DT-Web

DB00331 - Metformin


Identification
Name Metformin
Accession Number DB00331 (APRD01099)
Type small molecule
Description Metformin is a biguanide antihyperglycemic agent used for treating non-insulin-dependent diabetes mellitus (NIDDM). It improves glycemic control by decreasing hepatic glucose production, decreasing glucose absorption and increasing insulin-mediated glucose uptake. Metformin is the only oral antihyperglycemic agent that is not associated with weight gain. Metformin may induce weight loss and is the drug of choice for obese NIDDM patients. When used alone, metformin does not cause hypoglycemia; however, it may potentiate the hypoglycemic effects of sulfonylureas and insulin. Its main side effects are dyspepsia, nausea and diarrhea. Dose titration and/or use of smaller divided doses may decrease side effects. Metformin should be avoided in those with severely compromised renal function (creatinine clearance < 30 ml/min), acute/decompensated heart failure, severe liver disease and for 48 hours after the use of iodinated contrast dyes due to the risk of lactic acidosis. Lower doses should be used in the elderly and those with decreased renal function. Metformin decreases fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Metformin may also have a positive effect on lipid levels. In 2012, a combination tablet of linagliptin plus metformin hydrochloride was marketed under the name Jentadueto for use in patients when treatment with both linagliptin and metformin is appropriate.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 129.1636
Groups approved
Monoisotopic Weight 129.101445377
Pharmacology
Indication For use as an adjunct to diet and exercise in adult patients (18 years and older) with NIDDM. May also be used for the management of metabolic and reproductive abnormalities associated with polycystic ovary syndrome (PCOS). Jentadueto is for the treatment of patients when both linagliptin and metformin is appropriate.
Mechanism of action Metformin's mechanisms of action differ from other classes of oral antihyperglycemic agents. Metformin decreases blood glucose levels by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. These effects are mediated by the initial activation by metformin of AMP-activated protein kinase (AMPK), a liver enzyme that plays an important role in insulin signaling, whole body energy balance, and the metabolism of glucose and fats. Activation of AMPK is required for metformin's inhibitory effect on the production of glucose by liver cells. Increased peripheral utilization of glucose may be due to improved insulin binding to insulin receptors. Metformin administration also increases AMPK activity in skeletal muscle. AMPK is known to cause GLUT4 deployment to the plasma membrane, resulting in insulin-independent glucose uptake. The rare side effect, lactic acidosis, is thought to be caused by decreased liver uptake of serum lactate, one of the substrates of gluconeogenesis. In those with healthy renal function, the slight excess is simply cleared. However, those with severe renal impairment may accumulate clinically significant serum lactic acid levels. Other conditions that may precipitate lactic acidosis include severe hepatic disease and acute/decompensated heart failure.
Absorption Absorbed over 6 hours, bioavailability is 50 to 60% under fasting conditions. Administration with food decreases and delays absorption. Some evidence indicates that the level of absorption is not dose-related, suggesting that absorption occurs through a saturable process. Limited data from animal and human cell cultures indicate that absorption occurs through a passive, non-saturable process, possibly involving a paracellular route. Peak action occurs 3 hours after oral administration.
Protein binding Metformin is negligibly bound to plasma proteins.
Biotransformation Metformin is not metabolized.
Route of elimination Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion. Approximately 90% of the drug is eliminated in 24 hours in those with healthy renal function. Renal clearance of metformin is approximately 3.5 times that of creatinine clearance, indicating the tubular secretion is the primary mode of metformin elimination.
Toxicity Acute oral toxicity (LD50): 350 mg/kg [Rabbit]. It would be expected that adverse reactions of a more intense character including epigastric discomfort, nausea, and vomiting followed by diarrhea, drowsiness, weakness, dizziness, malaise and headache might be seen.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Cimetidine Cimetidine may increase the therapeutic and adverse effects of metformin by increasing its serum concentration. Consider alternate therapy.
Glucosamine Possible hyperglycemia
Somatropin recombinant Somatropin may antagonize the hypoglycemic effect of metformin. Monitor for changes in fasting and postprandial blood sugars.
