UniProtKB/Swiss-Prot P35670: Variant p.Asn1270Ser

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

1270 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 Asparagine (N) to Serine (S) at position 1270 (N1270S, p.Asn1270Ser). 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 polar (N) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 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; loss of copper transport activity; increased ATPase activity; does not affect localization to late endosomes. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121907990 [ dbSNP | Ensembl ]

Sequence information Variant position:

1270 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:

AKVQELQNKGKKVAMVGDGV N DSPALAQADMGVAIGTGTDV 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                         AKVQELQNKGKKVAMVGDGVNDSPALAQADMGVAIGTGTDV

Mouse                         AKVQELQNEGKKVAMVGDGVNDSPALAQADVGIAIGTGTDV

Rat                           AKVQELQNKGKKVAMVGDGVNDSPALAQADVGIAIGTGTDV

Sheep                         AKVQELQNQGKRVAMVGDGVNDSPALAQADVGIAIGTGTDV

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
Binding site	1267 – 1267
Binding site	1271 – 1271
Alternative sequence	234 – 1465	RPLSSANQNFNNSETLGHQGSHVVTLQLRIDGMHCKSCVLNIEENIGQLLGVQSIQVSLENKTAQVKYDPSCTSPVALQRAIEALPPGNFKVSLPDGAEGSGTDHRSSSSHSPGSPPRNQVQGTCSTTLIAIAGMTCASCVHSIEGMISQLEGVQQISVSLAEGTATVLYNPSVISPEELRAAIEDMGFEASVVSESCSTNPLGNHSAGNSMVQTTDGTPTSVQEVAPHTGRLPANHAPDILAKSPQSTRAVAPQKCFLQIKGMTCASCVSNIERNLQKEAGVLSVLVALMAGKAEIKYDPEVIQPLEIAQFIQDLGFEAAVMEDYAGSDGNIELTITGMTCASCVHNIESKLTRTNGITYASVALATSKALVKFDPEIIGPRDIIKIIEEIGFHASLAQRNPNAHHLDHKMEIKQWKKSFLCSLVFGIPVMALMIYMLIPSNEPHQSMVLDHNIIPGLSILNLIFFILCTFVQLLGGWYFYVQAYKSLRHRSANMDVLIVLATSIAYVYSLVILVVAVAEKAERSPVTFFDTPPMLFVFIALGRWLEHLAKSKTSEALAKLMSLQATEATVVTLGEDNLIIREEQVPMELVQRGDIVKVVPGGKFPVDGKVLEGNTMADESLITGEAMPVTKKPGSTVIAGSINAHGSVLIKATHVGNDTTLAQIVKLVEEAQMSKAPIQQLADRFSGYFVPFIIIMSTLTLVVWIVIGFIDFGVVQRYFPNPNKHISQTEVIIRFAFQTSITVLCIACPCSLGLATPTAVMVGTGVAAQNGILIKGGKPLEMAHKIKTVMFDKTGTITHGVPRVMRVLLLGDVATLPLRKVLAVVGTAEASSEHPLGVAVTKYCKEELGTETLGYCTDFQAVPGCGIGCKVSNVEGILAHSERPLSAPASHLNEAGSLPAEKDAVPQTFSVLIGNREWLRRNGLTISSDVSDAMTDHEMKGQTAILVAIDGVLCGMIAIADAVKQEAALAVHTLQSMGVDVVLITGDNRKTARAIATQVGINKVFAEVLPSHKVAKVQELQNKGKKVAMVGDGVNDSPALAQADMGVAIGTGTDVAIEAADVVLIRNDLLDVVASIHLSKRTVRRIRINLVLALIYNLVGIPIAAGVFMPIGIVLQPWMGSAAMAASSVSVVLSSLQLKCYKKPDLERYEAQAHGHMKPLTASQVSVHIGMDDRWRDSPRATPWDQVSYVSQVSLSSLTSDKPSRHSAAADDDGDKWSLLLNGRDEEQYI -> ETFIFC. In isoform 5.
Helix	1269 – 1271

