PI3
protein-codingpeptidase inhibitor 3, the group of WAP four-disulfide core domain containing
Gene summary
This gene encodes an elastase-specific inhibitor that functions as an antimicrobial peptide against Gram-positive and Gram-negative bacteria, and fungal pathogens. The protein contains a WAP-type four-disulfide core (WFDC) domain, and is thus a member of the WFDC domain family. Most WFDC gene members are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the centromeric cluster. Expression of this gene is upgulated by bacterial lipopolysaccharides and cytokines. [provided by RefSeq, Oct 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.6 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 PI3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002638.4. 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 | 13 | 2 | 15 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 14 | 2 | 0 | 16 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002629.1 | 2 | MANE Select | |
| Ensembl | ENSP00000243924.3 | 2 | MANE Select | |
| Ensembl | ENSP00000641389.1 | 2 | Standard | |
| Ensembl | ENSP00000641389.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Keratinization
- Developmental Biology
- Antimicrobial peptides
- Innate Immune System
- Immune System
Biological Process
- copulation
- negative regulation of endopeptidase activity
- peptide cross-linking
- antimicrobial humoral response
- cornification
Molecular Function
- endopeptidase inhibitor activity
- serine-type endopeptidase inhibitor activity
- structural constituent of epidermis
Cellular Component
- cornified envelope
- extracellular region
- cytosol
- extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000243924
- Coding exons
- 2
- Length
- 1669
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125734
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0997 | 67 | 69.3 | 0.966 | 0.00000418 | 749 |
| Missense (PolyPhen) | 12 | 18.053 | 0.66471 | 211 | ||
| Synonymous | -0.336 | 30 | 27.7 | 1.08 | 0.00000189 | 241 |
| Loss of Function | 0.816 | 1 | 2.35 | 0.426 | 1.01e-7 | 28 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Neutrophil and pancreatic elastase-specific inhibitor of skin. It may prevent elastase-mediated tissue proteolysis.;
Recessive Scores
- pRec
- 0.396
Intolerance Scores
- LoFtool
- 0.524
- RVIS EVS
- 0.57
- RVIS percentile EVS
- 81.99
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.764
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |