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MTHFD1 Gene(Protein Coding)

Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 1, Methenyltetrahydrofolate Cyclohydrolase, Formyltetrahydrofolate Synthetase

Aliases for MTHFD1 Gene

Aliases for MTHFD1 Gene

  • Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 1, Methenyltetrahydrofolate Cyclohydrolase, Formyltetrahydrofolate Synthetase 2 3
  • MTHFC 3 4 6
  • MTHFD 3 4 6
  • C1-THF Synthase 3 4
  • 5,10-Methylenetetrahydrofolate Dehydrogenase, 5,10-Methylenetetrahydrofolate Cyclohydrolase, 10-Formyltetrahydrofolate Synthetase 3
  • C-1-Tetrahydrofolate Synthase, Cytoplasmic 3
  • Cytoplasmic C-1-Tetrahydrofolate Synthase 3
  • EC 63

External Ids for MTHFD1 Gene

Previous HGNC Symbols for MTHFD1 Gene


Previous GeneCards Identifiers for MTHFD1 Gene

  • GC14P062182
  • GC14P058648
  • GC14P062845
  • GC14P063924
  • GC14P064854
  • GC14P045027

Summaries for MTHFD1 Gene

Entrez Gene Summary for MTHFD1 Gene

  • 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]

GeneCards Summary for MTHFD1 Gene

MTHFD1 (Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 1, Methenyltetrahydrofolate Cyclohydrolase, Formyltetrahydrofolate Synthetase) is a Protein Coding gene. Diseases associated with MTHFD1 include upper thoracic spina bifida cystica and cervicothoracic spina bifida cystica. Among its related pathways are Disease and Metabolism. GO annotations related to this gene include formate-tetrahydrofolate ligase activity and methylenetetrahydrofolate dehydrogenase (NADP+) activity. An important paralog of this gene is MTHFD2.

Gene Wiki entry for MTHFD1 Gene

No data available for UniProtKB/Swiss-Prot , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MTHFD1 Gene

Genomics for MTHFD1 Gene

Regulatory Elements for MTHFD1 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for MTHFD1 Gene

64,388,031 bp from pter
64,463,457 bp from pter
75,427 bases
Plus strand

Genomic View for MTHFD1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for MTHFD1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MTHFD1 Gene

Proteins for MTHFD1 Gene

  • Protein details for MTHFD1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    C-1-tetrahydrofolate synthase, cytoplasmic
    Protein Accession:
    Secondary Accessions:
    • B2R5Y2
    • G3V2B8
    • Q86VC9
    • Q9BVP5

    Protein attributes for MTHFD1 Gene

    935 amino acids
    Molecular mass:
    101559 Da
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for MTHFD1 Gene

neXtProt entry for MTHFD1 Gene

Proteomics data for MTHFD1 Gene at MOPED

Post-translational modifications for MTHFD1 Gene

  • Ubiquitination at Lys58, Lys150, Lys354, Lys370, Lys473, Lys543, Lys588, Lys684, Lys784, and Lys819
  • Modification sites at PhosphoSitePlus

Other Protein References for MTHFD1 Gene

Antibody Products

Domains for MTHFD1 Gene

Suggested Antigen Peptide Sequences for MTHFD1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • P11586
  • This trifunctional enzyme consists of two major domains: an N-terminal part containing the methylene-THF dehydrogenase and cyclohydrolase activities and a larger C-terminal part containing formyl-THF synthetase activity
  • In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.
  • In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.
genes like me logo Genes that share domains with MTHFD1: view

No data available for Gene Families for MTHFD1 Gene

Function for MTHFD1 Gene

Molecular function for MTHFD1 Gene

GENATLAS Biochemistry:
folate dependent,trifunctional enzyme catalyzing the oxidation of 5 methy THF for use in purine biosynthesis(see THFC,THFD,THFS)
UniProtKB/Swiss-Prot CatalyticActivity:
5,10-methylenetetrahydrofolate + NADP(+) = 5,10-methenyltetrahydrofolate + NADPH
UniProtKB/Swiss-Prot CatalyticActivity:
5,10-methenyltetrahydrofolate + H(2)O = 10-formyltetrahydrofolate
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate

Enzyme Numbers (IUBMB) for MTHFD1 Gene

Gene Ontology (GO) - Molecular Function for MTHFD1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity --
GO:0004329 formate-tetrahydrofolate ligase activity TAS --
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity TAS --
GO:0004486 methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity TAS --
GO:0004488 methylenetetrahydrofolate dehydrogenase (NADP+) activity IBA --
genes like me logo Genes that share ontologies with MTHFD1: view
genes like me logo Genes that share phenotypes with MTHFD1: view

Animal Model Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for MTHFD1

In Situ Assay Products

Flow Cytometry Products

No data available for Animal Models , Transcription Factor Targeting and HOMER Transcription for MTHFD1 Gene

Localization for MTHFD1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MTHFD1 Gene


