PRTN3

proteinase 3, the group of Granule associated serine proteases of immune defence

Basic information

Region (hg38): 19:840999-848175

Links

ENSG00000196415 ∙ NCBI:5657 ∙ OMIM:177020 ∙ HGNC:9495 ∙ Uniprot:P24158 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRTN3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRTN3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense			12	3	1	16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	12	6	1

Variants in PRTN3

This is a list of pathogenic ClinVar variants found in the PRTN3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-841019-G-A			Likely benign (Dec 09, 2017)
19-841023-C-T			Likely benign (Feb 16, 2018)
19-843571-G-C		not specified	Uncertain significance (Oct 25, 2023)
19-843590-G-C		not specified	Uncertain significance (Oct 27, 2021)
19-843597-G-T			Benign/Likely benign (Jan 01, 2024)
19-843609-G-T			Likely benign (May 18, 2018)
19-843973-C-T		not specified	Uncertain significance (Oct 25, 2023)
19-846150-A-G		not specified	Uncertain significance (Nov 22, 2023)
19-846169-G-A		not specified	Likely benign (Jul 06, 2021)
19-846246-T-G		not specified	Uncertain significance (Jul 08, 2021)
19-846256-T-G		not specified	Uncertain significance (Sep 17, 2021)
19-846268-A-C		not specified	Uncertain significance (Jul 06, 2021)
19-846274-C-A		not specified	Uncertain significance (Jan 02, 2024)
19-846298-A-G		not specified	Uncertain significance (Mar 31, 2023)
19-846366-G-C		not specified	Uncertain significance (Jun 07, 2024)
19-847877-C-G		not specified	Likely benign (May 05, 2023)
19-847878-G-A		not specified	Uncertain significance (May 28, 2024)
19-847901-C-T		not specified	Uncertain significance (Feb 17, 2024)
19-847910-C-T		not specified	Uncertain significance (Jan 08, 2024)
19-847944-G-A			Benign (Feb 01, 2024)
19-847957-G-C		not specified	Uncertain significance (Jan 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRTN3	protein_coding	protein_coding	ENST00000234347	5	7213

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000380	0.394	124663	0	19	124682	0.0000762

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.153	140	145	0.964	0.00000845	1598
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000978	0.0000930
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000501	0.000375
European (Non-Finnish)	0.0000606	0.0000533
Middle Eastern	0.00	0.00
South Asian	0.0000705	0.0000328
Other	0.000357	0.000329

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Neutrophil degranulation;Other interleukin signaling;Signaling by Interleukins;Cytokine Signaling in Immune system;Antimicrobial peptides;Innate Immune System;Immune System;Hemostasis;Common Pathway of Fibrin Clot Formation;Formation of Fibrin Clot (Clotting Cascade);C-MYB transcription factor network (Consensus)

Intolerance Scores

• loftool: 0.378
• rvis_EVS: 0.46
• rvis_percentile_EVS: 78.46

Haploinsufficiency Scores

• pHI: 0.146
• hipred: N
• hipred_score: 0.372

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.591

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Prtn3
• Phenotype: hematopoietic system phenotype; immune system phenotype; cellular phenotype

Gene ontology

• Biological process: proteolysis;membrane protein ectodomain proteolysis;phagocytosis;blood coagulation;positive regulation of cell population proliferation;cytokine-mediated signaling pathway;antimicrobial humoral response;collagen catabolic process;neutrophil degranulation;positive regulation of GTPase activity;cell-cell junction maintenance;negative regulation of phagocytosis;neutrophil extravasation;mature conventional dendritic cell differentiation
• Cellular component: extracellular region;extracellular space;cytosol;plasma membrane;azurophil granule lumen;plasma membrane raft;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: serine-type endopeptidase activity;signaling receptor binding;protein binding;serine-type peptidase activity;enzyme binding