Investigation of the Wilson gene ATP7B transcriptional start site and the effect of core promoter alterations.

ABSTRACT: Pathogenic genetic variants in the ATP7B gene cause Wilson disease, a recessive disorder of copper metabolism showing a significant variability in clinical phenotype. Promoter mutations have been rarely reported, and controversial data exist on the site of transcription initiation (the core promoter). We quantitatively investigated transcription initiation and found it to be located in immediate proximity of the translational start. The effects human single-nucleotide alterations of conserved bases in the core promoter on transcriptional activity were moderate, explaining why clearly pathogenic mutations within the core promoter have not been reported. Furthermore, the core promoter contains two frequent polymorphisms (rs148013251 and rs2277448) that could contribute to phenotypical variab

SUBMITTER: Hoflich C 

PROVIDER: S-EPMC8027023 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature