PLAU

plasminogen activator, urokinase

Basic information

Region (hg38): 10:73909176-73917496

Links

ENSG00000122861 ∙ NCBI:5328 ∙ OMIM:191840 ∙ HGNC:9052 ∙ Uniprot:P00749 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Quebec platelet disorder (Limited), mode of inheritance: AD
• Quebec platelet disorder (Supportive), mode of inheritance: AD
• Quebec platelet disorder (Limited), mode of inheritance: AD
• Quebec platelet disorder (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Quebec platelet disorder	AD	Hematologic	Fibrinolytic inhibitors can be effective for treatment of bleeding disorder	Hematologic	15026313; 18988861; 20007542

ClinVar

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

• Quebec platelet disorder (67 variants)
• not provided (19 variants)
• Inborn genetic diseases (13 variants)
• PLAU-related condition (1 variants)
• Hirschsprung disease, susceptibility to, 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLAU 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			1	4	4	9
missense			20	3	12	35
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	1	2	5
non coding			14	1	21	36
Total	0	0	36	8	37

Variants in PLAU

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

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

Position	Type	Phenotype	Significance	ClinVar
10-73911209-G-A		Quebec platelet disorder	Uncertain significance (Jan 13, 2018)
10-73911218-G-A		Quebec platelet disorder	Uncertain significance (Jan 13, 2018)
10-73911227-C-G		Quebec platelet disorder	Uncertain significance (Jan 13, 2018)
10-73911404-G-T			Benign (Jun 19, 2021)
10-73911531-C-T		Quebec platelet disorder	Benign/Likely benign (Oct 01, 2023)
10-73911536-A-G		Quebec platelet disorder	Benign (Jan 12, 2018)
10-73911538-C-A		Quebec platelet disorder	Benign (Jan 12, 2018)
10-73911572-C-A		Quebec platelet disorder • not specified	Conflicting classifications of pathogenicity (Sep 29, 2022)
10-73911598-G-T		Quebec platelet disorder	Benign (Jan 12, 2018)
10-73911618-T-C		Quebec platelet disorder	Likely benign (Jan 12, 2018)
10-73912117-G-A			Benign (Jun 19, 2021)
10-73912216-G-T		C10orf55-related disorder	Likely benign (May 17, 2021)
10-73912240-A-G		Quebec platelet disorder	Benign (May 22, 2017)
10-73912272-T-A		Quebec platelet disorder	Uncertain significance (Jan 12, 2018)
10-73912291-A-G		Quebec platelet disorder • PLAU-related disorder	Benign/Likely benign (Mar 01, 2023)
10-73912292-A-G		Quebec platelet disorder	Benign (Jan 13, 2018)
10-73912301-G-A		Hirschsprung disease, susceptibility to, 1 • Quebec platelet disorder	Benign/Likely benign (Dec 31, 2019)
10-73912319-A-T		not specified	Uncertain significance (Jan 06, 2023)
10-73912619-G-GT			Benign (Jun 19, 2021)
10-73912620-G-T			Benign (Jun 19, 2021)
10-73912717-A-G			Benign (Jun 19, 2021)
10-73912917-C-G		C10orf55-related disorder	Likely benign (May 31, 2023)
10-73912924-A-G		Quebec platelet disorder	Uncertain significance (Jan 12, 2018)
10-73912966-G-A		Quebec platelet disorder	Benign (Jan 13, 2018)
10-73912966-G-C		Quebec platelet disorder	Likely benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLAU	protein_coding	protein_coding	ENST00000372764	10	8321

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000231	0.979	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.664	227	257	0.883	0.0000149	2817
Missense in Polyphen		89	110.41	0.80612		1220
Synonymous	0.686	91	99.7	0.913	0.00000589	813
Loss of Function	2.11	13	24.2	0.537	0.00000120	269

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000540	0.000540
Ashkenazi Jewish	0.00	0.00
East Asian	0.000546	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.000546	0.000544
South Asian	0.000229	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
• Disease: DISEASE: Quebec platelet disorder (QPD) [MIM:601709]: An autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins. {ECO:0000269|PubMed:20007542}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Complement and coagulation cascades - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Osteopontin Signaling;Blood Clotting Cascade;Lung fibrosis;VEGFA-VEGFR2 Signaling Pathway;Dengue-2 Interactions with Complement and Coagulation Cascades;Dengue-2 Interactions with Blood Clotting Cascade;Wnt Signaling Pathway and Pluripotency;Wnt Signaling Pathway;Endochondral Ossification;Complement and Coagulation Cascades;Senescence and Autophagy in Cancer;DNA Damage Response (only ATM dependent);Neutrophil degranulation;Dissolution of Fibrin Clot;platelet amyloid precursor protein pathway;fibrinolysis pathway;Innate Immune System;Immune System;ATF-2 transcription factor network;Beta3 integrin cell surface interactions;Hemostasis;Osteopontin-mediated events;Beta5 beta6 beta7 and beta8 integrin cell surface interactions;Beta1 integrin cell surface interactions;AP-1 transcription factor network;amb2 Integrin signaling;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling;Validated transcriptional targets of AP1 family members Fra1 and Fra2;FGF signaling pathway;E2F transcription factor network;Beta2 integrin cell surface interactions (Consensus)

Recessive Scores

• pRec: 0.903

Intolerance Scores

• loftool: 0.248
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.6

Haploinsufficiency Scores

• pHI: 0.0825
• hipred: Y
• hipred_score: 0.508
• ghis: 0.431

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.950

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plau
• Phenotype: endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; vision/eye phenotype; muscle phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype; neoplasm; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; immune system phenotype

Gene ontology

• Biological process: response to hypoxia;proteolysis;chemotaxis;signal transduction;blood coagulation;regulation of signaling receptor activity;smooth muscle cell migration;regulation of smooth muscle cell migration;positive regulation of cell migration;plasminogen activation;regulation of cell adhesion mediated by integrin;regulation of cell population proliferation;fibrinolysis;neutrophil degranulation;regulation of wound healing;regulation of smooth muscle cell-matrix adhesion
• Cellular component: extracellular region;extracellular space;plasma membrane;focal adhesion;cell surface;specific granule membrane;extracellular exosome;tertiary granule membrane
• Molecular function: serine-type endopeptidase activity;protein binding