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Mthfr methylenetetrahydrofolate reductase [ Mus musculus (house mouse) ]

Gene ID: 17769, updated on 2-Nov-2024

Summary

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Official Symbol
Mthfrprovided by MGI
Official Full Name
methylenetetrahydrofolate reductaseprovided by MGI
Primary source
MGI:MGI:106639
See related
Ensembl:ENSMUSG00000029009 AllianceGenome:MGI:106639
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Summary
Enables methylenetetrahydrofolate reductase (NAD(P)H) activity. Acts upstream of or within methionine biosynthetic process. Is expressed in several structures, including central nervous system; cranium; heart; sensory organ; and testis. Used to study neural tube defect. Human ortholog(s) of this gene implicated in several diseases, including autoimmune disease (multiple); carcinoma (multiple); cardiovascular system disease (multiple); hematologic cancer (multiple); and liver disease (multiple). Orthologous to human MTHFR (methylenetetrahydrofolate reductase). [provided by Alliance of Genome Resources, Nov 2024]
Expression
Ubiquitous expression in ovary adult (RPKM 9.7), testis adult (RPKM 8.0) and 28 other tissues See more
Orthologs
human all
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Genomic context

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See Mthfr in Genome Data Viewer
Location:
4 E1; 4 78.67 cM
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 4 NC_000070.7 (148123534..148144019)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 4 NC_000070.6 (148039077..148059562)

Chromosome 4 - NC_000070.7Genomic Context describing neighboring genes Neighboring gene natriuretic peptide type A Neighboring gene chloride channel, voltage-sensitive 6 Neighboring gene STARR-seq mESC enhancer starr_12064 Neighboring gene NSA2 ribosome biogenesis homolog pseudogene Neighboring gene Mthfr promoter region Neighboring gene predicted gene 13201 Neighboring gene STARR-positive B cell enhancer ABC_E6283 Neighboring gene coiled-coil-helix-coiled-coil-helix domain containing 2, pseudogene Neighboring gene STARR-positive B cell enhancer ABC_E4727 Neighboring gene STARR-seq mESC enhancer starr_12067 Neighboring gene angiotensin II, type I receptor-associated protein Neighboring gene STARR-seq mESC enhancer starr_12068

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. Stability of DNA methylation patterns in mouse spermatogonia under conditions of MTHFR deficiency and methionine supplementation. Garner JL, et al. Biol Reprod, 2013 Nov. PMID 24048573
  2. Strain-specific defects in testicular development and sperm epigenetic patterns in 5,10-methylenetetrahydrofolate reductase-deficient mice. Chan D, et al. Endocrinology, 2010 Jul. PMID 20444942
  3. Sex-dependent behavioral effects of Mthfr deficiency and neonatal GABA potentiation in mice. Levav-Rabkin T, et al. Behav Brain Res, 2011 Jan 20. PMID 20813139
  4. Susceptibility to intestinal tumorigenesis in folate-deficient mice may be influenced by variation in one-carbon metabolism and DNA repair. Knock E, et al. J Nutr Biochem, 2011 Nov. PMID 21193302
  5. Gender-specific effect of Mthfr genotype and neonatal vigabatrin interaction on synaptic proteins in mouse cortex. Blumkin E, et al. Neuropsychopharmacology, 2011 Jul. PMID 21490592, Free PMC Article

See all (112) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Folate Deficiency and/or the Genetic Variant Mthfr[677C >T] Can Drive Hepatic Fibrosis or Steatosis in Mice, in a Sex-Specific Manner.
    Title: Folate Deficiency and/or the Genetic Variant Mthfr(677C >T) Can Drive Hepatic Fibrosis or Steatosis in Mice, in a Sex-Specific Manner.
  2. Mild methylenetetrahydrofolate reductase deficiency accelerates liver triacylglycerol and uric acid accumulation in fructose-fed mice.
    Title: Mild methylenetetrahydrofolate reductase deficiency accelerates liver triacylglycerol and uric acid accumulation in fructose-fed mice.
  3. MTHFR epigenetic derepression protects against diabetes cardiac fibrosis.
    Title: MTHFR epigenetic derepression protects against diabetes cardiac fibrosis.
  4. The 677C > T variant in methylenetetrahydrofolate reductase causes morphological and functional cerebrovascular deficits in mice.
    Title: The 677C > T variant in methylenetetrahydrofolate reductase causes morphological and functional cerebrovascular deficits in mice.
  5. SIRT1 pharmacological activation rescues vascular dysfunction and prevents thrombosis in MTHFR deficiency.
    Title: SIRT1 pharmacological activation rescues vascular dysfunction and prevents thrombosis in MTHFR deficiency.
  6. Paternal MTHFR deficiency leads to hypomethylation of young retrotransposons and reproductive decline across two successive generations.
    Title: Paternal MTHFR deficiency leads to hypomethylation of young retrotransposons and reproductive decline across two successive generations.
  7. Maternal and offspring Mthfr genotypes interact in a mouse model to induce autism spectrum disorder-like behavior.
    Title: Maternal and offspring methylenetetrahydrofolate-reductase genotypes interact in a mouse model to induce autism spectrum disorder-like behavior.
  8. The data suggest that MTHFR deficiency decreases recovery after stroke by reducing neuronal and astrocyte viability.
    Title: A genetic deficiency in folic acid metabolism impairs recovery after ischemic stroke.
  9. data provide evidence for a similar cross-species response to high dose folic acid supplementation, of sperm DNA hypomethylation, and implicate MTHFR downregulation as a possible mechanism.
    Title: Testicular MTHFR deficiency may explain sperm DNA hypomethylation associated with high dose folic acid supplementation.
  10. findings indicate that the loss of folate as a methyl donor is a modifier of allergic airway disease, and that epigenetic and expression changes correlate with this modification.
    Title: Methylene-tetrahydrofolate reductase contributes to allergic airway disease.
Submit: New GeneRIF Correction See all GeneRIFs (39)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)

