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UniProtKB/Swiss-Prot P35670: Variant p.Arg969Gln

Copper-transporting ATPase 2
Gene: ATP7B
Variant information

Variant position:  969
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 Glutamine (Q) at position 969 (R969Q, p.Arg969Gln).
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 polar (Q)
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; decreased copper transport activity; increased ATPase activity; no effect on localization.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  969
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:   VVQRYFPNPNKHISQTEVII  R FAFQTSITVLCIACPCSLGL
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                         VVQRYFPNPNKHISQTEVIIRFAFQTSITVLCIACPCSLGL

Mouse                         VVQKYFPSPSKHISQTEVIIRFAFQTSITVLCIACPCSLGL

Rat                           IVQKYFPSPSKHISQTEVIIRFAFQTSITVLCIACPCSLGL

Sheep                         VVQKYFPAPSKGISQAEVVLRFAFQTSITVLCIACPCSLGL

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.

TypePositionsDescription
Chain 1 – 1465 Copper-transporting ATPase 2
Topological domain 943 – 972 Extracellular
Alternative sequence 234 – 1465 RPLSSANQNFNNSETLGHQGSHVVTLQLRIDGMHCKSCVLNIEENIGQLLGVQSIQVSLENKTAQVKYDPSCTSPVALQRAIEALPPGNFKVSLPDGAEGSGTDHRSSSSHSPGSPPRNQVQGTCSTTLIAIAGMTCASCVHSIEGMISQLEGVQQISVSLAEGTATVLYNPSVISPEELRAAIEDMGFEASVVSESCSTNPLGNHSAGNSMVQTTDGTPTSVQEVAPHTGRLPANHAPDILAKSPQSTRAVAPQKCFLQIKGMTCASCVSNIERNLQKEAGVLSVLVALMAGKAEIKYDPEVIQPLEIAQFIQDLGFEAAVMEDYAGSDGNIELTITGMTCASCVHNIESKLTRTNGITYASVALATSKALVKFDPEIIGPRDIIKIIEEIGFHASLAQRNPNAHHLDHKMEIKQWKKSFLCSLVFGIPVMALMIYMLIPSNEPHQSMVLDHNIIPGLSILNLIFFILCTFVQLLGGWYFYVQAYKSLRHRSANMDVLIVLATSIAYVYSLVILVVAVAEKAERSPVTFFDTPPMLFVFIALGRWLEHLAKSKTSEALAKLMSLQATEATVVTLGEDNLIIREEQVPMELVQRGDIVKVVPGGKFPVDGKVLEGNTMADESLITGEAMPVTKKPGSTVIAGSINAHGSVLIKATHVGNDTTLAQIVKLVEEAQMSKAPIQQLADRFSGYFVPFIIIMSTLTLVVWIVIGFIDFGVVQRYFPNPNKHISQTEVIIRFAFQTSITVLCIACPCSLGLATPTAVMVGTGVAAQNGILIKGGKPLEMAHKIKTVMFDKTGTITHGVPRVMRVLLLGDVATLPLRKVLAVVGTAEASSEHPLGVAVTKYCKEELGTETLGYCTDFQAVPGCGIGCKVSNVEGILAHSERPLSAPASHLNEAGSLPAEKDAVPQTFSVLIGNREWLRRNGLTISSDVSDAMTDHEMKGQTAILVAIDGVLCGMIAIADAVKQEAALAVHTLQSMGVDVVLITGDNRKTARAIATQVGINKVFAEVLPSHKVAKVQELQNKGKKVAMVGDGVNDSPALAQADMGVAIGTGTDVAIEAADVVLIRNDLLDVVASIHLSKRTVRRIRINLVLALIYNLVGIPIAAGVFMPIGIVLQPWMGSAAMAASSVSVVLSSLQLKCYKKPDLERYEAQAHGHMKPLTASQVSVHIGMDDRWRDSPRATPWDQVSYVSQVSLSSLTSDKPSRHSAAADDDGDKWSLLLNGRDEEQYI -> ETFIFC. In isoform 5.


Literature citations

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;

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;

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;

Mutation analysis in patients of Mediterranean descent with Wilson disease: identification of 19 novel mutations.
Loudianos G.; Dessi V.; Lovicu M.; Angius A.; Altuntas B.; Giacchino R.; Marazzi M.; Marcellini M.; Sartorelli M.R.; Sturniolo G.C.; Kocak N.; Yuce A.; Akar N.; Pirastu M.; Cao A.;
J. Med. Genet. 36:833-836(1999)
Cited for: VARIANTS WD SER-710; ARG-711; LEU-840; VAL-874; GLN-969; VAL-1003; TRP-1041; PRO-1041; GLU-1061; VAL-1063; GLY-1068; GLN-1069; GLU-1089; PHE-1104; HIS-1151; THR-1169; LYS-1173; VAL-1222; PHE-1262; VAL-1327; PHE-1363 AND MET-1434; VARIANTS ARG-1207 AND ILE-1297;

Delineation of the spectrum of Wilson disease mutations in the Greek population and the identification of six novel mutations.
Loudianos G.; Lovicu M.; Solinas P.; Kanavakis E.; Tzetis M.; Manolaki N.; Panagiotakaki E.; Karpathios T.; Cao A.;
Genet. Test. 4:399-402(2000)
Cited for: VARIANTS WD SER-486; GLY-778; MET-890; GLN-969; GLU-1061; GLN-1069; SER-1099 AND THR-1148;

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;

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 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;

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;

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.