Result
| Gene | Variant | Type | Tumor | Drug | Drug level | Reference | More | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| KCNJ5 | L168R | MUT | Adrenal Adenoma | Amiloride | V | 1 | |||||||||||||||||||||||||
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Evidence region
CGI Patient Criteria- NoteThe discovery that somatic mutations of KCNJ5 confer a pathological Na+ permeability to the mutated channel pointed to disturbed ion homeostasis and membrane voltage control as determinants of the pathogenesis of APAs (9, 19). Here, we show that mutant KCNJ5 led to depolarization and increased intracellular Na+ and Ca2+ concentrations in the adrenocortical cell line NCI-H295R. High intracellular Na+ impaired Ca2+ export via Na+/Ca2+ exchangers (NCX) and possibly allowed Ca2+ influx through NCX working in reverse transport mode. Interestingly, Ca2+ channel blockers, such as verapamil, and Na+ channel blockers, such as amiloride, inhibited the mutated KCNJ5 channel. Gene name
Full name
potassium inwardly rectifying channel subfamily J member 5 Gene typeprotein-coding FunctionThis gene encodes an integral membrane protein which belongs to one of seven subfamilies of inward-rectifier potassium channel proteins called potassium channel subfamily J. The encoded protein is a subunit of the potassium channel which is homotetrameric. It is controlled by G-proteins and has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Naturally occurring mutations in this gene are associated with aldosterone-producing adenomas. [provided by RefSeq, Aug 2017] Drug name
Amiloride DrugBank ID Synonyms3,5-diamino-N-carbamimidoyl-6-chloropyrazine-2-carboxamide Alti-amiloride Hctz A pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with diuretics to spare potassium loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705) Target gene
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| KCNJ5 | L168R | MUT | Adrenal Adenoma | Verapamil | V | 1 | |||||||||||||||||||||||||
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Evidence region
CGI Patient Criteria- NoteThe discovery that somatic mutations of KCNJ5 confer a pathological Na+ permeability to the mutated channel pointed to disturbed ion homeostasis and membrane voltage control as determinants of the pathogenesis of APAs (9, 19). Here, we show that mutant KCNJ5 led to depolarization and increased intracellular Na+ and Ca2+ concentrations in the adrenocortical cell line NCI-H295R. High intracellular Na+ impaired Ca2+ export via Na+/Ca2+ exchangers (NCX) and possibly allowed Ca2+ influx through NCX working in reverse transport mode. Interestingly, Ca2+ channel blockers, such as verapamil, and Na+ channel blockers, such as amiloride, inhibited the mutated KCNJ5 channel. Gene name
Full name
potassium inwardly rectifying channel subfamily J member 5 Gene typeprotein-coding FunctionThis gene encodes an integral membrane protein which belongs to one of seven subfamilies of inward-rectifier potassium channel proteins called potassium channel subfamily J. The encoded protein is a subunit of the potassium channel which is homotetrameric. It is controlled by G-proteins and has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Naturally occurring mutations in this gene are associated with aldosterone-producing adenomas. [provided by RefSeq, Aug 2017] Drug name
Verapamil DrugBank ID SynonymsIproveratril Penta-verapamil - 80mg Verapamil is a phenylalkylamine calcium channel blocker used in the treatment of high blood pressure, heart arrhythmias, and angina,[L8791] and was the first calcium channel antagonist to be introduced into therapy in the early 1960s.[A188514] It is a member of the non-dihydropyridine class of calcium channel blockers, which includes drugs like [diltiazem] and [flunarizine], but is chemically unrelated to other cardioactive medications.[L8791] Verapamil is administered as a racemic mixture containing equal amounts of the S- and R-enantiomer, each of which is pharmacologically distinct - the S-enantiomer carries approximately 20-fold greater potency than the R-enantiomer, but is metabolized at a higher rate.[A188435] Target gene
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