UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1226

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 Leucine (L) to Isoleucine (I) at position 1226 (L1226I, p.Leu1226Ile).

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:

Similar physico-chemical property. Both residues are medium size and hydrophobic.

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

2

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.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs63750125 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1226

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

Protein sequence length:

1503

The length of the canonical sequence.

Location on the sequence:

VSAALQVTQTLQWVVRNWTD L ENSIVSVERMQDYAWTPKEA

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                         VSAALQVTQTLQWVVRNWTDLENSIVSVERMQDYAWTPKEA

Mouse                         VSAALQVTQTLQWVVRSWTDLENSMVAVERVQDYARIPKEA

Rat                           VSAALQVTQTLQWVVRSWTDLENSMVAVERVQDYVHTPKEA

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 – 1503	Multidrug resistance-associated protein 6
Topological domain	1220 – 1503	Cytoplasmic
Domain	947 – 1228	ABC transmembrane type-1 2
Alternative sequence	100 – 1503	Missing. In isoform 2.
Alternative sequence	872 – 1503	Missing. In isoform 3.

Literature citations

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95255: Variant p.Leu1226Ile