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Information on EC 1.5.1.20 - methylenetetrahydrofolate reductase [NAD(P)H] and Organism(s) Homo sapiens
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1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H]IUBMB Comments
A flavoprotein (FAD). The enzyme catalyses the reversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, playing an important role in folate metabolism by regulating the distribution of one-carbon moieties between cellular methylation reactions and nucleic acid synthesis. This enzyme, characterized from Protozoan parasites of the genus Leishmania, is unique among similar characterized eukaryotic enzymes in that it lacks the C-terminal allosteric regulatory domain (allowing it to catalyse a reversible reaction) and uses NADH and NADPH with equal efficiency under physiological conditions. cf. EC 1.5.1.53, methylenetetrahydrofolate reductase (NADPH); EC 1.5.1.54, methylenetetrahydrofolate reductase (NADH); and EC 1.5.7.1, methylenetetrahydrofolate reductase (ferredoxin).
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Word Map
- 1.5.1.20
- nitrite
- homocysteine
- medicine
- paracoccus
-
assimilatory
-
denitrification
- chlorate
- narghi
-
resde
- napc
-
molybdoenzyme
- pantotrophus
-
ammonification
- nutrition
- analysis
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
respiratory nitrate reductase, 10-methylenetetrahydrofolate reductase, napab, met13, n5,n10-methylenetetrahydrofolate reductase, n5,10-methylenetetrahydrofolate reductase, atmthfr-1, methylenetetrahydrofolate reductase (nadph), methylenetetrahydrofolic acid reductase, 5,10-ch2-h4folate reductase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
5,10-CH2-H4folate reductase
-
-
-
-
5,10-methylenetetrahydrofolate reductase
5,10-methylenetetrahydrofolate reductase (NADPH)
-
-
-
-
5,10-methylenetetrahydrofolic acid reductase
-
-
-
-
5,10-methylenetetrahydropteroylglutamate reductase
-
-
-
-
5-methyltetrahydrofolate:NAD oxidoreductase
-
-
-
-
5-methyltetrahydrofolate:NAD+ oxidoreductase
-
-
-
-
5-methyltetrahydrofolate:NADP+ oxidoreductase
-
-
-
-
methylenetetrahydrofolate (reduced riboflavin adenine dinucleotide) reductase
-
-
-
-
methylenetetrahydrofolate reductase
methylenetetrahydrofolate reductase (NADPH)
-
-
-
-
methylenetetrahydrofolic acid reductase
-
-
-
-
MTHFR
MTHFR2
-
-
-
-
N5,10-methylenetetrahydrofolate reductase
-
-
-
-
N5,N10-methylenetetrahydrofolate reductase
-
-
-
-
reductase, methylenetetrahydrofolate (reduced nicotinamide adenine dinucleotide phosphate)
-
-
-
-
reductase, methylenetetrahydrofolate (reduced riboflavin adenine dinucleotide)
-
-
-
-
5,10-methylenetetrahydrofolate reductase
-
-
-
-
5,10-methylenetetrahydrofolate reductase
-
-
methylenetetrahydrofolate reductase
-
-
-
-
methylenetetrahydrofolate reductase
-
-
654163, 684273, 684274, 684291, 684295, 684298, 684314, 684428, 684441, 684442, 684465, 684738, 684805, 685493, 685860, 685894, 685917, 685988, 685990, 685995, 686128, 686133, 686144, 686149, 686185, 686240, 686310, 686329, 686343, 686497, 686513, 686515, 686540, 686572, 686590, 686592, 686633, 686835, 686994, 687023, 687066, 687152, 687167, 687174, 687359, 687832, 687894, 687946, 687957, 688129, 688140, 688142, 688184, 688476, 688554, 688562, 688565, 688704, 688709, 688710, 688715, 688756, 688778, 689031, 689103, 689111, 689282, 689284, 689298, 689333, 689366, 689729, 689833, 689836, 690042, 690049, 690083, 690112, 690122, 690124, 690181, 690199
MTHFR
-
-
-
-
MTHFR
-
-
654163, 684226, 684273, 684274, 684280, 684291, 684295, 684297, 684298, 684314, 684428, 684441, 684442, 684465, 684469, 684473, 684738, 684805, 685493, 685860, 685862, 685893, 685894, 685895, 685917, 685988, 685990, 685995, 686128, 686133, 686144, 686149, 686158, 686185, 686240, 686310, 686329, 686343, 686497, 686513, 686515, 686517, 686540, 686572, 686589, 686590, 686592, 686633, 686829, 686835, 686994, 687023, 687066, 687152, 687167, 687170, 687174, 687359, 687832, 687894, 687946, 687957, 688057, 688129, 688135, 688140, 688142, 688184, 688476, 688554, 688562, 688565, 688688, 688704, 688709, 688710, 688715, 688756, 688778, 689009, 689031, 689103, 689111, 689166, 689282, 689284, 689298, 689329, 689330, 689333, 689366, 689729, 689833, 689836, 690042, 690049, 690083, 690112, 690122, 690124, 690162, 690181, 690199, 690212, 702155, 724809
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-
SYSTEMATIC NAME
IUBMB Comments
5-methyltetrahydrofolate:NAD(P)+ oxidoreductase
A flavoprotein (FAD). The enzyme catalyses the reversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, playing an important role in folate metabolism by regulating the distribution of one-carbon moieties between cellular methylation reactions and nucleic acid synthesis. This enzyme, characterized from Protozoan parasites of the genus Leishmania, is unique among similar characterized eukaryotic enzymes in that it lacks the C-terminal allosteric regulatory domain (allowing it to catalyse a reversible reaction) and uses NADH and NADPH with equal efficiency under physiological conditions. cf. EC 1.5.1.53, methylenetetrahydrofolate reductase (NADPH); EC 1.5.1.54, methylenetetrahydrofolate reductase (NADH); and EC 1.5.7.1, methylenetetrahydrofolate reductase (ferredoxin).
CAS REGISTRY NUMBER
COMMENTARY
71822-25-8
-
9028-69-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
-
-
-
-
?
5,10-methylenetetrahydrofolate + NADPH
?
-
first step in biosynthesis of methyl groups
-
-
?
5,10-methylenetetrahydrofolate + NADPH + H+
5-methyltetrahydrofolate + NADP+
-
-
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
5-methyltetrahydrofolate + oxidized menadione
5,10-methylenetetrahydrofolate + reduced menadione
-
-
-
?
additional information
?
-
-
in patients with defects in the enzyme the homocysteine concentrations are increased, hyperhomocysteinemia elevates the risk for cardiovascular disease
-
-
?
5,10-methylenetetrahydrofolate + acceptor
5-methyltetrahydrofolate + reduced acceptor
-
-
-
-
?
5,10-methylenetetrahydrofolate + acceptor
5-methyltetrahydrofolate + reduced acceptor
-
-
-
-
ir
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
-
-
-
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
physiological NADPH-CH2-H4folate oxidoreductase activity
5-methyltetrahydrofolate is the major methyl donor for the conversion of homocysteine to methionine
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
-
685862, 685893, 685988, 685995, 686128, 686133, 686144, 686158, 686185, 686240, 686310, 686329, 686497, 686513, 686515, 686517, 686540, 686572, 686592, 686633, 686835, 686994, 687946, 687957, 688057, 688129, 688135, 688140, 688142, 688184, 688554, 688565, 688688, 688704, 688709, 689031, 689103, 689111, 689166, 689282, 689284, 689298, 689329, 689330, 689333, 690042, 690049, 690112, 690124, 690212
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
-
-
-
ir
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
forward reaction: reduced acceptor is FADH2
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
reverse reaction: menadione as electron acceptor
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
forward reaction: NADPH as reduced acceptor
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
supply of the folate needed for the metabolism of homocysteine: 5-methyltetrahydrofolate is required for the methylation of homocysteine to methionine
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
homocysteine metabolism
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
homocysteine metabolism
5-methyltetrahydrofolate is the main form of circulating folate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
physiological direction is the 5-methyltetrahydrofolate formation
5-methyltetrahydrofolate is the main form of circulating folate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
remethylation of homocysteine to methionine
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
remethylation of homocysteine to methionine
5-methyltetrahydrofolate is the main form of circulating folate
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
-
-
-
-
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
physiological NADPH-CH2-H4folate oxidoreductase activity
5-methyltetrahydrofolate is the major methyl donor for the conversion of homocysteine to methionine
?
5,10-methylenetetrahydrofolate + NADPH
?
-
first step in biosynthesis of methyl groups
-
-
?
5,10-methylenetetrahydrofolate + NADPH + H+
5-methyltetrahydrofolate + NADP+
-
-
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
additional information
?
-
-
in patients with defects in the enzyme the homocysteine concentrations are increased, hyperhomocysteinemia elevates the risk for cardiovascular disease
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
supply of the folate needed for the metabolism of homocysteine: 5-methyltetrahydrofolate is required for the methylation of homocysteine to methionine
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
homocysteine metabolism
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
homocysteine metabolism
5-methyltetrahydrofolate is the main form of circulating folate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
physiological direction is the 5-methyltetrahydrofolate formation
5-methyltetrahydrofolate is the main form of circulating folate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
remethylation of homocysteine to methionine
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
remethylation of homocysteine to methionine
5-methyltetrahydrofolate is the main form of circulating folate
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
FAD is not required, NADPH is highly preferred before NADH
-
FAD
-
enzyme activity depends on the concentration of its cofactor FAD: maximum activity at 0.05 mM FAD
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(S)-SKI-72
binds MTHFR via its allosteric domain with nanomolar affinity. Assay of MTHFR activity in the presence of (S)-SKI-72 demonstrates inhibition of purified enzyme with submicromolar potency and endogenous MTHFR from HEK293 cell lysate in the low micromolar range, both of which are lower than AdoMet. Nevertheless, unlike AdoMet, (S)-SKI-72 is unable to completely abolish MTHFR activity, even at very high concentrations
(S)-SKI-73
a (S)-SKI-72 prodrug derivative, in which the 9'-amine moiety is cloaked with the trimethyl-locked quinone butanoate moiety, on intact HEK293 cells. Once (S)-SKI-73 passes inside the cell membrane, it is metabolised into (S)-SKI-72 and 60-N benzylhomosinefungin, which then accumulates inside the cell
-
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid
-
-
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
-
-
N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
-
-
N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
-
-
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
S-adenosylmethionine
-
inhibition of the enzyme in crude extracts from fresh liver biopsies, but not after purification from cadaver liver
S-adenosylmethionine
-
strong, reversible allosteric inhibition, prevented by S-adenosylhomocysteine
S-adenosylmethionine
SAM, allosteric inhibition by the reaction product. MTHFR phosphorylation, identified on 11 N-terminal residues (16 in total), increases sensitivity to SAM binding and inhibition
additional information
-
inhibiting MTHFR with either antisense or siRNA decreases the viability of methionine-dependent transformed gastric cancer cells
-
additional information
the regulatory domain of MTHFR can be targeted by small molecules and presents (S)-SKI-72 as an excellent candidate for development of MTHFR inhibitors, docking study, overview. Phosphorylation of MTHFR, which occurs mainly in the N-terminal serine rich region, further sensitises the protein to this inhibition. Enzyme inhibition may be reversed by the binding of S-adenosylhomocysteine (AdoHcy), the demethylated form of Ado-Met, to the regulatory domain. (S)-SKI-72 exhibits poor membrane permeability
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.012
5,10-methylenetetrahydrofolate
-
NADPH-5,10-methylenetetrahydrofolate-oxidoreductase reaction
0.0224
5,10-methylenetetrahydrofolate
pH 6.6, 46°C, enzyme mutant HsMTHFR1-656
0.0255
5,10-methylenetetrahydrofolate
pH 6.6, 46°C, enzyme mutant HsMTHFR38-644
0.038
5-methyltetrahydrofolate
-
5,10-methylenetetrahydrofolate-oxidoreductase reaction
additional information
additional information
Michaelis-Menten kinetics for wild-type and mutant enzymes
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
40.7
5,10-methylenetetrahydrofolate
pH 6.6, 46°C, enzyme mutant HsMTHFR1-656
51.4
5,10-methylenetetrahydrofolate
pH 6.6, 46°C, enzyme mutant HsMTHFR38-644
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1817
5,10-methylenetetrahydrofolate
pH 6.6, 46°C, enzyme mutant HsMTHFR1-656
2015.7
5,10-methylenetetrahydrofolate
pH 6.6, 46°C, enzyme mutant HsMTHFR38-644
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
enzyme inhibition kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0007
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid
Homo sapiens
-
-
0.0022
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
Homo sapiens
-
-
0.033
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
Homo sapiens
-
-
0.0018
N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
Homo sapiens
-
-
0.0035
N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
Homo sapiens
-
-
0.0012
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
Homo sapiens
-
-
0.0016
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
Homo sapiens
-
-
additional information
N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
additional information
N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
Homo sapiens
-
value above 0.048
additional information
N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
Homo sapiens
-
value above 0.05
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
specific activity in various patients with enzyme deficiencies
additional information
-
values of healthy and homocysteinemic humans before and after heat inactivation, specific activity of thermolabile variant of enzyme in homozygotes is 50% of normal enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.6
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
392157, 392164, 392165, 392166, 437719, 437721, 437722, 437723, 437725, 654163, 677069, 684226, 684273, 684274, 684280, 684291, 684295, 684297, 684298, 684314, 684428, 684441, 684442, 684465, 684469, 684473, 684738, 684805, 685493, 685860, 685862, 685893, 685894, 685895, 685917, 685988, 685990, 685995, 686128, 686133, 686144, 686149, 686158, 686185, 686240, 686310, 686329
-
-
-
686343, 686497, 686513, 686515, 686517, 686540, 686572, 686589, 686590, 686592, 686633, 686829, 686835, 686994, 687023, 687066, 687152, 687167, 687170, 687174, 687359, 687832, 687894, 687946, 687957, 688057, 688129, 688135, 688140, 688142, 688184
-
-
-
688476, 688554, 688562, 688565, 688688, 688704, 688709, 688710, 688715, 688756, 688778, 689009, 689031
-
-
-
689103, 689111, 689166, 689282, 689284, 689298, 689329, 689330, 689333, 689366, 689729, 689833, 689836, 690042, 690049, 690083, 690112, 690122, 690124, 690162, 690181, 690199, 690212, 697857, 698118, 699849, 702155, 712182, 713042, 724809
-
-
recombinant enzyme, expression in Escherichia coli, Baculovirus system, or HEK293 cells
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
-
-
-
684226, 684273, 684280, 684295, 684314, 684428, 684442, 684465, 684469, 684738, 684805, 685493, 685860, 685894, 685917, 685990, 686128, 686133, 686144, 686149, 686185, 686497, 686540, 686589, 686590, 686633, 686994, 687023, 687066, 687167, 687170, 687174, 687359, 687832, 687957, 688129, 688135, 688554, 688704, 688709, 688778, 689009, 689103, 689282, 689284, 689298, 689330, 689333, 689833, 689836, 690042, 690049, 690112, 690122, 690124, 690162, 690212
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
human MTHFR is a 656 amino acid multi-domain protein, and the catalytic domain is conserved across evolution
malfunction
metabolism
physiological function
additional information
malfunction
-
mutations in the enzyme lead to hyperhomocysteinemia. A C677T polymorphism is associated with an increased risk for the development of cardiovascular disease, Alzheimer's disease, and depression in adults and of neural tube defects in the fetus
malfunction
in accordance with its essential role, major and minor deficiencies of human MTHFR are the direct or indirect causes of human disease. Severe MTHFR deficiency is inherited in an autosomal recessive manner and is the most common inborn error of folate deficiency. Milder enzyme deficiencies, due to single nucleotide polymorphisms of the MTHFR gene, have been associated with various common disorders
malfunction
MTHFR deficiency and upregulation result in diverse disease states, rendering it an attractive drug target. The activity of MTHFR is inhibited by the binding of S-adenosylmethionine (AdoMet) to an allosteric regulatory domain distal to the enzyme's active site
metabolism
-
the enzyme plays a key role in folate metabolism and in the homeostasis of homocysteine
metabolism
the folate and methionine cycles are crucial for biosynthesis of lipids, nucleotides and proteins, and production of the methyl donor S-adenosylmethionine (SAM). 5,10-methylenetetrahydrofolate reductase (MTHFR) represents a key regulatory connection between these cycles, generating 5-methyltetrahydrofolate for initiation of the methionine cycle, and undergoing allosteric inhibition by its end product SAM
physiological function
the folate and methionine cycles are crucial for biosynthesis of lipids, nucleotides and proteins, and production of the methyl donor S-adenosylmethionine (SAM). 5,10-methylenetetrahydrofolate reductase (MTHFR) represents a key regulatory connection between these cycles, generating 5-methyltetrahydrofolate for initiation of the methionine cycle, and undergoing allosteric inhibition by its end product SAM. Molecular regulation of MTHFR, overview. Phosphorylation does not alter MTHFR kinetic parameters. Phosphorylated MTHFR appeares to protect thermally unstable SAM from degradation to SAH, while the non-phosphorylated protein is unable to perform this function
physiological function
the folate and methionine cycles, constituting one-carbon metabolism, are critical pathways for cell survival. Intersecting these two cycles, 5,10-methylenetetrahydrofolate reductase (MTHFR) directs one-carbon units from the folate to methionine cycle, to be exclusively used for methionine and S-adenosylmethionine (AdoMet) synthesis
additional information
human MTHFR reveals a unique architecture, appending the well-conserved catalytic TIM-barrel to a eukaryote-only SAM-binding domain. The latter domain of distinct fold provides the predominant interface for MTHFR homodimerization, positioning the N-terminal serine-rich phosphorylation region near the C-terminal SAM-binding domain. This explains how MTHFR phosphorylation, identified on 11 N-terminal residues (16 in total), increases sensitivity to SAM binding and inhibition. The 25-amino-acid inter-domain linker enables conformational plasticity and is proposed to be a key mediator of SAM regulation, molecular regulation of MTHFR, overview. The catalytic domain to form a beta8alpha8 (TIM) barrel, with residues critical for binding the cofactor FAD, the electron donor NADPH, and the product CH3-THF. The catalytic domain is sufficient for the entire catalytic cycle. Structure-function analysis, overview
additional information
the active site constitutes a distinct fold with a druggable pocket. Identification of 4 compounds that stabilize the regulatory domain. Three compounds are sinefungin analogues, closely related to AdoMet and S-adenosylhomocysteine (AdoHcy). The strongest thermal stabilisation is provided by (S)-SKI-72, a potent inhibitor originally developed for protein arginine methyltransferase 4 (PRMT4), docking study, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MTHR_HUMAN
656
0
74597
Swiss-Prot
other Location (Reliability: 2)
Q59GJ6_HUMAN
672
0
75049
TrEMBL
other Location (Reliability: 2)
A0A1C9J7R9_HUMAN
64
0
7120
TrEMBL
other Location (Reliability: 1)
A0A1W5XGE6_HUMAN
56
0
6212
TrEMBL
other Location (Reliability: 1)
A0A286YFD0_HUMAN
642
0
72065
TrEMBL
other Location (Reliability: 2)
Q5SNW7_HUMAN
696
0
78878
TrEMBL
Mitochondrion (Reliability: 4)
A0A286YF17_HUMAN
549
0
62000
TrEMBL
other Location (Reliability: 2)
L7P8G6_HUMAN
411
0
47364
TrEMBL
other Location (Reliability: 4)
A0A482KE01_HUMAN
64
0
7120
TrEMBL
other Location (Reliability: 1)
Q5SNW5_HUMAN
143
0
15818
TrEMBL
other Location (Reliability: 2)
Q30BY1_HUMAN
39
0
4441
TrEMBL
other Location (Reliability: 4)
F8W9T8_HUMAN
229
0
25324
TrEMBL
other Location (Reliability: 2)
A0MPA5_HUMAN
64
0
7222
TrEMBL
other Location (Reliability: 1)
A0A482KFZ6_HUMAN
60
0
6877
TrEMBL
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
70000
-
x * 77000, SDS-PAGE, x * 70000, SDS-PAGE of MTHFR mutant c.523G>A or mutant c.1166G>A
77000
77000
-
x * 77000, SDS-PAGE, x * 70000, SDS-PAGE of MTHFR mutant c.523G>A or mutant c.1166G>A
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 77000, SDS-PAGE, x * 70000, SDS-PAGE of MTHFR mutant c.523G>A or mutant c.1166G>A
dimer
additional information
catalytic and regulatroy domain of the enzyme are connected by a linker sequence, domain organisation of MTHFR, structure mdoel (PDB ID 6FCX). Domain organisation of MTHFR overview
dimer
an asymmetric MTHFR dimer with inter-domain flexibility. The extensive linker connects and interacts with both domains, the N-terminal catalytic domain (aa 40-337) consisting of an 8alpha/8beta TIM barrel, adorned with three extra alpha-helices, and the C-terminal regulatory domain (aa 363-644) making up a fold of two five-stranded beta-sheets arranged side-by-side in the core, flanked by a number of alpha-helices
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
-
treatment by alkaline phosphatase removes seven phosphoryl groups from enzyme. Treated enzyme is more active than native enzyme and less sensitive to inhibition by S-adenosylmethionie
phosphoprotein
MTHFR phosphorylation, identified on 11 N-terminal residues (16 in total). MTHFR phosphorylation, identified on 11 N-terminal residues (16 in total), increases sensitivity to SAM binding and inhibition. The residues are Ser9, Ser10, Ser18, Ser20, Ser21, Ser23, Ser25, Ser26, Ser29, Ser30, and Thr34, located within the N-terminal serine-rich region, including the putative phosphorylation determining residue Thr34. Phosphorylation of three further amino acids in the catalytic domain (Tyr90, Thr94, and Ser103) and two in the regulatory domain (Ser394 and Thr451). Phosphorylation does not alter MTHFR kinetic parameters. Dimeric mutant HsMTHFR38-644 is not phosphorylated
phosphoprotein
phosphorylation of MTHFR occurs mainly in the N-terminal serine rich region and further sensitises the protein to allosteric inhibition by adenosyl-L-methionine
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified enzyme in complex with FAD and SAH, X-ray diffraction structure determination and analysis at 2.5 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A1298C
A222V
A677V
-
the mutation is accompanied by hyperhomocysteinemia and protein C deficiency
C1141T
-
high level of enzyme activity, retains 40% of its activity after 20 min at 55°C
C667T
C677T
E429A
E429D
-
the muattion leads to elevated total homocysteine concentration and reduced folate and vitamin B12 levels, but is not associated with the development of bipolar disorders
I225V
-
natural polymorphism. Mutation results in an unusual melting curve peak at 53.4°C instead of 51.6°C or 60.4°C in melting curve analysis after real-time polymerase chain reaction
T34A
-
complete blocking of phosphorylation of enzyme. Mutant enzyme is more active than wild-type and less sensitive to inhibition by S-adenosylmethionie
additional information
A1298C
-
high level of enzyme activity, retains 40% of its activity after 20 min at 55°C
A1298C
-
MTHFR C677T/C677T and A1298C/A1298C, but not factor V-Leiden, genotypes are associated with stroke. The C677T but not A1298C MTHFR mutation is associated with elevated homocysteine levels in patients and control subjects
A1298C
-
natural polymorphism. Mutation is not associated with increased toxicity of methotrexate
A1298C
-
natural polymorphism, not associated with colorectal cancer risk. Patients with 1298CC and AC genotypes exhibit worse survival than those with the wild-type genotype. Variant C allele of A1298C affects negatively the response to 5-fluorouracil-based chemotherapy
A222V
-
most frequent genetic cause of mild hyperhomocysteinemia, enzyme with enhanced propensity to dissociate into monomers and to lose its FAD cofactor on dilution, increased thermolability of enzyme activity
A222V
-
common polymorphism of enzyme leading to thermolability of protein and mild elevation of plasma homocysteine thrombotic levels
A222V
-
mutant with reduced enzymatic activity, predicts serum folate and plasma homocysteine levels and is useful for predicting toxicity from capecitabine in patients with advanced colorectal cancer
A222V
-
no correlation can be proved between mutation, patient tumor site, presence of metastasis, and local tumor relapse, the polymorphism is not important in an individual's susceptibility to osteosarcoma and chondrosarcoma in Turkey and may not be a useful marker for identifying patients at high risk of developing sarcomas
A222V
-
the major genetic impact on total plasma homocysteine concentrations is attributable to the MTHFR mutation A222V
A222V
-
the muattion leads to elevated total homocysteine concentration and reduced folate and vitamin B12 levels, but is not associated with the development of bipolar disorders
A222V
-
the mutation corresponding to gene polymorphism C677T is associated with an increased risk of breast and ovarian cancer
A222V
-
the mutation is not associated with occlusive artery disease and deep venous thrombosis in Macedonians
A222V
the 677C>T polymorphism located in methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR) gene modulates the effects of this treatment on homocysteine and nitrite (as a biomarker of nitric oxide bioavailability) in obese women treated with simvastatin. Simvastatin treatment significantly reduces total cholesterol, low density lipoprotein-cholesterol, thiobarbituric acid-reactive substances, high-sensitivity C-reactive protein and homocysteine, whereas nitrite levels are increased. The reduction in homocysteine levels in carriers of the T allele is 20.3% compared with -9.4% in patients with the CC genotype. Importantly, before treatment, nitrite levels are significantly higher in patients with the CC genotype compared with T allele carriers, whereas after treatment these levels are similar between groups
C667T
-
high level of enzyme activity, loses almost all its activity after 20 min at 55°C, enzyme in patients with TT or TC genotype are more thermolabile than wild type enzyme at 46°C
C677T
-
MTHFR C677T/C677T and A1298C/A1298C, but not factor V-Leiden, genotypes are associated with stroke. The C677T but not A1298C MTHFR mutation is associated with elevated homocysteine levels in patients and control subjects
C677T
-
natural polymorphism. Homozygosity for the C677T variant presents a 3fold increased risk of colorectal cancer
C677T
-
