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UniProtKB/Swiss-Prot P21439: Variant p.Ile541Phe

Phosphatidylcholine translocator ABCB4
Gene: ABCB4
Chromosomal location: 7q21.1
Variant information

Variant position:  541
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 Isoleucine (I) to Phenylalanine (F) at position 541 (I541F, p.Ile541Phe).
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 (I) to large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Gallbladder disease 1 (GBD1) [MIM:600803]: One of the major digestive diseases. Gallstones composed of cholesterol (cholelithiasis) are the common manifestations in western countries. Most people with gallstones, however, remain asymptomatic through their lifetimes. {ECO:0000269|PubMed:11313316, ECO:0000269|PubMed:12891548, ECO:0000269|PubMed:22331132, ECO:0000269|PubMed:23533021, ECO:0000269|PubMed:24723470, ECO:0000269|PubMed:28012258, ECO:0000269|Ref.2}. 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.

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 and GBD1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  541
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:   KFDTLVGERGAQLSGGQKQR  I AIARALVRNPKILLLDEATS
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.

TypePositionsDescription
Chain 1 – 1286 Phosphatidylcholine translocator ABCB4
Topological domain 355 – 711 Cytoplasmic
Domain 394 – 630 ABC transporter 1


Literature citations

The wide spectrum of multidrug resistance 3 deficiency: from neonatal cholestasis to cirrhosis of adulthood.
Jacquemin E.; De Vree J.M.L.; Cresteil D.; Sokal E.M.; Sturm E.; Dumont M.; Scheffer G.L.; Paul M.; Burdelski M.; Bosma P.J.; Bernard O.; Hadchouel M.; Elferink R.P.;
Gastroenterology 120:1448-1458(2001)
Cited for: VARIANTS PFIC3 ARG-138; ILE-346; GLY-395; ALA-424; MET-425; PHE-541; ARG-556; GLY-564; SER-711 AND SER-983; VARIANT GLY-652;

Genotype-phenotype relationships in the low-phospholipid-associated cholelithiasis syndrome: a study of 156 consecutive patients.
Poupon R.; Rosmorduc O.; Boelle P.Y.; Chretien Y.; Corpechot C.; Chazouilleres O.; Housset C.; Barbu V.;
Hepatology 58:1105-1110(2013)
Cited for: VARIANTS GBD1 GLY-47; HIS-71; VAL-73; CYS-78; PHE-99; SER-124; SER-154; ILE-165; VAL-286; THR-301; PHE-320; GLY-406; SER-510; THR-511; LYS-513; ASP-528; PHE-541; HIS-545; HIS-549; THR-589; GLN-591; MET-593; LYS-647; LEU-726; LEU-729; VAL-975 AND TRP-1084; VARIANTS ALA-175; GLN-590; GLN-788 AND THR-934;

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.