2koy

Structural highlights

Disease

[ATP7B_HUMAN] Defects in ATP7B are the cause of Wilson disease (WD) [MIM:277900]. WD is an autosomal recessive disorder of copper metabolism in which copper cannot be incorporated into ceruloplasmin in liver, and cannot be excreted from the liver into the bile. Copper accumulates in the liver and subsequently in the brain and kidney. The disease is characterized by neurologic manifestations and signs of cirrhosis.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] [51]}

Function

[ATP7B_HUMAN] Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile.

References

1. ↑ Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, Wasco W, Ross B, Romano DM, Parano E, Pavone L, Brzustowicz LM, et al.. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet. 1993 Dec;5(4):344-50. PMID:8298641 doi:http://dx.doi.org/10.1038/ng1293-344
2. ↑ Thomas GR, Forbes JR, Roberts EA, Walshe JM, Cox DW. The Wilson disease gene: spectrum of mutations and their consequences. Nat Genet. 1995 Feb;9(2):210-7. PMID:7626145 doi:http://dx.doi.org/10.1038/ng0295-210
3. ↑ Figus A, Angius A, Loudianos G, Bertini C, Dessi V, Loi A, Deiana M, Lovicu M, Olla N, Sole G, et al.. Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations. Am J Hum Genet. 1995 Dec;57(6):1318-24. PMID:8533760
4. ↑ Waldenstrom E, Lagerkvist A, Dahlman T, Westermark K, Landegren U. Efficient detection of mutations in Wilson disease by manifold sequencing. Genomics. 1996 Nov 1;37(3):303-9. PMID:8938442 doi:10.1006/geno.1996.0564
5. ↑ Loudianos G, Dessi V, Angius A, Lovicu M, Loi A, Deiana M, Akar N, Vajro P, Figus A, Cao A, Pirastu M. Wilson disease mutations associated with uncommon haplotypes in Mediterranean patients. Hum Genet. 1996 Dec;98(6):640-2. PMID:8931691
6. ↑ Chuang LM, Wu HP, Jang MH, Wang TR, Sue WC, Lin BJ, Cox DW, Tai TY. High frequency of two mutations in codon 778 in exon 8 of the ATP7B gene in Taiwanese families with Wilson disease. J Med Genet. 1996 Jun;33(6):521-3. PMID:8782057
7. ↑ Shah AB, Chernov I, Zhang HT, Ross BM, Das K, Lutsenko S, Parano E, Pavone L, Evgrafov O, Ivanova-Smolenskaya IA, Anneren G, Westermark K, Urrutia FH, Penchaszadeh GK, Sternlieb I, Scheinberg IH, Gilliam TC, Petrukhin K. Identification and analysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-phenotype correlation, and functional analyses. Am J Hum Genet. 1997 Aug;61(2):317-28. PMID:9311736 doi:10.1086/514864
8. ↑ Fan Y, Yang R, Yu L, Wu M, Shi S, Ren M, Han Y, Hu J, Zhao S. Identification of a novel missense mutation in Wilson's disease gene. Chin Med J (Engl). 1997 Nov;110(11):887-90. PMID:9772425
9. ↑ Orru S, Thomas G, Loizedda A, Cox DW, Contu L. 24 bp deletion and Ala1278 to Val mutation of the ATP7B gene in a Sardinian family with Wilson disease. Hum Mutat. 1997;10(1):84-5. PMID:9222767 doi:<84::AID-HUMU14>3.0.CO;2-W 10.1002/(SICI)1098-1004(1997)10:1<84::AID-HUMU14>3.0.CO;2-W
