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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95255: Variant p.Val1298Phe

ATP-binding cassette sub-family C member 6
Gene: ABCC6
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Variant information Variant position: help 1298 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Valine (V) to Phenylalanine (F) at position 1298 (V1298F, p.Val1298Phe). 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: help Change from medium size and hydrophobic (V) to large size and aromatic (F) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In PXE; abolishes LTC4 and NEM-GS transport; does not affect plasma membrane localization; does not increase extracellular pyrophosphate levels. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 1298 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1503 The length of the canonical sequence.
Location on the sequence: help LPLAVQGVSFKIHAGEKVGI V GRTGAGKSSLASGLLRLQEA 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         LPLAVQGVSFKIHAGEKVGIVGRTGAGKSSLASGLLRLQEA

Mouse                         LPLAVQGVSLKIHAGEKVGIVGRTGAGKSSLAWGLLRLQEA

Rat                           LPMAVQGVSLKIHAGEKVGIVGRTGAGKSSLTWGLLRLQEA
Sequence annotation in neighborhood: help 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 – 1503 ATP-binding cassette sub-family C member 6
Topological domain 1220 – 1503 Cytoplasmic
Domain 1265 – 1499 ABC transporter 2
Modified residue 1286 – 1286 Phosphoserine
Alternative sequence 100 – 1503 Missing. In isoform 2.
Alternative sequence 872 – 1503 Missing. In isoform 3.
Beta strand 1294 – 1298



Literature citations
Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6).
Ilias A.; Urban Z.; Seidl T.L.; Le Saux O.; Sinko E.; Boyd C.D.; Sarkadi B.; Varadi A.;
J. Biol. Chem. 277:16860-16867(2002)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS PXE PHE-1298; ARG-1302 AND SER-1321; CATALYTIC ACTIVITY; COFACTOR; BIOPHYSICOCHEMICAL PROPERTIES; ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release.
Jansen R.S.; Kuecuekosmanoglu A.; de Haas M.; Sapthu S.; Otero J.A.; Hegman I.E.; Bergen A.A.; Gorgels T.G.; Borst P.; van de Wetering K.;
Proc. Natl. Acad. Sci. U.S.A. 110:20206-20211(2013)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT PXE PHE-1298; A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum.
Le Saux O.; Beck K.; Sachsinger C.; Silvestri C.; Treiber C.; Goering H.H.H.; Johnson E.W.; De Paepe A.; Pope F.M.; Pasquali-Ronchetti I.; Bercovitch L.; Terry S.; Boyd C.D.;
Am. J. Hum. Genet. 69:749-764(2001)
Cited for: VARIANTS PXE LYS-411; GLN-518; SER-568; PRO-673; GLN-765; PRO-1114; TRP-1121; PRO-1138; GLN-1138; ASP-1203; PHE-1298; ILE-1301; ARG-1302; PRO-1303; GLN-1314; TRP-1314; SER-1321; CYS-1339; HIS-1347; ASN-1361 AND THR-1424; VARIANTS ASP-61; ARG-207; GLY-265; GLU-281; VAL-319; LYS-497; ALA-614; GLN-632; HIS-953; CYS-1241 AND GLN-1268; Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum.
Pfendner E.G.; Vanakker O.M.; Terry S.F.; Vourthis S.; McAndrew P.E.; McClain M.R.; Fratta S.; Marais A.S.; Hariri S.; Coucke P.J.; Ramsay M.; Viljoen D.; Terry P.F.; De Paepe A.; Uitto J.; Bercovitch L.G.;
J. Med. Genet. 44:621-628(2007)
Cited for: VARIANTS PXE 60-ARG--TYR-62 DEL; ARG-317; ARG-364; TRP-382; GLY-391; ASN-392; HIS-463; HIS-495; GLN-518; PRO-535; SER-568; CYS-600; CYS-663; PRO-698; ASP-699; PRO-726; LYS-751; ARG-755; TRP-760; GLN-765; ASN-777; MET-811; SER-881; ILE-944; THR-950; ARG-992; CYS-1114; MET-1130; ALA-1133; GLN-1138; TRP-1138; THR-1139; GLN-1164; CYS-1221; HIS-1221; ILE-1226; PHE-1298; ARG-1302; PRO-1303; GLN-1314; TRP-1314; GLN-1335; CYS-1339; HIS-1339 AND THR-1342;
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.