1.17.4.4: vitamin-K-epoxide reductase (warfarin-sensitive)
This is an abbreviated version!
For detailed information about vitamin-K-epoxide reductase (warfarin-sensitive), go to the full flat file.
Word Map on EC 1.17.4.4
-
1.17.4.4
-
cyp2c9
-
anticoagulant
-
dosing
-
pharmacogenetic
-
bleeding
-
cyp4f2
-
thromboembolic
-
k-dependent
-
coagulation
-
acenocoumarol
-
interindividual
-
pharmacogenomics
-
fibrillation
-
gg
-
caucasian
-
prothrombin
-
atrial
-
demographic
-
pharmacodynamics
-
clot
-
valve
-
ethnic
-
thrombosis
-
genotype-guided
-
s-warfarin
-
rodenticides
-
gamma-glutamyl
-
non-genetic
-
phenprocoumon
-
warfarin-treated
-
4-hydroxycoumarins
-
gamma-carboxylase
-
coumadin
-
pharmacogenes
-
medicine
-
pivka-ii
-
slco1b1
-
calumenin
-
amiodarone
-
genotype-based
-
interpatient
-
cyp3a5
-
hypoprothrombinemia
-
undercarboxylated
-
clopidogrel
-
antivitamin
-
gamma-carboxylation
- 1.17.4.4
- cyp2c9
-
anticoagulant
-
dosing
-
pharmacogenetic
-
bleeding
- cyp4f2
-
thromboembolic
-
k-dependent
-
coagulation
-
acenocoumarol
-
interindividual
-
pharmacogenomics
- fibrillation
- gg
-
caucasian
- prothrombin
- atrial
-
demographic
-
pharmacodynamics
- clot
- valve
-
ethnic
- thrombosis
-
genotype-guided
-
s-warfarin
-
rodenticides
-
gamma-glutamyl
-
non-genetic
- phenprocoumon
-
warfarin-treated
- 4-hydroxycoumarins
- gamma-carboxylase
-
coumadin
-
pharmacogenes
- medicine
-
pivka-ii
-
slco1b1
- calumenin
- amiodarone
-
genotype-based
-
interpatient
- cyp3a5
- hypoprothrombinemia
-
undercarboxylated
- clopidogrel
-
antivitamin
-
gamma-carboxylation
Reaction
Synonyms
EC 1.1.4.1, phylloquinone epoxide reductase, reductase, phylloquinone epoxide, vitamin K 2,3-epoxide reductase, vitamin K 2,3-epoxide reductase complex subunit 1, vitamin K 2,3-epoxide reductase complex subunit-1, vitamin K epoxid reductase, vitamin K epoxide reductase, vitamin K epoxide reductase complex subunit 1, vitamin K oxidoreductase, Vitamin K reductase, vitamin K-2,3-epoxide reductase, vitamin K-2,3-epoxide reductase subunit 1, vitamin K-epoxide reductase, vitamin K1 epoxide reductase, vitaminK epoxide reductase, VKOR, VKOR complex, VKORC1, VKORC1 variant 2, VKORC1-like 1, VKORC1L1, VKORC1v2, warfarin sensitive vitamin K 2,3-epoxide reductase, warfarin-sensitive vitamin K1 2,3-epoxide reductase
ECTree
1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive)Advanced search results
results (
results (Engineering
Engineering on EC 1.17.4.4 - vitamin-K-epoxide reductase (warfarin-sensitive)
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
top
PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C101A
-
formation of of a high-molecular-weight complex that is positive for thiol-disulfide oxidoreductase MdbA and vitamin K epoxide reductase
C1173T
C132A
C135A
C16A
C43A
C43A/C51A
C51A
C85A
C96A
DELTAC43-C51
G6R
-
site-directed mutagenesis, the mutant shows altered membrane topology compared to the wild-type enzyme
G9R
-
site-directed mutagenesis, the mutant shows altered membrane topology compared to the wild-type enzyme
I123N
I86P
mutation has only a minor effect on the activity of wild-type enzyme, but it has a dramatic effect on the activity of the VKOR-CM mutant (a mutant with mutations in the charged residues flanking transmembrane domain 1), decreasing its activity to about 10%
K30L
-
site-directed mutagenesis, the mutation close to the transmembrane domain 1 leads to altered membrane topology compared to the wild-type enzyme
L120Q
-
naturally occuring mutation, the mutant is resistant to warfarin, but not to difenacoum, no synthesis of no 2-OH-vitamin K1 or 3-OH-vitamin K1
L128Q
-
naturally occuring mutation, no synthesis of no 2-OH-vitamin K1 or 3-OH-vitamin K1
L128R
R33G
-
site-directed mutagenesis, the mutation close to the transmembrane domain 1 leads to altered membrane topology compared to the wild-type enzyme
R35G
-
site-directed mutagenesis, the mutation close to the transmembrane domain 1 leads to altered membrane topology compared to the wild-type enzyme
R37G
-
