SERPINE1

serpin family E member 1, the group of Serpin peptidase inhibitors

Basic information

Region (hg38): 7:101127103-101139247

Previous symbols: [ "PLANH1", "PAI1" ]

Links

ENSG00000106366 ∙ NCBI:5054 ∙ OMIM:173360 ∙ HGNC:8583 ∙ Uniprot:P05121 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital plasminogen activator inhibitor type 1 deficiency (Strong), mode of inheritance: AR
• congenital plasminogen activator inhibitor type 1 deficiency (Supportive), mode of inheritance: AR
• congenital plasminogen activator inhibitor type 1 deficiency (Limited), mode of inheritance: AR
• congenital plasminogen activator inhibitor type 1 deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Plasminogen activator inhibitor-1 deficiency	AR	Hematologic	Individuals are susceptible to bleeding related to situations such as traumatic injury or surgery, and females manifest with menorrhagia, and precautions may be helpful to avoid severe sequelae; Medical treatment (eg, with fibrinolysis inhibitors) have been reported as beneficial in the prevention and treatment of bleeding episodes	Hematologic	2496147; 1435917; 9207454; 10754381; 15650551; 20664190; 21486382

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SERPINE1 gene.

• Congenital plasminogen activator inhibitor type 1 deficiency (76 variants)
• not provided (20 variants)
• Inborn genetic diseases (9 variants)
• Hemorrhage (2 variants)
• Susceptibility to severe coronavirus disease (COVID-19) due to an impaired coagulation process (1 variants)
• not specified (1 variants)
• Abnormal bleeding (1 variants)
• Thrombus (1 variants)
• Gastrointestinal hemorrhage (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SERPINE1 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	2	2	7
missense			22	1	1	24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region		1				1
non coding			38	7	20	65
Total	0	0	64	10	23

Variants in SERPINE1

This is a list of pathogenic ClinVar variants found in the SERPINE1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-101127137-G-A		Congenital plasminogen activator inhibitor type 1 deficiency	Uncertain significance (Jan 12, 2018)
7-101127145-G-A		Congenital plasminogen activator inhibitor type 1 deficiency	Uncertain significance (Jan 13, 2018)
7-101127153-C-T		Congenital plasminogen activator inhibitor type 1 deficiency	Uncertain significance (Jan 13, 2018)
7-101127192-C-T		Congenital plasminogen activator inhibitor type 1 deficiency	Uncertain significance (Jan 13, 2018)
7-101127226-G-C		Congenital plasminogen activator inhibitor type 1 deficiency	Uncertain significance (Jan 13, 2018)
7-101128436-G-A		Congenital plasminogen activator inhibitor type 1 deficiency • not specified • Susceptibility to severe coronavirus disease (COVID-19) due to an impaired coagulation process • SERPINE1-related disorder	Benign/Likely benign (Mar 12, 2023)
7-101128442-G-A		Congenital plasminogen activator inhibitor type 1 deficiency	Benign (Jun 09, 2021)
7-101128467-A-C			Likely benign (Dec 12, 2019)
7-101128472-C-A		Congenital plasminogen activator inhibitor type 1 deficiency	Uncertain significance (-)
7-101128507-C-T		SERPINE1-related disorder	Likely benign (Mar 05, 2019)
7-101128542-C-G		Congenital plasminogen activator inhibitor type 1 deficiency	Uncertain significance (Jan 13, 2018)
7-101128542-C-T			Uncertain significance (Jul 01, 2021)
7-101128550-C-T		not specified	Uncertain significance (May 03, 2023)
7-101128584-C-T		Congenital plasminogen activator inhibitor type 1 deficiency	Uncertain significance (Jan 13, 2018)
7-101128610-A-G		not specified	Uncertain significance (Dec 20, 2023)
7-101128640-G-A		not specified	Uncertain significance (Jul 25, 2023)
7-101128646-A-G		not specified	Uncertain significance (Mar 23, 2022)
7-101130178-T-C			Benign (Nov 12, 2018)
7-101130504-G-GC		Congenital plasminogen activator inhibitor type 1 deficiency	not provided (-)
7-101130506-G-A		Congenital plasminogen activator inhibitor type 1 deficiency	Benign/Likely benign (Dec 31, 2019)
7-101130525-C-A		not specified	Uncertain significance (Feb 14, 2023)
7-101130548-G-A		not specified	Uncertain significance (Feb 27, 2023)
7-101130552-C-T		Hemorrhage	Uncertain significance (-)
7-101130570-C-T		Thrombus	Uncertain significance (-)
7-101130605-G-C		Congenital plasminogen activator inhibitor type 1 deficiency	Conflicting classifications of pathogenicity (May 04, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SERPINE1	protein_coding	protein_coding	ENST00000223095	8	12178

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0436	0.951	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.453	213	232	0.916	0.0000149	2646
Missense in Polyphen		59	89.319	0.66055		1042
Synonymous	-0.0577	98	97.3	1.01	0.00000697	808
Loss of Function	2.45	5	15.4	0.326	6.77e-7	189

