This report describes Wilson disease (WND); WND exhibits autosomal recessive inheritance. The human gene implicated in this disease is ATP7B, which encodes Cu(2+)-transporting ATPase, beta polypeptide, a transmembrane copper-transporting P-type ATPase. There is one high-scoring ortholog in Drosophila, ATP7, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical amorphic alleles have been generated. ATP7A is also associated with Menkes disease (MIM:309400, FBhh0000076) and X-linked distal spinal muscular atrophy (MIM:300489, FBhh0000077). Dmel\ATP7 is orthologous to a paralogous gene in human, ATP7B.
The human ATP7B gene has not been introduced into flies.
A variant analogous to one specifically implicated in Wilson disease has been characterized in the fly and been shown to act like a partial loss-of-function mutation. A second variant, implicated in Wilson disease and a putative susceptibility locus for Alzheimer disease, was also shown to be a loss-of-function mutation. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): H778Q in the fly ATP7 gene (corresponds to H1069Q in the human ATP7B gene, allele designated ATP7WND.EGFP); K552R in the fly ATP7 gene (corresponds to K832R in the human ATP7B gene, allele designated ATP7ALZ.EGFP).
See the human disease model reports for copper metabolism disorders, ATP7-related (FBhh0000438) and copper metabolism disorder (postulated), SLC31A-related (FBhh0000439) for additional information on experimental results using Drosophila models of this and related diseases.
[updated Aug. 2019 by FlyBase; FBrf0222196]
[WILSON DISEASE; WND](https://omim.org/entry/277900)
[ATPase, Cu(2+)-TRANSPORTING, BETA POLYPEPTIDE; ATP7B](https://omim.org/entry/606882)
Wilson disease is a disorder of copper metabolism that can present with hepatic, neurologic, or psychiatric disturbances, or a combination of these, in individuals ranging from age three years to over 50 years; symptoms vary among and within families. Liver disease includes recurrent jaundice, simple acute self-limited hepatitis-like illness, autoimmune-type hepatitis, fulminant hepatic failure, or chronic liver disease. Neurologic presentations include movement disorders (tremors, poor coordination, loss of fine-motor control, chorea, choreoathetosis) or rigid dystonia (mask-like facies, rigidity, gait disturbance, pseudobulbar involvement). Psychiatric disturbance includes depression, neurotic behaviors, disorganization of personality, and, occasionally, intellectual deterioration. Kayser-Fleischer rings, frequently present, result from copper deposition in Descemet's membrane of the cornea and reflect a high degree of copper storage in the body. [from GeneReviews, Wilson Disease, pubmed:20301685 2015.12.13]
Wilson disease is an autosomal recessive disorder characterized by dramatic build-up of intracellular hepatic copper with subsequent hepatic and neurologic abnormalities. [From MIM:277900, 2015.12.18]
Wilson disease is caused by homozygous or compound heterozygous mutation in the ATP7B gene. [From MIM:277900, 2015.12.18]
The ATP7B gene encodes Cu(2+)-transporting ATPase, beta polypeptide, a polypeptide that acts as a plasma membrane copper-transport protein (summary by Harris, 2000, pubmed:10940336). [From MIM:606882, 2015.12.17]
Many to one: 2 human to 1 Drosophila.
High-scoring ortholog of human genes ATP7A and ATP7B (1 Drosophila to 2 human). Dmel\ATP7 shares 46-47% identity and 62% similarity with human genes.
