DT-Web

DB06262 - Droxidopa


Identification
Name Droxidopa
Accession Number DB06262
Type small molecule
Description Droxidopa is a precursor of noradrenaline that is used in the treatment of Parkinsonism. It is approved for use in Japan and is currently in trials in the U.S. The racaemic form (dl-threo-3,4-dihydroxyphenylserine) has also been used, and has been investigated in the treatment of orthostatic hypotension. There is a deficit of noradrenaline as well as of dopamine in Parkinson's disease and it has been proposed that this underlies the sudden transient freezing seen usually in advanced disease.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 213.1873
Groups approved
Monoisotopic Weight 213.063722467
Pharmacology
Indication For treatment of neurogenic orthostatic hypotension (NOH) associated with various disorders including Multiple System Atrophy, Familial Amyloid Polyneuropathy, hemodialysis induced hypotension and Parkinson's Disease. Also investigated for use/treatment in neurologic disorders, nephropathy, blood (blood forming organ disorders, unspecified), and dizzy/fainting spells.
Mechanism of action Droxidopa crosses the blood-brain barrier where it is converted to norepinephrine via decarboxylation by L-aromatic-amino-acid decarboxylase. Increased levels of norepinephrine in the central nervous system (CNS) may be beneficial to patients in a wide range of indications. Norephinephrine acts at alpha-adrenergic receptors as a vasoconstrictor and at beta-adrenergic receptors as a heart stimulator and artery dilator.
Absorption Oral bioavailability is 90%.
Protein binding Not Available
Biotransformation Droxidopa is metabolized by aromatic L-amino acid decarboxylase.
Route of elimination Droxidopa is mainly excreted in the urine, with the main metabolite being 3-O-methyldihydroxyphenylserine.
Toxicity Droxidopa has minimal toxic effects and an acute, oral LD50 of more than 5 g/kg in mice, rats, dogs, and monkeys. Side effects occur in in 0.78% of patients and include nausea, headache, increased blood pressure, hallucination, and anorexia.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Alpha-1A adrenergic receptor
Name Alpha-1A adrenergic receptor
Gene Name ADRA1A
Pharmacological action yes
Actions agonist
References
  • Senard JM, Brefel-Courbon C, Rascol O, Montastruc JL: Orthostatic hypotension in patients with Parkinson's disease: pathophysiology and management. Drugs Aging. 2001;18(7):495-505. - Pubmed
  • Bishop MJ: Recent advances in the discovery of alpha1-adrenoceptor agonists. Curr Top Med Chem. 2007;7(2):135-45. - Pubmed
  • Du L, Li M: Modeling the interactions between alpha(1)-adrenergic receptors and their antagonists. Curr Comput Aided Drug Des. 2010 Sep;6(3):165-78. - Pubmed
  • Lachnit WG, Tran AM, Clarke DE, Ford AP: Pharmacological characterization of an alpha 1A-adrenoceptor mediating contractile responses to noradrenaline in isolated caudal artery of rat. Br J Pharmacol. 1997 Mar;120(5):819-26. - Pubmed
  • Burt RP, Chapple CR, Marshall I: The role of diacylglycerol and activation of protein kinase C in alpha 1A-adrenoceptor-mediated contraction to noradrenaline of rat isolated epididymal vas deferens. Br J Pharmacol. 1996 Jan;117(1):224-30. - Pubmed
DTHybrid score 0.7687
Alpha-1B adrenergic receptor
Name Alpha-1B adrenergic receptor
Gene Name ADRA1B
Pharmacological action yes
Actions agonist
References
  • Bishop MJ: Recent advances in the discovery of alpha1-adrenoceptor agonists. Curr Top Med Chem. 2007;7(2):135-45. - Pubmed
  • Du L, Li M: Modeling the interactions between alpha(1)-adrenergic receptors and their antagonists. Curr Comput Aided Drug Des. 2010 Sep;6(3):165-78. - Pubmed
  • Testa R, Guarneri L, Poggesi E, Simonazzi I, Taddei C, Leonardi A: Mediation of noradrenaline-induced contractions of rat aorta by the alpha 1B-adrenoceptor subtype. Br J Pharmacol. 1995 Feb;114(4):745-50. - Pubmed
  • Izzo NJ Jr, Colucci WS: Regulation of alpha 1B-adrenergic receptor half-life: protein synthesis dependence and effect of norepinephrine. Am J Physiol. 1994 Mar;266(3 Pt 1):C771-5. - Pubmed
DTHybrid score 0.5292
Alpha-1D adrenergic receptor
Name Alpha-1D adrenergic receptor
Gene Name ADRA1D
Pharmacological action yes
Actions agonist
References
  • Bishop MJ: Recent advances in the discovery of alpha1-adrenoceptor agonists. Curr Top Med Chem. 2007;7(2):135-45. - Pubmed
  • Du L, Li M: Modeling the interactions between alpha(1)-adrenergic receptors and their antagonists. Curr Comput Aided Drug Des. 2010 Sep;6(3):165-78. - Pubmed
