DT-Web

DB01109 - Heparin


Identification
Name Heparin
Accession Number DB01109 (APRD00056)
Type small molecule
Description Unfractionated heparin (UH) is a heterogenous preparation of anionic, sulfated glycosaminoglycan polymers with weights ranging from 3000 to 30,000 Da. It is a naturally occurring anticoagulant released from mast cells. It binds reversibly to antithrombin III (ATIII) and greatly accelerates the rate at which ATIII inactivates coagulation enzymes thrombin (factor IIa) and factor Xa. UH is different from low molecular weight heparin (LMWH) in the following ways: the average molecular weight of LMWH is about 4.5 kDa whereas it is 15 kDa for UH; UH requires continuous infusions; activated partial prothrombin time (aPTT) monitoring is required when using UH; and UH has a higher risk of bleeding and higher risk of osteoporosis in long term use. Unfractionated heparin is more specific than LMWH for thrombin. Furthermore, the effects of UH can typically be reversed by using protamine sulfate.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight Not Available
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication Unfractionated heparin is indicated for prophylaxis and treatment of venous thrombosis and its extension, prevention of post-operative deep venous thrombosis and pulmonary embolism and prevention of clotting in arterial and cardiac surgery. In cardiology, it is used to prevent embolisms in patients with atrial fibrillation and as an adjunct antithrombin therapy in patients with unstable angina and/or non-Q wave myocardial infarctions (i.e. non-ST elevated acute coronary artery syndrome) who are on platelet glycoprotein (IIb/IIIa) receptor inhibitors. Additionally, it is used to prevent clotting during dialysis and surgical procedures, maintain the patency of intravenous injection devices and prevent in vitro coagulation of blood transfusions and in blood samples drawn for laboratory values.
Mechanism of action Under normal circumstances, antithrombin III (ATIII) inactivates thrombin (factor IIa) and factor Xa. This process occurs at a slow rate. Administered heparin binds reversibly to ATIII and leads to almost instantaneous inactivation of factors IIa and Xa The heparin-ATIII complex can also inactivate factors IX, XI, XII and plasmin. The mechanism of action of heparin is ATIII-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Heparin is not a thrombolytic or fibrinolytic. It prevents progression of existing clots by inhibiting further clotting. The lysis of existing clots relies on endogenous thrombolytics.
Absorption Heparin must be given parenterally as it is not absorbed through the gastrointestinal mucosa. It is usually given by iv infusion or deep sc injection. The onset of action is immediate after iv injection but can be delayed 20 to 60 minutes following sc injection. Plasma heparin concentrations may be increased and activated partial thromboplastin times (aPTTs) may be more prolonged in geriatric adults (older than 60 years of age) compared with younger adults.
Protein binding Very high, mostly to low-density lipoproteins. It is also extensively bound by globulins and fibrinogens.
Biotransformation Liver and the reticulo-endothelial system are the sites of biotransformation. The metabolic fate of heparin is not well understood.
Route of elimination The drug appears to be removed mainly by the reticuloendothelial system. A small fraction of unchanged heparin also appears to be excreted in urine. Heparin cannot be eliminated by hemodialysis.
Toxicity In mouse, the median lethal dose is greater than 5000 mg/kg. Another side effect is heparin-induced thrombocytopenia (HIT syndrome). Platelet counts usually do not fall until between days 5 and 12 of heparin therapy. HIT is caused by an immunological reaction that makes platelets form clots within the blood vessels, thereby using up coagulation factors. It can progress to thrombotic complications such as arterial thrombosis, gangrene, stroke, myocardial infarction and disseminated intravascular coagulation. Symptoms of overdose may show excessive prolongation of aPTT or by bleeding, which may be internal or external, major or minor. Therapeutic doses of heparin give for at least 4 months have been associated with osteoporosis and spontaneous vertebral fractures. Osteoporosis may be reversible once heparin is discontinued. Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates. Toxicity appears to have resulted from administration of large amounts (i.e., about 100-400 mg/kg daily) of benzyl alcohol in these neonates. Its use is principally associated with the use of bacteriostatic 0.9% sodium chloride intravascular flush or endotracheal tube lavage solutions.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Acetylsalicylic acid Increased risk of bleeding.