natural polymorphism. Mutation is associated with increased toxicity of methotrexate
C677T
-
no significant association between Mthfr mutation C677T and bipolar disorder
C677T
-
seventy-one percent of patients with macrovascular disorders have the MTHFR polymorphism
C677T
-
natural polymorphism, has protective effect on colorectal cancer, the TT genotype showing an odds ratios of 0.06 and the CT of 0.51. C677T genotypes do not affect patient survival. C677T allele carriers respond better to 5-fluorouracil-based chemotherapy than patients with the wild-type CC genotype
E429A
-
A1298C mutation of the MTHRF gene, enzyme with indistinguishable properties from the wild-type
E429A
-
mutant with reduced enzymatic activity, predicts serum folate and plasma homocysteine levels and is useful for predicting toxicity from capecitabine in patients with advanced colorectal cancer
E429A
-
the mutation corresponding to gene polymorphism A1298T is associated with an increased risk of breast cancer
E429A
-
the mutation has a minor elevating effect on total plasma homocysteine concentration
E429A
-
the mutation is not associated with occlusive artery disease and deep venous thrombosis in Macedonians
additional information
-
C677T mutation in the coding region of the gene, which replaces a conserved alanine by valine residue in enzyme with reduced activity, increased risk for cardiovascular disease, homozygosity results in a thermolabile enzyme and homocysteinaemia
additional information
-
C677T mutation in MTHFR gene is a polymorphism which leads to the substitution of Ala-222 by valine
additional information
-
A1298C mutation of the MTHFR gene, which leads to the substitution of Glu-429 by alanine
additional information
-
C677T mutation of the gene for methylenetetrahydrofolate reductase: thermolabile enzyme with reduced activity, due to the loss of its riboflavin cofactor, homozygous genotype TT is associated with an increase in plasma total homocysteine, 12% of the healthy white population with this polymorphism
additional information
-
homozygous C677T mutation in the MTHFR gene, resulting in a conserved amino acid change from alanine to valine: enzyme with reduced activity and higher thermolability, elevated plasma homocysteine concentrations, but no genetic risk factor for deep-vein thrombosis, irrespective of factor V Leiden genotype
additional information
-
C677T nucleotide polymorphism, thermolabile, homozygotic persons show hyperhomocysteinemia, the homocysteine level can be reduced by riboflavin supplementation which might be useful in therapy of hyperhomocysteinemia, the mutantion affects the vitamin metabolism
additional information
-
C677T and A1298C gene polymorphisms are associated with reduced enzyme activity, thereby making MTHFR polymorphisms a potential candidate as a cancer-predisposing factor, they may be associated with the individual susceptibility to develop diffuse large B cell lymphoma
additional information
-
C677T and A1298C MTHFR polymorphic variants are associated with the risk of Down syndrome in infants
additional information
-
existence of a joint effect between the MTHFR gene polymorphisms C677T and A1298C on the risk of gastric carcinoma, the single nucleotide polymorphisms are associated with the risk of gastric carcinoma in the east China population
additional information
-
gastric cancer risk is associated with C677T bit not A1298C gene polymorphism
additional information
-
gene polymorphism A1298T is associated with several diseases, such as cardiovascular and psychiatric diseases, neural tube defects, diabetes, and cancer
additional information
-
gene polymorphism C677T does not affect the risk for acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation
additional information
-
gene polymorphism C677T is responsible for thermolabile MTHFR with reduced enzymatic activity and is associated with Alzheimer's disease
additional information
-
genotypes MTHFR C677T and A1298C do not appear to be important risk factors for thromboembolic disorders
additional information
-
genotyping the MTHFR C677T and A1298T gene polymorphism play no role in the prediction of the disease-free survival of patients undergoing adjuvant 5-fluorouracil/methotrexate based chemotherapy against breast cancer
additional information
-
high concentrations of serum folate/vitamin B12 levels are associated with the risk of promoter methylation in tumor-specific genes, and this relationship is modified by MTHFR C677T genotypes in Iranian colorectal cancer patients
additional information
-
homo- and heterozygous MTHFR gene polymorphisms C677T and A1298C cause elevated plasma homocysteine concentrations after nitric oxide anesthesia
additional information
-
homocysteine levels in children and adolescents are associated with the MTHFR polymorphism C677T genotype
additional information
-
homozygocity for the C677T gene mutation of MTHFR is independently associated with the development of premature with premature myocardial infarction and normal coronary arteries
additional information
-
hyperhomocysteinemia is significantly related to the severity of coronary artery disease independent on MTHFR polymorphism C677T
additional information
-
in patients with acute myocardial infarction, MTHFR 677TT homozygosis is independently associated with a persistently occluded infarct-related artery after thrombolysis
additional information
-
increased MTHFR 677T allele load confers risk for negative symptoms in schizophrenia, while reducing severity of positive symptoms, the biochemical interaction of low serum folate with 677T-variant MTHFR may induce downstream effects salient to the expression of negative symptoms
additional information
-
individuals with a homozygous variant of the MTHFR C677T polymorphism have a reduced risk of colorectal cancer
additional information
-
MTHFR C677T and A1298C gene polymorphisms result in hyperhomocysteinemia which causes abnormal hepatic steatosis
additional information
-
MTHFR C677T and A1298C gene variants play a critical role in NHL outcome, possibly by interfering with the action of methotrexate with significant effects on toxicity and survival in non-Hodgkin's lymphoma patients
additional information
-
MTHFR C677T gene polymorphism leads to a thermolabile enzyme, mild hyperhomocysteinemia, and increased coronary artery disease risk, in Caucasian Brazilians the frequency of the 677T homozygous genotype is increased in coronary artery disease cases in males but not in females, in African Brazilians the mutation is not associated with coronary artery disease in either sex
additional information
-
MTHFR gene polymorphism A1298C is associated with an increased risk for acute lymphoblastic leukemia in Filipino children
additional information
-
MTHFR gene polymorphism C667T interacts with elevated total homocysteine levels leading to an increased risk of ischemic stroke
additional information
-
MTHFR gene polymorphism C677T affects follicular estradiol synthesis
additional information
-
MTHFR gene polymorphism C677T has significantly greater carotid intima-media thickness, higher homocysteine levels, and lower folic acid levels
additional information
-
MTHFR gene polymorphism C677T is a genetic marker for identifying women at increased risk of small for gestational age infants
additional information
-
MTHFR gene polymorphism C677T is a strong modifier of folate status
additional information
-
MTHFR gene polymorphism C677T is associated with idiopathic membranous glomerulonephritis
additional information
-
MTHFR gene polymorphism C677T is neither a determinant of baseline coronary flow indices nor does it modulate the effect of pravastatin on coronary reactivity
additional information
-
MTHFR gene polymorphism C677T modulates an individual's susceptibility to gastric cancer while no association is obeserved for the effect of the MTHFR gene polymorphism A1298C
additional information
-
MTHFR gene polymorphism C677T, but not A1298C has significant association with atlantoaxial dislocation
additional information
-
MTHFR gene polymorphisms A1298C and C677T lead to increased homocysteine plasma levels
additional information
-
MTHFR gene polymorphisms C677T and A1298C do not play a role for the pathogenesis of primary open-angle glaucoma
additional information
-
MTHFR gene polymorphisms C677T and A1298C in combination with angiotensin-converting enzyme insertion/deletion are risk factors for chronic allograft dysfunction
additional information
-
MTHFR genotypes are not associated with cognitive function, cognitive decline, or survival among nonagenarians
additional information
-
MTHFR polymorphisms C677T and A1298T are associated with colorectal cancer
additional information
-
neither the homozygote mutant form nor the heterozygote form of the gene polymorphisms C677T and A1298C is associated with placental abruption
additional information
-
no association between MTHFR C677T gene polymorphism and breast cancer in the Turkish popullation
additional information
-
no association between the maternal 1298C allele, the 677CT/1298AC genotype or any of the corresponding genotypes, and anencephaly
additional information
-
no association is observed between the C677T MTHFR gene polymorphism and the clinical outcome of patients treated with hematopoietic cell transplant
additional information
-
no association with the 5,10-methylenetetrahydrofolate reductase gene polymorphism C677T and major depressive disorder, gene polymorphism C677T results in the production of a mildly dysfunctional thermolabile enzyme and is associated with a significant elevation in the circulating concentrations of homocysteine and a decrease in serum folate concentrations
additional information
-
no associations between the putative functional MTHFR gene polymorphisms, C677T and A1298C, and schizophrenia or bipolar disorder
additional information
-
no correlatio between MTHFR gene polymorphisms C677T and A1298C and serum methotrextae levels in patients with rheumatoid arthritis
additional information
-
no evidence for transmission of the MTHFR 677T allele of gene polymorphism C677T associated with schizophrenia risk
additional information
-
no significant correlation is demonstrated for C677T MTHFR gene polymorphism and homocysteine levels in Brazilian patients with coronary arterial disease, ischemic stroke, and peripheral arterial obstructive disease
additional information
-
no statistically significant differences are seen between the allelic and genotypic distribution of the MTHFR polymorphism C677T in patients chronic allograft nephropathy and with normal renal function
additional information
-
positive association between the MTHFR variant homozygous allele 677TT and breast cancer risk
additional information
-
serum folate concentration is lower in individuals with the MTHFR 677TT genotype than in those with the MTHFR 677CC or 677CT genotypes
additional information
-
the A1298C polymorphism in MTHFR gene has effects on enzyme activity but it can not be considered a major risk factor for coronary artery disease in a selected Iranian population
additional information
-
the association of homocysteine with cardiovascular disease is not modified by MTHFR C677T gene polymorphism
additional information
-
the C1129T gene polymorphism leads to severe MTHFR deficiency which is associated with brain disease
additional information
-
the C667T and A1298C MTHFR gene polymorphisms are not contributing to the aetiology of idiopathic mental retardation in an Indian population
additional information
-
the C677T gene polymorphism causes a valine-to-alanine substitution which produces a thermolabile variant of the enzyme and is associated with higher levels of plasma total homocysteine and congitive test performance in older women
additional information
-
the C677T gene polymorphism decreases enzyme activity and does not significantly contribute to the inherited genetic susceptibility to breast and prostate cancer, while there is some evidence for possible genetic contribution of this polymorphism to the development of head and neck carcinoma
additional information
-
the C677T gene polymorphism does not influence the first and second trimester uterine artery Doppler flow
additional information
-
the C677T gene polymorphism in combination with catechol-O-methyltransferase G324A (Val108/158Met) polymorphism might increase schizophrenia susceptibility
additional information
-
the C677T gene polymorphism is a modulator of a B vitamin network with major effects on homocysteine metabolism und related to the plasma total homocysteine level
additional information
-
the C677T gene polymorphism is associated with hypertension in Caucasian and Asian populations
additional information
-
the C677T gene polymorphism is associated with increased homocysteine and decreased folate concentrations
additional information
-
the C677T gene polymorphism is associated with increased risk of gastric cancer susceptibility in Chinese populations, there is no association between gastric cancer risk and A1298C polymorphism
additional information
-
the C677T gene polymorphism is not associated with obesity
additional information
-
the C677T gene polymorphism is not associated with the risk to develop dyskinesia, motor fluctuation, and psychosis induced by levodopa in Parkinson's disease patients
additional information
-
the C677T MTHFR gene polymorphism contributes to certain executive function deficits in schizophrenia
additional information
-
the C677T MTHFR gene polymorphism is no important risk factor for thromboembolic stroke associated with atrial fibrillation
additional information
-
the C677T MTHFR gene polymorphism is not associated with chronic plaque psoriasis among Caucasians
additional information
-
the C677T MTHFR gene polymorphism results in lower activity of the enzyme and in a subsequent increase in homocysteine levels, is not an independnet predictor on medium-term prognosis after acute coronary syndromes
additional information
-
the C677T polymorphism modifies the age at onset of colorectal cancer in Caucasian Lynch syndrome subjects with the 677T allele having a protective effect, while there is no association between the MTHFR A1298C polymorphism and age at onset of colorectal cancer
additional information
-
the C677T/A1298C compound heterozygous MTHFR genotype is associated with branch retinal artery occlusion
additional information
-
the common MTHFR C677T gene polymorphism causing an Ala to Val protein change is associated with reduced enzyme activity thereby increasing plasma homocysteine level, C667Tis no contributing factor to thrombosis during cancer treatment
additional information
-
the coronary artery disease risk increase is mainly associated with mild hyperhomocysteinaemia in homozygous gene polymorphism C677T, whereas in heterozygous C677T it is mainly associated with the conventional risk factors
additional information
the disorders of folate metabolism caused by MTHFR gene polymorphisms C677T and A1298C may lead to several disease states including coronary heart disease, venous thrombosis, and several types of cancer
additional information
-
the effect of MTHFR polymorphisms C677T and A1298C on the risk of lung cancer is undetectable
additional information
-
the G1793A gene polymorphism has a lowering effect on total plasma homocysteine
additional information
the genetic risk for gall bladder cancer is not modulated by MTHFR C677T gene polymorphism
additional information
-
the homozygous C677T MTHFR gene polymorphism is associated with coronary artery obstruction
additional information
-
the homozygous mutation (677TT) of the gene polymorphism C677T reduces enzyme activity, alters cellular folate composition, and decreases S-adenosyl methionine synthesis via folate-dependent re-methylation
additional information
-
the MTHFR 677 T allele seems to protect against chronic hepatitis B virus infection in young African adults
additional information
-
the MTHFR C677T and A1298C gene polymorphisms are no signifikant risk factors in adult acute lympohoblastic leukemia in the Korean population
additional information
-
the MTHFR C677T gene polymorphism in combination with the thymidylate synthase enhancer region 2R(+) genotype is a risk factor of cholangiocarcinoma in a Korean population
additional information
-
the MTHFR C677T gene polymorphism may play a role in influencing liver fibrosis progression in patients with recurrent hepatitis C
additional information
-
the MTHFR C677T genotype is the dominant determinant of nonmethylfolate accumulation in red blood cells
additional information
-
the MTHFR C677T polymorphism is associated with primary closed-angle glaucoma but not primary open-angle glaucoma in patients of Pakistani origin
additional information
-
the MTHFR C677T variant CT and CT + TT genotypes decrease cervix cancer risk in North Indian women
additional information
-
the MTHFR gene polymorphism C677T has no contribution in hyperhomocysteinemia in epileptic patients receiving carbamazepine or valproic acid
additional information
-
the MTHFR gene polymorphism C677T is associated with diffuse multicystic encephalomalacia
additional information
-
the MTHFR gene polymorphism C677T is associated with impaired catalytic properties of the enzyme, betaine is a strong determinant of plasma tHcy in subjects with low serum folate and homozygous C677T genotype
additional information
-
the MTHFR gene polymorphism C677T is associated with lumbar spine and hip bone mineral density in children
additional information
-
the MTHFR gene polymorphism C677T is no risk factor for the progression of fatty liver disease to nonalcoholic steatohepatitis
additional information
-
the MTHFR gene polymorphism C677T is not associated with congenital heart disease and may be linked to the development of aortic arch anomalies
additional information
-
the MTHFR gene polymorphism C677T is not associated with the development of diabetic nephropathy in Turkish type 2 diabetic patients
additional information
-
the MTHFR gene polymorphisms C677T and A1298C are associated with altered enzyme activity
additional information
-
the presence of the T allele in the C677T MTHFR gene polymorphism is associated with higher homocysteine levels, which is more prominent in men than in women
additional information
-
the simultaneous presence of C677T and A1298A genotypes provides a significant risk of developing coronary artery disease, while the A1298C genotype combined with C677C shows a significant trend towards a decrease in coroary artery disease occurrence
additional information
-
the T allele of the MTHFR C677T genotype is significantly associated with atherothrombotic infarction
additional information
-
there is a correlation between MTHFR C677T gene mutations and recurrent fetal loss
additional information
-
there is a trend for a higher MTHFR 677T allele frequency in breast cancer cases than in controls
additional information
-
there is some evidence of association between MTHFR C677T gene polymorphism and diabetic nephropathy
additional information
-
analysis of two mutations in MTHFR gene in compound heterozygous patients with extremely low or undetectable enzyme activity. Mutation c.523G>A leads to an Ala>Thr transition in the catalytic domain of the enzyme, mutation c.1166G>A induces alternative splicing of exon 7 at the junction of the catalytic and regulatory domains. Both parents carry only one of these mutations and present with moderate and intermediate hyperhomocysteinemia, respectively, without neurological symptoms
additional information
-
a C677T polymorphism is associated with an increased risk for the development of cardiovascular disease, Alzheimers disease, and depression in adults and of neural tube defects in the fetus
additional information
construction of a full-length (amino acids 1-656, hsMTHFRFL) enzyme variant, a second variant encompassing just the catalytic domain and the regulatory domain (amino acids 38-644, hsMTHFRCD-RD), and a thrid variant encompassing the regulatory domain and part of the linker region (amino acids 348-656, hsMTHFRRD)
additional information
to examine the importance of the N-terminal serine-rich region to global protein phosphorylation, a recombinant HsMTHFR38-644 is produced, which removes the N-terminal 37 amino acids, including the entire serine-rich region as well as the poorly conserved C-terminal 12 amino acids predicted to be of high disorder. Purified HsMTHFR38-644 is not phosphorylated, determined by phosphorylation mapping, or native mass spectrometry, and treatment with CIP does not alter the protein molecular mass. Construction of truncated enzyme mutants, sMTHFR1-656 and HsMTHFR38-644. Dimeric mutant HsMTHFR38-644 is not phosphorylated
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
activity of enzyme from healthy and homocysteinemic humans after heat inactivation, the latter with a more thermolabile enzyme: residual activity in homozygotes is lower than 30% compared with 50% in control subjects
additional information
-
thermolability is enhanced when the FAD cofactor dissociates form enzyme
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
methyltetrahydrofolate and S-adenosylmethionine protects enzyme from the loss of FAD after dilution
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
62fold purification of recombinant enzyme, expressed in Sf9 cells from Spodoptera frugiperda
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of recombinant human MTHFR at high levels in Sf9 cells from Spodoptera frugiperda by using a baculovirus expression system
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
natural polymorphism I225V results in an unusual melting curve peak at 53.4°C instead of 51.6°C or 60.4°C in melting curve analysis after real-time polymerase chain reaction. Potential ability of melting analysis to identify new sequence variants
medicine
nutrition
-
homozygosity for the C677T natural polymorphism presents a 3fold increased risk of colorectal cancer. Low intake of methyl-donor nutrients is associated with an increased risk of colorectal cancer in homozygous participants for the C677T polymorphism
medicine
-
mutation in gene for methylenetetrahydrofolate reductase is a cause of moderate homocysteinaemia, which is a risk factor for arteriosclerosis and thrombosis, patients with MTHFR deficiency have low methionine concentrations in plasma
medicine
-
deficiency and thermolability of enzyme as cause of mild homocysteinemia with premature vascular disease
medicine
-
methylenetetrahydrofolate reductase deficiency as cause of homocysteinuria
medicine
-
C677T mution of MTHRF gene is the most frequent genetic cause of mild hyperhomocysteinemia, a risk factor for cardiovascular disease
medicine
-
association of A222V genotype with the Gc2 polymorphism of the vitamin D-binding protein. A222V mutant individuals additionally show a quantitative reduction of apolipoprotein A-I
medicine
-
MTHFR is important for postnatal growth and vitality and 5-methyltetrahydrofolate deficiency contributes to the high postnatal mortality, Mefolinate may be a good candidate drug for treatment of severe MTHFR deficiency
medicine
-
the consequences of a deficient MTHFR genotype are probably dependent on the folate intake status, there is no clear conclusion regarding the influence of MTHFR polymorphisms on 5-fluorouracil-based treatment in colorectal cancer
medicine
-
homozygosity for the C677T natural polymorphism presents a 3fold increased risk of colorectal cancer. Low intake of methyl-donor nutrients is associated with an increased risk of colorectal cancer in homozygous participants for the C677T polymorphism
medicine
-
in Parkinson patients, plasma homocysteine elevation may be caused by levodopa administration, and further promoted by MTHFR C677T heterozygotes and homozygote C677T/C677T, but not by A1298C genotypes. The promoting elevation in 1298A homozygotes is attributed to combining the 677T allele. Neither C677T nor A1298C genotypes contribute to elevating plasma homocysteine in Parkinson patients without levodopa treatment
medicine
-
meta-analysis of Mthfr polymorphisms affecting methotrexate toxicity. Polymorphism C677T is associated with increased toxicity of methotrexate,while polymorphism A1298C is not
medicine
-
MTHFR mutant C677T homozygotes who are also carriers of cystathione beta-synthase 844ins68 polymorphism have homocysteine and folate concentrations similar to those of individuals with the MTHFR heterozygous C677C/C677T and wild-type genotypes. Homocysteine levels in MTHFR double mutant subjects carrying the cystathione beta-synthase 844ins68 allele are 24.1% lower than in non-carriers, and serum folate levels are 27.7% higher. These suggests that the cystathione beta-synthase 844ins68 allele normalizes homocysteine and folate levels in MTHFR C677T/C677T individuals
medicine
-
mutations in the MTHFR gene decrease the onset risk of acute lymphoblastic leukemia with relapse in the setting of no folate supplementation in pregnancy, but not of relapse-free acute lymphoblastic leukemia
medicine
-
No significant difference is found in either Mthfr allele frequencies or genotype distribution between patients with bipolar disorder and controls in an association study in the Chinese population. The meta-analysis result shows no significant association between Mthfr C677T and bipolar disorder
medicine
-
no significant differences in plasma homocysteine levels and MTHFR genotypes are found in patients with systemic sclerosis compared to controls or in systemic sclerosis patients with limited cutaneous compared to diffuse disease. Seventy-one percent of patients with macrovascular disorders have MTHFR polymorphism C677T. In addition, 45% of patients with hyperhomocysteinemia have pulmonary hypertension. The presence of MTHFR C677T mutation influences the incidence of macrovascular abnormalities in SSc patients
medicine
-
plasma homocysteine levels are significantly elevated in patients lacking Mthfr activity or cystathione beta-synthase activity
medicine
-
study on association of factor V-Leiden and methylenetetrahydrofolate reductase C677T and A1298C mutations with stroke. MTHFR C677T/C677T and A1298C/A1298C, but not factor V-Leiden, genotypes are associated with stroke. The C677T but not A1298C MTHFR mutation is associated with elevated homocysteine levels in patients and control subjects. In addition to hypertension, the significant predictors for stroke are MTHFR C677T and C677T/C677T and A1298C/A1298C genotypes, together with hyperhomocysteinemia, indicating a synergistic effect of MTHFR mutations with elevated homocysteine and other risk factors in pathogenesis of stroke
medicine
-
MTHFR variant allele C677T has a protective effect on colorectal cancer development, whereas the variant allele of the A1298C does not produce any effect on disease risk. Both MTHFR polymorphisms are relevant and independent factors of patient outcome after 5-fluorouracil-based treatment of colorectal cancer
medicine
obese women without comorbidities and carrying the T variant of the 677C>T (p.A222V) polymorphism of gene MTHFR exhibit benefits with simvastatin treatment, mainly in terms of increased NO levels
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Zhou, J.; Kang, S.S.; Wong, P.W.K.; Fournier, B.; Rozen, R.
Purification and characterization of methylenetetrahydrofolate reductase from human cadaver liver [published erratum appears in Biochem Med Metab Biol 1990 Oct;44(2):200]
Biochem. Med. Metab. Biol.