  • Kenny BA, Chalmers DH, Philpott PC, Naylor AM: Characterization of an alpha 1D-adrenoceptor mediating the contractile response of rat aorta to noradrenaline. Br J Pharmacol. 1995 Jul;115(6):981-6. - Pubmed
  • Testa R, Destefani C, Guarneri L, Poggesi E, Simonazzi I, Taddei C, Leonardi A: The alpha 1d-adrenoceptor subtype is involved in the noradrenaline-induced contractions of rat aorta. Life Sci. 1995;57(13):PL159-63. - Pubmed
DTHybrid score 0.3899
Alpha-2A adrenergic receptor
Name Alpha-2A adrenergic receptor
Gene Name ADRA2A
Pharmacological action yes
Actions agonist
References
  • Davis MP: Recent advances in the treatment of pain. F1000 Med Rep. 2010 Aug 19;2:63. - Pubmed
  • Giovannoni MP, Ghelardini C, Vergelli C, Dal Piaz V: Alpha2-agonists as analgesic agents. Med Res Rev. 2009 Mar;29(2):339-68. - Pubmed
  • Nyronen T, Pihlavisto M, Peltonen JM, Hoffren AM, Varis M, Salminen T, Wurster S, Marjamaki A, Kanerva L, Katainen E, Laaksonen L, Savola JM, Scheinin M, Johnson MS: Molecular mechanism for agonist-promoted alpha(2A)-adrenoceptor activation by norepinephrine and epinephrine. Mol Pharmacol. 2001 May;59(5):1343-54. - Pubmed
DTHybrid score 0.6441
Alpha-2B adrenergic receptor
Name Alpha-2B adrenergic receptor
Gene Name ADRA2B
Pharmacological action yes
Actions agonist
References
  • Davis MP: Recent advances in the treatment of pain. F1000 Med Rep. 2010 Aug 19;2:63. - Pubmed
  • Giovannoni MP, Ghelardini C, Vergelli C, Dal Piaz V: Alpha2-agonists as analgesic agents. Med Res Rev. 2009 Mar;29(2):339-68. - Pubmed
  • Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. - Pubmed
DTHybrid score 0.4358
Alpha-2C adrenergic receptor
Name Alpha-2C adrenergic receptor
Gene Name ADRA2C
Pharmacological action yes
Actions agonist
References
  • Davis MP: Recent advances in the treatment of pain. F1000 Med Rep. 2010 Aug 19;2:63. - Pubmed
  • Giovannoni MP, Ghelardini C, Vergelli C, Dal Piaz V: Alpha2-agonists as analgesic agents. Med Res Rev. 2009 Mar;29(2):339-68. - Pubmed
  • Rump LC, Bohmann C, Schaible U, Schollhorn J, Limberger N: Alpha 2C-adrenoceptor-modulated release of noradrenaline in human right atrium. Br J Pharmacol. 1995 Nov;116(6):2617-24. - Pubmed
DTHybrid score 0.4085
Beta-1 adrenergic receptor
Name Beta-1 adrenergic receptor
Gene Name ADRB1
Pharmacological action yes
Actions agonist
References
  • Mersmann HJ: Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J Anim Sci. 1998 Jan;76(1):160-72. - Pubmed
  • El-Armouche A, Eschenhagen T: Beta-adrenergic stimulation and myocardial function in the failing heart. Heart Fail Rev. 2009 Dec;14(4):225-41. - Pubmed
  • Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. - Pubmed
DTHybrid score 0.9624
Beta-2 adrenergic receptor
Name Beta-2 adrenergic receptor
Gene Name ADRB2
Pharmacological action yes
Actions agonist
References
  • Mersmann HJ: Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J Anim Sci. 1998 Jan;76(1):160-72. - Pubmed
  • Sanders VM: The role of norepinephrine and beta-2-adrenergic receptor stimulation in the modulation of Th1, Th2, and B lymphocyte function. Adv Exp Med Biol. 1998;437:269-78. - Pubmed
  • Tarizzo VI, Coppes RP, Dahlof C, Zaagsma J: Pre- and postganglionic stimulation-induced noradrenaline overflow is markedly facilitated by a prejunctional beta 2-adrenoceptor-mediated control mechanism in the pithed rat. Naunyn Schmiedebergs Arch Pharmacol. 1994 Jun;349(6):570-7. - Pubmed
  • El-Armouche A, Eschenhagen T: Beta-adrenergic stimulation and myocardial function in the failing heart. Heart Fail Rev. 2009 Dec;14(4):225-41. - Pubmed
  • Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. - Pubmed
DTHybrid score 0.9677
Beta-3 adrenergic receptor
Name Beta-3 adrenergic receptor
Gene Name ADRB3
Pharmacological action yes
Actions agonist
References
  • Coman OA, Paunescu H, Ghita I, Coman L, Badararu A, Fulga I: Beta 3 adrenergic receptors: molecular, histological, functional and pharmacological approaches. Rom J Morphol Embryol. 2009;50(2):169-79. - Pubmed
  • Mersmann HJ: Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J Anim Sci. 1998 Jan;76(1):160-72. - Pubmed
  • El-Armouche A, Eschenhagen T: Beta-adrenergic stimulation and myocardial function in the failing heart. Heart Fail Rev. 2009 Dec;14(4):225-41. - Pubmed
  • Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. - Pubmed
DTHybrid score 0.5091
Phenylalanine-4-hydroxylase
Name Phenylalanine-4-hydroxylase
Gene Name PAH
Pharmacological action no
