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Aliases for MTHFS Gene

Aliases for MTHFS Gene

  • Methenyltetrahydrofolate Synthetase 2 3 5
  • 5,10-Methenyltetrahydrofolate Synthetase (5-Formyltetrahydrofolate Cyclo-Ligase) 2 3
  • 5-Formyltetrahydrofolate Cyclo-Ligase 2 3
  • Methenyl-THF Synthetase 3 4
  • 5,10-Methenyl-Tetrahydrofolate Synthetase 4
  • 5,10-Methenyltetrahydrofolate Synthetase 2
  • EC 4
  • HsT19268 3

External Ids for MTHFS Gene

Previous GeneCards Identifiers for MTHFS Gene

  • GC15M076098
  • GC15M073294
  • GC15M077713
  • GC15M077853
  • GC15M077924
  • GC15M080137
  • GC15M056895
  • GC15M080125

Summaries for MTHFS Gene

Entrez Gene Summary for MTHFS Gene

  • The protein encoded by this gene is an enzyme that catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate, a precursor of reduced folates involved in 1-carbon metabolism. An increased activity of the encoded protein can result in an increased folate turnover rate and folate depletion. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

GeneCards Summary for MTHFS Gene

MTHFS (Methenyltetrahydrofolate Synthetase) is a Protein Coding gene. Among its related pathways are One carbon pool by folate and Metabolism. Gene Ontology (GO) annotations related to this gene include folic acid binding and 5-formyltetrahydrofolate cyclo-ligase activity. An important paralog of this gene is ST20-MTHFS.

UniProtKB/Swiss-Prot for MTHFS Gene

  • Contributes to tetrahydrofolate metabolism. Helps regulate carbon flow through the folate-dependent one-carbon metabolic network that supplies carbon for the biosynthesis of purines, thymidine and amino acids. Catalyzes the irreversible conversion of 5-formyltetrahydrofolate (5-FTHF) to yield 5,10-methenyltetrahydrofolate.

Additional gene information for MTHFS Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MTHFS Gene

Genomics for MTHFS Gene

GeneHancer (GH) Regulatory Elements for MTHFS Gene

Promoters and enhancers for MTHFS Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH15I079894 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 587.4 +0.1 139 5.5 SMAD1 FOXA2 ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 POLR2B MTHFS ST20 BCL2A1 ZFAND6 RNU6-667P KIAA1024 ENSG00000279394 ST20-MTHFS
GH15I079921 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 37.2 -26.0 -25965 2.9 HDGF PKNOX1 FOXA2 SMAD1 ARID4B SIN3A DMAP1 YY1 POLR2B ZNF766 ST20 ENSG00000278600 ST20-AS1 ST20-MTHFS MTHFS BCL2A1
GH15I079964 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 14.1 -70.9 -70944 7.5 HDGF PKNOX1 FOXA2 SMAD1 SIN3A IRF4 ZNF207 ZNF143 ATF7 FOS BCL2A1 MTHFS ST20-MTHFS ST20 RNU6-667P LOC101929560 ZFAND6 GC15P079945
GH15I079883 Enhancer 0.9 ENCODE 37.4 +11.6 11588 5.4 ELF3 PKNOX1 FOXA2 RAD21 RARA ETS1 YY1 CREM THAP11 RXRA MTHFS ST20 BCL2A1 RNU6-667P ZFAND6 KIAA1024 ENSG00000279394 ST20-MTHFS
GH15I079853 Enhancer 0.9 ENCODE 30.1 +43.6 43638 1 PKNOX1 SIN3A FEZF1 ZNF2 TCF12 ZNF143 FOS ATF7 REST ZNF592 MTHFS RNU6-667P BCL2A1 KIAA1024 GC15P079856 ENSG00000261229 GC15M079834 ST20-MTHFS
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around MTHFS on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MTHFS gene promoter:

Genomic Locations for MTHFS Gene

Genomic Locations for MTHFS Gene
63,795 bases
Minus strand

Genomic View for MTHFS Gene

Genes around MTHFS on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MTHFS Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MTHFS Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MTHFS Gene

Proteins for MTHFS Gene

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

    Protein Symbol:
    Recommended name:
    5-formyltetrahydrofolate cyclo-ligase
    Protein Accession:
    Secondary Accessions:
    • H3BQ75

    Protein attributes for MTHFS Gene

    203 amino acids
    Molecular mass:
    23256 Da
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Monomer.
    • Sequence=CK002935; Type=Frameshift; Positions=178, 201; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for MTHFS Gene

