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Aliases for MTHFD2 Gene

Aliases for MTHFD2 Gene

  • Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 2, Methenyltetrahydrofolate Cyclohydrolase 2 3
  • NMDMC 3 4
  • Bifunctional Methylenetetrahydrofolate Dehydrogenase/Cyclohydrolase, Mitochondrial 3
  • NAD-Dependent Methylene Tetrahydrofolate Dehydrogenase Cyclohydrolase 3

External Ids for MTHFD2 Gene

Previous GeneCards Identifiers for MTHFD2 Gene

  • GC02P074563
  • GC02P074638
  • GC02P074383
  • GC02P074400
  • GC02P074337
  • GC02P074095
  • GC02P074425
  • GC02P074161

Summaries for MTHFD2 Gene

Entrez Gene Summary for MTHFD2 Gene

  • This gene encodes a nuclear-encoded mitochondrial bifunctional enzyme with methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities. The enzyme functions as a homodimer and is unique in its absolute requirement for magnesium and inorganic phosphate. Formation of the enzyme-magnesium complex allows binding of NAD. Alternative splicing results in two different transcripts, one protein-coding and the other not protein-coding. This gene has a pseudogene on chromosome 7. [provided by RefSeq, Mar 2009]

GeneCards Summary for MTHFD2 Gene

MTHFD2 (Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 2, Methenyltetrahydrofolate Cyclohydrolase) is a Protein Coding gene. Among its related pathways are Metabolism and Nucleotide Metabolism. GO annotations related to this gene include magnesium ion binding and formate-tetrahydrofolate ligase activity. An important paralog of this gene is MTHFD1L.

Gene Wiki entry for MTHFD2 Gene

No data available for UniProtKB/Swiss-Prot , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MTHFD2 Gene

Genomics for MTHFD2 Gene

Regulatory Elements for MTHFD2 Gene

Epigenetics Products

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

Genomic Location for MTHFD2 Gene

74,198,562 bp from pter
74,217,565 bp from pter
19,004 bases
Plus strand

Genomic View for MTHFD2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for MTHFD2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MTHFD2 Gene

Proteins for MTHFD2 Gene

  • Protein details for MTHFD2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial
    Protein Accession:
    Secondary Accessions:
    • Q53G90
    • Q53GV5
    • Q53S36
    • Q7Z650

    Protein attributes for MTHFD2 Gene

    350 amino acids
    Molecular mass:
    37895 Da
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Homodimer
    • This NAD-dependent bifunctional enzyme has very different kinetic properties than the larger NADP-dependent trifunctional enzyme and is unique in that it requires formation of an enzyme-magnesium complex to allow binding of NAD
    • Sequence=AAX93061.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAD96546.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAD96761.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAA34431.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for MTHFD2 Gene

    Alternative splice isoforms for MTHFD2 Gene


neXtProt entry for MTHFD2 Gene

Proteomics data for MTHFD2 Gene at MOPED

Post-translational modifications for MTHFD2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MTHFD2 Gene

Antibody Products

No data available for DME Specific Peptides for MTHFD2 Gene

Domains for MTHFD2 Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.
  • Belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.
genes like me logo Genes that share domains with MTHFD2: view

No data available for Gene Families for MTHFD2 Gene

Function for MTHFD2 Gene

Molecular function for MTHFD2 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
5,10-methylenetetrahydrofolate + NAD(+) = 5,10-methenyltetrahydrofolate + NADH
UniProtKB/Swiss-Prot CatalyticActivity:
5,10-methenyltetrahydrofolate + H(2)O = 10-formyltetrahydrofolate

Gene Ontology (GO) - Molecular Function for MTHFD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IDA 8218174
GO:0003824 catalytic activity --
GO:0004329 NOT formate-tetrahydrofolate ligase activity IBA --
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity ISS 8218174
GO:0004487 methylenetetrahydrofolate dehydrogenase (NAD+) activity IDA 8218174
genes like me logo Genes that share ontologies with MTHFD2: view
genes like me logo Genes that share phenotypes with MTHFD2: view

