Human Genetics

, Volume 114, Issue 2, pp 165–172 | Cite as

A comparison of the mutation spectra of Menkes disease and Wilson disease

Original Investigation


The genes for two copper-transporting ATPases, ATP7A and ATP7B, are defective in the heritable disorders of copper imbalance, Menkes disease (MNK) and Wilson disease (WND), respectively. A comparison of the two proteins shows extensive conservation in the signature domains, with amino acid identities outside of the conserved domains being limited. The mutation spectra of MNK and WND were compared to confirm and refine further regions critical for normal function. Mutations were found to be relatively widespread; however, the majority was concentrated within defined functional domains and membrane-spanning segments, reinforcing the importance of these regions for protein function. Of the total published point mutations in ATP7A, 23.0% are splice-site, 20.7% nonsense, 17.2% missense, and 39.1% small insertions/deletions. There is a high prevalence (58.2%) of missense mutations in ATP7B. For the other mutations in ATP7B, 7.4% are splice-site, 7.4% nonsense, and 27.0% small insertions/deletions. A region of possible importance is the intervening sequence between the last copper-binding domain and the first transmembrane helix, as this region has a high percentage of MNK mutations. Similarly, the region containing the ATP-binding domain has 24.6% of all WND mutations. The study of mutation locations is useful for defining critical regions or residues and for efficient molecular diagnosis.



This study was funded by a grant from the Canadian Institutes of Health Research (CIHR) to D.W.C., and G.H. was supported by postgraduate scholarships from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Alberta Heritage Foundation for Medical Research (AHFMR).

Supplementary material

Fig. 1A-C Amino acid comparisons of human ATP7A and ATP7B and their orthologues. (A) Human ATP7A and human ATP7B alignment. (B) Human ATP7B and its orthologues. (C) Human ATP7A and its orthologues

Figure1A-C.pdf (187 kb)
(PDF 187 KB)

Table 1 ATP7A mutation database

Table1.pdf (69 kb)
(PDF 69 KB)


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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  1. 1.Department of Medical Genetics, 8–39 Medical Sciences BuildingUniversity of AlbertaEdmontonCanada

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