UniProtKB/Swiss-Prot P15382: Variant p.Ser74Leu

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

Variant position:  74
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Serine (S) to Leucine (L) at position 74 (S74L, p.Ser74Leu).
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 polar (S) to medium size and hydrophobic (L)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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: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.
Any additional useful information about the variant.



Sequence information

Variant position:  74
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:   FGFFTLGIMLSYIRSKKLEH  S NDPFNVYIESDAWQEKDKAY
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                         FGFFTLGIMLSYIRSKKLEHSNDPFNVYIESDAWQEKDKAY

Mouse                         FGFFTLGIMLSYIRSKKLEHSHDPFNVYIESDAWQEKGKAV

Rat                           FGFFTLGIMLSYIRSKKLEHSHDPFNVYIESDAWQEKGKAL

Pig                           FGFFTLGIMLSYIRSKKLEHSHDPFNVYIESDAWQEKGKAL

Rabbit                        FGFFTLGIMLSYIRSQKLEHSHDPFNVYIEANDWQEKDRAY

Cat                           FGFFTLGIMLSYIRSKKLEHSHDPFNVYIESDTWQEKDKAY

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
Topological domain 67 – 129 Cytoplasmic
Mutagenesis 69 – 69 K -> H. Lowers current 2-fold and leads to faster deactivation of KCNQ1/KCNE1 channel.


Literature citations

Mutations in the hminK gene cause long QT syndrome and suppress IKs function.
Splawski I.; Tristani-Firouzi M.; Lehmann M.H.; Sanguinetti M.C.; Keating M.T.;
Nat. Genet. 17:338-340(1997)
Cited for: VARIANTS LQT5 LEU-74 AND ASN-76;

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.