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    Mthfr methylenetetrahydrofolate reductase [ Mus musculus (house mouse) ]

    Gene ID: 17769, updated on 9-Dec-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, Dec 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
    • 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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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