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{{Short description|Potassium channel}}
{{Infobox_gene}}
{{Infobox_gene}}


The '''renal outer medullary potassium channel''' ('''ROMK''') is an ATP-dependent [[potassium channel]] (K<sub>ir</sub>1.1) 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]].<ref name="pmid7680431">{{cite journal | vauthors = Ho K, Nichols CG, Lederer WJ, Lytton J, Vassilev PM, Kanazirska MV, Hebert SC | title = Cloning and expression of an inwardly rectifying ATP-regulated potassium channel | journal = Nature | volume = 362 | issue = 6415 | pages = 31–8 | date = March 1993 | pmid = 7680431 | doi = 10.1038/362031a0 }}</ref><ref name="pmid8190102">{{cite journal | vauthors = Yano H, Philipson LH, Kugler JL, Tokuyama Y, Davis EM, Le Beau MM, Nelson DJ, Bell GI, Takeda J | title = Alternative splicing of human inwardly rectifying K+ channel ROMK1 mRNA | journal = Molecular Pharmacology | volume = 45 | issue = 5 | pages = 854–60 | date = May 1994 | pmid = 8190102 | doi = }}</ref><ref name="pmid16382105">{{cite journal | vauthors = Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA | title = International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 509–26 | date = December 2005 | pmid = 16382105 | doi = 10.1124/pr.57.4.11 }}</ref> Multiple transcript variants encoding different isoforms have been found for this gene.<ref name="entrez"/>
The '''renal outer medullary potassium channel''' ('''ROMK''') is an ATP-dependent [[potassium channel]] (K<sub>ir</sub>1.1) 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]].<ref name="pmid7680431">{{cite journal | vauthors = Ho K, Nichols CG, Lederer WJ, Lytton J, Vassilev PM, Kanazirska MV, Hebert SC | title = Cloning and expression of an inwardly rectifying ATP-regulated potassium channel | journal = Nature | volume = 362 | issue = 6415 | pages = 31–8 | date = March 1993 | pmid = 7680431 | doi = 10.1038/362031a0 | bibcode = 1993Natur.362...31H | s2cid = 4332298 }}</ref><ref name="pmid8190102">{{cite journal | vauthors = Yano H, Philipson LH, Kugler JL, Tokuyama Y, Davis EM, Le Beau MM, Nelson DJ, Bell GI, Takeda J | title = Alternative splicing of human inwardly rectifying K+ channel ROMK1 mRNA | journal = Molecular Pharmacology | volume = 45 | issue = 5 | pages = 854–60 | date = May 1994 | pmid = 8190102 }}</ref><ref name="pmid16382105">{{cite journal | vauthors = Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA | title = International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 509–26 | date = December 2005 | pmid = 16382105 | doi = 10.1124/pr.57.4.11 | s2cid = 11588492 }}</ref> Multiple transcript variants encoding different isoforms have been found for this gene.<ref name="entrez"/>


== Function ==
== Function ==


[[Potassium channel]]s 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 potassium ion channel|inward-rectifier]] type potassium channel. It is inhibited by internal [[adenosine triphosphate|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 (hence the term "inwardly rectifying"). ROMK was identified as the pore forming component of mitoK<sub>ATP</sub> channels that are known to have a critical role during stroke or other ischemic attacks in the protection against hypoxia-induced brain injury.<ref name="entrez">{{cite web | title = Entrez Gene: potassium inwardly-rectifying channel| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3758| accessdate = }}</ref><ref name="mitoKATP">{{cite journal | vauthors = Foster DB, Ho AS, Rucker J, Garlid AO, Chen L, Sidor A, Garlid KD, O'Rourke B | title = Mitochondrial ROMK channel is a molecular component of mitoK(ATP) | journal = Circulation Research | volume = 111 | issue = 4 | pages = 446–54 | date = August 2012 | pmid = 22811560 | pmc = 3560389 | doi = 10.1161/circresaha.112.266445 }}</ref>
[[Potassium channel]]s 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 potassium ion channel|inward-rectifier]] type potassium channel. It is inhibited by internal [[adenosine triphosphate|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).<ref name="entrez">{{cite web | title = Entrez Gene: potassium inwardly-rectifying channel| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3758}}</ref> ROMK was identified as the pore-forming component of the [[ATP-sensitive potassium channel|mitochondrial ATP-sensitive potassium]] ([[ATP-sensitive potassium channel#Cardiovascular KATP channels and protection from ischemic injury|mitoK<sub>ATP</sub>]]) channel, known to play a critical role in [[cardioprotection]] against [[reperfusion injury|ischemic-reperfusion injury]] in the heart<ref name="mitoKATP">{{cite journal | vauthors = Foster DB, Ho AS, Rucker J, Garlid AO, Chen L, Sidor A, Garlid KD, O'Rourke B | title = Mitochondrial ROMK channel is a molecular component of mitoK(ATP) | journal = Circulation Research | volume = 111 | issue = 4 | pages = 446–54 | date = August 2012 | pmid = 22811560 | pmc = 3560389 | doi = 10.1161/circresaha.112.266445 }}</ref> as well as in the protection against [[cerebral hypoxia|hypoxia-induced brain injury]] from [[stroke]] or other [[ischemia|ischemic]] attacks.