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce gastric irritation.

Targets


5'-AMP-activated protein kinase subunit beta-1
Name 5'-AMP-activated protein kinase subunit beta-1
Gene Name PRKAB1
Pharmacological action yes
Actions inducer
References
  • Kovacic S, Soltys CL, Barr AJ, Shiojima I, Walsh K, Dyck JR: Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart. J Biol Chem. 2003 Oct 10;278(41):39422-7. Epub 2003 Jul 29. - Pubmed
  • Hardie DG: Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology. 2003 Dec;144(12):5179-83. Epub 2003 Sep 4. - Pubmed
  • Ruderman NB, Saha AK, Kraegen EW: Minireview: malonyl CoA, AMP-activated protein kinase, and adiposity. Endocrinology. 2003 Dec;144(12):5166-71. Epub 2003 Sep 18. - Pubmed
  • Leverve XM, Guigas B, Detaille D, Batandier C, Koceir EA, Chauvin C, Fontaine E, Wiernsperger NF: Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. Diabetes Metab. 2003 Sep;29(4 Pt 2):6S88-94. - Pubmed
  • Leclerc I, Woltersdorf WW, da Silva Xavier G, Rowe RL, Cross SE, Korbutt GS, Rajotte RV, Smith R, Rutter GA: Metformin, but not leptin, regulates AMP-activated protein kinase in pancreatic islets: impact on glucose-stimulated insulin secretion. Am J Physiol Endocrinol Metab. 2004 Jun;286(6):E1023-31. Epub 2004 Feb 10. - Pubmed
  • Vucicevic L, Misirkic M, Janjetovic K, Harhaji-Trajkovic L, Prica M, Stevanovic D, Isenovic E, Sudar E, Sumarac-Dumanovic M, Micic D, Trajkovic V: AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C. Biochem Pharmacol. 2009 Jun 1;77(11):1684-93. Epub 2009 Mar 14. - Pubmed
  • Towler MC, Hardie DG: AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007 Feb 16;100(3):328-41. - Pubmed
  • Musi N, Hirshman MF, Nygren J, Svanfeldt M, Bavenholm P, Rooyackers O, Zhou G, Williamson JM, Ljunqvist O, Efendic S, Moller DE, Thorell A, Goodyear LJ: Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes. 2002 Jul;51(7):2074-81. - Pubmed
DTHybrid score Not Available

Transporters


Solute carrier family 22 member 1
Name Solute carrier family 22 member 1
Gene Name SLC22A1
Actions substrate,inhibitor
References
  • Dresser MJ, Xiao G, Leabman MK, Gray AT, Giacomini KM: Interactions of n-tetraalkylammonium compounds and biguanides with a human renal organic cation transporter (hOCT2). Pharm Res. 2002 Aug;19(8):1244-7. - Pubmed
  • Wang DS, Jonker JW, Kato Y, Kusuhara H, Schinkel AH, Sugiyama Y: Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J Pharmacol Exp Ther. 2002 Aug;302(2):510-5. - Pubmed
  • Zolk O: Current understanding of the pharmacogenomics of metformin. Clin Pharmacol Ther. 2009 Dec;86(6):595-8. - Pubmed
  • Tzvetkov MV, Vormfelde SV, Balen D, Meineke I, Schmidt T, Sehrt D, Sabolic I, Koepsell H, Brockmoller J: The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin. Clin Pharmacol Ther. 2009 Sep;86(3):299-306. Epub 2009 Jun 17. - Pubmed
  • Ahlin G, Karlsson J, Pedersen JM, Gustavsson L, Larsson R, Matsson P, Norinder U, Bergstrom CA, Artursson P: Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1. J Med Chem. 2008 Oct 9;51(19):5932-42. Epub 2008 Sep 13. - Pubmed
DTHybrid score 0.3918
Solute carrier family 22 member 2
Name Solute carrier family 22 member 2
Gene Name SLC22A2
Actions substrate,inhibitor
References
  • Dresser MJ, Xiao G, Leabman MK, Gray AT, Giacomini KM: Interactions of n-tetraalkylammonium compounds and biguanides with a human renal organic cation transporter (hOCT2). Pharm Res. 2002 Aug;19(8):1244-7. - Pubmed