Subcellular locations from

Jensen Localization Image for MTHFD1 Gene COMPARTMENTS Subcellular localization image for MTHFD1 gene
Compartment Confidence
cytosol 4
mitochondrion 4

Gene Ontology (GO) - Cellular Components for MTHFD1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IEA --
GO:0005829 cytosol TAS --
GO:0016020 membrane IDA 19946888
GO:0070062 extracellular exosome IDA 19056867
genes like me logo Genes that share ontologies with MTHFD1: view

Pathways for MTHFD1 Gene

SuperPathways for MTHFD1 Gene

Superpath Contained pathways
1 Defective BTD causes biotidinase deficiency
2 One carbon pool by folate
3 Metabolism
4 folate polyglutamylation
5 Disease
genes like me logo Genes that share pathways with MTHFD1: view

UniProtKB/Swiss-Prot P11586-C1TC_HUMAN

  • Pathway: One-carbon metabolism; tetrahydrofolate interconversion

Gene Ontology (GO) - Biological Process for MTHFD1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000105 histidine biosynthetic process IEA --
GO:0001843 neural tube closure ISS --
GO:0006164 purine nucleotide biosynthetic process IEA --
GO:0006555 methionine metabolic process ISS --
GO:0006730 one-carbon metabolic process IMP 25633902
genes like me logo Genes that share ontologies with MTHFD1: view

Compounds for MTHFD1 Gene

(12) HMDB Compounds for MTHFD1 Gene

Compound Synonyms Cas Number PubMed IDs
5,10-Methenyltetrahydrofolic acid
  • 5,10-Methenyltetrahydrofolate
  • 5,10-methylene-THF
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
  • adenosindiphosphorsaeure
Formic acid
  • Add-F

(5) Drugbank Compounds for MTHFD1 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
2'-Monophosphoadenosine 5'-Diphosphoribose
  • beta-DPNH
606-68-8 target
Tetrahydrofolic acid
  • 5,6,7,8-tetrahydrofolate
135-16-0 target cofactor

(13) Novoseek inferred chemical compound relationships for MTHFD1 Gene

Compound -log(P) Hits PubMed IDs
5,10-methenyltetrahydrofolate 96.5 16
10-formyltetrahydrofolate 91.7 7
folate 81.5 17
ch2h4folate 76.8 1
cystathionine 74.4 2

(1) PharmGKB related drug/compound annotations for MTHFD1 Gene

Drug/compound Annotation
methotrexate CA
genes like me logo Genes that share compounds with MTHFD1: view

Transcripts for MTHFD1 Gene

Unigene Clusters for MTHFD1 Gene

Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for MTHFD1

Primer Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for MTHFD1 Gene

No ASD Table

Relevant External Links for MTHFD1 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for MTHFD1 Gene

mRNA expression in normal human tissues for MTHFD1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MTHFD1 Gene

This gene is overexpressed in Liver (6.2).

Protein differential expression in normal tissues for MTHFD1 Gene

This gene is overexpressed in Liver (10.8) and Lymph node (8.3).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for MTHFD1 Gene

SOURCE GeneReport for Unigene cluster for MTHFD1 Gene Hs.652308

mRNA Expression by UniProt/SwissProt for MTHFD1 Gene

Tissue specificity: Ubiquitous
genes like me logo Genes that share expressions with MTHFD1: view