[[Klotho (biology)|Klotho]] is a [[beta-glucuronidase]]-like enzyme that activates ROMK by removal of [[sialic acid]].<ref name="pmid18606998">{{cite journal | vauthors=Cha SK, Ortega B, Kurosu H, Rosenblatt KP, Kuro-O M, Huang CL | title=Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1 | journal=[[Proceedings of the National Academy of Sciences of the United States of America]] | volume=105 | issue=28 | pages=9805–9810 | year=2008 | doi = 10.1073/pnas.0803223105 | pmc=2474477 | pmid=18606998 | bibcode=2008PNAS..105.9805C | doi-access=free }}</ref><ref name="pmid20375979">{{cite journal | author=Huang CL | title=Regulation of ion channels by secreted Klotho: mechanisms and implications | journal=[[Kidney International]] | volume=77 | issue=10 | pages=855–860 | year=2010 | doi = 10.1038/ki.2010.73 | pmid=20375979 | doi-access=free }}</ref>


== Clinical significance ==
== Clinical significance ==
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== Role in hypokalemia and magnesium deficiency ==
== Role in hypokalemia and magnesium deficiency ==
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 kddjdjsof 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 <ref>{{Cite journal|last=Huang|first=Chou-Long|date=2007|title=Mechanism of Hypokalemia in Magnesium Deficiency|url=|journal=Science in Renal Medicine|volume=18|pages=2649 -2651|via=}}</ref>.
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.<ref>{{cite journal | vauthors = Huang CL, Kuo E | title = Mechanism of hypokalemia in magnesium deficiency | journal = Journal of the American Society of Nephrology | volume = 18 | issue = 10 | pages = 2649–2652 | date = October 2007 | pmid = 17804670 | doi = 10.1681/asn.2007070792 | doi-access = free }}</ref> Sgk1 kinase has also been reported to phosphorylate ROMK, resulting in an increase of channels on the apical surface of the distal tubule.<ref>{{cite journal | vauthors = Yoo D, Kim BY, Campo C, Nance L, King A, Maouyo D, Welling PA | title = Cell surface expression of the ROMK (Kir 1.1) channel is regulated by the aldosterone-induced kinase, SGK-1, and protein kinase A | journal = The Journal of Biological Chemistry | volume = 278 | issue = 25 | pages = 23066–23075 | date = June 2003 | pmid = 12684516 | doi = 10.1074/jbc.M212301200 | doi-access = free }}</ref> Sgk1 is in turn regulated by the mineralocorticoid receptor such an effect may contribute to the kaliuretic action of aldosterone.