Actions inhibitor
References
  • Martinez A, Andersson KK, Haavik J, Flatmark T: EPR and 1H-NMR spectroscopic studies on the paramagnetic iron at the active site of phenylalanine hydroxylase and its interaction with substrates and inhibitors. Eur J Biochem. 1991 Jun 15;198(3):675-82. - Pubmed
  • Martinez A, Haavik J, Flatmark T: Cooperative homotropic interaction of L-noradrenaline with the catalytic site of phenylalanine 4-monooxygenase. Eur J Biochem. 1990 Oct 5;193(1):211-9. - Pubmed
  • Molinoff PB: The regulation of the noradrenergic neuron. J Psychiatr Res. 1974;11:339-45. - Pubmed
DTHybrid score 0.6899

Enzymes


Aromatic-L-amino-acid decarboxylase
Name Aromatic-L-amino-acid decarboxylase
Gene Name DDC
Actions substrate
References
  • Goldstein DS: L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug. Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):189-203. - Pubmed
  • Maruyama W, Naoi M, Narabayashi H: [The effect of droxidopa on the monoamine metabolsim in the human brain]. Rinsho Shinkeigaku. 1994 Oct;34(10):985-90. - Pubmed
DTHybrid score 0.4148

Transporters


Sodium-dependent noradrenaline transporter
Name Sodium-dependent noradrenaline transporter
Gene Name SLC6A2
Actions substrate
References
  • Habecker BA, Willison BD, Shi X, Woodward WR: Chronic depolarization stimulates norepinephrine transporter expression via catecholamines. J Neurochem. 2006 May;97(4):1044-51. Epub 2006 Mar 29. - Pubmed
  • Bonisch H, Bruss M: The norepinephrine transporter in physiology and disease. Handb Exp Pharmacol. 2006;(175):485-524. - Pubmed
  • Mandela P, Ordway GA: KCl stimulation increases norepinephrine transporter function in PC12 cells. J Neurochem. 2006 Sep;98(5):1521-30. Epub 2006 Jul 31. - Pubmed
  • Gutman DA, Owens MJ: Serotonin and norepinephrine transporter binding profile of SSRIs. Essent Psychopharmacol. 2006;7(1):35-41. - Pubmed
  • Ksiazek P, Buraczynska K, Buraczynska M: Norepinephrine transporter gene (NET) polymorphism in patients with type 2 diabetes. Kidney Blood Press Res. 2006;29(6):338-43. Epub 2006 Nov 23. - Pubmed
DTHybrid score 0.4882
Monocarboxylate transporter 10
Name Monocarboxylate transporter 10
Gene Name SLC16A10
Actions inhibitor
References
  • Kim DK, Kanai Y, Chairoungdua A, Matsuo H, Cha SH, Endou H: Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J Biol Chem. 2001 May 18;276(20):17221-8. Epub 2001 Feb 20. - Pubmed
DTHybrid score 0.3756

Predictions


Id Partner name Gene Name Score
3109 Phenylalanine-4-hydroxylase phhA 0.6899
4119 Cytochrome P450 2D6 CYP2D6 0.3393
4512 Cytochrome P450 3A4 CYP3A4 0.2478
320 5-hydroxytryptamine 1A receptor HTR1A 0.2244
502 5-hydroxytryptamine 2A receptor HTR2A 0.2218
23 D(1A) dopamine receptor DRD1 0.217
831 D(2) dopamine receptor DRD2 0.2162
1588 Multidrug resistance protein 1 ABCB1 0.1993
824 Sodium-dependent serotonin transporter SLC6A4 0.1937
4200 Cytochrome P450 1A2 CYP1A2 0.1902
713 Sodium-dependent dopamine transporter SLC6A3 0.1887
590 5-hydroxytryptamine 2C receptor HTR2C 0.1537
885 5-hydroxytryptamine 1B receptor HTR1B 0.153
432 D(4) dopamine receptor DRD4 0.1373
638 D(3) dopamine receptor DRD3 0.1292
163 D(1B) dopamine receptor DRD5 0.1269
492 Histamine H1 receptor HRH1 0.1171
5666 Parathyroid hormone PTH 0.1158
6144 Solute carrier family 22 member 2 SLC22A2 0.1138
725 5-hydroxytryptamine 1D receptor HTR1D 0.1132
6145 Solute carrier family 22 member 1 SLC22A1 0.1081
1181 Alpha-1-acid glycoprotein 1 ORM1 0.1021
131 Synaptic vesicular amine transporter SLC18A2 0.0949
676 Tyrosine 3-monooxygenase TH 0.0946
6016 Cytochrome P450 2C19 CYP2C19 0.0892
103 Muscarinic acetylcholine receptor M1 CHRM1 0.088
3941 Amine oxidase [flavin-containing] A MAOA 0.0877
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0791
436 5-hydroxytryptamine 2B receptor HTR2B 0.0773
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0735
6147 Solute carrier family 22 member 3 SLC22A3 0.0718
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0715
716 5-hydroxytryptamine 7 receptor HTR7 0.0696
807 D-alanine--D-alanine ligase A ddlA 0.0692
894 Alanine racemase alr 0.0691
2453 Alanine racemase alr 0.0691
4757 Cytochrome P450 2C9 CYP2C9 0.0679
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0657
6024 Cytochrome P450 1A1 CYP1A1 0.0647
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0639
118 Organic cation/carnitine transporter 2 SLC22A5 0.0598
3939 Amine oxidase [flavin-containing] B MAOB 0.0593
4118 Cytochrome P450 3A5 CYP3A5 0.0587
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.0581
134 Tryptophan 5-hydroxylase 1 TPH1 0.0565
3923 Cholinesterase BCHE 0.0556
1256 5-hydroxytryptamine 6 receptor HTR6 0.0538
7 Nitric oxide synthase, inducible NOS2 0.0516
866 Large neutral amino acids transporter small subunit 2 SLC7A8 0.0513
291 Nitric-oxide synthase, endothelial NOS3 0.051
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0486
1820 Beta-nerve growth factor NGF 0.0449
6107 Cytochrome P450 3A7 CYP3A7 0.0428
1566 Corticoliberin CRH 0.0413
199 Monocarboxylate transporter 8 SLC16A2 0.0411
4146 Phosphatidylinositol 3-kinase regulatory subunit gamma PIK3R3 0.0408
4145 Phosphatidylinositol 3-kinase regulatory subunit beta PIK3R2 0.0408
6013 Cytochrome P450 2E1 CYP2E1 0.0404
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.04
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.04
6070 Nischarin NISCH 0.0397
587 Serum albumin ALB 0.0383
763 Tyrosine aminotransferase TAT 0.0369
5493 Tyrosine aminotransferase Not Available 0.0369
2675 Pteridine reductase 1 PTR1 0.035
42 Phenylalanyl-tRNA synthetase alpha chain FARSA 0.0347
6602 Phenylalanyl-tRNA synthetase alpha chain pheS 0.0347
31 Phenylalanyl-tRNA synthetase, mitochondrial FARS2 0.0347
618 Phenylalanyl-tRNA synthetase beta chain FARSB 0.0347
6603 Phenylalanyl-tRNA synthetase beta chain pheT 0.0347
1281 Phosphatidylinositol 3-kinase regulatory subunit alpha PIK3R1 0.0345
6030 Cytochrome P450 2B6 CYP2B6 0.0345
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 0.034
4063 Tryptophanyl-tRNA synthetase, mitochondrial WARS2 0.0311
90 Tryptophan 5-hydroxylase 2 TPH2 0.0311
528 5-hydroxytryptamine 1E receptor HTR1E 0.0308
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0304
1636 Trace amine-associated receptor 1 TAAR1 0.03
76 Nitric-oxide synthase, brain NOS1 0.0299
3810 Catechol O-methyltransferase COMT 0.0294
2360 Dihydroneopterin aldolase folB 0.0293
777 Tumor necrosis factor TNF 0.0293
341 5-hydroxytryptamine 3 receptor HTR3A 0.029
2532 Pantoate--beta-alanine ligase panC 0.0285
574 Branched-chain-amino-acid aminotransferase, cytosolic BCAT1 0.0282
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0275
6020 Aldehyde oxidase AOX1 0.0258
765 Indoleamine 2,3-dioxygenase IDO1 0.0257
252 Tryptophanyl-tRNA synthetase, cytoplasmic WARS 0.0245
6645 D-amino-acid oxidase DAO 0.0245
2300 Lysozyme E 0.0243
3633 Lysozyme R 0.0243
5597 Lysozyme 17 0.0243
4924 Cytochrome P450 2C8 CYP2C8 0.0233
5925 Neuropeptide Y NPY 0.0231
1176 Mitogen-activated protein kinase 1 MAPK1 0.023
2452 Tryptophanyl-tRNA synthetase trpS 0.0229
314 System N amino acid transporter 1 SLC38A3 0.0229
6012 Tryptophan 2,3-dioxygenase TDO2 0.0227
694 Matrix protein 2 M 0.0226
6138 Multidrug resistance protein 3 ABCB4 0.022
124 Histamine H2 receptor HRH2 0.0218
465 Calmodulin CALM1 0.0214
833 Organic cation/carnitine transporter 1 SLC22A4 0.0207
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0199
4069 Threonyl-tRNA synthetase, mitochondrial TARS2 0.0197
261 Threonyl-tRNA synthetase, cytoplasmic TARS 0.0197
246 Valyl-tRNA synthetase VARS 0.0196
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0181
734 D1 dopamine receptor-interacting protein calcyon CALY 0.018
534 Threonine synthase-like 1 THNSL1 0.0178
301 Kynurenine--oxoglutarate transaminase 1 CCBL1 0.017
5469 Head decoration protein shp 0.0168
233 Potassium channel subfamily K member 2 KCNK2 0.0165
5718 Cytochrome P450 2A6 CYP2A6 0.016
795 Branched-chain-amino-acid aminotransferase, mitochondrial BCAT2 0.016
2457 Bacillolysin nprS 0.016
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.016
290 Prostaglandin G/H synthase 2 PTGS2 0.0159
601 Propionyl-CoA carboxylase beta chain, mitochondrial PCCB 0.0157
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0151
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0151
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.015
815 Histidyl-tRNA synthetase, cytoplasmic HARS 0.0147
96 Histidine ammonia-lyase HAL 0.0147
6257 Histidine ammonia-lyase Not Available 0.0147
6536 Histidine ammonia-lyase hutH 0.0147
2461 D-alanyl-D-alanine carboxypeptidase Not Available 0.0147
5756 D-alanyl-D-alanine carboxypeptidase dac 0.0147
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0147
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0146
3 Histidine decarboxylase HDC 0.0144
38 Cystinosin CTNS 0.0141
3998 B(0,+)-type amino acid transporter 1 SLC7A9 0.0141
1963 Neutral and basic amino acid transport protein rBAT SLC3A1 0.0141
