UniProtKB/SwissProt variant VAR

Variant information

Variant position:

908

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 Glutamate (E) at position 908 (K908E, p.Lys908Glu).

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 acidic (E)

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

Variant description:

In BFIS3; increased voltage-gated sodium channel activity; gain of function.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs796053122 [ dbSNP | Ensembl ]

Sequence information

Variant position:

908

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

Protein sequence length:

2005

The length of the canonical sequence.

Location on the sequence:

LAIIVFIFAVVGMQLFGKSY K ECVCKISNDCELPRWHMHDF

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                         LAIIVFIFAVVGMQLFGKSYKECVCKISNDCELPRWHMHDF

Mouse                         LAIIVFIFAVVGMQLFGKSYKECVCKISNDCELPRWHMHDF

Rat                           LAIIVFIFAVVGMQLFGKSYKECVCKISNDCELPRWHMHHF

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 – 2005	Sodium channel protein type 2 subunit alpha
Topological domain	899 – 927	Extracellular
Repeat	741 – 1013	II
Site	909 – 909	Binds SCN2B; via carbonyl oxygen
Site	916 – 916	Binds Mu-conotoxin KIIIA; via amide nitrogen
Site	920 – 920	Binds Mu-conotoxin KIIIA; via carbonyl oxygen
Disulfide bond	910 – 910	Interchain; with SCN2B or SCN4B
Disulfide bond	910 – 910	Interchain; with the conotoxin GVIIJ (when the channel is not linked to SCN2B or SCN4B; the bond to SCN2B or SCN4B protects the channel from the inhibition by toxin)
Helix	904 – 909

Literature citations

Relationship of electrophysiological dysfunction and clinical severity in SCN2A-related epilepsies.
Lauxmann S.; Verbeek N.E.; Liu Y.; Zaichuk M.; Mueller S.; Lemke J.R.; van Kempen M.J.A.; Lerche H.; Hedrich U.B.S.;
Hum. Mutat. 39:1942-1956(2018)
Cited for: VARIANTS BFIS3 GLU-208 AND GLU-908; CHARACTERIZATION OF VARIANTS BFIS3 GLU-208 AND GLU-908; VARIANT EIEE11 ILE-773; CHARACTERIZATION OF VARIANT EIEE11 ILE-773;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99250: Variant p.Lys908Glu