DT-Web

DB00999 - Hydrochlorothiazide


Identification
Name Hydrochlorothiazide
Accession Number DB00999 (APRD00092)
Type small molecule
Description A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 297.739
Groups approved
Monoisotopic Weight 296.964474846
Pharmacology
Indication For the treatment of high blood pressure and management of edema.
Mechanism of action Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.
Absorption 50-60%
Protein binding 67.9%
Biotransformation Hydrochlorothiazide is not metabolized.
Route of elimination Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
Toxicity The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in the mouse and rat.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Deslanoside Possible electrolyte variations and arrhythmias
Diazoxide Significant hyperglycemic effect
Digitoxin Possible electrolyte variations and arrhythmias
Digoxin Possible electrolyte variations and arrhythmias
Dihydrocodeine Dihydrocodeine may enhance the hypotensive effects of thiazide diuretics. It is recommended to monitor therapy.
Dofetilide Increased risk of cardiotoxicity and arrhythmias
Indacaterol Concomitant therapy may increase the risk of hypokalemia via intracellular shunting. Monitor for adverse effects and especially for cardiovascular effects associated with hypokalemia.
Insulin Lispro Concomitant therapy with diuretics may reduce the blood-glucose-lowering effect of insulin lispro.
Lithium The thiazide diuretic, hydrochlorothiazide, may increase serum levels of lithium.
Tenoxicam Tenoxicam may antagonize the blood pressure lowering effect of Hydrochlorothiazide. Monitor for changes in the therapeutic effect of Hydrochlorothiazide if Tenoxicam is initiated, discontinued or dose changed.
Trandolapril The thiazide diuretic, Hydrochlorothiazide, may increase the hypotensive effect of Trandolapril. Hydrochlorothiazide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Food Interactions
  • Take with food.
  • Increase potassium intake; add a banana or orange juice; unless instructed otherwise.
  • Avoid alcohol.
  • Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.
  • Avoid natural licorice.
  • Avoid excess salt/sodium unless otherwise instructed by your physician.

Targets


Solute carrier family 12 member 3
Name Solute carrier family 12 member 3
Gene Name SLC12A3
Pharmacological action yes
Actions inhibitor
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Ran XW, Wang C, Dai F, Jiang JJ, Tong NW, Li XJ, Liang JZ: [A case of Gitelman's syndrome presenting with severe hypocalcaemia and hypokalemic periodic paralysis] Sichuan Da Xue Xue Bao Yi Xue Ban. 2005 Jul;36(4):583-7. - Pubmed
  • Turner ST, Schwartz GL, Chapman AB, Boerwinkle E: WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic. Hypertension. 2005 Oct;46(4):758-65. Epub 2005 Sep 19. - Pubmed
  • Abuladze N, Yanagawa N, Lee I, Jo OD, Newman D, Hwang J, Uyemura K, Pushkin A, Modlin RL, Kurtz I: Peripheral blood mononuclear cells express mutated NCCT mRNA in Gitelman's syndrome: evidence for abnormal thiazide-sensitive NaCl cotransport. J Am Soc Nephrol. 1998 May;9(5):819-26. - Pubmed
  • Barry EL, Gesek FA, Kaplan MR, Hebert SC, Friedman PA: Expression of the sodium-chloride cotransporter in osteoblast-like cells: effect of thiazide diuretics. Am J Physiol. 1997 Jan;272(1 Pt 1):C109-16. - Pubmed
  • Kurschat C, Heering P, Grabensee B: [Gitelman's syndrome: an important differential diagnosis of hypokalemia] Dtsch Med Wochenschr. 2003 May 30;128(22):1225-8. - Pubmed
DTHybrid score 0.9594
Carbonic anhydrase 1
Name Carbonic anhydrase 1
Gene Name CA1
Pharmacological action unknown
Actions inhibitor
References
