Cargando…
Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects
The human albumin gene, the most abundant serum protein, is located in the long arm of chromosome 4, near the centromere, position 4q11–3. It is divided by 14 intervening introns into 15 exons, the last of which is untranslated. To date, 74 nucleotide substitutions (mainly missense) have been report...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835714/ https://www.ncbi.nlm.nih.gov/pubmed/35163085 http://dx.doi.org/10.3390/ijms23031159 |
_version_ | 1784649500318498816 |
---|---|
author | Caridi, Gianluca Lugani, Francesca Angeletti, Andrea Campagnoli, Monica Galliano, Monica Minchiotti, Lorenzo |
author_facet | Caridi, Gianluca Lugani, Francesca Angeletti, Andrea Campagnoli, Monica Galliano, Monica Minchiotti, Lorenzo |
author_sort | Caridi, Gianluca |
collection | PubMed |
description | The human albumin gene, the most abundant serum protein, is located in the long arm of chromosome 4, near the centromere, position 4q11–3. It is divided by 14 intervening introns into 15 exons, the last of which is untranslated. To date, 74 nucleotide substitutions (mainly missense) have been reported, determining the circulating variants of albumin or pre-albumin. In a heterozygous state, this condition is known as alloalbuminaemia or bisalbuminaemia (OMIM # 103600). The genetic variants are not associated with disease, neither in the heterozygous nor in the homozygous form. Only the variants resulting in familial dysalbuminaemic hyperthyroxinaemia and hypertriiodothyroninaemia are of clinical relevance because affected individuals are at risk of inappropriate treatment or may have adverse drug effects. In 28 other cases, the pathogenic variants (mainly affecting splicing, nonsense, and deletions), mostly in the homozygous form, cause a premature stop in the synthesis of the protein and lead to the condition known as congenital analbuminaemia. In this review, we will summarize the current knowledge of genetic and molecular aspects, functional consequences and potential therapeutic uses of the variants. We will also discuss the molecular defects resulting in congenital analbuminaemia, as well as the biochemical and clinical features of this rare condition |
format | Online Article Text |
id | pubmed-8835714 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88357142022-02-12 Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects Caridi, Gianluca Lugani, Francesca Angeletti, Andrea Campagnoli, Monica Galliano, Monica Minchiotti, Lorenzo Int J Mol Sci Review The human albumin gene, the most abundant serum protein, is located in the long arm of chromosome 4, near the centromere, position 4q11–3. It is divided by 14 intervening introns into 15 exons, the last of which is untranslated. To date, 74 nucleotide substitutions (mainly missense) have been reported, determining the circulating variants of albumin or pre-albumin. In a heterozygous state, this condition is known as alloalbuminaemia or bisalbuminaemia (OMIM # 103600). The genetic variants are not associated with disease, neither in the heterozygous nor in the homozygous form. Only the variants resulting in familial dysalbuminaemic hyperthyroxinaemia and hypertriiodothyroninaemia are of clinical relevance because affected individuals are at risk of inappropriate treatment or may have adverse drug effects. In 28 other cases, the pathogenic variants (mainly affecting splicing, nonsense, and deletions), mostly in the homozygous form, cause a premature stop in the synthesis of the protein and lead to the condition known as congenital analbuminaemia. In this review, we will summarize the current knowledge of genetic and molecular aspects, functional consequences and potential therapeutic uses of the variants. We will also discuss the molecular defects resulting in congenital analbuminaemia, as well as the biochemical and clinical features of this rare condition MDPI 2022-01-21 /pmc/articles/PMC8835714/ /pubmed/35163085 http://dx.doi.org/10.3390/ijms23031159 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Caridi, Gianluca Lugani, Francesca Angeletti, Andrea Campagnoli, Monica Galliano, Monica Minchiotti, Lorenzo Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects |
title | Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects |
title_full | Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects |
title_fullStr | Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects |
title_full_unstemmed | Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects |
title_short | Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects |
title_sort | variations in the human serum albumin gene: molecular and functional aspects |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835714/ https://www.ncbi.nlm.nih.gov/pubmed/35163085 http://dx.doi.org/10.3390/ijms23031159 |
work_keys_str_mv | AT caridigianluca variationsinthehumanserumalbumingenemolecularandfunctionalaspects AT luganifrancesca variationsinthehumanserumalbumingenemolecularandfunctionalaspects AT angelettiandrea variationsinthehumanserumalbumingenemolecularandfunctionalaspects AT campagnolimonica variationsinthehumanserumalbumingenemolecularandfunctionalaspects AT gallianomonica variationsinthehumanserumalbumingenemolecularandfunctionalaspects AT minchiottilorenzo variationsinthehumanserumalbumingenemolecularandfunctionalaspects |