Kcnh1-flox Mouse

Kcnh1, also known as potassium voltage-gated channel subfamily H member 1, encodes a member of the EAG (ether-à-go-go) family. It controls potassium flux, regulating the resting membrane potential in both excitable and non-excitable cells, and is involved in intracellular signaling, cell proliferation, and tumorigenesis [4].

Mutations in Kcnh1 have been associated with multiple syndromic neurodevelopmental disorders. In Temple-Baraitser syndrome, a patient was found to have a pathogenic missense mutation in Kcnh1 (c. 1529 A > C; Asn510Thr) presenting with severe mental retardation, anomalies of thumb and great toe, and absence/hypoplasia of the nails [1]. In Zimmermann-Laband syndrome, heterozygous missense mutations in Kcnh1 account for a proportion of cases, with associated facial dysmorphism, intellectual disability, nail and terminal phalangeal hypoplasia/aplasia, and hypertrichosis [5]. Epilepsy is a key phenotypic feature in most individuals with Kcnh1-related syndromes [2]. Also, Kcnh1 may be related to coronary artery ectasia [3], and its missense variants perturb cilia morphology, assembly/disassembly, and Sonic Hedgehog signaling [4].

In conclusion, Kcnh1 is crucial for regulating potassium flux and has diverse functions in intracellular signaling and cell processes. Its mutations are associated with multiple neurodevelopmental and other disorders, highlighting its significance in understanding the molecular mechanisms underlying these conditions.