  • Zolk O: Current understanding of the pharmacogenomics of metformin. Clin Pharmacol Ther. 2009 Dec;86(6):595-8. - Pubmed
  • Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. - Pubmed
  • Kimura N, Masuda S, Tanihara Y, Ueo H, Okuda M, Katsura T, Inui K: Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86. - Pubmed
DTHybrid score 0.3286
Solute carrier family 22 member 3
Name Solute carrier family 22 member 3
Gene Name SLC22A3
Actions substrate
References
  • Muller J, Lips KS, Metzner L, Neubert RH, Koepsell H, Brandsch M: Drug specificity and intestinal membrane localization of human organic cation transporters (OCT). Biochem Pharmacol. 2005 Dec 5;70(12):1851-60. Epub 2005 Nov 2. - Pubmed
DTHybrid score 0.2817
Multidrug and toxin extrusion protein 1
Name Multidrug and toxin extrusion protein 1
Gene Name SLC47A1
Actions inhibitor
References
  • Meyer zu Schwabedissen HE, Verstuyft C, Kroemer HK, Becquemont L, Kim RB: Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional characterization, interaction with OCT2 (SLC22A2), and single nucleotide polymorphisms. Am J Physiol Renal Physiol. 2010 Apr;298(4):F997-F1005. Epub 2010 Jan 6. - Pubmed
DTHybrid score 0.3327
Equilibrative nucleoside transporter 4
Name Equilibrative nucleoside transporter 4
Gene Name Not Available
Actions substrate
References
  • Zhou M, Xia L, Wang J: Metformin transport by a newly cloned proton-stimulated organic cation transporter (plasma membrane monoamine transporter) expressed in human intestine. Drug Metab Dispos. 2007 Oct;35(10):1956-62. Epub 2007 Jun 28. - Pubmed
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
118 Organic cation/carnitine transporter 2 SLC22A5 0.0991
1729 Solute carrier family 22 member 6 SLC22A6 0.0855
1588 Multidrug resistance protein 1 ABCB1 0.0778
4119 Cytochrome P450 2D6 CYP2D6 0.076
4512 Cytochrome P450 3A4 CYP3A4 0.0752
833 Organic cation/carnitine transporter 1 SLC22A4 0.0725
6142 Solute carrier family 22 member 8 SLC22A8 0.0716
492 Histamine H1 receptor HRH1 0.0533
4118 Cytochrome P450 3A5 CYP3A5 0.0502
851 5'-AMP-activated protein kinase subunit beta-2 PRKAB2 0.0496
4200 Cytochrome P450 1A2 CYP1A2 0.0493
748 5'-AMP-activated protein kinase catalytic subunit alpha-1 PRKAA1 0.047
388 AMP deaminase 1 AMPD1 0.0457
6107 Cytochrome P450 3A7 CYP3A7 0.0442
6016 Cytochrome P450 2C19 CYP2C19 0.0415
704 Long-chain-fatty-acid--CoA ligase 1 ACSL1 0.0385
386 Acetyl-coenzyme A synthetase, cytoplasmic ACSS2 0.0385
821 Acetyl-coenzyme A synthetase 2-like, mitochondrial ACSS1 0.0385
297 Adenylate cyclase type 1 ADCY1 0.0385
4757 Cytochrome P450 2C9 CYP2C9 0.0373
1291 cAMP response element-binding protein CREB1 0.0353
378 Alpha-2C adrenergic receptor ADRA2C 0.0327
2684 Histidine triad nucleotide-binding protein 1 HINT1 0.0316
766 Beta-2 adrenergic receptor ADRB2 0.0306
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0302
338 DNA polymerase UL30 0.0301
379 DNA polymerase UL54 0.0301
697 DNA polymerase ORF28 0.0301
2482 DNA polymerase 43 0.0301
4104 DNA polymerase BALF5 0.0301
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0298
813 Neuronal acetylcholine receptor subunit alpha-2 CHRNA2 0.0295
509 Thymidine kinase TK 0.0292
570 Thymidine kinase TK 0.0292
2559 Thymidine kinase TK 0.0292
3430 Thymidine kinase tdk 0.0292
3518 Thymidine kinase TK 0.0292
5301 Thymidine kinase tdk 0.0292
5771 Thymidine kinase ORF36 0.0292
7009 Thymidine kinase ORF36 0.0292
