UniProtKB/SwissProt variant VAR

Variant information

Variant position:

419

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 Arginine (R) to Histidine (H) at position 419 (R419H, p.Arg419His).

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 basic (R) to medium size and polar (H)

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:

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:11138003, ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:11668628, 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; loss of normal maturation of glycan chains.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs119479067 [ dbSNP | Ensembl ]

Sequence information

Variant position:

419

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

Protein sequence length:

651

The length of the canonical sequence.

Location on the sequence:

FLLFFVLRVRSNVLKGAIQD R VGLLYQFVGATPYTGMLNAV

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                         FLLFF------------------------------------------------VLRV-------------------------------RSNVLKGAIQD----------------------------------------------------------------------------------------------RVGLLYQFVGAT--------------------------------------------------------------------------------------------------------------------------------PYTGM--------LNAV

Mouse                         FLIFY------------------------------------

Rat                           FLIFY------------------------------------

Slime mold                    YIVFFYSVCFFALKYLNFEDKKSKLAVKKLKKKKKVIVCKE

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 – 651	ATP-binding cassette sub-family G member 5
Topological domain	405 – 421	Extracellular
Domain	388 – 645	ABC transmembrane type-2
Mutagenesis	432 – 432	Y -> A. Strongly decreases cholesterol secretion into bile.

Literature citations

Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption.
Lee M.-H.; Lu K.; Hazard S.; Yu H.; Shulenin S.; Hidaka H.; Kojima H.; Allikmets R.; Sakuma N.; Pegoraro R.; Srivastava A.K.; Salen G.; Dean M.; Patel S.B.;
Nat. Genet. 27:79-83(2001)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS STSL HIS-389; HIS-419 AND PRO-419; VARIANT GLU-604; FUNCTION; TISSUE SPECIFICITY;

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 [MRNA] OF 1-88 (ISOFORM 1); VARIANTS STSL GLN-146; HIS-389; PRO-419; HIS-419 AND SER-550; VARIANT GLU-604;

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 GLN-146; HIS-389; PRO-419; HIS-419 AND LYS-437; FUNCTION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9H222: Variant p.Arg419His