UniProtKB/Swiss-Prot P35670: Variant p.Val1140Ala

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

1140 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Valine (V) to Alanine (A) at position 1140 (V1140A, p.Val1140Ala). 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 medium size and hydrophobic (V) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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:

No effect on copper transport activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1801249 [ dbSNP | Ensembl ]

Sequence information Variant position:

1140 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:

LSAPASHLNEAGSLPAEKDA V PQTFSVLIGNREWLRRNGLT 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                         LSAPASHLNEAGSLPAEKDAVPQTFSVLIGNREWLRRNGLT

Mouse                         ---LTAHPVGVGNPPTGEGAGPQTFSVLIGNREWMRRNGLT

Rat                           ---PTAHPIGVGNPPIGEGTGPQTFSVLIGNREWMRRNGLT

Sheep                         QGPPTAHQNRVGSEPSETDAATQTFSVLIGNREWMRRNGLT

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
Topological domain	995 – 1322	Cytoplasmic
Alternative sequence	234 – 1465	RPLSSANQNFNNSETLGHQGSHVVTLQLRIDGMHCKSCVLNIEENIGQLLGVQSIQVSLENKTAQVKYDPSCTSPVALQRAIEALPPGNFKVSLPDGAEGSGTDHRSSSSHSPGSPPRNQVQGTCSTTLIAIAGMTCASCVHSIEGMISQLEGVQQISVSLAEGTATVLYNPSVISPEELRAAIEDMGFEASVVSESCSTNPLGNHSAGNSMVQTTDGTPTSVQEVAPHTGRLPANHAPDILAKSPQSTRAVAPQKCFLQIKGMTCASCVSNIERNLQKEAGVLSVLVALMAGKAEIKYDPEVIQPLEIAQFIQDLGFEAAVMEDYAGSDGNIELTITGMTCASCVHNIESKLTRTNGITYASVALATSKALVKFDPEIIGPRDIIKIIEEIGFHASLAQRNPNAHHLDHKMEIKQWKKSFLCSLVFGIPVMALMIYMLIPSNEPHQSMVLDHNIIPGLSILNLIFFILCTFVQLLGGWYFYVQAYKSLRHRSANMDVLIVLATSIAYVYSLVILVVAVAEKAERSPVTFFDTPPMLFVFIALGRWLEHLAKSKTSEALAKLMSLQATEATVVTLGEDNLIIREEQVPMELVQRGDIVKVVPGGKFPVDGKVLEGNTMADESLITGEAMPVTKKPGSTVIAGSINAHGSVLIKATHVGNDTTLAQIVKLVEEAQMSKAPIQQLADRFSGYFVPFIIIMSTLTLVVWIVIGFIDFGVVQRYFPNPNKHISQTEVIIRFAFQTSITVLCIACPCSLGLATPTAVMVGTGVAAQNGILIKGGKPLEMAHKIKTVMFDKTGTITHGVPRVMRVLLLGDVATLPLRKVLAVVGTAEASSEHPLGVAVTKYCKEELGTETLGYCTDFQAVPGCGIGCKVSNVEGILAHSERPLSAPASHLNEAGSLPAEKDAVPQTFSVLIGNREWLRRNGLTISSDVSDAMTDHEMKGQTAILVAIDGVLCGMIAIADAVKQEAALAVHTLQSMGVDVVLITGDNRKTARAIATQVGINKVFAEVLPSHKVAKVQELQNKGKKVAMVGDGVNDSPALAQADMGVAIGTGTDVAIEAADVVLIRNDLLDVVASIHLSKRTVRRIRINLVLALIYNLVGIPIAAGVFMPIGIVLQPWMGSAAMAASSVSVVLSSLQLKCYKKPDLERYEAQAHGHMKPLTASQVSVHIGMDDRWRDSPRATPWDQVSYVSQVSLSSLTSDKPSRHSAAADDDGDKWSLLLNGRDEEQYI -> ETFIFC. In isoform 5.

