UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1511

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 Isoleucine (I) to Serine (S) at position 1511 (I1511S, p.Ile1511Ser).

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 (I) to small size and polar (S)

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

Variant description:

In HHF1; no effect on cell membrane expression; no effect on traffic efficiency; dramatically reduced potassium channel response to activators such as MgADP or to diazoxide.

Any additional useful information about the variant.

Sequence information

Variant position:

1511

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:

LARAFVRKTSIFIMDEATAS I DMATENILQKVVMTAFADRT

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                         LARAFVRKTSIFIMDEATASIDMATENILQKVVMTAFADRT

Rat                           LARAFVRKTSIFIMDEATASIDMATENILQKVVMTAFADRT

Slime mold                    IGRALLKKANIIVLDEASSSIDIASDALIQETIRTKFADCT

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	1298 – 1581	Cytoplasmic
Domain	1344 – 1578	ABC transporter 2
Alternative sequence	51 – 1581	Missing. In isoform 3.

Literature citations

Monoallelic ABCC8 mutations are a common cause of diazoxide-unresponsive diffuse form of congenital hyperinsulinism.
Saint-Martin C.; Zhou Q.; Martin G.M.; Vaury C.; Leroy G.; Arnoux J.B.; de Lonlay P.; Shyng S.L.; Bellanne-Chantelot C.;
Clin. Genet. 87:448-454(2015)
Cited for: VARIANTS HHF1 MET-511; ASP-716; LYS-824; THR-889; PRO-890; PRO-1352; SER-1378; PHE-1386; TYR-1388; PRO-1389; VAL-1457; ILE-1480; GLU-1505 AND SER-1511; CHARACTERIZATION OF VARIANTS HHF1 MET-511; LYS-824; THR-889; PRO-890; SER-1378; VAL-1457; ILE-1480; GLU-1505 AND SER-1511; FUNCTION; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q09428: Variant p.Ile1511Ser