Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q15842: Variant p.Val65Met

ATP-sensitive inward rectifier potassium channel 8
Gene: KCNJ8
Feedback?
Variant information Variant position: help 65 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help US 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 Valine (V) to Methionine (M) at position 65 (V65M, p.Val65Met). 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 Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 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 HTOCD; uncertain significance; displays gain of function; increased open state stability, reduced sensitivity to ATP inhibition and increased channel activity; almost completely abolishes high affinity sensitivity to glibenclamide, an inhibitor of ATP-sensitive potassium channels. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 65 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 424 The length of the canonical sequence.
Location on the sequence: help LAHKNIREQGRFLQDIFTTL V DLKWRHTLVIFTMSFLCSWL 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                         LAHKNIREQGRFLQDIFTTLVDLKWRHTLVIFTMSFLCSWL

Mouse                         LAHKNIREQGRFLQDIFTTLVDLKWRHTLVIFTMSFLCSWL

Rat                           LAHKNIREQGRFLQDIFTTLVDLKWRHTLVIFTMSFLCSWL

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 – 424 ATP-sensitive inward rectifier potassium channel 8
Topological domain 1 – 69 Cytoplasmic
Mutagenesis 65 – 65 V -> L. No effect on channel activity.



Literature citations
Conserved functional consequences of disease-associated mutations in the slide-helix of Kir6.1 and Kir6.2 subunits of the ATP-sensitive potassium channel.
Cooper P.E.; McClenaghan C.; Chen X.; Stary-Weinzinger A.; Nichols C.G.;
J. Biol. Chem. 292:17387-17398(2017)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT HTOCD MET-65; MUTAGENESIS OF VAL-65; Mutation of KCNJ8 in a patient with Cantu syndrome with unique vascular abnormalities - support for the role of K(ATP) channels in this condition.
Brownstein C.A.; Towne M.C.; Luquette L.J.; Harris D.J.; Marinakis N.S.; Meinecke P.; Kutsche K.; Campeau P.M.; Yu T.W.; Margulies D.M.; Agrawal P.B.; Beggs A.H.;
Eur. J. Med. Genet. 56:678-682(2013)
Cited for: VARIANT HTOCD MET-65;
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.