rs1950902
This is a variant in the MTHFD1 gene that changes a lysine to an arginine.
▶ClinVar annotation
Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia; not specified
View on ClinVar →▶Research that mentions this SNP (6)
▶Association of main folate metabolic pathway gene polymorphisms with neural tube defects in Han population of Northern ChinaAssociationN=321Yulian Fang et al.(2018)· Child's Nervous System
A case-control study of 152 NTD patients and 169 controls in Han Chinese population identified three folate metabolism pathway SNPs associated with neural tube defects: rs2236225 in MTHFD1 (allele A, OR=1.500; AA genotype OR=2.862), rs1801133 in MTHFR (allele T, OR=1.552; TT genotype OR=2.344), and rs1801394 in MTRR (allele G, OR=1.533; GG genotype OR=2.355). The study demonstrates genetic variation in folate metabolism significantly affects NTD susceptibility.
▶MTHFR rs2274976 polymorphism is a risk marker for nonsyndromic cleft lip with or without cleft palate in the Brazilian populationAssociationN=1,712Sibele Nascimento de Aquino et al.(2014)· Birth Defects Research Part A: Clinical and Molecular Teratology
Case-control study of 501 young stroke patients and 1,211 controls examining 58 polymorphisms in 17 genes involved in methionine metabolism. Multiple logistic regression identified four independent risk factors for early-onset ischaemic stroke: rs10037045 BHMT (OR 1.38, p=0.033), rs682985 BHMT2 (OR 1.46, p=0.017), rs1051319 CBS (OR 3.75, p<0.0001), and rs202680 FOLH1 (OR 3.00, p<0.0001). Haplotype analyses identified significant associations with BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS haplotypes and stroke risk.
▶Gene variants in the folate‐mediated one‐carbon metabolism (FOCM) pathway as risk factors for conotruncal heart defectsAssociationN=1,236Huiping Zhu et al.(2012)· American Journal of Medical Genetics Part A
This case-control study examined 29 polymorphisms in four folate-mediated one-carbon metabolism pathway genes (MTHFD1, SHMT1, MTHFR, DHFR) in Hispanic and non-Hispanic white populations to assess their association with conotruncal heart defects. MTHFD1 rs11627387 was associated with a 1.7-fold increased risk in both Hispanic mothers (OR=1.7, 95% CI=1.1-2.5) and Hispanic infants (OR=1.7, 95% CI=1.2-2.3). MTHFR rs1801133 (C677T) showed a 2.8-fold increased risk among Hispanic mothers with low dietary folate intake, while rs1801131 (A1298C) showed a 2.0-fold increased risk among those with higher folate intake. Gene-folate interactions were observed, suggesting maternal multivitamin use and dietary folate intake may modify conotruncal heart defect risk.
▶Maternal and infant gene–folate interactions and the risk of neural tube defectsAssociationN=676Analee J. Etheredge et al.(2012)· American Journal of Medical Genetics Part A
Case-control study (222 cases, 454 controls) examining gene-folate interactions in five folate-related genes (MTHFD1, MTHFR, SHMT1, DHFR, TYMS) and neural tube defect risk. Maternal MTHFR SNPs rs1476413, rs1801131, and rs1801133 showed decreased NTD risk with low folate intake (OR=0.55-0.69, 80% CI); infant MTHFD1 SNPs rs2236224, rs2236225, and rs11627387 showed increased risk (OR=1.53-4.25, 80% CI); maternal SHMT1 rs669340 showed protective gene-only effect (OR=0.69, 95% CI: 0.49-0.96).
▶Genetic variants in one‐carbon metabolism‐related genes contribute to NSCLC prognosis in a Chinese populationAssociationN=564Guangfu Jin et al.(2010)· Cancer
This association study screened 57 SNPs from 11 one-carbon metabolism genes in 564 NSCLC patients to identify genetic variants affecting lung cancer prognosis. Key findings included favorable prognostic associations for MTR rs3768160 A>G (HR=0.78, 95% CI 0.62-0.98), MTRR rs2966952 G>A (HR=0.84, 95% CI 0.71-0.99), and DHFR rs1650697 G>A (HR=0.83, 95% CI 0.70-0.99), with unfavorable prognosis for MTHFD1 rs1950902 G>A (HR=1.18, 95% CI 0.99-1.40). Combined analysis of these four SNPs demonstrated a locus-dosage effect on NSCLC survival (P trend = 6.9×10⁻⁵) and identified combined genotypes as an independent prognostic factor.
▶The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defectsMeta-analysisN=7,164Karen E. Christensen et al.(2009)· Human Mutation
A systematic review and meta-analysis of 9 case-control studies (1917 CHD cases, 1863 controls, 1718 maternal cases, 1666 maternal controls) examining MTHFD1 G1958A (rs2236225) polymorphism association with congenital heart disease (CHD). The fetal meta-analysis found no significant overall association, but subgroup analysis showed the AA genotype increased Tetralogy of Fallot (TOF) risk (OR=2.82-3.09). Maternal analysis revealed the GA genotype increased CHD risk (OR=1.22-1.17). Racial differences were observed, with Caucasians showing increased risk.
About MTHFD1
This gene encodes a protein that possesses three distinct enzymatic activities, 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase. Each of these activities catalyzes one of three sequential reactions in the interconversion of 1-carbon derivatives of tetrahydrofolate, which are substrates for methionine, thymidylate, and de novo purine syntheses. The trifunctional enzymatic activities are conferred by two major domains, an aminoterminal portion containing the dehydrogenase and cyclohydrolase activities and a larger synthetase domain. [provided by RefSeq, Jul 2008]
View all MTHFD1 variants →Gene information from NCBI Gene. Variant classifications from ClinVar.
Community Wiki
No community notes yet for this variant. Sign in to start one.
Comments
Sign in to join the discussion.
Loading comments…