10. ↑ Kemppainen R, Palatsi R, Kallioinen M, Oikarinen A. A homozygous nonsense mutation and a combination of two mutations of the Wilson disease gene in patients with different lysyl oxidase activities in cultured fibroblasts. J Invest Dermatol. 1997 Jan;108(1):35-9. PMID:8980283
11. ↑ Duc HH, Hefter H, Stremmel W, Castaneda-Guillot C, Hernandez Hernandez A, Cox DW, Auburger G. His1069Gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype. Eur J Hum Genet. 1998 Nov-Dec;6(6):616-23. PMID:9887381 doi:10.1038/sj.ejhg.5200237
12. ↑ Kalinsky H, Funes A, Zeldin A, Pel-Or Y, Korostishevsky M, Gershoni-Baruch R, Farrer LA, Bonne-Tamir B. Novel ATP7B mutations causing Wilson disease in several Israeli ethnic groups. Hum Mutat. 1998;11(2):145-51. PMID:9482578 doi:<145::AID-HUMU7>3.0.CO;2-I 10.1002/(SICI)1098-1004(1998)11:2<145::AID-HUMU7>3.0.CO;2-I
13. ↑ Kim EK, Yoo OJ, Song KY, Yoo HW, Choi SY, Cho SW, Hahn SH. Identification of three novel mutations and a high frequency of the Arg778Leu mutation in Korean patients with Wilson disease. Hum Mutat. 1998;11(4):275-8. PMID:9554743 doi:<275::AID-HUMU4>3.0.CO;2-L 10.1002/(SICI)1098-1004(1998)11:4<275::AID-HUMU4>3.0.CO;2-L
14. ↑ Yamaguchi A, Matsuura A, Arashima S, Kikuchi Y, Kikuchi K. Mutations of ATP7B gene in Wilson disease in Japan: identification of nine mutations and lack of clear founder effect in a Japanese population. Hum Mutat. 1998;Suppl 1:S320-2. PMID:9452121
15. ↑ Loudianos G, Dessi V, Lovicu M, Angius A, Nurchi A, Sturniolo GC, Marcellini M, Zancan L, Bragetti P, Akar N, Yagci R, Vegnente A, Cao A, Pirastu M. Further delineation of the molecular pathology of Wilson disease in the Mediterranean population. Hum Mutat. 1998;12(2):89-94. PMID:9671269 doi:<89::AID-HUMU3>3.0.CO;2-G 10.1002/(SICI)1098-1004(1998)12:2<89::AID-HUMU3>3.0.CO;2-G
16. ↑ Tsai CH, Tsai FJ, Wu JY, Chang JG, Lee CC, Lin SP, Yang CF, Jong YJ, Lo MC. Mutation analysis of Wilson disease in Taiwan and description of six new mutations. Hum Mutat. 1998;12(6):370-6. PMID:9829905 doi:<370::AID-HUMU2>3.0.CO;2-S 10.1002/(SICI)1098-1004(1998)12:6<370::AID-HUMU2>3.0.CO;2-S
17. ↑ Wu Z, Wang N, Murong S, Lin M. [Missense mutations of exons 14 and 18 of Wilson's disease gene in Chinese patients]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 1999 Apr;16(2):91-3. PMID:10194254
18. ↑ Haas R, Gutierrez-Rivero B, Knoche J, Boker K, Manns MP, Schmidt HH. Mutation analysis in patients with Wilson disease: identification of 4 novel mutations. Mutation in brief no. 250. Online. Hum Mutat. 1999;14(1):88. PMID:10447265 doi:<88::AID-HUMU15>3.0.CO;2-H 10.1002/(SICI)1098-1004(1999)14:1<88::AID-HUMU15>3.0.CO;2-H
19. ↑ Loudianos G, Dessi V, Lovicu M, Angius A, Figus A, Lilliu F, De Virgiliis S, Nurchi AM, Deplano A, Moi P, Pirastu M, Cao A. Molecular characterization of wilson disease in the Sardinian population--evidence of a founder effect. Hum Mutat. 1999;14(4):294-303. PMID:10502776 doi:<294::AID-HUMU4>3.0.CO;2-9 10.1002/(SICI)1098-1004(199910)14:4<294::AID-HUMU4>3.0.CO;2-9
