MTHFR E429A - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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(MTHFR Glu429Ala)

Short summary


Variant evidence
Computational -

SIFT: Affect protein function
GVGD: GV 0.00; GD 106.71; Class C65
Variant Effect Predictor (Ensembl ):
Mutation Tasting prediction: Polymorphism p value: 0.003380; no protein features affected.

Functional -
Case/Control -
Familial -
Clinical importance
Severity -
Treatability -
Penetrance -


Insufficiently evaluated pharmacogenetic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern


Summary of published research, and additional commentary


Allele frequency

  • G @ chr1:11854476: 25.5% (2748/10758) in EVS
  • G @ chr1:11777062: 24.2% (31/128) in GET-Evidence
  • Frequency shown in summary reports: 25.5% (2748/10758)


Shen H, Newmann AS, Hu Z, Zhang Z, Xu Y, Wang L, Hu X, Guo J, Wang X, Wei Q. Methylenetetrahydrofolate reductase polymorphisms/haplotypes and risk of gastric cancer: a case-control analysis in China. Oncol Rep. 2005 Feb;13(2):355-60. PubMed PMID: 15643524.


Wessels JA, de Vries-Bouwstra JK, Heijmans BT, Slagboom PE, Goekoop-Ruiterman YP, Allaart CF, Kerstens PJ, van Zeben D, Breedveld FC, Dijkmans BA, Huizinga TW, Guchelaar HJ. Efficacy and toxicity of methotrexate in early rheumatoid arthritis are associated with single-nucleotide polymorphisms in genes coding for folate pathway enzymes. Arthritis Rheum. 2006 Apr;54(4):1087-95. PubMed PMID: 16572443.


Nagele P, Zeugswetter B, Wiener C, Burger H, Hüpfl M, Mittlböck M, Födinger M. Influence of methylenetetrahydrofolate reductase gene polymorphisms on homocysteine concentrations after nitrous oxide anesthesia. Anesthesiology. 2008 Jul;109(1):36-43. PubMed PMID: 18580170.


Warren RB, Smith RL, Campalani E, Eyre S, Smith CH, Barker JN, Worthington J, Griffiths CE. Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms. Br J Dermatol. 2009 Feb;160(2):438-41. Epub 2008 Oct 25. PubMed PMID: 19016697; PubMed Central PMCID: PMC2680291.




hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het G @ chr1:11854476


hu0D879F - CGI sample GS00253-DNA_G01_200_37
hom G @ chr1:11854476









hu43860C - CGI sample GS00253-DNA_A01_200_37
het G @ chr1:11854476








huAE6220 - CGI sample GS00253-DNA_H01_200_37
het G @ chr1:11854476


huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het G @ chr1:11854476


huC30901 - CGI sample GS00253-DNA_B01_200_37
het G @ chr1:11854476



huE80E3D - CGI sample GS00253-DNA_D01_200_37
het G @ chr1:11854476



GS06985 - var-GS06985-1100-36-ASM
het G @ chr1:11777063


GS06994 - var-GS06994-1100-36-ASM
hom G @ chr1:11777063


GS18526 - var-GS18526-1100-36-ASM
hom G @ chr1:11777063


GS18555 - var-GS18555-1100-36-ASM
het G @ chr1:11777063


GS18956 - var-GS18956-1100-36-ASM
het G @ chr1:11777063


GS19669 - var-GS19669-1100-36-ASM
het G @ chr1:11777063


GS19700 - var-GS19700-1100-36-ASM
het G @ chr1:11777063


GS19704 - var-GS19704-1100-36-ASM
het G @ chr1:11777063


Other external references

  • rs1801131
  • [folic acid; methotrexate]
    Well studied, associated with multiple phenotypes.
  • [Stomach Neoplasms]
    In a case control study of Asian gastric cancer (n=633), individuals with 6 variant alleles of three MTHFR common variants (i.e. C677T, A1298C and G1793A) were at increased risk for gastric cardia adenocarcinoma (OR =4.64, 95% CI =1.34-16.01) compared with those having 0-2 variants.
  • [Arthritis, Rheumatoid]
    [folic acid; methotrexate]
    At 6 months methotrexate and folic acid therapy, of early rheumatoid arthritis patients with the MTHFR 1298AA genotype showed good improvement relative to combined CA and AA genotypes (OR 2.3), while 1298C allele carriers developed more adverse drug events (OR 2.5) (e.g. pneumonitis, gastrointestinal ADEs, skin and mucosal ADEs, and elevated liver enzyme levels). Patients with MTHFR 1298AA / 677CC diplotype showed greater clinical improvement.
  • [Psoriasis]
    [folic acid; methotrexate]
    In 330 patients who completed 3 months methotrexate treatment for psoriasis, no significant genotypic associations were found between clinical outcome (e.g. efficacy, toxicity) and 50 SNPs in pathway genes for methotrexate metabolism (ATIC, FPGS, GGH, MTHFR), including 47 common ( >5% minor allele frequency) haplotype-tagging SNPs (r(2) > 0.8) plus 3 additional SNPs.
  • [nitrous oxide]
    Risk or phenotype-associated allele(s): C/C. Phenotype:Patients with a homozygous MTHFR 1298A>C mutation (n = 25) developed higher plasma homocysteine concentrations (median [interquartile range], 14.9 [10.0-26.4] microm) than wild-type or heterozygous patients (9.3 [7.5-15.5] microm; n = 115). The change in homocysteine after nitrous oxide anesthesia was tripled in homozygous patients compared with wild-type (5.6 microm [+60%] vs. 1.8 microm [+22%]). Study size: 140. Study population/ethnicity: healthy patients undergoing elective surgery. Type of association: GN.
  • Score: 0.099 (benign)
    Web search results (233 hits -- see all)
  • MTHFR - SNPedia
    The MTHFR gene encodes the vitamin-dependent enzyme, methylenetetrahydrofolate reductase. ... rs1801131, also known as E429A. rs2274976, also known as R594Q. It is ...
  • _115N7_Science_989-1106
    T) polymorphism in the MTHFR gene, body mass index, and sex are major factors ... MTHFR E429A (A. C) F: GGAGGAGCTGCTGAAGATGTG. VIC: ACCAGTGAAGAAAGTGT. F: ...
  • PLoS ONE: Lack of Association between Genetic Polymorphisms ...
    PLoS ONE: an inclusive, peer-reviewed, open-access resource from the PUBLIC LIBRARY OF ... The frequency of the MTHFR c.1286A>C (p.E429A) variant allele also differs across ...
  • The variant methylenetetrahydrofolate reductase c.1298A>C (p ...
    ... of two missense variants of the MTHFR gene, i.e. MTHFR c.677C>T (p.A222V) and c.1298A>C (p.E429A), in 138 patients with clinically definite multiple ...
  • Nanogen
    MTHFR A1298C Q - PCR Alert Kit is a qualitative nucleic acids ... reductase (MTHFR) protein for single nucleotide polymorphism (SNP) A1298C (E429A). This technique ...
  • Accurate and Rapid "Multiplex Heteroduplexing" Method for ...
    Three other polymorphisms [A1298C (E429A) in MTHFR, A2756G (D919G) in MS, and a ... For both MTHFR C677T and MS A2756G, partial digestion or digestion failure leads ...
  • University of Colorado DNA Diagnostic Laboratory: Tests
    Please contact the laboratory for prices: 303-724-3801, ... RC-1 North, Rm P18-4404J, 12800 E. 19th Ave, Aurora, CO 80045. Mailing ...
  • The prevalence of folate-remedial MTHFR enzyme variants in humans
    The prevalence of folate-remedial MTHFR enzyme variants in humans. ... For A222V combinations with common variants (A222V E429A and A222V R594Q), we observed minor allele ...
  • Rs1801131 - SNPedia
    rs1801131 is a SNP in the MTHFR gene, representing an A>C mutation at mRNA ... to-ala (E429A) substitution (hence this SNP is also known as A1298C or E429A) ...
    There is suggestion that not only neural tube defects (NTDs) but ... genes important in folate metabolism and uptake (MTHFR A222V and E429A, MTRR I22M, RFC-1 H27R, BHMT R239Q, ...

Other in silico analyses

  • NBLOSUM100 score = 3
  • GET-Evidence autoscore = 3

Edit history

Gene search

"GENE" or "GENE A123C":

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