UniProtKB/SwissProt variant VAR

Variant information

Variant position:

766

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 Alanine (A) to Aspartate (D) at position 766 (A766D, p.Ala766Asp).

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 small size and hydrophobic (A) to medium size and acidic (D)

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

Variant description:

In PXE; autosomal recessive; affects protein expression and trafficking; expression is reduced to less than 10%, when compared with the WT protein.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs72653789 [ dbSNP | Ensembl ]

Sequence information

Variant position:

766

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:

IGEQGMNLSGGQKQRLSLAR A VYRKAAVYLLDDPLAALDAH

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                         IGEQGMNLSGGQKQRLSLARAVYRKAAVYLLDDPLAALDAH

Mouse                         IGEQGMNLSGGQKQRLSLARAVYKKAAIYLLDDPLAALDAH

Rat                           VGEQGMNLSGGQKQRLSLARAVYRRAAVYLMDDPLAALDAH

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	ATP-binding cassette sub-family C member 6
Topological domain	597 – 939	Cytoplasmic
Domain	629 – 853	ABC transporter 1
Alternative sequence	100 – 1503	Missing. In isoform 2.
Helix	755 – 768

Literature citations

Novel ABCC6 mutations in pseudoxanthoma elasticum.
Chassaing N.; Martin L.; Mazereeuw J.; Barrie L.; Nizard S.; Bonafe J.L.; Calvas P.; Hovnanian A.;
J. Invest. Dermatol. 122:608-613(2004)
Cited for: VARIANTS PXE VAL-74 DEL; 363-GLN--ARG-373 DEL; GLY-391; GLN-518; ASP-766; MET-1130; GLN-1138 HIS-1238; PRO-1335 AND LYS-1400;

Structural analysis reveals pathomechanisms associated with pseudoxanthoma elasticum-causing mutations in the ABCC6 transporter.
Ran Y.; Zheng A.; Thibodeau P.H.;
J. Biol. Chem. 293:15855-15866(2018)
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 622-859; CHARACTERIZATION OF VARIANTS PXE CYS-663; PRO-673; PRO-677; PRO-698; ASP-699; PRO-726; ARG-755; TRP-760; GLN-765; ASP-766; ASN-777; MET-811 AND PRO-820; GLYCOSYLATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95255: Variant p.Ala766Asp