PLG

plasminogen

Basic information

Region (hg38): 6:160702194-160754097

Links

ENSG00000122194 ∙ NCBI:5340 ∙ OMIM:173350 ∙ HGNC:9071 ∙ Uniprot:P00747 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypoplasminogenemia (Supportive), mode of inheritance: AR
• angioedema, hereditary, 4 (Strong), mode of inheritance: AD
• hypoplasminogenemia (Strong), mode of inheritance: AR
• hypoplasminogenemia (Definitive), mode of inheritance: AR
• hypoplasminogenemia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Angioedema, hereditary, 4; Plasminogen deficiency, type I	AD/AR	Hematologic; Ophthalmologic	In Hereditary angioedema, individuals may have angioedema episodes that can be triggered by factors such as stress, oral contraceptives, ACE inhibitors, and angiotensin II receptor blockers, and medical management (eg, with tranexamic acid, icatibant) may be beneficial; In Plasminogen deficiency, medical treatment (eg, with hyaluronidase-containing eyedrops, topical corticosteroids, heparin, FFP, immunosuppression, and lysine-conjugated plasminogen) has been described as variably beneficial	Dermatologic; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic; Pulmonary	3723296; 9242524; 9834305; 10233898; 16849641; 17900274; 21174000; 28795768; 29548426; 29952006; 29987869; 33799813

ClinVar

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

• not provided (4 variants)
• Angioedema, hereditary, 4 (1 variants)
• PLG-related disorder (1 variants)
• Hereditary angioneurotic edema (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLG 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			2	69	11	82
missense	1		153	8	8	170
nonsense	2		1			3
start loss						0
frameshift		1				1
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	3				4
splice region			7	15	2	24
non coding			3	31	55	89
Total	4	4	161	108	74

Highest pathogenic variant AF is 0.0000132

Variants in PLG

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

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

Position	Type	Phenotype	Significance	ClinVar
6-160702270-G-A			Benign (Jun 21, 2021)
6-160702316-G-A		not specified • Inborn genetic diseases	Likely benign (Jan 23, 2024)
6-160702320-G-A		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
6-160702321-T-C		Angioedema, hereditary, 4;Plasminogen deficiency, type I • Inborn genetic diseases	Uncertain significance (Dec 07, 2023)
6-160702340-A-G		Angioedema, hereditary, 4;Plasminogen deficiency, type I	Likely benign (Oct 15, 2021)
6-160702344-C-G			Uncertain significance (Nov 07, 2023)
6-160702360-C-G			Likely benign (Sep 20, 2023)
6-160702364-G-A			Likely benign (Oct 27, 2023)
6-160702364-G-GT			Benign (Jun 02, 2022)
6-160702368-T-A			Likely benign (Jun 06, 2023)
6-160702371-T-C			Likely benign (Jul 30, 2022)
6-160702381-G-T			Benign (Nov 12, 2018)
6-160702419-T-C			Benign (Nov 12, 2018)
6-160706093-G-A			Benign (Jun 19, 2021)
6-160706391-G-A			Benign (Jan 26, 2024)
6-160706403-C-G		not specified	Uncertain significance (Jan 03, 2024)
6-160706407-G-T			Uncertain significance (Jun 30, 2022)
6-160706413-G-C			Uncertain significance (Sep 11, 2023)
6-160706441-C-A			Likely benign (Oct 18, 2023)
6-160706443-A-C		Plasminogen deficiency, type I	Uncertain significance (Oct 14, 2022)
6-160706469-A-G		Plasminogen deficiency, type I • Otitis media, susceptibility to • Deep venous thrombosis	Conflicting classifications of pathogenicity (Jan 18, 2024)
6-160706472-A-C		Plasminogen deficiency, type I;Angioedema, hereditary, 4	Uncertain significance (Dec 21, 2023)
6-160706475-C-A			Uncertain significance (Jun 24, 2023)
6-160706517-G-A			Uncertain significance (Jan 03, 2024)
6-160706521-A-G			Uncertain significance (Jan 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLG	protein_coding	protein_coding	ENST00000308192	19	51078

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0103	0.990	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.213	434	447	0.972	0.0000245	5290
Missense in Polyphen		115	172.25	0.66763		1991
Synonymous	-0.933	182	167	1.09	0.0000101	1525
Loss of Function	4.57	13	46.7	0.279	0.00000238	544

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000114	0.000114
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells. {ECO:0000269|PubMed:14699093}.
• Disease: DISEASE: Plasminogen deficiency (PLGD) [MIM:217090]: A disorder characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. {ECO:0000269|PubMed:10233898, ECO:0000269|PubMed:1427790, ECO:0000269|PubMed:1986355, ECO:0000269|PubMed:6216475, ECO:0000269|PubMed:6238949, ECO:0000269|PubMed:8392398, ECO:0000269|PubMed:9242524, ECO:0000269|PubMed:9858247}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Complement and coagulation cascades - Homo sapiens (human);Influenza A - Homo sapiens (human);Staphylococcus aureus infection - Homo sapiens (human);Neuroactive ligand-receptor interaction - 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;Human Complement System;Dengue-2 Interactions with Complement and Coagulation Cascades;Dengue-2 Interactions with Blood Clotting Cascade;Fibrin Complement Receptor 3 Signaling Pathway;Complement and Coagulation Cascades;Signal Transduction;Dissolution of Fibrin Clot;platelet amyloid precursor protein pathway;fibrinolysis pathway;Metabolism of proteins;Signaling by PDGF;Extracellular matrix organization;Activation of Matrix Metalloproteinases;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis;Degradation of the extracellular matrix;Angiopoietin receptor Tie2-mediated signaling;Signaling by Receptor Tyrosine Kinases;amb2 Integrin signaling;p75(NTR)-mediated signaling;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling;Syndecan-4-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.774

Intolerance Scores

• loftool: 0.211
• rvis_EVS: 0.63
• rvis_percentile_EVS: 83.57

Haploinsufficiency Scores

• pHI: 0.233
• hipred: Y
• hipred_score: 0.558
• ghis: 0.429

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.949

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plg
• 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; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; 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); endocrine/exocrine gland 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); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: platelet degranulation;proteolysis;blood coagulation;negative regulation of cell population proliferation;negative regulation of cell-substrate adhesion;extracellular matrix disassembly;fibrinolysis;cellular protein metabolic process;tissue remodeling;interaction with symbiont;negative regulation of fibrinolysis;positive regulation of fibrinolysis;modification by host of symbiont morphology or physiology via secreted substance;interaction with symbiont via secreted substance involved in symbiotic interaction;negative regulation of cell-cell adhesion mediated by cadherin
• Cellular component: extracellular region;extracellular space;plasma membrane;cell surface;platelet alpha granule lumen;extrinsic component of external side of plasma membrane;other organism cell membrane;collagen-containing extracellular matrix;extracellular exosome;blood microparticle
• Molecular function: endopeptidase activity;serine-type endopeptidase activity;signaling receptor binding;protein binding;serine-type peptidase activity;enzyme binding;kinase binding;protein domain specific binding;apolipoprotein binding;chaperone binding;proteasome core complex binding;protein antigen binding