UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1160

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 Glutamate (E) to Lysine (K) at position 1160 (E1160K, p.Glu1160Lys).

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 acidic (E) to large size and basic (K)

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:

Epilepsy, familial focal, with variable foci 4 (FFEVF4) [MIM:617935]: An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Seizure types commonly include temporal lobe epilepsy, frontal lobe epilepsy, and nocturnal frontal lobe epilepsy. Some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. A subset of patients have structural brain abnormalities. Penetrance of the disorder is incomplete. FFEVF4 is characterized by onset of focal seizures in the first years of life. {ECO:0000269|PubMed:24157691, ECO:0000269|PubMed:28235671}. 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 FFEVF4; affects voltage-dependent sodium channel activity; increased level of persistent sodium current compared to wild-type channels and increased current activation in response to depolarizing voltage ramps.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs377632429 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1160

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

Protein sequence length:

2000

The length of the canonical sequence.

Location on the sequence:

EGSTVDVVLPREGEQAETEP E EDLKPEACFTEGCIKKFPFC

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                         EGSTVDVVLPREGEQAETEPEEDLKPEACFTEGCIKKFPFC

Mouse                         EGSTVDVAPPREGEQAEIEPEEDLKPEACFTEGCIKKFPFC

Rat                           EGSTVDVAPPREGEQAEIEPEEDLKPEACFTEGCIKKFPFC

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 – 2000	Sodium channel protein type 3 subunit alpha
Topological domain	984 – 1207	Cytoplasmic

Literature citations

Novel SCN3A variants associated with focal epilepsy in children.
Vanoye C.G.; Gurnett C.A.; Holland K.D.; George A.L. Jr.; Kearney J.A.;
Neurobiol. Dis. 62:313-322(2014)
Cited for: INVOLVEMENT IN FFEVF4; FUNCTION; VARIANTS FFEVF4 GLN-357; ASN-815; LYS-1160 AND VAL-1372;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9NY46: Variant p.Glu1160Lys