ArticlePloS one2012
Three new alpha1-antitrypsin deficiency variants help to define a C-terminal region regulating conformational change and polymerization.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 50 citations in OpenAlex.
- Clinical implications of a novel SERPINA1 variant c.236 T > A: Challenges in characterizing new rare alpha-1 antitrypsin mutations.Molecular genetics and metabolism reports · 2026Article
- Susceptibility of alpha-1 antitrypsin deficiency variants to polymer-blocking therapy.JCI insight · 2025Article
- α‑1 Antitrypsin is a potential target of inflammation and immunomodulation (Review).Molecular medicine reports · 2025Review
- Tracing genetic diversity captures the molecular basis of misfolding disease.Nature communications · 2024Article
- Characterization of Novel Alpha-1-Antitrypsin Coding Variants in a Mammalian Cellular Model.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Distribution of alpha1 antitrypsin rare alleles in six countries: Results from the Progenika diagnostic network.Human genomics · 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
- Capturing the conversion of the pathogenic alpha-1-antitrypsin fold by ATF6 enhanced proteostasis.Cell chemical biology · 2023Article
- Improving the Laboratory Diagnosis of M-like Variants Related to Alpha1-Antitrypsin Deficiency.International journal of molecular sciences · 2022Article
- 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
- The molecular species responsible for αThe FEBS journal · 2021Article
- Known Mutations at the Cause of Alpha-1 Antitrypsin Deficiency an Updated Overview ofThe application of clinical genetics · 2021Review
- The structural basis for Z αScience advances · 2020Article
- Leveraging Population Genomics for Individualized Correction of the Hallmarks of Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2020Review
- Protein modeling to assess the pathogenicity of rare variants of SERPINA1 in patients suspected of having Alpha 1 Antitrypsin Deficiency.BMC medical genetics · 2019Article
- Characterisation of a type II functionally-deficient variant of alpha-1-antitrypsin discovered in the general population.PloS one · 2019Article
- Mineralization of alpha-1-antitrypsin inclusion bodies in Mmalton alpha-1-antitrypsin deficiency.Orphanet journal of rare diseases · 2018Article
- Intermittent C1-Inhibitor Deficiency Associated with Recessive Inheritance: Functional and Structural Insight.Scientific reports · 2018Article
- The pathological Trento variant of alpha-1-antitrypsin (E75V) shows nonclassical behaviour during polymerization.The FEBS journal · 2017Article
- Identification of a novel alpha1-antitrypsin variant.Respiratory medicine case reports · 2017Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Alpha1-antitrypsin (AAT) deficiency is a hereditary disorder associated with reduced AAT plasma levels, predisposing adults to pulmonary emphysema. The most common genetic AAT variants found in patients are the mildly deficient S and the severely deficient Z alleles, but several other pathogenic rare alleles have been reported. While the plasma AAT deficiency is a common trait of the disease, only a few AAT variants, including the prototypic Z AAT and some rare variants, form cytotoxic polymers in the endoplasmic reticulum of hepatocytes and predispose to liver disease. Here we report the identification of three new rare AAT variants associated to reduced plasma levels and characterize their molecular behaviour in cellular models. The variants, called Mpisa (Lys259Ile), Etaurisano (Lys368Glu) and Yorzinuovi (Pro391His), showed reduced secretion compared to control M AAT, and accumulated to different extents in the cells as ordered polymeric structures resembling those formed by the Z variant. Structural analysis of the mutations showed that they may facilitate polymerization both by loosening 'latch' interactions constraining the AAT reactive loop and through effects on core packing. In conclusion, the new AAT deficiency variants, besides increasing the risk of lung disease, may predispose to liver disease, particularly if associated with the common Z variant. The new mutations cluster structurally, thus defining a region of the AAT molecule critical for regulating its conformational state.
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