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Pathway Description
Omeprazole Action Pathway (old)
Homo sapiens
Drug Action Pathway
Created: 2013-08-22
Last Updated: 2023-09-12
Omeprazole, sold as Prilosec. Losec and Zegerid, is a proton pump inhibitor (PPI) class drug that suppresses the final step in gastric acid production, and was the first proton pump inhibitor to e developed. In this pathway, omeprazole is taken orally and is oxidized in the stomach to form the active metabolite of omeprazole. This active metabolite then binds covalently to the potassium-transporting ATPase protein subunits, found at the secretory surface of the gastric parietal cell, preventing any stimulus. Because the drug binds covalently, its effects are dose-dependent and last much longer than similar drugs that bind to the protein non-covalently. This is because additional ATPase enzymes must be created to replace the ones covalently bound by pantoprazole. Omeprazole is used to manage gastroesophageal reflux disease, to prevent stomach ulcers, and can be used to help treat the effects of a H. pylori infection.
References
Omeprazole Pathway (old) References
DiPiro, J.T., Talbert, R.L., Yee, G.C., Matzke, G.R., Wells, B.G, & Posey, M.L. Pharmacotherapy: A pathologic approach. (6th ed) (2005) p.621-623. New York: McGraw-Hill Medical Publishing Division.
Horn J: The proton-pump inhibitors: similarities and differences. Clin Ther. 2000 Mar;22(3):266-80; discussion 265. doi: 10.1016/S0149-2918(00)80032-6.
Pubmed: 10963283
Losec. (2009). e-CPS (online version of Compendium of Pharmaceuticals and Specialties). Retrieved July 1, 2009.
Shi S, Klotz U: Proton pump inhibitors: an update of their clinical use and pharmacokinetics. Eur J Clin Pharmacol. 2008 Oct;64(10):935-51. doi: 10.1007/s00228-008-0538-y. Epub 2008 Aug 5.
Pubmed: 18679668
Ma JY, Song YH, Sjostrand SE, Rask L, Mardh S: cDNA cloning of the beta-subunit of the human gastric H,K-ATPase. Biochem Biophys Res Commun. 1991 Oct 15;180(1):39-45. doi: 10.1016/s0006-291x(05)81251-3.
Pubmed: 1656976
Dunham A, Matthews LH, Burton J, Ashurst JL, Howe KL, Ashcroft KJ, Beare DM, Burford DC, Hunt SE, Griffiths-Jones S, Jones MC, Keenan SJ, Oliver K, Scott CE, Ainscough R, Almeida JP, Ambrose KD, Andrews DT, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Bannerjee R, Barlow KF, Bates K, Beasley H, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burrill W, Carder C, Carter NP, Chapman JC, Clamp ME, Clark SY, Clarke G, Clee CM, Clegg SC, Cobley V, Collins JE, Corby N, Coville GJ, Deloukas P, Dhami P, Dunham I, Dunn M, Earthrowl ME, Ellington AG, Faulkner L, Frankish AG, Frankland J, French L, Garner P, Garnett J, Gilbert JG, Gilson CJ, Ghori J, Grafham DV, Gribble SM, Griffiths C, Hall RE, Hammond S, Harley JL, Hart EA, Heath PD, Howden PJ, Huckle EJ, Hunt PJ, Hunt AR, Johnson C, Johnson D, Kay M, Kimberley AM, King A, Laird GK, Langford CJ, Lawlor S, Leongamornlert DA, Lloyd DM, Lloyd C, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, McLaren SJ, McMurray A, Milne S, Moore MJ, Nickerson T, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter KM, Rice CM, Searle S, Sehra HK, Shownkeen R, Skuce CD, Smith M, Steward CA, Sycamore N, Tester J, Thomas DW, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Wilming L, Wray PW, Wright MW, Young L, Coulson A, Durbin R, Hubbard T, Sulston JE, Beck S, Bentley DR, Rogers J, Ross MT: The DNA sequence and analysis of human chromosome 13. Nature. 2004 Apr 1;428(6982):522-8. doi: 10.1038/nature02379.