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine protease inhibitor. Inhibits TMPRSS7 (PubMed:15853774). Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it is required for fibrinolysis down-regulation and is responsible for the controlled degradation of blood clots (PubMed:8481516, PubMed:9207454, PubMed:17912461). As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading (PubMed:9175705). Acts as a regulator of cell migration, independently of its role as protease inhibitor (PubMed:15001579, PubMed:9168821). It is required for stimulation of keratinocyte migration during cutaneous injury repair (PubMed:18386027). It is involved in cellular and replicative senescence (PubMed:16862142). Plays a role in alveolar type 2 cells senescence in the lung (By similarity). Is involved in the regulation of cementogenic differentiation of periodontal ligament stem cells, and regulates odontoblast differentiation and dentin formation during odontogenesis (PubMed:25808697, PubMed:27046084). {ECO:0000250|UniProtKB:P22777, ECO:0000269|PubMed:15001579, ECO:0000269|PubMed:15853774, ECO:0000269|PubMed:16862142, ECO:0000269|PubMed:17912461, ECO:0000269|PubMed:18386027, ECO:0000269|PubMed:25808697, ECO:0000269|PubMed:27046084, ECO:0000269|PubMed:8481516, ECO:0000269|PubMed:9168821, ECO:0000269|PubMed:9175705, ECO:0000269|PubMed:9207454}.
• Disease: DISEASE: Plasminogen activator inhibitor-1 deficiency (PAI-1D) [MIM:613329]: A hematologic disorder characterized by increased bleeding after trauma, injury, or surgery. Affected females have menorrhagia. The bleeding defect is due to increased fibrinolysis of fibrin blood clots due to deficiency of plasminogen activator inhibitor-1, which inhibits tissue and urinary activators of plasminogen. {ECO:0000269|PubMed:8481516, ECO:0000269|PubMed:9207454}. Note=The disease is caused by mutations affecting the gene represented in this entry. A rare PAI-1D mutation resulting in a frameshift and protein truncation has been found in an Old Order Amish community. Homozygous mutation carriers suffer from episodes of major hemorrhage, while heterozygous carriers do not manifest abnormal bleeding (PubMed:9207454). Heterozygosity for the mutation is associated with longer leukocyte telomere length, lower fasting insulin levels, lower prevalence of diabetes mellitus, and a longer life span (PubMed:29152572). {ECO:0000269|PubMed:29152572, ECO:0000269|PubMed:9207454}.
• Pathway: Complement and coagulation cascades - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Selenium Micronutrient Network;Vitamin B12 Metabolism;Folate Metabolism;Blood Clotting Cascade;Transcriptional activity of SMAD2-SMAD3-SMAD4 heterotrimer;Adipogenesis;Oncostatin M Signaling Pathway;BMAL1-CLOCK,NPAS2 activates circadian gene expression;Photodynamic therapy-induced HIF-1 survival signaling;Hypothesized Pathways in Pathogenesis of Cardiovascular Disease;Dengue-2 Interactions with Complement and Coagulation Cascades;Dengue-2 Interactions with Blood Clotting Cascade;miRNA regulation of p53 pathway in prostate cancer;Complement and Coagulation Cascades;TGF-beta Receptor Signaling;Senescence and Autophagy in Cancer;Dissolution of Fibrin Clot;Circadian Clock;platelet amyloid precursor protein pathway;fibrinolysis pathway;Extracellular matrix organization;BMAL1:CLOCK,NPAS2 activates circadian gene expression;HIF-2-alpha transcription factor network;p73 transcription factor network;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis;Direct p53 effectors;ECM proteoglycans;HIF-1-alpha transcription factor network;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling;Regulation of nuclear SMAD2/3 signaling;E2F transcription factor network (Consensus)

Recessive Scores

• pRec: 0.869

Intolerance Scores

• loftool: 0.170
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.71

Haploinsufficiency Scores

• pHI: 0.423
• hipred: Y
• hipred_score: 0.775
• ghis: 0.513

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.948

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Serpine1
• Phenotype: homeostasis/metabolism 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); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; liver/biliary system phenotype; respiratory 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); hematopoietic 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)

Gene ontology

• Biological process: chronological cell aging;angiogenesis;platelet degranulation;circadian rhythm;regulation of signaling receptor activity;negative regulation of plasminogen activation;negative regulation of endopeptidase activity;negative regulation of smooth muscle cell migration;positive regulation of blood coagulation;negative regulation of blood coagulation;extracellular matrix organization;negative regulation of cell migration;positive regulation of interleukin-8 production;negative regulation of cell adhesion mediated by integrin;positive regulation of leukotriene production involved in inflammatory response;fibrinolysis;positive regulation of angiogenesis;positive regulation of transcription by RNA polymerase II;positive regulation of receptor-mediated endocytosis;positive regulation of inflammatory response;defense response to Gram-negative bacterium;negative regulation of fibrinolysis;negative regulation of vascular wound healing;negative regulation of wound healing;cellular response to lipopolysaccharide;positive regulation of monocyte chemotaxis;replicative senescence;dentinogenesis;positive regulation of odontoblast differentiation;negative regulation of extrinsic apoptotic signaling pathway via death domain receptors;negative regulation of smooth muscle cell-matrix adhesion;negative regulation of endothelial cell apoptotic process
• Cellular component: extracellular region;extracellular space;plasma membrane;platelet alpha granule lumen;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: protease binding;serine-type endopeptidase inhibitor activity;signaling receptor binding;protein binding