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UniProtKB/Swiss-Prot Q14654: Variant p.Arg201Cys

ATP-sensitive inward rectifier potassium channel 11
Gene: KCNJ11
Variant information

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

Type of variant:  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:  From Arginine (R) to Cysteine (C) at position 201 (R201C, p.Arg201Cys).
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 (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 PNDM2; with neurologic features; produces smaller current and less change in ATP sensitivity than mutations associated with severe disease R-52 and G-59.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for 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.

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.





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.

Chain 1 – 390 ATP-sensitive inward rectifier potassium channel 11
Topological domain 167 – 390 Cytoplasmic

Literature citations

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 PNDM2 LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330;

Permanent neonatal diabetes due to paternal germline mosaicism for an activating mutation of the KCNJ11 gene encoding the Kir6.2 subunit of the beta-cell potassium adenosine triphosphate channel.
Gloyn A.L.; Cummings E.A.; Edghill E.L.; Harries L.W.; Scott R.; Costa T.; Temple I.K.; Hattersley A.T.; Ellard S.;
J. Clin. Endocrinol. Metab. 89:3932-3935(2004)
Cited for: VARIANT PNDM2 CYS-201;

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)

Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features.
Proks P.; Antcliff J.F.; Lippiat J.; Gloyn A.L.; Hattersley A.T.; Ashcroft F.M.;
Proc. Natl. Acad. Sci. U.S.A. 101:17539-17544(2004)

KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes.
Massa O.; Iafusco D.; D'Amato E.; Gloyn A.L.; Hattersley A.T.; Pasquino B.; Tonini G.; Dammacco F.; Zanette G.; Meschi F.; Porzio O.; Bottazzo G.; Crino A.; Lorini R.; Cerutti F.; Vanelli M.; Barbetti F.;
Hum. Mutat. 25:22-27(2005)
Cited for: VARIANTS PNDM2 PRO-50; MET-59; ARG-170; ASN-170 AND CYS-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 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;

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.