Copper ion transmembrane transporter involved in the export of copper out of the cells. It is involved in copper homeostasis in the liver, where it ensures the efflux of copper from hepatocytes into the bile in response to copper overload. (updated: Oct. 10, 2018)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
This protein is predicted to be membranous by TOPCONS.
Total structural coverage: 0%
No model available.
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The reference OMIM entry for this protein is 277900
Wilson disease
Wnd; wd
Hepatolenticular degeneration
A number sign (#) is used with this entry because Wilson disease is caused by homozygous or compound heterozygous mutation in the ATP7B gene (606882) on chromosome 13q14.
DESCRIPTION
Wilson disease is an autosomal recessive disorder characterized by dramatic build-up of intracellular hepatic copper with subsequent hepatic and neurologic abnormalities. De Bie et al. (2007) provided a detailed review of the molecular pathogenesis of Wilson disease.
CLINICAL FEATURES
In Wilson disease, the basal ganglia and liver undergo changes that express themselves in neurologic manifestations and signs of cirrhosis, respectively. A disturbance in copper metabolism is somehow involved in the mechanism. Low ceruloplasmin (
117700) is found in the serum. Shokeir and Shreffler (1969) advanced the hypothesis that ceruloplasmin functions in enzymatic transfer of copper to copper-containing enzymes such as cytochrome oxidase. Supporting the hypothesis was the finding of markedly reduced levels of activity of cytochrome oxidase in Wilson disease and moderate reductions in heterozygotes. The Kayser-Fleischer ring is a deep copper-colored ring at the periphery of the cornea which is frequently found in Wilson disease and is thought to represent copper deposits. Bearn and McKusick (1958) and Whelton and Pope (1968) described azure lunulae of the fingernails in patients with Wilson disease. These are presumably of the same significance as the Kayser-Fleischer ring and possibly arise by the same mechanism. Hypercalciuria and nephrocalcinosis are not uncommon in patients with Wilson disease. Hypercalciuria associated with this disorder was first reported by Litin et al. (1959). Wiebers et al. (1979) observed renal stones in 7 of 54 patients with Wilson disease. Penicillamine therapy was accompanied by a decrease in urinary calcium excretion to normal values in 3 patients, but hypercalciuria persisted in 3. Azizi et al. (1989) described hypercalciuria and nephrolithiasis as presenting signs in Wilson disease and postulated tubular defect in calcium reabsorption. Hoppe et al. (1993) described a 17-year-old male with a 6-year history of hypercalciuria, nephrocalcinosis, and nephrolithiasis, in whom Wilson disease was finally diagnosed. Bearn (1960) suggested that Jewish WND patients from eastern Europe are different from other groups of patients in that the age at onset is later, the disease is generally milder, and the serum copper and serum ceruloplasmin levels are 'particularly liable to be of normal concentration.' Bonne-Tamir et al. (1990) provided a full analysis of Wilson disease in Israel. From a study of 28 Canadian families, Cox et al. (1972) suggested that there are at least 3 forms of Wilson disease. In a rare 'atypical form,' the heterozygotes show about 50% of the normal level of ceruloplasmin. This gene may have been of German-Mennonite derivation. In the 2 typical forms heterozygotes have normal ceruloplasmin levels, although they can be identified by decreased reappearance of radioactive copper into serum and ceruloplasmin. The authors referred to the 2 'typical forms' as the Slavic and the juvenile type. The Slavic type has a late age of onset and is predominantly a neurologic disease. The juvenile type, which occurs in western Europeans and several other ethnic groups, has onset before age 16 years and is frequently a hepatic disease. Czaja et al. (1987) demonstrated reduced ceruloplasmin gene transcription in 4 patients with Wi ...
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Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 277900 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).