== References ==
== References ==
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== Further reading ==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
* {{cite journal | vauthors = O'Connell AD, Leng Q, Dong K, MacGregor GG, Giebisch G, Hebert SC | title = Phosphorylation-regulated endoplasmic reticulum retention signal in the renal outer-medullary K+ channel (ROMK) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 28 | pages = 9954–9 | date = July 2005 | pmid = 15987778 | pmc = 1175014 | doi = 10.1073/pnas.0504332102 }}
* {{cite journal | vauthors = O'Connell AD, Leng Q, Dong K, MacGregor GG, Giebisch G, Hebert SC | title = Phosphorylation-regulated endoplasmic reticulum retention signal in the renal outer-medullary K+ channel (ROMK) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 28 | pages = 9954–9 | date = July 2005 | pmid = 15987778 | pmc = 1175014 | doi = 10.1073/pnas.0504332102 | bibcode = 2005PNAS..102.9954O | doi-access = free }}
* {{cite journal | vauthors = Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA | title = International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 509–26 | date = December 2005 | pmid = 16382105 | doi = 10.1124/pr.57.4.11 }}
* {{cite journal | vauthors = Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA | title = International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 509–26 | date = December 2005 | pmid = 16382105 | doi = 10.1124/pr.57.4.11 | s2cid = 11588492 }}
* {{cite journal | vauthors = Brochard K, Boyer O, Blanchard A, Loirat C, Niaudet P, Macher MA, Deschenes G, Bensman A, Decramer S, Cochat P, Morin D, Broux F, Caillez M, Guyot C, Novo R, Jeunemaître X, Vargas-Poussou R | title = Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome | journal = Nephrology, Dialysis, Transplantation | volume = 24 | issue = 5 | pages = 1455–64 | date = May 2009 | pmid = 19096086 | doi = 10.1093/ndt/gfn689 }}
* {{cite journal | vauthors = Brochard K, Boyer O, Blanchard A, Loirat C, Niaudet P, Macher MA, Deschenes G, Bensman A, Decramer S, Cochat P, Morin D, Broux F, Caillez M, Guyot C, Novo R, Jeunemaître X, Vargas-Poussou R | title = Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome | journal = Nephrology, Dialysis, Transplantation | volume = 24 | issue = 5 | pages = 1455–64 | date = May 2009 | pmid = 19096086 | doi = 10.1093/ndt/gfn689 | doi-access = free }}
* {{cite journal | vauthors = Lee JR, Shieh RC | title = Structural changes in the cytoplasmic pore of the Kir1.1 channel during pHi-gating probed by FRET | journal = Journal of Biomedical Science | volume = 16 | issue = 1 | pages = 29 | date = March 2009 | pmid = 19272129 | pmc = 2672938 | doi = 10.1186/1423-0127-16-29 }}
* {{cite journal | vauthors = Lee JR, Shieh RC | title = Structural changes in the cytoplasmic pore of the Kir1.1 channel during pHi-gating probed by FRET | journal = Journal of Biomedical Science | volume = 16 | issue = 1 | pages = 29 | date = March 2009 | pmid = 19272129 | pmc = 2672938 | doi = 10.1186/1423-0127-16-29 | doi-access = free }}
* {{cite journal | vauthors = Nüsing RM, Pantalone F, Gröne HJ, Seyberth HW, Wegmann M | title = Expression of the potassium channel ROMK in adult and fetal human kidney | journal = Histochemistry and Cell Biology | volume = 123 | issue = 6 | pages = 553–9 | date = June 2005 | pmid = 15895241 | doi = 10.1007/s00418-004-0742-5 }}
* {{cite journal | vauthors = Nüsing RM, Pantalone F, Gröne HJ, Seyberth HW, Wegmann M | title = Expression of the potassium channel ROMK in adult and fetal human kidney | journal = Histochemistry and Cell Biology | volume = 123 | issue = 6 | pages = 553–9 | date = June 2005 | pmid = 15895241 | doi = 10.1007/s00418-004-0742-5 | s2cid = 24421285 }}
