ArticlePloS one2019
Characterisation of a type II functionally-deficient variant of alpha-1-antitrypsin discovered in the general population.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Susceptibility of alpha-1 antitrypsin deficiency variants to polymer-blocking therapy.JCI insight · 2025Article
- Identification of an exosite at the neutrophil elastase/alpha-1-antitrypsin interface.The FEBS journal · 2025Article
- α‑1 Antitrypsin is a potential target of inflammation and immunomodulation (Review).Molecular medicine reports · 2025Review
- Spatial covariance reveals isothiocyanate natural products adjust redox stress to restore function in alpha-1-antitrypsin deficiency.Cell reports. Medicine · 2025Article
- Characterization of Novel Alpha-1-Antitrypsin Coding Variants in a Mammalian Cellular Model.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Probing of the reactive center loop region of alpha-1-antitrypsin by mutagenesis predicts new type-2 dysfunctional variants.Cellular and molecular life sciences : CMLS · 2023Article
- Identification and characterization of two SERPINC1 mutations causing congenital antithrombin deficiency.Thrombosis journal · 2023Article
- Identification of an alpha-1 antitrypsin variant with enhanced specificity for factor XIa by phage display, bacterial expression, and combinatorial mutagenesis.Scientific reports · 2021Article
- Host/genetic factors associated with COVID-19 call for precision medicine.Precision clinical medicine · 2020Article
- Implications of a Change of Paradigm in Alpha1 Antitrypsin Deficiency Augmentation Therapy: From Biochemical to Clinical Efficacy.Journal of clinical medicine · 2020Review
- Intrahepatic heteropolymerization of M and Z alpha-1-antitrypsin.JCI insight · 2020Article
- Evaluation of Alpha 1-Antitrypsin for the Early Diagnosis of Colorectal Cancer.Pathology oncology research : POR · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Lung disease in alpha-1-antitrypsin deficiency (AATD) results from dysregulated proteolytic activity, mainly by neutrophil elastase (HNE), in the lung parenchyma. This is the result of a substantial reduction of circulating alpha-1-antitrypsin (AAT) and the presence in the plasma of inactive polymers of AAT. Moreover, some AAT mutants have reduced intrinsic activity toward HNE, as demonstrated for the common Z mutant, as well as for other rarer variants. Here we report the identification and characterisation of the novel AAT reactive centre loop variant Gly349Arg (p.G373R) present in the ExAC database. This AAT variant is secreted at normal levels in cellular models of AATD but shows a severe reduction in anti-HNE activity. Biochemical and molecular dynamics studies suggest it exhibits unfavourable RCL presentation to cognate proteases and compromised insertion of the RCL into β-sheet A. Identification of a fully dysfunctional AAT mutant that does not show a secretory defect underlines the importance of accurate genotyping of patients with pulmonary AATD manifestations regardless of the presence of normal levels of AAT in the circulation. This subtype of disease is reminiscent of dysfunctional phenotypes in anti-thrombin and C1-inibitor deficiencies so, accordingly, we classify this variant as the first pure functionally-deficient (type II) AATD mutant.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.