Thrombophilia with a likely monogenic cause

Gene: PLG

I don't know

The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.

Created: 11 Dec 2025, 7:07 p.m. | Last Modified: 11 Dec 2025, 7:07 p.m.

Panel Version: 2.9

Comment on list classification: PLG deficiency causes hypoplasminogenemia characterised by chronic pseudomembranous lesions consisting of fibrin deposition and inflammation, with ligneous conjunctivitis being the predominant clinical feature.

Predisposition to thrombosis was indicated in knockout mice which develop spontaneous, severe thromboses in multiple organs (PMID: 7705657). However, studies in humans have shown that severe PLG deficiency is rare and only weakly associated with thrombosis, largely in combination with other risk factors (PMID: 9684804; 12850227; 16849641; 27976734).

Overall the evidence indicates that this gene should be demoted from Green to Amber/Red at the next GMS panel update.

Created: 18 Jun 2025, 10:11 a.m. | Last Modified: 18 Jun 2025, 10:14 a.m.

Panel Version: 2.7

I don't know

Conflicting reports about the association of variants in this gene and risk of thrombosis. Multiple reports of unaffected homozygotes, non-segregation in families.

Created: 29 Apr 2024, 11:48 p.m. | Last Modified: 29 Apr 2024, 11:48 p.m.

Panel Version: 2.5

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Dysplasminogenemia, MIM# 217090

Publications

• 35244080
• 27976734

Green List (high evidence)

Gene rating submitted by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group.

Created: 18 Feb 2019, 1:40 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
217090 Plasminogen deficiency, type I

Green List (high evidence)

Gene rating submitted by Mandy Nesbitt SheffieldDiagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North EastGLH for the GMS Haematology specialist test group

Created: 14 Feb 2019, 1:57 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
217090 Plasminogen deficiency, type I

Green List (high evidence)

Gene rating submitted by Mike Mitchell Viapath St. Thomas' Hospital January 2019 on behalf of London South GLH for the GMS Haematology specialist test group.

Created: 7 Feb 2019, 2:43 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

I don't know

Initial gene list (Consensus Genes for SPEC HAEM Panels 31.01.19 North West v1 FINAL.xlsx) collated by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group. Gene Symbol submitted: PLG; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 217090 Plasminogen deficiency, type I; PMID(s): none submitted

Created: 18 Feb 2019, 1:51 p.m.

Initial gene list (Consensus Genes for Panels_Haem_SHEFFIELD-29.01.2019.xlsx) collated by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group. Gene Symbol submitted: PLG; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 217090 Plasminogen deficiency, type I; PMID(s): none submitted

Created: 14 Feb 2019, 2:01 p.m.

Initial gene list (Consensus Genes for Panels_Bleeding and Thrombosis_South London.xlsx) collated by Mike Mitchell Viapath St. Thomas' Hospital January 2019 on behalf of London South GLH for the GMS Haematology specialist test group. Gene Symbol submitted: PLG; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: not submitted; PMID(s): none submitted

Created: 7 Feb 2019, 2:49 p.m.

Initial gene list (Consensus Genes for Panels 17.12.18_Haem_WWMGLH_v3.xlxs) collated by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group. Gene Symbol submitted: PLG; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 217090 Plasminogen deficiency, type I; PMID(s): 16849641; 27193180; 25674820

Created: 5 Feb 2019, 7:23 p.m.

Green List (high evidence)

Gene rating submitted by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group.

Created: 5 Feb 2019, 7:23 p.m.

Variants in this GENE are reported as part of current diagnostic practice