UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1153

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

Type of variant:

LP/P [Disclaimer]

The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Arginine (R) to Cysteine (C) at position 1153 (R1153C, p.Arg1153Cys).

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 (C)

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

Variant description:

In PFIC2; impairs taurocholate transport activity; significantly reduces protein expression; decreases cell surface protein expression; loss of ell membrane localization.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs72549395 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1153

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

Protein sequence length:

1321

The length of the canonical sequence.

Location on the sequence:

DQGKVMIDGHDSKKVNVQFL R SNIGIVSQEPVLFACSIMDN

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                         DQGKVMIDGHDSKKVNVQFLRSNIGIVSQEPVLFACSIMDN

Mouse                         DQGTVMIDGHDSKKVNVQFLRSNIGIVSQEPVLFDCSIMDN

Rat                           DQGTVMIDGHDSKKVNIQFLRSNIGIVSQEPVLFDCSIMDN

Rabbit                        DHGKVMIDGHDSRKVNIQFLRSNIGIVSQEPVLFACSIKDN

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 – 1321	Bile salt export pump
Topological domain	1033 – 1321	Cytoplasmic
Domain	1078 – 1316	ABC transporter 2

Literature citations

A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis.
Strautnieks S.S.; Bull L.N.; Knisely A.S.; Kocoshis S.A.; Dahl N.; Arnell H.; Sokal E.M.; Dahan K.; Childs S.; Ling V.; Tanner M.S.; Kagalwalla A.F.; Nemeth A.; Pawlowska J.; Baker A.; Mieli-Vergani G.; Freimer N.B.; Gardiner R.M.; Thompson R.J.;
Nat. Genet. 20:233-238(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS PFIC2 GLY-297; GLU-461; GLY-482; ARG-982; CYS-1153 AND GLN-1268;

Polymorphic variants in the human bile salt export pump (BSEP; ABCB11): functional characterization and interindividual variability.
Ho R.H.; Leake B.F.; Kilkenny D.M.; Meyer Zu Schwabedissen H.E.; Glaeser H.; Kroetz D.L.; Kim R.B.;
Pharmacogenet. Genomics 20:45-57(2010)
Cited for: VARIANTS LEU-56; VAL-206; ALA-444; HIS-558; SER-591; GLN-592; VAL-677 AND LYS-1186; CHARACTERIZATION OF VARIANTS LEU-56; VAL-206; ALA-444; HIS-558; SER-591; GLN-592; VAL-677 AND LYS-1186; VARIANT PFIC2 GLY-297; CHARACTERIZATION OF VARIANTS PFIC2 GLY-297; ARG-982 AND CYS-1153; FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95342: Variant p.Arg1153Cys