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0292
6021 Adenosine kinase ADK 0.029
128 Adenine phosphoribosyltransferase APRT 0.0283
556 Alpha-1A adrenergic receptor ADRA1A 0.0275
124 Histamine H2 receptor HRH2 0.0271
587 Serum albumin ALB 0.0269
862 Multidrug resistance-associated protein 1 ABCC1 0.0266
776 Bile salt export pump ABCB11 0.0265
6024 Cytochrome P450 1A1 CYP1A1 0.0263
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.0254
629 Alpha-2B adrenergic receptor ADRA2B 0.0253
6140 Ileal sodium/bile acid cotransporter SLC10A2 0.0247
4198 Fructose-1,6-bisphosphatase 1 FBP1 0.0239
193 Beta-1 adrenergic receptor ADRB1 0.0237
6013 Cytochrome P450 2E1 CYP2E1 0.0236
4924 Cytochrome P450 2C8 CYP2C8 0.0228
318 Alpha-2A adrenergic receptor ADRA2A 0.0225
4148 Serine/threonine-protein kinase mTOR MTOR 0.0221
6143 Solute carrier family 22 member 7 SLC22A7 0.022
10 Glycogen phosphorylase, liver form PYGL 0.0216
6030 Cytochrome P450 2B6 CYP2B6 0.0209
3923 Cholinesterase BCHE 0.0205
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0204
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0204
4097 Neuronal acetylcholine receptor subunit alpha-9 CHRNA9 0.0202
1024 Solute carrier family 22 member 11 SLC22A11 0.0197
2347 Proto-oncogene serine/threonine-protein kinase Pim-1 PIM1 0.0195
2358 cAMP-specific 3',5'-cyclic phosphodiesterase 4D PDE4D 0.0193
1525 Heparin-binding growth factor 2 FGF2 0.0192
831 D(2) dopamine receptor DRD2 0.019
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0189
541 cAMP-specific 3',5'-cyclic phosphodiesterase 4B PDE4B 0.0188
632 Alpha-1B adrenergic receptor ADRA1B 0.0183
713 Sodium-dependent dopamine transporter SLC6A3 0.0175
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0174
789 Alpha-1D adrenergic receptor ADRA1D 0.0172
131 Synaptic vesicular amine transporter SLC18A2 0.0172
6070 Nischarin NISCH 0.0172
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0167
768 FK506-binding protein 1A FKBP1A 0.0162
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0159
502 5-hydroxytryptamine 2A receptor HTR2A 0.0159
6010 Thiamine transporter 1 SLC19A2 0.0159
341 5-hydroxytryptamine 3 receptor HTR3A 0.0159
23 D(1A) dopamine receptor DRD1 0.0158
2472 Voltage-gated potassium channel kcsA 0.0157
6366 Voltage-gated potassium channel kcsA 0.0157
5718 Cytochrome P450 2A6 CYP2A6 0.0155
4773 Deoxycytidine kinase DCK 0.0153
474 Acetylcholinesterase ACHE 0.0152
3939 Amine oxidase [flavin-containing] B MAOB 0.0147
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0147
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0146
677 Choline-phosphate cytidylyltransferase A PCYT1A 0.0145
2164 Multidrug resistance-associated protein 4 ABCC4 0.0144
5626 Nucleoside diphosphate kinase B NME2 0.0143
6148 Multidrug resistance-associated protein 7 ABCC10 0.0143
175 Thiamin pyrophosphokinase 1 TPK1 0.0142
1898 Cytochrome P450 1B1 CYP1B1 0.014
824 Sodium-dependent serotonin transporter SLC6A4 0.0137
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0131
1064 DNA (cytosine-5)-methyltransferase 1 DNMT1 0.013
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0126
4203 Histamine N-methyltransferase HNMT 0.0126
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 0.0126
672 Prostaglandin F2-alpha receptor PTGFR 0.0125
5126 Arginase rocF 0.0125
543 Penicillin-binding protein 1B mrcB 0.0123
6186 Penicillin-binding protein 1B ponB 0.0123
6822 Penicillin-binding protein 1b pbp1b 0.0123