    Alternative splice isoforms for MTHFS Gene


neXtProt entry for MTHFS Gene

Post-translational modifications for MTHFS Gene

  • Ubiquitination at Lys10 and Lys76
  • Modification sites at PhosphoSitePlus

Other Protein References for MTHFS Gene

No data available for DME Specific Peptides for MTHFS Gene

Domains & Families for MTHFS Gene

Gene Families for MTHFS Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for MTHFS Gene

Suggested Antigen Peptide Sequences for MTHFS Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the 5-formyltetrahydrofolate cyclo-ligase family.
  • Belongs to the 5-formyltetrahydrofolate cyclo-ligase family.
genes like me logo Genes that share domains with MTHFS: view

Function for MTHFS Gene

Molecular function for MTHFS Gene

GENATLAS Biochemistry:
5,10-methenyl tetrahydrofolate (THF) synthetase,preferentially expressed in the liver,5-formyltetrahydrofolate cyclo-ligase,catalyzing the obligatory initial metabolic step,in the inctracellular conversion of 5-formyl THF to other reduced folates
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate.
UniProtKB/Swiss-Prot Function:
Contributes to tetrahydrofolate metabolism. Helps regulate carbon flow through the folate-dependent one-carbon metabolic network that supplies carbon for the biosynthesis of purines, thymidine and amino acids. Catalyzes the irreversible conversion of 5-formyltetrahydrofolate (5-FTHF) to yield 5,10-methenyltetrahydrofolate.

Enzyme Numbers (IUBMB) for MTHFS Gene

Phenotypes From GWAS Catalog for MTHFS Gene

Gene Ontology (GO) - Molecular Function for MTHFS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005524 ATP binding IEA,IDA 19738041
GO:0005542 folic acid binding IDA 7766710
GO:0016874 ligase activity IEA --
GO:0030272 5-formyltetrahydrofolate cyclo-ligase activity TAS,IEA --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with MTHFS: view
genes like me logo Genes that share phenotypes with MTHFS: view

Animal Models for MTHFS Gene

MGI Knock Outs for MTHFS:

miRNA for MTHFS Gene

miRTarBase miRNAs that target MTHFS

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MTHFS Gene

Localization for MTHFS Gene

Subcellular locations from UniProtKB/Swiss-Prot for MTHFS 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 MTHFS gene
Compartment Confidence
mitochondrion 5
cytosol 5
plasma membrane 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for MTHFS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA,IDA 7766710
GO:0005759 mitochondrial matrix IDA 7766710
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with MTHFS: view

Pathways & Interactions for MTHFS Gene

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

Gene Ontology (GO) - Biological Process for MTHFS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006536 glutamate metabolic process IMP 12764149
GO:0009396 folic acid-containing compound biosynthetic process IBA --
GO:0015942 formate metabolic process NAS 8522195
GO:0035999 tetrahydrofolate interconversion IMP 12764149
GO:0046653 tetrahydrofolate metabolic process IDA 7766710
genes like me logo Genes that share ontologies with MTHFS: view

No data available for SIGNOR curated interactions for MTHFS Gene

Drugs & Compounds for MTHFS Gene

(6) Drugs for MTHFS Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
leucovorin Approved Nutra 3402,1193
Phosphoric acid Approved Pharma 0
Folic Acid Approved, Vet_approved Nutra 4610
Magnesium Approved Nutra 0
ATP Investigational Nutra Agonist 0

(6) Additional Compounds for MTHFS Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
5,10-Methenyltetrahydrofolic acid
  • 5,10-Methenyl-THF
  • 5,10-Methenyltetrahydrofolate
  • Anhydro-leucovorin
  • Anhydro-leucovorin a
  • Anhydroleucovorin
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
Hydrogen Ion
  • Hydrogen cation
  • Hydron
  • Proton
  • NFB Orthophosphate
  • O-Phosphoric acid
  • Ortho-phosphate
  • Orthophosphate (PO43-)
  • Orthophosphate(3-)
genes like me logo Genes that share compounds with MTHFS: view

Transcripts for MTHFS Gene

Unigene Clusters for MTHFS Gene

5,10-methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclo-ligase):
Representative Sequences:

Clone Products

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

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5a · 5b
SP2: - -
SP3: -

Relevant External Links for MTHFS Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for MTHFS Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MTHFS Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

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

This gene is overexpressed in Liver (x10.4) and Whole Blood (x6.6).

