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UniProtKB/Swiss-Prot P15382: Variant p.Ala8Val

Potassium voltage-gated channel subfamily E member 1
Gene: KCNE1
Chromosomal location: 21q22.1
Variant information

Variant position:  8
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Alanine (A) to Valine (V) at position 8 (A8V, p.Ala8Val).
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 hydrophobic (V)
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

Involvement in disease:  Long QT syndrome 5 (LQT5) [MIM:613695]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. {ECO:0000269|PubMed:10400998, ECO:0000269|PubMed:10973849, ECO:0000269|PubMed:11692163, ECO:0000269|PubMed:16414944, ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:9354802, ECO:0000269|PubMed:9445165}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In LQT5; unknown pathological significance.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  8
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  129
The length of the canonical sequence.

Location on the sequence:   MILSNTT  A VTPFLTKLWQETVQQGGNMS
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                         MILSNTTAVTPFLTKLWQETVQQGGNMS

Mouse                         MSLPNSTTVLPFLARLWQETAEQGGNVS

Rat                           MALSNSTTVLPFLASLWQETDEPGGNMS

Pig                           MALSNSTTVLPFLASLWQETDEPGGNMS

Rabbit                        MIPPNATAVMPFLTTLGEETAHLQGSSA

Cat                           MILPNTTATTPFLNALWQGTAHQGGNTS

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 – 129 Potassium voltage-gated channel subfamily E member 1
Site 19 – 19 Interacts with the scolopendra toxin SSD609
Glycosylation 5 – 5 N-linked (GlcNAc...) asparagine
Glycosylation 7 – 7 O-linked (GalNAc...) threonine
Glycosylation 26 – 26 N-linked (GlcNAc...) asparagine
Mutagenesis 5 – 5 N -> Q. No measurable effect on assembly with KCNQ1 or cell surface expression of the KCNE1/KCNQ1 channel complex, and loss of glycosylation at N-5; when associated with T-28.
Mutagenesis 6 – 6 T -> F. No measurable effect on assembly with KCNQ1 or cell surface expression of the KCNE1/KCNQ1 channel complex. Loss of glycosylation at T-7.
Mutagenesis 7 – 7 T -> A. 50% reduction of cell surface expression of the KCNE1/KCNQ1 channel complex, and loss of glycosylation at N-5 and T-7; when associated with T-28.
Mutagenesis 15 – 15 K -> D. No change in inhibition of the complex KCNQ1-KCNE1 by the scolopendra toxin SSD609.
Mutagenesis 19 – 19 E -> K. Loss inhibition of the complex KCNQ1-KCNE1 by the scolopendra toxin SSD609.
Mutagenesis 28 – 28 S -> T. No measurable effect on assembly with KCNQ1 or cell surface expression of the KCNE1/KCNQ1 channel complex, and loss of glycosylation at N-5; when associated with Q-5. 50% reduction of cell surface expression of the KCNE1/KCNQ1 channel complex, and loss of glycosylation at N-5 and T-7; when associated with A-7.
Helix 4 – 9


Literature citations

Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.
Kapplinger J.D.; Tester D.J.; Salisbury B.A.; Carr J.L.; Harris-Kerr C.; Pollevick G.D.; Wilde A.A.; Ackerman M.J.;
Heart Rhythm 6:1297-1303(2009)
Cited for: VARIANTS LQT5 VAL-8; MET-10; LEU-28; HIS-32; SER-55; PRO-58; PRO-59; CYS-67; HIS-67; MET-70; ASN-76; LYS-83 AND MET-125;

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.