  • Puscas I, Coltau M, Baican M, Domuta G, Hecht A: Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action. Drugs Exp Clin Res. 1999;25(6):271-9. - Pubmed
  • Couloigner V, Loiseau A, Sterkers O, Amiel C, Ferrary E: Effect of locally applied drugs on the endolymphatic sac potential. Laryngoscope. 1998 Apr;108(4 Pt 1):592-8. - Pubmed
  • Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. Epub 2008 Dec 24. - Pubmed
DTHybrid score 0.9926
Carbonic anhydrase 2
Name Carbonic anhydrase 2
Gene Name CA2
Pharmacological action unknown
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Meyerson LR, Nesta D: [3H]acetazolamide binding to carbonic anhydrase in normal and transformed cells. Biochem Pharmacol. 1991 Mar 15-Apr 1;41(6-7):995-1000. - Pubmed
  • Schaeffer P, Vigne P, Frelin C, Lazdunski M: Identification and pharmacological properties of binding sites for the atypical thiazide diuretic, indapamide. Eur J Pharmacol. 1990 Jul 17;182(3):503-8. - Pubmed
  • Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. Epub 2008 Dec 24. - Pubmed
DTHybrid score 1.9708
Carbonic anhydrase 4
Name Carbonic anhydrase 4
Gene Name CA4
Pharmacological action unknown
Actions inhibitor
References
  • Puscas I, Coltau M, Baican M, Domuta G, Hecht A: Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action. Drugs Exp Clin Res. 1999;25(6):271-9. - Pubmed
  • Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. Epub 2008 Dec 24. - Pubmed
DTHybrid score 0.7554
Carbonic anhydrase 9
Name Carbonic anhydrase 9
Gene Name CA9
Pharmacological action unknown
Actions inhibitor
References
  • Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. Epub 2008 Dec 24. - Pubmed
DTHybrid score 0.4699
Carbonic anhydrase 12
Name Carbonic anhydrase 12
Gene Name CA12
Pharmacological action unknown
Actions inhibitor
References
  • Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. Epub 2008 Dec 24. - Pubmed
DTHybrid score 0.47
Calcium-activated potassium channel subunit alpha 1
Name Calcium-activated potassium channel subunit alpha 1
Gene Name KCNMA1
Pharmacological action unknown
Actions other/unknown
References
  • Tricarico D, Barbieri M, Mele A, Carbonara G, Camerino DC: Carbonic anhydrase inhibitors are specific openers of skeletal muscle BK channel of K+-deficient rats. FASEB J. 2004 Apr;18(6):760-1. Epub 2004 Feb 6. - Pubmed
DTHybrid score 0.4742

Transporters


Solute carrier family 22 member 6
Name Solute carrier family 22 member 6
Gene Name SLC22A6
Actions inhibitor
References
  • Race JE, Grassl SM, Williams WJ, Holtzman EJ: Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3). Biochem Biophys Res Commun. 1999 Feb 16;255(2):508-14. - Pubmed
  • Uwai Y, Saito H, Hashimoto Y, Inui KI: Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther. 2000 Oct;295(1):261-5. - Pubmed
DTHybrid score 0.3952

Predictions


Id Partner name Gene Name Score
558 Solute carrier family 12 member 1 SLC12A1 0.1963
6126 Carbonic anhydrase 7 CA7 0.1642
806 Sodium/potassium-transporting ATPase alpha-1 chain ATP1A1 0.1464
6123 Carbonic anhydrase 5A, mitochondrial CA5A 0.1066
1405 Thiopurine S-methyltransferase TPMT 0.1043
2176 Protein S100-P S100P 0.0971
6131 Carbonic anhydrase 14 CA14 0.087
4512 Cytochrome P450 3A4 CYP3A4 0.0861
6122 Carbonic anhydrase 3 CA3 0.0828
6124 Carbonic anhydrase 5B, mitochondrial CA5B 0.066
1024 Solute carrier family 22 member 11 SLC22A11 0.0639
4757 Cytochrome P450 2C9 CYP2C9 0.062
6142 Solute carrier family 22 member 8 SLC22A8 0.0572
253 Sodium/potassium-transporting ATPase gamma chain FXYD2 0.0571
310 Solute carrier family 12 member 2 SLC12A2 0.0567
6013 Cytochrome P450 2E1 CYP2E1 0.0532
3426 Glutamine synthetase glnA 0.0507