* {{cite journal | vauthors = Cho JT, Guay-Woodford LM | title = Heterozygous mutations of the gene for Kir 1.1 (ROMK) in antenatal Bartter syndrome presenting with transient hyperkalemia, evolving to a benign course | journal = Journal of Korean Medical Science | volume = 18 | issue = 1 | pages = 65–8 | date = February 2003 | pmid = 12589089 | pmc = 3055000 | doi = 10.3346/jkms.2003.18.1.65 }}
* {{cite journal | vauthors = Cho JT, Guay-Woodford LM | title = Heterozygous mutations of the gene for Kir 1.1 (ROMK) in antenatal Bartter syndrome presenting with transient hyperkalemia, evolving to a benign course | journal = Journal of Korean Medical Science | volume = 18 | issue = 1 | pages = 65–8 | date = February 2003 | pmid = 12589089 | pmc = 3055000 | doi = 10.3346/jkms.2003.18.1.65 }}
* {{cite journal | vauthors = Ji W, Foo JN, O'Roak BJ, Zhao H, Larson MG, Simon DB, Newton-Cheh C, State MW, Levy D, Lifton RP | title = Rare independent mutations in renal salt handling genes contribute to blood pressure variation | journal = Nature Genetics | volume = 40 | issue = 5 | pages = 592–599 | date = May 2008 | pmid = 18391953 | pmc = 3766631 | doi = 10.1038/ng.118 }}
* {{cite journal | vauthors = Ji W, Foo JN, O'Roak BJ, Zhao H, Larson MG, Simon DB, Newton-Cheh C, State MW, Levy D, Lifton RP | title = Rare independent mutations in renal salt handling genes contribute to blood pressure variation | journal = Nature Genetics | volume = 40 | issue = 5 | pages = 592–599 | date = May 2008 | pmid = 18391953 | pmc = 3766631 | doi = 10.1038/ng.118 }}
* {{cite journal | vauthors = Nozu K, Fu XJ, Kaito H, Kanda K, Yokoyama N, Przybyslaw Krol R, Nakajima T, Kajiyama M, Iijima K, Matsuo M | title = A novel mutation in KCNJ1 in a Bartter syndrome case diagnosed as pseudohypoaldosteronism | journal = Pediatric Nephrology | volume = 22 | issue = 8 | pages = 1219–23 | date = August 2007 | pmid = 17401586 | doi = 10.1007/s00467-007-0468-4 }}
* {{cite journal | vauthors = Nozu K, Fu XJ, Kaito H, Kanda K, Yokoyama N, Przybyslaw Krol R, Nakajima T, Kajiyama M, Iijima K, Matsuo M | title = A novel mutation in KCNJ1 in a Bartter syndrome case diagnosed as pseudohypoaldosteronism | journal = Pediatric Nephrology | volume = 22 | issue = 8 | pages = 1219–23 | date = August 2007 | pmid = 17401586 | doi = 10.1007/s00467-007-0468-4 | s2cid = 36736809 | url = http://www.lib.kobe-u.ac.jp/repository/90000603.pdf }}
* {{cite journal | vauthors = Lin D, Kamsteeg EJ, Zhang Y, Jin Y, Sterling H, Yue P, Roos M, Duffield A, Spencer J, Caplan M, Wang WH | title = Expression of tetraspan protein CD63 activates protein-tyrosine kinase (PTK) and enhances the PTK-induced inhibition of ROMK channels | journal = The Journal of Biological Chemistry | volume = 283 | issue = 12 | pages = 7674–81 | date = March 2008 | pmid = 18211905 | doi = 10.1074/jbc.M705574200 }}
* {{cite journal | vauthors = Lin D, Kamsteeg EJ, Zhang Y, Jin Y, Sterling H, Yue P, Roos M, Duffield A, Spencer J, Caplan M, Wang WH | title = Expression of tetraspan protein CD63 activates protein-tyrosine kinase (PTK) and enhances the PTK-induced inhibition of ROMK channels | journal = The Journal of Biological Chemistry | volume = 283 | issue = 12 | pages = 7674–81 | date = March 2008 | pmid = 18211905 | doi = 10.1074/jbc.M705574200 | doi-access = free | hdl = 2066/70313 | hdl-access = free }}
* {{cite journal | vauthors = Wang HR, Liu Z, Huang CL | title = Domains of WNK1 kinase in the regulation of ROMK1 | journal = American Journal of Physiology. Renal Physiology | volume = 295 | issue = 2 | pages = F438-45 | date = August 2008 | pmid = 18550644 | pmc = 2519181 | doi = 10.1152/ajprenal.90287.2008 }}
