UniProtKB/SwissProt variant VAR

Variant information

Variant position:

554

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 Lysine (K) to Asparagine (N) at position 554 (K554N, p.Lys554Asn).

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 (K) to medium size and polar (N)

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:

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.

Involvement in disease:

Seizures, benign familial neonatal 1 (BFNS1) [MIM:121200]: A disorder characterized by clusters of seizures occurring in the first days of life. Most patients have spontaneous remission by 12 months of age and show normal psychomotor development. Some rare cases manifest an atypical severe phenotype associated with epileptic encephalopathy and psychomotor retardation. The disorder is distinguished from benign familial infantile seizures by an earlier age at onset. In some patients, neonatal convulsions are followed later in life by myokymia, a benign condition characterized by spontaneous involuntary contractions of skeletal muscles fiber groups that can be observed as vermiform movement of the overlying skin. Electromyography typically shows continuous motor unit activity with spontaneous oligo- and multiplet-discharges of high intraburst frequency (myokymic discharges). Some patients may have isolated myokymia. {ECO:0000269|PubMed:11175290, ECO:0000269|PubMed:11572947, ECO:0000269|PubMed:14534157, ECO:0000269|PubMed:15249611, ECO:0000269|PubMed:23360469, ECO:0000269|PubMed:25982755, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:9425895}. 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 BFNS1 and EIEE7; decreases the voltage-dependence of the channel.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs267607198 [ dbSNP | Ensembl ]

Sequence information

Variant position:

554

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:

PGLKVSIRAVCVMRFLVSKR K FKESLRPYDVMDVIEQYSAG

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                         PGLKVSIRAVCVMRFLVSKRKFKESLRPYDVMDVIEQYSAG

Mouse                         PGLKVSIRAVCVMRFLVSKRKFKESLRPYDVMDVIEQYSAG

Rat                           PGLKVSIRAVCVMRFLVSKRKFKESLRPYDVMDVIEQYSAG

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
Topological domain	313 – 872	Cytoplasmic
Alternative sequence	394 – 872	Missing. In isoform 6.
Helix	535 – 556

Literature citations

A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation.
Borgatti R.; Zucca C.; Cavallini A.; Ferrario M.; Panzeri C.; Castaldo P.; Soldovieri M.V.; Baschirotto C.; Bresolin N.; Dalla Bernardina B.; Taglialatela M.; Bassi M.T.;
Neurology 63:57-65(2004)
Cited for: VARIANT BFNS1 ASN-554; VARIANT EIEE7 ASN-554; CHARACTERIZATION OF VARIANT BFNS1 ASN-554;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43526: Variant p.Lys554Asn