Hepatolenticular degeneration, also named Wilson disease, is an autosomal recessive genetic disease that characterized by copper metabolism disorder. WD mainly caused by the dysfunction of mutant ATP7B variants. This review summaries the mechanisms that different mutations affect the function of ATP7B, including inducing the mislocalization of mutant proteins, affecting the interactions between proteins or domains, regulating catalytic activity of ATP7B, and modifying the splicing of ATP7B gene. Further more, the genotype-phenotype correlation of a few mutations has been reviewed. Several mutations, such as p.R778L, are considered to be associated with more serious clinical symptoms, and the differences in environmental, diet, and lifestyle habits may also have effects on the susceptibility or the onset age of the patients. The research of the pathogenesis and clinical characterization of ATP7B gene mutations in the molecular level helps to deepen the understanding of WD, and suggests that personalized treatments should be used in future clinical practice.

Hepatolenticular degeneration; Gene mutation; Molecular mechanism; Clinical phenotype; ATPase Cu²⁺ transporting beta polypeptide gene