PLAT
plasminogen activator, tissue type
Basic information
Region (hg38): 8:42174718-42207709
Links
Phenotypes
GenCC
Source:
- 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
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 | 18 | ||||
| missense | 25 | 32 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 25 | 18 | 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 | Thrombocytopenia;Abnormal bleeding | Uncertain significance (-) | ||
| 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-G-A | not specified | Uncertain significance (Mar 31, 2024) | ||
| 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) | ||
| 8-42179966-C-A | not specified | Uncertain significance (Mar 31, 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) |
GnomAD
Source:
| 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:
- 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