Biochemical and Cellular Properties of ATP7B Variants

Wilson disease (WD) is caused by mutations in the ATP-dependent copper transporter ATP7B. Over 500 WD mutations have been identified, and frequencies of most common mutations have been established for different populations. Over the years, significant progress has been made in predicting consequences of various substitutions and testing these predictions experimentally. In this chapter, we focus on biochemical and cellular effects of representative WD-causing mutations and summarize available data for the best characterized variants. We highlight a spectrum of consequences of WD mutations, which range from the complete loss of structural integrity or transport function to a disruption of some aspects of ATP7B behavior without significant change in the others. The emerging role of single nucleotide polymorphisms as factors modifying properties of ATP7B is also discussed.