithelial electrical resistance), and the secretion of pro-inflammatory cytokines using ELISA. **Therapeutic Potential:** As a secreted protease inhibitor with high specificity for lung epithelium, [WFDC3](/details-gene/140686) presents potential as a therapeutic agent. Rather than inhibition, the strategy would likely involve **augmentation** or protein replacement. In diseases characterized by protease-antiprotease imbalance and chronic infection, such as cystic fibrosis or chronic obstructive pulmonary disease (COPD), delivery of recombinant [WFDC3](/details-gene/140686) protein via inhalation could help restore homeostasis, protect lung tissue from proteolytic damage, and enhance antimicrobial defense.

Genular Protein ID: 2136616611

Symbol: WFDC3_HUMAN

Name: WAP four-disulfide core domain protein 3

UniProtKB Accession Codes:

Q8IUB2 A6PVF2 Q0P6A5 Q3T1C5 Q8TC52 Q9BQP3 Q9BQP4

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 5 Ensembl 1 ExpressionAtlas 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MEROPS 1 MINT 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 12206714

Title: A locus on human chromosome 20 contains several genes expressing protease inhibitor domains with homology to whey acidic protein.

PubMed ID: 12206714

DOI: 10.1042/bj20020869

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

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

Sequence Information:

  • Length: 231
  • Mass: 24687
  • Checksum: 886B905654751DB3
  • Sequence:
    • MMLSCLFLLK ALLALGSLES WITAGEHAKE GECPPHKNPC KELCQGDELC PAEQKCCTTG 
CGRICRDIPK GRKRDCPRVI RKQSCLKRCI TDETCPGVKK CCTLGCNKSC VVPISKQKLA 
EFGGECPADP LPCEELCDGD ASCPQGHKCC STGCGRTCLG DIEGGRGGDC PKVLVGLCIV 
GCVMDENCQA GEKCCKSGCG RFCVPPVLPP KLTMNPNWTV RSDSELEIPV P