site-directed mutagenesis, the mutation close to the transmembrane domain 1 leads to altered membrane topology compared to the wild-type enzyme
R58G
R98W
S7R
-
site-directed mutagenesis, the mutant shows altered membrane topology compared to the wild-type enzyme
V29L
V45A
V66M
Y139C
Y139F
Y139S
A26S
-
mutant shows about 70% relative VKOR activity as compared to the wild type enzyme
A48T
-
mutant shows about 120% relative VKOR activity as compared to the wild type enzyme
E37G
-
mutant shows about 75% relative VKOR activity as compared to the wild type enzyme
L128S
-
mutant shows about 20% relative VKOR activity as compared to the wild type enzyme
R12W
-
mutant shows about 35% relative VKOR activity as compared to the wild type enzyme
R58G
-
mutant shows about 40% relative VKOR activity as compared to the wild type enzyme
R61L
-
mutant shows about 50% relative VKOR activity as compared to the wild type enzyme
Y139C
-
mutant shows about 30% relative VKOR activity as compared to the wild type enzyme
W59G
-
the single nucleotide polymorphism T175G in gene VKORC1 causes 4-hydroxycoumarin derivative-resistance
A143V
-
mutant shows about 140% relative VKOR activity as compared to the wild type enzyme
A26T
E67K
-
the mutant shows a reduced vitamin K epoxide turnover of about 33% compared to the wild type protein, and has no effect on warfarin sensitivity in vitro
I141V
-
mutant shows about 45% relative VKOR activity as compared to the wild type enzyme
I90L
-
mutant shows about 90% relative VKOR activity as compared to the wild type enzyme
L120Q
L128Q
R33P
-
VKOR activity of the Arg33Pro variant is reduced to 42% of wild type activity
Y139C
Y139F
Y139S
Y39N
-
mutant shows about 30% relative VKOR activity as compared to the wild type enzyme
Y139F
-
the mutation mediates resistance towards chlorophacinone and bromadiolone
-
additional information
C1173T
-
a single nucleotide polymorphism, SNP, for haplotypes associated with a lower oral anticoagulant dose requirement
C1173T
natural genetic polymorphism of the enzyme in a Chinese and a Caucasian population, genotyping, the exchange for T at position 1173 in asian patients results in a phenotype with higher sensitivity to oral anticoagulants, overview
C132A
mutation eliminates enzymatic activity in conversion of vitamin K to vitamin K hydroquinone
C135A
mutation eliminates enzymatic activity in conversion of vitamin K to vitamin K hydroquinone
C16A
about 85% of wild-type activity in conversion of vitamin K to vitamin K hydroquinone. Mutant enzyme retains 40% of the wild-type activityin conversion of vitamin K to vitamin K hydroquinone
C43A
-
naturally occuring mutant, active in presence of DTT, which helps to bypass C43
C43A
-
site-directed mutagenesis, the mutant shows vitamin K epoxide reduction activity similar to the wild-type enzyme, but only with the membrane-permeant reductant DTT, no mutant activity with thioredoxin as reductant
C43A
about 75% of wild-type activity in conversion of vitamin K to vitamin K hydroquinone. Mutant enzyme retains 25% of the wild-type activityin conversion of vitamin K to vitamin K hydroquinone
C43A/C51A
-
site-directed mutagenesis, the mutation has a minor effect on VKOR activity, the mutant of the altered four-transmembrane domain form of VKOR is more active than the wild-type three-transmembrane domain enzyme
C43A/C51A
about 50% of wild-type activity in conversion of vitamin K to vitamin K hydroquinone. The deletion mutant enzyme retains 85% of the wild-type activity in the conversion of vitamin K 2,3-epoxide to vitamin K
C51A
-
naturally occuring mutant, active in presence of DTT, which helps to bypass C43
C51A
-
site-directed mutagenesis, the mutation has a minor effect on VKOR activity, the mutant of the altered four-transmembrane domain form of VKOR is more active than the wild-type three-transmembrane domain enzyme
C51A
-
site-directed mutagenesis, the mutant shows vitamin K epoxide reduction activity similar to the wild-type enzyme, but only with the membrane-permeant reductant DTT, no mutant activity with thioredoxin as reductant
