UniProtKB/Swiss-Prot P35670: Variant p.Arg778Leu

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

778 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Arginine (R) to Leucine (L) at position 778 (R778L, p.Arg778Leu). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from large size and basic (R) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

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

Links to websites of interest for the variant.

Variant rs28942074 [ dbSNP | Ensembl ]

Sequence information Variant position:

778 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1465 The length of the canonical sequence.
Location on the sequence:

RSPVTFFDTPPMLFVFIALG R WLEHLAKSKTSEALAKLMSL The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         RSPVTFFDTPPMLFVFIALGRWLEHLAKSKTSEALAKLMSL

Mouse                         KSPVTFFDTPPMLFVFIALGRWLEHVAKSKTSEALAKLMSL

Rat                           KSPVTFFDTPPMLFVFIALGRWLEHVAKSKTSEALAKLMSL

Sheep                         RSPVTFFDTPPMLFVFIALGRWLEHVVKSKTSEALARLMSL

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

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.