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1990
Homo sapiens
Matthews, R.G.; Sheppard, C.; Goulding, C.
Methylenetetrahydrofolate reductase and methionine synthase: biochemistry and molecular biology
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Escherichia coli, Homo sapiens, Sus scrofa
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Ravera, M.; Viazzi, F.; Berruti, V.; Leoncini, G.; Zagami, P.; Bezante, G.P.; Rosatto, N.; Ravazzolo, R.; Pontremoli, R.; Deferrari, G.
5,10-Methylenetetrahydrofolate reductase polymorphism and early organ damage in primary hypertension
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2001
Homo sapiens
Shan, X.; Wang, L.; Hoffmaster, R.; Kruger, W.D.
Functional characterization of human methylenetetrahydrofolate reductase in Saccharomyces cerevisiae
J. Biol. Chem.
274
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1999
Homo sapiens
Suormala, T.; Gamse, G.; Fowler, B.
5,10-Methylenetetrahydrofolate reductase (MTHFR) assay in the forward direction: residual activity in MTHFR deficiency
Clin. Chem.
48
835-843
2002
Homo sapiens
Weisberg, I.; Tran, P.; Christensen, B.; Sibani, S.; Rozen, R.
A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity
Mol. Genet. Metab.
64
169-172
1998
Homo sapiens (P42898)
Blom, H.J.
Mutated 5,10-methylenetetrahydrofolate reductase and moderate hyperhomocysteinaemia
Eur. J. Pediatr.
157
131-134
1998
Homo sapiens
-
McNulty, H.; McKinley, M.C.; Wilson, B.; McPartlin, J.; Strain, J.J.; Weir, D.G.; Scott, J.M.
Impaired functioning of thermolabile methylenetetrahydrofolate reductase is dependent on riboflavin status: Implications for riboflavin requirements
Am. J. Clin. Nutr.
76
436-441
2002
Homo sapiens
Engbersen, A.M.T.; Franken, D.G.; Boers, G.H.J.; Stevens, E.M.B.; Trijbels, F.J.M.; Blom, H.J.
Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia
Am. J. Hum. Genet.
56
142-150
1995
Homo sapiens
Rosenblatt, D.S.; Lue-Shing, H.; Matiaszuk, N.; Low-Nang, L.; Arzoumanian, A.; Cooper, B.A.
Thermolability of residual methylene-tetrahydrofolate reductase (MR) activity, methionine synthase activity and methyl-cobalamin levels in cultured fibroblasts from patients with MR deficiency
Adv. Exp. Med. Biol.
338
703-706
1993
Homo sapiens
Kluijtmans, L.A.J.; den Heijer, M.; Reitsma, P.H.; Heil, S.G.; Blom, H.J.; Rosendaal, F.R.
Thermolabile methylenetetrahydrofolate reductase and factor V Leiden in the risk of deep-vein thrombosis
Thromb. Haemost.
79
254-258
1998
Homo sapiens
Yamada, K.; Chen, Z.; Rozen, R.; Matthews, R.G.
Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase
Proc. Natl. Acad. Sci. USA
98
14853-14858
2001
Escherichia coli, Homo sapiens
Rozen, R.
Methylenetetrahydrofolate reductase: a link between folate and riboflavin?
Am. J. Clin. Nutr.
76
301-302
2002
Homo sapiens
Yamada, K.; Strahler, J.R.; Andrews, P.C.; Matthews, R.G.
Regulation of human methylenetetrahydrofolate reductase by phosphorylation
Proc. Natl. Acad. Sci. USA
102
10454-10459
2005
Homo sapiens
Greco, M.; Chiriaco, F.; Del Boccio, P.; Tagliaferro, L.; Acierno, R.; Menegazzi, P.; Pinca, E.; Pignatelli, F.; Storelli, C.; Federici, G.; Urbani, A.; Maffia, M.
A proteomic approach for the characterization of C677T mutation of the human gene methylenetetrahydrofolate reductase
Proteomics
6
5350-5361
2006
Homo sapiens
Lin, J.J.; Yueh, K.C.; Liu, C.S.; Liu, J.T.; Lin, S.Z.
5,10-methylenetetrahydrofolate reductase C677T gene polymorphism can influence age at onset of Parkinsons disease
Acta Neurol. Taiwan
16
150-157
2007
Homo sapiens
Elkins, J.S.; Johnston, S.C.; Ziv, E.; Kado, D.; Cauley, J.A.; Yaffe, K.
Methylenetetrahydrofolate reductase C677T polymorphism and cognitive function in older women
Am. J. Epidemiol.
166
672-678
2007
Homo sapiens
Boccia, S.; Hung, R.; Ricciardi, G.; Gianfagna, F.; Ebert, M.P.; Fang, J.Y.; Gao, C.M.; Goetze, T.; Graziano, F.; Lacasana-Navarro, M.; Lin, D.; Lopez-Carrillo, L.; Qiao, Y.L.; Shen, H.; Stolzenberg-Solomon, R.; Takezaki, T.; Weng, Y.R.; Zhang, F.F.; van Duijn, C.M.; Boffetta, P.; Taioli, E.
Meta- and pooled analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer risk: a huge-GSEC review
Am. J. Epidemiol.
167
505-516
2008
Homo sapiens
Hustad, S.; Midttun, O.; Schneede, J.; Vollset, S.E.; Grotmol, T.; Ueland, P.M.
The methylenetetrahydrofolate reductase 677C>T polymorphism as a modulator of a B vitamin network with major effects on homocysteine metabolism
Am. J. Hum. Genet.
80
846-855
2007
Homo sapiens
Martinez-Frias, M.L.
The biochemical structure and function of methylenetetrahydrofolate reductase provide the rationale to interpret the epidemiological results on the risk for infants with Down syndrome
Am. J. Med. Genet. A
146A
1477-1482
2008
Homo sapiens
Muntjewerff, J.W.; Hoogendoorn, M.L.; Aukes, M.F.; Kahn, R.S.; Sinke, R.J.; Blom, H.J.; den Heijer, M.
No evidence for a preferential transmission of the methylenetetrahydrofolate reductase 677T allele in families with schizophrenia offspring
Am. J. Med. Genet. B Neuropsychiatr. Genet.
144B
891-894
2007
Homo sapiens
Gaysina, D.; Cohen, S.; Craddock, N.; Farmer, A.; Hoda, F.; Korszun, A.; Owen, M.J.; Craig, I.W.; McGuffin, P.
No association with the 5,10-methylenetetrahydrofolate reductase gene and major depressive disorder: Results of the depression case control (DeCC) study and a meta-analysis
Am. J. Med. Genet. B Neuropsychiatr. Genet.
147B
699-706
2007
Homo sapiens
Joensson, E.G.; Larsson, K.; Vares, M.; Hansen, T.; Wang, A.G.; Djurovic, S.; Ronningen, K.S.; Andreassen, O.A.; Agartz, I.; Werge, T.; Terenius, L.; Hall, H.
Two methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, schizophrenia and bipolar disorder: An association study
Am. J. Med. Genet. B Neuropsychiatr. Genet.
147B
976-982
2007
Homo sapiens
Ananth, C.V.; Peltier, M.R.; De Marco, C.; Elsasser, D.A.; Getahun, D.; Rozen, R.; Smulian, J.C.; Smulian, J.C.
Associations between 2 polymorphisms in the methylenetetrahydrofolate reductase gene and placental abruption
Am. J. Obstet. Gynecol.
197
385e1-385e7
2007
Homo sapiens
Nagele, P.; Zeugswetter, B.; Wiener, C.; Burger, H.; Huepfl, M.; Mittlboeck, M.; Foedinger, M.
Influence of methylenetetrahydrofolate reductase gene polymorphisms on homocysteine concentrations after nitrous oxide anesthesia
Anesthesiology
109
36-43
2008
Homo sapiens
Siraj, A.K.; Ibrahim, M.; Al-Rasheed, M.; Bu, R.; Bavi, P.; Jehan, Z.; Abubaker, J.; Murad, W.; Al-Dayel, F.; Ezzat, A.; El-Solh, H.; Uddin, S.; Al-Kuraya, K.
Genetic polymorphisms of methylenetetrahydrofolate reductase and promoter methylation of MGMT and FHIT genes in diffuse large B cell lymphoma risk in Middle East
Ann. Hematol.
86
887-895
2007
Homo sapiens
Eroglu, A.; Egin, Y.; Cam, R.; Akar, N.
The 19-bp deletion of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR) C677T, Factor V Leiden, prothrombin G20210A polymorphisms in cancer patients with and without thrombosis
Ann. Hematol.
88
73-76
2008
Homo sapiens
Pare, L.; Altes, A.; Ramon y Cajal, T.; Del Rio, E.; Alonso, C.; Sedano, L.; Barnadas, A.; Baiget, M.
Influence of thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphisms on the disease-free survival of breast cancer patients receiving adjuvant 5-fluorouracil/methotrexate-based therapy
Anticancer Drugs
18
821-825
2007
Homo sapiens
Ko, K.H.; Kim, N.K.; Yim, D.J.; Hong, S.P.; Park, P.W.; Rim, K.S.; Kim, S.; Hwang, S.G.
Polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR C677T) and thymidylate synthase enhancer region (TSER) as a risk factor of cholangiocarcinoma in a Korean population
Anticancer Res.
26
4229-4233
2007
Homo sapiens
Oh, D.; Kim, N.K.; Jang, M.J.; Kim, H.C.; Lee, J.H.; Lee, J.A.; Ahn, M.J.; Kim, C.S.; Kim, H.S.; Park, S.; Chio, H.S.; Min, Y.H.; Min, Y.H.
Association of the 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) polymorphisms in Korean patients with adult acute lymphoblastic leukemia
Anticancer Res.
27
3419-3424
2007
Homo sapiens
Shekari, M.; Sobti, R.C.; Kordi Tamandani, D.M.; Suri, V.
Impact of methylenetetrahydrofolate reductase (MTHFR) codon (677) and methionine synthase (MS) codon (2756) on risk of cervical carcinogenesis in North Indian population
Arch. Gynecol. Obstet.
278
517-524
2008
Homo sapiens
Rallidis, L.S.; Gialeraki, A.; Komporozos, C.; Vavoulis, P.; Pavlakis, G.; Travlou, A.; Lekakis, I.; Kremastinos, D.T.
Role of methylenetetrahydrofolate reductase 677C->T polymorphism in the development of premature myocardial infarction
Atherosclerosis
200
115-120
2008
Homo sapiens
Boccia, S.; Gianfagna, F.; Persiani, R.; La Greca, A.; Arzani, D.; Rausei, S.; Dugo, D.; Magistrelli, P.; Villari, P.; Van Duijn, C.M.; Ricciardi, G.
Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and susceptibility to gastric adenocarcinoma in an Italian population
Biomarkers
12
635-644
2007
Homo sapiens
Ruiz, J.R.; Hurtig-Wennloef, A.; Ortega, F.B.; Patterson, E.; Nilsson, T.K.; Castillo, M.J.; Sjoestroem, M.
Homocysteine levels in children and adolescents are associated with the methylenetetrahydrofolate reductase 677C>T genotype, but not with physical activity, fitness or fatness: the European Youth Heart Study
Br. J. Nutr.
97
255-262
2007
Homo sapiens
Sharp, L.; Little, J.; Brockton, N.T.; Cotton, S.C.; Masson, L.F.; Haites, N.E.; Cassidy, J.
Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer: a case-control study in a population with relatively low folate intake
Br. J. Nutr.
99
379-389
2008
Homo sapiens
Jakubowska, A.; Gronwald, J.; Menkiszak, J.; Gorski, B.; Huzarski, T.; Byrski, T.; Edler, L.; Lubinski, J.; Scott, R.J.; Hamann, U.
Methylenetetrahydrofolate reductase polymorphisms modify BRCA1-associated breast and ovarian cancer risks
Breast Cancer Res. Treat.
104
299-308
2007
Homo sapiens
Macis, D.; Maisonneuve, P.; Johansson, H.; Bonanni, B.; Botteri, E.; Iodice, S.; Santillo, B.; Penco, S.; Gucciardo, G.; DAiuto, G.; Rosselli Del Turco, M.; Amadori, M.; Costa, A.; Decensi, A.
Methylenetetrahydrofolate reductase (MTHFR) and breast cancer risk: a nested-case-control study and a pooled meta-analysis
Breast Cancer Res. Treat.
