This report describes essential tremor (postulated), KCNS2-related. Based on analysis of a family with hereditary essential tremor inherited in a dominant pattern, a specific variant in the KCNS2 gene was postulated to be causative. KCNS2 encodes a member of the potassium voltage-gated channel gene family; it is described a neuronal modulatory alpha subunit. The Drosophila gene most closely related to human KCNS2 is Dmel\Shab; KCNS2 is one of 12 human genes for which Shab is the most closely related gene in flies. (In Drosophila, there are nine members of the potassium voltage-gated (Kv) channel gene family, alpha subunits; in human, there are 40 genes in this family.)
UAS constructs of the human Hsap\KCNS2 gene have been introduced into flies, including wild-type and a variant form postulated to be implicated in this form of hereditary essential tremor. Variant(s) implicated in human disease tested (as transgenic human gene, KCNS2): the D379E variant form has been introduced into flies. Pan-neuronal expression of either the wild-type or mutant form of Hsap\KCNS2 (in a wild-type Shab background) results in ether-anesthetization-induced tremor and other neural phenotypes, including sleep dysfunction. The D379E variant form shows significantly higher levels of inactivation than the wild-type KCNS2 subunit, and a significantly higher frequency of spontaneous firing rate of action potentials, consistent with neuronal hyperexcitability.
[updated Sep. 2018 by FlyBase; FBrf0222196]
Essential tremor may be the most common human movement disorder. The main feature of essential tremor is postural tremor of the arms, but the head, legs, trunk, voice, jaw, and facial muscles also may be involved. Aggravated by emotions, hunger, fatigue, and temperature extremes, the condition may cause a functional disability or even incapacitation (summary by Higgins et al., 1997; pubmed:9399207). [from MIM:190300; 2018.02.12]
In human, there are 40 genes in the potassium voltage-gated channel (Kv) gene family, alpha subunits (https://www.genenames.org/cgi-bin/genefamilies/set/274). In Drosophila, there are 9 members of this gene family (FBgg0000499).
Voltage-gated potassium channels (Kv) form the largest and most diversified class of ion channels. These proteins are present in both excitable and nonexcitable cells. Their main functions are associated with the regulation of the resting membrane potential and the control of the shape and frequency of action potentials. The KCNS2 gene encodes a neuronal modulatory alpha subunit, Kv9.2 (summary by Salinas et al., 1997; pubmed:9305895). [from MIM:602906; 2018.09.13]
Many to one (12 human to 1 Drosophila).
Best reverse ortholog of 12 different human genes encoding subunits of potassium voltage-gated channels. Highest scoring human orthologs are KCNB1 and KCNB2; KCNS2 encodes a smaller modulatory subunit. Dmel\Shab shares 35-44% identity and 54-63% similarity with the 12 human genes.
