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Pathway Description
Lysinuric Protein Intolerance
Homo sapiens
Disease Pathway
Created: 2013-08-20
Last Updated: 2021-06-01
Lysinuric protein intolerance (Hyperdibasic aminoaciduria II; Dibasic aminoaciduria II; Hyperdibasic aminoaciduria II; LPI), also called hyperdibasic aminoaciduria type 2 or familial protein intolerance, is an autosomal recessive metabolic disorder affecting amino acid transport. LPI is caused by a defect in SLC7A7, Solute carrier family 7, a cationic amino acid transporter. A defect in this enzyme results in accumulation of ammmonia and reticulocytes in blood; glutamine in plasma, carnitine and ferritin in serum, and arginine, lysine and ornithine in urine. Symptoms include bone marrow abnormality, growth retardation, hyperammoniemia, mental retardation, pancreatitis, and seizures.
References
Lysinuric Protein Intolerance References
[OMIM: Entry 222700](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=222700)
Engelke, U., van der Graaf, M., Heerschap, A., Hoenderop, S., Moolenaar, S., Morava, E., Wevers, R. Handbook of 1H-NMR spectroscopy in inborn errors of metabolism: body fluid NMR spectroscopy and in vivo MR spectroscopy (2nd ed) (2007) p.61 Heilbronn: SPS Verlagsgesellschaft
Borsani G, Bassi MT, Sperandeo MP, De Grandi A, Buoninconti A, Riboni M, Manzoni M, Incerti B, Pepe A, Andria G, Ballabio A, Sebastio G: SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance. Nat Genet. 1999 Mar;21(3):297-301. doi: 10.1038/6815.
Pubmed: 10080183
Kato T, Mizutani N, Ban M: Renal transport of lysine and arginine in lysinuric protein intolerance. Eur J Pediatr. 1982 Nov;139(3):181-4.
Pubmed: 6819142
Lauteala T, Mykkanen J, Sperandeo MP, Gasparini P, Savontaus ML, Simell O, Andria G, Sebastio G, Aula P: Genetic homogeneity of lysinuric protein intolerance. Eur J Hum Genet. 1998 Nov-Dec;6(6):612-5. doi: 10.1038/sj.ejhg.5200236.
Pubmed: 9887380
Nunes V, Niinikoski H: Lysinuric Protein Intolerance
Pubmed: 20301535
Kidney Function References
Mount DB: Thick ascending limb of the loop of Henle. Clin J Am Soc Nephrol. 2014 Nov 7;9(11):1974-86. doi: 10.2215/CJN.04480413. Epub 2014 Oct 15.
Pubmed: 25318757
Giebisch G: Renal potassium channels: function, regulation, and structure. Kidney Int. 2001 Aug;60(2):436-45. doi: 10.1046/j.1523-1755.2001.060002436.x.
Pubmed: 11473623
Subramanya AR, Ellison DH: Distal convoluted tubule. Clin J Am Soc Nephrol. 2014 Dec 5;9(12):2147-63. doi: 10.2215/CJN.05920613. Epub 2014 May 22.
Pubmed: 24855283
Mastroianni N, De Fusco M, Zollo M, Arrigo G, Zuffardi O, Bettinelli A, Ballabio A, Casari G: Molecular cloning, expression pattern, and chromosomal localization of the human Na-Cl thiazide-sensitive cotransporter (SLC12A3). Genomics. 1996 Aug 1;35(3):486-93.
Pubmed: 8812482
Syren ML, Tedeschi S, Cesareo L, Bellantuono R, Colussi G, Procaccio M, Ali A, Domenici R, Malberti F, Sprocati M, Sacco M, Miglietti N, Edefonti A, Sereni F, Casari G, Coviello DA, Bettinelli A: Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome. Hum Mutat. 2002 Jul;20(1):78. doi: 10.1002/humu.9045.