Aprotinin Aprotinin, in the presence of heparin, has been found to prolong the activated clotting time (ACT) as measured by a celite surface activation method. The kaolin activated clotting time appears to be much less affected.
corticotropin-releasing factor Contraindication: Heparin may enhance the adverse/toxic effect of Corticorelin. Significant hypotension and bradycardia have been previously attributed to this combination. Corticorelin prescribing information describes a case in which a patient experienced a substantial fall in blood pressure and heart rate, resulting in asystole and requiring resuscitation.
Drospirenone Heparin can increase risk of hyperkalemia for patients on drospirenone
Drotrecogin alfa The potential benefits of drotrecogin alfa should be weighed against an increased risk of bleeding in patients receiving therapeutic doses of heparin. Monitor for bleeding during concomitant therapy, and immediately stop infusion of drotrecogin if clinically important bleeding occurs. In patients receiving prophylactic heparin doses, consider continuing this during drotrecogin.
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Ticlopidine Increased bleeding risk. Monitor aPTT.
Tobramycin Increased risk of nephrotoxicity
Treprostinil The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the anticoagulant, Heparin. Monitor for increased bleeding during concomitant thearpy.
Food Interactions
  • Adequate calcium intake is recommended, needs increased with long term use, supplement recommended.
  • Many herbs with anticoagulant properties (e.g. ginger, garlic, ginseng, green tea, evening primrose) may increase the risk of bleeding in patients on anticoagulant therapy such as heparin

Targets


Antithrombin-III
Name Antithrombin-III
Gene Name SERPINC1
Pharmacological action yes
Actions potentiator
References
  • Mirow N, Zimmermann B, Maleszka A, Knobl H, Tenderich G, Koerfer R, Herberg FW: Plasma protein binding properties to immobilized heparin and heparin-albumin conjugate. Artif Organs. 2007 Jun;31(6):466-71. - Pubmed
  • Pappalardo F, Franco A, Crescenzi G, De Simone F, Torracca L, Zangrillo A: Anticoagulation management in patients undergoing open heart surgery by activated clotting time and whole blood heparin concentration. Perfusion. 2006 Dec;21(5):285-90. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Chuang YJ, Swanson R, Raja SM, Olson ST: Heparin enhances the specificity of antithrombin for thrombin and factor Xa independent of the reactive center loop sequence. Evidence for an exosite determinant of factor Xa specificity in heparin-activated antithrombin. J Biol Chem. 2001 May 4;276(18):14961-71. Epub 2001 Feb 7. - Pubmed
  • Petitou M, Herault JP, Bernat A, Driguez PA, Duchaussoy P, Lormeau JC, Herbert JM: Synthesis of thrombin-inhibiting heparin mimetics without side effects. Nature. 1999 Apr 1;398(6726):417-22. - Pubmed
  • Schedin-Weiss S, Richard B, Olson ST: Kinetic evidence that allosteric activation of antithrombin by heparin is mediated by two sequential conformational changes. Arch Biochem Biophys. 2010 Dec 15;504(2):169-76. Epub 2010 Sep 15. - Pubmed
  • Gettins PG, Olson ST: Activation of antithrombin as a factor IXa and Xa inhibitor involves mitigation of repression rather than positive enhancement. FEBS Lett. 2009 Nov 3;583(21):3397-400. Epub 2009 Oct 9. - Pubmed
DTHybrid score 1.1581
Coagulation factor X
Name Coagulation factor X