Pathways from PubChem

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General gene information

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Markers

Homology

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables FAD binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables NADP binding ISO
Inferred from Sequence Orthology
more info
  
enables flavin adenine dinucleotide binding ISO
Inferred from Sequence Orthology
more info
  
enables methylenetetrahydrofolate reductase (NAD(P)H) activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables methylenetetrahydrofolate reductase (NAD(P)H) activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables methylenetetrahydrofolate reductase (NAD(P)H) activity ISO
Inferred from Sequence Orthology
more info
  
enables methylenetetrahydrofolate reductase (NAD(P)H) activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables methylenetetrahydrofolate reductase (NADPH) activity IEA
Inferred from Electronic Annotation
more info
  
enables modified amino acid binding ISO
Inferred from Sequence Orthology
more info
  
enables protein-containing complex binding ISO
Inferred from Sequence Orthology
more info
  
Process Evidence Code Pubs
acts_upstream_of heterochromatin organization ISO
Inferred from Sequence Orthology
more info
  
involved_in homocysteine metabolic process ISO
Inferred from Sequence Orthology
more info
  
involved_in methionine biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within methionine biosynthetic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in methionine metabolic process ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of neural tube closure ISO
Inferred from Sequence Orthology
more info
  
involved_in tetrahydrofolate interconversion IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in tetrahydrofolate interconversion IEA
Inferred from Electronic Annotation
more info
  
involved_in tetrahydrofolate interconversion ISO
Inferred from Sequence Orthology
more info
  
involved_in tetrahydrofolate interconversion ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in tetrahydrofolate metabolic process ISO
Inferred from Sequence Orthology
more info
  

General protein information

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Preferred Names
methylenetetrahydrofolate reductase (NADPH)
Names
5,10-methylenetetrahydrofolate reductase
NP_001155270.1
NP_034970.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001161798.1 → NP_001155270.1  methylenetetrahydrofolate reductase (NADPH) isoform a

    See identical proteins and their annotated locations for NP_001155270.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (a).
    Source sequence(s)
    AK150159, BB726553, BC100550
    Consensus CDS
    CCDS51376.1
    UniProtKB/TrEMBL
    A2A7F7, Q3UDB2
    Related
    ENSMUSP00000069774.9, ENSMUST00000069604.15
    Conserved Domains (1) summary
    cl00246
    Location:100 → 666
    MTHFR; Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to 5-methyltetrahydrofolate by methylenetetrahydrofolate reductase, a cytoplasmic, NAD(P)-dependent enzyme. 5-methyltetrahydrofolate is utilized by methionine synthase ...

  2. NM_010840.3 → NP_034970.2  methylenetetrahydrofolate reductase (NADPH) isoform b

    See identical proteins and their annotated locations for NP_034970.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream translational start codon, compared to variant 1. The encoded isoform (b) is shorter at the N-terminus, compared to isoform a.
    Source sequence(s)
    AK030192, AL606929, BB726553, BC100550
    Consensus CDS
    CCDS18929.1
    UniProtKB/Swiss-Prot
    Q8CDE4, Q9WU20
    UniProtKB/TrEMBL
    F6Z4F8
    Related
    ENSMUSP00000095395.5, ENSMUST00000097788.11
    Conserved Domains (1) summary
    cl00246
    Location:59 → 625
    MTHFR; Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to 5-methyltetrahydrofolate by methylenetetrahydrofolate reductase, a cytoplasmic, NAD(P)-dependent enzyme. 5-methyltetrahydrofolate is utilized by methionine synthase ...

RNA

  1. NR_027809.1 RNA Sequence

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) lacks a segment of the 3' region, compared to variant 1. This variant has an intact ORF compared to variant 1, but it is represented as non-coding because it is a nonsense-mediated mRNA decay (NMD) candidate due to the presence of an intron at the 3' end.
    Source sequence(s)
    AK149795, AK150159, BB726553, BC100550

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000070.7 Reference GRCm39 C57BL/6J

    Range
    148123534..148144019
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9WU20.2 GenPept UniProtKB/Swiss-Prot:Q9WU20

Gene LinkOut

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