106
263-271
2007
Homo sapiens
Langsenlehner, T.; Renner, W.; Yazdani-Biuki, B.; Langsenlehner, U.
Methylenetetrahydrofolate reductase (MTHFR) and breast cancer risk: a nested-case-control study and a pooled meta-analysis
Breast Cancer Res. Treat.
107
459-460
2008
Homo sapiens
Pande, M.; Chen, J.; Amos, C.I.; Lynch, P.M.; Broaddus, R.; Frazier, M.L.
Influence of methylenetetrahydrofolate reductase gene polymorphisms C677T and A1298C on age-associated risk for colorectal cancer in a caucasian lynch syndrome population
Cancer Epidemiol. Biomarkers Prev.
16
1753-1759
2007
Homo sapiens
Hekim, N.; Ergen, A.; Yaylim, I.; Yilmaz, H.; Zeybek, U.; Ozturk, O.; Isbir, T.
No association between methylenetetrahydrofolate reductase C677T polymorphism and breast cancer
Cell Biochem. Funct.
25
115-117
2007
Homo sapiens
Sazci, A.; Ergul, E.; Aygun, C.; Akpinar, G.; Senturk, O.; Hulagu, S.
Methylenetetrahydrofolate reductase gene polymorphisms in patients with nonalcoholic steatohepatitis (NASH)
Cell Biochem. Funct.
26
291-296
2008
Homo sapiens
Sun, D.F.; Weng, Y.R.; Chen, Y.X.; Lu, R.; Wang, X.; Fang, J.Y.
Knock-down of methylenetetrahydrofolate reductase reduces gastric cancer cell survival: An in vitro study
Cell Biol. Int.
32
879-887
2008
Homo sapiens
Doelek, B.; Eraslan, S.; Ero?lu, S.; Kesim, B.E.; Ulutin, T.; Yalciner, A.; Laleli, Y.R.; Goezuekirmizi, N.
Molecular analysis of factor V Leiden, factor V Hong Kong, factor II G20210A, methylenetetrahydrofolate reductase C677T, and A1298C mutations related to Turkish thrombosis patients
Clin. Appl. Thromb. Hemost.
13
435-438
2007
Homo sapiens
Reljic, A.; Simundic, A.M.; Topic, E.; Nikolac, N.; Justinic, D.; Stefanovic, M.
The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cancer risk: the Croatian case-control study
Clin. Biochem.
40
981-985
2007
Homo sapiens
Sharma, R.; Hoskins, J.M.; Rivory, L.P.; Zucknick, M.; London, R.; Liddle, C.; Clarke, S.J.
Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphisms and toxicity to capecitabine in advanced colorectal cancer patients
Clin. Cancer Res.
14
817-825
2008
Homo sapiens
Zee, R.Y.; Mora, S.; Cheng, S.; Erlich, H.A.; Lindpaintner, K.; Rifai, N.; Buring, J.E.; Ridker, P.M.
Homocysteine, 5,10-methylenetetrahydrofolate reductase 677C>T polymorphism, nutrient intake, and incident cardiovascular disease in 24,968 initially healthy women
Clin. Chem.
53
845-851
2007
Homo sapiens
Naghibalhossaini, F.; Mokarram, P.; Khalili, I.
Easy detection of 5,10-methylenetetrahydrofolate reductase 1298A/C genotype by mutagenically separated PCR assay
Clin. Chem. Lab. Med.
46
987-989
2008
Homo sapiens
Angius, A.; Simpore, J.; Persico, I.; Sassu, A.; Prodi, D.A.; Musumeci, S.
Methylenetetrahydrofolate reductase gene polymorphisms in Burkina Faso: impact on plasma fasting homocysteine and after methionine loading test
Clin. Lab.
53
29-33
2007
Homo sapiens
Spiroski, I.; Kedev, S.; Antov, S.; Arsov, T.; Krstevska, M.; Dzhekova-Stojkova, S.; Kostovska, S.; Trajkov, D.; Petlichkovski, A.; Strezova, A.; Efinska-Mladenovska, O.; Spiroski, M.
Association of methylenetetrahydrofolate reductase (MTHFR-677 and MTHFR-1298) genetic polymorphisms with occlusive artery disease and deep venous thrombosis in Macedonians
Croat. Med. J.
49
39-49
2008
Homo sapiens
Eroglu, Z.; Erdogan, M.; Tetik, A.; Karadeniz, M.; Cetinalp, S.; Kosova, B.; Gunduz, C.; Ozgen, A.G.; Yilmaz, C.
The relationship of the methylenetetrahydrofolate reductase C677T gene polymorphism in Turkish type 2 diabetic patients with and without nephropathy
Diabetes Metab. Res. Rev.
23
621-624
2007
Homo sapiens
Serin, E.; Gueclue, M.; Atac, F.B.; Verdi, H.; Kayaselcuk, F.; Ozer, B.; Bilezikci, B.; Yilmaz, U.
Methylenetetrahydrofolate reductase C677T mutation and nonalcoholic fatty liver disease
Digest. Dis. Sci.
52
1183-1186
2007
Homo sapiens
Srivastava, A.; Pandey, S.N.; Pandey, P.; Choudhuri, G.; Mittal, B.
No association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in susceptibility to gallbladder cancer
DNA Cell Biol.
27
127-132
2008
Homo sapiens (P42898)
Heur, M.; Kosmorsky, G.S.; Peachey, N.S.; Bala, E.
Branch retinal artery occlusion associated with compound heterozygous genotype for methylenetetrahydrofolate reductase
Doc. Ophthalmol.
114
163-168
2007
Homo sapiens
Sun, L.; Sun, Y.H.; Wang, B.; Cao, H.Y.; Yu, C.
Methylenetetrahydrofolate reductase polymorphisms and susceptibility to gastric cancer in Chinese populations: a meta-analysis
Eur. J. Cancer Prev.
17
446-452
2008
Homo sapiens
Lewis, S.J.; Lawlor, D.A.; Nordestgaard, B.G.; Tybjaerg-Hansen, A.; Ebrahim, S.; Zacho, J.; Ness, A.; Leary, S.; Smith, G.D.
The methylenetetrahydrofolate reductase C677T genotype and the risk of obesity in three large population-based cohorts
Eur. J. Endocrinol.
159
35-40
2008
Homo sapiens
Qian, X.; Lu, Z.; Tan, M.; Liu, H.; Lu, D.
A meta-analysis of association between C677T polymorphism in the methylenetetrahydrofolate reductase gene and hypertension
Eur. J. Hum. Genet.
15
1239-1245
2007
Homo sapiens
Summers, C.M.; Hammons, A.L.; Mitchell, L.E.; Woodside, J.V.; Yarnell, J.W.; Young, I.S.; Evans, A.; Whitehead, A.S.
Influence of the cystathionine beta-synthase 844ins68 and methylenetetrahydrofolate reductase 677C>T polymorphisms on folate and homocysteine concentrations
Eur. J. Hum. Genet.
16
1010-1013
2008
Homo sapiens
Stonek, F.; Hafner, E.; Metzenbauer, M.; Stuempflen, I.; Philipp, K.
Carriage of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism does not influence the first and second trimester uterine artery Doppler flow
Eur. J. Obstet. Gynecol. Reprod. Biol.
140
178-182
2008
Homo sapiens
Muntjewerff, J.W.; Gellekink, H.; den Heijer, M.; Hoogendoorn, M.L.; Kahn, R.S.; Sinke, R.J.; Blom, H.J.
Polymorphisms in catechol-O-methyltransferase and methylenetetrahydrofolate reductase in relation to the risk of schizophrenia
Eur. Neuropsychopharmacol.
18
99-106
2008
Homo sapiens
Azarpira, N.; Ramzi, M.; Aghdaie, M.H.; Daraie, M.; Geramizadeh, B.
Methylenetetrahydrofolate reductase C677T genotypes and clinical outcome following hematopoietic cell transplant
Exp. Clin. Transplant.
5
693-697
2007
Homo sapiens
Azarpira, N.; Raisjalali, G.; Darai, M.
Polymorphism of the methylenetetrahydrofolate reductase C677T gene with chronic allograft nephropathy in renal transplant recipients
Exp. Clin. Transplant.
6
54-58
2008
Homo sapiens
Weger, W.; Hofer, A.; Stanger, O.; Wolf, P.; El-Shabrawi, Y.; Renner, W.; Kerl, H.; Salmhofer, W.
The methylenetetrahydrofolate reductase 677C>T gene polymorphism is not associated with chronic plaque psoriasis
Exp. Dermatol.
17
748-751
2008
Homo sapiens
Chwatko, G.; Boers, G.H.; Strauss, K.A.; Shih, D.M.; Jakubowski, H.
Mutations in methylenetetrahydrofolate reductase or cystathionine beta-synthase gene, or a high-methionine diet, increase homocysteine thiolactone levels in humans and mice
FASEB J.
21
1707-1713
2007
Homo sapiens, Mus musculus
Hecht, S.; Pavlik, R.; Lohse, P.; Noss, U.; Friese, K.; Thaler, C.J.
Common 677C-->T mutation of the 5,10-methylenetetrahydrofolate reductase gene affects follicular estradiol synthesis
Fertil. Steril.
91
56-61
2008
Homo sapiens
Ozger, H.; Kilicoglu, O.; Yilmaz, H.; Ergen, H.A.; Yaylim, I.; Zeybek, U.; Isbir, T.
Methylenetetrahydrofolate reductase C677T gene polymorphism in osteosarcoma and chondrosarcoma patients
Folia Biol. (Praha)
54
53-57
2008
Homo sapiens
Gemmati, D.; Ongaro, A.; Tognazzo, S.; Catozzi, L.; Federici, F.; Mauro, E.; Della Porta, M.; Campioni, D.; Bardi, A.; Gilli, G.; Pellati, A.; Caruso, A.; Scapoli, G.L.; De Mattei, M.
Methylenetetrahydrofolate reductase C677T and A1298C gene variants in adult non-Hodgkins lymphoma patients: association with toxicity and survival
Haematologica
92
478-485
2007
Homo sapiens
Rios, D.L.; DOnofrio, L.O.; Carvalho, H.G.; Santos-Filho, A.; Galvao-Castro, B.
Sex-specific effect of the thermolabile C677T mutation in the methylenetetrahydrofolate reductase gene on angiographically assessed coronary artery disease in Brazilians
Hum. Biol.
79
453-461
2007
Homo sapiens
Rassoul, F.; Richter, V.; Hentschel, B.; Geisel, J.; Herrmann, W.; Kuntze, T.
Plasma homocysteine levels & 677C-->T methylenetetrahydrofolate reductase gene polymorphism in patients with coronary artery disease of different severity
Indian J. Med. Res.
127
154-158
2008
Homo sapiens
Cakir, O.; Ayyildiz, O.; Goz, M.; Sit, D.; Eren, N.
Myocardial infarction and venous thrombosis in a 42-year old woman with heterozygous methylenetetrahydrofolate reductase (MTHRF) gene mutation, hyperhomocysteinemia, and protein C deficiency
Int. J. Cardiol.
117
e98-100
2007
Homo sapiens
Kim, J.M.; Stewart, R.; Kim, S.W.; Yang, S.J.; Shin, I.S.; Shin, H.Y.; Yoon, J.S.
Methylenetetrahydrofolate reductase gene and risk of Alzheimers disease in Koreans
Int. J. Geriatr. Psychiatry
23
454-459
2008
Homo sapiens
Sugimoto, K.; Murata, M.; Onizuka, M.; Inamoto, Y.; Terakura, S.; Kuwatsuka, Y.; Oba, T.; Miyamura, K.; Kodera, Y.; Naoe, T.
Decreased risk of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation in patients with the 5,10-methylenetetrahydrofolate reductase 677TT genotype
Int. J. Hematol.
87
451-458
2008
Homo sapiens
Boettiger, A.K.; Hurtig-Wennloef, A.; Sjoestroem, M.; Yngve, A.; Nilsson, T.K.
Association of total plasma homocysteine with methylenetetrahydrofolate reductase genotypes 677C>T, 1298A>C, and 1793G>A and the corresponding haplotypes in Swedish children and adolescents
Int. J. Mol. Med.
19
659-665
2007
Homo sapiens
Arai, H.; Yamamoto, A.; Matsuzawa, Y.; Saito, Y.; Yamada, N.; Oikawa, S.; Mabuchi, H.; Teramoto, T.; Sasaki, J.; Nakaya, N.; Itakura, H.; Ishikawa, Y.; Ouchi, Y.; Horibe, H.; Egashira, T.; Hattori, H.; Kita, T.