Gene Name F10
Pharmacological action yes
Actions inhibitor
References
  • Ignjatovic V, Summerhayes R, Gan A, Than J, Chan A, Cochrane A, Bennett M, Horton S, Shann F, Lane G, Ross-Smith M, Monagle P: Monitoring Unfractionated Heparin (UFH) therapy: which Anti-Factor Xa assay is appropriate? Thromb Res. 2007;120(3):347-51. Epub 2006 Nov 21. - Pubmed
  • Patey SJ, Edwards EA, Yates EA, Turnbull JE: Heparin derivatives as inhibitors of BACE-1, the Alzheimer's beta-secretase, with reduced activity against factor Xa and other proteases. J Med Chem. 2006 Oct 5;49(20):6129-32. - Pubmed
  • Rezaie AR: Heparin-binding exosite of factor Xa. Trends Cardiovasc Med. 2000 Nov;10(8):333-8. - Pubmed
  • Rosenberg RD: Role of heparin and heparinlike molecules in thrombosis and atherosclerosis. Fed Proc. 1985 Feb;44(2):404-9. - Pubmed
DTHybrid score 1.7084
P-selectin
Name P-selectin
Gene Name SELP
Pharmacological action unknown
Actions inhibitor
References
  • Simonis D, Fritzsche J, Alban S, Bendas G: Kinetic analysis of heparin and glucan sulfates binding to P-selectin and its impact on the general understanding of selectin inhibition. Biochemistry. 2007 May 22;46(20):6156-64. Epub 2007 Apr 26. - Pubmed
  • Maugeri N, Di Fabio G, Barbanti M, de Gaetano G, Donati MB, Cerletti C: Parnaparin, a low-molecular-weight heparin, prevents P-selectin-dependent formation of platelet-leukocyte aggregates in human whole blood. Thromb Haemost. 2007 Jun;97(6):965-73. - Pubmed
  • Simonis D, Christ K, Alban S, Bendas G: Affinity and kinetics of different heparins binding to P- and L-selectin. Semin Thromb Hemost. 2007 Jul;33(5):534-9. - Pubmed
  • Asberg AE, Videm V: Inhibition of platelet receptors involved in neutrophil-platelet interaction in model cardiopulmonary bypass. Artif Organs. 2007 Aug;31(8):617-26. - Pubmed
  • Gao Y, Li N, Fei R, Chen Z, Zheng S, Zeng X: P-Selectin-mediated acute inflammation can be blocked by chemically modified heparin, RO-heparin. Mol Cells. 2005 Jun 30;19(3):350-5. - Pubmed
  • Koenig A, Norgard-Sumnicht K, Linhardt R, Varki A: Differential interactions of heparin and heparan sulfate glycosaminoglycans with the selectins. Implications for the use of unfractionated and low molecular weight heparins as therapeutic agents. J Clin Invest. 1998 Feb 15;101(4):877-89. - Pubmed
  • Nelson RM, Cecconi O, Roberts WG, Aruffo A, Linhardt RJ, Bevilacqua MP: Heparin oligosaccharides bind L- and P-selectin and inhibit acute inflammation. Blood. 1993 Dec 1;82(11):3253-8. - Pubmed
DTHybrid score 0.8935

Enzymes


Heparanase
Name Heparanase
Gene Name HPSE
Actions substrate
References
  • Wang B, Jia J, Zhang X, Zcharia E, Vlodavsky I, Pejler G, Li JP: Heparanase affects secretory granule homeostasis of murine mast cells through degrading heparin. J Allergy Clin Immunol. 2011 May 14. - Pubmed
  • Nadir Y, Brenner B: Heparanase procoagulant effects and inhibition by heparins. Thromb Res. 2010 Apr;125 Suppl 2:S72-6. - Pubmed
  • Levy-Adam F, Feld S, Suss-Toby E, Vlodavsky I, Ilan N: Heparanase facilitates cell adhesion and spreading by clustering of cell surface heparan sulfate proteoglycans. PLoS One. 2008 Jun 11;3(6):e2319. - Pubmed
  • Vlodavsky I, Ilan N, Naggi A, Casu B: Heparanase: structure, biological functions, and inhibition by heparin-derived mimetics of heparan sulfate. Curr Pharm Des. 2007;13(20):2057-73. - Pubmed
