ArticleAmerican journal of respiratory cell and molecular biology2016
Deficiency Mutations of Alpha-1 Antitrypsin. Effects on Folding, Function, and Polymerization.
Article in American journal of respiratory cell and molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 39 citations in OpenAlex.
- Functional and clinical significance of novel SERPINA1 variants on alpha-1 antitrypsin deficiency.Respiratory research · 2026Article
- Susceptibility of alpha-1 antitrypsin deficiency variants to polymer-blocking therapy.JCI insight · 2025Article
- Top-Down Ion Mobility Mass Spectrometry Reveals a Disease Associated Conformational Ensemble of Alpha-1-antitrypsin.Journal of the American Chemical Society · 2025Article
- α‑1 Antitrypsin is a potential target of inflammation and immunomodulation (Review).Molecular medicine reports · 2025Review
- A novel pathological mutant reveals the role of torsional flexibility in the serpin breach in adoption of an aggregation-prone intermediate.The FEBS journal · 2024Article
- Native and Ion Mobility Mass Spectrometry Characterization of Alpha 1 Antitrypsin Variants and Oligomers.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Diffuse panniculitis in a teenage male with ZZ αERJ open research · 2023Article
- Novel SERPINA1 Alleles Identified through a Large Alpha-1 Antitrypsin Deficiency Screening Program and Review of Known Variants.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2023Article
- Impact of the PEG length and PEGylation site on the structural, thermodynamic, thermal, and proteolytic stability of mono-PEGylated alpha-1 antitrypsin.Protein science : a publication of the Protein Society · 2022Article
- Nascent chains can form co-translational folding intermediates that promote post-translational folding outcomes in a disease-causing protein.Nature communications · 2021Article
- Proteomics of Multiple Sclerosis: Inherent Issues in Defining the Pathoetiology and Identifying (Early) Biomarkers.International journal of molecular sciences · 2021Review
- The Importance of N186 in the Alpha-1-Antitrypsin Shutter Region Is Revealed by the Novel Bologna Deficiency Variant.International journal of molecular sciences · 2021Article
- Development of a small molecule that corrects misfolding and increases secretion of Z αEMBO molecular medicine · 2021Article
- High-resolution ex vivo NMR spectroscopy of human Z αNature communications · 2020Article
- The structural basis for Z αScience advances · 2020Article
- 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
- Monocytes and Macrophages in Alpha-1 Antitrypsin Deficiency.International journal of chronic obstructive pulmonary disease · 2020Review
- Obstacles to Early Diagnosis and Treatment of Alpha-1 Antitrypsin Deficiency: Current Perspectives.Therapeutics and clinical risk management · 2020Review
- Characterisation of a type II functionally-deficient variant of alpha-1-antitrypsin discovered in the general population.PloS one · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Misfolding, polymerization, and defective secretion of functional alpha-1 antitrypsin underlies the predisposition to severe liver and lung disease in alpha-1 antitrypsin deficiency. We have identified a novel (Ala336Pro, Baghdad) deficiency variant and characterized it relative to the wild-type (M) and Glu342Lys (Z) alleles. The index case is a homozygous individual of consanguineous parentage, with levels of circulating alpha-1 antitrypsin in the moderate deficiency range, but is a biochemical phenotype that could not be classified by standard methods. The majority of the protein was present as functionally inactive polymer, and the remaining monomer was 37% active relative to the wild-type protein. These factors combined indicate an 85 to 95% functional deficiency, similar to that seen with ZZ homozygotes. Biochemical, biophysical, and computational studies further defined the molecular basis of this deficiency. These studies demonstrated that native Ala336Pro alpha-1 antitrypsin could populate the polymerogenic intermediate-and therefore polymerize-more readily than either wild-type alpha-1 antitrypsin or the Z variant. In contrast, folding was far less impaired in Ala336Pro alpha-1 antitrypsin than in the Z variant. The data are consistent with a disparate contribution by the "breach" region and "shutter" region of strand 5A to folding and polymerization mechanisms. Moreover, the findings demonstrate that, in these variants, folding efficiency does not correlate directly with the tendency to polymerize in vitro or in vivo. They therefore differentiate generalized misfolding from polymerization tendencies in missense variants of alpha-1 antitrypsin. Clinically, they further support the need to quantify loss-of-function in alpha-1 antitrypsin deficiency to individualize patient care.
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.