SLPI
protein-codingsecretory leukocyte peptidase inhibitor, the group of WAP four-disulfide core domain containing
Gene summary
This gene encodes a secreted inhibitor which protects epithelial tissues from serine proteases. It is found in various secretions including seminal plasma, cervical mucus, and bronchial secretions, and has affinity for trypsin, leukocyte elastase, and cathepsin G. Its inhibitory effect contributes to the immune response by protecting epithelial surfaces from attack by endogenous proteolytic enzymes. This antimicrobial protein has antibacterial, antifungal and antiviral activity. [provided by RefSeq, Nov 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005441
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLPI variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003064.4. 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 | 18 | 1 | 19 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 3 | |||
| Total | 1 | 0 | 20 | 1 | 0 | 22 |
Highest pathogenic variant AF is 6.842744e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003055.1 | 4 | MANE Select | |
| Ensembl | ENSP00000342082.2 | 4 | MANE Select | |
| Ensembl | ENSP00000675198.1 | 3 | Standard | |
| Ensembl | ENSP00000773367.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- immune response
- negative regulation of endopeptidase activity
- antibacterial humoral response
- negative regulation of protein binding
- response to lipopolysaccharide
Molecular Function
- DNA binding
- mRNA binding
- endopeptidase inhibitor activity
- serine-type endopeptidase inhibitor activity
- protein binding
Cellular Component
- extracellular region
- extracellular space
- specific granule lumen
- collagen-containing extracellular matrix
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338380
- Coding exons
- 4
- Length
- 2326
- Individuals with no LoFs
- 125641
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 93
- Defined
- 125734
- p
- 0.000370
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0423 | 71 | 72.0 | 0.986 | 0.00000343 | 865 |
| Missense (PolyPhen) | 25 | 22.805 | 1.0963 | 295 | ||
| Synonymous | -1.08 | 32 | 25.1 | 1.27 | 0.00000125 | 241 |
| Loss of Function | 0.471 | 5 | 6.27 | 0.797 | 2.63e-7 | 83 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00038 | 0.00038 | rare |
| Ashkenazi Jewish | 0.0056 | 0.0056 | notable |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G (PubMed:3533531, PubMed:3462719, PubMed:2039600, PubMed:2110563, PubMed:10702419, PubMed:24121345). Modulates the inflammatory and immune responses after bacterial infection, and after infection by the intracellular parasite L.major. Down-regulates responses to bacterial lipopolysaccharide (LPS) (By similarity). Plays a role in regulating the activation of NF-kappa-B and inflammatory responses (PubMed:10702419, PubMed:24352879). Has antimicrobial activity against mycobacteria, but not against salmonella. Contributes to normal resistance against infection by M.tuberculosis. Required for normal resistance to infection by L.major. Required for normal wound healing, probably by preventing tissue damage by limiting protease activity (By similarity). Together with ELANE, required for normal differentiation and proliferation of bone marrow myeloid cells (PubMed:24352879). {ECO:0000250|UniProtKB:P97430, ECO:0000269|PubMed:10702419, ECO:0000269|PubMed:2039600, ECO:0000269|PubMed:2110563, ECO:0000269|PubMed:24121345, ECO:0000269|PubMed:24352879, ECO:0000269|PubMed:3462719, ECO:0000269|PubMed:3533531, ECO:0000305}.;
Recessive Scores
- pRec
- 0.411
Intolerance Scores
- LoFtool
- 0.587
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.752
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |