UniProtKB/SwissProt variant VAR

Copper-transporting ATPase 2
Gene: ATP7B
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Variant information Variant position:

778
Type of variant:

LP/P [Disclaimer]
Residue change:

From Arginine (R) to Leucine (L) at position 778 (R778L, p.Arg778Leu).
Physico-chemical properties:

Change from large size and basic (R) to medium size and hydrophobic (L)
BLOSUM score:

-2
Variant description:

In WD; most common mutation; decreased copper transport activity; extensively localized throughout the cell in the distribution pattern of the endoplasmic reticulum.
Other resources:

Variant rs28942074 [ dbSNP | Ensembl ]

Sequence information Variant position:

778
Protein sequence length:

1465
Location on the sequence:

RSPVTFFDTPPMLFVFIALG R WLEHLAKSKTSEALAKLMSL
Residue conservation:

Human                         RSPVTFFDTPPMLFVFIALGRWLEHLAKSKTSEALAKLMSL

Mouse                         KSPVTFFDTPPMLFVFIALGRWLEHVAKSKTSEALAKLMSL

Rat                           KSPVTFFDTPPMLFVFIALGRWLEHVAKSKTSEALAKLMSL

Sheep                         RSPVTFFDTPPMLFVFIALGRWLEHVVKSKTSEALARLMSL

Sequence annotation in neighborhood:

Type	Positions	Description
Chain	1 – 1465	Copper-transporting ATPase 2
Transmembrane	765 – 785	Helical
Alternative sequence	234 – 1465	RPLSSANQNFNNSETLGHQGSHVVTLQLRIDGMHCKSCVLNIEENIGQLLGVQSIQVSLENKTAQVKYDPSCTSPVALQRAIEALPPGNFKVSLPDGAEGSGTDHRSSSSHSPGSPPRNQVQGTCSTTLIAIAGMTCASCVHSIEGMISQLEGVQQISVSLAEGTATVLYNPSVISPEELRAAIEDMGFEASVVSESCSTNPLGNHSAGNSMVQTTDGTPTSVQEVAPHTGRLPANHAPDILAKSPQSTRAVAPQKCFLQIKGMTCASCVSNIERNLQKEAGVLSVLVALMAGKAEIKYDPEVIQPLEIAQFIQDLGFEAAVMEDYAGSDGNIELTITGMTCASCVHNIESKLTRTNGITYASVALATSKALVKFDPEIIGPRDIIKIIEEIGFHASLAQRNPNAHHLDHKMEIKQWKKSFLCSLVFGIPVMALMIYMLIPSNEPHQSMVLDHNIIPGLSILNLIFFILCTFVQLLGGWYFYVQAYKSLRHRSANMDVLIVLATSIAYVYSLVILVVAVAEKAERSPVTFFDTPPMLFVFIALGRWLEHLAKSKTSEALAKLMSLQATEATVVTLGEDNLIIREEQVPMELVQRGDIVKVVPGGKFPVDGKVLEGNTMADESLITGEAMPVTKKPGSTVIAGSINAHGSVLIKATHVGNDTTLAQIVKLVEEAQMSKAPIQQLADRFSGYFVPFIIIMSTLTLVVWIVIGFIDFGVVQRYFPNPNKHISQTEVIIRFAFQTSITVLCIACPCSLGLATPTAVMVGTGVAAQNGILIKGGKPLEMAHKIKTVMFDKTGTITHGVPRVMRVLLLGDVATLPLRKVLAVVGTAEASSEHPLGVAVTKYCKEELGTETLGYCTDFQAVPGCGIGCKVSNVEGILAHSERPLSAPASHLNEAGSLPAEKDAVPQTFSVLIGNREWLRRNGLTISSDVSDAMTDHEMKGQTAILVAIDGVLCGMIAIADAVKQEAALAVHTLQSMGVDVVLITGDNRKTARAIATQVGINKVFAEVLPSHKVAKVQELQNKGKKVAMVGDGVNDSPALAQADMGVAIGTGTDVAIEAADVVLIRNDLLDVVASIHLSKRTVRRIRINLVLALIYNLVGIPIAAGVFMPIGIVLQPWMGSAAMAASSVSVVLSSLQLKCYKKPDLERYEAQAHGHMKPLTASQVSVHIGMDDRWRDSPRATPWDQVSYVSQVSLSSLTSDKPSRHSAAADDDGDKWSLLLNGRDEEQYI -> ETFIFC. In isoform 5.
Alternative sequence	624 – 785	Missing. In isoform 2.
Helix	767 – 786

Literature citations
Copper-dependent trafficking of Wilson disease mutant ATP7B proteins.
Forbes J.R.; Cox D.W.;
Hum. Mol. Genet. 9:1927-1935(2000)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS WD ASN-765; VAL-776; LEU-778 AND SER-943; Functional characterization of missense mutations in ATP7B: Wilson disease mutation or normal variant?
Forbes J.R.; Cox D.W.;
Am. J. Hum. Genet. 63:1663-1674(1998)
Cited for: CHARACTERIZATION OF VARIANTS WD ASN-765; VAL-769; VAL-776; LEU-778; GLN-778; SER-943; MET-977 AND LEU-992; CHARACTERIZATION OF VARIANT ALA-995; Mutation analysis and the correlation between genotype and phenotype of Arg778Leu mutation in chinese patients with Wilson disease.
Wu Z.Y.; Wang N.; Lin M.T.; Fang L.; Murong S.X.; Yu L.;
Arch. Neurol. 58:971-976(2001)
Cited for: VARIANTS VAL-390; ALA-406; LEU-456; GLY-723; ARG-832; ARG-875; VAL-929; LYS-952 AND ALA-1140; VARIANTS WD VAL-769; GLN-778; LEU-778; VAL-874; GLY-919; MET-935; ASP-943; PRO-1041; ILE-1106; HIS-1142; LYS-1173 AND SER-1270; Mutation analysis of 218 Chinese patients with Wilson disease revealed no correlation between the canine copper toxicosis gene MURR1 and Wilson disease.
Wu Z.Y.; Zhao G.X.; Chen W.J.; Wang N.; Wan B.; Lin M.T.; Murong S.X.; Yu L.;
J. Mol. Med. 84:438-442(2006)
Cited for: VARIANTS WD LEU-778; MET-935; LEU-992; ARG-1268 AND SER-1270; Distinct clinical courses according to presenting phenotypes and their correlations to ATP7B mutations in a large Wilson's disease cohort.
Lee B.H.; Kim J.H.; Lee S.Y.; Jin H.Y.; Kim K.J.; Lee J.J.; Park J.Y.; Kim G.H.; Choi J.H.; Kim K.M.; Yoo H.W.;
Liver Int. 31:831-839(2011)
Cited for: VARIANTS WD ARG-108; VAL-729; GLN-778; LEU-778; TRP-827; VAL-874; ASP-891; 899-ILE--GLN-907 DEL; GLY-919; ASP-943; SER-943; GLN-969; MET-977; LEU-992; THR-1010; ALA-1024; ILE-1029; ALA-1031; VAL-1035; PHE-1083; TYR-1091; ILE-1106; THR-1148; CYS-1151; SER-1168; SER-1186; MET-1216; ALA-1267; SER-1270; LEU-1273 AND ASP-1295; CHARACTERIZATION OF VARIANTS WD TRP-827; THR-1010; CYS-1151 AND ASP-1295; Mutational analysis of ATP7B in north Chinese patients with Wilson disease.
Li K.; Zhang W.M.; Lin S.; Wen L.; Wang Z.F.; Xie D.; Wei M.; Qiu Z.Q.; Dai Y.; Lin M.C.; Kung H.F.; Yao F.X.;
J. Hum. Genet. 58:67-72(2013)
Cited for: VARIANTS WD ASN-44; PHE-157; GLY-606; HIS-732; PRO-732; GLY-756; GLN-778; LEU-778; PHE-795; PRO-874; VAL-874; MET-890; GLY-919; ARG-921; ASP-943; TYR-975; TYR-980; PRO-987; LEU-992; CYS-1151; ALA-1178; GLU-1266; SER-1270 AND LEU-1273; VARIANT VAL-929; High frequency of two mutations in codon 778 in exon 8 of the ATP7B gene in Taiwanese families with Wilson disease.
Chuang L.-M.; Wu H.-P.; Jang M.-H.; Wang T.-R.; Sue W.-C.; Lin B.J.; Cox D.W.; Tai T.-Y.;
J. Med. Genet. 33:521-523(1996)
Cited for: VARIANTS WD GLN-778 AND LEU-778; Identification of three novel mutations and a high frequency of the Arg778Leu mutation in Korean patients with Wilson disease.
Kim E.K.; Yoo O.J.; Song K.Y.; Yoo H.W.; Choi S.Y.; Cho S.W.; Hahn S.H.;
Hum. Mutat. 11:275-278(1998)
Cited for: VARIANTS WD LEU-778; VAL-874 AND PHE-1083; VARIANTS ARG-832; ILE-864; MET-1109 AND ALA-1140; Mutations of ATP7B gene in Wilson disease in Japan: identification of nine mutations and lack of clear founder effect in a Japanese population.
Yamaguchi A.; Matsuura A.; Arashima S.; Kikuchi Y.; Kikuchi K.;
Hum. Mutat. Suppl. 1:S320-S322(1998)
Cited for: VARIANTS WD LEU-778; VAL-874; GLY-919; SER-1186; ALA-1267 AND SER-1270; Mutation analysis of Wilson disease in Taiwan and description of six new mutations.
Tsai C.-H.; Tsai F.-J.; Wu J.-Y.; Chang J.-G.; Lee C.-C.; Lin S.-P.; Yang C.-F.; Jong Y.-J.; Lo M.-C.;
Hum. Mutat. 12:370-376(1998)
Cited for: VARIANTS VAL-390; ALA-406; LEU-456; MET-935 AND ALA-1140; VARIANTS WD GLN-778; LEU-778; ASP-943; LEU-992; HIS-1142; CYS-1153 AND SER-1270; Molecular analysis and diagnosis in Japanese patients with Wilson's disease.
Shimizu N.; Nakazono H.; Takeshita Y.; Ikeda C.; Fujii H.; Watanabe A.; Yamaguchi Y.; Hemmi H.; Shimatake H.; Aoki T.;
Pediatr. Int. 41:409-413(1999)
Cited for: VARIANTS WD LEU-778; VAL-874; GLY-919; ILE-1029; VAL-1035; SER-1186 AND ASN-1222; Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson's disease.
Okada T.; Shiono Y.; Hayashi H.; Satoh H.; Sawada T.; Suzuki A.; Takeda Y.; Yano M.; Michitaka K.; Onji M.; Mabuchi H.;
Hum. Mutat. 15:454-462(2000)
Cited for: VARIANTS WD ILE-769; LEU-778; TRP-778; VAL-874; GLY-919; THR-1003; PHE-1083; SER-1186; ALA-1267; SER-1270; THR-1336 AND PRO-1373; VARIANTS ALA-406; LEU-456 AND ALA-1140; Novel mutations of the ATP7B gene in Japanese patients with Wilson disease.
Kusuda Y.; Hamaguchi K.; Mori T.; Shin R.; Seike M.; Sakata T.;
J. Hum. Genet. 45:86-91(2000)
Cited for: VARIANTS WD LEU-778; VAL-874 AND VAL-1297 DEL; VARIANTS LEU-290; ALA-406; LEU-456; ARG-832; ALA-1140 AND GLU-1407; Identification of novel mutations and the three most common mutations in the human ATP7B gene of Korean patients with Wilson disease.
Yoo H.-W.;
Genet. Med. 4:43S-48S(2002)
Cited for: VARIANTS WD HIS-768; LEU-778; VAL-874; PHE-1083; SER-1168; ILE-1255; ALA-1267 AND SER-1270; Two families with Wilson disease in which siblings showed different phenotypes.
Takeshita Y.; Shimizu N.; Yamaguchi Y.; Nakazono H.; Saitou M.; Fujikawa Y.; Aoki T.;
J. Hum. Genet. 47:543-547(2002)
Cited for: VARIANTS WD LEU-778; VAL-874 AND GLY-919; Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease.
Gu Y.-H.; Kodama H.; Du S.-L.; Gu Q.-J.; Sun H.-J.; Ushijima H.;
Clin. Genet. 64:479-484(2003)
Cited for: VARIANTS WD VAL-85; GLY-765; LEU-778; MET-890; GLY-919; MET-935; TYR-975; LEU-992; ARG-1098; THR-1148; LYS-1173 AND ASN-1248; VARIANTS ASP-14; ALA-406; LEU-456; ARG-832; ALA-1140; ASN-1143 AND SER-1245; Correlation of ATP7B genotype with phenotype in Chinese patients with Wilson disease.
Liu X.-Q.; Zhang Y.-F.; Liu T.-T.; Hsiao K.-J.; Zhang J.-M.; Gu X.-F.; Bao K.-R.; Yu L.-H.; Wang M.-X.;
World J. Gastroenterol. 10:590-593(2004)
Cited for: VARIANTS WD LEU-778; ASP-943; ILE-1106 AND MET-1216; VARIANT ALA-1140; Genetic and clinical analysis in a cohort of patients with Wilson's disease in southwestern China.
Liu Y.; Zhou H.; Guo H.; Bai Y.;
Arch. Med. Res. 46:164-169(2015)
Cited for: VARIANTS WD LEU-778; GLY-919; LEU-992; LYS-1136 AND GLU-1149; VARIANT LEU-456;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P35670: Variant p.Arg778Leu