CMRES
MCID: CMR002
MIFTS: 48

Coumarin Resistance (CMRES) malady

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Coumarin Resistance

Aliases & Descriptions for Coumarin Resistance:

Name: Coumarin Resistance 54 25 66 13 69
Warfarin Resistance 54 50 25 66 52
Warfarin Sensitivity 54 50 25 69
Poor Metabolism of Coumarin 25 66
Coumadin Sensitivity 50 25
Warfarin Response 25 29
Drug Resistance 42
Cmres 66

Characteristics:

HPO:

32
coumarin resistance:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 54 122700
MeSH 42 D004351

Summaries for Coumarin Resistance

NIH Rare Diseases : 50 warfarin resistance is a condition that is characterized by a high tolerance for a "blood-thinning" medication called warfarin. warfarin is an anticoagulant that is often prescribed to people who are at an increased risk for blood clots. some people with a warfarin resistance do not respond to the drug at all, while others can achieve the benefits of warfarin treatment at a high dose. in either case, affected people will still be at an elevated risk for blood clots when given the standard dose of warfarin. the metabolism of warfarin and the drug's effects in the body are complex traits that are determined by several genes as well as environmental and lifestyle factors such as gender, age, weight, diet, and other medications. one specific genetic polymorphism in the vkorc1 gene accounts for approximately 20% of variation in the response to warfarin and can be passed on to future generations in an autosomal dominant manner. last updated: 9/15/2015

MalaCards based summary : Coumarin Resistance, also known as warfarin resistance, is related to multidrug-resistant tuberculosis and cyp2c9-related altered drug metabolism, and has symptoms including abnormality of metabolism/homeostasis and abnormality of blood and blood-forming tissues. An important gene associated with Coumarin Resistance is VKORC1 (Vitamin K Epoxide Reductase Complex Subunit 1), and among its related pathways/superpathways are Arachidonic acid metabolism and Linoleic acid metabolism. The drugs Warfarin and Acenocoumarol have been mentioned in the context of this disorder. Affiliated tissues include heart, and related phenotype is Increased shRNA abundance (Z-score > 2).

UniProtKB/Swiss-Prot : 66 Coumarin resistance: A condition characterized by partial or complete resistance to warfarin or other 4-hydroxycoumarin derivatives. These drugs are used as anti-coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement.

Genetics Home Reference : 25 Warfarin sensitivity is a condition in which individuals have a low tolerance for the drug warfarin. Warfarin is an anticoagulant, which means that it thins the blood, preventing blood clots from forming. Warfarin is often prescribed to prevent blood clots in people with heart valve disease who have replacement heart valves, people with an irregular heart beat (atrial fibrillation), or those with a history of heart attack, stroke, or a prior blood clot in the deep veins of the arms or legs (deep vein thrombosis).

OMIM : 54 Warfarin is a widely prescribed anticoagulant for the prevention of thromboembolic diseases for subjects with deep vein... (122700) more...

Related Diseases for Coumarin Resistance

Graphical network of the top 20 diseases related to Coumarin Resistance:



Diseases related to Coumarin Resistance

Symptoms & Phenotypes for Coumarin Resistance

Symptoms by clinical synopsis from OMIM:

122700

Clinical features from OMIM:

122700

Human phenotypes related to Coumarin Resistance:

32
id Description HPO Frequency HPO Source Accession
1 abnormality of metabolism/homeostasis 32 HP:0001939
2 abnormality of blood and blood-forming tissues 32 HP:0001871

GenomeRNAi Phenotypes related to Coumarin Resistance according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-157 9.5 F9
2 Increased shRNA abundance (Z-score > 2) GR00366-A-164 9.5 F9
3 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.5 CYP2C9
4 Increased shRNA abundance (Z-score > 2) GR00366-A-176 9.5 F9
5 Increased shRNA abundance (Z-score > 2) GR00366-A-183 9.5 F9 CYP2C9
6 Increased shRNA abundance (Z-score > 2) GR00366-A-199 9.5 CYP2C9
7 Increased shRNA abundance (Z-score > 2) GR00366-A-207 9.5 CYP2C9
8 Increased shRNA abundance (Z-score > 2) GR00366-A-208 9.5 F9
9 Increased shRNA abundance (Z-score > 2) GR00366-A-41 9.5 F9
10 Increased shRNA abundance (Z-score > 2) GR00366-A-44 9.5 F9
11 Increased shRNA abundance (Z-score > 2) GR00366-A-50 9.5 CYP2C9
12 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.5 CYP2C9
13 Increased shRNA abundance (Z-score > 2) GR00366-A-81 9.5 F9
14 Increased shRNA abundance (Z-score > 2) GR00366-A-88 9.5 F9

