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

Gene ID: 4522, updated on 3-Nov-2024

Summary

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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
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Genomic context

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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

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. MTHFD1 regulates the NADPH redox homeostasis in MYCN-amplified neuroblastoma.
    Title: MTHFD1 regulates the NADPH redox homeostasis in MYCN-amplified neuroblastoma.
  2. The negative effect of G1958A polymorphism on MTHFD1 protein stability and HCC growth.
    Title: The negative effect of G1958A polymorphism on MTHFD1 protein stability and HCC growth.
  3. Association Between MTHFD1 1958G > A Variant and non-Syndromic Cleft lip and Palate: An Updated Meta-Analysis.
    Title: Association Between MTHFD1 1958G > A Variant and non-Syndromic Cleft lip and Palate: An Updated Meta-Analysis.
  4. [Association of maternal MTHFD1 and MTHFD2 gene polymorphisms with congenital heart disease in offspring].", trans "MTHFD1MTHFD2.
    Title: [Association of maternal MTHFD1 and MTHFD2 gene polymorphisms with congenital heart disease in offspring].
  5. Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.
    Title: Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.
  6. Association of methionine synthase (rs1805087), methionine synthase reductase (rs1801394), and methylenetetrahydrofolate dehydrogenase 1 (rs2236225) genetic polymorphisms with recurrent implantation failure.
    Title: Association of methionine synthase (rs1805087), methionine synthase reductase (rs1801394), and methylenetetrahydrofolate dehydrogenase 1 (rs2236225) genetic polymorphisms with recurrent implantation failure.
  7. A comprehensive association analysis between homocysteine metabolic pathway gene methylation and ischemic stroke in a Chinese hypertensive population.
    Title: A comprehensive association analysis between homocysteine metabolic pathway gene methylation and ischemic stroke in a Chinese hypertensive population.
  8. Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy.
    Title: Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy.
  9. Independent and Interactive Influences of Environmental UVR, Vitamin D Levels, and Folate Variant MTHFD1-rs2236225 on Homocysteine Levels.
    Title: Independent and Interactive Influences of Environmental UVR, Vitamin D Levels, and Folate Variant MTHFD1-rs2236225 on Homocysteine Levels.
  10. Biochemical analysis of patients with mutations in MTHFD1 and a diagnosis of methylenetetrahydrofolate dehydrogenase 1 deficiency.
    Title: Biochemical analysis of patients with mutations in MTHFD1 and a diagnosis of methylenetetrahydrofolate dehydrogenase 1 deficiency.
Submit: New GeneRIF Correction See all GeneRIFs (92)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia
MedGen: C4540434 OMIM: 617780 GeneReviews: Not available
not available
Neural tube defects, folate-sensitive
MedGen: C1866558 OMIM: 601634 GeneReviews: Not available
not available

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables formate-tetrahydrofolate ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables formate-tetrahydrofolate ligase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables methenyltetrahydrofolate cyclohydrolase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables methenyltetrahydrofolate cyclohydrolase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables methylenetetrahydrofolate dehydrogenase (NAD+) activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables methylenetetrahydrofolate dehydrogenase (NADP+) activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables methylenetetrahydrofolate dehydrogenase (NADP+) activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
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

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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)

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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.

Genomic

  1. NG_012450.2 RefSeqGene

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

mRNA and Protein(s)

  1. NM_001364837.1 → NP_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:310 → 907
    PLN02759; Formate--tetrahydrofolate ligase
    COG0190
    Location:6 → 294
    FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme transport and metabolism]

  2. NM_005956.4 → NP_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:310 → 935
    PLN02759; Formate--tetrahydrofolate ligase
    COG0190
    Location:6 → 294
    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)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P11586.4 GenPept UniProtKB/Swiss-Prot:P11586

Gene LinkOut

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