Artículo
An update on genetic variants of the NKX2-5
Kolomenski, Jorge Emilio
; Delea, Marisol; Simonetti, Leandro; Fabbro, Mónica C.; Espeche, Lucia Daniela; Taboas, Melisa; Nadra, Alejandro Daniel
; Bruque, Carlos David
; Dain, Liliana Beatriz
Fecha de publicación:
05/2020
Editorial:
Wiley-liss, div John Wiley & Sons Inc.
Revista:
Human Mutation
ISSN:
1059-7794
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
NKX2-5 is a homeodomain transcription factor that plays a crucial role in heart development. It is the first gene where a single genetic variant (GV) was found to be associated with congenital heart diseases in humans. In this study, we carried out a comprehensive survey of NKX2-5 GVs to build a unified, curated, and updated compilation of all available GVs. We retrieved a total of 1,380 unique GVs. From these, 970 had information on their frequency in the general population and 143 have been linked to pathogenic phenotypes in humans. In vitro effect was ascertained for 38 GVs. The homeodomain had the biggest cluster of pathogenic variants in the protein: 49 GVs in 60 residues, 23 in its third α-helix, where 11 missense variants may affect protein–DNA interaction or the hydrophobic core. We also pinpointed the likely location of pathogenic GVs in four linear motifs. These analyses allowed us to assign a putative explanation for the effect of 90 GVs. This study pointed to reliable pathogenicity for GVs in helix 3 of the homeodomain and may broaden the scope of functional and structural studies that can be done to better understand the effect of GVs in NKX2-5 function.
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Articulos(IQUIBICEN)
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Kolomenski, Jorge Emilio; Delea, Marisol; Simonetti, Leandro; Fabbro, Mónica C.; Espeche, Lucia Daniela; et al.; An update on genetic variants of the NKX2-5; Wiley-liss, div John Wiley & Sons Inc.; Human Mutation; 41; 7; 5-2020; 1187-1208
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