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    MTHFR methylenetetrahydrofolate reductase [ Homo sapiens (human) ]

    Gene ID: 4524, updated on 25-Sep-2022

    Summary

    Official Symbol
    MTHFRprovided by HGNC
    Official Full Name
    methylenetetrahydrofolate reductaseprovided by HGNC
    Primary source
    HGNC:HGNC:7436
    See related
    Ensembl:ENSG00000177000 MIM:607093; AllianceGenome:HGNC:7436
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Summary
    The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.[provided by RefSeq, Oct 2009]
    Expression
    Ubiquitous expression in lung (RPKM 7.5), thyroid (RPKM 7.2) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See MTHFR in Genome Data Viewer
    Location:
    1p36.22
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    110 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (11785723..11805964, complement)
    110 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (11329802..11350048, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (11845780..11866021, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene atrophin-1-like Neighboring gene chromosome 1 open reading frame 167 Neighboring gene C1orf167 antisense RNA 1 Neighboring gene chloride voltage-gated channel 6 Neighboring gene NPPA antisense RNA 1 Neighboring gene VISTA enhancer hs2123 Neighboring gene natriuretic peptide A

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Homocystinuria due to methylene tetrahydrofolate reductase deficiency
    MedGen: C1856058 OMIM: 236250 GeneReviews: Not available
    Compare labs
    Neural tube defects, folate-sensitive
    MedGen: C1866558 OMIM: 601634 GeneReviews: Not available
    Compare labs
    Schizophrenia
    MedGen: C0036341 OMIM: 181500 GeneReviews: Not available
    Compare labs
    Thrombophilia due to thrombin defect
    MedGen: C3160733 OMIM: 188050 GeneReviews: Prothrombin Thrombophilia
    Compare labs

    EBI GWAS Catalog

    Description
    Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.
    EBI GWAS Catalog
    Genome-wide association study identifies eight loci associated with blood pressure.
    EBI GWAS Catalog
    Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.
    EBI GWAS Catalog
    Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway.
    EBI GWAS Catalog
    Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma homocysteine in a healthy population: a genome-wide evaluation of 13 974 participants in the Women's Genome Health Study.
    EBI GWAS Catalog
    Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry.
    EBI GWAS Catalog

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in S-adenosylmethionine metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of heterochromatin organization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in homocysteine metabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in methionine biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in methionine metabolic process IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    acts_upstream_of neural tube closure IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    acts_upstream_of neural tube closure NAS
    Non-traceable Author Statement
    more info
    PubMed 
    acts_upstream_of regulation of histone methylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to amino acid IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to folic acid IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to hypoxia IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to interleukin-1 IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to vitamin B2 IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to xenobiotic stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in tetrahydrofolate interconversion IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in tetrahydrofolate interconversion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in tetrahydrofolate interconversion IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in tetrahydrofolate interconversion IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in tetrahydrofolate interconversion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in synapse IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    methylenetetrahydrofolate reductase
    Names
    5,10-methylenetetrahydrofolate reductase (NADPH)
    methylenetetrahydrofolate reductase (NAD(P)H)
    NP_001317287.1
    NP_005948.3
    XP_005263519.1
    XP_005263520.1
    XP_011539797.1
    XP_011539798.1
    XP_016856817.1
    XP_047277130.1
    XP_047277134.1
    XP_047277135.1
    XP_047277136.1
    XP_047277137.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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.

    Genomic

    1. NG_013351.1 RefSeqGene

      Range
      5001..25374
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_726

    mRNA and Protein(s)

    1. NM_001330358.2NP_001317287.1  methylenetetrahydrofolate reductase isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AL953897
      Consensus CDS
      CCDS81262.1
      UniProtKB/Swiss-Prot
      P42898
      Related
      ENSP00000365767.3, ENST00000376583.7
    2. NM_001410750.1NP_001397679.1  methylenetetrahydrofolate reductase isoform 3

      Status: REVIEWED

      Source sequence(s)
      AL953897
    3. NM_005957.5NP_005948.3  methylenetetrahydrofolate reductase isoform 2

      See identical proteins and their annotated locations for NP_005948.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.
      Source sequence(s)
      AB209113, AJ237672, AL953897, AY046560, BC053509
      Consensus CDS
      CCDS137.1
      UniProtKB/Swiss-Prot
      P42898, Q9UQR2
      UniProtKB/TrEMBL
      Q59GJ6, Q8IU67
      Related
      ENSP00000365775.3, ENST00000376590.9
      Conserved Domains (1) summary
      cl00246
      Location:60626
      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 ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 110 details...Open this link in a new tab

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      11785723..11805964 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047421181.1XP_047277137.1  methylenetetrahydrofolate reductase isoform X7

    2. XM_005263462.5XP_005263519.1  methylenetetrahydrofolate reductase isoform X4

      See identical proteins and their annotated locations for XP_005263519.1

      UniProtKB/Swiss-Prot
      P42898, Q9UQR2
      Conserved Domains (1) summary
      cl00246
      Location:60626
      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 ...
    3. XM_047421179.1XP_047277135.1  methylenetetrahydrofolate reductase isoform X6

      UniProtKB/TrEMBL
      A0A286YFD0
      Related
      ENSP00000493098.1, ENST00000641407.1
    4. XM_047421180.1XP_047277136.1  methylenetetrahydrofolate reductase isoform X7

      Related
      ENSP00000493262.1, ENST00000641446.1
    5. XM_047421178.1XP_047277134.1  methylenetetrahydrofolate reductase isoform X4

      UniProtKB/Swiss-Prot
      Q9UQR2
      Related
      ENSP00000365777.1, ENST00000376592.6
    6. XM_047421174.1XP_047277130.1  methylenetetrahydrofolate reductase isoform X3

    7. XM_011541495.4XP_011539797.1  methylenetetrahydrofolate reductase isoform X1

      UniProtKB/TrEMBL
      Q5SNW7
      Related
      ENSP00000398908.3, ENST00000423400.7
      Conserved Domains (1) summary
      cl00246
      Location:100666
      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 ...
    8. XM_011541496.4XP_011539798.1  methylenetetrahydrofolate reductase isoform X2

      Conserved Domains (1) summary
      cl00246
      Location:101625
      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 ...
    9. XM_017001328.3XP_016856817.1  methylenetetrahydrofolate reductase isoform X5

    10. XM_005263463.5XP_005263520.1  methylenetetrahydrofolate reductase isoform X8

      Conserved Domains (1) summary
      cl00246
      Location:1544
      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 ...

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      11329802..11350048 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)