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Dihydrofolate reductase

Function

Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2.

Involvement in disease

Megaloblastic anemia due to dihydrofolate reductase deficiency

DHFRD

An inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.

None

The disease is caused by variants affecting the gene represented in this entry.

Pathway

Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.

Sequence Similarities

Belongs to the dihydrofolate reductase family.

Tissue Specificity

Widely expressed in fetal and adult tissues, including throughout the fetal and adult brains and whole blood. Expression is higher in the adult brain than in the fetal brain.

Cellular localization

Alternative names

Dihydrofolate reductase, DHFR

swissprot:P00374 omim:126060 entrezGene:1719