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The classification of ATP‐binding cassette subfamily A member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system

IMPORTANCE: The ATP‐binding cassette subfamily A member 3 (ABCA3) protein plays a vital role in surfactant homeostasis. Mutations in the ABCA3 gene lead to the development of interstitial lung disease. In the most severe manifestation, mutations can lead to a fatal respiratory distress syndrome in n...

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Autores principales: Denman, Laura, Yonker, Lael M., Kinane, Thomas Bernard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331442/
https://www.ncbi.nlm.nih.gov/pubmed/32851225
http://dx.doi.org/10.1002/ped4.12020
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author Denman, Laura
Yonker, Lael M.
Kinane, Thomas Bernard
author_facet Denman, Laura
Yonker, Lael M.
Kinane, Thomas Bernard
author_sort Denman, Laura
collection PubMed
description IMPORTANCE: The ATP‐binding cassette subfamily A member 3 (ABCA3) protein plays a vital role in surfactant homeostasis. Mutations in the ABCA3 gene lead to the development of interstitial lung disease. In the most severe manifestation, mutations can lead to a fatal respiratory distress syndrome in neonates. ABCA3 belongs to the same ATP‐binding cassette transporter superfamily as the cystic fibrosis transmembrane conductance regulator (CFTR), the gene that causes cystic fibrosis. OBJECTIVE: To classify ABCA3 mutations in a manner similar to CFTR mutations in order to take advantage of recent advances in therapeutics. METHODS: Sequence homology between the CFTR protein and the ABCA3 protein was established. The region of CFTR that is a target for the new potentiator class of drugs was of particular interest. We performed a literature search to obtain all published mutations that were thought to be disease causing. We classified these mutations using the established CFTR classification system. When possible, we drew on previous experimental classification of ABCA3 mutations. RESULTS: Although the proteins share the same overall structure, only a 19% identity was established between CFTR and ABCA3. The CFTR therapeutic target region has a 22% homology with the corresponding ABCA3 region. Totally 233 unique protein mutations were identified. All protein mutations were classified and mapped to a schematic diagram of the ABCA3 protein. INTERPRETATION: This new classification system for ABCA3, based on CFTR classification, will likely aid further research of clinical outcomes and identification of mutation‐tailored therapeutics, with the aim for improving clinical care for patients with ABCA3 mutations.
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spelling pubmed-73314422020-08-25 The classification of ATP‐binding cassette subfamily A member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system Denman, Laura Yonker, Lael M. Kinane, Thomas Bernard Pediatr Investig Original Articles IMPORTANCE: The ATP‐binding cassette subfamily A member 3 (ABCA3) protein plays a vital role in surfactant homeostasis. Mutations in the ABCA3 gene lead to the development of interstitial lung disease. In the most severe manifestation, mutations can lead to a fatal respiratory distress syndrome in neonates. ABCA3 belongs to the same ATP‐binding cassette transporter superfamily as the cystic fibrosis transmembrane conductance regulator (CFTR), the gene that causes cystic fibrosis. OBJECTIVE: To classify ABCA3 mutations in a manner similar to CFTR mutations in order to take advantage of recent advances in therapeutics. METHODS: Sequence homology between the CFTR protein and the ABCA3 protein was established. The region of CFTR that is a target for the new potentiator class of drugs was of particular interest. We performed a literature search to obtain all published mutations that were thought to be disease causing. We classified these mutations using the established CFTR classification system. When possible, we drew on previous experimental classification of ABCA3 mutations. RESULTS: Although the proteins share the same overall structure, only a 19% identity was established between CFTR and ABCA3. The CFTR therapeutic target region has a 22% homology with the corresponding ABCA3 region. Totally 233 unique protein mutations were identified. All protein mutations were classified and mapped to a schematic diagram of the ABCA3 protein. INTERPRETATION: This new classification system for ABCA3, based on CFTR classification, will likely aid further research of clinical outcomes and identification of mutation‐tailored therapeutics, with the aim for improving clinical care for patients with ABCA3 mutations. John Wiley and Sons Inc. 2018-05-11 /pmc/articles/PMC7331442/ /pubmed/32851225 http://dx.doi.org/10.1002/ped4.12020 Text en © 2018 Chinese Medical Association. Pediatric Investigation published by John Wiley & Sons Australia, Ltd on behalf of Futang Research Center of Pediatric Development. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Denman, Laura
Yonker, Lael M.
Kinane, Thomas Bernard
The classification of ATP‐binding cassette subfamily A member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system
title The classification of ATP‐binding cassette subfamily A member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system
title_full The classification of ATP‐binding cassette subfamily A member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system
title_fullStr The classification of ATP‐binding cassette subfamily A member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system
title_full_unstemmed The classification of ATP‐binding cassette subfamily A member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system
title_short The classification of ATP‐binding cassette subfamily A member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system
title_sort classification of atp‐binding cassette subfamily a member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331442/
https://www.ncbi.nlm.nih.gov/pubmed/32851225
http://dx.doi.org/10.1002/ped4.12020
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