C51A
mutant enzyme retains essentially wild-type activity in conversion of vitamin K to vitamin K hydroquinone
C85A
about 55% of wild-type activity in conversion of vitamin K to vitamin K hydroquinone. Mutant enzyme retains 105% of the wild-type activityin conversion of vitamin K to vitamin K hydroquinone
C96A
about 50% of wild-type activity in conversion of vitamin K to vitamin K hydroquinone. Mutant enzyme retains 40% of the wild-type activityin conversion of vitamin K to vitamin K hydroquinone
DELTAC43-C51
about 50% of wild-type activity in conversion of vitamin K to vitamin K hydroquinone. The deletion mutant enzyme retains 112% of the wild-type activity in the conversion of vitamin K 2,3-epoxide to vitamin K
L128R
VKOR activity is reduced to 5.2% of the activity of the wild-type enzyme
L128R
site-directed mutagenesis, the mutant is resistant to warfarin and oral anti-coagulants
R58G
VKOR activity is reduced to 20.6% of the activity of the wild-type enzyme
R98W
-
two patients suffering from combined deficiency of vitamin K-dependent clotting factors type 2 possess a R98W substitution at the presumed cytoplasmic end of TM alpha-helix 2 of vitamin-K-epoxide reductase. Because the residue is far-removed from the proposed active site its mutation is, therefore assumed to disrupt VKORC1 structure or VKOR complex assembly rather than catalysis
R98W
VKOR activity is reduced to 8.9% of the activity of the wild-tyoe enzyme
V29L
VKOR activity is reduced to 96.6% of the activity of the wild-type enzyme.Above 0.02 mM warfarin the mutant enzyme retains higher VKOR activity than the wild-type enzyme
V29L
site-directed mutagenesis, the mutant is resistant to warfarin and oral anti-coagulants
V45A
VKOR activity is reduced to 23% of the activity of the wild-type enzyme
V45A
site-directed mutagenesis, the mutant is resistant to warfarin and oral anti-coagulants
V66M
naturally occuring VKORC1 mutant showing warfarin-resistance, patients with this mutation need a very high dosage of anticoagulants in therapy, overview
Y139C
VKOR activity is reduced to 48% of the activity of the wild-type enzyme. Above 0.02 mM warfarin the mutant enzyme retains higher VKOR activity than the wild-type enzyme
Y139C
-
naturally occuring mutation, the mutant is resistant to warfarin, but not to difenacoum, additional synthesis of 3-hydroxyvitamin K1
Y139C
-
site-directed mutagenesis, the mutation dramatically affects the vitamin K epoxide reductase activity
Y139F
-
naturally occuring mutation, the mutant is resistant to warfarin, but not to difenacoum, additional synthesis of 3-hydroxyvitamin K1
Y139F
-
the mutant is warfarin insensitive and shows altered membrane topology compared to the wild-type enzyme
Y139S
-
naturally occuring mutation, the mutant is resistant to warfarin, but not to difenacoum, additional synthesis of 3-hydroxyvitamin K1
Y139S
-
site-directed mutagenesis, the mutation dramatically affects the vitamin K epoxide reductase activity, additional production of 3-hydroxyvitamin K1 in the mutant
A26T
-
mutant shows about 60% relative VKOR activity as compared to the wild type enzyme
A26T
-
the mutation has only a moderate effect on VKOR activity with a reduction to approximately 56% of wild type activity
L120Q
naturally occuring mutant, resitant to warfarin and other anticoagulants
L120Q
naturally occuring mutant, the mutant rat is resistant to some anticoagulants
L128Q
-
mutant shows moderately reduced VKOR activity (about 60% compared to wild type protein) and is resistant to warfarin inhibition to a variable degree
L128Q
naturally occuring mutant, resitant to warfarin and other anticoagulants
L128Q
naturally occuring mutant, the mutant rat is resistant to some anticoagulants
Y139C
-
mutant shows moderately reduced VKOR activity (about 60% compared to wild type protein) and is resistant to warfarin inhibition to a variable degree
Y139C
naturally occuring mutant, resitant to warfarin and other anticoagulants
Y139C
naturally occuring mutant, the mutant rat is resistant to some anticoagulants