Pubmed: 12112667
Simon DB, Nelson-Williams C, Bia MJ, Ellison D, Karet FE, Molina AM, Vaara I, Iwata F, Cushner HM, Koolen M, Gainza FJ, Gitleman HJ, Lifton RP: Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nat Genet. 1996 Jan;12(1):24-30. doi: 10.1038/ng0196-24.
Pubmed: 8528245
Kawakami K, Ohta T, Nojima H, Nagano K: Primary structure of the alpha-subunit of human Na,K-ATPase deduced from cDNA sequence. J Biochem. 1986 Aug;100(2):389-97. doi: 10.1093/oxfordjournals.jbchem.a121726.
Pubmed: 2430951
Ruiz A, Bhat SP, Bok D: Characterization and quantification of full-length and truncated Na,K-ATPase alpha 1 and beta 1 RNA transcripts expressed in human retinal pigment epithelium. Gene. 1995 Apr 3;155(2):179-84. doi: 10.1016/0378-1119(94)00812-7.
Pubmed: 7536695
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Vanmolkot KR, Kors EE, Hottenga JJ, Terwindt GM, Haan J, Hoefnagels WA, Black DF, Sandkuijl LA, Frants RR, Ferrari MD, van den Maagdenberg AM: Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions. Ann Neurol. 2003 Sep;54(3):360-6. doi: 10.1002/ana.10674.
Pubmed: 12953268
De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L, Morgante L, Ballabio A, Aridon P, Casari G: Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nat Genet. 2003 Feb;33(2):192-6. doi: 10.1038/ng1081. Epub 2003 Jan 21.
Pubmed: 12539047
Swoboda KJ, Kanavakis E, Xaidara A, Johnson JE, Leppert MF, Schlesinger-Massart MB, Ptacek LJ, Silver K, Youroukos S: Alternating hemiplegia of childhood or familial hemiplegic migraine? A novel ATP1A2 mutation. Ann Neurol. 2004 Jun;55(6):884-7. doi: 10.1002/ana.20134.
Pubmed: 15174025
Heinzen EL, Swoboda KJ, Hitomi Y, Gurrieri F, Nicole S, de Vries B, Tiziano FD, Fontaine B, Walley NM, Heavin S, Panagiotakaki E, Fiori S, Abiusi E, Di Pietro L, Sweney MT, Newcomb TM, Viollet L, Huff C, Jorde LB, Reyna SP, Murphy KJ, Shianna KV, Gumbs CE, Little L, Silver K, Ptacek LJ, Haan J, Ferrari MD, Bye AM, Herkes GK, Whitelaw CM, Webb D, Lynch BJ, Uldall P, King MD, Scheffer IE, Neri G, Arzimanoglou A, van den Maagdenberg AM, Sisodiya SM, Mikati MA, Goldstein DB: De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat Genet. 2012 Sep;44(9):1030-4. doi: 10.1038/ng.2358. Epub 2012 Jul 29.
Pubmed: 22842232
Ishii A, Saito Y, Mitsui J, Ishiura H, Yoshimura J, Arai H, Yamashita S, Kimura S, Oguni H, Morishita S, Tsuji S, Sasaki M, Hirose S: Identification of ATP1A3 mutations by exome sequencing as the cause of alternating hemiplegia of childhood in Japanese patients. PLoS One. 2013;8(2):e56120. doi: 10.1371/journal.pone.0056120. Epub 2013 Feb 8.
Pubmed: 23409136
Demos MK, van Karnebeek CD, Ross CJ, Adam S, Shen Y, Zhan SH, Shyr C, Horvath G, Suri M, Fryer A, Jones SJ, Friedman JM: A novel recurrent mutation in ATP1A3 causes CAPOS syndrome. Orphanet J Rare Dis. 2014 Jan 28;9:15. doi: 10.1186/1750-1172-9-15.
