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Updated: Jun 12, 2026
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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
KvDB; mining and mapping sequence variants in voltage-gated potassium channels.
Lucy F Stead1, Ian C Wood, David R Westhead
1University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
Human Mutation
|June 5, 2010
Summary
We developed KvDB, a database for voltage-gated potassium channel variants. Disease-causing variants are often in specific channel segments, linking location to neurological or cardiac disorders.
Area of Science:
- Biophysics
- Molecular Biology
- Genetics
Background:
- Voltage-gated potassium (Kv) channels are crucial for cellular electrical activity.
- Kv channel dysfunction is linked to various human diseases.
- A comprehensive database of Kv channel variants is needed for research.
Purpose of the Study:
- To create KvDB, a specialized database for Kv channel variants.
- To analyze variant locations and their association with disease phenotypes.
- To provide insights into Kv channel function and disease mechanisms.
Main Methods:
- Development of KvDB, a curated database of Kv channel variants.
- Analysis of variant topological locations within Kv channel structures.
- Structural mapping of functionally characterized variants.
Main Results:
- KvDB houses natural and experimental Kv channel variant data with analytical tools.
- Variants in S4, S4-S5, S5, S5-S6, and S6 segments are frequently disease-associated.
- Variant location correlates with specific disorders (e.g., voltage-sensing for neurological, pore for cardiac).
- LQT2 variants often in N-terminus, LQT1 variants in S4-S5, suggesting distinct disease mechanisms.
- Identified intersubunit interactions influencing Kv channel activation voltage.
Conclusions:
- KvDB provides a valuable resource for Kv channel research.
- Variant location is a key determinant of Kv channel-related disease.
- Mechanistic insights into Kv channel function and disease pathogenesis are gained through variant analysis.
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