20. ↑ Curtis D, Durkie M, Balac (Morris) P, Sheard D, Goodeve A, Peake I, Quarrell O, Tanner S. A study of Wilson disease mutations in Britain. Hum Mutat. 1999;14(4):304-11. PMID:10502777 doi:<304::AID-HUMU5>3.0.CO;2-W 10.1002/(SICI)1098-1004(199910)14:4<304::AID-HUMU5>3.0.CO;2-W
21. ↑ Ivanova-Smolenskaya IA, Ovchinnikov IV, Karabanov AV, Deineko NL, Poleshchuk VV, Markova ED, Illarioshkin SN. The His1069Gln mutation in the ATP7B gene in Russian patients with Wilson disease. J Med Genet. 1999 Feb;36(2):174. PMID:10051024
22. ↑ Loudianos G, Dessi V, Lovicu M, Angius A, Altuntas B, Giacchino R, Marazzi M, Marcellini M, Sartorelli MR, Sturniolo GC, Kocak N, Yuce A, Akar N, Pirastu M, Cao A. Mutation analysis in patients of Mediterranean descent with Wilson disease: identification of 19 novel mutations. J Med Genet. 1999 Nov;36(11):833-6. PMID:10544227
23. ↑ Shimizu N, Nakazono H, Takeshita Y, Ikeda C, Fujii H, Watanabe A, Yamaguchi Y, Hemmi H, Shimatake H, Aoki T. Molecular analysis and diagnosis in Japanese patients with Wilson's disease. Pediatr Int. 1999 Aug;41(4):409-13. PMID:10453196
24. ↑ Loudianos G, Lovicu M, Solinas P, Kanavakis E, Tzetis M, Manolaki N, Panagiotakaki E, Karpathios T, Cao A. Delineation of the spectrum of Wilson disease mutations in the Greek population and the identification of six novel mutations. Genet Test. 2000;4(4):399-402. PMID:11216666 doi:10.1089/109065700750065162
25. ↑ Garcia-Villarreal L, Daniels S, Shaw SH, Cotton D, Galvin M, Geskes J, Bauer P, Sierra-Hernandez A, Buckler A, Tugores A. High prevalence of the very rare Wilson disease gene mutation Leu708Pro in the Island of Gran Canaria (Canary Islands, Spain): a genetic and clinical study. Hepatology. 2000 Dec;32(6):1329-36. PMID:11093740 doi:S0270-9139(00)72637-1
26. ↑ Okada T, Shiono Y, Hayashi H, Satoh H, Sawada T, Suzuki A, Takeda Y, Yano M, Michitaka K, Onji M, Mabuchi H. Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson's disease. Hum Mutat. 2000;15(5):454-62. PMID:10790207 doi:<454::AID-HUMU7>3.0.CO;2-J 10.1002/(SICI)1098-1004(200005)15:5<454::AID-HUMU7>3.0.CO;2-J
27. ↑ Kusuda Y, Hamaguchi K, Mori T, Shin R, Seike M, Sakata T. Novel mutations of the ATP7B gene in Japanese patients with Wilson disease. J Hum Genet. 2000;45(2):86-91. PMID:10721669 doi:10.1007/s100380050017
28. ↑ Lee CC, Wu JY, Tsai FJ, Kodama H, Abe T, Yang CF, Tsai CH. Molecular analysis of Wilson disease in Taiwan: identification of one novel mutation and evidence of haplotype-mutation association. J Hum Genet. 2000;45(5):275-9. PMID:11043508 doi:10.1007/s100380070015
29. ↑ Genschel J, Czlonkowska A, Sommer G, Buettner C, Bochow B, Lochs H, Schmidt H. Three novel mutations (P760L, L1305P, Q1351Stop) causing Wilson disease. Hum Mutat. 2001 Feb;17(2):156. PMID:11180609 doi:<156::AID-HUMU18>3.0.CO;2-0 10.1002/1098-1004(200102)17:2<156::AID-HUMU18>3.0.CO;2-0
