UniProtKB/SwissProt variant VAR

Variant information

Variant position:

132

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 Phenylalanine (F) to Leucine (L) at position 132 (F132L, p.Phe132Leu).

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 aromatic (F) to medium size and hydrophobic (L)

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:

Diabetes mellitus, permanent neonatal (PNDM) [MIM:606176]: A rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy. {ECO:0000269|PubMed:16613899, ECO:0000269|PubMed:16885549, ECO:0000269|PubMed:17213273, ECO:0000269|PubMed:17668386}. 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 PNDM; with neurologic features; reduces the sensitivity of the K(ATP) channel to inhibition by MgATP; increases whole-cell K(ATP) current.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs80356637 [ dbSNP | Ensembl ]

Sequence information

Variant position:

132

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

Protein sequence length:

1581

The length of the canonical sequence.

Location on the sequence:

MAFMAAVTSVVYYHNIETSN F PKLLIALLVYWTLAFITKTI

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                         MAFMAAVTSVVYYHNIETSNFPKLLIALLVYWTLAFITKTI

Rat                           MAFMAAITSVVYYHNIETSNFPKLLIALLIYWTLAFITKTI

Slime mold                    LVYLEMKKGQSRSWEIR------------LYWVFAFFVATV

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 – 1581	ATP-binding cassette sub-family C member 8
Topological domain	123 – 134	Cytoplasmic
Alternative sequence	51 – 1581	Missing. In isoform 3.

Literature citations

A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes.
Proks P.; Arnold A.L.; Bruining J.; Girard C.; Flanagan S.E.; Larkin B.; Colclough K.; Hattersley A.T.; Ashcroft F.M.; Ellard S.;
Hum. Mol. Genet. 15:1793-1800(2006)
Cited for: VARIANT PNDM LEU-132; CHARACTERIZATION OF VARIANT PNDM LEU-132;

Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.
Ellard S.; Flanagan S.E.; Girard C.A.; Patch A.M.; Harries L.W.; Parrish A.; Edghill E.L.; Mackay D.J.; Proks P.; Shimomura K.; Haberland H.; Carson D.J.; Shield J.P.; Hattersley A.T.; Ashcroft F.M.;
Am. J. Hum. Genet. 81:375-382(2007)
Cited for: VARIANTS PNDM LEU-45; SER-72; ALA-86; GLY-86; LEU-132; VAL-132; SER-207; LYS-208; GLU-209; LYS-211; PRO-225; ILE-229; ASP-263; LYS-382; GLU-1184; LYS-1326; ARG-1400 AND LEU-1522; CHARACTERIZATION OF VARIANTS PNDM LEU-132; SER-207; ILE-229; GLU-1184 AND LEU-1522;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q09428: Variant p.Phe132Leu