UniProtKB/SwissProt variant VAR

Variant information

Variant position:

656

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

Type of variant:

Unclassified

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 Alanine (A) at position 656 (E656A, p.Glu656Ala).

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 small size and hydrophobic (A)

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:

Found in a patient with epilepsy; unknown pathological significance; no effect on voltage-dependent sensitivity.

Any additional useful information about the variant.

Sequence information

Variant position:

656

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

Protein sequence length:

1236

The length of the canonical sequence.

Location on the sequence:

KSANRESRILINPGNHLKIQ E GTLGFFIASDAKEVKRAFFY

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                         KSANRESR----ILINPGNHLKIQEGTLGFFIASDAKEVKRAFFY

Mouse                         KSANRESRSRKRILINPGNHLKIQEGTLGFFIASDAKEVKR

Rat                           KSANRESRSRKRILINPGNHLKIQEGTLGFFIASDAKEVKR

Bovine                        KSANRESR----ILINPGNHLKIQEGTLGFFIASDAKEVKR

Rabbit                        KSANRESR----ILINPGNHLKIQEGTLGFFIASDAKEVKR

Chicken                       KSEKRESS----ILINPGNHVKIQEGTLGFFIASDAKEVKR

Xenopus laevis                KSEKGESR----ILINPGNHMKIKEGTLGFFIASDAKEVKR

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 – 1236	Calcium-activated potassium channel subunit alpha-1
Topological domain	389 – 1236	Cytoplasmic
Alternative sequence	169 – 1236	Missing. In isoform 6.
Alternative sequence	643 – 643	R -> RSRKR. In isoform 3.

Literature citations

De novo BK channel variant causes epilepsy by affecting voltage gating but not Ca2+ sensitivity.
Li X.; Poschmann S.; Chen Q.; Fazeli W.; Oundjian N.J.; Snoeijen-Schouwenaars F.M.; Fricke O.; Kamsteeg E.J.; Willemsen M.; Wang Q.K.;
Eur. J. Hum. Genet. 26:220-229(2018)
Cited for: FUNCTION; INVOLVEMENT IN EIG16; VARIANT EIG16 SER-1053; CHARACTERIZATION OF VARIANT EIG16 SER-1053; VARIANTS ASN-518; ALA-656 AND SER-1217; CHARACTERIZATION OF VARIANTS ASN-518; ALA-656 AND SER-1217;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q12791: Variant p.Glu656Ala