30. ↑ Caca K, Ferenci P, Kuhn HJ, Polli C, Willgerodt H, Kunath B, Hermann W, Mossner J, Berr F. High prevalence of the H1069Q mutation in East German patients with Wilson disease: rapid detection of mutations by limited sequencing and phenotype-genotype analysis. J Hepatol. 2001 Nov;35(5):575-81. PMID:11690702
31. ↑ Butler P, McIntyre N, Mistry PK. Molecular diagnosis of Wilson disease. Mol Genet Metab. 2001 Mar;72(3):223-30. PMID:11243728 doi:10.1006/mgme.2000.3143
32. ↑ Ohya K, Abo W, Tamaki H, Sugawara C, Endo T, Nomachi S, Fukushi M, Kinebuchi M, Matsuura A. Presymptomatic diagnosis of Wilson disease associated with a novel mutation of the ATP7B gene. Eur J Pediatr. 2002 Feb;161(2):124-6. PMID:11954751
33. ↑ Yoo HW. Identification of novel mutations and the three most common mutations in the human ATP7B gene of Korean patients with Wilson disease. Genet Med. 2002 Nov-Dec;4(6 Suppl):43S-48S. PMID:12544487 doi:10.109700125817-200211001-00009
34. ↑ Loudianos G, Lovicu M, Dessi V, Tzetis M, Kanavakis E, Zancan L, Zelante L, Galvez-Galvez C, Cao A. Abnormal mRNA splicing resulting from consensus sequence splicing mutations of ATP7B. Hum Mutat. 2002 Oct;20(4):260-6. PMID:12325021 doi:10.1002/humu.10121
35. ↑ Takeshita Y, Shimizu N, Yamaguchi Y, Nakazono H, Saitou M, Fujikawa Y, Aoki T. Two families with Wilson disease in which siblings showed different phenotypes. J Hum Genet. 2002;47(10):543-7. PMID:12376745 doi:10.1007/s100380200082
36. ↑ Gu YH, Kodama H, Du SL, Gu QJ, Sun HJ, Ushijima H. Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease. Clin Genet. 2003 Dec;64(6):479-84. PMID:14986826
37. ↑ Majumdar R, Al-Jumah M, Zaidan R. A rare homozygous missense mutation in ATP7B exon 19 in a case of Wilson disease. Eur Neurol. 2004;51(1):52-4. Epub 2003 Nov 21. PMID:14639035 doi:10.1159/000075092
38. ↑ Deguti MM, Genschel J, Cancado EL, Barbosa ER, Bochow B, Mucenic M, Porta G, Lochs H, Carrilho FJ, Schmidt HH. Wilson disease: novel mutations in the ATP7B gene and clinical correlation in Brazilian patients. Hum Mutat. 2004 Apr;23(4):398. PMID:15024742 doi:10.1002/humu.9227
39. ↑ Pendlebury ST, Rothwell PM, Dalton A, Burton EA. Strokelike presentation of Wilson disease with homozygosity for a novel T766R mutation. Neurology. 2004 Nov 23;63(10):1982-3. PMID:15557537
40. ↑ Liu XQ, Zhang YF, Liu TT, Hsiao KJ, Zhang JM, Gu XF, Bao KR, Yu LH, Wang MX. Correlation of ATP7B genotype with phenotype in Chinese patients with Wilson disease. World J Gastroenterol. 2004 Feb 15;10(4):590-3. PMID:14966923
41. ↑ Dedoussis GV, Genschel J, Sialvera TE, Bochow B, Manolaki N, Manios Y, Tsafantakis E, Schmidt H. Wilson disease: high prevalence in a mountainous area of Crete. Ann Hum Genet. 2005 May;69(Pt 3):268-74. PMID:15845031 doi:10.1046/j.1529-8817.2005.00171.x