6844 Penicillin-binding protein 1b pbp1b 0.0123
1636 Trace amine-associated receptor 1 TAAR1 0.0122
159 Penicillin-binding protein 2B penA 0.0122
6121 Penicillin-binding protein 2B penA 0.0122
645 Penicillin-binding protein 1A mrcA 0.0121
5805 Penicillin-binding protein 1A ponA 0.0121
6185 Penicillin-binding protein 1A mrcA 0.0121
6799 Penicillin-binding protein 1A pbpA 0.0121
3941 Amine oxidase [flavin-containing] A MAOA 0.012
1341 Histamine H3 receptor HRH3 0.0117
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0116
4209 ATP-sensitive inward rectifier potassium channel 8 KCNJ8 0.0116
5294 Nucleoside diphosphate kinase A NME1 0.0115
6136 Multidrug resistance-associated protein 5 ABCC5 0.0114
164 Histamine H4 receptor HRH4 0.0112
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0112
740 Argininosuccinate synthase ASS1 0.0111
865 Argininosuccinate synthase ASS1 0.0111
2680 Argininosuccinate synthase argG 0.0111
3194 Argininosuccinate synthase argG 0.0111
7 Nitric oxide synthase, inducible NOS2 0.0109
320 5-hydroxytryptamine 1A receptor HTR1A 0.0109
161 Tubulin beta chain TUBB 0.0106
312 Tubulin beta chain TUB2 0.0106
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0106
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0106
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0106
982 Cocaine- and amphetamine-regulated transcript protein CARTPT 0.0101
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.0101
6106 Cytochrome P450 2C18 CYP2C18 0.01
624 Guanidinoacetate N-methyltransferase GAMT 0.0097
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0097
828 Phenylalanine-4-hydroxylase PAH 0.0097
3109 Phenylalanine-4-hydroxylase phhA 0.0097
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0097
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0096
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0093
342 P protein [Includes: DNA-directed DNA polymerase P 0.0091
612 P protein [Includes: DNA-directed DNA polymerase P 0.0091
6141 Sodium/bile acid cotransporter SLC10A1 0.0091
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0089
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.0087
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0087
694 Matrix protein 2 M 0.0086
756 Sex hormone-binding globulin SHBG 0.0086
147 Aldehyde dehydrogenase, mitochondrial ALDH2 0.0085
465 Calmodulin CALM1 0.0085
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0084
1517 Beta-3 adrenergic receptor ADRB3 0.0081
6165 Copper-transporting ATPase 1 ATP7A 0.008
6163 Copper-transporting ATPase 2 ATP7B 0.008
6432 Transporter snf 0.008
1830 5'-nucleotidase NT5E 0.0077
6146 High affinity copper uptake protein 1 SLC31A1 0.0077
3704 Spermidine/putrescine-binding periplasmic protein precursor potD 0.0077
136 Estrogen receptor ESR1 0.0077
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0075
163 D(1B) dopamine receptor DRD5 0.0075
6014 Cytochrome P450 2A13 CYP2A13 0.0075
125 DNA polymerase beta POLB 0.0074
4152 Superoxide dismutase [Cu-Zn] SOD1 0.0074
908 Glutathione S-transferase theta-1 GSTT1 0.0073
702 UMP-CMP kinase CMPK1 0.0072
432 D(4) dopamine receptor DRD4 0.0071
6171 Solute carrier family 28 member 3 SLC28A3 0.007
2300 Lysozyme E 0.007
3633 Lysozyme R 0.007
5597 Lysozyme 17 0.007
3929 Phosphoethanolamine/phosphocholine phosphatase PHOSPHO1 0.007
3927 Choline transporter-like protein 3 SLC44A3 0.007
3926 Choline transporter-like protein 2 SLC44A2 0.007
3933 Choline/ethanolaminephosphotransferase CEPT1 0.007
