UniProtKB/SwissProt variant VAR

Variant information

Variant position:

201

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 Arginine (R) to Cysteine (C) at position 201 (R201C, p.Arg201Cys).

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 large size and basic (R) to medium size and polar (C)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-3

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:

Epileptic encephalopathy, early infantile, 7 (EIEE7) [MIM:613720]: An autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. {ECO:0000269|PubMed:12742592, ECO:0000269|PubMed:15249611, ECO:0000269|PubMed:24463883, ECO:0000269|PubMed:25740509, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26138355, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847}. 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 EIEE7; gain-of-function mutation; results in loss of voltage-dependent channel gating and highly increased potassium currents.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs796052623 [ dbSNP | Ensembl ]

Sequence information

Variant position:

201

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

Protein sequence length:

872

The length of the canonical sequence.

Location on the sequence:

AVLAAGSQGNVFATSALRSL R FLQILRMIRMDRRGGTWKLL

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                         AVLAAGSQGNVFATSALRSLRFLQILRMIRMDRRGGTWKLL

Mouse                         AVLAAGSQGNVFATSALRSLRFLQILRMIRMDRRGGTWKLL

Rat                           AVLAAGSQGNVFATSALRSLRFLQILRMIRMDRRGGTWKLL

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 – 872	Potassium voltage-gated channel subfamily KQT member 2
Transmembrane	196 – 218	Helical; Voltage-sensor; Name=Segment S4
Modified residue	217 – 217	Phosphothreonine
Mutagenesis	217 – 217	T -> A. No effect on current or expression.
Mutagenesis	217 – 217	T -> D. Abolishes currents without reducing channel protein expression.

Literature citations

Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of Kv7.2 and Kv7.3 potassium channel subunits.
Miceli F.; Soldovieri M.V.; Ambrosino P.; De Maria M.; Migliore M.; Migliore R.; Taglialatela M.;
J. Neurosci. 35:3782-3793(2015)
Cited for: CHARACTERIZATION OF VARIANT EIEE7 CYS-201; FUNCTION;

Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis.
Trump N.; McTague A.; Brittain H.; Papandreou A.; Meyer E.; Ngoh A.; Palmer R.; Morrogh D.; Boustred C.; Hurst J.A.; Jenkins L.; Kurian M.A.; Scott R.H.;
J. Med. Genet. 53:310-317(2016)
Cited for: VARIANTS EIEE7 CYS-201; GLN-213 AND SER-561; VARIANTS BFNS1 TRP-213 AND 581-ARG--LYS-872 DEL;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43526: Variant p.Arg201Cys