UniProtKB/Swiss-Prot Q14654: Variant p.Arg201His

ATP-sensitive inward rectifier potassium channel 11
Gene: KCNJ11
Chromosomal location: 11p15.1
Variant information

Variant position:  201
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Arginine (R) to Histidine (H) at position 201 (R201H, p.Arg201His).
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 (H)
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

Variant description:  In PNDM; ability of ATP to block mutant channels greatly reduced.
Any additional useful information about the variant.



Sequence information

Variant position:  201
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  390
The length of the canonical sequence.

Location on the sequence:   LIFSKHAVIALRHGRLCFML  R VGDLRKSMIISATIHMQVVR
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                         LIFSKHAVIALRHGRLCFMLRVGDLRKSMIISATIHMQVVR

Mouse                         LIFSKHAVITLRHGRLCFMLRVGDLRKSMIISATIHMQVVR

Rat                           LIFSKHAVITLRHGRLCFMLRVGDLRKSMIISATIHMQVVR

Rabbit                        LIFSKHAVIALRQGRLCFMLRVGDLRKSMIISATIHMQVVR

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 – 390 ATP-sensitive inward rectifier potassium channel 11
Topological domain 167 – 390 Cytoplasmic


Literature citations

Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy.
Sagen J.V.; Raeder H.; Hathout E.; Shehadeh N.; Gudmundsson K.; Baevre H.; Abuelo D.; Phornphutkul C.; Molnes J.; Bell G.I.; Gloyn A.L.; Hattersley A.T.; Molven A.; Soevik O.; Njoelstad P.R.;
Diabetes 53:2713-2718(2004)
Cited for: VARIANTS PNDM VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333;

Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients.
Vaxillaire M.; Populaire C.; Busiah K.; Cave H.; Gloyn A.L.; Hattersley A.T.; Czernichow P.; Froguel P.; Polak M.;
Diabetes 53:2719-2722(2004)
Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330;

Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes.
Gloyn A.L.; Pearson E.R.; Antcliff J.F.; Proks P.; Bruining G.J.; Slingerland A.S.; Howard N.; Srinivasan S.; Silva J.M.C.L.; Molnes J.; Edghill E.L.; Frayling T.M.; Temple I.K.; Mackay D.; Shield J.P.H.; Sumnik Z.; van Rhijn A.; Wales J.K.H.; Clark P.; Gorman S.; Aisenberg J.; Ellard S.; Njoelstad P.R.; Ashcroft F.M.; Hattersley A.T.;
N. Engl. J. Med. 350:1838-1849(2004)
Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296; CHARACTERIZATION OF VARIANT PNDM HIS-201;

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 PNDM 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 PNDM 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.