WFDC12 Gene

HGNC Family WAP four-disulfide core domain containing (WFDC)
Name WAP four-disulfide core domain 12
Description This gene encodes a member of the WAP-type four-disulfide core (WFDC) domain family. The WFDC domain, or WAP signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor. Most WFDC gene members are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the centromeric cluster. [provided by RefSeq, Jul 2008]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nA novel gene, originally termed huWAP2 and located upstream of the gene encoding the protease inhibitor elafin, encodes a small 111–amino acid polypeptide with a whey acidic protein (WAP) motif. This protein shows homology to other WAP-type protease inhibitors and is notably expressed in multiple tissues, including the prostate, skin, lung, and esophagus, suggesting a broader role in tissue defense and homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWithin the epidermis, WFDC12 expression is distinctively induced during the late stages of keratinocyte differentiation, with its product localizing to the outermost layer of live cells and colocalizing with corneodesmosomes. Functionally, WFDC12 exhibits inhibitory activity against proteases such as neutrophil elastase and epidermal kallikrein-related peptidases. Its expression pattern, altered in skin disorders including psoriasis, atopic dermatitis, Darier disease, and notably upregulated uniquely in normal-appearing skin of Netherton syndrome patients, underscores its potential role in maintaining epidermal barrier integrity and regulating protease activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in epidermal homeostasis, WFDC12 has been implicated in inflammatory skin conditions and cancer. In murine models of atopic dermatitis, overexpression of WFDC12 in the epidermis enhanced the migration of antigen‐presenting cells to lymph nodes, increased T helper cell infiltration, and boosted inflammatory mediators via upregulation of arachidonic acid metabolism and accumulation of platelet-activating factor, thereby exacerbating disease symptoms. Moreover, in esophageal squamous cell carcinoma, lower expression levels of WFDC12 correlated with increased cell proliferation and migration in vitro, suggesting a potential protective, tumor‐suppressive function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ake Lundwall, Adam Clauss "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a novel protease inhibitor gene that is highly expressed in the prostate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/bbrc.2001.6224"}], "href": "https://doi.org/10.1006/bbrc.2001.6224"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11779191"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11779191"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Polina Kalinina, Vera Vorstandlechner, Maria Buchberger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Whey Acidic Protein WFDC12 Is Specifically Expressed in Terminally Differentiated Keratinocytes and Regulates Epidermal Serine Protease Activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jid.2020.09.025"}], "href": "https://doi.org/10.1016/j.jid.2020.09.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33157095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33157095"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Guolin Li, Linna Gu, Fulei Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WFDC12-overexpressing contributes to the development of atopic dermatitis via accelerating ALOX12/15 metabolism and PAF accumulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-023-05686-3"}], "href": "https://doi.org/10.1038/s41419-023-05686-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36882395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36882395"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yu Zhuang, Lan Wang, Chengjian Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Construction of a novel pyrotosis-related prognostic model of esophageal square cell carcinoma and determination of the anti-tumor effect of WFDC12."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Funct Integr Genomics (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10142-023-01103-2"}], "href": "https://doi.org/10.1007/s10142-023-01103-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37225895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37225895"}]}]}]}
Synonyms DJ211D12.4, WAP2, C20ORF122, SWAM2
Proteins WFD12_HUMAN
NCBI Gene ID 128488
API
Download Associations
Predicted Functions View WFDC12's ARCHS4 Predicted Functions.
Co-expressed Genes View WFDC12's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View WFDC12's ARCHS4 Predicted Functions.

Functional Associations

WFDC12 has 1,439 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 62 datasets.

Click the + buttons to view associations for WFDC12 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Achilles Cell Line Gene Essentiality Profiles cell lines with fitness changed by WFDC12 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 WFDC12 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 WFDC12 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 WFDC12 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of WFDC12 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of WFDC12 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 WFDC12 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of WFDC12 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 WFDC12 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of WFDC12 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of WFDC12 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 WFDC12 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
CM4AI KOLF21J CRISPRi Gene Perturbation Atlas gene perturbations changing expression of WFDC12 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing WFDC12 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with WFDC12 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of WFDC12 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with WFDC12 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Disease Associations diseases associated with WFDC12 gene/protein from the curated CTD Gene-Disease Associations dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by WFDC12 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with WFDC12 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at WFDC12 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 WFDC12 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of WFDC12 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 WFDC12 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with WFDC12 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing WFDC12 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of WFDC12 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of WFDC12 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of WFDC12 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of WFDC12 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of WFDC12 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving WFDC12 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving WFDC12 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving WFDC12 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing WFDC12 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by WFDC12 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by WFDC12 gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by WFDC12 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of WFDC12 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of WFDC12 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with WFDC12 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of WFDC12 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of WFDC12 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for WFDC12 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of WFDC12 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Mouse Transcription Factor Targets 2025 transcription factors regulating expression of WFDC12 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of WFDC12 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of WFDC12 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of WFDC12 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain WFDC12 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of WFDC12 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of WFDC12 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of WFDC12 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at WFDC12 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
Rummagene Transcription Factor Associations 2026 transcription factors regulating expression of WFDC12 gene from the Rummagene Transcription Factor Associations 2026 dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of WFDC12 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of WFDC12 gene from the RummaGEO Gene Perturbation Signatures dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of WFDC12 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of WFDC12 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of WFDC12 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with WFDC12 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with WFDC12 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.