Literature citations
Molecular cloning of mutant ATP7B.
Carlini E.J.; Booth-Genthe C.L.;
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3); VARIANTS ALA-406; LEU-456; LYS-952 AND ALA-1140; Submission
Totoki Y.; Toyoda A.; Takeda T.; Sakaki Y.; Tanaka A.; Yokoyama S.; Ohara O.; Nagase T.; Kikuno R.F.;
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 786-1465; VARIANTS ARG-832 AND ALA-1140; 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; Molecular pathogenesis of Wilson disease among Indians: a perspective on mutation spectrum in ATP7B gene, prevalent defects, clinical heterogeneity and implication towards diagnosis.
Gupta A.; Chattopadhyay I.; Dey S.; Nasipuri P.; Das S.K.; Gangopadhyay P.K.; Ray K.;
Cell. Mol. Neurobiol. 27:1023-1033(2007)
Cited for: VARIANTS LEU-149; LEU-456; LEU-825; ALA-1140 AND ARG-1207; VARIANTS WD SER-591; ALA-1031 AND ALA-1178; His1069Gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype.
Ha-Hao D.; Hefter H.; Stremmel W.; Castaneda-Guillot C.; Hernandez Hernandez A.; Cox D.W.; Auburger G.;
Eur. J. Hum. Genet. 6:616-623(1998)
Cited for: VARIANTS WD ALA-710; CYS-741; ILE-1031; GLN-1069 AND ARG-1176; VARIANTS LEU-456; GLY-949 AND ALA-1140; Novel ATP7B mutations causing Wilson disease in several Israeli ethnic groups.
Kalinsky H.; Funes A.; Zeldin A.; Pel-Or Y.; Korostishevsky M.; Gershoni-Baruch R.; Farrer L.A.; Bonne-Tamir B.;
Hum. Mutat. 11:145-151(1998)
Cited for: VARIANTS WD ARG-645; ASN-765; GLN-969; ALA-1064; GLN-1069; VAL-1213 AND 1216-VAL-VAL-1217 DEL; VARIANTS SER-565; GLY-723; ARG-832 AND ALA-1140; 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; 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; 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; 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; Mutation analysis of Wilson disease in the Spanish population -identification of a prevalent substitution and eight novel mutations in the ATP7B gene.
Margarit E.; Bach V.; Gomez D.; Bruguera M.; Jara P.; Queralt R.; Ballesta F.;
Clin. Genet. 68:61-68(2005)
Cited for: VARIANTS WD ARG-645; LEU-690; ARG-869; SER-943; MET-977; GLU-1061; GLN-1069; SER-1099; MET-1216 AND PRO-1232; VARIANTS ALA-406; LEU-456; ARG-832 AND ALA-1140; Mutation analysis of the ATP7B gene and genotype/phenotype correlation in 227 patients with Wilson disease.
Vrabelova S.; Letocha O.; Borsky M.; Kozak L.;
Mol. Genet. Metab. 86:277-285(2005)
Cited for: VARIANTS WD SER-641; SER-710; ARG-737; GLY-778; GLU-918; GLN-969; MET-977; VAL-1018; SER-1033; TRP-1041; VAL-1063; LYS-1064; GLN-1069; THR-1102; ASP-1111; THR-1148; ARG-1176; SER-1186; ASN-1271; LEU-1273; PRO-1305; ASP-1341 AND CYS-1355; VARIANTS LEU-456; ARG-832 AND ALA-1140; New mutations in the Wilson disease gene, ATP7B: implications for molecular testing.
Davies L.P.; Macintyre G.; Cox D.W.;
Genet. Test. 12:139-145(2008)
Cited for: VARIANTS WD ALA-536; ARG-657; VAL-971; MET-974; PRO-1004; ALA-1149; ASN-1164; GLY-1173; THR-1228; VAL-1230; VAL-1267; THR-1328 AND ILE-1359; VARIANTS ALA-406; LEU-456; ARG-832; LYS-952 AND ALA-1140; Sequence variation in the ATP-binding domain of the Wilson disease transporter, ATP7B, affects copper transport in a yeast model system.
Hsi G.; Cullen L.M.; Macintyre G.; Chen M.M.; Glerum D.M.; Cox D.W.;
Hum. Mutat. 29:491-501(2008)
Cited for: CHARACTERIZATION OF VARIANTS WD HIS-532; ALA-626; HIS-642; TRP-1041; LYS-1064; PHE-1083; ASP-1106; VAL-1169; THR-1183 AND SER-1186; CHARACTERIZATION OF VARIANT ALA-1140; FUNCTION; Mutation analysis of ATP7B gene in Turkish Wilson disease patients: identification of five novel mutations.
Simsek Papur O.; Akman S.A.; Cakmur R.; Terzioglu O.;
Eur. J. Med. Genet. 56:175-179(2013)
Cited for: VARIANTS WD SER-710; ASN-765; GLY-778; TRP-778; ILE-788; VAL-874; TRP-919; SER-943; GLN-969; THR-1003; VAL-1003; ILE-1036; TRP-1041; GLN-1069; CYS-1151; THR-1245 AND SER-1270; VARIANTS ALA-406; LEU-456; ARG-832; LYS-952; ALA-1140; ARG-1207 AND LEU-1243; Diagnostic challenges of Wilson's disease presenting as acute pancreatitis, cholangitis, and jaundice.
Nussinson E.; Shahbari A.; Shibli F.; Chervinsky E.; Trougouboff P.; Markel A.;
World J. Hepatol. 5:649-653(2013)
Cited for: VARIANT ALA-1140;

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.