549 Choline-phosphate cytidylyltransferase B PCYT1B 0.007
1686 Choline transporter-like protein 1 SLC44A1 0.007
264 Choline/ethanolamine kinase [Includes: Choline kinase beta CHKB 0.007
861 Choline kinase alpha CHKA 0.007
769 High-affinity choline transporter 1 SLC5A7 0.007
3925 Choline transporter-like protein 4 SLC44A4 0.007
700 Choline dehydrogenase, mitochondrial CHDH 0.007
576 Choline O-acetyltransferase CHAT 0.007
3922 Phospholipase D2 PLD2 0.007
3924 Phospholipase D1 PLD1 0.007
5682 Ribonuclease pancreatic RNASE1 0.0069
638 D(3) dopamine receptor DRD3 0.0069
3560 Gentamicin 3'-acetyltransferase aacC1 0.0067
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0067
749 Amiloride-sensitive cation channel 1, neuronal ACCN1 0.0066
6137 Multidrug resistance-associated protein 6 ABCC6 0.0065
3611 Cytidine deaminase cdd 0.0065
3707 Cytidine deaminase cdd 0.0065
4211 Cytidine deaminase CDA 0.0065
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0065
896 Glutathione S-transferase Mu 1 GSTM1 0.0064
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0063
6138 Multidrug resistance protein 3 ABCB4 0.0061
153 Dopamine beta-hydroxylase DBH 0.0061
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0061
1757 Myeloperoxidase MPO 0.0059
387 Amiloride-sensitive amine oxidase [copper-containing] ABP1 0.0059
7187 Amiloride-sensitive amine oxidase [copper-containing] ABP1 0.0059
389 Amiloride-sensitive cation channel 2, neuronal ACCN2 0.0058
213 Amiloride-sensitive sodium channel subunit alpha SCNN1A 0.0058
550 Amiloride-sensitive sodium channel subunit delta SCNN1D 0.0058
6111 DNA polymerase epsilon subunit 4 POLE4 0.0058
827 Sodium/hydrogen exchanger 1 SLC9A1 0.0058
27 Amiloride-sensitive sodium channel subunit beta SCNN1B 0.0058
552 Amiloride-sensitive sodium channel subunit gamma SCNN1G 0.0058
6112 DNA polymerase epsilon subunit 3 POLE3 0.0058
6108 Ribonucleoside-diphosphate reductase subunit M2 B RRM2B 0.0058
6110 DNA polymerase epsilon subunit 2 POLE2 0.0058
6109 DNA polymerase epsilon catalytic subunit A POLE 0.0058
904 Glutathione S-transferase P GSTP1 0.0058
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0056
477 DNA topoisomerase 4 subunit A parC 0.0056
886 DNA topoisomerase 4 subunit A parC 0.0056
6226 DNA topoisomerase 4 subunit A parC 0.0056
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0056
404 DNA gyrase subunit A gyrA 0.0055
6224 DNA gyrase subunit A gyrA 0.0055
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0055
1360 Sphingomyelin phosphodiesterase SMPD1 0.0055
1759 85 kDa calcium-independent phospholipase A2 PLA2G6 0.0055
1770 Phospholipase C PLCL1 0.0055
2841 Phospholipase C plc 0.0055
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0055
3610 Thioredoxin reductase 1, cytoplasmic TXNRD1 0.0054
738 Monocarboxylate transporter 1 SLC16A1 0.0052
869 Estrogen receptor beta ESR2 0.0052
4218 Ribonucleoside-diphosphate reductase M2 subunit RRM2 0.005
3947 Xanthine dehydrogenase/oxidase XDH 0.0049
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0048
3810 Catechol O-methyltransferase COMT 0.0048
948 Neuronal acetylcholine receptor subunit beta-2 CHRNB2 0.0048
6080 Neuronal acetylcholine receptor subunit alpha-5 CHRNA5 0.0048
6082 Neuronal acetylcholine receptor subunit beta-3 CHRNB3 0.0048
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0048
380 Cytochrome P450 17A1 CYP17A1 0.0047
731 HIV-1 protease HIV-1 protease 0.0047
29 Tubulin beta-1 chain TUBB1 0.0046
