Dominant negative variants in KIF5B cause osteogenesis imperfecta via down regulation of mTOR signaling.

ABSTRACT:

Background

Kinesin motor proteins transport intracellular cargo, including mRNA, proteins, and organelles. Pathogenic variants in kinesin-related genes have been implicated in neurodevelopmental disorders and skeletal dysplasias. We identified de novo, heterozygous variants in KIF5B, encoding a kinesin-1 subunit, in four individuals with osteogenesis imperfecta. The variants cluster within the highly conserved kinesin motor domain and are predicted to interfere with nucleotide binding, although the mechanistic consequences on cell signaling and function are unknown.

Methods

To understand the in vivo genetic mechanism of KIF5B variants, we modeled the p.Thr87Ile variant that was found in two patients in the C. elegans ortholog, unc-116, at the corresponding position (Thr90Ile

SUBMITTER: Marom R 

PROVIDER: S-EPMC10656020 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature