UniProtKB/Swiss-Prot Q96T55: Variant p.Ala277Glu

Potassium channel subfamily K member 16
Gene: KCNK16
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Variant information Variant position:

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

LB/B 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 Alanine (A) to Glutamate (E) at position 277 (A277E, p.Ala277Glu). 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 small size and hydrophobic (A) to medium size and acidic (E) 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:

Gain of function associated with an increased risk for type 2 diabetes in individuals of east Asian ancestry; displays increased localization at the plasma membrane and increased channel open probability; results in markedly increased ER Ca(2+) leak and ATF6 transcription factor activity in response to metabolic stress. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1535500 [ dbSNP | Ensembl ]

Sequence information Variant position:

277 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

309 The length of the canonical sequence.
Location on the sequence:

LLHRCCQLWLLSLRQGCGAK A APGRRPRRGSTAARGVQVTP 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                         LLHRCCQLWLLSLRQGCGAKAAPGRRPRRGSTAARGVQVTP

Mouse                         LLHRCSRLWQLIRGLDLKDGAAPDSEPR------------S

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 – 309	Potassium channel subfamily K member 16
Topological domain	259 – 309	Cytoplasmic
Alternative sequence	222 – 309	TDPSKHYISVYRSLAAIWILLGLAWLALILPLGPLLLHRCCQLWLLSLRQGCGAKAAPGRRPRRGSTAARGVQVTPQDFPISKKGLGS -> HPLNFITPSGLLPSQEPFQTPHGKPESQQIPGSFQKVSSMNVWPLSGMHSPGLAFPLPDCNIPDQERFRPLHPGAWKFWPLPLPSSNSKWAPMWLGSSAQV. In isoform c.
Alternative sequence	269 – 309	LRQGCGAKAAPGRRPRRGSTAARGVQVTPQDFPISKKGLGS -> RGLGVKDGAASDPSGLPRPQKIPISA. In isoform b.

Literature citations
Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
Cho Y.S.; Chen C.H.; Hu C.; Long J.; Ong R.T.; Sim X.; Takeuchi F.; Wu Y.; Go M.J.; Yamauchi T.; Chang Y.C.; Kwak S.H.; Ma R.C.; Yamamoto K.; Adair L.S.; Aung T.; Cai Q.; Chang L.C.; Chen Y.T.; Gao Y.; Hu F.B.; Kim H.L.; Kim S.; Kim Y.J.; Lee J.J.; Lee N.R.; Li Y.; Liu J.J.; Lu W.; Nakamura J.; Nakashima E.; Ng D.P.; Tay W.T.; Tsai F.J.; Wong T.Y.; Yokota M.; Zheng W.; Zhang R.; Wang C.; So W.Y.; Ohnaka K.; Ikegami H.; Hara K.; Cho Y.M.; Cho N.H.; Chang T.J.; Bao Y.; Hedman A.K.; Morris A.P.; McCarthy M.I.; Takayanagi R.; Park K.S.; Jia W.; Chuang L.M.; Chan J.C.; Maeda S.; Kadowaki T.; Lee J.Y.; Wu J.Y.; Teo Y.Y.; Tai E.S.; Shu X.O.; Mohlke K.L.; Kato N.; Han B.G.; Seielstad M.;
Nat. Genet. 44:67-72(2011)
Cited for: VARIANT GLU-277; Type 2 Diabetes-Associated K+ Channel TALK-1 Modulates beta-Cell Electrical Excitability, Second-Phase Insulin Secretion, and Glucose Homeostasis.
Vierra N.C.; Dadi P.K.; Jeong I.; Dickerson M.; Powell D.R.; Jacobson D.A.;
Diabetes 64:3818-3828(2015)
Cited for: FUNCTION; TRANSPORTER ACTIVITY; SUBCELLULAR LOCATION (ISOFORM A); MUTAGENESIS OF GLY-110; CHARACTERIZATION OF VARIANT GLU-277; TALK-1 channels control beta cell endoplasmic reticulum Ca2+ homeostasis.
Vierra N.C.; Dadi P.K.; Milian S.C.; Dickerson M.T.; Jordan K.L.; Gilon P.; Jacobson D.A.;
Sci. Signal. 10:0-0(2017)
Cited for: FUNCTION; SUBCELLULAR LOCATION (ISOFORMS A AND B); TISSUE SPECIFICITY; MUTAGENESIS OF GLY-110; CHARACTERIZATION OF VARIANT GLU-277;

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.