42. ↑ Kumar S, Thapa BR, Kaur G, Prasad R. Identification and molecular characterization of 18 novel mutations in the ATP7B gene from Indian Wilson disease patients: genotype. Clin Genet. 2005 May;67(5):443-5. PMID:15811015 doi:10.1111/j.1399-0004.2005.00440.x
43. ↑ Margarit E, Bach V, Gomez D, Bruguera M, Jara P, Queralt R, Ballesta F. Mutation analysis of Wilson disease in the Spanish population -- identification of a prevalent substitution and eight novel mutations in the ATP7B gene. Clin Genet. 2005 Jul;68(1):61-8. PMID:15952988 doi:CGE439
44. ↑ Todorov T, Savov A, Jelev H, Panteleeva E, Konstantinova D, Krustev Z, Mihaylova V, Tournev I, Tankova L, Tzolova N, Kremensky I. Spectrum of mutations in the Wilson disease gene (ATP7B) in the Bulgarian population. Clin Genet. 2005 Nov;68(5):474-6. PMID:16207219 doi:10.1111/j.1399-0004.2005.00516.x
45. ↑ Gromadzka G, Schmidt HH, Genschel J, Bochow B, Rodo M, Tarnacka B, Litwin T, Chabik G, Czlonkowska A. Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease. Clin Genet. 2005 Dec;68(6):524-32. PMID:16283883 doi:10.1111/j.1399-0004.2005.00528.x
46. ↑ Cox DW, Prat L, Walshe JM, Heathcote J, Gaffney D. Twenty-four novel mutations in Wilson disease patients of predominantly European ancestry. Hum Mutat. 2005 Sep;26(3):280. PMID:16088907 doi:10.1002/humu.9358
47. ↑ Vrabelova S, Letocha O, Borsky M, Kozak L. Mutation analysis of the ATP7B gene and genotype/phenotype correlation in 227 patients with Wilson disease. Mol Genet Metab. 2005 Sep-Oct;86(1-2):277-85. Epub 2005 Jun 20. PMID:15967699 doi:S1096-7192(05)00161-7
48. ↑ Barada K, Nemer G, ElHajj II, Touma J, Cortas N, Boustany RM, Usta J. Early and severe liver disease associated with homozygosity for an exon 7 mutation, G691R, in Wilson's disease. Clin Genet. 2007 Sep;72(3):264-7. PMID:17718866 doi:10.1111/j.1399-0004.2007.00853.x
49. ↑ Davies LP, Macintyre G, Cox DW. New mutations in the Wilson disease gene, ATP7B: implications for molecular testing. Genet Test. 2008 Mar;12(1):139-45. doi: 10.1089/gte.2007.0072. PMID:18373411 doi:10.1089/gte.2007.0072
50. ↑ Hsi G, Cullen LM, Macintyre G, Chen MM, Glerum DM, Cox DW. Sequence variation in the ATP-binding domain of the Wilson disease transporter, ATP7B, affects copper transport in a yeast model system. Hum Mutat. 2008 Apr;29(4):491-501. doi: 10.1002/humu.20674. PMID:18203200 doi:10.1002/humu.20674
51. ↑ Abdel Ghaffar TY, Elsayed SM, Elnaghy S, Shadeed A, Elsobky ES, Schmidt H. Phenotypic and genetic characterization of a cohort of pediatric Wilson disease patients. BMC Pediatr. 2011 Jun 17;11:56. doi: 10.1186/1471-2431-11-56. PMID:21682854 doi:10.1186/1471-2431-11-56
52. ↑ Dmitriev OY, Bhattacharjee A, Nokhrin S, Uhlemann EM, Lutsenko S. Difference in stability of the N-domain underlies distinct intracellular properties of the E1064A and H1069Q mutants of copper-transporting ATPase ATP7B. J Biol Chem. 2011 May 6;286(18):16355-62. Epub 2011 Mar 11. PMID:21398519 doi:http://dx.doi.org/10.1074/jbc.M110.198101