  • Katz BZ, Muhl L, Zwang E, Ilan N, Herishanu Y, Deutsch V, Naparstek E, Vlodavsky I, Preissner KT: Heparanase modulates heparinoids anticoagulant activities via non-enzymatic mechanisms. Thromb Haemost. 2007 Dec;98(6):1193-9. - Pubmed
  • Nasser NJ, Sarig G, Brenner B, Nevo E, Goldshmidt O, Zcharia E, Li JP, Vlodavsky I: Heparanase neutralizes the anticoagulation properties of heparin and low-molecular-weight heparin. J Thromb Haemost. 2006 Mar;4(3):560-5. - Pubmed
DTHybrid score 0.7782

Predictions


Id Partner name Gene Name Score
1334 Tissue factor pathway inhibitor TFPI 0.3283
1953 Proto-oncogene protein c-fos FOS 0.2772
852 Heparin cofactor 2 SERPIND1 0.2155
183 Vascular endothelial growth factor A VEGFA 0.2039
2020 Stromal cell-derived factor 1 CXCL12 0.0902
647 Integrin alpha-4 ITGA4 0.0783
54 Prothrombin F2 0.0698
1757 Myeloperoxidase MPO 0.0521
4857 Zinc-alpha-2-glycoprotein AZGP1 0.0344
1756 E-selectin SELE 0.0342
5414 Fiber protein L5 0.034
5418 Fiber protein L5 0.034
5416 Coat protein VP1 Not Available 0.0296
3629 Endo-N-acetylneuraminidase Not Available 0.0296
1130 Lithostathine 1 alpha REG1A 0.0295
3547 Enterotoxin type B entB 0.0275
2324 Botulinum neurotoxin type B botB 0.0272
2570 Tetanus toxin tetX 0.0238
2723 Cholera enterotoxin subunit B ctxB 0.02
369 Coagulation factor VII F7 0.0188
4604 Liver carboxylesterase 1 CES1 0.0187
448 Vitamin K-dependent gamma-carboxylase GGCX 0.0177
798 Osteocalcin BGLAP 0.0167
3831 Low-density lipoprotein receptor-related protein 1 LRP1 0.016
6182 Cytochrome P450 2J2 CYP2J2 0.0145
19 Coagulation factor VIII F8 0.0113
2139 Tissue factor F3 0.0111
3851 Serine protease hepsin HPN 0.01
400 Coagulation factor IX F9 0.0084
5461 Coagulation factor IX F9 0.0084
1547 Coagulation factor XI F11 0.0081
422 Vitamin K-dependent protein C PROC 0.0071
3842 Multiple coagulation factor deficiency protein 2 MCFD2 0.007
3841 ERGIC-53 protein LMAN1 0.007
3840 Asialoglycoprotein receptor 2 ASGR2 0.007
1847 78 kDa glucose-regulated protein HSPA5 0.007
1635 von Willebrand factor VWF 0.007
4118 Cytochrome P450 3A5 CYP3A5 0.0067
1588 Multidrug resistance protein 1 ABCB1 0.0063
1516 Calnexin CANX 0.0061
6589 Delta-hemolysin hld 0.0056
6424 Light-harvesting protein B-800/820 beta chain Not Available 0.0056
6591 ATP synthase C chain atpH 0.0056
6587 Rubredoxin rub 0.0056
6423 Light-harvesting protein B-800/820 alpha chain Not Available 0.0056
6586 Protein S100-G S100G 0.0056
6588 Methionyl-tRNA formyltransferase fmt 0.0056
4718 Putative ATP-dependent Clp protease proteolytic subunit, mitochondrial CLPP 0.0056
6592 Probable L-ascorbate-6-phosphate lactonase ulaG ulaG 0.0056
6585 HLA class I histocompatibility antigen, B-27 alpha chain HLA-B 0.0056
6593 Immunoglobulin G-binding protein G spg 0.0056
4512 Cytochrome P450 3A4 CYP3A4 0.0055
3175 Glutamate--cysteine ligase gshA 0.0053
3830 Calreticulin CALR 0.005
3839 Phytanoyl-CoA dioxygenase, peroxisomal PHYH 0.0049
6495 Cytochrome c oxidase subunit 7C, mitochondrial COX7C 0.0049
6493 Cytochrome c oxidase subunit 6C COX6C 0.0048
6498 Cytochrome c oxidase subunit 6B1 COX6B1 0.0048
6279 Beta-2-microglobulin B2M 0.0048
6497 Cytochrome c oxidase subunit 6A2, mitochondrial COX6A2 0.0048
6496 Cytochrome c oxidase subunit 8A, mitochondrial COX8A 0.0048
6499 Cytochrome c oxidase polypeptide 7A1, mitochondrial COX7A1 0.0048
6494 Cytochrome c oxidase subunit 7B, mitochondrial COX7B 0.0048
5793 Cytochrome c oxidase subunit 2 MT-CO2 0.0048
6559 Cytochrome c oxidase subunit 2 ctaC 0.0048
