Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q14654: Variant p.His46Tyr

ATP-sensitive inward rectifier potassium channel 11
Gene: KCNJ11
Feedback?
Variant information Variant position: help 46 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Histidine (H) to Tyrosine (Y) at position 46 (H46Y, p.His46Tyr). 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: help Change from medium size and polar (H) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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: help In PNDM2. Any additional useful information about the variant.


Sequence information Variant position: help 46 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 390 The length of the canonical sequence.
Location on the sequence: help YRARQRRARFVSKKGNCNVA H KNIREQGRFLQDVFTTLVDL 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         YRARQRRARFVSKKGNCNVAHKNIREQGRFLQDVFTTLVDL

Mouse                         YRTRERRARFVSKKGNCNVAHKNIREQGRFLQDVFTTLVDL

Rat                           YRTRERRARFVSKKGNCNVAHKNIREQGRFLQDVFTTLVDL

Rabbit                        YRARERRARFVSKKGNCNVAHKNIREQGRFLQDVFTTLVDL
Sequence annotation in neighborhood: help 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 – 390 ATP-sensitive inward rectifier potassium channel 11
Topological domain 1 – 68 Cytoplasmic
Alternative sequence 1 – 87 Missing. In isoform 2.
Mutagenesis 64 – 64 V -> M. Displays gain of function; increased open state stability, reduced ATP sensitivity and increased channel activity; almost completely abolishes high affinity sensitivity to glibenclamide, an inhibitor of ATP-sensitive potassium channels.



Literature citations
Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype.
Flanagan S.E.; Edghill E.L.; Gloyn A.L.; Ellard S.; Hattersley A.T.;
Diabetologia 49:1190-1197(2006)
Cited for: VARIANTS PNDM2 TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330; Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers.
Stanik J.; Gasperikova D.; Paskova M.; Barak L.; Javorkova J.; Jancova E.; Ciljakova M.; Hlava P.; Michalek J.; Flanagan S.E.; Pearson E.; Hattersley A.T.; Ellard S.; Klimes I.;
J. Clin. Endocrinol. Metab. 92:1276-1282(2007)
Cited for: VARIANTS PNDM2 TYR-46; PRO-164 AND HIS-201;
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.