PRTN3
protein-codingproteinase 3, the group of Granule associated serine proteases of immune defence
Gene summary
Enables enzyme binding activity; serine-type endopeptidase activity; and signaling receptor binding activity. Involved in several processes, including mature conventional dendritic cell differentiation; neutrophil extravasation; and positive regulation of GTPase activity. Located in azurophil granule lumen; cytosol; and plasma membrane raft. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.2 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 PRTN3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002777.4. 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 | 3 | 3 | ||||
| missense | 39 | 5 | 44 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 39 | 8 | 0 | 47 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002768.3 | 5 | MANE Select | |
| Ensembl | ENSP00000234347.3 | 5 | MANE Select | |
| Ensembl | ENSP00000475174.1 | 4 | Standard | |
| Ensembl | ENSP00000475174.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Other interleukin signaling
- Signaling by Interleukins
- Cytokine Signaling in Immune system
- Antimicrobial peptides
Biological Process
- proteolysis
- membrane protein ectodomain proteolysis
- phagocytosis
- blood coagulation
- positive regulation of cell population proliferation
Molecular Function
- serine-type endopeptidase activity
- signaling receptor binding
- protein binding
- serine-type peptidase activity
- enzyme binding
Cellular Component
- extracellular region
- extracellular space
- cytosol
- plasma membrane
- azurophil granule lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000234347
- Coding exons
- 5
- Length
- 7213
- Individuals with no LoFs
- 124663
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 124682
- p
- 0.0000762
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.153 | 140 | 145 | 0.964 | 0.00000845 | 1598 |
| Missense (PolyPhen) | 35 | 51.675 | 0.67731 | 618 | ||
| Synonymous | -0.637 | 68 | 61.6 | 1.10 | 0.00000349 | 544 |
| Loss of Function | 0.233 | 7 | 7.70 | 0.909 | 4.12e-7 | 80 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000067 | 0.000062 | rare |
| Latino/Admixed American | 0.000031 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00050 | 0.00038 | rare |
| European (Non-Finnish) | 0.000061 | 0.000053 | rare |
| South Asian | 0.000071 | 0.000033 | rare |
| Other | 0.00036 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:3198760, PubMed:2033050, PubMed:28240246). By cleaving and activating receptor F2RL1/PAR-2, enhances endothelial cell barrier function and thus vascular integrity during neutrophil transendothelial migration (PubMed:23202369). May play a role in neutrophil transendothelial migration, probably when associated with CD177 (PubMed:22266279). {ECO:0000269|PubMed:2033050, ECO:0000269|PubMed:22266279, ECO:0000269|PubMed:23202369, ECO:0000269|PubMed:28240246, ECO:0000269|PubMed:3198760}.;
- Disease
- DISEASE: Note=Is the major autoantigen in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (Wegener's granulomatosis) (PubMed:2377228, PubMed:2679910). This complex, systemic disease is characterized by granulomatous inflammation with necrotizing lesions in the respiratory tract, glomerulonephritis, vasculitis, and anti-neutrophil cytoplasmatic autoantibodies detected in patient sera (PubMed:2377228, PubMed:2679910). PRTN3 causes emphysema when administered by tracheal insufflation to hamsters (PubMed:3198760). {ECO:0000269|PubMed:3198760, ECO:0000303|PubMed:2377228, ECO:0000303|PubMed:2679910}.;
Intolerance Scores
- LoFtool
- 0.378
- RVIS EVS
- 0.46
- RVIS percentile EVS
- 78.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.591
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |