{{Rsnum
|rsid=1801394
|Gene=MTRR
|Chromosome=5
|position=7870860
|Orientation=plus
|ReferenceAllele=A
|MissenseAllele=G
|GMAF=0.376
|Gene_s=FASTKD3,MTRR
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 36.5 | 34.9 | 28.6
| HCB | 54.5 | 40.9 | 4.5
| JPT | 53.5 | 32.6 | 14.0
| YRI | 59.0 | 36.1 | 4.9
| ASW | 0.0 | 0.0 | 0.0
| CHB | 54.5 | 40.9 | 4.5
| CHD | 0.0 | 0.0 | 0.0
| GIH | 0.0 | 0.0 | 0.0
| LWK | 0.0 | 0.0 | 0.0
| MEX | 0.0 | 0.0 | 0.0
| MKK | 0.0 | 0.0 | 0.0
| TSI | 0.0 | 0.0 | 0.0
| HapMapRevision=28
}}
[[rs1801394]], also known as A66G or Ile22Met, is a SNP in the methionine synthase [[MTRR]] gene. This gene encodes one of the two enzymes involved in the production of methionine (the other is [[MTR]]). The protein encoded by an [[rs1801394]] allele has a lower affinity for MTR ({{PMID|12416982}}) and is inconsistently associated with homocysteine level, although it is a risk factor for neural tube defects ({{PMID|10444342}}) and Down syndrome ({{PMID|10930360|OA=1
}}) in conditions of higher homocysteine.

Based on a study of British patients with primary brain tumors, (1,005 glioma cases and 631 meningioma cases), [[rs1801394]](G;G) individuals were at higher risk for meningioma (odds ratio 1.41, CI: 1.02-1.94). In general, genotypes associated with increased 5,10-methylenetetrahydrofolate levels are associated with elevated risk for these types of brain [[cancer]].{{PMID|18483342}}

{{Venter SNP
|rsid=1801394
|allele=G
|frequency=
|uid=1103654018638
|type=heterozygous_SNP
|hugo=MTRR
|ensembl gene=ENSG00000124275
|ensembl transcript=ENST00000264668
|sift=TOLERATED
|disease=Defects in MTRR are the cause of methylcobalamin deficiency type E (cblE) (MIM:236270); also known as vitamin B12- responsive homocystinuria or homocystinuria-megaloblastic anemia complementation type E. Patients who are defective in reductive activation of methionine synthase exhibit megaloblastic anemia, developmental delay, hypomethioninemia, and hyperhomocysteinemia, a risk factor in cardiovascular disease and neural tube defects. It is an autosomal recessive disease.
}}

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

{{PMID Auto
|PMID=18682255
|Title=Arsenic metabolism is influenced by polymorphisms in genes involved in one-carbon metabolism and reduction reactions
}}

{{PMID Auto
|PMID=20883119
|Title=Common polymorphisms in six genes of the methyl group metabolism pathway and obesity in European adolescents
}}

{{PharmGKB
|RSID=rs1801394
|Name_s=MTRR:66A>G; MTRR 66A>G
|Gene_s=MTRR, FASTKD3
|Feature=
|Evidence=PubMed ID:17024475
|Annotation=Risk or phenotype-associated allele: G Phenotype: Maternal MTRR 66GG genotype was associated with an overall increase in Spina bifida risk. Study size: 413 Study population/ethnicity: Mothers with a child affected by Spina Bifida and control women; Netherlands Significance metric(s): OR= 2.1 (95% CI 1.3-3.3) Type of association: CO
|Drugs=
|Drug Classes=
|Diseases=Neural Tube Defects; Spina Bifida Cystica
|Curation Level=Curated
|PharmGKB Accession ID=PA165223225
}}
{{PMID Auto
|PMID=21211571
|Title=MTHFR and MTRR genotype and haplotype analysis and colorectal cancer susceptibility in a case-control study from the Czech Republic
}}

{{omim
|id=602568
|rsnum=1801394
|variant=0003
}}

{{PMID Auto
|PMID=22005284
|Title=Importance of gene variants and co-factors of folate metabolic pathway in the etiology of idiopathic intellectual disability
}}

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

{{PMID Auto
|PMID=22796266
|Title=Polymorphisms of tumor-related genes IL-10, PSCA, MTRR and NOC3L are associated with the risk of gastric cancer in the Chinese Han population
}}

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

{{PMID|18191955|OA=1
}} Correlating observed odds ratios from lung cancer case-control studies to SNP functional scores predicted by bioinformatic tools.