Literature citations
The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.
Tanzi R.E.; Petrukhin K.; Chernov I.; Pellequer J.L.; Wasco W.; Ross B.; Romano D.M.; Parano E.; Pavone L.; Brzustowicz L.M.; Devoto M.; Peppercorn J.; Bush A.I.; Sternlieb I.; Pirastu M.; Gusella J.F.; Evgrafov O.; Penchaszadeh G.K.; Honig B.; Edelman I.S.; Soares M.B.; Scheinberg I.H.; Gilliam T.C.;
Nat. Genet. 5:344-350(1993)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 149-1465 (ISOFORM 2); VARIANTS WD GLN-1069 AND SER-1270; VARIANT ARG-875; A mutation of the Wilson disease protein, ATP7B, is degraded in the proteasomes and forms protein aggregates.
Harada M.; Sakisaka S.; Terada K.; Kimura R.; Kawaguchi T.; Koga H.; Kim M.; Taniguchi E.; Hanada S.; Suganuma T.; Furuta K.; Sugiyama T.; Sata M.;
Gastroenterology 120:967-974(2001)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS WD GLN-1069 AND SER-1270; 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; Diverse functional properties of Wilson disease ATP7B variants.
Huster D.; Kuehne A.; Bhattacharjee A.; Raines L.; Jantsch V.; Noe J.; Schirrmeister W.; Sommerer I.; Sabri O.; Berr F.; Moessner J.; Stieger B.; Caca K.; Lutsenko S.;
Gastroenterology 142:947-956(2012)
Cited for: CHARACTERIZATION OF VARIANTS WD VAL-85; SER-492; TRP-616; ALA-626; ARG-645; SER-710; LEU-760; ASN-765; VAL-769; LEU-840; THR-857; VAL-874; GLN-969; LEU-992; LEU-1052; LYS-1064; GLN-1069; PHE-1083; VAL-1213; VAL-1222; ARG-1266; SER-1270 AND LEU-1273; CHARACTERIZATION OF VARIANTS ALA-406; LEU-456 AND ARG-832; MUTAGENESIS OF ASP-1027 AND THR-1031; FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; A genetic study of Wilson's disease in the United Kingdom.
Coffey A.J.; Durkie M.; Hague S.; McLay K.; Emmerson J.; Lo C.; Klaffke S.; Joyce C.J.; Dhawan A.; Hadzic N.; Mieli-Vergani G.; Kirk R.; Elizabeth Allen K.; Nicholl D.; Wong S.; Griffiths W.; Smithson S.; Giffin N.; Taha A.; Connolly S.; Gillett G.T.; Tanner S.; Bonham J.; Sharrack B.; Palotie A.; Rattray M.; Dalton A.; Bandmann O.;
Brain 136:1476-1487(2013)
Cited for: VARIANTS WD TRP-136; TRP-148; CYS-382; ALA-536; LYS-541; ILE-597; CYS-614; SER-641; ARG-645; ILE-665; ALA-731; PRO-745; VAL-769; TRP-778; ARG-869; TRP-919; VAL-936; MET-977; MET-991; ALA-995; ILE-1017; VAL-1021; TRP-1041; VAL-1058; GLN-1069; SER-1070; VAL-1074; GLY-1250; ARG-1266; SER-1270; ILE-1298; LEU-1298; TYR-1431 AND PHE-1432; 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; Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.
Figus A.; Angius A.; Loudianos G.; Bertini C.; Dessi V.; Loi A.; Deiana M.; Lovicu M.; Olla N.; Sole G.; de Virgiliis S.; Lilliu F.; Farci A.M.G.; Nurchi A.; Giacchino R.; Barabino A.; Marazzi M.; Zancan L.; Greggio N.A.; Macellini M.; Solinas A.; Deplano A.; Barbera C.; Devoto M.; Ozsoylu S.; Kocak N.; Akar N.; Karayalcin S.; Mokini V.; Cullufi P.; Balestrieri A.; Cao A.; Pirastu M.;
Am. J. Hum. Genet. 57:1318-1324(1995)
Cited for: VARIANTS WD ALA-626; ASN-765; GLY-778; THR-857; GLN-969; LYS-1064 AND SER-1270; Identification and analysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-phenotype correlation, and functional analyses.
Shah A.B.; Chernov I.; Zhang H.T.; Ross B.M.; Das K.; Lutsenko S.; Parano E.; Pavone L.; Evgrafov O.; Ivanova-Smolenskaya I.A.; Anneren G.; Westermark K.; Urrutia F.H.; Penchaszadeh G.K.; Sternlieb I.; Scheinberg I.H.; Gilliam T.C.; Petrukhin K.;
Am. J. Hum. Genet. 61:317-328(1997)
Cited for: VARIANTS WD ALA-626; ARG-645; PRO-708; SER-710; TRP-778; PHE-795; ARG-869; VAL-1035; ALA-1064; GLN-1069; CYS-1186; TYR-1222; VAL-1266; SER-1270; PRO-1322 AND ARG-1353; 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; 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; High prevalence of the H1069Q mutation in East German patients with Wilson disease: rapid detection of mutations by limited sequencing and phenotype-genotype analysis.
Caca K.; Ferenci P.; Kuehn H.-J.; Polli C.; Willgerodt H.; Kunath B.; Hermann W.; Moessner J.; Berr F.;
J. Hepatol. 35:575-581(2001)
Cited for: VARIANTS WD TRP-616; ALA-710; SER-710; LEU-760; ASN-765; VAL-769; GLN-969; LEU-992; GLN-1069 AND SER-1270; VARIANTS ALA-406; LEU-456 AND ARG-832; 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; Spectrum of mutations in the Wilson disease gene (ATP7B) in the Bulgarian population.
Todorov T.; Savov A.; Jelev H.; Panteleeva E.; Konstantinova D.; Krustev Z.; Mihaylova V.; Tournev I.; Tankova L.; Tzolova N.; Kremensky I.;
Clin. Genet. 68:474-476(2005)
Cited for: VARIANTS WD GLN-616; ALA-626; TRP-778; GLY-778; VAL-874; GLN-969; THR-1003; GLN-1069; 1217-VAL-LEU-1218 DEL; SER-1270; TYR-1279; ASP-1341; SER-1352 AND PRO-1368; 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; Spectrum of mutations in the ATP binding domain of ATP7B gene of Wilson Disease in a regional Indian cohort.
Guggilla S.R.; Senagari J.R.; Rao P.N.; Madireddi S.;
Gene 569:83-87(2015)
Cited for: VARIANTS WD PRO-990; VAL-1003; ARG-1010; TRP-1041; PRO-1043; GLU-1061; ARG-1101; SER-1104; MET-1113; SER-1270 AND LYS-1293;

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.