Animal Models for MTHFD2 Gene

MGI Knock Outs for MTHFD2:

Animal Model Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for MTHFD2

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for MTHFD2 Gene

Localization for MTHFD2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MTHFD2 Gene


Subcellular locations from

Jensen Localization Image for MTHFD2 Gene COMPARTMENTS Subcellular localization image for MTHFD2 gene
Compartment Confidence
mitochondrion 5
cytosol 2

Gene Ontology (GO) - Cellular Components for MTHFD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IDA 22664934
GO:0005739 mitochondrion ISS 8218174
GO:0005829 NOT cytosol IBA --
genes like me logo Genes that share ontologies with MTHFD2: view

Pathways for MTHFD2 Gene

genes like me logo Genes that share pathways with MTHFD2: view

Pathways by source for MTHFD2 Gene

Gene Ontology (GO) - Biological Process for MTHFD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006730 one-carbon metabolic process IBA --
GO:0009396 folic acid-containing compound biosynthetic process IEA --
GO:0046653 tetrahydrofolate metabolic process IDA 8218174
GO:0055114 oxidation-reduction process IEA --
genes like me logo Genes that share ontologies with MTHFD2: view

Drugs for MTHFD2 Gene

(2) Drugbank Compounds for MTHFD2 Gene

Compound Status Synonyms Cas Number PubChem ID Type Actions PubMed IDs
Tetrahydrofolic acid
  • (6S)-Tetrahydrofolate
135-16-0 91443 Target cofactor approved, nutraceutical
  • 1,4-dihydronicotinamide adenine dinucleotide
606-68-8 439153 Target nutraceutical

(14) HMDB Compounds for MTHFD2 Gene

Compound Synonyms Cas Number PubMed IDs
  • 10-Formyl-(6RS)-tetrahydrofolic acid
5,10-Methenyltetrahydrofolic acid
  • 5,10-Methenyl-THF
  • (6R)-5,10-methylenetetrahydrofolate
Adenosine triphosphate
  • 5'-(Tetrahydrogen triphosphate) Adenosine
  • Adenosindiphosphorsaeure
genes like me logo Genes that share compounds with MTHFD2: view

Transcripts for MTHFD2 Gene

Unigene Clusters for MTHFD2 Gene

Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase:
Representative Sequences:

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for MTHFD2

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for MTHFD2 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b · 7c ^ 8a · 8b ^ 9a · 9b · 9c · 9d ^ 10 ^ 11a · 11b · 11c
SP1: - - - -
SP2: - - -
SP3: - - - - - -
SP4: - - - - - - -
SP6: - - -
SP7: - - - - - - - - - - - -

Relevant External Links for MTHFD2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for MTHFD2 Gene

mRNA expression in normal human tissues for MTHFD2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues for MTHFD2 Gene

This gene is overexpressed in Liver (48.5) and Breast (6.1).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for MTHFD2 Gene

SOURCE GeneReport for Unigene cluster for MTHFD2 Gene Hs.469030

genes like me logo Genes that share expressions with MTHFD2: view

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Expression partners for MTHFD2 Gene

