SERPINE1

Chr 7ADAR

serpin family E member 1

Also known as: PAI, PAI-1, PAI1, PLANH1

NCBI Gene: 5054ENSG00000106366UniProt: P05121

This gene encodes a member of the serine proteinase inhibitor (serpin) superfamily. This member is the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), and hence is an inhibitor of fibrinolysis. The protein also functions as a component of innate antiviral immunity. Defects in this gene are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency), and high concentrations of the gene product are associated with thrombophilia. [provided by RefSeq, Aug 2020]

Primary Disease Associations & Inheritance

{Transcription of plasminogen activator inhibitor, modulator of}
Plasminogen activator inhibitor-1 deficiencyMIM #613329
ADAR
160
ClinVar variants
22
Pathogenic / LP
0.04
pLI score
6
Active trials
Clinical Summary— SERPINE1
🧬
Gene-Disease Validity (ClinGen)
congenital plasminogen activator inhibitor type 1 deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 98 VUS of 160 total submissions
💊
Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.69LOEUF
pLI 0.044
Z-score 2.45
OE 0.33 (0.17–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.45Z-score
OE missense 0.92 (0.82–1.03)
213 obs / 232.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.17–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.82–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 5 / 15.4Missense obs/exp: 213 / 232.4Syn Z: -0.06

ClinVar Variant Classifications

160 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic3
VUS98
Likely Benign16
Benign23
Conflicting1
19
Pathogenic
3
Likely Pathogenic
98
VUS
16
Likely Benign
23
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
18
0
19
Likely Pathogenic
0
0
3
0
3
VUS
1
51
43
3
98
Likely Benign
0
4
7
5
16
Benign
0
1
19
3
23
Conflicting
—1
Total2569011160

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SERPINE1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Transcription of plasminogen activator inhibitor, modulator of}

Molecular basis of disorder known

Plasminogen activator inhibitor-1 deficiency

MIM #613329

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
📖
GeneReview available — SERPINE1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Benefits of the Mediterranean Diet: Insights From the PREDIMED Study.
Martínez-González MA et al.·Prog Cardiovasc Dis
2015Review
Decoding per- and polyfluoroalkyl substances (PFAS) in hepatocellular carcinoma: a multi-omics and computational toxicology approach.
Hong Y et al.·J Transl Med
2025
Multi-modal analysis of human hepatic stellate cells identifies novel therapeutic targets for metabolic dysfunction-associated steatotic liver disease.
Kim HY et al.·J Hepatol
2025
Crosstalk between small-cell lung cancer cells and astrocytes mimics brain development to promote brain metastasis.
Qu F et al.·Nat Cell Biol
2023
Therapy-induced senescent tumor cell-derived extracellular vesicles promote colorectal cancer progression through SERPINE1-mediated NF-κB p65 nuclear translocation.
Zhang D et al.·Mol Cancer
2024
Gastric cancer-derived exosomal let-7 g-5p mediated by SERPINE1 promotes macrophage M2 polarization and gastric cancer progression.
Ye Z et al.·J Exp Clin Cancer Res
2025
Single-cell profiling reveals transcriptomic signatures of vascular endothelial cells in non-healing diabetic foot ulcers.
Lu Y et al.·Front Endocrinol (Lausanne)
2023
Senescent fibroblasts secrete CTHRC1 to promote cancer stemness in hepatocellular carcinoma.
Huang H et al.·Cell Commun Signal
2025
Comprehensive review of thrombophilia: pathophysiology, prevalence, risk factors, and molecular diagnosis.
Altwayan R et al.·Transfus Clin Biol
2025Review
Quercetin ameliorates ox-LDL-induced cellular senescence of aortic endothelial cells and macrophages by p16/p21, p53/SERPINE1, and AMPK/mTOR pathways.
Liang X et al.·Eur J Med Res
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SERPINE1 Drives Neuropathic Pain in a Resiniferatoxin-Induced Model via AKT-Mediated Neuronal Apoptosis.
Wang D et al.·Brain Res Bull
2026Functional
The VAX2-SERPINE1 axis modulates colorectal cancer cell proliferation and apoptosis through WNT/beta-catenin signaling.
Zhang J et al.·Transl Oncol
2026🔓 Open Access
Multi-omics characterization of benzo[a]pyrene toxicity networks identifies SERPINE1 and STK3 as prognostic biomarkers and therapeutic targets in head and neck squamous cell carcinoma.
Guo Y et al.·Naunyn Schmiedebergs Arch Pharmacol
2026
A Serpine1-F2-PAR1 axis facilitates apoptosis and disease severity during GCRV infection in grass carp.
Li Y et al.·Fish Shellfish Immunol
2026
Integration of Multi-Omics and Machine Learning Identifies TGFB1 and SERPINE1 as Biomarkers of Vascular Smooth Muscle Cell Senescence in Intracranial Aneurysms.
Qiu H et al.·Transl Stroke Res
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
IBS - Irritable Bowel Syndrome

Comparison Between Low FODMAP and SSRD in IBS

ENROLLING BY INVITATION
NCT05192603Phase NARegion SkaneStarted 2022-03-01
low FODMAP or SSRD
Diabetes Mellitus, Type 1Inflammation

The Role of the Adrenergic System in Hypoglycaemia Induced Inflammatory Response in People With Type 1 Diabetes and People Without Type 1 Diabetes-RAID-II

ACTIVE NOT RECRUITING
NCT06422494Phase NARadboud University Medical CenterStarted 2025-01-01
hyperinsulinaemic hypoglycaemic clampPropranolol Hydrochloride 1 MG/MLPhentolamine
HypertriglyceridemiaNormal

Cardiometabolic Properties of Omega-3 Functionalized With Hydroxytyrosol

ACTIVE NOT RECRUITING
NCT06992323Phase NANational Research Council, SpainStarted 2025-02-17
EPA + HTEPASunflower Oil
ALS (Amyotrophic Lateral Sclerosis)

This Study Evaluates the Safety, Target Engagement, and Preliminary Efficacy of Galunisertib (TGF-βR1/ALK5 Inhibitor)Combined With Nerandomilast (PDE4 Inhibitor) in GREM2-positive ALS, a Biomarker-defined Subgroup Hypothesized to Reflect Heightened TGF-β/SMAD-driven Astrocytic and Fibrotic Signaling

NOT YET RECRUITING
NCT07321860Phase PHASE2, PHASE3Gipfel Life Sciences GmbHStarted 2026-06-30
Galunisertib + Nerandomilast Combination
Cushing Syndrome

Cushing's Syndrome Before and After Treatment (CORRECT)

RECRUITING
NCT05521529University of AarhusStarted 2023-02-16
no intervention, as this is an observational study
Obese Patients (BMI ≥ 30 kg/m²)AnxietyDepressive Disorder

Therapeutic Potential of a Synbiotic to Improve Mental Health in Subjects With Obesity.

RECRUITING
NCT06901739Phase NACelia BañulsStarted 2025-04-15
SynbioticPlacebo

External Resources

Links to major genomics databases and tools