Clinically Relevant Variants Causing KCNQ1-KCNE2 Gain-of-Function Affect the Ca Sensitivity of the Channel.

Dominant variants are well-known for underlying cardiac arrhythmia syndromes. The two heterozygous missense variants, R116L and P369L, cause an allelic disorder characterized by pituitary hormone deficiency and maternally inherited gingival fibromatosis. Increased K conductance upon co-expression of KCNQ1 mutant channels with the beta subunit KCNE2 is suggested to underlie the phenotype; however, the reason for KCNQ1-KCNE2 (Q1E2) channel gain-of-function is unknown.