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UniProtKB/Swiss-Prot O95255: Variant p.Pro1346Ser

Multidrug resistance-associated protein 6
Gene: ABCC6
Variant information

Variant position:  1346
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Proline (P) to Serine (S) at position 1346 (P1346S, p.Pro1346Ser).
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 (P) 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

Involvement in disease:  Pseudoxanthoma elasticum (PXE) [MIM:264800]: A multisystem disorder characterized by accumulation of mineralized and fragmented elastic fibers in the skin, vascular walls, and Burch membrane in the eye. Clinically, patients exhibit characteristic lesions of the posterior segment of the eye including peau d'orange, angioid streaks, and choroidal neovascularizations, of the skin including soft, ivory colored papules in a reticular pattern that predominantly affect the neck and large flexor surfaces, and of the cardiovascular system with peripheral and coronary arterial occlusive disease as well as gastrointestinal bleedings. {ECO:0000269|PubMed:10811882, ECO:0000269|PubMed:10835642, ECO:0000269|PubMed:10954200, ECO:0000269|PubMed:11427982, ECO:0000269|PubMed:11536079, ECO:0000269|PubMed:11702217, ECO:0000269|PubMed:11880368, ECO:0000269|PubMed:15086542, ECO:0000269|PubMed:15098239, ECO:0000269|PubMed:15459974, ECO:0000269|PubMed:16086317, ECO:0000269|PubMed:17617515, ECO:0000269|PubMed:19339160, ECO:0000269|PubMed:20034067, ECO:0000269|PubMed:25615550}. Note=The disease is caused by mutations affecting the gene represented in this entry. Homozygous or compound heterozygous ABCC6 mutations have been found in the overwhelming majority of cases. Individuals carrying heterozygous mutations express limited manifestations of the pseudoxanthoma elasticum phenotype.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PXE; autosomal recessive.
Any additional useful information about the variant.

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

Sequence information

Variant position:  1346
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1503
The length of the canonical sequence.

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.




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.

Chain 1 – 1503 Multidrug resistance-associated protein 6
Topological domain 1220 – 1503 Cytoplasmic
Domain 1265 – 1499 ABC transporter 2
Alternative sequence 100 – 1503 Missing. In isoform 2.
Alternative sequence 872 – 1503 Missing. In isoform 3.

Literature citations

ABCC6 mutations in Italian families affected by pseudoxanthoma elasticum (PXE).
Gheduzzi D.; Guidetti R.; Anzivino C.; Tarugi P.; Di Leo E.; Quaglino D.; Ronchetti I.P.;
Hum. Mutat. 24:438-439(2004)
Cited for: VARIANTS PXE ARG-364; LYS-411; GLY-440; GLN-518; CYS-600; MET-810; PRO-820; CYS-1114; MET-1130; GLN-1138; CYS-1339; SER-1346 AND LYS-1400;

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.