MTHFR
Domain
Contains a serine-rich phosphorylation region at the N-terminal and an eukaryote-only S-adenosylmethionine (SAM)-binding domain at the C-terminal. Through asymmetric homodimerization, the two regions are positioned next to each other and N-terminal phosphorylation increases sensitivity to SAM binding and inhibition.
Function
Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connection between the folate and methionine cycles (Probable).
Involvement in disease
Homocystinuria due to deficiency of N(5,10)-methylenetetrahydrofolate reductase activity
MTHFRD
An autosomal recessive inborn error of folate metabolism. Clinical severity is variable, ranging from severe neurologic features to absence of symptoms. Clinical features include homocysteinuria, homocysteinemia, developmental delay, severe intellectual disability, perinatal death, psychiatric disturbances, and later-onset neurodegenerative disorders.
None
The disease is caused by variants affecting the gene represented in this entry.
Ischemic stroke
ISCHSTR
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.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Neural tube defects, folate-sensitive
NTDFS
The most common NTDs are open spina bifida (myelomeningocele) and anencephaly.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Schizophrenia
SCZD
A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Pathway
One-carbon metabolism; tetrahydrofolate interconversion.
Post-translational modifications
Phosphorylation of an N-terminal serine-rich phosphorylation region increases sensitivity to S-adenosylmethionine and inhibition.
Sequence Similarities
Belongs to the methylenetetrahydrofolate reductase family.
Alternative names
Methylenetetrahydrofolate reductase (NADPH), MTHFR