In Silico and In Vivo Analysis of Amino Acid Substitutions That Cause Laminopathies.

ABSTRACT: Mutations in the LMNA gene cause diseases called laminopathies. LMNA encodes lamins A and C, intermediate filaments with multiple roles at the nuclear envelope. LMNA mutations are frequently single base changes that cause diverse disease phenotypes affecting muscles, nerves, and fat. Disease-associated amino acid substitutions were mapped in silico onto three-dimensional structures of lamin A/C, revealing no apparent genotype-phenotype connections. In silico analyses revealed that seven of nine predicted partner protein binding pockets in the Ig-like fold domain correspond to sites of disease-associated amino acid substitutions. Different amino acid substitutions at the same position within lamin A/C cause distinct diseases, raising the question of whether the nature o

SUBMITTER: Hinz BE 

PROVIDER: S-EPMC8536974 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature