G52R (LQT5)
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| Current amplitude (@+60mV) | Shift in V1/2 of activation | Expression System | Other | Reference |
|---|---|---|---|---|
| KCNQ1: 2.82±1.37 uA Q1+WT-E1: 12.9±3.00 uA |
KCNQ1: -27.8±2.2 mV Q1+WT-E1: -29.8±6.8 mV |
Xenopus oocytes |
Equimolar coexpression of WT and mutant Q1/E1 showed mild DOMINANT-NEGATIVE effect |
Ma et al. 2003 |
| Q1+GR-E1: 3.53±0.97 nA |
GR -17.3±2.2mV |
|||
|
Reduced |
Positive |
COMMENTS
G52R-KCNE1 has been identified in a Chinese LQTS family with six clinically affected individuals. The overall penetrance was 75%. Patients carrying the mutation reported history of syncope triggered by exercise or emotional stress.
Heterologous expression showed that G52R-KCNE1 fails to induce the
physiological increase in IKs current amplitudes usually observed when
this gene product (MinK) is co-expressed with its alpha subunit
(KCNQ1-KvLQT1).. Therefore the authors conclude that "the main function
of KCNE1 was almost lost" as a consequence of G52R substitution.
Furthermore, G52R-KCNE1 slightly delayed the activation of the KCNQ1
channel and shifted the midpoint of KCNQ1 current-activation positively
by about 10 mV, thus, indicating that G52R-KCNE1 did traffic to the
plasma membrane and interacted with KCNQ1.
When co-expressed together with wild-type KCNE1 and G52R-KCNE1, a mild
dominant negative effect was shown.