3987 Glutamine synthetase GLUL 0.0507
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0506
6016 Cytochrome P450 2C19 CYP2C19 0.0385
587 Serum albumin ALB 0.0381
6024 Cytochrome P450 1A1 CYP1A1 0.0361
997 Protein kinase C beta type PRKCB 0.036
634 Squalene monooxygenase SQLE 0.0336
7196 Squalene monooxygenase ERG1 0.0336
1970 Protein kinase C alpha type PRKCA 0.033
2408 Tyrosine-protein kinase SYK SYK 0.0328
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0311
4119 Cytochrome P450 2D6 CYP2D6 0.0295
1025 Aquaporin-1 AQP1 0.029
6143 Solute carrier family 22 member 7 SLC22A7 0.0285
6127 Carbonic anhydrase-related protein CA8 0.0282
6129 Carbonic anhydrase-related protein 11 CA11 0.0281
6128 Carbonic anhydrase-related protein 10 CA10 0.0281
6133 Sodium channel subunit beta-2 SCN2B 0.0281
6132 Sodium channel subunit beta-1 SCN1B 0.0281
6134 Sodium channel subunit beta-3 SCN3B 0.0281
6135 Sodium channel subunit beta-4 SCN4B 0.0281
4200 Cytochrome P450 1A2 CYP1A2 0.0257
20 Prostaglandin G/H synthase 1 PTGS1 0.0256
2236 Casein kinase II subunit alpha CSNK2A1 0.0254
290 Prostaglandin G/H synthase 2 PTGS2 0.025
6130 Carbonic anhydrase 13 CA13 0.025
3803 Sodium channel protein type 3 subunit alpha SCN3A 0.0246
5718 Cytochrome P450 2A6 CYP2A6 0.0239
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0232
6263 cAMP-dependent protein kinase catalytic subunit alpha PRKACA 0.0223
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0219
3802 Sodium channel protein type 2 subunit alpha SCN2A 0.0217
3804 Sodium channel protein type 4 subunit alpha SCN4A 0.0207
3623 Divalent-cation tolerance protein cutA cutA 0.0206
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.02
1995 Sodium channel protein type 9 subunit alpha SCN9A 0.0198
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.0198
241 Calcium-transporting ATPase type 2C member 1 ATP2C1 0.0197
537 ATP synthase delta chain, mitochondrial ATP5D 0.0188
1588 Multidrug resistance protein 1 ABCB1 0.0182
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0179
559 NADH-ubiquinone oxidoreductase chain 1 MT-ND1 0.0174
118 Organic cation/carnitine transporter 2 SLC22A5 0.0173
482 Glycine receptor subunit alpha-1 GLRA1 0.017
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.017
382 Glutamate receptor, ionotropic kainate 1 GRIK1 0.0168
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0162
6020 Aldehyde oxidase AOX1 0.0155
3941 Amine oxidase [flavin-containing] A MAOA 0.0151
633 Penicillin-binding proteins 1A/1B pbpA 0.0149
6012 Tryptophan 2,3-dioxygenase TDO2 0.0145
2164 Multidrug resistance-associated protein 4 ABCC4 0.0142
404 DNA gyrase subunit A gyrA 0.0139
6224 DNA gyrase subunit A gyrA 0.0139
705 Glutamate receptor 1 GRIA1 0.0137
3226 UPF0234 protein HI1034 HI_1034 0.0135
4924 Cytochrome P450 2C8 CYP2C8 0.0134
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0132
3384 Macrophage migration inhibitory factor MIF 0.0132
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0131
3939 Amine oxidase [flavin-containing] B MAOB 0.0131
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0124
308 30S ribosomal protein S12 rpsL 0.0122
6704 30S ribosomal protein S12 rpsL 0.0122
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.0117
338 DNA polymerase UL30 0.0116
379 DNA polymerase UL54 0.0116
697 DNA polymerase ORF28 0.0116
2482 DNA polymerase 43 0.0116
4104 DNA polymerase BALF5 0.0116
4790 Glycosyltransferase GtfA gtfA 0.011
3105 M-phase inducer phosphatase 2 CDC25B 0.0108
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0107
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0106
3639 Thymidine phosphorylase deoA 0.0103
3936 Thymidine phosphorylase TYMP 0.0103