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.014
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.014
150 Cationic amino acid transporter 3 SLC7A3 0.0137
235 High-affinity cationic amino acid transporter 1 SLC7A1 0.0137
58 Cationic amino acid transporter 4 SLC7A4 0.0137
3426 Glutamine synthetase glnA 0.0136
3987 Glutamine synthetase GLUL 0.0136
349 Serine--pyruvate aminotransferase AGXT 0.0135
482 Glycine receptor subunit alpha-1 GLRA1 0.0134
471 Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+) SLC6A14 0.0134
358 Cystathionine beta-synthase CBS 0.013
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.013
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0129
399 Tyrosyl-tRNA synthetase, mitochondrial YARS2 0.0127
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0126
4292 Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase lpxA 0.0124
242 Asparagine synthetase [glutamine-hydrolyzing] ASNS 0.0124
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0122
3076 Antigen 85-C fbpC 0.0122
3977 ASRGL1 protein ASRGL1 0.0121
6432 Transporter snf 0.012
263 Neutral amino acid transporter B(0) SLC1A5 0.0119
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0118
701 Isoleucine-tRNA synthetase IARS 0.011
546 Isoleucyl-tRNA synthetase, cytoplasmic IARS 0.011
4080 Isoleucyl-tRNA synthetase, mitochondrial IARS2 0.011
114 Alanine--glyoxylate aminotransferase 2, mitochondrial AGXT2 0.0109
221 Lysyl-tRNA synthetase KARS 0.0109
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0108
4092 Probable asparaginyl-tRNA synthetase, mitochondrial NARS2 0.0107
669 Asparaginyl-tRNA synthetase, cytoplasmic NARS 0.0107
169 Cysteine desulfurase, mitochondrial NFS1 0.0105
184 L-serine dehydratase SDS 0.0102
431 Serine racemase SRR 0.0102
491 Serine palmitoyltransferase 1 SPTLC1 0.0102
727 Serine palmitoyltransferase 2 SPTLC2 0.0102
5650 NimA-related protein DR_0842 0.0101
72 Seryl-tRNA synthetase, cytoplasmic SARS 0.0099
33 Cystine/glutamate transporter SLC7A11 0.0098
501 Leucine carboxyl methyltransferase 1 LCMT1 0.0097
675 Leucine carboxyl methyltransferase 2 LCMT2 0.0097
846 Leucyl-tRNA synthetase, cytoplasmic LARS 0.0097
227 Probable leucyl-tRNA synthetase, mitochondrial LARS2 0.0097
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0095
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0095
619 Low-affinity cationic amino acid transporter 2 SLC7A2 0.0095
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0095
696 Kappa-type opioid receptor OPRK1 0.0094
6847 Lactase-phlorizin hydrolase LCT 0.0093
630 Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial ACADSB 0.0093
1680 Solute carrier family 2, facilitated glucose transporter member 1 SLC2A1 0.0089
256 Tyrosyl-tRNA synthetase, cytoplasmic YARS 0.0089
1656 CYP2B protein CYP2B 0.0088
280 4-aminobutyrate aminotransferase, mitochondrial ABAT 0.0087
500 Monocarboxylate transporter 4 SLC16A3 0.0087
489 Monocarboxylate transporter 2 SLC16A7 0.0086
586 Aspartate aminotransferase, cytoplasmic GOT1 0.0086
1374 Natriuretic peptides B NPPB 0.008
1827 Gap junction alpha-1 protein GJA1 0.008
1908 Vascular cell adhesion protein 1 VCAM1 0.008
3254 Bifunctional protein putA [Includes: Proline dehydrogenase putA 0.0077
474 Acetylcholinesterase ACHE 0.0077
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0076
738 Monocarboxylate transporter 1 SLC16A1 0.0076
499 Arginine decarboxylase ADC 0.0074
467 Delta-type opioid receptor OPRD1 0.0074
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0073
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0073
3899 Alanine--glyoxylate aminotransferase 2-like 2 AGXT2L2 0.007
735 Alanine aminotransferase 1 GPT 0.0068
3904 Alanine aminotransferase 2 GPT2 0.0068
4120 NADPH--cytochrome P450 reductase POR 0.0067
740 Argininosuccinate synthase ASS1 0.0067
865 Argininosuccinate synthase ASS1 0.0067
2680 Argininosuccinate synthase argG 0.0067
3194 Argininosuccinate synthase argG 0.0067
89 Cysteine sulfinic acid decarboxylase CSAD 0.0067
194 NADH dehydrogenase [ubiquinone] 1 subunit C2 NDUFC2 0.0066
435 Kynureninase KYNU 0.0066
4654 Kynureninase kynU 0.0066
594 Thyroxine-binding globulin SERPINA7 0.0066
1360 Sphingomyelin phosphodiesterase SMPD1 0.0066
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0065
6106 Cytochrome P450 2C18 CYP2C18 0.0064
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0064
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0063
20 Prostaglandin G/H synthase 1 PTGS1 0.0062
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0061