Orthologs for MTHFD2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MTHFD2 Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia MTHFD2 35
  • 89.33 (n)
  • 90.86 (a)
  • 91 (a)
(Canis familiaris)
Mammalia MTHFD2 35
  • 89.81 (n)
  • 92.29 (a)
  • 75 (a)
(Mus musculus)
Mammalia Mthfd2 35
  • 85.62 (n)
  • 92 (a)
Mthfd2 16
Mthfd2 36
  • 92 (a)
(Pan troglodytes)
Mammalia MTHFD2 35
  • 99.43 (n)
  • 99.71 (a)
  • 100 (a)
(Rattus norvegicus)
Mammalia Mthfd2 35
  • 84.53 (n)
  • 90.83 (a)
(Monodelphis domestica)
Mammalia -- 36
  • 83 (a)
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 76 (a)
(Gallus gallus)
Aves MTHFD2 35
  • 77.53 (n)
  • 85.58 (a)
  • 82 (a)
(Anolis carolinensis)
Reptilia -- 36
  • 80 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia mthfd2 35
  • 74.45 (n)
  • 84.74 (a)
(Danio rerio)
Actinopterygii LOC101886265 35
  • 70.23 (n)
  • 81.55 (a)
mthfd2 36
  • 76 (a)
fruit fly
(Drosophila melanogaster)
Insecta Nmdmc 37
  • 56 (a)
Nmdmc 35
  • 57.21 (n)
  • 57.43 (a)
Nmdmc 36
  • 57 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004677 35
  • 62.01 (n)
  • 61.69 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ADE3 36
  • 13 (a)
(Hordeum vulgare)
Liliopsida Hv.8473 35
(Oryza sativa)
Liliopsida Os.7067 35
(Triticum aestivum)
Liliopsida Ta.3377 35
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.890 35
Species with no ortholog for MTHFD2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • 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)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • worm (Caenorhabditis elegans)

Evolution for MTHFD2 Gene

Gene Tree for MTHFD2 (if available)
Gene Tree for MTHFD2 (if available)

Paralogs for MTHFD2 Gene

Paralogs for MTHFD2 Gene

(4) SIMAP similar genes for MTHFD2 Gene using alignment to 7 proteins:

genes like me logo Genes that share paralogs with MTHFD2: view

Variants for MTHFD2 Gene

Sequence variations from dbSNP and Humsavar for MTHFD2 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type MAF
rs8001 -- 74,215,280(-) TACCA(C/T)ACCAG utr-variant-3-prime, nc-transcript-variant
rs12196 -- 74,214,672(-) TTCCC(C/T)AATTT utr-variant-3-prime, nc-transcript-variant
rs15132 -- 74,215,228(+) TCAGA(C/T)TTTCT utr-variant-3-prime, nc-transcript-variant
rs828853 -- 74,215,304(-) GGAAG(A/C)CAGAA downstream-variant-500B
rs828903 -- 74,209,594(+) gtttc(A/G)tcatg intron-variant

Structural Variations from Database of Genomic Variants (DGV) for MTHFD2 Gene

Variant ID Type Subtype PubMed ID
nsv874286 CNV Loss 21882294
nsv834261 CNV Loss 17160897

Relevant External Links for MTHFD2 Gene

HapMap Linkage Disequilibrium report

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MTHFD2 Gene

Disorders for MTHFD2 Gene

Relevant External Links for MTHFD2

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator

No disorders were found for MTHFD2 Gene.

No data available for MalaCards , OMIM , UniProtKB/Swiss-Prot , University of Copenhagen DISEASES , Novoseek inferred disease relationships and Genatlas for MTHFD2 Gene

Publications for MTHFD2 Gene

  1. Nucleotide sequence of the human NAD-dependent methylene tetrahydrofolate dehydrogenase-cyclohydrolase. (PMID: 2587219) Peri K.G. … Mackenzie R.E. (Nucleic Acids Res. 1989) 2 3 4
  2. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard D.S. … Malek J. (Genome Res. 2004) 3 4
  3. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. (PMID: 15815621) Hillier L.W. … Wilson R.K. (Nature 2005) 3 4
  4. Oral facial clefts and gene polymorphisms in metabolism of folate/one-carbon and vitamin A: a pathway-wide association study. (PMID: 19048631) Boyles A.L. … Lie R.T. (Genet. Epidemiol. 2009) 3 48
  5. An association study of 45 folate-related genes in spina bifida: Involvement of cubilin (CUBN) and tRNA aspartic acid methyltransferase 1 (TRDMT1). (PMID: 19161160) Franke B. … Blom H.J. (Birth Defects Res. Part A Clin. Mol. Teratol. 2009) 3 48

Products for MTHFD2 Gene

Sources for MTHFD2 Gene

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