Y139F
the natural occuring mutation confers resistance to enzyme inhibitor warfarin, the mutant rats do not show vitamin K deficiency
Y139F
-
highly resistant to warfarin and increased resistance to further anticoagulants
Y139F
-
the mutation mediates resistance towards chlorophacinone and bromadiolone
Y139F
naturally occuring mutant, resitant to warfarin and other anticoagulants
Y139F
naturally occuring mutant, the mutant rat is resistant to some anticoagulants
Y139S
-
mutant shows moderately reduced VKOR activity and is resistant to warfarin inhibition to a variable degree
Y139S
naturally occuring mutant, resitant to warfarin and other anticoagulants
Y139S
naturally occuring mutant, the mutant rat is resistant to some anticoagulants
additional information
VKORC1 contains missense mutations in the two heritable human diseases: combined deficiency of vitamin-K-dependent clotting factors type 2 (VKCFD2, Online Mendelian Inheritance in Man 607473) and resistance to coumarin-type anticoagulant drugs (warfarin resistance, WR, Online Mendelian Inheritance in man 122700)
additional information
-
VKORC1 contains missense mutations in the two heritable human diseases: combined deficiency of vitamin-K-dependent clotting factors type 2 (VKCFD2, Online Mendelian Inheritance in Man 607473) and resistance to coumarin-type anticoagulant drugs (warfarin resistance, WR, Online Mendelian Inheritance in man 122700)
additional information
-
deficient enzyme mutants cause VKCFD2 disease phenotype
additional information
-
enzyme overexpression stimulates cell proliferation, while inhibition of enzyme expression by antisense constructs reduces it, overview
additional information
-
expression of the enzyme in HEK-293 cells significantly improves carboxylation in a HEK-293 cell line overexpressing factor X
additional information
-
mutations in VKORC1 cause 2 distinctive phenotypes: a homozygous missense mutation in the VKORC1 gene leads to combined deficiency of vitamin Kdependent coagulation factors type 2, VKCFD2, and heterozygous missense mutations are responsible for hereditary warfarin resistance, expression of the enzyme in HEK-293 cells significantly improves carboxylation in a HEK-293 cell line overexpressing factor X
additional information
in vitro expression of VKORC1 gene constructs, including coding region and promoter, fails to reveal any genotype effect on transcription and mRNA processing
additional information
-
in vitro expression of VKORC1 gene constructs, including coding region and promoter, fails to reveal any genotype effect on transcription and mRNA processing
additional information
-
patient with warfarin resistance due to a 383T>G transition in exon 2 of the VKORC1 gene, patient is heterozygous for the mutation
additional information
genetic variation in the vitamin K epoxide reductase gene is associated with variation in plasma phylloquinone concentrations
additional information
-
genetic variation in the vitamin K epoxide reductase gene is associated with variation in plasma phylloquinone concentrations
additional information
-
VKORC1 gene polymorphisms are associated with warfarin dose requirements in Turkish patients
additional information
construction of warfarin-resistant VKORC1 variants following naturally occuring mutations in patients
additional information
-
construction of warfarin-resistant VKORC1 variants following naturally occuring mutations in patients
additional information
-
knockout of endogenous VKOR activity, i.e. VKOR and VKORC1L1 enzymes, in HEK-293 cells by transcription activator-like effector nucleases (TALENs)-mediated genome editing, overview. VKOR knockout cells regained KO reductase activity through VKORC1L1 after culturing for several generations (Figure 3A). In addition, this activity is sensitive to warfarin inhibition as the wild-type cells
additional information
-
allelic mutations in the orthologous gene of VKORC1 can cause warfarin resistance
additional information
-
allelic mutations in the orthologous gene can cause warfarin resistance