758 Thyroid hormone receptor alpha THRA 0.0061
3947 Xanthine dehydrogenase/oxidase XDH 0.006
183 Vascular endothelial growth factor A VEGFA 0.0059
164 Histamine H4 receptor HRH4 0.0058
532 Neutral amino acid transporter A SLC1A4 0.0057
4070 Probable alanyl-tRNA synthetase, mitochondrial AARS2 0.0057
323 Alanyl-tRNA synthetase, cytoplasmic AARS 0.0057
868 Cystathionine gamma-lyase CTH 0.0057
6047 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A PDE1A 0.0056
3877 Growth-inhibiting protein 18 GIG18 0.0055
668 Glutamate--cysteine ligase regulatory subunit GCLM 0.0054
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0054
346 Thyroid hormone receptor beta-1 THRB 0.0054
3874 Proline synthetase co-transcribed bacterial homolog protein PROSC 0.0053
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0053
426 Aspartate aminotransferase, mitochondrial GOT2 0.0053
171 Cysteine dioxygenase CDO-1 0.0053
774 Cysteinyl-tRNA synthetase, cytoplasmic CARS 0.0052
1314 Thiamine transporter 2 SLC19A3 0.0052
4064 Probable cysteinyl-tRNA synthetase, mitochondrial CARS2 0.0052
3811 Cytochrome P450 19A1 CYP19A1 0.0052
207 Glutathione synthetase GSS 0.0052
5269 Glutathione synthetase gshB 0.0052
1618 High affinity nerve growth factor receptor NTRK1 0.0051
834 Arginase-2, mitochondrial ARG2 0.0051
593 Proton-coupled amino acid transporter 1 SLC36A1 0.0051
6150 Solute carrier organic anion transporter family member 4C1 SLCO4C1 0.0051
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.005
577 Argininosuccinate lyase ASL 0.0049
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0049
3971 CAD protein [Includes: Glutamine-dependent carbamoyl-phosphate synthase CAD 0.0049
480 Methionine-R-sulfoxide reductase B2 MSRB2 0.0048
317 Methionine-R-sulfoxide reductase SEPX1 0.0048
3996 Betaine--homocysteine S-methyltransferase 2 BHMT2 0.0048
3921 Methionine adenosyltransferase 2 subunit beta MAT2B 0.0048
3995 Methionyl-tRNA synthetase, mitochondrial MARS2 0.0048
600 Methionyl-tRNA synthetase, cytoplasmic MARS 0.0048
186 Glutamate--cysteine ligase catalytic subunit GCLC 0.0046
198 Sodium channel protein type 10 subunit alpha SCN10A 0.0046
6141 Sodium/bile acid cotransporter SLC10A1 0.0046
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0045
2981 Phospholipase A2, membrane associated PLA2G2A 0.0044
1757 Myeloperoxidase MPO 0.0044
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0043
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0043
575 2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial GCAT 0.0043
455 5-aminolevulinate synthase, nonspecific, mitochondrial ALAS1 0.0043
681 Glycine dehydrogenase [decarboxylating], mitochondrial GLDC 0.0043
1999 Methylated-DNA--protein-cysteine methyltransferase MGMT 0.0043
397 Monocarboxylate transporter 3 SLC16A8 0.0041
218 Monocarboxylate transporter 5 SLC16A4 0.0041
195 Monocarboxylate transporter 7 SLC16A6 0.0041
429 Monocarboxylate transporter 6 SLC16A5 0.0041
6182 Cytochrome P450 2J2 CYP2J2 0.0041
191 Peptide methionine sulfoxide reductase MSRA 0.0041
847 Mu-type opioid receptor OPRM1 0.004
373 Transthyretin TTR 0.004
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.004
626 Cysteine dioxygenase type 1 CDO1 0.004
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0039
941 Betaine--homocysteine S-methyltransferase 1 BHMT 0.0039
3884 SHMT2 protein SHMT2 0.0039
3901 SHMT2 protein SHMT2 0.0039
3885 Hypothetical protein DKFZp686P09201 DKFZp686P09201 0.0039
3879 Serine hydroxymethyltransferase 2 Not Available 0.0039
321 Serine hydroxymethyltransferase, mitochondrial SHMT2 0.0039
3893 DDC protein DDC 0.0038
334 S-adenosylmethionine synthetase isoform type-2 MAT2A 0.0038
3891 Putative L-Dopa decarboxylase DDC 0.0037
6086 Gamma-aminobutyric acid receptor subunit gamma-2 GABRG2 0.0036
453 S-adenosylmethionine synthetase isoform type-1 MAT1A 0.0036
4100 Gamma-aminobutyric-acid receptor subunit beta-2 GABRB2 0.0036
52 Pyruvate kinase isozymes R/L PKLR 0.0035
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0035
6859 Protein S100-A4 S100A4 0.0035
4085 Peptidyl-prolyl cis-trans isomerase C PPIC 0.0035
4088 Probable prolyl-tRNA synthetase, mitochondrial PARS2 0.0035
4083 Peptidyl-prolyl cis-trans isomerase H PPIH 0.0035
4087 Pyrroline 5-carboxylate reductase isoform P5CR2 0.0035
4090 Chromosome 14 open reading frame 149 C14orf149 0.0035
4082 Proline oxidase, mitochondrial PRODH 0.0035
797 Sodium-dependent proline transporter SLC6A7 0.0035
4086 Peptidyl-prolyl cis-trans isomerase G PPIG 0.0035
