UniProtKB/SwissProt variant VAR

Variant information

Variant position:

768

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 Tryptophan (W) at position 768 (R768W, p.Arg768Trp).

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 large size and aromatic (W)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-3

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:

Dubin-Johnson syndrome (DJS) [MIM:237500]: Autosomal recessive disorder characterized by conjugated hyperbilirubinemia, an increase in the urinary excretion of coproporphyrin isomer I, deposition of melanin-like pigment in hepatocytes, and prolonged retention of sulfobromophthalein, but otherwise normal liver function. {ECO:0000269|PubMed:10053008, ECO:0000269|PubMed:10464142, ECO:0000269|PubMed:11093739, ECO:0000269|PubMed:11266082, ECO:0000269|PubMed:11477083, ECO:0000269|PubMed:22290738, ECO:0000269|PubMed:25336012, ECO:0000269|PubMed:9425227}. 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 DJS.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs56199535 [ dbSNP | Ensembl ]

Sequence information

Variant position:

768

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

Protein sequence length:

1545

The length of the canonical sequence.

Location on the sequence:

GGDLAEIGEKGINLSGGQKQ R ISLARATYQNLDIYLLDDPL

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 – 1545	Canalicular multispecific organic anion transporter 1
Topological domain	609 – 971	Cytoplasmic
Domain	637 – 861	ABC transporter 1

Literature citations

Mutations in the canalicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome.
Wada M.; Toh S.; Taniguchi K.; Nakamura T.; Uchiumi T.; Kohno K.; Yoshida I.; Kimura A.; Sakisaka S.; Adachi Y.; Kuwano M.;
Hum. Mol. Genet. 7:203-207(1998)
Cited for: VARIANT DJS TRP-768;

Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome.
Toh S.; Wada M.; Uchiumi T.; Inokuchi A.; Makino Y.; Horie Y.; Adachi Y.; Sakisaka S.; Kuwano M.;
Am. J. Hum. Genet. 64:739-746(1999)
Cited for: VARIANTS DJS TRP-768 AND ARG-1382;

Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects.
Ito S.; Ieiri I.; Tanabe M.; Suzuki A.; Higuchi S.; Otsubo K.;
Pharmacogenetics 11:175-184(2001)
Cited for: VARIANT DJS TRP-768; VARIANTS ILE-417; PHE-789 AND THR-1450;

Neonatal Dubin-Johnson syndrome: novel compound heterozygous mutation in the ABCC2 gene.
Okada H.; Kusaka T.; Fuke N.; Kunikata J.; Kondo S.; Iwase T.; Nan W.; Hirota T.; Ieiri I.; Itoh S.;
Pediatr. Int. 56:E62-E62(2014)
Cited for: VARIANT DJS TRP-768; VARIANT ILE-417;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q92887: Variant p.Arg768Trp