PLG

Chr 6

plasminogen

Plasminogen is a serine protease zymogen that is activated to plasmin, which dissolves fibrin clots and degrades extracellular matrix proteins including fibronectin, laminin, and von Willebrand factor. Mutations cause plasminogen deficiency (type I), dysplasminogenemia, and hereditary angioedema type 4, with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene is highly constrained against loss-of-function variants (LOEUF 0.443), indicating that complete loss of function is likely poorly tolerated.

ResearchSummary from RefSeq, OMIM, UniProt

Protease which primary function is to degrade fibrin, the main component of blood clots (PubMed:6094526, PubMed:6919539). Also cleaves other components of blood clots like thrombospondin-1/THBS1 and von Willebrand factor (VWF) (PubMed:24449821, PubMed:7679575). Can also directly and/or through the activation of other proteases degrade the various components of the extracellular matrix including collagen, fibronectin and laminin (PubMed:14699093, PubMed:28849762, PubMed:9171346). Thereby, regulates a variety of biological processes including embryonic development, tissue remodeling, and inflammation (PubMed:9171346). In ovulation, weakens the walls of the Graafian follicle (By similarity). In vitro, it is also able to cleave several complement zymogens, such as C1, C4 and C5 (PubMed:6447255)

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPlasminogen deficiency

UniProtAngioedema, hereditary, 4

Clinical highlights

Gene-disease validity (ClinGen)

hypoplasminogenemia · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

183

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.44

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.010

Z-score 4.57

OE 0.28 (0.18–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.21Z-score

OE missense 0.97 (0.90–1.05)

434 obs / 446.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.18–0.44)

0≤0.351.4

Missense OE?0.97 (0.90–1.05)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 13 / 46.7Missense obs/exp: 434 / 446.7Syn Z: -0.93

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PLG · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Coronary Artery DiseasePercutaneous Coronary InterventionAcute Coronary Syndromes

Study of the Long-term Effects of P2Y12 Inhibitor Monotherapy and Coagulation Markers After Percutaneous Coronary Angioplasty.

RECRUITING

NCT07582835Phase PHASE3Cardiocentro TicinoStarted 2026-04-20

ClopidogrelTicagrelorPrasugrel

Polycystic Ovary SyndromeHypothalamic Amenorrhea

Body Fat as Determinant of Female Gonadal Dysfunction

RECRUITING

NCT03841981Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalStarted 2020-01-31

Anthropometric and physical examinationIndirect calorimetry, accelerometer and seven-day dietary recallBiochemical, hormonal and metabolic phenotyping

HypertriglyceridemiaNormal

Cardiometabolic Properties of Omega-3 Functionalized With Hydroxytyrosol

ACTIVE NOT RECRUITING

NCT06992323Phase NANational Research Council, SpainStarted 2025-02-17

EPA + HTEPASunflower Oil

Metastatic Thyroid Gland CarcinomaUnresectable Thyroid Gland Carcinoma

Dabrafenib and Lapatinib in Treating Patients With Refractory Thyroid Cancer That Cannot Be Removed by Surgery

ACTIVE NOT RECRUITING

NCT01947023Phase PHASE1National Cancer Institute (NCI)Started 2013-09-27

Biopsy ProcedureBiospecimen CollectionComputed Tomography

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

Plasminogen Deficiency

Study of Individuals Affected With Hypoplasminogenemia

RECRUITING

NCT03797495Indiana Hemophilia &Thrombosis Center, Inc.Started 2018-12-18

Relapsing Remitting Multiple Sclerosis (RRMS)

Indole-3-PROpionic Acid Clinical Trials - Multiple Sclerosis

RECRUITING

NCT07318129Phase NAGlostrup University Hospital, CopenhagenStarted 2026-01-26

PlaceboIndole-3-propionic acid (IPA)

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

Heart Failure

Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List

RECRUITING

NCT06868797Phase NACentral Hospital, Nancy, FranceStarted 2025-08-29

Biological sample for the measurement of suPAR levels.

Acute-On-Chronic Liver FailureAlcoholic HepatitisLiver Cirrhosis, Alcoholic

A-TANGO Phase 2 Study

NOT YET RECRUITING

NCT06890039Phase PHASE2Yaqrit LtdStarted 2025-09-01