UniProtKB/SwissProt variant VAR

Variant information

Variant position:

403

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 Tyrosine (Y) to Histidine (H) at position 403 (Y403H, p.Tyr403His).

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 large size and aromatic (Y) to medium size and polar (H)

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 PFIC3; does not alter cytoplasmic and cell membrane location; inhibits efflux activity for PC and cholesterol.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121918443 [ dbSNP | Ensembl ]

Sequence information

Variant position:

403

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:

RGHKPDSIKGNLEFNDVHFS Y PSRANVKILKGLNLKVQSGQ

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

Literature citations

Molecular characterization and structural implications of 25 new ABCB4 mutations in progressive familial intrahepatic cholestasis type 3 (PFIC3).
Degiorgio D.; Colombo C.; Seia M.; Porcaro L.; Costantino L.; Zazzeron L.; Bordo D.; Coviello D.A.;
Eur. J. Hum. Genet. 15:1230-1238(2007)
Cited for: VARIANTS PFIC3 GLU-126; PRO-250; VAL-286; PHE-320; LEU-357; VAL-364; HIS-403; ALA-475; THR-511; LYS-558; ALA-593; VAL-630; PRO-701; ILE-715; GLU-723; THR-726; VAL-737; ASP-840; SER-954 AND THR-1193; VARIANTS ALA-175; GLN-590 AND MET-775;

Clinical features and genotype-phenotype correlations in children with progressive familial intrahepatic cholestasis type 3 related to ABCB4 mutations.
Colombo C.; Vajro P.; Degiorgio D.; Coviello D.A.; Costantino L.; Tornillo L.; Motta V.; Consonni D.; Maggiore G.; Balli F.; Berardi S.; Calacoci M.; Castellano E.; Marazzi M.G.; Gaslini G.; D'Antiga L.; Ferretti E.; Giannini A.; Indolfi G.; Iorio R.; Martelossi S.; Moretti C.; Nebbia G.; Oliveri F.; Poggiani C.; Raggi M.; Riva S.; Sciveres M.; Torre G.; Zancan L.;
J. Pediatr. Gastroenterol. Nutr. 52:73-83(2011)
Cited for: VARIANTS PFIC3 ARG-70; VAL-73; PHE-320 AND HIS-403; VARIANT GLY-652;

Two ABCB4 point mutations of strategic NBD-motifs do not prevent protein targeting to the plasma membrane but promote MDR3 dysfunction.
Degiorgio D.; Corsetto P.A.; Rizzo A.M.; Colombo C.; Seia M.; Costantino L.; Montorfano G.; Tomaiuolo R.; Bordo D.; Sansanelli S.; Li M.; Tavian D.; Rastaldi M.P.; Coviello D.A.;
Eur. J. Hum. Genet. 22:633-639(2014)
Cited for: VARIANT PFIC3 ARG-481; CHARACTERIZATION OF VARIANTS PFIC3 HIS-403 AND ARG-481; FUNCTION; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P21439: Variant p.Tyr403His