Pubmed: 15057823
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Maeda M, Oshiman K, Tamura S, Futai M: Human gastric (H+ + K+)-ATPase gene. Similarity to (Na+ + K+)-ATPase genes in exon/intron organization but difference in control region. J Biol Chem. 1990 Jun 5;265(16):9027-32.
Pubmed: 2160952
Newman PR, Greeb J, Keeton TP, Reyes AA, Shull GE: Structure of the human gastric H,K-ATPase gene and comparison of the 5'-flanking sequences of the human and rat genes. DNA Cell Biol. 1990 Dec;9(10):749-62. doi: 10.1089/dna.1990.9.749.
Pubmed: 2176086
Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. doi: 10.1038/nature02399.
Pubmed: 15057824
Heiss NS, Poustka A: Genomic structure of a novel chloride channel gene, CLIC2, in Xq28. Genomics. 1997 Oct 1;45(1):224-8. doi: 10.1006/geno.1997.4922.
Pubmed: 9339381
Takano K, Liu D, Tarpey P, Gallant E, Lam A, Witham S, Alexov E, Chaubey A, Stevenson RE, Schwartz CE, Board PG, Dulhunty AF: An X-linked channelopathy with cardiomegaly due to a CLIC2 mutation enhancing ryanodine receptor channel activity. Hum Mol Genet. 2012 Oct 15;21(20):4497-507. doi: 10.1093/hmg/dds292. Epub 2012 Jul 19.
Pubmed: 22814392
Cromer BA, Gorman MA, Hansen G, Adams JJ, Coggan M, Littler DR, Brown LJ, Mazzanti M, Breit SN, Curmi PM, Dulhunty AF, Board PG, Parker MW: Structure of the Janus protein human CLIC2. J Mol Biol. 2007 Nov 30;374(3):719-31. doi: 10.1016/j.jmb.2007.09.041. Epub 2007 Sep 20.
Pubmed: 17945253
Barlow JH, Lowe N, Edwards YH, Butterworth PH: Human carbonic anhydrase I cDNA. Nucleic Acids Res. 1987 Mar 11;15(5):2386. doi: 10.1093/nar/15.5.2386.
Pubmed: 3104879
Lowe N, Brady HJ, Barlow JH, Sowden JC, Edwards M, Butterworth PH: Structure and methylation patterns of the gene encoding human carbonic anhydrase I. Gene. 1990 Sep 14;93(2):277-83. doi: 10.1016/0378-1119(90)90236-k.
Pubmed: 2121614
Gantz I, Munzert G, Tashiro T, Schaffer M, Wang L, DelValle J, Yamada T: Molecular cloning of the human histamine H2 receptor. Biochem Biophys Res Commun. 1991 Aug 15;178(3):1386-92. doi: 10.1016/0006-291x(91)91047-g.
Pubmed: 1714721
Nishi T, Koike T, Oka T, Maeda M, Futai M: Identification of the promoter region of the human histamine H2-receptor gene. Biochem Biophys Res Commun. 1995 May 16;210(2):616-23. doi: 10.1006/bbrc.1995.1703.
Pubmed: 7755641
Murakami H, Sun-Wada GH, Matsumoto M, Nishi T, Wada Y, Futai M: Human histamine H2 receptor gene: multiple transcription initiation and tissue-specific expression. FEBS Lett. 1999 May 28;451(3):327-31. doi: 10.1016/s0014-5793(99)00618-3.
Pubmed: 10371214
Zimonjic DB, Popescu NC, Matsui T, Ito M, Chihara K: Localization of the human cholecystokinin-B/gastrin receptor gene (CCKBR) to chromosome 11p15.5-->p15.4 by fluorescence in situ hybridization. Cytogenet Cell Genet. 1994;65(3):184-5. doi: 10.1159/000133628.
Pubmed: 8222757
Pisegna JR, de Weerth A, Huppi K, Wank SA: Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal localization. Biochem Biophys Res Commun. 1992 Nov 30;189(1):296-303. doi: 10.1016/0006-291x(92)91557-7.
Pubmed: 1280419
Lee YM, Beinborn M, McBride EW, Lu M, Kolakowski LF Jr, Kopin AS: The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization. J Biol Chem. 1993 Apr 15;268(11):8164-9.
Pubmed: 7681836
Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ: Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J. 1987 Dec 20;6(13):3923-9.