6669 Cytochrome c oxidase subunit 2 ctaC 0.0048
6490 Cytochrome c oxidase subunit 3 MT-CO3 0.0048
6491 Cytochrome c oxidase subunit 5A, mitochondrial COX5A 0.0048
6489 Cytochrome c oxidase subunit 4 isoform 1, mitochondrial COX4I1 0.0048
371 Cytochrome c oxidase subunit 1 MT-CO1 0.0048
6558 Cytochrome c oxidase subunit 1 ctaD 0.0048
6319 Respiratory nitrate reductase 1 gamma chain narI 0.0048
6318 Respiratory nitrate reductase 1 beta chain narH 0.0048
6317 Respiratory nitrate reductase 1 alpha chain narG 0.0048
6428 Light-harvesting protein B-800/850 beta chain Not Available 0.0045
6427 Light-harvesting protein B-800/850 alpha chain Not Available 0.0045
6533 Light-harvesting protein B-800/850 alpha chain A1 0.0045
6576 Geranylgeranyl transferase type-2 subunit beta RABGGTB 0.0042
6575 Geranylgeranyl transferase type-2 subunit alpha RABGGTA 0.0042
2132 Protein S100-B S100B 0.0041
4878 Glycoprotein hormones alpha chain CGA 0.0041
4856 CD209 antigen CD209 0.0041
1052 Cytotoxic T-lymphocyte protein 4 CTLA4 0.0041
1072 Granzyme B GZMB 0.0041
4871 Endo-beta-N-acetylglucosaminidase F3 endOF3 0.0041
4850 Beta-2-glycoprotein 1 APOH 0.0041
4880 Membrane cofactor protein CD46 0.0041
4889 Ig epsilon chain C region IGHE 0.0041
4189 Alpha-galactosidase A GLA 0.0041
4869 Major capsid protein A430L 0.0041
4852 Reticulon-4 receptor RTN4R 0.0041
4877 Beta-mannanase man 0.0041
442 Envelope glycoprotein gp41 0.0041
4859 Envelope glycoprotein env 0.0041
4845 ADAM 33 ADAM33 0.0041
757 Fusion glycoprotein F0 F 0.0041
4875 Fusion glycoprotein F0 F 0.0041
1563 Platelet glycoprotein Ib alpha chain GP1BA 0.0041
1354 Beta-glucuronidase GUSB 0.0041
4882 Dipeptidyl aminopeptidase-like protein 6 DPP6 0.0041
4721 Beta-1,4-mannanase manA 0.0041
3352 Structural polyprotein Not Available 0.0041
3628 Structural polyprotein Not Available 0.0041
4892 Structural polyprotein Not Available 0.0041
6352 Reaction center protein H chain puhA 0.0036
6456 Reaction center protein H chain puhA 0.0036
6682 Reaction center protein H chain puhA 0.0036
6353 Reaction center protein L chain pufL 0.0036
6454 Reaction center protein L chain pufL 0.0036
6683 Reaction center protein L chain pufL 0.0036
6351 Photosynthetic reaction center cytochrome c subunit pufC 0.0036
6354 Reaction center protein M chain pufM 0.0036
6455 Reaction center protein M chain pufM 0.0036
6684 Reaction center protein M chain pufM 0.0036
793 T-cell surface antigen CD2 CD2 0.0036
119 Carcinoembryonic antigen-related cell adhesion molecule 1 CEACAM1 0.0036
4861 Interleukin-6 receptor alpha chain IL6R 0.0036
4193 Atrial natriuretic peptide clearance receptor NPR3 0.0036
3837 Cytokine receptor common beta chain CSF2RB 0.0036
559 NADH-ubiquinone oxidoreductase chain 1 MT-ND1 0.0035
1184 Interferon beta IFNB1 0.0033
1379 Interleukin-12 subunit beta IL12B 0.0033
6858 Inactive carboxylesterase 4 CES1P1 0.0033
4890 Hemagglutinin HA 0.0033
6566 Hemagglutinin Not Available 0.0033
3027 Streptavidin Not Available 0.0032
554 Low-density lipoprotein receptor LDLR 0.0032
4200 Cytochrome P450 1A2 CYP1A2 0.0032
2998 Sialic acid-binding Ig-like lectin 7 SIGLEC7 0.0031
6120 Cation-independent mannose-6-phosphate receptor IGF2R 0.0031
2297 Genome polyprotein Not Available 0.0031
2322 Genome polyprotein Not Available 0.0031
2694 Genome polyprotein Not Available 0.0031
2719 Genome polyprotein Not Available 0.0031
2860 Genome polyprotein Not Available 0.0031
