PLAT

plasminogen activator, tissue type

Basic information

Region (hg38): 8:42174717-42207709

Links

ENSG00000104368 ∙ NCBI:5327 ∙ OMIM:173370 ∙ HGNC:9051 ∙ Uniprot:P00750 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thrombophilia, familial, due to decreased release of tissue plasminogen activator (Moderate), mode of inheritance: AR
• thrombophilia, familial, due to decreased release of tissue plasminogen activator (Disputed Evidence), mode of inheritance: AD

ClinVar

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

• not provided (24 variants)
• Inborn genetic diseases (18 variants)
• Hereditary angioedema with normal C1Inh (1 variants)
• Pulmonary embolism;Deep venous thrombosis (1 variants)
• Deep venous thrombosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLAT 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				11	7	18
missense			19	6		25
nonsense					1	1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	19	17	8

Variants in PLAT

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

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

Position	Type	Phenotype	Significance	ClinVar
8-42176001-G-A			Benign (Dec 31, 2019)
8-42176049-C-T		not specified	Uncertain significance (Sep 17, 2021)
8-42176053-C-T			Likely benign (Dec 31, 2019)
8-42176054-G-A		not specified	Uncertain significance (Oct 03, 2022)
8-42176111-C-T		not specified	Likely benign (May 25, 2022)
8-42176118-C-T		not specified	Uncertain significance (Mar 23, 2023)
8-42176143-C-T			Benign (Dec 31, 2019)
8-42178946-C-G		Abnormal bleeding;Thrombocytopenia	Uncertain significance (May 01, 2020)
8-42178948-A-T			Benign (Dec 31, 2019)
8-42179016-A-G			Likely benign (Oct 23, 2018)
8-42179048-G-A		not specified	Uncertain significance (Oct 13, 2023)
8-42179941-C-T		not specified	Uncertain significance (Aug 17, 2022)
8-42179961-T-G		not specified	Uncertain significance (Apr 22, 2022)
8-42179964-GTC-ATA		Hereditary angioedema with normal C1Inh	not provided (Feb 01, 2020)
8-42179965-T-C		not specified	Uncertain significance (Jan 03, 2024)
8-42179978-C-G		not specified	Uncertain significance (Aug 04, 2023)
8-42179988-G-T		not specified	Uncertain significance (Dec 06, 2022)
8-42180018-C-A		Deep venous thrombosis	Uncertain significance (Feb 01, 2019)
8-42180023-C-G		not specified	Uncertain significance (Aug 12, 2021)
8-42180036-C-T		not specified	Likely benign (Sep 13, 2023)
8-42180038-G-A			Likely benign (Jun 05, 2018)
8-42180250-T-C		not specified	Uncertain significance (Jun 22, 2023)
8-42180291-T-C			Likely benign (Jun 13, 2018)
8-42180297-G-C			Benign (Jul 04, 2018)
8-42180297-G-T			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLAT	protein_coding	protein_coding	ENST00000220809	13	33007

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000566	1.00	125727	0	20	125747	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.421	332	354	0.937	0.0000225	3665
Missense in Polyphen		110	139.76	0.78707		1506
Synonymous	-0.121	154	152	1.01	0.0000110	1060
Loss of Function	3.20	13	32.7	0.397	0.00000154	368

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000372	0.000368
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000477	0.0000462
European (Non-Finnish)	0.0000621	0.0000615
Middle Eastern	0.000109	0.000109
South Asian	0.0000986	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. Plays a direct role in facilitating neuronal migration.
• Disease: DISEASE: Note=Increased activity of TPA results in increased fibrinolysis of fibrin blood clots that is associated with excessive bleeding. Defective release of TPA results in hypofibrinolysis that can lead to thrombosis or embolism. {ECO:0000269|PubMed:1762144}.
• Pathway: Complement and coagulation cascades - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Aminocaproic Acid Action Pathway;Tranexamic Acid Action Pathway;Urokinase Action Pathway;Reteplase Action Pathway;Streptokinase Action Pathway;Tenecteplase Action Pathway;Alteplase Action Pathway;Anistreplase Action Pathway;Aprotinin Action Pathway;Phenindione Action Pathway;Dicoumarol Action Pathway;Warfarin Action Pathway;Acenocoumarol Action Pathway;Coagulation ;Bivalirudin Action Pathway;Argatroban Action Pathway;Ardeparin Action Pathway;Heparin Action Pathway;Fondaparinux Action Pathway;Enoxaparin Action Pathway;Phenprocoumon Action Pathway;Dicumarol Action Pathway;Ximelagatran Action Pathway;Lepirudin Action Pathway;Selenium Micronutrient Network;Vitamin B12 Metabolism;Folate Metabolism;Blood Clotting Cascade;NOTCH1 regulation of human endothelial cell calcification;Dengue-2 Interactions with Complement and Coagulation Cascades;Dengue-2 Interactions with Blood Clotting Cascade;Fibrin Complement Receptor 3 Signaling Pathway;Endochondral Ossification;Complement and Coagulation Cascades;Senescence and Autophagy in Cancer;Signal Transduction;Dissolution of Fibrin Clot;platelet amyloid precursor protein pathway;fibrinolysis pathway;keratinocyte differentiation;Signaling by PDGF;Hemostasis;Signaling by Receptor Tyrosine Kinases;amb2 Integrin signaling;Beta2 integrin cell surface interactions (Consensus)

Recessive Scores

• pRec: 0.842

Intolerance Scores

• loftool: 0.110
• rvis_EVS: -0.44
• rvis_percentile_EVS: 24.6

Haploinsufficiency Scores

• pHI: 0.215
• hipred: Y
• hipred_score: 0.706
• ghis: 0.482

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.601

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plat
• Phenotype: 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); endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; skeleton phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); hematopoietic system phenotype; 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); digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype; immune system phenotype

Gene ontology

• Biological process: response to hypoxia;cellular protein modification process;proteolysis;blood coagulation;smooth muscle cell migration;plasminogen activation;fibrinolysis;negative regulation of proteolysis;platelet-derived growth factor receptor signaling pathway;trans-synaptic signaling by BDNF, modulating synaptic transmission
• Cellular component: extracellular region;extracellular space;cytoplasm;cell surface;secretory granule;apical part of cell;collagen-containing extracellular matrix;extracellular exosome;Schaffer collateral - CA1 synapse;glutamatergic synapse
• Molecular function: serine-type endopeptidase activity;signaling receptor binding;protein binding;phosphoprotein binding