Pubmed: 3443095
Bonner TI, Young AC, Brann MR, Buckley NJ: Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes. Neuron. 1988 Jul;1(5):403-10. doi: 10.1016/0896-6273(88)90190-0.
Pubmed: 3272174
Kitano T, Liu YH, Ueda S, Saitou N: Human-specific amino acid changes found in 103 protein-coding genes. Mol Biol Evol. 2004 May;21(5):936-44. doi: 10.1093/molbev/msh100. Epub 2004 Mar 10.
Pubmed: 15014171
Gastric Acid Production References
Wolfe MM, Soll AH: The physiology of gastric acid secretion. N Engl J Med. 1988 Dec 29;319(26):1707-15. doi: 10.1056/NEJM198812293192605.
Pubmed: 3060722
Schubert ML: Gastric acid secretion. Curr Opin Gastroenterol. 2016 Nov;32(6):452-460. doi: 10.1097/MOG.0000000000000308.
Pubmed: 27607343
Schubert ML: Functional anatomy and physiology of gastric secretion. Curr Opin Gastroenterol. 2015 Nov;31(6):479-85. doi: 10.1097/MOG.0000000000000213.
Pubmed: 26376477
Heitzmann D, Warth R: No potassium, no acid: K+ channels and gastric acid secretion. Physiology (Bethesda). 2007 Oct;22:335-41. doi: 10.1152/physiol.00016.2007.
Pubmed: 17928547
Ma JY, Song YH, Sjostrand SE, Rask L, Mardh S: cDNA cloning of the beta-subunit of the human gastric H,K-ATPase. Biochem Biophys Res Commun. 1991 Oct 15;180(1):39-45. doi: 10.1016/s0006-291x(05)81251-3.
Pubmed: 1656976
Dunham A, Matthews LH, Burton J, Ashurst JL, Howe KL, Ashcroft KJ, Beare DM, Burford DC, Hunt SE, Griffiths-Jones S, Jones MC, Keenan SJ, Oliver K, Scott CE, Ainscough R, Almeida JP, Ambrose KD, Andrews DT, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Bannerjee R, Barlow KF, Bates K, Beasley H, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burrill W, Carder C, Carter NP, Chapman JC, Clamp ME, Clark SY, Clarke G, Clee CM, Clegg SC, Cobley V, Collins JE, Corby N, Coville GJ, Deloukas P, Dhami P, Dunham I, Dunn M, Earthrowl ME, Ellington AG, Faulkner L, Frankish AG, Frankland J, French L, Garner P, Garnett J, Gilbert JG, Gilson CJ, Ghori J, Grafham DV, Gribble SM, Griffiths C, Hall RE, Hammond S, Harley JL, Hart EA, Heath PD, Howden PJ, Huckle EJ, Hunt PJ, Hunt AR, Johnson C, Johnson D, Kay M, Kimberley AM, King A, Laird GK, Langford CJ, Lawlor S, Leongamornlert DA, Lloyd DM, Lloyd C, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, McLaren SJ, McMurray A, Milne S, Moore MJ, Nickerson T, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter KM, Rice CM, Searle S, Sehra HK, Shownkeen R, Skuce CD, Smith M, Steward CA, Sycamore N, Tester J, Thomas DW, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Wilming L, Wray PW, Wright MW, Young L, Coulson A, Durbin R, Hubbard T, Sulston JE, Beck S, Bentley DR, Rogers J, Ross MT: The DNA sequence and analysis of human chromosome 13. Nature. 2004 Apr 1;428(6982):522-8. doi: 10.1038/nature02379.
Pubmed: 15057823
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Maeda M, Oshiman K, Tamura S, Futai M: Human gastric (H+ + K+)-ATPase gene. Similarity to (Na+ + K+)-ATPase genes in exon/intron organization but difference in control region. J Biol Chem. 1990 Jun 5;265(16):9027-32.
Pubmed: 2160952
Newman PR, Greeb J, Keeton TP, Reyes AA, Shull GE: Structure of the human gastric H,K-ATPase gene and comparison of the 5'-flanking sequences of the human and rat genes. DNA Cell Biol. 1990 Dec;9(10):749-62. doi: 10.1089/dna.1990.9.749.
