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Aliases for MTHFD2 Gene

Aliases for MTHFD2 Gene

  • Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 2, Methenyltetrahydrofolate Cyclohydrolase 2 3 5
  • NMDMC 3 4
  • 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 Glucose / Energy Metabolism and Metabolism of water-soluble vitamins and cofactors. 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

Enhancers for MTHFD2 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around MTHFD2 on UCSC Golden Path with GeneCards custom track

Promoters for MTHFD2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around MTHFD2 on UCSC Golden Path with GeneCards custom track

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

Genes around MTHFD2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MTHFD2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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

No data available for DME Specific Peptides for MTHFD2 Gene

Domains & Families 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:0003824 catalytic activity IEA --
GO:0004487 methylenetetrahydrofolate dehydrogenase (NAD+) activity IDA,TAS --
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

miRNA for MTHFD2 Gene

miRTarBase miRNAs that target MTHFD2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , 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
extracellular 5
mitochondrion 5
cytosol 2

No data available for Gene Ontology (GO) - Cellular Components for MTHFD2 Gene

Pathways & Interactions for MTHFD2 Gene

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

Gene Ontology (GO) - Biological Process for MTHFD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0046655 folic acid metabolic process TAS --
genes like me logo Genes that share ontologies with MTHFD2: view

No data available for SIGNOR curated interactions for MTHFD2 Gene

Drugs & Compounds for MTHFD2 Gene

(6) Drugs for MTHFD2 Gene - From: DrugBank and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Tetrahydrofolic acid Approved Nutra Target, cofactor 0
Adenosine triphosphate Approved Nutra 0
Formic acid Experimental Pharma 0
NADH Nutra Target 0
NAD Pharma Full agonist, Agonist 0

(8) Additional Compounds for MTHFD2 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • 10-Formyl-(6RS)-tetrahydrofolic acid
  • 10-Formyl-H4PteGlu1
  • 10-Formyl-tetrahydrofolate
  • 10-Formyl-THF
  • 10-Formyltetrahydrofolate
5,10-Methenyltetrahydrofolic acid
  • 5,10-Methenyl-THF
  • 5,10-Methenyltetrahydrofolate
  • Anhydro-leucovorin
  • Anhydro-leucovorin a
  • Anhydroleucovorin
  • (6R)-5,10-methylenetetrahydrofolate
  • 5,10-Methenyltetrahydropteroylglutamate
  • 5,10-Methylene-6-Hydrofolate
  • 5,10-Methylene-6-Hydrofolic acid
  • 5,10-Methylene-THF
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
Hydrogen Ion
  • Hydrogen cation
  • Hydron
  • Proton
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:

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 from HIPED for MTHFD2 Gene

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

Integrated Proteomics: protein expression in normal tissues and cell lines 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 expression patterns with MTHFD2: view

Primer Products

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Protein tissue co-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
rs828853 -- 74,215,304(-) GGAAG(A/C)CAGAA downstream-variant-500B
rs828903 -- 74,209,594(+) gtttc(A/G)tcatg intron-variant
rs1667607 -- 74,203,846(+) ATCTA(G/T)TTTAG intron-variant
rs1667608 -- 74,203,851(+) GTTTA(G/T)TTTAG intron-variant
rs1667627 -- 74,202,065(-) ATACT(A/G)AAGTT 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

Variation tolerance for MTHFD2 Gene

Residual Variation Intolerance Score: 33.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.14; 23.12% of all genes are more intolerant (likely to be disease-causing)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Relevant External Links for MTHFD2 Gene

Disorders for MTHFD2 Gene

Relevant External Links for MTHFD2

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:

No disorders were found for MTHFD2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot 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 67
  2. NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase is the mammalian homolog of the mitochondrial enzyme encoded by the yeast MIS1 gene. (PMID: 8218174) Yang X.M. … MacKenzie R.E. (Biochemistry 1993) 2 3
  3. Reversible oxidation of phosphatase and tensin homolog (PTEN) alters its interactions with signaling and regulatory proteins. (PMID: 26561776) Verrastro I. … Pitt A.R. (Free Radic. Biol. Med. 2016) 3
  4. The BioPlex Network: A Systematic Exploration of the Human Interactome. (PMID: 26186194) Huttlin E.L. … Gygi S.P. (Cell 2015) 3
  5. Panorama of ancient metazoan macromolecular complexes. (PMID: 26344197) Wan C. … Emili A. (Nature 2015) 3

Products for MTHFD2 Gene

Sources for MTHFD2 Gene