* {{cite journal | vauthors = Wang HR, Liu Z, Huang CL | title = Domains of WNK1 kinase in the regulation of ROMK1 | journal = American Journal of Physiology. Renal Physiology | volume = 295 | issue = 2 | pages = F438–45 | date = August 2008 | pmid = 18550644 | pmc = 2519181 | doi = 10.1152/ajprenal.90287.2008 }}
* {{cite journal | vauthors = Yoo D, Kim BY, Campo C, Nance L, King A, Maouyo D, Welling PA | title = Cell surface expression of the ROMK (Kir 1.1) channel is regulated by the aldosterone-induced kinase, SGK-1, and protein kinase A | journal = The Journal of Biological Chemistry | volume = 278 | issue = 25 | pages = 23066–75 | date = June 2003 | pmid = 12684516 | doi = 10.1074/jbc.M212301200 }}
* {{cite journal | vauthors = Yoo D, Kim BY, Campo C, Nance L, King A, Maouyo D, Welling PA | title = Cell surface expression of the ROMK (Kir 1.1) channel is regulated by the aldosterone-induced kinase, SGK-1, and protein kinase A | journal = The Journal of Biological Chemistry | volume = 278 | issue = 25 | pages = 23066–75 | date = June 2003 | pmid = 12684516 | doi = 10.1074/jbc.M212301200 | doi-access = free }}
* {{cite journal | vauthors = Cha SK, Hu MC, Kurosu H, Kuro-o M, Moe O, Huang CL | title = Regulation of renal outer medullary potassium channel and renal K(+) excretion by Klotho | journal = Molecular Pharmacology | volume = 76 | issue = 1 | pages = 38–46 | date = July 2009 | pmid = 19349416 | pmc = 2701452 | doi = 10.1124/mol.109.055780 }}
* {{cite journal | vauthors = Cha SK, Hu MC, Kurosu H, Kuro-o M, Moe O, Huang CL | title = Regulation of renal outer medullary potassium channel and renal K(+) excretion by Klotho | journal = Molecular Pharmacology | volume = 76 | issue = 1 | pages = 38–46 | date = July 2009 | pmid = 19349416 | pmc = 2701452 | doi = 10.1124/mol.109.055780 }}
* {{cite journal | vauthors = Nanazashvili M, Li H, Palmer LG, Walters DE, Sackin H | title = Moving the pH gate of the Kir1.1 inward rectifier channel | journal = Channels | volume = 1 | issue = 1 | pages = 21–8 | year = 2007 | pmid = 19170254 | doi = 10.4161/chan.3707 }}
* {{cite journal | vauthors = Nanazashvili M, Li H, Palmer LG, Walters DE, Sackin H | title = Moving the pH gate of the Kir1.1 inward rectifier channel | journal = Channels | volume = 1 | issue = 1 | pages = 21–8 | year = 2007 | pmid = 19170254 | doi = 10.4161/chan.3707 | doi-access = free }}
* {{cite journal | vauthors = Liu Z, Wang HR, Huang CL | title = Regulation of ROMK channel and K+ homeostasis by kidney-specific WNK1 kinase | journal = The Journal of Biological Chemistry | volume = 284 | issue = 18 | pages = 12198–206 | date = May 2009 | pmid = 19244242 | pmc = 2673288 | doi = 10.1074/jbc.M806551200 }}
* {{cite journal | vauthors = Liu Z, Wang HR, Huang CL | title = Regulation of ROMK channel and K+ homeostasis by kidney-specific WNK1 kinase | journal = The Journal of Biological Chemistry | volume = 284 | issue = 18 | pages = 12198–206 | date = May 2009 | pmid = 19244242 | pmc = 2673288 | doi = 10.1074/jbc.M806551200 | doi-access = free }}
* {{cite journal | vauthors = Yoo D, Flagg TP, Olsen O, Raghuram V, Foskett JK, Welling PA | title = Assembly and trafficking of a multiprotein ROMK (Kir 1.1) channel complex by PDZ interactions | journal = The Journal of Biological Chemistry | volume = 279 | issue = 8 | pages = 6863–73 | date = February 2004 | pmid = 14604981 | doi = 10.1074/jbc.M311599200 }}
* {{cite journal | vauthors = Yoo D, Flagg TP, Olsen O, Raghuram V, Foskett JK, Welling PA | title = Assembly and trafficking of a multiprotein ROMK (Kir 1.1) channel complex by PDZ interactions | journal = The Journal of Biological Chemistry | volume = 279 | issue = 8 | pages = 6863–73 | date = February 2004 | pmid = 14604981 | doi = 10.1074/jbc.M311599200 | doi-access = free }}