Polymorphisms of apolipoprotein E and methylenetetrahydrofolate reductase in the Japanese population
J. Artheroscler. Thromb.
14
167-171
2007
Homo sapiens
Bennouar, N.; Allami, A.; Azeddoug, H.; Bendris, A.; Laraqui, A.; El Jaffali, A.; El Kadiri, N.; Benzidia, R.; Benomar, A.; Fellat, S.; Benomar, M.
Thermolabile methylenetetrahydrofolate reductase C677T polymorphism and homocysteine are risk factors for coronary artery disease in Moroccan population
J. Biomed. Biotechnol.
2007
80687
2007
Homo sapiens
Steer, C.; Emmett, P.; Lewis, S.; Smith, G.D.; Tobias, J.
The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with spinal BMD in nine-year-old children
J. Bone Miner. Res.
24
117-124
2008
Homo sapiens
Aygun, C.; Tanyeri, B.; Ceyhan, M.; Bagci, H.; Kucukoduk, S.
Diffuse multicystic encephalomalacia in a preterm baby due to homozygous methylenetetrahydrofolate reductase 677 C->T mutation
J. Child Neurol.
23
695-698
2008
Homo sapiens
Holm, P.I.; Hustad, S.; Ueland, P.M.; Vollset, S.E.; Grotmol, T.; Schneede, J.
Modulation of the homocysteine-betaine relationship by methylenetetrahydrofolate reductase 677 C->t genotypes and B-vitamin status in a large-scale epidemiological study
J. Clin. Endocrinol. Metab.
92
1535-1541
2007
Homo sapiens
Nishio, K.; Goto, Y.; Kondo, T.; Ito, S.; Ishida, Y.; Kawai, S.; Naito, M.; Wakai, K.; Hamajima, N.
Serum folate and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism adjusted for folate intake
J. Epidemiol.
18
125-131
2008
Homo sapiens
Bathum, L.; von Bornemann Hjelmborg, J.; Christiansen, L.; McGue, M.; Jeune, B.; Christensen, K.
Methylenetetrahydrofolate reductase 677C>T and methionine synthase 2756A>G mutations: no impact on survival, cognitive functioning, or cognitive decline in nonagenarians
J. Gerontol. A Biol. Sci. Med. Sci.
62
196-201
2007
Homo sapiens
Bronowicki, J.P.; Abdelmouttaleb, I.; Peyrin-Biroulet, L.; Venard, V.; Khiri, H.; Chabi, N.; Amouzou, E.K.; Barraud, H.; Halfon, P.; Sanni, A.; Bigard, M.A.; Le Faou, A.; Gueant, J.L.
Methylenetetrahydrofolate reductase 677 T allele protects against persistent HBV infection in West Africa
J. Hepatol.
48
532-539
2008
Homo sapiens
Zintzaras, E.; Uhlig, K.; Koukoulis, G.N.; Papathanasiou, A.A.; Stefanidis, I.
Methylenetetrahydrofolate reductase gene polymorphism as a risk factor for diabetic nephropathy: a meta-analysis
J. Hum. Genet.
52
881-890
2007
Homo sapiens
Mao, R.; Fan, Y.; Jin, Y.; Bai, J.; Fu, S.
Methylenetetrahydrofolate reductase gene polymorphisms and lung cancer: a meta-analysis
J. Hum. Genet.
53
340-348
2008
Homo sapiens
Li, D.; Karp, N.; Wu, Q.; Wang, X.L.; Melnyk, S.; James, S.J.; Rozen, R.
Mefolinate (5-methyltetrahydrofolate), but not folic acid, decreases mortality in an animal model of severe methylenetetrahydrofolate reductase deficiency
J. Inherit. Metab. Dis.
31
403-411
2008
Homo sapiens
Agarwal, R.P.; Peters, S.M.; Shemirani, M.; von Ahsen, N.
Improved real-time multiplex polymerase chain reaction detection of methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C polymorphisms using nearest neighbor model-based probe design
J. Mol. Diagn.
9
345-350
2007
Homo sapiens (P42898)
Li, S.; Ji, M.; He, N.; Lu, Z.
Application of microarray-based method for methylenetetrahydrofolate reductase (MTHFR) polymorphisms in the risk of gastric carcinoma in east China population
J. Nanosci. Nanotechnol.
7
3245-3249
2007
Homo sapiens
Pradhan, M.; Behari, S.; Kalra, S.K.; Ojha, P.; Agarwal, S.; Jain, V.K.
Association of methylenetetrahydrofolate reductase genetic polymorphisms with atlantoaxial dislocation
J. Neurosurg. Spine
7
623-630
2007
Homo sapiens
Solis, C.; Veenema, K.; Ivanov, A.A.; Tran, S.; Li, R.; Wang, W.; Moriarty, D.J.; Maletz, C.V.; Caudill, M.A.
Folate intake at RDA levels is inadequate for Mexican American men with the methylenetetrahydrofolate reductase 677TT genotype
J. Nutr.
138
67-72
2008
Homo sapiens
Smulders, Y.M.; Smith, D.E.; Kok, R.M.; Teerlink, T.; Gellekink, H.; Vaes, W.H.; Stehouwer, C.D.; Jakobs, C.
Red blood cell folate vitamer distribution in healthy subjects is determined by the methylenetetrahydrofolate reductase C677T polymorphism and by the total folate status
J. Nutr. Biochem.
18
693-699
2007
Homo sapiens
Kawamoto, R.; Kohara, K.; Oka, Y.; Tomita, H.; Tabara, Y.; Miki, T.
An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and ischemic stroke
J. Stroke Cerebrovasc. Dis.
14
67-74
2007
Homo sapiens
Ghaedi, M.; Aleyasin, A.; Boroumand, M.A.; Abbasi, S.H.; Davoodi, S.; Mirakhori, M.
Common polymorphism A1298C in methylenetetrahydrofolate reductase gene is not a risk factor for coronary artery disease in selected Iranian patients
J. Tehran Univ. Heart Cent.
2
161-166
2007
Homo sapiens
-
Sabino, A.; Fernandes, A.P.; Lima, L.M.; Ribeiro, D.D.; Sousa, M.O.; de Castro Santos, M.E.; Mota, A.P.; Dusse, L.M.; das Gracas Carvalho, M.
Polymorphism in the methylenetetrahydrofolate reductase (C677T) gene and homocysteine levels: a comparison in Brazilian patients with coronary arterial disease, ischemic stroke and peripheral arterial obstructive disease
J. Thromb. Thrombolysis
27
82-87
2009
Homo sapiens
Patti, G.; Fossati, C.; Nusca, A.; Mega, S.; Pasceri, V.; DAmbrosio, A.; Giannetti, B.; Annibali, O.; Avvisati, G.; Di Sciascio, G.
Methylenetetrahydrofolate reductase (MTHFR) C677T genetic polymorphism and late infarct-related coronary artery patency after thrombolysis
J. Thromb. Thrombolysis
27
413-420
2008
Homo sapiens
Fukino, K.; Kawashima, T.; Suzuki, M.; Ueno, K.
Methylenetetrahydrofolate reductase and reduced folate carrier-1 genotypes and methotrexate serum concentrations in patients with rheumatoid arthritis
J. Toxicol. Sci.
32
449-452
2007
Homo sapiens
Chiang, E.P.; Wang, Y.C.; Tang, F.Y.
Folate restriction and methylenetetrahydrofolate reductase 677T polymorphism decreases adoMet synthesis via folate-dependent remethylation in human-transformed lymphoblasts
Leukemia
21
651-658
2007
Homo sapiens
Toniutto, P.; Fabris, C.; Falleti, E.; Cussigh, A.; Fontanini, E.; Bitetto, D.; Fornasiere, E.; Minisini, R.; De Feo, T.; Marangoni, F.; Pirisi, M.
Methylenetetrahydrofolate reductase C677T polymorphism and liver fibrosis progression in patients with recurrent hepatitis C
Liver Int.
28
257-263
2008
Homo sapiens
Strauss, K.A.; Morton, D.H.; Puffenberger, E.G.; Hendrickson, C.; Robinson, D.L.; Wagner, C.; Stabler, S.P.; Allen, R.H.; Chwatko, G.; Jakubowski, H.; Niculescu, M.D.; Mudd, S.H.
Prevention of brain disease from severe 5,10-methylenetetrahydrofolate reductase deficiency
Mol. Genet. Metab.
91
165-175
2007
Homo sapiens
Munoz, J.B.; Lacasana, M.; Cavazos, R.G.; Borja-Aburto, V.H.; Galaviz-Hernandez, C.; Garduno, C.A.
Methylenetetrahydrofolate reductase gene polymorphisms and the risk of anencephaly in Mexico
Mol. Hum. Reprod.
13
419-424
2007
Homo sapiens
Kasap, M.; Sazci, A.; Ergul, E.; Akpinar, G.
Molecular phylogenetic analysis of methylenetetrahydrofolate reductase family of proteins
Mol. Phylogenet. Evol.
42
838-846
2007
Agrobacterium tumefaciens (Q7CXU3), Aquifex aeolicus (O67422), Arabidopsis thaliana (O80585), Aspergillus nidulans (Q5B0P7), Aspergillus oryzae (Q2UEQ8), Bacteroides thetaiotaomicron (Q8A146), Bifidobacterium longum (Q8G652), Bordetella bronchiseptica (A0A0H3LLF9), Bordetella parapertussis, Bos taurus (Q5I598), Bradyrhizobium japonicum (Q89UJ7), Brucella suis (A0A0H3G3R1), Caenorhabditis elegans (Q17693), Candida albicans (Q5AEI0), Candidatus Blochmannia floridanus (Q7VRL4), Caulobacter vibrioides (Q9A6F4), Chromobacterium violaceum (Q7NZF6), Collimonas fungivorans (Q6J6A1), Corynebacterium diphtheriae (Q6NGB6), Corynebacterium glutamicum (Q8NNM2), Coxiella burnetii (Q83A63), Desulfovibrio vulgaris (Q72DD2), Dictyostelium discoideum (Q54X84), Escherichia coli, Fusarium graminearum, Gloeobacter violaceus (Q7NMH7), Homo sapiens (P42898), Leptospira interrogans (Q9L5C1), Macaca fascicularis (Q60HE5), Macaca mulatta, Mesorhizobium loti (Q98K87), Methanosarcina mazei (Q8PZQ4), Mus musculus (Q9WU20), Oryza sativa (Q10BJ7), Pasteurella multocida (Q9CP31), Photorhabdus luminescens (Q7MYD0), Prochlorococcus marinus (Q7VE38), Pseudomonas syringae (Q87V72), Pyricularia grisea, Ralstonia solanacearum (Q8Y389), Rattus norvegicus, Rhodopirellula baltica (Q7UNJ7), Rhodopseudomonas palustris (Q6N3J2), Saccharomyces cerevisiae (P53128), Schizosaccharomyces pombe (Q10258), Shigella flexneri (Q0SY49), Sinorhizobium meliloti (Q92NK1), Streptococcus pneumoniae (Q8DQT1), Tetraodon nigroviridis (Q4T956), Thermus thermophilus (Q72H39), Vibrio cholerae (Q9KNP6), Vibrio parahaemolyticus (Q87L52), Vibrio vulnificus (Q7MH66), Wolinella succinogenes (Q7M8S8), Xenopus laevis (Q7ZWU2), Xylella fastidiosa (Q9PEA7), Zea mays (Q9SE94), [Candida] glabrata (Q6FU20)
Michael, S.; Qamar, R.; Akhtar, F.; Khan, W.A.; Ahmed, A.
C677T polymorphism in the methylenetetrahydrofolate reductase gene is associated with primary closed angle glaucoma
Mol. Vis.
14
661-665
2008
Homo sapiens
Kim, D.H.
The interactive effect of methyl-group diet and polymorphism of methylenetetrahydrofolate reductase on the risk of colorectal cancer
Mutat. Res.
622
14-18
2007
Homo sapiens
Linnebank, M.; Semmler, A.; Moskau, S.; Smulders, Y.; Blom, H.; Simon, M.
The methylenetetrahydrofolate reductase (MTHFR) variant c.677C>T (A222V) influences overall survival of patients with glioblastoma multiforme
Neuro-oncology
10
548-552
2008
Homo sapiens
Dutta, S.; Das Bhowmik, A.; Sinha, S.; Chattopadhyay, A.; Mukhopadhyay, K.
