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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
  • 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 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 MTHFD2L.

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 Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH02F074471 1.2 ENCODE 12 +273.9 273888 2.5 HDGF PKNOX1 CREB3L1 WRNIP1 ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 LBX2 ENSG00000270571 MTHFD2 WBP1 DUSP11 DGUOK-AS1 MRPL53 MOGS
GH02F074528 1.2 ENCODE 12 +331.8 331764 4.4 HDGF ARNT MLX CREB3L1 WRNIP1 ARID4B SIN3A DMAP1 YY1 SLC30A9 LBX2 WBP1 CCDC142 PCGF1 DUSP11 ENSG00000270571 MOGS MTHFD2 ENSG00000273245 TTC31
GH02F074119 1.1 ENCODE 12.1 -78.2 -78200 1.6 HDGF CREB3L1 MLX ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 FNBP1P1 LOC107985899 SEMA4F SMYD5 MTHFD2 C2orf81 DCTN1 FBXO41 ENSG00000279181
GH02F074480 1.1 ENCODE 12 +283.9 283859 3.0 ARNT CREB3L1 MLX ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 ZNF143 ENSG00000270571 LBX2 PCGF1 MTHFD2 WBP1 DUSP11 ENSG00000273245 TTC31 MRPL53
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

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

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

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:0000287 magnesium ion binding IDA 8218174
GO:0003824 catalytic activity IEA --
GO:0004329 NOT formate-tetrahydrofolate ligase activity IBA --
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity ISS,TAS --
GO:0004487 methylenetetrahydrofolate dehydrogenase (NAD+) activity IEA,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

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

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

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MTHFD2 gene
Compartment Confidence
extracellular 5
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,IBA 8218174
GO:0005759 mitochondrial matrix TAS --
GO:0005829 NOT cytosol IBA --
genes like me logo Genes that share ontologies with MTHFD2: view

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:0006730 one-carbon metabolic process IBA --
GO:0008152 metabolic process IEA --
GO:0009396 folic acid-containing compound biosynthetic process IEA --
GO:0046653 tetrahydrofolate metabolic process IDA 8218174
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

(7) 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
Water Approved Pharma 0
Adenosine triphosphate Approved Nutra 0
Formic acid Experimental Pharma 0
NADH Nutra Target 0

(7) 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:

Inhibitory RNA Products

Clone Products

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 from GTEx, Illumina, BioGPS, and SAGE 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, MaxQB, and MOPED for MTHFD2 Gene

NURSA nuclear receptor signaling pathways regulating expression of MTHFD2 Gene:


SOURCE GeneReport for Unigene cluster for MTHFD2 Gene:

genes like me logo Genes that share expression patterns with MTHFD2: view

Primer Products

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt 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
(Pan troglodytes)
Mammalia MTHFD2 34 35
  • 99.43 (n)
(Canis familiaris)
Mammalia MTHFD2 34 35
  • 89.81 (n)
(Bos Taurus)
Mammalia MTHFD2 34 35
  • 89.33 (n)
(Mus musculus)
Mammalia Mthfd2 34 16 35
  • 85.62 (n)
(Rattus norvegicus)
Mammalia Mthfd2 34
  • 84.53 (n)
(Monodelphis domestica)
Mammalia -- 35
  • 83 (a)
(Ornithorhynchus anatinus)
Mammalia -- 35
  • 76 (a)
(Gallus gallus)
Aves MTHFD2 34 35
  • 77.53 (n)
(Anolis carolinensis)
Reptilia -- 35
  • 80 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia mthfd2 34
  • 74.45 (n)
(Danio rerio)
Actinopterygii mthfd2 35
  • 76 (a)
LOC101886265 34
  • 70.23 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004677 34
  • 62.01 (n)
fruit fly
(Drosophila melanogaster)
Insecta Nmdmc 36 34 35
  • 57.21 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ADE3 35
  • 13 (a)
(Hordeum vulgare)
Liliopsida Hv.8473 34
(Oryza sativa)
Liliopsida Os.7067 34
(Triticum aestivum)
Liliopsida Ta.3377 34
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.890 34
Species where no ortholog for MTHFD2 was found in the sources mined by GeneCards:
  • 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
rs10186488 -- 74,215,275(+) TCTGT(C/T)TGGTA nc-transcript-variant, utr-variant-3-prime
rs10186497 -- 74,215,293(+) AATTT(C/T)TGAAA nc-transcript-variant, utr-variant-3-prime
rs10189152 -- 74,212,395(+) cccag(C/T)agcca intron-variant
rs10192236 -- 74,213,176(+) tagga(C/T)tacag intron-variant
rs10198300 -- 74,199,537(+) atgaa(C/T)gtatt intron-variant

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

Variant ID Type Subtype PubMed ID
nsv1117245 CNV tandem duplication 24896259
nsv834261 CNV loss 17160897
nsv961419 CNV duplication 23825009

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)

Relevant External Links for MTHFD2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for

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
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 64
  2. Genetic susceptibility to distinct bladder cancer subphenotypes. (PMID: 19692168) Guey L.T. … Malats N. (Eur. Urol. 2010) 3 46 64
  3. A Large-scale genetic association study of esophageal adenocarcinoma risk. (PMID: 20453000) Liu C.Y. … Christiani D.C. (Carcinogenesis 2010) 3 46 64
  4. Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia. (PMID: 20634891) Jugessur A. … Murray J.C. (PLoS ONE 2010) 3 46 64
  5. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson S.L. … O'Brien S.J. (PLoS ONE 2010) 3 46 64

Products for MTHFD2 Gene

Sources for MTHFD2 Gene

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