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The Contribution of Genetic Sequencing Information to the Identification and Functional Characterization of Two-Pore Domain Potassium (K2P) Channels as Viable Therapeutic Targets

Title: The Contribution of Genetic Sequencing Information to the Identification and Functional Characterization of Two-Pore Domain Potassium (K2P) Channels as Viable Therapeutic Targets
Authors: Alistair Mathie; Samuel R. Bourne; Rachel Forfar; Walter E. Perfect; Emma L. Veale
Publisher Information: Springer Nature
Publication Year: 2024
Collection: University of Westminster: WestminsterResearch
Description: Genetic information can provide important information linking two-pore domain potassium (K2P) channels with disease states, both for diseases where the mutation causes the disease (monogenic diseases) and where the mutation is more subtly associated with the disease and changes the likelihood of a patient developing the disease (polygenic diseases). In this review, we describe examples of monogenic diseases where both gain and loss of channel function can lead to the same disease state (TASK3/KCNK9 in Birk-Barel mental retardation syndrome/KCNK9 imprinting syndrome), where mutations in one channel can lead to altered expression of another to cause the disease (TRESK/KCNK18 in migraine), and where mutations in the same channel can lead to different diseases (TASK1/KCNK3 in sleep apnea, pulmonary hypertension, and atrial fibrillation; TRAAK/KCNK4 in FHEIG syndrome and Rolandic epilepsy). While this functional genomic information is extremely useful in its own right for patients that are identified as having the mutations, it also has wider implications, when particular K2P channels have a role in physiological processes underlying disease states. As such, modifying the activity of the channels associated with both monogenic and polygenic diseases may be of more general therapeutic benefit even for patients where these proteins are functioning normally.
Document Type: book part
Language: unknown
Relation: https://doi.org/10.1007/978-3-031-52197-3_6; Alistair Mathie, Samuel R. Bourne, Rachel Forfar, Walter E. Perfect and Emma L. Veale 2024. The Contribution of Genetic Sequencing Information to the Identification and Functional Characterization of Two-Pore Domain Potassium (K2P) Channels as Viable Therapeutic Targets. in: Stephens, G. and Stevens, E. (ed.) Ion Channels as Targets in Drug Discovery Springer Nature. pp. 199-220
Availability: https://westminsterresearch.westminster.ac.uk/item/w9v59/the-contribution-of-genetic-sequencing-information-to-the-identification-and-functional-characterization-of-two-pore-domain-potassium-k2p-channels-as-viable-therapeutic-targets
Accession Number: edsbas.7382E5B7
Database: BASE