3991 Glutamine-dependent NAD(+) synthetase NADSYN1 0.0034
3984 Probable glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial PET112L 0.0034
5 Glutaminase liver isoform, mitochondrial GLS2 0.0034
917 Glutaminase kidney isoform, mitochondrial GLS 0.0034
355 GMP synthase [glutamine-hydrolyzing] GMPS 0.0034
4353 GMP synthase [glutamine-hydrolyzing] guaA 0.0034
3982 Phosphoribosylformylglycinamidine synthase PFAS 0.0034
5261 Phosphoribosylformylglycinamidine synthase purL 0.0034
420 Glutamate decarboxylase 1 GAD1 0.0034
3900 Glutamate decarboxylase 1 GAD1 0.0034
665 Phosphoserine aminotransferase PSAT1 0.0034
4652 Phosphoserine aminotransferase serC 0.0034
3895 Kynurenine--oxoglutarate transaminase 3 CCBL2 0.0034
801 Kynurenine/alpha-aminoadipate aminotransferase mitochondrial AADAT 0.0034
110 Pyruvate dehydrogenase E1 component subunit beta, mitochondrial PDHB 0.0034
771 Pyruvate carboxylase, mitochondrial PC 0.0034
1898 Cytochrome P450 1B1 CYP1B1 0.0034
367 Serine hydroxymethyltransferase, cytosolic SHMT1 0.0034
6142 Solute carrier family 22 member 8 SLC22A8 0.0033
1671 Excitatory amino acid transporter 3 SLC1A1 0.0033
840 Methionine synthase reductase, mitochondrial MTRR 0.0033
98 Pyruvate kinase isozymes M1/M2 PKM2 0.0032
210 Bifunctional aminoacyl-tRNA synthetase [Includes: Glutamyl-tRNA synthetase EPRS 0.0031
2632 Adenylosuccinate synthetase purA 0.0031
3323 Adenylosuccinate synthetase purA 0.0031
3975 Adenylosuccinate synthetase ADSS 0.0031
4598 Adenylosuccinate synthetase Adss 0.0031
6817 Adenylosuccinate synthetase purA 0.0031
3972 Adenylosuccinate synthetase isozyme 2 ADSS 0.0031
533 Aminoacylase-1 ACY1 0.0031
3969 Multifunctional protein ADE2 [Includes: Phosphoribosylaminoimidazole- succinocarboxamide synthase PAICS 0.0031
799 Aspartyl-tRNA synthetase, cytoplasmic DARS 0.0031
209 Aspartoacylase ASPA 0.0031
3979 Aspartoacylase-2 ACY3 0.0031
3976 Aspartyl-tRNA synthetase, mitochondrial DARS2 0.0031
513 Calcium-binding mitochondrial carrier protein Aralar2 SLC25A13 0.0031
305 Mitochondrial aspartate-glutamate carrier protein SLC25A13 0.0031
262 Calcium-binding mitochondrial carrier protein Aralar1 SLC25A12 0.0031
3908 P-selectin cytoplasmic tail-associated protein pcap 0.0031
3896 CDNA FLJ46802 fis, clone TRACH3032150, moderately similar to Cysteine sulfinic acid decarboxylase GADL1 0.0031
3911 Uncharacterized protein C20orf38 SPTLC3 0.0031
3906 Serine dehydratase-like SDSL 0.0031
3881 Selenocysteine lyase variant Not Available 0.0031
3887 Phosphorylase PYGB 0.0031
3915 Cysteine sulfinic acid decarboxylase-related protein 1 CSAD 0.0031
3914 Alanine-glyoxylate aminotransferase homolog TLH6 0.0031
3878 GAD1 protein GAD1 0.0031
3883 Ornithine aminotransferase variant Not Available 0.0031
306 Pyridoxal phosphate phosphatase PDXP 0.0031
3909 Hepatic peroxysomal alanine:glyoxylate aminotransferase Not Available 0.0031
855 Sphingosine-1-phosphate lyase 1 SGPL1 0.0031
809 Methionine synthase MTR 0.0031
2935 Methionine synthase metH 0.0031
3880 Serine hydroxymethyltransferase 1 Not Available 0.0031
3910 O-phosphoseryl-tRNA(Sec) selenium transferase SEPSECS 0.0031
3894 KIAA0251 protein PDXDC1 0.0031
3875 Glycogen phosphorylase, brain form PYGB 0.0031
3882 Brain glycogen phosphorylase variant Not Available 0.0031
3903 Aminolevulinate, delta-, synthase 2 ALAS2 0.0031
3886 Migration-inducing protein 4 ALAS1 0.0031
3905 Molybdenum cofactor sulfurase MOCOS 0.0031
914 Formimidoyltransferase-cyclodeaminase FTCD 0.003
4084 Peptidyl-prolyl cis-trans isomerase B PPIB 0.003
4000 Prolyl 4-hydroxylase subunit alpha-2 P4HA2 0.0029
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0029
1008 CTP synthase 1 CTPS 0.0029
3988 Protein-glutamine gamma-glutamyltransferase K TGM1 0.0029
3985 Glucosamine--fructose-6-phosphate aminotransferase [isomerizing] 2 GFPT2 0.0029
3990 Protein-glutamine gamma-glutamyltransferase 4 TGM4 0.0029
3986 Protein-glutamine gamma-glutamyltransferase 6 TGM6 0.0029
3992 Protein-glutamine gamma-glutamyltransferase Z TGM7 0.0029
3983 Protein-glutamine gamma-glutamyltransferase 5 TGM5 0.0029
3989 Glutaminyl-tRNA synthetase QARS 0.0029
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0028
3913 Glutamic acid decarboxylase GAD65 0.0027
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0027
248 Pyrroline-5-carboxylate reductase 1 PYCR1 0.0027
802 Pyrroline-5-carboxylate reductase 2 PYCR2 0.0027
585 Aspartyl/asparaginyl beta-hydroxylase ASPH 0.0027
4160 Voltage-dependent calcium channel subunit alpha-2/delta-2 CACNA2D2 0.0027
