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MGP001723

UniProt Annotations

Entry Information

Gene Name	potassium channel, inwardly rectifying subfamily J, member 5
Protein Entry	KCNJ5_HUMAN
UniProt ID	P48544
Species	Human

Comments

Comment type	Description
Disease	Familial hyperaldosteronism 3 (FH3) [MIM:613677]: A form of hyperaldosteronism characterized by hypertension secondary to massive adrenal mineralocorticoid production. Like patients with familial hyperaldosteronism type 1 (glucocorticoid-remediable aldosteronism), patients with FH3 present with childhood hypertension, elevated aldosteronism levels, and high levels of the hybrid steroids 18-oxocortisol and 18-hydroxycortisol. However, hypertension and aldosteronism are not reversed by administration of exogenous glucocorticoids and patients require adrenalectomy to control hypertension. {ECO:0000269\|PubMed:21311022, ECO:0000269\|PubMed:22203740, ECO:0000269\|PubMed:22308486}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Long QT syndrome 13 (LQT13) [MIM:613485]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. {ECO:0000269\|PubMed:20560207}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Note=Somatic mutations in KCNJ5 have been found in aldosterone-producing adrenal adenomas (APA) and can be responsible for aldosteronism associated with cell autonomous proliferation. APAs are typically solitary, well circumscribed tumors diagnosed between ages 30 and 70. They come to medical attention due to new or worsening hypertension, often with hypokalemia. The precise role of KCNJ5 mutations in APA is under debate. They produce increased sodium conductance and cell depolarization, which in adrenal glomerulosa cells produces calcium entry, the signal for aldosterone production and cell proliferation. However, they may not be causative of APA development but may be a consequence of tumorigenesis, playing only a contributory role toward aldosterone overproduction and tumor growth (PubMed:22275527). Somatic mutations in KCNJ5 have not been found in non-aldosterone secreting adrenal adenomas suggesting that they are specifically associated with APA (PubMed:22275527 and PubMed:22848660). {ECO:0000269\|PubMed:22275527}.
Function	This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium.
Similarity	Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ5 subfamily. {ECO:0000305}.
Subcellular Location	Membrane; Multi-pass membrane protein.
Subunit	May associate with GIRK1 and GIRK2 to form a G-protein- activated heteromultimer pore-forming unit. The resulting inward current is much larger (By similarity). {ECO:0000250}.
Tissue Specificity	Islets, exocrine pancreas and heart. Expressed in the adrenal cortex, particularly the zona glomerulosa. {ECO:0000269\|PubMed:21311022}.