Drugs & Therapeutics for Coumarin Resistance

Drugs for Coumarin Resistance (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Warfarin Approved Phase 4 81-81-2 6691 54678486
2
Acenocoumarol Approved Phase 4 152-72-7 9052 54676537
3
Phenprocoumon Approved Phase 4 435-97-2 9908 54680692
4 Anticoagulants Phase 4
5
Ticlopidine Approved Phase 3 55142-85-3 5472
6
Clopidogrel Approved, Nutraceutical Phase 3 120202-66-6, 113665-84-2 60606
7 Cytochrome P-450 Enzyme Inhibitors Phase 3
8 Fibrinolytic Agents Phase 3
9 Neurotransmitter Agents Phase 3
10 Platelet Aggregation Inhibitors Phase 3
11 Prasugrel hydrochloride Phase 3 389574-19-0
12 Purinergic P2 Receptor Antagonists Phase 3
13 Purinergic P2Y Receptor Antagonists Phase 3

Interventional clinical trials:


id Name Status NCT ID Phase
1 EUropean Pharmacogenetics of AntiCoagulant Therapy - Warfarin Completed NCT01119300 Phase 4
2 EUropean Pharmacogenetics of AntiCoagulant Therapy - Acenocoumarol Completed NCT01119261 Phase 4
3 EUropean Pharmacogenetics of AntiCoagulant Therapy - Phenprocoumon Completed NCT01119274 Phase 4
4 Prasugrel Versus High Dose Clopidogrel in Clopidogrel Resistant Patients Undergoing Chronic Hemodialysis Completed NCT01155765 Phase 3

Search NIH Clinical Center for Coumarin Resistance

Cochrane evidence based reviews: drug resistance

Genetic Tests for Coumarin Resistance

Genetic tests related to Coumarin Resistance:

id Genetic test Affiliating Genes
1 Warfarin Response 29

Anatomical Context for Coumarin Resistance

MalaCards organs/tissues related to Coumarin Resistance:

39
Heart

Publications for Coumarin Resistance

Articles related to Coumarin Resistance:

id Title Authors Year
1
gyrB mutations which confer coumarin resistance also affect DNA supercoiling and ATP hydrolysis by Escherichia coli DNA gyrase. ( 1323022 )
1992
2
Coumarin resistance: a diagnostic and therapeutic approach. ( 910171 )
1977
3
Coumarin resistance in a Negro woman. ( 4123117 )
1973

Variations for Coumarin Resistance

UniProtKB/Swiss-Prot genetic disease variations for Coumarin Resistance:

66 (show all 18)
id Symbol AA change Variation ID SNP ID
1 VKORC1 p.Val29Leu VAR_021821 rs104894539
2 VKORC1 p.Val45Ala VAR_021822 rs104894540
3 VKORC1 p.Arg58Gly VAR_021823 rs104894541
4 VKORC1 p.Leu128Arg VAR_021825 rs104894542
5 VKORC1 p.Ala26Thr VAR_065785
6 VKORC1 p.Asp36Gly VAR_065786
7 VKORC1 p.Asp36Tyr VAR_065787 rs61742245
8 VKORC1 p.Ser52Trp VAR_065788
9 VKORC1 p.Ser56Phe VAR_065789
10 VKORC1 p.Trp59Cys VAR_065790
11 VKORC1 p.Trp59Leu VAR_065791
12 VKORC1 p.Val66Gly VAR_065792
13 VKORC1 p.Val66Met VAR_065793 rs72547529
14 VKORC1 p.Gly71Ala VAR_065794
15 VKORC1 p.Asn77Ser VAR_065795
16 VKORC1 p.Asn77Tyr VAR_065796 rs755767348
17 VKORC1 p.Ile123Asn VAR_065797
18 VKORC1 p.Tyr139His VAR_065798

ClinVar genetic disease variations for Coumarin Resistance:

