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UniProtKB/Swiss-Prot Q09428: Variant p.Ile1511Ser

ATP-binding cassette sub-family C member 8
Gene: ABCC8
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

Involvement in disease:  Familial hyperinsulinemic hypoglycemia 1 (HHF1) [MIM:256450]: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. {ECO:0000269|PubMed:10202168, ECO:0000269|PubMed:10334322, ECO:0000269|PubMed:10615958, ECO:0000269|PubMed:11018078, ECO:0000269|PubMed:11226335, ECO:0000269|PubMed:11867634, ECO:0000269|PubMed:12364426, ECO:0000269|PubMed:12941782, ECO:0000269|PubMed:15562009, ECO:0000269|PubMed:15579781, ECO:0000269|PubMed:15807877, ECO:0000269|PubMed:16357843, ECO:0000269|PubMed:16429405, ECO:0000269|PubMed:24814349, ECO:0000269|PubMed:25720052, ECO:0000269|PubMed:8650576, ECO:0000269|PubMed:8751851, ECO:0000269|PubMed:8923011, ECO:0000269|PubMed:9618169, ECO:0000269|PubMed:9648840, ECO:0000269|PubMed:9769320}. 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 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.

TypePositionsDescription
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;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.