rs10380

badMag 3.8

This is a variant in the MTRR gene that changes a histidine to an tyrosine.

Key Literature Trait Associations

Congenital heart disease

The rs10380 TT genotype was associated with significantly increased risk of congenital heart disease (CHD) in offspring in a Han Chinese case-control study (OR 2.27, 95% CI: 1.20–4.31 for TT vs. CC). Maternal folic acid supplementation during pregnancy was associated with reduced CHD risk overall (OR 0.55), suggesting that the elevated risk conferred by rs10380 may be partially mitigated by adequate periconceptional folate intake. The association is consistent with MTRR's role in folate-dependent cardiac morphogenesis.

Li L et al. “Association of maternal folic acid supplementation and offspring MTRR gene polymorphism with congenital heart disease: a hospital-based case-control study in Han population.” Journal of Health, Population, and Nutrition (2024)
Allele T
OR 2.27
p —
N 1,200
Preliminary work
Han Chinese

Pancreatic cancer

The rs10380 His595Tyr variant in MTRR was significantly associated with pancreatic cancer susceptibility in a Japanese case-control study. Carriers of the risk allele showed an odds ratio of 1.45 (95% CI: 1.11–1.88, p=0.0063) in joint analysis. The association was significant under a recessive model after correction testing (p=0.023). Functional follow-up confirmed that risk haplotype cells had elevated homocysteine and reduced DNA methylation, suggesting impaired one-carbon metabolism as the mechanistic basis for increased cancer risk.

Ohnami S et al. “His595Tyr polymorphism in the methionine synthase reductase (MTRR) gene is associated with pancreatic cancer risk.” Gastroenterology (2008)
Allele T
OR 1.45
p 6.3e-3
N 1,549
Preliminary work
Japanese

Methionine Synthase Reductase Activity

The MTRR H595Y variant (rs10380) is a missense polymorphism (His595Tyr) in methionine synthase reductase. The T allele changes a histidine to tyrosine residue. This variant is less well-studied than MTRR A66G (rs1801394) and has not shown consistent independent associations with homocysteine levels or disease risk in published studies.

Ohnami S et al. “His595Tyr polymorphism in the methionine synthase reductase (MTRR) gene is associated with pancreatic cancer risk.” Gastroenterology (2008)
Allele T
OR —
p —
N 1,549
Preliminary work
Japanese
Laraqui A et al. “Influence of methionine synthase (A2756G) and methionine synthase reductase (A66G) polymorphisms on plasma homocysteine levels and relation to risk of coronary artery disease.” Acta Cardiologica 61(1):51-61 (2006)
Allele T
OR —
p 8.0e-2
Candidate gene study

Spina bifida

A large candidate-gene study of 118 folate-related SNPs found that rs10380 in MTRR was associated with spina bifida risk (OR 3.4, 95% CI: 1.6–7.1) in a California-based population. However, the authors noted that multiple SNPs in linkage disequilibrium contributed, and no single gene was strongly implicated. The finding should be interpreted cautiously given the study's exploratory nature and lack of replication in independent cohorts for this specific SNP.

Shaw GM et al. “118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects.” Bmc Medical Genetics (2009)
Allele T
OR 3.40
p —
N 832
Preliminary work
European

Antipsychotic treatment response

rs10380 (reported as H622Y in an alternative transcript) was identified as a novel pharmacogenomic variant associated with differential antipsychotic treatment outcomes in first-episode schizophrenia patients in two South African cohorts (discovery n=103, replication n=87). The variant was predicted computationally to impair MTRR protein function and showed consistent effects across multiple antipsychotic drug classes. The study was small and the finding requires replication in larger, diverse populations before clinical application.

“The identification of novel genetic variants associated with antipsychotic treatment response outcomes in first-episode schizophrenia patients”
Allele T
OR —
p —
N 190
Candidate gene study
South African
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ClinVar annotation

Uncertain Significance★★★☆
10 submitters3 publications

Disorders of Intracellular Cobalamin Metabolism; Gastrointestinal stromal tumor; Methylcobalamin deficiency type cblE (HMAE); not specified

View on ClinVar →
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Research that mentions this SNP (2)

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Gene‐by‐gene interactions associated with the risk of conotruncal heart defects
AssociationN=414Chen Lyu et al.(2020)· Molecular Genetics & Genomic Medicine

This gene-by-gene interaction study of conotruncal heart defects (CTDs) identified one significant SNP pair (rs4764267 in MGST1 and rs6556883 in GLRX) with adjusted p-value of 0.04, and another marginally significant pair (rs11892646 in DNMT3A and rs56219526 in MTRR) with adjusted p-value of 0.06. The analysis combined sequencing (328 case-parental triads) and microarray (86 triads) data, with both SNP pairs located in genes involved in transsulfuration and homocysteine metabolism pathways.

Traits studied:Conotruncal heart defects
PubMedDOIMetascience Observatory
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Association of main folate metabolic pathway gene polymorphisms with neural tube defects in Han population of Northern China
AssociationN=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.

Traits studied:NTDsNeural tube defects
PubMedDOIMetascience Observatory

Gene information from NCBI Gene. Variant classifications from ClinVar.

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