UniProtKB/SwissProt variant VAR

Variant information

Variant position:

535

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 Glycine (G) to Aspartate (D) at position 535 (G535D, p.Gly535Asp).

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 glycine (G) to medium size and acidic (D)

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:

Cholestasis, progressive familial intrahepatic, 3 (PFIC3) [MIM:602347]: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. {ECO:0000269|PubMed:11313315, ECO:0000269|PubMed:12671900, ECO:0000269|PubMed:17726488, ECO:0000269|PubMed:21119540, ECO:0000269|PubMed:24045840, ECO:0000269|PubMed:24594635, ECO:0000269|PubMed:24806754, ECO:0000269|PubMed:28012258, ECO:0000269|PubMed:9419367}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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 PFIC3; reduced phosphatidylcholine transporter activity; does not alter plasma membrane location.

Any additional useful information about the variant.

Sequence information

Variant position:

535

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

Protein sequence length:

1286

The length of the canonical sequence.

Location on the sequence:

IMKLPQKFDTLVGERGAQLS G GQKQRIAIARALVRNPKILL

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.

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 – 1286	Phosphatidylcholine translocator ABCB4
Topological domain	355 – 711	Cytoplasmic
Domain	394 – 630	ABC transporter 1
Helix	535 – 547

Literature citations

A multidrug resistance 3 gene mutation causing cholelithiasis, cholestasis of pregnancy, and adulthood biliary cirrhosis.
Lucena J.-F.; Herrero J.I.; Quiroga J.; Sangro B.; Garcia-Foncillas J.; Zabalegui N.; Sola J.; Herraiz M.; Medina J.F.; Prieto J.;
Gastroenterology 124:1037-1042(2003)
Cited for: VARIANT PFIC3 ASP-535;

Functional defect of variants in the adenosine triphosphate-binding sites of ABCB4 and their rescue by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770).
Delaunay J.L.; Bruneau A.; Hoffmann B.; Durand-Schneider A.M.; Barbu V.; Jacquemin E.; Maurice M.; Housset C.; Callebaut I.; Ait-Slimane T.;
Hepatology 65:560-570(2017)
Cited for: CHARACTERIZATION OF VARIANTS GBD1 ARG-536; LEU-726; LEU-1183 AND SER-1185; CHARACTERIZATION OF VARIANT PFIC3 ASP-535; SUBCELLULAR LOCATION; FUNCTION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P21439: Variant p.Gly535Asp