KCNJ1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | KCNJ1 , KIR1.1, ROMK, ROMK1, potassium voltage-gated channel subfamily J member 1, potassium inwardly rectifying channel subfamily J member 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 600359 MGI: 1927248 HomoloGene: 56764 GeneCards: KCNJ1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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The renal outer medullary potassium channel (ROMK) is an ATP-dependent potassium channel (Kir1.1) that transports potassium out of cells. It plays an important role in potassium recycling in the thick ascending limb (TAL) and potassium secretion in the cortical collecting duct (CCD) of the nephron. In humans, ROMK is encoded by the KCNJ1 (potassium inwardly-rectifying channel, subfamily J, member 1) gene. [5] [6] [7] Multiple transcript variants encoding different isoforms have been found for this gene. [8]
Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. It is inhibited by internal ATP and probably plays an important role in potassium homeostasis. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell, which has (hence the term "inwardly rectifying" referring to corresponding currents in electrophysiology, but has limited physiological relevance). [8] ROMK was identified as the pore-forming component of the mitochondrial ATP-sensitive potassium (mitoKATP) channel, known to play a critical role in cardioprotection against ischemic-reperfusion injury in the heart [9] as well as in the protection against hypoxia-induced brain injury from stroke or other ischemic attacks.
Klotho is a beta-glucuronidase-like enzyme that activates ROMK by removal of sialic acid. [10] [11]
Mutations in this gene have been associated with antenatal Bartter syndrome, which is characterized by salt wasting, hypokalemic alkalosis, hypercalciuria, and low blood pressure. [8]
The ROMK channels are inhibited by magnesium in the nephron's normal physiologic state. In states of hypokalemia (a state of potassium deficiency), concurrent magnesium deficiency results in a state of hypokalemia that may be more difficult to correct with potassium replacement alone. This may be directly due to decreased inhibition of the outward potassium current in states where magnesium is low. Conversely, magnesium deficiency alone is not likely to cause a state of hypokalemia. [12] Sgk1 kinase has also been reported to phosphorylate ROMK, resulting in an increase of channels on the apical surface of the distal tubule. [13] Sgk1 is in turn regulated by the mineralocorticoid receptor such an effect may contribute to the kaliuretic action of aldosterone.
Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cell functions.
Inward-rectifier potassium channels (Kir, IRK) are a specific lipid-gated subset of potassium channels. To date, seven subfamilies have been identified in various mammalian cell types, plants, and bacteria. They are activated by phosphatidylinositol 4,5-bisphosphate (PIP2). The malfunction of the channels has been implicated in several diseases. IRK channels possess a pore domain, homologous to that of voltage-gated ion channels, and flanking transmembrane segments (TMSs). They may exist in the membrane as homo- or heterooligomers and each monomer possesses between 2 and 4 TMSs. In terms of function, these proteins transport potassium (K+), with a greater tendency for K+ uptake than K+ export. The process of inward-rectification was discovered by Denis Noble in cardiac muscle cells in 1960s and by Richard Adrian and Alan Hodgkin in 1970 in skeletal muscle cells.
The Kir2.1 inward-rectifier potassium channel is a lipid-gated ion channel encoded by the KCNJ2 gene.
WNK , also known as WNK1, is an enzyme that is encoded by the WNK1 gene. WNK1 is serine-threonine protein kinase and part of the "with no lysine/K" kinase WNK family. The predominant role of WNK1 is the regulation of cation-Cl− cotransporters (CCCs) such as the sodium chloride cotransporter (NCC), basolateral Na-K-Cl symporter (NKCC1), and potassium chloride cotransporter (KCC1) located within the kidney. CCCs mediate ion homeostasis and modulate blood pressure by transporting ions in and out of the cell. WNK1 mutations as a result have been implicated in blood pressure disorders/diseases; a prime example being familial hyperkalemic hypertension (FHHt).
G protein-activated inward rectifier potassium channel 2 is a protein that in humans is encoded by the KCNJ6 gene. Mutation in KCNJ6 gene has been proposed to be the cause of Keppen-Lubinsky Syndrome (KPLBS).
Potassium inwardly-rectifying channel, subfamily J, member 4, also known as KCNJ4 or Kir2.3, is a human gene.
Potassium inwardly-rectifying channel, subfamily J, member 8, also known as KCNJ8, is a human gene encoding the Kir6.1 protein. A mutation in KCNJ8 has been associated with cardiac arrest in the early repolarization syndrome.
G protein-activated inward rectifier potassium channel 4(GIRK-4) is a protein that in humans is encoded by the KCNJ5 gene and is a type of G protein-gated ion channel.
ATP-sensitive inward rectifier potassium channel 12 is a lipid-gated ion channel that in humans is encoded by the KCNJ12 gene.
G protein-activated inward rectifier potassium channel 1(GIRK-1) is encoded in the human by the gene KCNJ3.
ATP-sensitive inward rectifier potassium channel 10 is a protein that in humans is encoded by the KCNJ10 gene.
Potassium inwardly-rectifying channel, subfamily J, member 15, also known as KCNJ15 is a human gene, which encodes the Kir4.2 protein.
Serine/threonine protein kinase WNK4 also known as WNK lysine deficient protein kinase 4 or WNK4, is an enzyme that in humans is encoded by the WNK4 gene. Missense mutations cause a genetic form of pseudohypoaldosteronism type 2, also called Gordon syndrome.
Potassium inwardly-rectifying channel, subfamily J, member 16 (KCNJ16) is a human gene encoding the Kir5.1 protein.
Potassium inwardly-rectifying channel, subfamily J, member 14 (KCNJ14), also known as Kir2.4, is a human gene.
G protein-activated inward rectifier potassium channel 3 is a protein that in humans is encoded by the KCNJ9 gene.
Potassium inwardly-rectifying channel, subfamily J, member 13 (KCNJ13) is a human gene encoding the Kir7.1 protein.
Tertiapin is a 21-amino acid peptide isolated from venom of the European honey bee. It blocks two different types of potassium channels, inward rectifier potassium channels (Kir) and calcium activated large conductance potassium channels (BK).
Serine/threonine-protein kinase WNK3, also known as protein kinase lysine-deficient 3, is a protein that in humans is encoded by the WNK3 gene.
Serine/threonine-protein kinase Sgk1 also known as serum and glucocorticoid-regulated kinase 1 is an enzyme that in humans is encoded by the SGK1 gene.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.