{{PMID|18199722}} Dietary vitamin B6 intake and the risk of colorectal cancer.

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

{{PMID|18521744|OA=1
}} BRCA1 promoter methylation is associated with increased mortality among women with breast cancer.

{{PMID|18708404|OA=1
}} B-vitamin intake, one-carbon metabolism, and survival in a population-based study of women with breast cancer.

{{PMID|18708408|OA=1
}} Vitamins B2, B6, and B12 and risk of new colorectal adenomas in a randomized trial of aspirin use and folic acid supplementation.

{{PMID|18936436|OA=1
}} Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.

{{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|19336559|OA=1
}} Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors.

{{PMID|19376481|OA=1
}} One-carbon metabolism and breast cancer: an epidemiological perspective.

{{PMID|19657388|OA=1
}} Lack of association between genetic polymorphisms in enzymes associated with folate metabolism and unexplained reduced sperm counts.

{{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|19776626|OA=1
}} Polymorphisms in methionine synthase, methionine synthase reductase and serine hydroxymethyltransferase, folate and alcohol intake, and colon cancer risk.

{{PMID|20852008}} Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer.

{{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.

{{ClinVar
|rsid=1801394
|Reversed=0
|FwdREF=A
|FwdALT=G
|REF=A
|ALT=G
|RSPOS=7870973
|CHROM=5
|GMAF=0.3768
|dbSNPBuildID=89
|SSR=0
|SAO=1
|VP=0x05017800000017051f110100
|GENEINFO=MTRR:4552; FASTKD3:79072
|GENE_NAME=MTRR; FASTKD3
|GENE_ID=4552; 79072
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000005.9:g.7870973A>G
|CLNORIGIN=1
|CLNSIG=255
|Tags=PM;TPA;PMC;SLO;VLD;G5A;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;OM
|CAF=0.624; 0.376
|CLNACC=RCV000007444.1; RCV000007445.1
|CLNDBN=Neural tube defects, folate-sensitive, susceptibility to; Down syndrome, susceptibility to
|CLNSRC=OMIM Allelic Variant
|CLNSRCID=602568.0003
|COMMON=1
|Disease=Neural tube defects; Down syndrome
}}

{{GET Evidence
|gene=MTRR
|aa_change=Ile49Met
|aa_change_short=I49M
|impact=pathogenic
|qualified_impact=Low clinical importance, Likely pathogenic
|inheritance=recessive
|quality_scores=Array
|dbsnp_id=rs1801394
|overall_frequency_n=4854
|overall_frequency_d=10758
|overall_frequency=0.451199
|n_genomes=33
|n_genomes_annotated=0
|n_haplomes=43
|n_articles=7
|n_articles_annotated=7
|qualityscore_in_silico=3
|qualitycomment_in_silico=Y
|qualityscore_case_control=3
|qualitycomment_case_control=Y
|qualityscore_familial=0
|qualityscore_severity=4
|qualitycomment_severity=Y
|qualityscore_treatability=2
|qualitycomment_treatability=Y
|gene_in_genetests=Y
|in_pharmgkb=Y
|genetests_testable=Y
|genetests_reviewed=Y
|nblosum100=-1
|autoscore=4
|webscore=N
|n_web_uneval=5
|variant_evidence=0
|clinical_importance=1
|summary_short=This common variant (HapMap allele frequency of 31.3%) in a protein involved in folate (B9) and cobalamin (B12) metabolism and is often reported as "MTRR I22M" (an alternative transcript position). Mothers homozygous for this variant are associated with having around a increased chance of a child with Down syndrome (risk of 0.4%, average risk in population is 0.25%). Notably, age plays a far larger role in the rate of Down syndrome (risk is 4.5% for a mother 45-years-of-age), and it is unknown how this variant may combine with the effect of age. There are conflicting reports associating this variant with incidence of neural tube defects, possibly when combined with MTHFR A222V.
}}

{{PMID Auto
|PMID=23401104
|Title=Folate-genetics and colorectal neoplasia: what we know and need to know next
}}

{{PMID Auto
|PMID=24261678
|Title=MTRR A66G polymorphism and leukemia risk: evidence from published studies
}}

{{PMID Auto
|PMID=22021659
|Title=Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia.
|OA=1
}}

{{PMID Auto
|PMID=22706675
|Title=Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE).
}}

{{PMID Auto
|PMID=23560644
|Title=Polymorphisms in genes involved in the free-radical process in patients with sudden sensorineural hearing loss and Meniere's disease.
}}

{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | FTDNA}}
{{on chip | HumanOmni1Quad}}