Protein differential expression in normal tissues from HIPED for MTHFS Gene

This gene is overexpressed in Liver (19.7), Peripheral blood mononuclear cells (12.1), and Gallbladder (6.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for MTHFS Gene

Protein tissue co-expression partners for MTHFS Gene

NURSA nuclear receptor signaling pathways regulating expression of MTHFS Gene:


SOURCE GeneReport for Unigene cluster for MTHFS Gene:


Evidence on tissue expression from TISSUES for MTHFS Gene

  • Liver(4.6)
  • Pancreas(4.3)
  • Nervous system(4.3)
  • Stomach(2.2)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with MTHFS: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for MTHFS Gene

Orthologs for MTHFS Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MTHFS Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia MTHFS 34 33
  • 99.18 (n)
(Rattus norvegicus)
Mammalia Mthfs 33
  • 86.04 (n)
(Bos Taurus)
Mammalia MTHFS 33 34
  • 85.76 (n)
(Mus musculus)
Mammalia Gm2382 33 34
  • 85.39 (n)
Mthfs 34
  • 83 (a)
Mthfsl 16
(Canis familiaris)
Mammalia -- 34
  • 85 (a)
  • 83.77 (n)
(Monodelphis domestica)
Mammalia -- 34
  • 80 (a)
-- 34
  • 80 (a)
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 71 (a)
(Gallus gallus)
Aves MTHFS 33 34
  • 70.9 (n)
(Anolis carolinensis)
Reptilia -- 34
  • 67 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia mthfs 33
  • 63.04 (n)
Str.18593 33
African clawed frog
(Xenopus laevis)
Amphibia Xl.17255 33
(Danio rerio)
Actinopterygii LOC100332843 33
  • 60.71 (n)
  • 60 (a)
Dr.16718 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.3066 33
fruit fly
(Drosophila melanogaster)
Insecta CG34424 33 34
  • 49.66 (n)
CG11079 35
  • 35 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP006824 33
  • 49.47 (n)
(Caenorhabditis elegans)
Secernentea CELE_Y106G6E.4 33
  • 44.27 (n)
Y106G6E.4 35 34
  • 38 (a)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ADL385C 33
  • 46.13 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes FAU1 33 34 36
  • 44.44 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0A10285g 33
  • 44.33 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons 5-FCL 33
  • 46.92 (n)
(Oryza sativa)
Liliopsida Os07g0578600 33
  • 47.62 (n)
bread mold
(Neurospora crassa)
Ascomycetes NCU06353 33
  • 44.56 (n)
Species where no ortholog for MTHFS was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • 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)
  • 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)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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)
  • wheat (Triticum aestivum)

Evolution for MTHFS Gene

Gene Tree for MTHFS (if available)
Gene Tree for MTHFS (if available)

Paralogs for MTHFS Gene

Paralogs for MTHFS Gene

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

Variants for MTHFS Gene

Sequence variations from dbSNP and Humsavar for MTHFS Gene

SNP ID Clin Chr 15 pos Variation AA Info Type
rs1000009187 -- 79,848,487(-) T/G intron_variant
rs1000012239 -- 79,874,104(-) C/T intron_variant
rs1000076340 -- 79,890,269(-) G/A intron_variant
rs1000084032 -- 79,848,817(-) T/G intron_variant
rs1000165756 -- 79,873,797(-) C/G intron_variant

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

Variant ID Type Subtype PubMed ID
esv2678719 CNV deletion 23128226
esv28440 CNV loss 19812545
esv3637008 CNV loss 21293372
nsv833065 CNV loss 17160897
nsv833066 CNV loss 17160897

Variation tolerance for MTHFS Gene

Residual Variation Intolerance Score: 79.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.39; 27.43% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MTHFS Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

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

Disorders for MTHFS Gene

Additional Disease Information for MTHFS

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for MTHFS Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for MTHFS Gene

Publications for MTHFS Gene

  1. Cloning and characterization of the human 5,10-methenyltetrahydrofolate synthetase-encoding cDNA. (PMID: 8522195) Dayan A … Jolivet J (Gene 1995) 2 3 4 22 58
  2. Structural basis for the inhibition of human 5,10-methenyltetrahydrofolate synthetase by N10-substituted folate analogues. (PMID: 19738041) Wu D … Liu ZJ (Cancer research 2009) 3 4 22 58
  3. Genome-wide association study for renal traits in the Framingham Heart and Atherosclerosis Risk in Communities Studies. (PMID: 18522750) Kottgen A … Fox CS (BMC medical genetics 2008) 3 22 44 58
  4. One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia. (PMID: 17891500) Lee KM … Armstrong BK (Human genetics 2007) 3 22 44 58
  5. 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 JC (PloS one 2010) 3 44 58

Products for MTHFS Gene

Sources for MTHFS Gene

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