Pubmed: 24468074
Keryanov S, Gardner KL: Physical mapping and characterization of the human Na,K-ATPase isoform, ATP1A4. Gene. 2002 Jun 12;292(1-2):151-66. doi: 10.1016/s0378-1119(02)00647-9.
Pubmed: 12119109
Hlivko JT, Chakraborty S, Hlivko TJ, Sengupta A, James PF: The human Na,K-ATPase alpha 4 isoform is a ouabain-sensitive alpha isoform that is expressed in sperm. Mol Reprod Dev. 2006 Jan;73(1):101-15. doi: 10.1002/mrd.20383.
Pubmed: 16175638
Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. doi: 10.1038/nature04727.
Pubmed: 16710414
Kawakami K, Nojima H, Ohta T, Nagano K: Molecular cloning and sequence analysis of human Na,K-ATPase beta-subunit. Nucleic Acids Res. 1986 Apr 11;14(7):2833-44. doi: 10.1093/nar/14.7.2833.
Pubmed: 3008098
Lane LK, Shull MM, Whitmer KR, Lingrel JB: Characterization of two genes for the human Na,K-ATPase beta subunit. Genomics. 1989 Oct;5(3):445-53.
Pubmed: 2559024
Hernando N, Martin-Vasallo P, Ghosh S, Ghosh PK, Swaroop A, Coca-Prados M: Nucleotide sequence of a cDNA for the beta 2 subunit isoform of Na+,K(+)-ATPase from human retina. Biochim Biophys Acta. 1994 Jan 3;1189(1):109-11. doi: 10.1016/0005-2736(94)90287-9.
Pubmed: 8305453
Ruiz A, Bhat SP, Bok D: Expression and synthesis of the Na,K-ATPase beta 2 subunit in human retinal pigment epithelium. Gene. 1996 Oct 17;176(1-2):237-42. doi: 10.1016/0378-1119(96)00258-2.
Pubmed: 8918259
Avila J, Alvarez de la Rosa D, Gonzalez-Martinez LM, Lecuona E, Martin-Vasallo P: Structure and expression of the human Na,K-ATPase beta 2-subunit gene. Gene. 1998 Feb 27;208(2):221-7. doi: 10.1016/s0378-1119(97)00661-6.
Pubmed: 9524271
Malik N, Canfield VA, Beckers MC, Gros P, Levenson R: Identification of the mammalian Na,K-ATPase 3 subunit. J Biol Chem. 1996 Sep 13;271(37):22754-8. doi: 10.1074/jbc.271.37.22754.
Pubmed: 8798450
Malik N, Canfield V, Sanchez-Watts G, Watts AG, Scherer S, Beatty BG, Gros P, Levenson R: Structural organization and chromosomal localization of the human Na,K-ATPase beta 3 subunit gene and pseudogene. Mamm Genome. 1998 Feb;9(2):136-43.
Pubmed: 9457675
Sweadner KJ, Wetzel RK, Arystarkhova E: Genomic organization of the human FXYD2 gene encoding the gamma subunit of the Na,K-ATPase. Biochem Biophys Res Commun. 2000 Dec 9;279(1):196-201. doi: 10.1006/bbrc.2000.3907.
Pubmed: 11112438
Kim JW, Lee Y, Lee IA, Kang HB, Choe YK, Choe IS: Cloning and expression of human cDNA encoding Na+, K(+)-ATPase gamma-subunit. Biochim Biophys Acta. 1997 Feb 7;1350(2):133-5. doi: 10.1016/s0167-4781(96)00219-9.
Pubmed: 9048881
Meij IC, Koenderink JB, van Bokhoven H, Assink KF, Groenestege WT, de Pont JJ, Bindels RJ, Monnens LA, van den Heuvel LP, Knoers NV: Dominant isolated renal magnesium loss is caused by misrouting of the Na(+),K(+)-ATPase gamma-subunit. Nat Genet. 2000 Nov;26(3):265-6. doi: 10.1038/81543.
Pubmed: 11062458
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