The ATP7B Gene

Abstract The ATP7B gene (chromosome 13q14.13) spans approximately 80 kb of genomic DNA, comprises 21 protein-coding exons, encodes a messenger ribonucleic acid of approximately 7.5–8.5 kb, and produces a protein containing 1465 amino acid residues. Metal-binding transcription factors may play an important role in regulation. Genetic analysis must suit the spectrum of pathogenic variants present in the population: genotyping for common mutations and/or sequencing to identify rare or novel pathogenic variants. Other rare mutational mechanisms also occur: large-scale deletions, promoter mutations, uniparental disomy, and pseudo-dominant inheritance. Diagnostic laboratories use additional quality control systems to ensure high quality of service. Approximately 800 pathogenic variants have been published. Distinguishing between pathogenic and benign variants requires the use of multiple lines of evidence. In the United Kingdom, sequencing of the protein-coding region of the ATP7B gene, with promoter sequencing and exon deletion/duplication analysis, has a 98% pickup rate for identifying significant gene alterations. The disease prevalence may be significantly higher than 1:30,000.