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    MTHFD1 methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 [ Homo sapiens (human) ]

    Gene ID: 4522, updated on 6-Oct-2024

    Summary

    Official Symbol
    MTHFD1provided by HGNC
    Official Full Name
    methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1provided by HGNC
    Primary source
    HGNC:HGNC:7432
    See related
    Ensembl:ENSG00000100714 MIM:172460; AllianceGenome:HGNC:7432
    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
    Also known as
    CIMAH; MTHFC; MTHFD
    Summary
    This gene encodes a protein that possesses three distinct enzymatic activities, 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase. Each of these activities catalyzes one of three sequential reactions in the interconversion of 1-carbon derivatives of tetrahydrofolate, which are substrates for methionine, thymidylate, and de novo purine syntheses. The trifunctional enzymatic activities are conferred by two major domains, an aminoterminal portion containing the dehydrogenase and cyclohydrolase activities and a larger synthetase domain. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in liver (RPKM 96.4), fat (RPKM 36.5) and 22 other tissues See more
    Orthologs
    NEW
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    Genomic context

    See MTHFD1 in Genome Data Viewer
    Location:
    14q23.3
    Exon count:
    28
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (64388353..64460025)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (58596072..58667774)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (64855071..64926743)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903328 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8523 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8524 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8525 Neighboring gene estrogen receptor 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5832 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8526 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:64805694-64806376 Neighboring gene testis expressed 21, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8529 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8530 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8531 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr14:64858021-64858754 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:64858755-64859488 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:64859797-64860574 Neighboring gene Sharpr-MPRA regulatory region 9441 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8532 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5833 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5834 Neighboring gene zinc finger and BTB domain containing 25 Neighboring gene A-kinase anchoring protein 5 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8533 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8534 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5835 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8535 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:64970928-64971598 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5837 Neighboring gene HSPA2 and ZBTB1 antisense RNA 1 Neighboring gene zinc finger and BTB domain containing 1

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues 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
    Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia
    MedGen: C4540434 OMIM: 617780 GeneReviews: Not available
    Compare labs
    Neural tube defects, folate-sensitive
    MedGen: C1866558 OMIM: 601634 GeneReviews: Not available
    Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.
    EBI GWAS Catalog

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in 10-formyltetrahydrofolate biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in 10-formyltetrahydrofolate biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in embryonic neurocranium morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in embryonic viscerocranium morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in heart development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in methionine biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in methionine metabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in neural tube closure ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in neutrophil homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in one-carbon metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    acts_upstream_of purine nucleotide biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in purine nucleotide biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in purine ribonucleotide biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in serine family amino acid biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in serine family amino acid metabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in somite development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in tetrahydrofolate interconversion IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    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 ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in transsulfuration IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in extracellular exosome HDA PubMed 
    located_in membrane HDA PubMed 
    located_in mitochondrion TAS
    Traceable Author Statement
    more info
    PubMed 

    General protein information

    Preferred Names
    C-1-tetrahydrofolate synthase, cytoplasmic
    Names
    5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methylenetetrahydrofolate cyclohydrolase, 10-formyltetrahydrofolate synthetase
    C1-THF synthase
    cytoplasmic C-1-tetrahydrofolate synthase
    epididymis secretory sperm binding protein
    methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase
    NP_001351766.1
    NP_005947.3

    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_012450.2 RefSeqGene

      Range
      5313..76985
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1243

    mRNA and Protein(s)

    1. NM_001364837.1NP_001351766.1  C-1-tetrahydrofolate synthase, cytoplasmic isoform 2

      Status: REVIEWED

      Source sequence(s)
      AK302747, AL122035
      Consensus CDS
      CCDS91885.1
      UniProtKB/TrEMBL
      B7Z809, F5H2F4
      Related
      ENSP00000438588.2, ENST00000545908.6
      Conserved Domains (2) summary
      PLN02759
      Location:310907
      PLN02759; Formate--tetrahydrofolate ligase
      COG0190
      Location:6294
      FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme transport and metabolism]
    2. NM_005956.4NP_005947.3  C-1-tetrahydrofolate synthase, cytoplasmic isoform 1

      Status: REVIEWED

      Source sequence(s)
      AL122035, BQ959308, J04031
      Consensus CDS
      CCDS9763.1
      UniProtKB/Swiss-Prot
      A0A024R652, A0A384N5Y3, B2R5Y2, G3V2B8, P11586, Q86VC9, Q9BVP5
      UniProtKB/TrEMBL
      V9GYY3
      Related
      ENSP00000498336.1, ENST00000652337.1
      Conserved Domains (2) summary
      PLN02759
      Location:310935
      PLN02759; Formate--tetrahydrofolate ligase
      COG0190
      Location:6294
      FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme transport and metabolism]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      64388353..64460025
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      58596072..58667774
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)