High-throughput discovery of trafficking-deficient variants in the cardiac potassium channel K
Deep mutational scanning
K(V)11.1
KCNH2
Membrane trafficking
hERG
Journal
Heart rhythm
ISSN: 1556-3871
Titre abrégé: Heart Rhythm
Pays: United States
ID NLM: 101200317
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
15
02
2020
revised:
27
05
2020
accepted:
31
05
2020
pubmed:
12
6
2020
medline:
30
9
2021
entrez:
12
6
2020
Statut:
ppublish
Résumé
KCHN2 encodes the K The purpose of this study was to report a high-throughput, multiplexed screening method for KCNH2 genetic variants capable of measuring the cell surface abundance of hundreds of missense variants in the resulting K We developed a method to quantitate K We generated trafficking scores for 220 of 231 missense variants in the pilot region. For 5 of 5 variants, high-throughput trafficking scores validated when tested in single variant flow cytometry and confocal microscopy experiments. We further explored these results with planar patch electrophysiology and found that loss-of-trafficking variants do not produce I We describe a new method for detecting K
Sections du résumé
BACKGROUND
KCHN2 encodes the K
OBJECTIVE
The purpose of this study was to report a high-throughput, multiplexed screening method for KCNH2 genetic variants capable of measuring the cell surface abundance of hundreds of missense variants in the resulting K
METHODS
We developed a method to quantitate K
RESULTS
We generated trafficking scores for 220 of 231 missense variants in the pilot region. For 5 of 5 variants, high-throughput trafficking scores validated when tested in single variant flow cytometry and confocal microscopy experiments. We further explored these results with planar patch electrophysiology and found that loss-of-trafficking variants do not produce I
CONCLUSION
We describe a new method for detecting K
Identifiants
pubmed: 32522694
pii: S1547-5271(20)30542-7
doi: 10.1016/j.hrthm.2020.05.041
pmc: PMC7704534
mid: NIHMS1601535
pii:
doi:
Substances chimiques
ERG1 Potassium Channel
0
KCNH2 protein, human
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2180-2189Subventions
Organisme : NCRR NIH HHS
ID : UL1 RR024975
Pays : United States
Organisme : NHLBI NIH HHS
ID : F32 HL137385
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM109110
Pays : United States
Organisme : NHGRI NIH HHS
ID : K99 HG010904
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL144980
Pays : United States
Organisme : NIH HHS
ID : S10 OD025281
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149826
Pays : United States
Organisme : NHLBI NIH HHS
ID : R00 HL135442
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA068485
Pays : United States
Informations de copyright
Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
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