862 Multidrug resistance-associated protein 1 ABCC1 0.0101
6154 Multidrug and toxin extrusion protein 1 SLC47A1 0.01
645 Penicillin-binding protein 1A mrcA 0.01
5805 Penicillin-binding protein 1A ponA 0.01
6185 Penicillin-binding protein 1A mrcA 0.01
6799 Penicillin-binding protein 1A pbpA 0.01
5849 cAMP-dependent protein kinase type I-alpha regulatory subunit PRKAR1A 0.0092
1244 Low-density lipoprotein receptor-related protein 2 LRP2 0.009
738 Monocarboxylate transporter 1 SLC16A1 0.009
6030 Cytochrome P450 2B6 CYP2B6 0.0088
723 Cytosolic phospholipase A2 PLA2G4A 0.0083
2016 Dipeptidase 1 DPEP1 0.0082
1768 Guanine nucleotide-binding protein G(I)/G(S)/G(O) gamma-2 subunit GNG2 0.0082
1571 G protein-activated inward rectifier potassium channel 1 KCNJ3 0.0082
1268 Neuropeptide S receptor NPSR1 0.0082
1581 G protein-activated inward rectifier potassium channel 2 KCNJ6 0.0082
6145 Solute carrier family 22 member 1 SLC22A1 0.008
6935 Small conductance calcium-activated potassium channel protein 2 KCNN2 0.0077
6933 Calcium-activated potassium channel subunit beta-4 KCNMB4 0.0077
6931 Calcium-activated potassium channel subunit beta-1 KCNMB1 0.0077
6932 Calcium-activated potassium channel subunit beta-3 KCNMB3 0.0077
6934 Small conductance calcium-activated potassium channel protein 1 KCNN1 0.0077
6936 Small conductance calcium-activated potassium channel protein 3 KCNN3 0.0077
543 Penicillin-binding protein 1B mrcB 0.0077
6186 Penicillin-binding protein 1B ponB 0.0077
6822 Penicillin-binding protein 1b pbp1b 0.0077
6844 Penicillin-binding protein 1b pbp1b 0.0077
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0075
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0073
22 30S ribosomal protein S4 rpsD 0.0072
6714 30S ribosomal protein S4 rpsD 0.0072
776 Bile salt export pump ABCB11 0.0072
3806 cGMP-dependent 3',5'-cyclic phosphodiesterase PDE2A 0.0071
6144 Solute carrier family 22 member 2 SLC22A2 0.007
6072 Potassium channel subfamily K member 3 KCNK3 0.0069
6073 Potassium channel subfamily K member 9 KCNK9 0.0069
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0069
4118 Cytochrome P450 3A5 CYP3A5 0.0068
140 30S ribosomal protein S9 rpsI 0.0068
6719 30S ribosomal protein S9 rpsI 0.0068
6725 30S ribosomal protein S9 rpsI 0.0068
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0068
3627 UPF0190 protein yedY yedY 0.0067
1392 Catenin beta-1 CTNNB1 0.0067
3352 Structural polyprotein Not Available 0.0067
3628 Structural polyprotein Not Available 0.0067
4892 Structural polyprotein Not Available 0.0067
6107 Cytochrome P450 3A7 CYP3A7 0.0067
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0066
6155 ATP-binding cassette transporter sub-family C member 11 ABCC11 0.0064
477 DNA topoisomerase 4 subunit A parC 0.0064
886 DNA topoisomerase 4 subunit A parC 0.0064
6226 DNA topoisomerase 4 subunit A parC 0.0064
5463 Calcium-activated potassium channel subunit beta 2 KCNMB2 0.0063
5626 Nucleoside diphosphate kinase B NME2 0.006
2320 Thymidine kinase, cytosolic TK1 0.0059
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0058
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0056
6140 Ileal sodium/bile acid cotransporter SLC10A2 0.0056
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0055
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0055
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0054
833 Organic cation/carnitine transporter 1 SLC22A4 0.0054
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0054
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0053
6270 Group IIE secretory phospholipase A2 PLA2G2E 0.0053
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.0052
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0052