Pubmed: 2176086
Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. doi: 10.1038/nature02399.
Pubmed: 15057824
Heiss NS, Poustka A: Genomic structure of a novel chloride channel gene, CLIC2, in Xq28. Genomics. 1997 Oct 1;45(1):224-8. doi: 10.1006/geno.1997.4922.
Pubmed: 9339381
Takano K, Liu D, Tarpey P, Gallant E, Lam A, Witham S, Alexov E, Chaubey A, Stevenson RE, Schwartz CE, Board PG, Dulhunty AF: An X-linked channelopathy with cardiomegaly due to a CLIC2 mutation enhancing ryanodine receptor channel activity. Hum Mol Genet. 2012 Oct 15;21(20):4497-507. doi: 10.1093/hmg/dds292. Epub 2012 Jul 19.
Pubmed: 22814392
Cromer BA, Gorman MA, Hansen G, Adams JJ, Coggan M, Littler DR, Brown LJ, Mazzanti M, Breit SN, Curmi PM, Dulhunty AF, Board PG, Parker MW: Structure of the Janus protein human CLIC2. J Mol Biol. 2007 Nov 30;374(3):719-31. doi: 10.1016/j.jmb.2007.09.041. Epub 2007 Sep 20.
Pubmed: 17945253
Barlow JH, Lowe N, Edwards YH, Butterworth PH: Human carbonic anhydrase I cDNA. Nucleic Acids Res. 1987 Mar 11;15(5):2386. doi: 10.1093/nar/15.5.2386.
Pubmed: 3104879
Lowe N, Brady HJ, Barlow JH, Sowden JC, Edwards M, Butterworth PH: Structure and methylation patterns of the gene encoding human carbonic anhydrase I. Gene. 1990 Sep 14;93(2):277-83. doi: 10.1016/0378-1119(90)90236-k.
Pubmed: 2121614
Gantz I, Munzert G, Tashiro T, Schaffer M, Wang L, DelValle J, Yamada T: Molecular cloning of the human histamine H2 receptor. Biochem Biophys Res Commun. 1991 Aug 15;178(3):1386-92. doi: 10.1016/0006-291x(91)91047-g.
Pubmed: 1714721
Nishi T, Koike T, Oka T, Maeda M, Futai M: Identification of the promoter region of the human histamine H2-receptor gene. Biochem Biophys Res Commun. 1995 May 16;210(2):616-23. doi: 10.1006/bbrc.1995.1703.
Pubmed: 7755641
Murakami H, Sun-Wada GH, Matsumoto M, Nishi T, Wada Y, Futai M: Human histamine H2 receptor gene: multiple transcription initiation and tissue-specific expression. FEBS Lett. 1999 May 28;451(3):327-31. doi: 10.1016/s0014-5793(99)00618-3.
Pubmed: 10371214
Zimonjic DB, Popescu NC, Matsui T, Ito M, Chihara K: Localization of the human cholecystokinin-B/gastrin receptor gene (CCKBR) to chromosome 11p15.5-->p15.4 by fluorescence in situ hybridization. Cytogenet Cell Genet. 1994;65(3):184-5. doi: 10.1159/000133628.
Pubmed: 8222757
Pisegna JR, de Weerth A, Huppi K, Wank SA: Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal localization. Biochem Biophys Res Commun. 1992 Nov 30;189(1):296-303. doi: 10.1016/0006-291x(92)91557-7.
Pubmed: 1280419
Lee YM, Beinborn M, McBride EW, Lu M, Kolakowski LF Jr, Kopin AS: The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization. J Biol Chem. 1993 Apr 15;268(11):8164-9.
Pubmed: 7681836
Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ: Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J. 1987 Dec 20;6(13):3923-9.
Pubmed: 3443095
Bonner TI, Young AC, Brann MR, Buckley NJ: Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes. Neuron. 1988 Jul;1(5):403-10. doi: 10.1016/0896-6273(88)90190-0.
Pubmed: 3272174
Kitano T, Liu YH, Ueda S, Saitou N: Human-specific amino acid changes found in 103 protein-coding genes. Mol Biol Evol. 2004 May;21(5):936-44. doi: 10.1093/molbev/msh100. Epub 2004 Mar 10.
Pubmed: 15014171
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