* {{cite journal | vauthors = Tobin MD, Tomaszewski M, Braund PS, Hajat C, Raleigh SM, Palmer TM, Caulfield M, Burton PR, Samani NJ | title = Common variants in genes underlying monogenic hypertension and hypotension and blood pressure in the general population | journal = Hypertension | volume = 51 | issue = 6 | pages = 1658–64 | date = June 2008 | pmid = 18443236 | doi = 10.1161/HYPERTENSIONAHA.108.112664 }}
* {{cite journal | vauthors = Tobin MD, Tomaszewski M, Braund PS, Hajat C, Raleigh SM, Palmer TM, Caulfield M, Burton PR, Samani NJ | title = Common variants in genes underlying monogenic hypertension and hypotension and blood pressure in the general population | journal = Hypertension | volume = 51 | issue = 6 | pages = 1658–64 | date = June 2008 | pmid = 18443236 | doi = 10.1161/HYPERTENSIONAHA.108.112664 | doi-access = free | hdl = 2381/4837 | hdl-access = free }}
* {{cite journal | vauthors = He G, Wang HR, Huang SK, Huang CL | title = Intersectin links WNK kinases to endocytosis of ROMK1 | journal = The Journal of Clinical Investigation | volume = 117 | issue = 4 | pages = 1078–87 | date = April 2007 | pmid = 17380208 | pmc = 1821066 | doi = 10.1172/JCI30087 }}
* {{cite journal | vauthors = He G, Wang HR, Huang SK, Huang CL | title = Intersectin links WNK kinases to endocytosis of ROMK1 | journal = The Journal of Clinical Investigation | volume = 117 | issue = 4 | pages = 1078–87 | date = April 2007 | pmid = 17380208 | pmc = 1821066 | doi = 10.1172/JCI30087 }}
* {{cite journal | vauthors = Murthy M, Cope G, O'Shaughnessy KM | title = The acidic motif of WNK4 is crucial for its interaction with the K channel ROMK | journal = Biochemical and Biophysical Research Communications | volume = 375 | issue = 4 | pages = 651–4 | date = October 2008 | pmid = 18755144 | doi = 10.1016/j.bbrc.2008.08.076 }}
* {{cite journal | vauthors = Murthy M, Cope G, O'Shaughnessy KM | title = The acidic motif of WNK4 is crucial for its interaction with the K channel ROMK | journal = Biochemical and Biophysical Research Communications | volume = 375 | issue = 4 | pages = 651–4 | date = October 2008 | pmid = 18755144 | doi = 10.1016/j.bbrc.2008.08.076 }}
* {{cite journal | vauthors = Lazrak A, Liu Z, Huang CL | title = Antagonistic regulation of ROMK by long and kidney-specific WNK1 isoforms | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 5 | pages = 1615–20 | date = January 2006 | pmid = 16428287 | pmc = 1360592 | doi = 10.1073/pnas.0510609103 }}
* {{cite journal | vauthors = Lazrak A, Liu Z, Huang CL | title = Antagonistic regulation of ROMK by long and kidney-specific WNK1 isoforms | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 5 | pages = 1615–20 | date = January 2006 | pmid = 16428287 | pmc = 1360592 | doi = 10.1073/pnas.0510609103 | bibcode = 2006PNAS..103.1615L | doi-access = free }}
* {{cite journal | vauthors = Welling PA, Ho K | title = A comprehensive guide to the ROMK potassium channel: form and function in health and disease | journal = American Journal of Physiology. Renal Physiology | volume = 297 | issue = 4 | pages = F849-63 | date = October 2009 | pmid = 19458126 | doi = 10.1152/ajprenal.00181.2009 }}
* {{cite journal | vauthors = Welling PA, Ho K | title = A comprehensive guide to the ROMK potassium channel: form and function in health and disease | journal = American Journal of Physiology. Renal Physiology | volume = 297 | issue = 4 | pages = F849–63 | date = October 2009 | pmid = 19458126 | doi = 10.1152/ajprenal.00181.2009 | pmc=2775575}}
{{refend}}
{{refend}}