976 Platelet glycoprotein IX GP9 0.0046
303 Diamine acetyltransferase 2 SAT2 0.0045
623 Spermine oxidase SMOX 0.0045
1317 Spermine synthase SMS 0.0045
6081 Neuronal acetylcholine receptor subunit alpha-6 CHRNA6 0.0044
20 Prostaglandin G/H synthase 1 PTGS1 0.0043
603 DNA polymerase alpha catalytic subunit POLA1 0.0043
737 Mineralocorticoid receptor NR3C2 0.0043
3755 Nucleoside-specific channel-forming protein tsx precursor tsx 0.0043
2539 Tubulin alpha-1 chain TUBA4A 0.0042
885 5-hydroxytryptamine 1B receptor HTR1B 0.0041
360 Ribonucleoside-diphosphate reductase large subunit RRM1 0.0041
6078 Neuronal acetylcholine receptor subunit beta-4 CHRNB4 0.0041
123 Diamine acetyltransferase 1 SAT1 0.004
817 DNA topoisomerase 2-alpha TOP2A 0.004
614 Progesterone receptor PGR 0.0039
102 DNA topoisomerase I, mitochondrial TOP1MT 0.0038
3811 Cytochrome P450 19A1 CYP19A1 0.0037
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0037
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0037
6085 Fatty acid-binding protein, intestinal FABP2 0.0036
527 Prostacyclin receptor PTGIR 0.0036
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0036
6167 Organic solute transporter subunit beta OSTB 0.0036
6166 Organic solute transporter subunit alpha OSTA 0.0036
723 Cytosolic phospholipase A2 PLA2G4A 0.0036
1074 Urokinase-type plasminogen activator PLAU 0.0036
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0034
1864 RET proto-oncogene RET 0.0034
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.0033
1950 Epithelial discoidin domain-containing receptor 1 DDR1 0.0033
6094 BCR/ABL fusion protein isoform X9 BCR/ABL fusion 0.0033
6170 ATP-binding cassette sub-family A member 3 ABCA3 0.0033
277 Purine nucleoside phosphorylase PNP 0.0033
2870 Purine nucleoside phosphorylase punA 0.0033
2945 Purine nucleoside phosphorylase punA 0.0033
4659 Purine nucleoside phosphorylase TM_1596 0.0033
4825 Purine nucleoside phosphorylase TTHA1435 0.0033
2251 Thymidylate kinase tmk 0.0033
2254 Thymidylate kinase DTYMK 0.0033
3522 Thymidylate kinase tmk 0.0033
3478 Glucose-1-phosphate thymidylyltransferase rmlA 0.0032
4277 Glucose-1-phosphate thymidylyltransferase rmlA 0.0032
1284 Nuclear receptor subfamily 1 group I member 2 NR1I2 0.0032
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.0032
2257 Uridine phosphorylase udp 0.0031
5132 Uridine phosphorylase udp 0.0031
449 Ornithine decarboxylase ODC1 0.0031
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0031
6212 Tubulin gamma-1 chain TUBG1 0.0031
6210 Tubulin delta chain TUBD1 0.0031
6211 Tubulin epsilon chain TUBE1 0.0031
1353 DNA topoisomerase 1 TOP1 0.003
3552 DNA topoisomerase 1 topA 0.003
6155 ATP-binding cassette transporter sub-family C member 11 ABCC11 0.003
6218 Pannexin-1 PANX1 0.003
751 Potassium channel subfamily K member 6 KCNK6 0.003
4095 Neuronal acetylcholine receptor subunit alpha-7 CHRNA7 0.0029
947 Neuronal acetylcholine receptor subunit alpha-4 CHRNA4 0.0029
6002 Prostaglandin E2 receptor EP4 subtype PTGER4 0.0028
436 5-hydroxytryptamine 2B receptor HTR2B 0.0028
6180 UDP-glucuronosyltransferase 2B4 UGT2B4 0.0027
1618 High affinity nerve growth factor receptor NTRK1 0.0027
172 Potassium channel subfamily K member 1 KCNK1 0.0027
6031 Cytochrome P450 3A43 CYP3A43 0.0027
725 5-hydroxytryptamine 1D receptor HTR1D 0.0027
4131 Prostaglandin E2 receptor, EP3 subtype PTGER3 0.0027
406 Prostaglandin E2 receptor, EP2 subtype PTGER2 0.0026
