familial hyperaldosteronism At least four KCNJ5 gene mutations have been identified in people with familial hyperaldosteronism type III. Familial hyperaldosteronism is a disorder that causes high blood pressure (hypertension). Mutations in the KCNJ5 gene are thought to result in the production of potassium channels that are less selective, allowing other ions (predominantly sodium) to pass as well. The flow of sodium ions into adrenal gland cells affects the electrical charge across the cell membrane, activating another type of channel that allows calcium ions to enter. The influx of calcium ions overactivates a process called the calcium/calmodulin pathway that increases aldosterone production, resulting in excess aldosterone and the hypertension associated with familial hyperaldosteronism type III. other disorders Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the KCNJ5 gene have been identified in approximately 40 percent of nonhereditary (sporadic) tumors of the adrenal glands called aldosterone-producing adenomas. These noncancerous (benign) tumors cause hypertension that gets worse over time. As in familial hyperaldosteronism (described above), KCNJ5 gene mutations in cells of the adrenal gland result in increased aldosterone production, leading to hypertension.

     The KCNJ5 gene provides instructions for making a protein that functions as a potassium channel, which means that it transports positively charged atoms (ions) of potassium into and out of cells. Potassium channels produced from the KCNJ5 gene are thought to help regulate production of the hormone aldosterone. In the adrenal glands, which are small hormone-producing glands located on top of each kidney, the channels control the flow of ions into the cell. The flow of ions creates an electrical charge across the cell membrane, which affects the triggering of certain biochemical processes (pathways) that regulate aldosterone production. Aldosterone helps control blood pressure by maintaining proper salt and fluid levels in the body.

The following transcription factors affect gene expression:

• STAT3

Tissue specificity:

Islets, exocrine pancreas and heart. Expressed in the adrenal cortex, particularly the zona glomerulosa.

Molecular Function:

• G-Protein Activated Inward Rectifier Potassium Channel Activity

Biological Processes:

• Potassium Ion Transport
• Potassium Ion Import

Drug Bank:

• Glyburide
• Ethanol