6136 Multidrug resistance-associated protein 5 ABCC5 0.0052
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.0051
438 Taste receptor type 1 member 2 TAS1R2 0.0051
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0049
277 Purine nucleoside phosphorylase PNP 0.0049
2870 Purine nucleoside phosphorylase punA 0.0049
2945 Purine nucleoside phosphorylase punA 0.0049
4659 Purine nucleoside phosphorylase TM_1596 0.0049
4825 Purine nucleoside phosphorylase TTHA1435 0.0049
5294 Nucleoside diphosphate kinase A NME1 0.0048
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0048
2207 Rhodopsin RHO 0.0047
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0046
373 Transthyretin TTR 0.0046
3917 Methylenetetrahydrofolate reductase MTHFR 0.0046
3686 Acyl-CoA thioesterase I precursor tesA 0.0045
6177 UDP-glucuronosyltransferase 1-10 UGT1A10 0.0045
6106 Cytochrome P450 2C18 CYP2C18 0.0045
260 Cytochrome P450 51 ERG11 0.0045
761 Cytochrome P450 51 ERG11 0.0045
3163 Cytochrome P450 51 cyp51 0.0045
6339 Ig kappa chain V-II region RPMI 6410 Not Available 0.0044
6046 Voltage-gated calcium channel beta 1 subunit splice variant CavB1d CACNB1 0.0044
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0043
817 DNA topoisomerase 2-alpha TOP2A 0.0043
5698 Riboflavin synthase alpha chain ribE 0.0043
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.0041
115 Penicillin-binding protein 2 mrdA 0.0041
6069 Penicillin-binding protein 2 mrdA 0.0041
6118 Penicillin-binding protein 2 penA 0.0041
6187 Penicillin-binding protein 2 pbpA 0.0041
6686 Penicillin-binding protein 2 pbp2 0.0041
6939 Penicillin-binding protein 2 mrdA 0.0041
7163 Penicillin-binding protein 2 pbpA 0.0041
887 DNA gyrase subunit B gyrB 0.0041
4150 DNA gyrase subunit B gyrB 0.0041
6225 DNA gyrase subunit B gyrB 0.0041
408 Riboflavin kinase RFK 0.0041
6141 Sodium/bile acid cotransporter SLC10A1 0.0041
24 Thymidylate synthase TMP1 0.0041
359 Thymidylate synthase TYMS 0.0041
2626 Thymidylate synthase thyA 0.0041
2729 Thymidylate synthase thyA 0.0041
5352 Thymidylate synthase THYA 0.0041
315 Arginase-1 ARG1 0.004
275 Arachidonate 5-lipoxygenase ALOX5 0.004
6045 Voltage-dependent calcium channel subunit alpha-2/delta-3 CACNA2D3 0.004
1558 Transient receptor potential cation channel subfamily V member 1 TRPV1 0.004
3811 Cytochrome P450 19A1 CYP19A1 0.0039
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0039
1 Peptidoglycan synthetase ftsI ftsI 0.0038
4155 Peptidoglycan synthetase ftsI ftsI 0.0038
4162 Potassium voltage-gated channel subfamily KQT member 3 KCNQ3 0.0037
5353 Glutamate decarboxylase alpha gadA 0.0037
6181 UDP-glucuronosyltransferase 1-8 UGT1A8 0.0036
244 Angiotensin-converting enzyme ACE 0.0036
492 Histamine H1 receptor HRH1 0.0035
6148 Multidrug resistance-associated protein 7 ABCC10 0.0035
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0035
7 Nitric oxide synthase, inducible NOS2 0.0035
889 3-oxoacyl-[acyl-carrier-protein] synthase 1 fabB 0.0035
6860 3-oxoacyl-[acyl-carrier-protein] synthase 1 kasA 0.0035
3932 Glutathione S-transferase A2 GSTA2 0.0034
291 Nitric-oxide synthase, endothelial NOS3 0.0034
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0033
65 Matrix metalloproteinase-9 Not Available 0.0033
332 Beta-lactamase blaZ 0.0033
2478 Beta-lactamase ampC 0.0033
2613 Beta-lactamase ampC 0.0033
2635 Beta-lactamase ampC 0.0033
2700 Beta-lactamase penP 0.0033
5445 Beta-lactamase blaB 0.0033
6019 Beta-lactamase SHV-7 0.0033
6701 Beta-lactamase cphA 0.0033
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.0032
6149 Solute carrier family 22 member 10 SLC22A10 0.0032
139 Aldo-keto reductase family 1 member C1 AKR1C1 0.0031