Expression partners for MTHFD1 Gene

In Situ Assay Products

Orthologs for MTHFD1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MTHFD1 Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia MTHFD1 35
  • 89.23 (n)
  • 92.62 (a)
  • 93 (a)
(Canis familiaris)
Mammalia MTHFD1 35
  • 91.23 (n)
  • 94.55 (a)
  • 87 (a)
(Mus musculus)
Mammalia Mthfd1 35
  • 87.27 (n)
  • 93.16 (a)
Mthfd1 16
Mthfd1 36
  • 93 (a)
(Pan troglodytes)
Mammalia MTHFD1 35
  • 97.43 (n)
  • 96.54 (a)
  • 89 (a)
(Rattus norvegicus)
Mammalia Mthfd1 35
  • 87.88 (n)
  • 93.48 (a)
(Monodelphis domestica)
Mammalia MTHFD1 36
  • 89 (a)
(Ornithorhynchus anatinus)
Mammalia MTHFD1 36
  • 84 (a)
(Gallus gallus)
Aves MTHFD1 35
  • 75.83 (n)
  • 80.86 (a)
  • 81 (a)
(Anolis carolinensis)
Reptilia MTHFD1 36
  • 81 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia mthfd1 35
  • 73.53 (n)
  • 82.53 (a)
Str.3283 35
African clawed frog
(Xenopus laevis)
Amphibia mthfd1-prov 35
(Danio rerio)
Actinopterygii mthfd1 35
mthfd1b 35
  • 70.35 (n)
  • 77.06 (a)
mthfd1a 36
  • 57 (a)
mthfd1b 36
  • 77 (a)
fruit fly
(Drosophila melanogaster)
Insecta pug 37
  • 61 (a)
pug 35
  • 60.06 (n)
  • 61.35 (a)
pug 36
  • 59 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002830 35
  • 59.36 (n)
  • 62.73 (a)
(Caenorhabditis elegans)
Secernentea dao-3 37
  • 53 (a)
K07E3.4a 37
  • 70 (a)
K07E3.4b 37
  • 70 (a)
K07E3.4 35
  • 64.03 (n)
  • 70.62 (a)
dao-3 36
  • 52 (a)
K07E3.4 36
  • 70 (a)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ACL121C 35
  • 56.28 (n)
  • 57.55 (a)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0E16545g 35
  • 59.2 (n)
  • 60 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ADE3 35
  • 58.17 (n)
  • 59.07 (a)
ADE3 36
  • 58 (a)
MIS1 38
thale cress
(Arabidopsis thaliana)
eudicotyledons THFS 35
  • 61.49 (n)
  • 67.63 (a)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.7494 35
(Oryza sativa)
Liliopsida Os09g0446800 35
  • 60.42 (n)
  • 68.27 (a)
(Triticum aestivum)
Liliopsida Ta.14577 35
(Zea mays)
Liliopsida Zm.13856 35
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.2498 35
bread mold
(Neurospora crassa)
Ascomycetes NCU03877 35
  • 58.32 (n)
  • 61.27 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPBC839.16 35
  • 57.71 (n)
  • 59.28 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.4044 36
  • 69 (a)
Species with no ortholog for MTHFD1:
  • Actinobacteria (Mycobacterium tuberculosis)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for MTHFD1 Gene

Gene Tree for MTHFD1 (if available)
Gene Tree for MTHFD1 (if available)

Paralogs for MTHFD1 Gene

Paralogs for MTHFD1 Gene

Selected SIMAP similar genes for MTHFD1 Gene using alignment to 6 proteins: Pseudogenes for MTHFD1 Gene

genes like me logo Genes that share paralogs with MTHFD1: view

Variants for MTHFD1 Gene

Sequence variations from dbSNP and Humsavar for MTHFD1 Gene

SNP ID Clin Chr 14 pos Sequence Context AA Info Type MAF
rs746488 -- 64,387,955(+) CGGAG(A/T)CTCGC upstream-variant-2KB
rs1076991 -- 64,388,323(-) TGGCC(A/G)GGGGA utr-variant-5-prime
rs1256140 -- 64,439,766(+) GCACG(C/T)GCCTG intron-variant
rs1256141 -- 64,441,048(+) TTAGC(C/T)GGGCA intron-variant
rs1256142 -- 64,444,076(-) CCCTG(C/T)TGCAT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for MTHFD1 Gene

Variant ID Type Subtype PubMed ID
esv2748779 CNV Deletion 23290073
nsv902019 CNV Gain 21882294
esv2670925 CNV Deletion 23128226
nsv902022 CNV Gain 21882294

Relevant External Links for MTHFD1 Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MTHFD1 Gene

Disorders for MTHFD1 Gene

(1) OMIM Diseases for MTHFD1 Gene (172460)


  • Folate-sensitive neural tube defects (FS-NTD) [MIM:601634]: The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. {ECO:0000269 PubMed:12384833, ECO:0000269 PubMed:16552426, ECO:0000269 PubMed:9611072}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
  • Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.

(3) Novoseek inferred disease relationships for MTHFD1 Gene

Disease -log(P) Hits PubMed IDs
neural tube defects 75.9 4
lymphoblastic leukemia acute childhood 56.8 1
spina bifida 44.4 1

Relevant External Links for MTHFD1

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with MTHFD1: view

No data available for University of Copenhagen DISEASES and Genatlas for MTHFD1 Gene

Publications for MTHFD1 Gene

  1. A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group. (PMID: 12384833) Brody L.C. … Swanson D.A. (Am. J. Hum. Genet. 2002) 3 4 23 48
  2. Confirmation of the R653Q polymorphism of the trifunctional C1- synthase enzyme as a maternal risk for neural tube defects in the Irish population. (PMID: 16552426) Parle-McDermott A. … Scott J.M. (Eur. J. Hum. Genet. 2006) 3 4 23 48
  3. The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects. (PMID: 18767138) Christensen K.E. … Rozen R. (Hum. Mutat. 2009) 3 4 23 48
  4. Prognostic significance of folate metabolism polymorphisms for lung cancer. (PMID: 17533396) Matakidou A. … Houlston R.S. (Br. J. Cancer 2007) 3 23 25 48
  5. One-carbon metabolism enzyme polymorphisms and uteroplacental insufficiency. (PMID: 18771981) Furness D.L. … Dekker G.A. (Am. J. Obstet. Gynecol. 2008) 3 23 48

Products for MTHFD1 Gene

Sources for MTHFD1 Gene

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