ATP7B codes for a protein that transports copper out of cells. Varied defects (over 20 distinct mutations) in ATP7B are associated with Wilson's disease [PMID 15523622]. The specific mutation affects the ceruloplasmin level, severity, and age of onset [PMID 16283883].
More than 800 pathogenic variants have been identified (see the Wilson Disease Mutation Database), although less than 200 are currently listed in ClinVar, and many lack dbSNP rs-ids. The most frequent ATP7B pathogenic variants in two different populations are:
- In Europeans: rs76151636, aka p.His1069Gln, occurring at a frequency of 26%-70% in Wilson patient populations and associated with neurologic or hepatic disease and a mean onset age of about 20 years.
- In Asians: rs28942074, aka p.Arg778Leu, found at a frequency of about 10- 30% in all Chinese, Korean and Japanese Wilson patient populations studied.
Other mutations associated with Wilson's include:
- p.Ala982Thr [PMID 24476933 ]
- 1168A-->G (Ile390Val)
- 2785A-->G (Ile929Val)
- 3316G-->A (Val1106Ile)
- Thr935Met. [PMID 11405812]
Arg778Leu and Thr935Met accounted for almost half of Chinese Wilson's patients in one study. [PMID 11405812]