342 P protein [Includes: DNA-directed DNA polymerase P 0.0031
612 P protein [Includes: DNA-directed DNA polymerase P 0.0031
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0031
654 Flavin reductase BLVRB 0.0029
6147 Solute carrier family 22 member 3 SLC22A3 0.0029
3688 Branched-chain-amino-acid aminotransferase ilvE 0.0028
6043 Putative G-protein coupled receptor 44 GPR44 0.0028
1757 Myeloperoxidase MPO 0.0028
4252 Penicillin-binding protein 5 dacA 0.0028
159 Penicillin-binding protein 2B penA 0.0028
6121 Penicillin-binding protein 2B penA 0.0028
1867 Major prion protein PRNP 0.0028
650 Aldo-keto reductase family 1 member C3 AKR1C3 0.0028
3685 Catabolite gene activator crp 0.0027
4655 Adenylate cyclase cyaC 0.0027
4759 Adenylate cyclase cyaB2 0.0027
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0026
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0026
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0026
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0026
293 Gamma-glutamyl hydrolase GGH 0.0026
4773 Deoxycytidine kinase DCK 0.0026
130 Prostacyclin synthase PTGIS 0.0025
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0025
509 Thymidine kinase TK 0.0025
570 Thymidine kinase TK 0.0025
2559 Thymidine kinase TK 0.0025
3430 Thymidine kinase tdk 0.0025
3518 Thymidine kinase TK 0.0025
5301 Thymidine kinase tdk 0.0025
5771 Thymidine kinase ORF36 0.0025
7009 Thymidine kinase ORF36 0.0025
707 72 kDa type IV collagenase MMP2 0.0025
6180 UDP-glucuronosyltransferase 2B4 UGT2B4 0.0024
6207 30S ribosomal protein S14 rpsN 0.0024
6209 30S ribosomal protein S19 rpsS 0.0024
6712 30S ribosomal protein S19 rpsS 0.0024
6726 30S ribosomal protein S19 rpsS 0.0024
471 Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+) SLC6A14 0.0024
2249 Aspartate aminotransferase aspC 0.0023
2671 Aspartate aminotransferase aspC 0.0023
5490 Aspartate aminotransferase Not Available 0.0023
1650 Heme carrier protein 1 SLC46A1 0.0023
6167 Organic solute transporter subunit beta OSTB 0.0023
4760 Mll3241 protein mll3241 0.0023
6166 Organic solute transporter subunit alpha OSTA 0.0023
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 0.0022
1196 Complement decay-accelerating factor CD55 0.0021
6033 High affinity interleukin-8 receptor A CXCR1 0.0021
718 Folate receptor gamma FOLR3 0.0021
299 Folate receptor beta FOLR2 0.0021
804 Mitochondrial folate transporter/carrier SLC25A32 0.0021
1198 Serum paraoxonase/arylesterase 1 PON1 0.0021
6223 Penicillin-binding protein 1C pbpC 0.0021
40 RAF proto-oncogene serine/threonine-protein kinase RAF1 0.0021
527 Prostacyclin receptor PTGIR 0.0021
672 Prostaglandin F2-alpha receptor PTGFR 0.002
146 Androgen receptor AR 0.002
1714 Mitogen-activated protein kinase 3 MAPK3 0.0019
867 Penicillin-binding protein 3 pbpC 0.0019
6119 Penicillin-binding protein 3 pbp3 0.0019
7154 Penicillin-binding protein 3 pbp3 0.0019
7157 Penicillin-binding protein 3 LMHCC_2184 0.0019
7162 Penicillin-binding protein 3 pbpB 0.0019
7172 Penicillin-binding protein 3 pbp3 0.0019
1654 Interleukin-1 beta IL1B 0.0019
2808 Chloramphenicol acetyltransferase 3 cat3 0.0019
698 B-Raf proto-oncogene serine/threonine-protein kinase BRAF 0.0018
53 Solute carrier family 12 member 5 SLC12A5 0.0018
663 Solute carrier family 12 member 4 SLC12A4 0.0018
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0018
6014 Cytochrome P450 2A13 CYP2A13 0.0018
2417 Chloramphenicol acetyltransferase cat 0.0017
3278 Chloramphenicol acetyltransferase cat 0.0017
2810 Dr hemagglutinin structural subunit draA 0.0017
2718 Chloramphenicol 3-O phosphotransferase Not Available 0.0017
6179 UDP-glucuronosyltransferase 2B17 UGT2B17 0.0017
380 Cytochrome P450 17A1 CYP17A1 0.0017