950 Alpha platelet-derived growth factor receptor PDGFRA 0.0026
951 Macrophage colony-stimulating factor 1 receptor CSF1R 0.0026
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0026
590 5-hydroxytryptamine 2C receptor HTR2C 0.0025
228 Beta platelet-derived growth factor receptor PDGFRB 0.0025
4217 Telomerase reverse transcriptase TERT 0.0024
6149 Solute carrier family 22 member 10 SLC22A10 0.0024
1629 Transcription factor AP-1 JUN 0.0024
4604 Liver carboxylesterase 1 CES1 0.0024
73 Prostaglandin E2 receptor, EP1 subtype PTGER1 0.0023
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0023
504 Mast/stem cell growth factor receptor KIT 0.0023
2449 Tubulin alpha-3 chain TUBA1A 0.0022
146 Androgen receptor AR 0.0021
17 Proto-oncogene tyrosine-protein kinase ABL1 ABL1 0.002
489 Monocarboxylate transporter 2 SLC16A7 0.0019
467 Delta-type opioid receptor OPRD1 0.0019
696 Kappa-type opioid receptor OPRK1 0.0019
6091 Gamma-aminobutyric acid receptor subunit theta GABRQ 0.0019
4192 DNA topoisomerase 2-beta TOP2B 0.0019
2320 Thymidine kinase, cytosolic TK1 0.0018
847 Mu-type opioid receptor OPRM1 0.0018
6086 Gamma-aminobutyric acid receptor subunit gamma-2 GABRG2 0.0017
6092 Gamma-aminobutyric acid receptor subunit rho-2 GABRR2 0.0017
6090 Gamma-aminobutyric acid receptor subunit pi GABRP 0.0017
6088 Gamma-aminobutyric acid receptor subunit gamma-3 GABRG3 0.0017
6115 Gamma-aminobutyric acid receptor subunit rho-3 GABRR3 0.0017
4100 Gamma-aminobutyric-acid receptor subunit beta-2 GABRB2 0.0017
6093 Gamma-aminobutyric acid receptor subunit delta GABRD 0.0017
6087 Gamma-aminobutyric acid receptor subunit gamma-1 GABRG1 0.0017
6089 Gamma-aminobutyric acid receptor subunit epsilon GABRE 0.0017
142 Gamma-aminobutyric-acid receptor subunit rho-1 GABRR1 0.0017
198 Sodium channel protein type 10 subunit alpha SCN10A 0.0017
4098 Gamma-aminobutyric-acid receptor subunit beta-1 GABRB1 0.0016
4099 Gamma-aminobutyric-acid receptor subunit beta-3 GABRB3 0.0016
4120 NADPH--cytochrome P450 reductase POR 0.0016
6161 Probable low affinity copper uptake protein 2 SLC31A2 0.0016
841 Gamma-aminobutyric-acid receptor subunit alpha-6 GABRA6 0.0016
530 Gamma-aminobutyric-acid receptor subunit alpha-4 GABRA4 0.0015
523 Gamma-aminobutyric-acid receptor subunit alpha-5 GABRA5 0.0015
580 Gamma-aminobutyric-acid receptor subunit alpha-3 GABRA3 0.0015
423 Gamma-aminobutyric-acid receptor subunit alpha-2 GABRA2 0.0015
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0014
3587 Gastrotropin FABP6 0.0012
468 Cytochrome P450 4A11 CYP4A11 0.0012
33 Cystine/glutamate transporter SLC7A11 0.001
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0009
290 Prostaglandin G/H synthase 2 PTGS2 0.0008
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0007
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0007
392 Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A 0.0007
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0007
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0007
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0007
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0006
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0006
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0006
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0006
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0006
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0005
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