Screening for methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Indian patients with idiopathic mental retardation
Nutr. Neurosci.
11
18-24
2008
Homo sapiens
Stonek, F.; Hafner, E.; Philipp, K.; Hefler, L.A.; Bentz, E.K.; Tempfer, C.B.
Methylenetetrahydrofolate reductase C677T polymorphism and pregnancy complications
Obstet. Gynecol.
110
363-368
2007
Homo sapiens
Zetterberg, M.; Tasa, G.; Palmer, M.S.; Juronen, E.; Toover, E.; Blennow, K.; Zetterberg, H.
Methylenetetrahydrofolate reductase genetic polymorphisms in patients with primary open-angle glaucoma
Ophthalmic Genet.
28
47-50
2007
Homo sapiens
Alcasabas, P.; Ravindranath, Y.; Goyette, G.; Haller, A.; Del Rosario, L.; Lesaca-Medina, M.Y.; Darga, L.; Ostrea, E.M.; Taub, J.W.; Everson, R.B.
5,10-Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the risk of acute lymphoblastic leukemia (ALL) in Filipino children
Pediatr. Blood Cancer
51
178-182
2008
Homo sapiens
Koo, H.S.; Lee, H.S.; Hong, Y.M.
Methylenetetrahydrofolate reductase TT genotype as a predictor of cardiovascular risk in hypertensive adolescents
Pediatr. Cardiol.
29
136-141
2008
Homo sapiens
Bueyuekcelik, M.; Karakoek, M.; Baspinar, O.; Balat, A.
Arterial thrombosis associated with factor V Leiden and methylenetetrahydrofolate reductase C677T mutation in childhood membranous glomerulonephritis
Pediatr. Nephrol.
23
491-494
2008
Homo sapiens
Etienne-Grimaldi, M.C.; Francoual, M.; Formento, J.L.; Milano, G.
Methylenetetrahydrofolate reductase (MTHFR) variants and fluorouracil-based treatments in colorectal cancer
Pharmacogenomics
8
1561-1566
2007
Homo sapiens
Wintner, S.; Hafner, E.; Stonek, F.; Stuempflen, I.; Metzenbauer, M.; Philipp, K.
Association of congenital cardiac defects and the C677T methylenetetrahydrofolate reductase polymorphism
Prenat. Diagn.
27
704-708
2007
Homo sapiens
Ozbek, Z.; Kucukali, C.I.; Ozkok, E.; Orhan, N.; Aydin, M.; Kilic, G.; Sazci, A.; Kara, I.
Effect of the methylenetetrahydrofolate reductase gene polymorphisms on homocysteine, folate and vitamin B12 in patients with bipolar disorder and relatives
Prog. Neuropsychopharmacol. Biol. Psychiatry
32
1331-1337
2008
Homo sapiens
Vurucu, S.; Demirkaya, E.; Kul, M.; Unay, B.; Gul, D.; Akin, R.; Gokcay, E.
Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy
Prog. Neuropsychopharmacol. Biol. Psychiatry
32
844-848
2008
Homo sapiens
Guerzoni, A.R.; Pavarino-Bertelli, E.C.; Godoy, M.F.; Graca, C.R.; Biselli, P.M.; Souza, D.R.; Bertollo, E.M.
Methylenetetrahydrofolate reductase gene polymorphism and its association with coronary artery disease
Sao Paulo Med. J.
125
4-8
2007
Homo sapiens
Roffman, J.L.; Weiss, A.P.; Deckersbach, T.; Freudenreich, O.; Henderson, D.C.; Purcell, S.; Wong, D.H.; Halsted, C.H.; Goff, D.C.
Effects of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on executive function in schizophrenia
Schizophr. Res.
92
181-188
2007
Homo sapiens
Berge, E.; Haug, K.B.; Sandset, E.C.; Haugbro, K.K.; Turkovic, M.; Sandset, P.M.
The factor V Leiden, prothrombin gene 20210GA, methylenetetrahydrofolate reductase 677CT and platelet glycoprotein IIIa 1565TC mutations in patients with acute ischemic stroke and atrial fibrillation
Stroke
38
1069-1071
2007
Homo sapiens
Garcia-Pinilla, J.M.; Espinosa-Caliani, S.; Jimenez-Navarro, M.; Gomez-Doblas, J.J.; Cabrera-Bueno, F.; Reyes-Engel, A.; de Teresa-Galvan, E.
Influence of 677 C->T polymorphism of methylenetetrahydrofolate reductase on medium-term prognosis after acute coronary syndromes
Tex. Heart Inst. J.
34
142-147
2007
Homo sapiens
Altomare, I.; Adler, A.; Aledort, L.M.
The 5, 10 methylenetetrahydrofolate reductase C677T mutation and risk of fetal loss: a case series and review of the literature
Thromb. J.
5
17
2007
Homo sapiens
Freitas, A.I.; Mendonca, I.; Guerra, G.; Brion, M.; Reis, R.P.; Carracedo, A.; Brehm, A.
Methylenetetrahydrofolate reductase gene, homocysteine and coronary artery disease: The A1298C polymorphism does matter. Inferences from a case study (Madeira, Portugal)
Thromb. Res.
122
648-656
2008
Homo sapiens
de Alvarenga, M.P.; Pavarino-Bertelli, E.C.; Abbud-Filho, M.; Ferreira-Baptista, M.A.; Haddad, R.; Eberlin, M.N.; Goloni-Bertollo, E.M.
Combination of angiotensin-converting enzyme and methylenetetrahydrofolate reductase gene polymorphisms as determinant risk factors for chronic allograft dysfunction
Transplant. Proc.
39
78-80
2007
Homo sapiens
Nieminen, T.; Knuuti, J.; Haemelahti, P.; Kaehoenen, M.; Laaksonen, R.; Janatuinen, T.; Vesalainen, R.; Nuutila, P.; Jokela, H.; Lehtimaeki, T.
Coronary reactivity, homocysteine and methylenetetrahydrofolate reductase gene variation in young men during pravastatin therapy
Vascul. Pharmacol.
47
113-117
2007
Homo sapiens
Mokarram, P.; Naghibalhossaini, F.; Saberi Firoozi, M.; Hosseini, S.V.; Izadpanah, A.; Salahi, H.; Malek-Hosseini, S.A.; Talei, A.; Mojallal, M.
Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B(12) status
World J. Gastroenterol.
14
3662-3671
2008
Homo sapiens
Kim, O.J.; Hong, S.P.; Ahn, J.Y.; Hong, S.H.; Hwang, T.S.; Kim, S.O.; Yoo, W.; Oh, D.; Kim, N.K.
Influence of combined methionine synthase (MTR 2756A > G) and methylenetetrahydrofolate reductase (MTHFR 677C > T) polymorphisms to plasma homocysteine levels in Korean patients with ischemic stroke
Yonsei Med. J.
48
201-209
2007
Homo sapiens
Guerreiro, C.S.; Carmona, B.; Goncalves, S.; Carolino, E.; Fidalgo, P.; Brito, M.; Leitao, C.N.; Cravo, M.
Risk of colorectal cancer associated with the C677T polymorphism in 5,10-methylenetetrahydrofolate reductase in Portuguese patients depends on the intake of methyl-donor nutrients
Am. J. Clin. Nutr.
88
1413-1418
2008
Homo sapiens
Szamosi, S.; Csiki, Z.; Szomjak, E.; Szolnoki, E.; Szoke, G.; Szekanecz, Z.; Szegedi, G.; Shoenfeld, Y.; Szucs, G.
Plasma homocysteine levels, the prevalence of methylenetetrahydrofolate reductase gene C677T polymorphism and macrovascular disorders in systemic sclerosis: risk factors for accelerated macrovascular damage?
Clin. Rev. Allergy Immunol.
36
145-149
2009
Homo sapiens
Jakubowski, H.; Perla-Kajan, J.; Finnell, R.H.; Cabrera, R.M.; Wang, H.; Gupta, S.; Kruger, W.D.; Kraus, J.P.; Shih, D.M.
Genetic or nutritional disorders in homocysteine or folate metabolism increase protein N-homocysteinylation in mice
FASEB J.
23
1721-1727
2009
Homo sapiens
Gilfix, B.M.
An unusual melting curve on a LightCycler due to a new mutation in methylenetetrahydrofolate reductase
Genet. Test. Mol. Biomarkers
13
769-771
2009
Homo sapiens
Yuan, R.Y.; Sheu, J.J.; Yu, J.M.; Hu, C.J.; Tseng, I.J.; Ho, C.S.; Yeh, C.Y.; Hung, Y.L.; Chiang, T.R.
Methylenetetrahydrofolate reductase polymorphisms and plasma homocysteine in levodopa-treated and non-treated Parkinsons disease patients
J. Neurol. Sci.
287
64-68
2009
Homo sapiens
Fisher, M.C.; Cronstein, B.N.
Metaanalysis of methylenetetrahydrofolate reductase (MTHFR) polymorphisms affecting methotrexate toxicity
J. Rheumatol.
36
539-545
2009
Homo sapiens
Almawi, W.; Khan, A.; Al-Othman, S.; Bakhiet, M.
Case-control study of methylenetetrahydrofolate reductase mutations and hyperhomocysteinemia and risk of stroke
J. Stroke Cerebrovasc. Dis.
18
407-408
2009
Homo sapiens
Karas Kuzelicki, N.; Milek, M.; Jazbec, J.; Mlinaric-Rascan, I.
5,10-Methylenetetrahydrofolate reductase (MTHFR) low activity genotypes reduce the risk of relapse-related acute lymphoblastic leukemia (ALL)
Leuk. Res.
33
1344-1348
2009
Homo sapiens
Chen, Z.; Liu, Y.; Zhang, D.; Liu, Z.; Wang, P.; Zhou, D.; Zhao, T.; Wang, T.; Xu, H.; Li, S.; Feng, G.; He, L.; Yu, L.
C677T methylenetetrahydrofolate reductase gene polymorphisms in bipolar disorder: an association study in the Chinese population and a meta-analysis of genetic association studies
Neurosci. Lett.
449
48-51
2009
Homo sapiens
McGuire, J.J.; Haile, W.H.
Metabolism-blocked antifolates as potential anti-rheumatoid arthritis agents: 4-amino-4-deoxy-5,8,10-trideazapteroyl-D,L-4-methyleneglutamic acid (CH-1504) and its analogs
Biochem. Pharmacol.
77
1161-1172
2009
Homo sapiens
Fernandez-Peralta, A.M.; Daimiel, L.; Nejda, N.; Iglesias, D.; Medina Arana, V.; Gonzalez-Aguilera, J.J.
Association of polymorphisms MTHFR C677T and A1298C with risk of colorectal cancer, genetic and epigenetic characteristic of tumors, and response to chemotherapy
Int. J. Colorectal Dis.
25
141-151
2010
Homo sapiens
Forges, T.; Chery, C.; Audonnet, S.; Feillet, F.; Gueant, J.L.
Life-threatening methylenetetrahydrofolate reductase (MTHFR) deficiency with extremely early onset: characterization of two novel mutations in compound heterozygous patients
Mol. Genet. Metab.
100
143-148
2010
Homo sapiens
Trimmer, E.
Methylenetetrahydrofolate reductase: Biochemical characterization and medical significance
Curr. Pharm. Des.
19
2574-2593
2013
Homo sapiens
Villela, M.P.; Andrade, V.L.; Eccard, B.; Jordao, A.A.; Sertorio, J.T.; Tanus-Santos, J.E.; Silva, I.F.; Silveira, J.N.; Sandrim, V.C.
Homocysteine and nitrite levels are modulated by MTHFR 677C>T polymorphism in obese women treated with simvastatin
Clin. Exp. Pharmacol. Physiol.
41
744-747
2014
Homo sapiens (P42898)
Bezerra, G.A.; Holenstein, A.; Foster, W.R.; Xie, B.; Hicks, K.G.; Buerer, C.; Lutz, S.; Mukherjee, A.; Sarkar, D.; Bhattacharya, D.; Rutter, J.; Talukdar, A.; Brown, P.J.; Luo, M.; Shi, L.; Froese, D.S.; Yue, W.W.
Identification of small molecule allosteric modulators of 5,10-methylenetetrahydrofolate reductase (MTHFR) by targeting its unique regulatory domain
Biochimie
183
100-107
2021
Homo sapiens (P42898)
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Homo sapiens (P42898)
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