1502 Peroxisome proliferator-activated receptor delta PPARD 0.0016
459 Retinoic acid receptor RXR-alpha RXRA 0.0016
6031 Cytochrome P450 3A43 CYP3A43 0.0016
494 Caspase-1 CASP1 0.0015
183 Vascular endothelial growth factor A VEGFA 0.0015
1507 Cytochrome c CYCS 0.0015
4217 Telomerase reverse transcriptase TERT 0.0014
3760 Penicillin-binding protein 5 precursor dacA 0.0014
822 Aldose reductase AKR1B1 0.0014
677 Choline-phosphate cytidylyltransferase A PCYT1A 0.0013
6184 D-alanyl-D-alanine carboxypeptidase dacC dacC 0.0013
2077 Caspase-3 CASP3 0.0013
819 Penicillin-binding protein 4 dacB 0.0012
702 UMP-CMP kinase CMPK1 0.0012
2981 Phospholipase A2, membrane associated PLA2G2A 0.0012
6137 Multidrug resistance-associated protein 6 ABCC6 0.0012
2021 Thrombomodulin THBD 0.0011
2461 D-alanyl-D-alanine carboxypeptidase Not Available 0.0011
5756 D-alanyl-D-alanine carboxypeptidase dac 0.0011
3961 G protein-activated inward rectifier potassium channel 4 KCNJ5 0.0011
3868 Calcineurin subunit B isoform 2 PPP3R2 0.0011
421 Calcium signal-modulating cyclophilin ligand CAMLG 0.0011
1192 Sulfotransferase 1A1 SULT1A1 0.001
70 Type-1 angiotensin II receptor AGTR1 0.001
1275 Estrogen sulfotransferase SULT1E1 0.001
6218 Pannexin-1 PANX1 0.001
1050 Bile salt sulfotransferase SULT2A1 0.001
1039 Histone deacetylase 9 HDAC9 0.0009
521 ATP-binding cassette transporter sub-family C member 9 ABCC9 0.0009
6102 Arylamine N-acetyltransferase 2 NAT2 0.0009
6002 Prostaglandin E2 receptor EP4 subtype PTGER4 0.0009
132 ATP-binding cassette sub-family A member 1 ABCA1 0.0009
5818 Folate receptor alpha FOLR1 0.0008
1524 Peptidyl-prolyl cis-trans isomerase A PPIA 0.0008
6700 Peptidyl-prolyl cis-trans isomerase A ppiA 0.0008
6042 Prostaglandin reductase 2 PTGR2 0.0008
630 Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial ACADSB 0.0008
4037 Hypothetical protein GPX1 0.0008
4297 Hypothetical protein SP_1951 0.0008
4521 Hypothetical protein BC_2969 0.0008
4540 Hypothetical protein TM_1070 0.0008
4555 Hypothetical protein MT1739 0.0008
4569 Hypothetical protein mshD 0.0008
4578 Hypothetical protein PA3270 0.0008
4747 Hypothetical protein PA3967 0.0008
5177 Hypothetical protein TM_0096 0.0008
5194 Hypothetical protein PA1204 0.0008
5240 Hypothetical protein Rv2991 0.0008
5370 Hypothetical protein TM_1158 0.0008
5710 Hypothetical protein Tb927.5.1360 0.0008
4527 Putative hydrolase ycdX ycdX 0.0008
4536 Transcriptional regulator, IclR family TM_0065 0.0008
2501 Protein ygbM ygbM 0.0008
4545 Molybdopterin-converting factor subunit 2 moaE 0.0008
4522 Arginine N-succinyltransferase subunit alpha astA 0.0008
4106 Guanylate kinase GUK1 0.0008
4516 Guanylate kinase gmk 0.0008
4538 Hypothetical protein VC1899 VC_1899 0.0008
4529 Oxalate decarboxylase oxdC oxdC 0.0008
4514 Citrate lyase beta subunit-like protein citE 0.0008
4781 Citrate lyase beta subunit-like protein DR_1240 0.0008
4526 Oligopeptide ABC transporter, periplasmic oligopeptide-binding protein TM_1223 0.0008
4524 Mannose-6-phosphate isomerase yvyI 0.0008
4535 Glutaconyl-CoA decarboxylase subunit alpha gcdA 0.0008
4547 Iron binding protein FbpA fbpA 0.0008
4548 Gyrase B gyrB 0.0008
4546 Aminotransferase, putative TM_1131 0.0008
658 Para-aminobenzoate synthase component 1 pabB 0.0008
4515 Peripheral plasma membrane protein CASK CASK 0.0008
4131 Prostaglandin E2 receptor, EP3 subtype PTGER3 0.0008
182 2-oxoglutarate dehydrogenase E1 component, mitochondrial OGDH 0.0008
406 Prostaglandin E2 receptor, EP2 subtype PTGER2 0.0008
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0008
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0008
3587 Gastrotropin FABP6 0.0008
