High-throughput functional mapping of variants in an arrhythmia gene, KCNE1, reveals novel biology.

ABSTRACT:

Background

KCNE1 encodes a 129-residue cardiac potassium channel (I_Ks) subunit. KCNE1 variants are associated with long QT syndrome and atrial fibrillation. However, most variants have insufficient evidence of clinical consequences and thus limited clinical utility.

Results

Here, we demonstrate the power of variant effect mapping, which couples saturation mutagenesis with high-throughput sequencing, to ascertain the function of thousands of protein coding KCNE1 variants. We comprehensively assayed KCNE1 variant cell surface expression (2,554/2,709 possible single amino acid variants) and function (2,539 variants). We identified 470 loss-of-surface expression and 588 loss-of-function variants. Out of the 588 loss-of-function variants, only 155 had low cell s

SUBMITTER: Muhammad A 

PROVIDER: S-EPMC10168370 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature