WFDC2 (HE4) Gene: Structure, Function, and Clinical Relevance
A comprehensive biomedical overview of the WFDC2 gene encoding HE4, a biomarker in ovarian cancer and epithelial tissues.
Gene Information Card
| Symbol | WFDC2 |
|---|---|
| Full Name | WAP four-disulfide core domain 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 20q13.12 |
| NCBI Gene ID | 10406 ncbi.nlm.nih.gov/gene/10406 |
| Ensembl ID | ENSG00000101443 |
| UniProt ID | Q14508 |
| OMIM ID | 617548 |
| HGNC ID | 15960 |
| Aliases | HE4, WAP5, dJ461P17.6, EDDM4 |
Description
The WFDC2 gene encodes HE4 (human epididymis protein 4), a member of the WAP-type four-disulfide core domain family. HE4 is a secreted protein with putative protease inhibitor activity, expressed in the epididymis, respiratory epithelium, and ovary. It is widely used as a serum biomarker for epithelial ovarian cancer, particularly in combination with CA-125.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ovarian cancer | Overexpression of HE4 in serous and endometrioid ovarian carcinomas; used as a diagnostic and monitoring biomarker | ClinVar, COSMIC, multiple clinical studies |
| Endometrial cancer | Elevated HE4 expression associated with tumor progression and poor prognosis | ClinVar, literature |
| Lung cancer | Aberrant expression in non-small cell lung cancer; potential biomarker | COSMIC, literature |
| Renal cell carcinoma | HE4 overexpression reported in clear cell RCC | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Epididymis | None | High |
| Trachea | None | High |
| Lung | None | Moderate |
| Ovary | None | Moderate |
| Prostate | None | Low |
| Breast | None | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| OVCAR-3 | High | Ovarian cancer cell line |
| SK-OV-3 | Moderate | Ovarian cancer cell line |
| A549 | Low | Lung cancer cell line |
| MCF-7 | Low | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | Rare | Uncertain significance |
| c.256G>A | Missense | Rare | Uncertain significance |
| c.364C>T | Nonsense | Rare | Likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., c.364C>T) predicted to truncate the protein and abolish WAP domain function.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported.
Dominant Negative (DN)
No evidence for dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Proteolysis and protease inhibition
• Innate immune response (antimicrobial peptides)
Protein Summary
HE4 is a 124-amino acid secreted protein containing two WAP-type four-disulfide core domains. It functions as a putative serine protease inhibitor and antimicrobial peptide. HE4 is overexpressed in epithelial ovarian cancers and is used clinically as a serum biomarker for diagnosis, monitoring, and prognosis. The protein is also expressed in normal epididymis and respiratory epithelium.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WFDC2 Knockout HEK293 Cell Line | EDJ-KQ7038 | Human | 10406 | Details Get a Quote |
| WFDC2 Knockout HeLa Cell Line | EDJ-KQ55401 | Human | 10406 | Details Get a Quote |
| WFDC2 Knockout A-549 Cell Line | EDJ-KQ63880 | Human | 10406 | Details Get a Quote |
| WFDC2 Knockout HCT 116 Cell Line | EDJ-KQ72338 | Human | 10406 | Details Get a Quote |
