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UniProtKB/Swiss-Prot Q14721: Variant p.Val378Ala

Potassium voltage-gated channel subfamily B member 1
Gene: KCNB1
Variant information

Variant position:  378
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 Valine (V) to Alanine (A) at position 378 (V378A, p.Val378Ala).
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 hydrophobic (V) to small size and hydrophobic (A)
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, 26 (EIEE26) [MIM:616056]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE26 patients manifest multiple types of seizures, delayed psychomotor development, poor or absent speech, hypotonia, hypsarrhythmia. {ECO:0000269|PubMed:25164438, ECO:0000269|PubMed:26477325, ECO:0000269|PubMed:26503721}. 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 EIEE26; change in the ion selectivity from potassium-selective to nonselective cation channels and significant decrease in cell membrane localization.
Any additional useful information about the variant.



Sequence information

Variant position:  378
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  858
The length of the canonical sequence.

Location on the sequence:   DTKFKSIPASFWWATITMTT  V GYGDIYPKTLLGKIVGGLCC
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                         DTKFKSIPASFWWATITMTTVGYGDIYPKTLLGKIVGGLCC

Mouse                         DTKFKSIPASFWWATITMTTVGYGDIYPKTLLGKIVGGLCC

Rat                           DTKFKSIPASFWWATITMTTVGYGDIYPKTLLGKIVGGLCC

Pig                           DTKFKSIPASFWWATITMTTVGYGDIYPKTLLGKIVGGLCC

Rabbit                        DTKFKSIPASFWWATITMTTVGYGDIYPKTLLGKIVGGLCC

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.

TypePositionsDescription
Chain 1 – 858 Potassium voltage-gated channel subfamily B member 1
Intramembrane 377 – 384
Motif 377 – 382 Selectivity filter


Literature citations

A novel epileptic encephalopathy mutation in KCNB1 disrupts Kv2.1 ion selectivity, expression, and localization.
Thiffault I.; Speca D.J.; Austin D.C.; Cobb M.M.; Eum K.S.; Safina N.P.; Grote L.; Farrow E.G.; Miller N.; Soden S.; Kingsmore S.F.; Trimmer J.S.; Saunders C.J.; Sack J.T.;
J. Gen. Physiol. 146:399-410(2015)
Cited for: VARIANT EIEE26 ALA-378; CHARACTERIZATION OF VARIANT EIEE26 ALA-378; SUBCELLULAR LOCATION;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.