MTHFD1

MTHFD1

A gene on chromosome 14q24 that encodes an enzyme that has three distinct enzymatic activities:
• 5,10-methylenetetrahydrofolate dehydrogenase (E.C. 1.5.1.5);
• 5,10-methenyltetrahydrofolate cyclohydrolase (E.C. 3.5.4.9); and
• 10-formyltetrahydrofolate synthetase (E.C. 6.3.4.3).
These activities interconvert methyl (1-carbon) derivatives of tetrahydrofolate, which serve as substrates for methionine, thymidylate and de novo purine synthesis.

Molecular pathology
Defects in MTHFD1 may increase susceptibility to folate-sensitive neural tube defects and colorectal cancer.
References in periodicals archive ?
Wessels et al11 established a model for predicting MTX efficacy in RA patients which consisted of sex, rheumatoid factor and smoking status, the DAS, and 4 polymorphisms in the AMPD1, ATIC, ITPA, and MTHFD1 genes.
All SNPs were in HWE except the MTHFD1 SNP rs2236225 in affected individuals only (data not shown).
When segregating the A allele, MTHFD1 rs2236225 was significant by PDT in the broad phenotypic group (p = 0.
Of all the SNPs tested, only MTHFD1 rs2236225 was out of HWE (p = 0.
FOLR1 folate receptor 1 NM_016725 FOLR2 folate receptor 2 NM_000803 SLC19A1 solute carrier family 19 member 1 U15939 TCN2 transcobalamin II NM_000355 MTHFD1 methylenetetrahydrofolate dehydrogenase 1 J04031 SHMT1 serine hydroxyl-methyltranferase 1 NM_004169 MTHFR 5,10 methylene-tetrahydrofolate reductase NM_005957 MTR 5-methyltetrahydrofolate-homocysteine NM_000254 methyltransferase rs12060570 Intronic MTRR 5-methyltetrahydrofolate-homocysteine AF025794 methyltransferase reductase BHMT betaine-homocysteine methyltransferase BC012616 CBS cystathionine-beta-synthase NM_000071 Gene symbol rs no.
The MTHFD1 1958G>A (R653Q) allele is associated with neural tube defects (15).
Models were also fitted with MTHFDI included to determine any multilocus effects across MTHFR and MTHFD1.
The genotype frequencies for MTHFR and MTHFD1 in the 3 groups are shown in Table 1.
32), and the fit of the model was not improved by including MTHFD1 1958G>A.
We postulated that mutations occurring simultaneously in both the MTHFR and MTHFD1 genes could impair 5,10-MTHF and 5-methyltetrahydrofolate formation and hence lead to reduced SAM concentrations and decreased TPMT stability.
The coinheritance of variant MTHFR and MTHFD1 alleles did not have an additive effect on TPMT activity, consistent with reports concluding that MTHFD1 does not directly influence reactions for which a methyl group is required and does not affect SAM concentrations through 5,10-MTHF pools (15).