1792 Tissue-type plasminogen activator PLAT 0.0008
389 Amiloride-sensitive cation channel 2, neuronal ACCN2 0.0008
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0008
273 Apoptosis regulator Bcl-2 BCL2 0.0008
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0008
4496 C-terminal-binding protein 1 CTBP1 0.0008
73 Prostaglandin E2 receptor, EP1 subtype PTGER1 0.0007
4517 Probable butyrate kinase 2 buk2 0.0007
3261 Signal recognition particle protein ffh 0.0007
4528 Phenazine biosynthesis protein PhzD phzD1 0.0007
4533 Glyoxalase family protein BC_1747 0.0007
56 Delta-aminolevulinic acid dehydratase ALAD 0.0007
2356 Delta-aminolevulinic acid dehydratase hemB 0.0007
3613 Delta-aminolevulinic acid dehydratase hemB 0.0007
3674 Delta-aminolevulinic acid dehydratase hemB 0.0007
3759 Glutathione S-transferase gst 0.0007
4541 Glutathione S-transferase GST 0.0007
4542 Glutaminase 1 glsA1 0.0007
4544 Glutaminase 1 glsA1 0.0007
2929 (S)-2-haloacid dehalogenase dhlB 0.0007
2995 (S)-2-haloacid dehalogenase Not Available 0.0007
3237 Beta-lactamase OXA-2 bla 0.0007
4532 Gephyrin GPHN 0.0007
6085 Fatty acid-binding protein, intestinal FABP2 0.0007
170 Succinate semialdehyde dehydrogenase, mitochondrial ALDH5A1 0.0007
2230 Catalase CAT 0.0007
3249 Catalase katA 0.0007
3625 Catalase katA 0.0007
4539 Catalase katA 0.0007
4941 Catalase katB 0.0007
4531 Putative ketoacyl reductase actIII 0.0007
2775 Dihydroorotate dehydrogenase pyrD 0.0007
3467 Methylglyoxal synthase mgsA 0.0007
3583 6-phosphogluconolactonase pgl 0.0007
33 Cystine/glutamate transporter SLC7A11 0.0007
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0006
773 Folylpolyglutamate synthase, mitochondrial FPGS 0.0006
1313 Lactoylglutathione lyase GLO1 0.0006
2525 3-phosphoshikimate 1-carboxyvinyltransferase aroA 0.0006
3201 3-phosphoshikimate 1-carboxyvinyltransferase aroA 0.0006
280 4-aminobutyrate aminotransferase, mitochondrial ABAT 0.0006
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0006
124 Histamine H2 receptor HRH2 0.0006
489 Monocarboxylate transporter 2 SLC16A7 0.0006
2688 Peptide deformylase def 0.0006
2708 Peptide deformylase def 0.0006
3004 Peptide deformylase def 0.0006
4337 Peptide deformylase def 0.0006
4338 Peptide deformylase def 0.0006
5368 Peptide deformylase def 0.0006
5371 Peptide deformylase def 0.0006
6375 Peptide deformylase def 0.0006
6378 Peptide deformylase def 0.0006
6379 Peptide deformylase def 0.0006
6776 Peptide deformylase def 0.0006
6900 Peptide deformylase def 0.0006
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0006
4534 Cytohesin-2 CYTH2 0.0006
3810 Catechol O-methyltransferase COMT 0.0006
2548 Subtilisin Carlsberg apr 0.0006
4269 Hypoxanthine-guanine phosphoribosyltransferase, putative HGPRTase 0.0006
2287 Bifunctional purine biosynthesis protein PURH [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase ATIC 0.0006
6150 Solute carrier organic anion transporter family member 4C1 SLCO4C1 0.0005
4604 Liver carboxylesterase 1 CES1 0.0005
760 Fibroblast growth factor 1 FGF1 0.0005
810 Heme oxygenase 1 HMOX1 0.0005
3391 Heme oxygenase 1 pbsA1 0.0005
3027 Streptavidin Not Available 0.0005
500 Monocarboxylate transporter 4 SLC16A3 0.0005
136 Estrogen receptor ESR1 0.0005
365 Dihydrofolate reductase DHFR 0.0004
2381 Dihydrofolate reductase DFR1 0.0004
2833 Dihydrofolate reductase Not Available 0.0004
2931 Dihydrofolate reductase folA 0.0004
3544 Dihydrofolate reductase folA 0.0004
3682 Dihydrofolate reductase folA 0.0004
6642 Dihydrofolate reductase folA 0.0004
6756 Dihydrofolate reductase dfrA 0.0004
76 Nitric-oxide synthase, brain NOS1 0.0004
5682 Ribonuclease pancreatic RNASE1 0.0004
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