Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification

Nat Genet. 1994 Jun;7(2):195-200. doi: 10.1038/ng0694-195.


Methylenetetrahydrofolate reductase (MTHFR) catalyses the reduction of methylenetetrahydrofolate to methyltetrahydrofolate, a cofactor for homocysteine methylation to methionine. MTHFR deficiency, an autosomal recessive disorder, results in homocysteinemia. Using degenerate oligonucleotides based on porcine peptide sequence data, we isolated a 90-bp cDNA by PCR from pig liver RNA. This cDNA was used to isolate a human cDNA, the predicted amino acid sequence of which shows strong homology to porcine MTHFR and to bacterial metF genes. The human gene has been localized to chromosome 1p36.3. Two mutations were identified in MTHFR-deficient patients: a missense mutation (Arg to Gln), in a residue conserved in bacterial enzymes, and a nonsense mutation (Arg to Ter).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / genetics
  • Base Sequence
  • Cardiovascular Diseases / enzymology
  • Cardiovascular Diseases / genetics
  • Chromosome Mapping
  • Chromosomes, Human, Pair 1
  • DNA, Complementary / genetics*
  • DNA, Complementary / isolation & purification
  • Female
  • Homocysteine / blood
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Molecular Sequence Data
  • Nervous System Diseases / enzymology
  • Nervous System Diseases / genetics
  • Oxidoreductases Acting on CH-NH Group Donors / deficiency
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Pedigree
  • Point Mutation*
  • Sequence Homology, Amino Acid
  • Swine


  • Bacterial Proteins
  • DNA, Complementary
  • Homocysteine
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)

Associated data

  • GENBANK/U09806