Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

Official Name

methylenetetrahydrofolate reductase [NAD(P)H]

Name from literature

methylenetetrahydrofolate reductase

Pathway from literature

methyl group metabolism

Pathway from KEGG

Metabolism of Cofactors and Vitamins; One carbon pool by folate; map00670

Energy Metabolism; Methane metabolism; map00680


Human (9606)

Genome localization

1p36.3[4524 ],


A flavoprotein (FAD). Menadione can also serve as an electron acceptor.

Rate-limiting Description

"Although the pathway is a network of interrelated enzymes, redundancy exists; evaluating the rate-limiting enzyme and its interaction with environment and other genes within the same pathway is critical in assessing breast cancer risk." (17372271)

Regulatory Information

Regulatory type


regulatory enzyme;

"Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in folate and homocysteine metabolism." (17349292#17063264)


"Impaired activity correlated with the phosphorylation state of MTHFR, with more severe mutations resulting in lower abundance of the phosphorylated protein." (18523009#16024724)



Gene ontology

Gene ontology

GO:0004489 (F) methylenetetrahydrofolate reductase (NADPH)... [Q59GJ6, Q5SNW5, Q30BY1, P42898, A0MPA5, Q5SNW9, Q5SNW6 ];
GO:0008015 (P) blood circulation [P42898 ];
GO:0006555 (P) methionine metabolic process [Q59GJ6, Q5SNW5, Q30BY1, A0MPA5, Q5SNW9, Q5SNW6 ];
GO:0005829 (C) cytosol [P42898 ];
GO:0005515 (F) protein binding [P42898 ];
GO:0055114 (P) oxidation reduction [Q59GJ6, Q5SNW5, Q30BY1, P42898, A0MPA5, Q5SNW9, Q5SNW6 ];

Disease relevance


Defects in MTHFR are the cause of methylenetetrahydrofolate reductase deficiency (MTHFRD) [MIM:236250]. MTHFRD is autosomal recessive disorder with a wide range of features including homocysteinuria, homocysteinemia [MIM:603174], developmental delay, severe mental retardation, perinatal death, psychiatric disturbances, and later-onset neurodegenerative disorders [P42898 ];

Defects in MTHFR may be a cause of susceptibility to ischemic stroke [MIM:601367];
also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors [P42898 ];

Defects in MTHFR may be a cause of susceptibility to folate-sensitive neural tube defects (folate-sensitive NTD) [MIM:601634]. The most common NTDs are open spina bifida (myelomeningocele) and anencephaly [P42898 ];



A0MPA5; P42898; Q30BY1; Q59GJ6; Q5SNW5; Q5SNW6; Q5SNW9

Entrez Gene




  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min