Methylenetetrahydrofolate reductase (MTHFR) is the rate-limiting enzyme in the methyl cycle, and it is encoded by the MTHFR gene.[5] Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Natural variation in this gene is common in otherwise healthy people. Although some variants have been reported to influence susceptibility to occlusive vascular disease, neural tube defects, Alzheimer's disease and other forms of dementia, colon cancer, and acute leukemia, findings from small early studies have not been reproduced. Some mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.[6][7][8] Complex I deficiency with recessive spastic paraparesis has also been linked to MTHFR variants. In addition, the aberrant promoter hypermethylation of this gene is associated with male infertility and recurrent spontaneous abortion.[9][10]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000177000 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029009 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Goyette P, Sumner JS, Milos R, Duncan AM, Rosenblatt DS, Matthews RG, Rozen R (June 1994). "Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification". Nature Genetics. 7 (2): 195–200. doi:10.1038/ng0694-195. PMID 7920641. S2CID 23877329.
- ^ "Entrez Gene: MTHFR methylene tetrahydrofolate reductase (NAD(P)H)".
- ^ Födinger M, Hörl WH, Sunder-Plassmann G (2000). "Molecular biology of 5,10-methylenetetrahydrofolate reductase". Journal of Nephrology. 13 (1): 20–33. PMID 10720211.
- ^ Trimmer EE (2013). "Methylenetetrahydrofolate reductase: biochemical characterization and medical significance". Current Pharmaceutical Design. 19 (14): 2574–93. doi:10.2174/1381612811319140008. PMID 23116396.
- ^ Cite error: The named reference
Rotondo_2012was invoked but never defined (see the help page). - ^ Rotondo JC, Selvatici R, Di Domenico M, Marci R, Vesce F, Tognon M, Martini F (September 2013). "Methylation loss at H19 imprinted gene correlates with methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples from infertile males". Epigenetics. 8 (9): 990–7. doi:10.4161/epi.25798. PMC 3883776. PMID 23975186.