2928 Genome polyprotein Not Available 0.0031
3160 Genome polyprotein Not Available 0.0031
3260 Genome polyprotein Not Available 0.0031
4783 Genome polyprotein Not Available 0.0031
5726 Genome polyprotein Not Available 0.0031
5779 Genome polyprotein Not Available 0.0031
5867 Genome polyprotein Not Available 0.0031
6253 Genome polyprotein Not Available 0.0031
6301 Genome polyprotein Not Available 0.0031
6380 Genome polyprotein Not Available 0.0031
6381 Genome polyprotein Not Available 0.0031
6437 Genome polyprotein Not Available 0.0031
6520 Genome polyprotein Not Available 0.0031
6521 Genome polyprotein Not Available 0.0031
6652 Genome polyprotein Not Available 0.0031
6734 Genome polyprotein Not Available 0.0031
6735 Genome polyprotein Not Available 0.0031
6736 Genome polyprotein Not Available 0.0031
6737 Genome polyprotein Not Available 0.0031
6738 Genome polyprotein Not Available 0.0031
6739 Genome polyprotein Not Available 0.0031
6744 Genome polyprotein Not Available 0.0031
6748 Genome polyprotein Not Available 0.0031
6894 Genome polyprotein Not Available 0.0031
6898 Genome polyprotein Not Available 0.0031
18 High affinity immunoglobulin epsilon receptor subunit alpha FCER1A 0.0031
604 Vitamin K-dependent protein Z PROZ 0.003
4081 Vitamin K epoxide reductase complex subunit 1-like protein 1 VKORC1L1 0.003
3444 Cyanovirin-N Not Available 0.003
3140 Hemagglutinin-neuraminidase HN 0.003
3609 Hemagglutinin-neuraminidase HN 0.003
3258 Mannosyl-oligosaccharide alpha-1,2-mannosidase MSDC 0.003
1859 Prostatic acid phosphatase ACPP 0.0029
4787 Envelope glycoprotein gp160 env 0.0029
4820 Envelope glycoprotein gp160 env 0.0029
5727 Envelope glycoprotein gp160 env 0.0029
5682 Ribonuclease pancreatic RNASE1 0.0029
1245 Vitamin K-dependent protein S PROS1 0.0028
4666 Fucose-binding lectin PA-IIL lecB 0.0028
595 Fibrinogen alpha chain FGA 0.0028
2372 Bifunctional tail protein 9 0.0028
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0027
2577 Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase MAN1B1 0.0026
3480 Mannan endo-1,4-beta-mannosidase manA 0.0026
958 Insulin-like growth factor 1 receptor IGF1R 0.0025
64 Neuraminidase NA 0.0025
641 Neuraminidase NA 0.0025
2676 Neuraminidase NA 0.0025
3026 Neuraminidase NA 0.0025
3519 Neuraminidase NA 0.0025
6007 Neuraminidase NA 0.0025
1243 Cathepsin D CTSD 0.0024
1439 Lactotransferrin LTF 0.0024
1782 Neutrophil gelatinase-associated lipocalin LCN2 0.0024
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0024
2430 Chondroitinase B cslB 0.0023
3814 Complement C1r subcomponent C1R 0.0023
2581 Chondroitinase AC cslA 0.0022
4924 Cytochrome P450 2C8 CYP2C8 0.0022
6847 Lactase-phlorizin hydrolase LCT 0.0022
6307 Ig gamma-2 chain C region IGHG2 0.0022
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0021
6016 Cytochrome P450 2C19 CYP2C19 0.0021
6500 Phospholipase A2 PLA2G1B 0.0021
787 Vitamin K epoxide reductase complex subunit 1 VKORC1 0.0021
2207 Rhodopsin RHO 0.0021
4757 Cytochrome P450 2C9 CYP2C9 0.002
3917 Methylenetetrahydrofolate reductase MTHFR 0.0019
4785 Ig gamma-1 chain C region IGHG1 0.0018
6020 Aldehyde oxidase AOX1 0.0018
76 Nitric-oxide synthase, brain NOS1 0.0018
3947 Xanthine dehydrogenase/oxidase XDH 0.0017
952 Dipeptidyl peptidase 4 DPP4 0.0016
3923 Cholinesterase BCHE 0.0014
5718 Cytochrome P450 2A6 CYP2A6 0.0013
20 Prostaglandin G/H synthase 1 PTGS1 0.0013
6024 Cytochrome P450 1A1 CYP1A1 0.0013
6013 Cytochrome P450 2E1 CYP2E1 0.0012
↑