{{Rsnum
|rsid=2236225
|Gene=MTHFD1
|Chromosome=14
|position=64442127
|Orientation=minus
|ReferenceAllele=A
|MissenseAllele=G
|GMAF=0.3462
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=MTHFD1
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 34.5 | 47.8 | 17.7
| HCB | 59.6 | 37.5 | 2.9
| JPT | 53.1 | 41.6 | 5.3
| YRI | 64.6 | 32.0 | 3.4
| ASW | 57.9 | 40.4 | 1.8
| CHB | 59.6 | 37.5 | 2.9
| CHD | 65.4 | 33.6 | 0.9
| GIH | 27.0 | 52.0 | 21.0
| LWK | 60.0 | 36.4 | 3.6
| MEX | 17.2 | 46.6 | 36.2
| MKK | 34.0 | 55.8 | 10.3
| TSI | 36.3 | 47.1 | 16.7
| HapMapRevision=28
}}
{{PMID|19130090|OA=1
}} [[rs1076991]] C > T exerts a significant effect on promoter activity in vitro and along with [[rs2236225]] G > A influences embryonic development.

{{omim
|desc=NEURAL TUBE DEFECTS, [[Folate]]-SENSITIVE, SUSCEPTIBILITY TO
|id=172460
|rsnum=2236225
|variant=0002
}}

{{Venter SNP
|rsid=2236225
|allele=A
|frequency=0.458
|uid=1103649084632
|type=heterozygous_SNP
|hugo=MTHFD1
|ensembl gene=ENSG00000100714
|ensembl transcript=ENST00000216605
|sift=TOLERATED
|disease=Defects in MTHFD1 may be associated with elevated risk for neural tube defects (NTD) such as spina bifida.
}}

{{PMID Auto
|PMID=20217437
|Title=Association analysis of CbetaS 844ins68 and MTHFD1 G1958A polymorphisms with Alzheimer's disease in Chinese
}}

{{PharmGKB
|RSID=rs2236225
|Name_s=R653Q; MTHFD1:1958G>A; MTHFD1:Arg653Gln
|Gene_s=MTHFD1
|Feature=
|Evidence=PubMed ID:12384833
|Annotation=Risk or phenotype-associated allele: A Phenotype: Homozygous AA genotype in mothers was associated with increased risk for having a child with a neural tube defect. Study size: 319 Study population/ethnicity: Mothers, fathers and affected offspring of families with a child with a neural tube defect, Ireland. Significance metric(s): OR = 1.52 (95% CI 1.16-1.99); p = 0.003 Type of association: CO
|Drugs=
|Drug Classes=
|Diseases=Neural Tube Defects
|Curation Level=Curated
|PharmGKB Accession ID=PA165291540
}}

{{PMID Auto
|PMID=21429654
|Title=Polymorphic variants of folate and choline metabolism genes and the risk of endometriosis-associated infertility
}}

{{ClinVar
|rsid=2236225
|Reversed=1
|FwdREF=C
|FwdALT=T
|REF=G
|ALT=A
|RSPOS=64908845
|CHROM=14
|GMAF=0.3466
|dbSNPBuildID=98
|SSR=0
|SAO=1
|VP=0x05016800000015051f110100
|GENEINFO=MTHFD1:4522
|GENE_NAME=MTHFD1
|GENE_ID=4522
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000014.8:g.64908845G>A
|CLNORIGIN=1
|CLNSIG=255
|Tags=RV;PM;PMC;SLO;VLD;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;OM
|CAF=0.6538; 0.3462
|CLNACC=RCV000014603.1
|CLNDBN=Neural tube defects, folate-sensitive, susceptibility to
|CLNSRC=OMIM Allelic Variant
|CLNSRCID=172460.0002
|COMMON=1
|Disease=Neural tube defects
}}

{{PMID|16816108|OA=1
}} Common genetic polymorphisms affect the human requirement for the nutrient choline.

{{PMID|17035141|OA=1
}} Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions.

{{PMID|17613168|OA=1
}} Gene response elements, genetic polymorphisms and epigenetics influence the human dietary requirement for choline.

{{PMID|17616785|OA=1
}} Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not.

{{PMID|18203168|OA=1
}} Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts.

{{PMID|18221821}} Association of polymorphisms in one-carbon metabolizing genes and lung cancer risk: a case-control study in Chinese population.

{{PMID|18661527|OA=1
}} Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate.

{{PMID|18789905|OA=1
}} Genetic polymorphisms in methyl-group metabolism and epigenetics: lessons from humans and mouse models.

{{PMID|18992148|OA=1
}} Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study.

{{PMID|19064578|OA=1
}} No association of single nucleotide polymorphisms in one-carbon metabolism genes with prostate cancer risk.

{{PMID|19112534|OA=1
}} Lack of association of polymorphisms in homocysteine metabolism genes with pseudoexfoliation syndrome and glaucoma.

{{PMID|19167960|OA=1
}} Genetic variants in phosphatidylethanolamine N-methyltransferase and methylenetetrahydrofolate dehydrogenase influence biomarkers of choline metabolism when folate intake is restricted.

{{PMID|19261726|OA=1
}} Epigenetic mechanisms for nutrition determinants of later health outcomes.

{{PMID|19379518|OA=1
}} Development of a fingerprinting panel using medically relevant polymorphisms.

{{PMID|19493349|OA=1
}} 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects.

{{PMID|19706844}} Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis.

{{PMID|19808787|OA=1
}} Genetics of human neural tube defects.

{{PMID|20018050|OA=1
}} Application of sex-specific single-nucleotide polymorphism filters in genome-wide association data.

{{PMID|20565774|OA=1
}} Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.

{{PMID|20890936}} Maternal polymorphisms in folic acid metabolic genes are associated with nonsyndromic cleft lip and/or palate in the Brazilian population.

{{PMID|21349258}} Folate and choline metabolism gene variants and development of uterine cervical carcinoma.

{{PMID|21688148|OA=1
}} Polymorphic variants of genes involved in homocysteine metabolism in celiac disease.

{{PMID|22183302}} Folate and choline metabolism gene variants in relation to ovarian cancer risk in the Polish population.

{{GET Evidence
|gene=MTHFD1
|aa_change=Arg653Gln
|aa_change_short=R653Q
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs2236225
|overall_frequency_n=4043
|overall_frequency_d=10758
|overall_frequency=0.375813
|n_genomes=30
|n_genomes_annotated=0
|n_haplomes=40
|n_articles=1
|n_articles_annotated=1
|qualityscore_in_silico=3
|qualitycomment_in_silico=Y
|in_omim=Y
|in_pharmgkb=Y
|pph2_score=0.008
|nblosum100=0
|autoscore=2
|webscore=N
}}

{{PMID Auto
|PMID=24254627
|Title=MTHFR rs2274976 polymorphism is a risk marker for nonsyndromic cleft lip with or without cleft palate in the brazilian population
}}

{{PMID Auto
|PMID=22903727
|Title=Maternal and infant gene-folate interactions and the risk of neural tube defects.
|OA=1
}}

{{PMID Auto
|PMID=25039261
|Title=Association Study of MTHFD1 Coding Polymorphisms R134K and R653Q With Migraine Susceptibility
}}

{{PMID Auto
|PMID=25074646
|Title=Associations of Common Variants in Methionine Metabolism Pathway Genes with Plasma Homocysteine and the Risk of Type 2 Diabetes in Han Chinese
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Affy GenomeWide 6}}
{{on chip | FTDNA2}}
{{on chip | FTDNA}}
{{on chip | Illumina Human 1M}}