== External links ==
== External links ==
* {{MeshName|ROMK1+protein,+human}}
* {{MeshName|ROMK1+protein,+human}}
* [http://www.ndif.org/Terms/ROMK.html NDI terminology page]
* [https://web.archive.org/web/20050502213547/http://www.ndif.org/Terms/ROMK.html NDI terminology page]



{{NLM content}}
{{NLM content}}
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[[Category:Ion channels]]
[[Category:Ion channels]]

{{membrane-protein-stub}}

Revision as of 10:15, 6 January 2024

KCNJ1
Identifiers
AliasesKCNJ1, KIR1.1, ROMK, ROMK1, potassium voltage-gated channel subfamily J member 1, potassium inwardly rectifying channel subfamily J member 1
External IDsOMIM: 600359; MGI: 1927248; HomoloGene: 56764; GeneCards: KCNJ1; OMA:KCNJ1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

3758

56379

Ensembl

ENSG00000151704

ENSMUSG00000041248

UniProt

P48048

O88335

RefSeq (mRNA)

NM_153767
NM_000220
NM_153764
NM_153765
NM_153766

NM_001168354
NM_019659

RefSeq (protein)

NP_000211
NP_722448
NP_722449
NP_722450
NP_722451

NP_001161826
NP_062633

Location (UCSC)Chr 11: 128.84 – 128.87 MbChr 9: 32.28 – 32.31 Mb
PubMed search[3][4]
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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]

Function

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]

Clinical significance

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]

Role in hypokalemia and magnesium deficiency

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.

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000151704 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000041248 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Ho K, Nichols CG, Lederer WJ, Lytton J, Vassilev PM, Kanazirska MV, Hebert SC (March 1993). "Cloning and expression of an inwardly rectifying ATP-regulated potassium channel". Nature. 362 (6415): 31–8. Bibcode:1993Natur.362...31H. doi:10.1038/362031a0. PMID 7680431. S2CID 4332298.
  6. ^ Yano H, Philipson LH, Kugler JL, Tokuyama Y, Davis EM, Le Beau MM, Nelson DJ, Bell GI, Takeda J (May 1994). "Alternative splicing of human inwardly rectifying K+ channel ROMK1 mRNA". Molecular Pharmacology. 45 (5): 854–60. PMID 8190102.
  7. ^ Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA (December 2005). "International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews. 57 (4): 509–26. doi:10.1124/pr.57.4.11. PMID 16382105. S2CID 11588492.
  8. ^ a b c "Entrez Gene: potassium inwardly-rectifying channel".
  9. ^ Foster DB, Ho AS, Rucker J, Garlid AO, Chen L, Sidor A, Garlid KD, O'Rourke B (August 2012). "Mitochondrial ROMK channel is a molecular component of mitoK(ATP)". Circulation Research. 111 (4): 446–54. doi:10.1161/circresaha.112.266445. PMC 3560389. PMID 22811560.
  10. ^ Cha SK, Ortega B, Kurosu H, Rosenblatt KP, Kuro-O M, Huang CL (2008). "Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1". Proceedings of the National Academy of Sciences of the United States of America. 105 (28): 9805–9810. Bibcode:2008PNAS..105.9805C. doi:10.1073/pnas.0803223105. PMC 2474477. PMID 18606998.
  11. ^ Huang CL (2010). "Regulation of ion channels by secreted Klotho: mechanisms and implications". Kidney International. 77 (10): 855–860. doi:10.1038/ki.2010.73. PMID 20375979.
  12. ^ Huang CL, Kuo E (October 2007). "Mechanism of hypokalemia in magnesium deficiency". Journal of the American Society of Nephrology. 18 (10): 2649–2652. doi:10.1681/asn.2007070792. PMID 17804670.
  13. ^ Yoo D, Kim BY, Campo C, Nance L, King A, Maouyo D, Welling PA (June 2003). "Cell surface expression of the ROMK (Kir 1.1) channel is regulated by the aldosterone-induced kinase, SGK-1, and protein kinase A". The Journal of Biological Chemistry. 278 (25): 23066–23075. doi:10.1074/jbc.M212301200. PMID 12684516.

Further reading


This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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