EPPIN-WFDC6: A Sperm-Associated Antimicrobial and Protease Inhibitor Gene with Implications in Male Fertility
Comprehensive genomic, expression, and variant analysis of the EPPIN-WFDC6 locus, a key regulator of sperm motility and innate immunity.
Gene Information Card
| Symbol | EPPIN-WFDC6 |
|---|---|
| Full Name | EPPIN-WFDC6 readthrough transcript |
| Gene Type | Protein coding (readthrough) |
| Chromosomal Location | 20q12-q13.1 |
| NCBI Gene ID | 100289187 ncbi.nlm.nih.gov/gene/100289187 |
| Ensembl ID | ENSG00000255374 |
| UniProt ID | Q6UWB4 (EPPIN); Q6UWB3 (WFDC6) |
| OMIM ID | 609962 (EPPIN); 609963 (WFDC6) |
| HGNC ID | HGNC:40011 (EPPIN-WFDC6) |
| Aliases | EPPIN, WFDC6, SPINLW1, WAP7, WAP8 |
Description
EPPIN-WFDC6 is a readthrough transcript that produces a fusion protein combining the EPPIN (epididymal protease inhibitor) and WFDC6 (WAP four-disulfide core domain 6) proteins. This gene is predominantly expressed in the male reproductive tract, particularly in the epididymis and testis. The encoded protein functions as a serine protease inhibitor and antimicrobial peptide, playing a critical role in sperm motility, capacitation, and innate immunity. It is also implicated in prostate cancer and male infertility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Male infertility | Altered expression or variants affecting protease inhibitor function may impair sperm motility and capacitation. | PMID: 21802021; ClinVar |
| Prostate cancer | EPPIN is overexpressed in prostate cancer and may promote tumor progression via protease inhibition and antimicrobial activity. | PMID: 15604258; COSMIC |
| Epididymitis | Antimicrobial function of EPPIN-WFDC6 may modulate inflammatory response in the epididymis. | UniProt annotation |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | Not available (readthrough) | Not determined |
| Epididymis | Not available | Not determined |
| Prostate | Not available | Not determined |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| LNCaP (prostate cancer) | Not available | EPPIN expression detected by RT-PCR |
| PC-3 (prostate cancer) | Not available | EPPIN expression detected |
| HeLa (cervical cancer) | Not available | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.245G>A (p.Arg82His) in EPPIN | Missense | Rare | Potential effect on protease inhibitor activity |
| c.IVS2+1G>T in EPPIN | Splice site | Rare | May cause exon skipping and loss of function |
| c.358C>T (p.Arg120Ter) in WFDC6 | Nonsense | Rare | Premature truncation, likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Variants that disrupt the WAP domain or protease inhibitor activity may lead to loss of function, contributing to infertility or increased susceptibility to infections.
Gain of Function (GOF)
No evidence of gain-of-function mutations; overexpression in cancer may be due to transcriptional dysregulation rather than mutation.
Dominant Negative (DN)
No known dominant-negative effects; the protein functions as a monomer.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Not curated in major pathway databases; involved in protease inhibition and antimicrobial defense.
Protein Summary
The EPPIN-WFDC6 readthrough protein is a fusion of EPPIN and WFDC6, both containing WAP domains. It is secreted into the epididymal lumen and binds to sperm surface, regulating sperm motility and capacitation. It also exhibits antimicrobial activity against bacteria, contributing to male reproductive tract immunity. The protein is a potential target for male contraceptive development and a biomarker for prostate cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EPPIN-WFDC6 Knockout HEK293 Cell Line | EDJ-KQ52475 | Human | 100526773 | Details Get a Quote |
| EPPIN-WFDC6 Knockout HeLa Cell Line | EDJ-KQ60938 | Human | 100526773 | Details Get a Quote |
| EPPIN-WFDC6 Knockout A-549 Cell Line | EDJ-KQ69413 | Human | 100526773 | Details Get a Quote |
| EPPIN-WFDC6 Knockout HCT 116 Cell Line | EDJ-KQ77764 | Human | 100526773 | Details Get a Quote |
