EPPIN
protein-codingepididymal peptidase inhibitor, the group of WAP four-disulfide core domain containing
Gene summary
This gene encodes an epididymal protease inhibitor, which contains both kunitz-type and WAP-type four-disulfide core (WFDC) protease inhibitor consensus sequences. Most WFDC genes are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene is a member of the WFDC gene family and belongs to the telomeric cluster. The protein can inhibit human sperm motility and exhibits antimicrobial activity against E. coli, and polymorphisms in this gene are associated with male infertility. Read-through transcription also exists between this gene and the downstream WFDC6 (WAP four-disulfide core domain 6) gene. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]
- SPINLW1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EPPIN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020398.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 1 | 1 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 1 | 0 | 0 | 1 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065131.1 | 4 | MANE Select | |
| Ensembl | ENSP00000361746.4 | 4 | MANE Select | |
| RefSeq | NP_001289790.1 | 3 | Standard | |
| Ensembl | ENSP00000338114.3 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Antimicrobial peptides
- Innate Immune System
- Immune System
Biological Process
- negative regulation of peptidase activity
- negative regulation of endopeptidase activity
- antimicrobial humoral response
- defense response to bacterium
- protein complex oligomerization
Molecular Function
- serine-type endopeptidase inhibitor activity
- protein binding
Cellular Component
- extracellular space
- cell surface
- protein-containing complex
- sperm plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000555685
- Coding exons
- 5
- Length
- 10767
- Individuals with no LoFs
- 125670
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 64
- Defined
- 125734
- p
- 0.000255
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0443 | 97 | 95.8 | 1.01 | 0.00000481 | 1196 |
| Missense (PolyPhen) | 33 | 26.552 | 1.2428 | 344 | ||
| Synonymous | 0.740 | 31 | 36.7 | 0.845 | 0.00000217 | 295 |
| Loss of Function | 1.10 | 8 | 12.1 | 0.660 | 7.11e-7 | 129 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.0012 | 0.0012 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine protease inhibitor that plays an essential role in male reproduction and fertility. Modulates the hydrolysis of SEMG1 by KLK3/PSA (a serine protease), provides antimicrobial protection for spermatozoa in the ejaculate coagulum, and binds SEMG1 thereby inhibiting sperm motility. {ECO:0000269|PubMed:15229136, ECO:0000269|PubMed:17644992}.;
Recessive Scores
- pRec
- 0.0901
Intolerance Scores
- RVIS EVS
- 0.44
- RVIS percentile EVS
- 77.45
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |