UniProtKB/SwissProt variant VAR

Variant information

Variant position:

47

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 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 Valine (V) to Phenylalanine (F) at position 47 (V47F, p.Val47Phe).

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 medium size and hydrophobic (V) to large size and aromatic (F)

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

Involvement in disease:

Jervell and Lange-Nielsen syndrome 2 (JLNS2) [MIM:612347]: An autosomal recessive disorder characterized by congenital deafness, prolongation of the QT interval, syncopal attacks due to ventricular arrhythmias, and a high risk of sudden death. {ECO:0000269|PubMed:10400998, ECO:0000269|PubMed:21676880, ECO:0000269|PubMed:9328483, ECO:0000269|PubMed:9354783}. 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 JLNS2.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs199473353 [ dbSNP | Ensembl ]

Sequence information

Variant position:

47

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:

MSGLARRSPRSSDGKLEALY V LMVLGFFGFFTLGIMLSYIR

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                         MSG-LARRSPRSSDGKLEALYVLMVLGFFGFFTLGIMLSYIR

Mouse                         VSG-LARKSQLRDDSKLEALYILMVLGFFGFFTLGIMLSYI

Rat                           MSADLARRSQLRDDSKLEALYILMVLGFFGFFTLGIMLSYI

Pig                           MSADLARRSQLRDDSKLEALYILMVLGFFGFFTLGIMLSYI

Rabbit                        SATSLARRGPLGDDGQMEALYILMVLGFFGFFTLGIMLSYI

Cat                           TSG-LARRSPGGDDSQLEALYILMVLGFFGFFTLGIMLSYI

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 – 129	Potassium voltage-gated channel subfamily E member 1
Transmembrane	44 – 66	Helical
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.
Mutagenesis	32 – 32	R -> D. Increase in inhibition of the complex KCNQ1-KCNE1 by the scolopendra toxin SSD609.
Helix	46 – 71

Literature citations

Cellular dysfunction of LQT5-minK mutants: abnormalities of IKs, IKr and trafficking in long QT syndrome.
Bianchi L.; Shen Z.; Dennis A.T.; Priori S.G.; Napolitano C.; Ronchetti E.; Bryskin R.; Schwartz P.J.; Brown A.M.;
Hum. Mol. Genet. 8:1499-1507(1999)
Cited for: VARIANTS JLNS2 PHE-47; HIS-51 AND ASN-76; VARIANT LQT5 ARG-87;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P15382: Variant p.Val47Phe