UniProtKB/Swiss-Prot Q14654: Variant p.Val64Leu

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

64 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Valine (V) to Leucine (L) at position 64 (V64L, p.Val64Leu). 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:

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:

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:

In PNDM2; uncertain significance; the patient also carries Y-60 in cis; only subtle effects, if any, on channel ATP sensitivity; thought to attenuate the deleterious effect of the Y-60 mutation associated in cis on the channel ATP sensitivity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs115716690 [ dbSNP | Ensembl ]

Sequence information Variant position:

64 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:

VAHKNIREQGRFLQDVFTTL V DLKWPHTLLIFTMSFLCSWL 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                         VAHKNIREQGRFLQDVFTTLVDLKWPHTLLIFTMSFLCSWL

Mouse                         VAHKNIREQGRFLQDVFTTLVDLKWPHTLLIFTMSFLCSWL

Rat                           VAHKNIREQGRFLQDVFTTLVDLKWPHTLLIFTMSFLCSWL

Rabbit                        VAHKNIREQGRFLQDVFTTLVDLKWTHTLLIFTMSFLCSWL

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.

Type	Positions	Description
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.
Helix	59 – 64

Literature citations
Interaction between mutations in the slide helix of Kir6.2 associated with neonatal diabetes and neurological symptoms.
Maennikkoe R.; Jefferies C.; Flanagan S.E.; Hattersley A.; Ellard S.; Ashcroft F.M.;
Hum. Mol. Genet. 19:963-972(2010)
Cited for: INVOLVEMENT IN PNDM2; VARIANTS PNDM2 TYR-60 AND LEU-64; CHARACTERIZATION OF VARIANTS PNDM2 TYR-60 AND LEU-64; 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 PNDM2 LEU-64; MUTAGENESIS OF VAL-64;

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.