2554 Peptidyl-prolyl cis-trans isomerase, mitochondrial PPIF 0.0027
776 Bile salt export pump ABCB11 0.0026
2795 Methionine aminopeptidase 2 METAP2 0.0026
3917 Methylenetetrahydrofolate reductase MTHFR 0.0026
3949 Prolyl 3-hydroxylase 2 LEPREL1 0.0025
3945 Prolyl 3-hydroxylase 1 LEPRE1 0.0025
3951 Prolyl 3-hydroxylase 3 LEPREL2 0.0025
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0025
1596 Protein-glutamine gamma-glutamyltransferase 2 TGM2 0.0024
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 0.0024
6 Coagulation factor XIII A chain F13A1 0.0024
67 Prolyl 4-hydroxylase subunit alpha-1 P4HA1 0.0023
203 Pyridoxine-5'-phosphate oxidase PNPO 0.0023
472 Ornithine aminotransferase, mitochondrial OAT 0.0023
1524 Peptidyl-prolyl cis-trans isomerase A PPIA 0.0023
6700 Peptidyl-prolyl cis-trans isomerase A ppiA 0.0023
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0023
413 Amidophosphoribosyltransferase PPAT 0.0023
2515 Amidophosphoribosyltransferase purF 0.0023
3714 Amidophosphoribosyltransferase purF 0.0023
505 Glutamate [NMDA] receptor subunit epsilon-3 GRIN2C 0.0022
4058 Glycine N-acyltransferase-like protein 2 GLYATL2 0.0022
4057 Glycine N-acyltransferase GLYAT 0.0022
4059 Glycine N-acyltransferase-like protein 1 GLYATL1 0.0022
4056 N-arachidonyl glycine receptor GPR18 0.0022
4061 Peroxisomal sarcosine oxidase PIPOX 0.0022
4055 Bile acid CoA:amino acid N-acyltransferase BAAT 0.0022
1236 Sodium- and chloride-dependent glycine transporter 1 SLC6A9 0.0022
4062 Sodium- and chloride-dependent glycine transporter 2 SLC6A5 0.0022
4060 Vesicular inhibitory amino acid transporter SLC32A1 0.0022
1088 5-aminolevulinate synthase, erythroid-specific, mitochondrial ALAS2 0.0022
1466 Glycyl-tRNA synthetase GARS 0.0022
3978 Adenylosuccinate synthetase isozyme 1 ADSSL1 0.0021
904 Glutathione S-transferase P GSTP1 0.002
2339 Protein-glutamine gamma-glutamyltransferase E TGM3 0.002
449 Ornithine decarboxylase ODC1 0.002
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.0019
10 Glycogen phosphorylase, liver form PYGL 0.0018
4054 Glycine cleavage system H protein, mitochondrial GCSH 0.0017
62 Glycine receptor subunit beta GLRB 0.0017
383 Glycine amidinotransferase, mitochondrial GATM 0.0016
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0016
411 Glycine N-methyltransferase GNMT 0.0016
5682 Ribonuclease pancreatic RNASE1 0.0016
820 Glycine receptor subunit alpha-2 GLRA2 0.0014
1152 Glycogen phosphorylase, muscle form PYGM 0.0014
461 Glycine receptor subunit alpha-3 GLRA3 0.0014
4023 N-acetylglutamate synthase, mitochondrial NAGS 0.0011
4024 Mitochondrial glutamate carrier 2 SLC25A18 0.0011
4025 Mitochondrial glutamate carrier 1 SLC25A22 0.0011
4021 Probable glutamyl-tRNA synthetase, mitochondrial EARS2 0.0011
664 Glutamate decarboxylase 2 GAD2 0.0011
3890 Glutamate decarboxylase 2 GAD2 0.0011
4026 Aspartyl aminopeptidase DNPEP 0.0011
4022 Glutamate--ammonia ligase domain-containing protein 1 LGSN 0.0011
1912 Excitatory amino acid transporter 1 SLC1A3 0.0011
4016 Excitatory amino acid transporter 5 SLC1A7 0.0011
4019 Excitatory amino acid transporter 4 SLC1A6 0.0011
4017 5-oxoprolinase OPLAH 0.0011
1047 Excitatory amino acid transporter 2 SLC1A2 0.0011
926 Metabotropic glutamate receptor 7 GRM7 0.0011
920 Glutamate receptor, ionotropic kainate 5 GRIK5 0.0011
4018 Glutamate receptor delta-2 subunit GRID2 0.0011
915 Delta 1-pyrroline-5-carboxylate synthetase ALDH18A1 0.0011
922 Glutamate receptor 4 GRIA4 0.0011
927 Metabotropic glutamate receptor 8 GRM8 0.0011
925 Metabotropic glutamate receptor 4 GRM4 0.0011
924 Glutamate receptor, ionotropic kainate 3 GRIK3 0.0011
919 Glutamate receptor, ionotropic kainate 4 GRIK4 0.0011
4020 Glutamyl aminopeptidase ENPEP 0.0011
4027 Glutamate receptor delta-1 subunit GRID1 0.0011
830 Glutamate dehydrogenase 2, mitochondrial GLUD2 0.0009
625 Glutamate carboxypeptidase 2 FOLH1 0.0009
382 Glutamate receptor, ionotropic kainate 1 GRIK1 0.0008
916 Metabotropic glutamate receptor 1 GRM1 0.0008
923 Glutamate receptor 3 GRIA3 0.0008
201 Glutamate dehydrogenase 1, mitochondrial GLUD1 0.0008
448 Vitamin K-dependent gamma-carboxylase GGCX 0.0008
83 Alpha-aminoadipic semialdehyde synthase, mitochondrial AASS 0.0008
773 Folylpolyglutamate synthase, mitochondrial FPGS 0.0007
705 Glutamate receptor 1 GRIA1 0.0006
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0006
918 Glutamate receptor, ionotropic kainate 2 GRIK2 0.0005
921 Glutamate receptor 2 GRIA2 0.0005
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