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UniProtKB/Swiss-Prot Q9H221: Variant p.Leu596Arg

ATP-binding cassette sub-family G member 8
Gene: ABCG8
Variant information

Variant position:  596
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 Arginine (R) at position 596 (L596R, p.Leu596Arg).
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 (L) to large size and basic (R)
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:  Sitosterolemia (STSL) [MIM:210250]: Rare autosomal recessive disorder characterized by increased intestinal absorption of all sterols including cholesterol, plant and shellfish sterols, and decreased biliary excretion of dietary sterols into bile. Sitosterolemia patients have hypercholesterolemia, very high levels of plant sterols in the plasma, and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease. {ECO:0000269|PubMed:11099417, ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:15054092}. 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 STSL; strongly decreased maturation of glycan chains.
Any additional useful information about the variant.

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



Sequence information

Variant position:  596
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  673
The length of the canonical sequence.

Location on the sequence:   FMINLSSLWTVPAWISKVSF  L RWCFEGLMKIQFSRRTYKMP
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                         FMINLSSLWTVPAWISKVSFLRWCFEGLMKIQFSRRTYKMP

Mouse                         FMINLDNLWIVPAWISKLSFLRWCFSGLMQIQFNGHLYTTQ

Rat                           FMINLNNLWIVPAWISKMSFLRWCFSGLMQIQFNGHIYTTQ

Slime mold                    FYVPTNELPRAFGWLHWVNPAFYGYSSVVINQFEDLQLKCT

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 – 673 ATP-binding cassette sub-family G member 8
Topological domain 577 – 639 Extracellular
Domain 411 – 665 ABC transmembrane type-2


Literature citations

Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.
Berge K.E.; Tian H.; Graf G.A.; Yu L.; Grishin N.V.; Schultz J.; Kwiterovich P.; Shan B.; Barnes R.; Hobbs H.H.;
Science 290:1771-1775(2000)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); FUNCTION; VARIANTS STSL THR-231; GLN-263; ARG-574 AND ARG-596; VARIANT CYS-54;

Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively.
Lu K.; Lee M.-H.; Hazard S.; Brooks-Wilson A.; Hidaka H.; Kojima H.; Ose L.; Stalenhoef A.F.H.; Mietinnen T.; Bjorkhem I.; Bruckert E.; Pandya A.; Brewer H.B. Jr.; Salen G.; Dean M.; Srivastava A.K.; Patel S.B.;
Am. J. Hum. Genet. 69:278-290(2001)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2); FUNCTION; TISSUE SPECIFICITY; VARIANTS STSL HIS-184; THR-231; LYS-238; GLN-263; HIS-405; PRO-501; SER-543; PHE-570 DEL; PRO-572; ARG-574; GLU-574 AND ARG-596; VARIANTS HIS-19; CYS-54; VAL-259; LYS-400; ARG-575 AND ALA-632;

Missense mutations in ABCG5 and ABCG8 disrupt heterodimerization and trafficking.
Graf G.A.; Cohen J.C.; Hobbs H.H.;
J. Biol. Chem. 279:24881-24888(2004)
Cited for: CHARACTERIZATION OF VARIANTS STSL HIS-184; THR-231; GLN-263; PRO-501; SER-543; GLU-574 AND ARG-596; FUNCTION;

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.