6 (show all 16)
id Gene Variation Type Significance SNP ID Assembly Location
1 VKORC1 NM_024006.5(VKORC1): c.85G> T (p.Val29Leu) single nucleotide variant Pathogenic rs104894539 GRCh37 Chromosome 16, 31105966: 31105966
2 VKORC1 NM_024006.5(VKORC1): c.134T> C (p.Val45Ala) single nucleotide variant Pathogenic rs104894540 GRCh37 Chromosome 16, 31105917: 31105917
3 VKORC1 NM_024006.5(VKORC1): c.172A> G (p.Arg58Gly) single nucleotide variant Pathogenic rs104894541 GRCh37 Chromosome 16, 31105879: 31105879
4 VKORC1 NM_024006.5(VKORC1): c.383T> G (p.Leu128Arg) single nucleotide variant Pathogenic rs104894542 GRCh37 Chromosome 16, 31102564: 31102564
5 VKORC1 NM_024006.4(VKORC1): c.-1639G> A single nucleotide variant drug response rs9923231 GRCh37 Chromosome 16, 31107689: 31107689
6 VKORC1 NM_024006.5(VKORC1): c.106G> T (p.Asp36Tyr) single nucleotide variant drug response rs61742245 GRCh37 Chromosome 16, 31105945: 31105945
7 CYP2C9 NM_000771.3(CYP2C9): c.622T> G (p.Leu208Val) single nucleotide variant Pathogenic rs72558191 GRCh38 Chromosome 10, 94947919: 94947919
8 CYP2C9 NM_000771.3(CYP2C9): c.1075A> C (p.Ile359Leu) single nucleotide variant drug response rs1057910 GRCh37 Chromosome 10, 96741053: 96741053
9 CYP2C9 NM_000771.3(CYP2C9): c.430C> T (p.Arg144Cys) single nucleotide variant drug response rs1799853 GRCh37 Chromosome 10, 96702047: 96702047
10 F9 F9, ALA-10THR single nucleotide variant Pathogenic
11 F9 F9, ALA-10VAL undetermined variant Pathogenic
12 CYP2A6 NM_000762.5(CYP2A6): c.479T> A (p.Leu160His) single nucleotide variant drug response rs1801272 GRCh37 Chromosome 19, 41354533: 41354533
13 CYP2A6 CYP2A6*12A deletion drug response GRCh38 Chromosome 19, 40848764: 40881588
14 VKORC1 NM_024006.5(VKORC1): c.174-136C> T single nucleotide variant drug response rs9934438 GRCh37 Chromosome 16, 31104878: 31104878
15 VKORC1 NM_024006.5(VKORC1): c.-226-1362dupG duplication drug response rs397509427 GRCh37 Chromosome 16, 31107638: 31107638
16 VKORC1 NM_024006.5(VKORC1): c.-1639G= single nucleotide variant drug response rs9923231 GRCh37 Chromosome 16, 31107689: 31107689

Expression for Coumarin Resistance

Search GEO for disease gene expression data for Coumarin Resistance.

Pathways for Coumarin Resistance

Pathways related to Coumarin Resistance according to GeneCards Suite gene sharing:

(show all 12)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
11.72 CYP2C9 CYP4F2
2
Show member pathways
11.56 CYP2C9 CYP4F2
3
Show member pathways
11.26 CYP2A6 CYP2C9
4
Show member pathways
11.2 CYP2A6 CYP2C9
5 10.94 CYP2A6 CYP2C9
6
Show member pathways
10.84 CYP2A6 CYP2C9
7
Show member pathways
10.8 CYP2C9 CYP4F2
8 10.7 CYP2A6 CYP2C9
9 10.58 CYP2A6 CYP2C9
10 10.46 CYP2A6 CYP2C9
11 10.07 CYP2A6 CYP2C9
12 9.98 CYP4F2 F9 VKORC1

GO Terms for Coumarin Resistance

Cellular components related to Coumarin Resistance according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.46 CYP2A6 CYP2C9 CYP4F2 MCFD2
2 intracellular membrane-bounded organelle GO:0043231 9.43 CYP2A6 CYP2C9 CYP4F2
3 organelle membrane GO:0031090 9.13 CYP2A6 CYP2C9 CYP4F2
4 endoplasmic reticulum membrane GO:0005789 9.02 CYP2A6 CYP2C9 CYP4F2 MCFD2 VKORC1

Biological processes related to Coumarin Resistance according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.71 CYP2A6 CYP2C9 CYP4F2 VKORC1
2 blood coagulation GO:0007596 9.54 CYP4F2 F9 VKORC1
3 ER to Golgi vesicle-mediated transport GO:0006888 9.46 F9 MCFD2
4 steroid metabolic process GO:0008202 9.43 CYP2A6 CYP2C9
5 exogenous drug catabolic process GO:0042738 9.32 CYP2A6 CYP2C9
6 peptidyl-glutamic acid carboxylation GO:0017187 9.26 F9 VKORC1
7 omega-hydroxylase P450 pathway GO:0097267 9.16 CYP2C9 CYP4F2
8 epoxygenase P450 pathway GO:0019373 9.13 CYP2A6 CYP2C9 CYP4F2
9 drug metabolic process GO:0017144 8.92 CYP2A6 CYP2C9 CYP4F2 VKORC1

Molecular functions related to Coumarin Resistance according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 metal ion binding GO:0046872 9.8 CYP2A6 CYP2C9 CYP4F2 F9 MCFD2
2 oxidoreductase activity GO:0016491 9.62 CYP2A6 CYP2C9 CYP4F2 VKORC1
3 iron ion binding GO:0005506 9.43 CYP2A6 CYP2C9 CYP4F2
4 monooxygenase activity GO:0004497 9.37 CYP2C9 CYP4F2
5 heme binding GO:0020037 9.33 CYP2A6 CYP2C9 CYP4F2
6 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0016705 9.13 CYP2A6 CYP2C9 CYP4F2
7 arachidonic acid epoxygenase activity GO:0008392 8.8 CYP2A6 CYP2C9 CYP4F2

Sources for Coumarin Resistance

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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