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GCID:
GC14P064388
GIFtS:
63

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 5
  • C1-THF Synthase 3 4
  • MTHFC 3 4
  • MTHFD 3 4
  • 5,10-Methylenetetrahydrofolate Dehydrogenase, 5,10-Methylenetetrahydrofolate Cyclohydrolase, 10-Formyltetrahydrofolate Synthetase 3
  • Cytoplasmic C-1-Tetrahydrofolate Synthase 3
  • EC 6.3.4.3 63

External Ids for MTHFD1 Gene

Previous HGNC Symbols for MTHFD1 Gene

  • MTHFC
  • MTHFD

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 neural tube defects, folate-sensitive and neural tube defects. Among its related pathways are Metabolism and Metabolism of water-soluble vitamins and cofactors. 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

Promoters for MTHFD1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around MTHFD1 on UCSC Golden Path with GeneCards custom track

Genomic Location for MTHFD1 Gene

Chromosome:
14
Start:
64,388,031 bp from pter
End:
64,463,457 bp from pter
Size:
75,427 bases
Orientation:
Plus strand

Genomic View for MTHFD1 Gene

Genes around MTHFD1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MTHFD1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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:
    P11586-C1TC_HUMAN
    Recommended name:
    C-1-tetrahydrofolate synthase, cytoplasmic
    Protein Accession:
    P11586
    Secondary Accessions:
    • B2R5Y2
    • G3V2B8
    • Q86VC9
    • Q9BVP5

    Protein attributes for MTHFD1 Gene

    Size:
    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 Lys 58, Lys 150, Lys 354, Lys 370, Lys 543, Lys 588, Lys 784, and Lys 819
  • Modification sites at PhosphoSitePlus

Other Protein References for MTHFD1 Gene

Antibody Products

Domains & Families for MTHFD1 Gene

Gene Families for MTHFD1 Gene

Suggested Antigen Peptide Sequences for MTHFD1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P11586

UniProtKB/Swiss-Prot:

C1TC_HUMAN :
  • 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.
Domain:
  • 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.
Family:
  • 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

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:0004486 methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity TAS --
GO:0004488 methylenetetrahydrofolate dehydrogenase (NADP+) activity IEA,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

  • Taconic Biosciences Mouse Models for MTHFD1

miRNA for MTHFD1 Gene

miRTarBase miRNAs that target MTHFD1

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for MTHFD1 Gene

Localization for MTHFD1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MTHFD1 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MTHFD1 Gene COMPARTMENTS Subcellular localization image for MTHFD1 gene
Compartment Confidence
cytosol 5
extracellular 5
mitochondrion 5

No data available for Gene Ontology (GO) - Cellular Components for MTHFD1 Gene

Pathways & Interactions for MTHFD1 Gene

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 IEA,ISS --
GO:0006164 purine nucleotide biosynthetic process IEA,ISS --
GO:0006730 one-carbon metabolic process IMP 25633902
GO:0006766 vitamin metabolic process TAS --
genes like me logo Genes that share ontologies with MTHFD1: view

No data available for SIGNOR curated interactions for MTHFD1 Gene

Drugs & Compounds for MTHFD1 Gene

(14) Drugs for MTHFD1 Gene - From: DrugBank, HMDB, Novoseek, and PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Tetrahydrofolic acid Approved Nutra Target, cofactor 0
Methotrexate Approved Pharma Folate antagonist,inhibits DFHR, Cytotoxic agent 1444
Adenosine triphosphate Approved Nutra 0
2'-Monophosphoadenosine 5'-Diphosphoribose Experimental Pharma Target 0
LY249543 Experimental Pharma Target 0

(17) Additional Compounds for MTHFD1 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
10-formyltetrahydrofolate
  • 10-Formyl-(6RS)-tetrahydrofolic acid
  • 10-Formyl-H4PteGlu1
  • 10-Formyl-tetrahydrofolate
  • 10-Formyl-THF
  • 10-Formyltetrahydrofolate
2800-34-2
5,10-Methenyltetrahydrofolic acid
  • 5,10-Methenyl-THF
  • 5,10-Methenyltetrahydrofolate
  • Anhydro-leucovorin
  • Anhydro-leucovorin a
  • Anhydroleucovorin
7444-29-3
5,10-Methylene-THF
  • (6R)-5,10-methylenetetrahydrofolate
  • 5,10-Methenyltetrahydropteroylglutamate
  • 5,10-Methylene-6-Hydrofolate
  • 5,10-Methylene-6-Hydrofolic acid
  • 5,10-Methylene-THF
31690-11-6
ADP
  • 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 MTHFD1: view

Transcripts for MTHFD1 Gene

Unigene Clusters for MTHFD1 Gene

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

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

No ASD Table

Relevant External Links for MTHFD1 Gene

GeneLoc Exon Structure for
MTHFD1
ECgene alternative splicing isoforms for
MTHFD1

Expression for MTHFD1 Gene

mRNA expression in normal human tissues for MTHFD1 Gene

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

This gene is overexpressed in Liver (x6.2).

Protein differential expression in normal tissues from HIPED for MTHFD1 Gene

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

Integrated Proteomics: protein expression in normal tissues and cell lines 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

P11586-C1TC_HUMAN
Tissue specificity: Ubiquitous.
genes like me logo Genes that share expression patterns with MTHFD1: view

Protein tissue co-expression partners for MTHFD1 Gene

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for MTHFD1 Gene

Orthologs for MTHFD1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MTHFD1 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia MTHFD1 35
  • 89.23 (n)
  • 92.62 (a)
MTHFD1 36
  • 93 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MTHFD1 35
  • 91.23 (n)
  • 94.55 (a)
MTHFD1 36
  • 87 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Mthfd1 35
  • 87.27 (n)
  • 93.16 (a)
Mthfd1 16
Mthfd1 36
  • 93 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia MTHFD1 35
  • 97.43 (n)
  • 96.54 (a)
MTHFD1 36
  • 89 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Mthfd1 35
  • 87.88 (n)
  • 93.48 (a)
oppossum
(Monodelphis domestica)
Mammalia MTHFD1 36
  • 89 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MTHFD1 36
  • 84 (a)
OneToOne
chicken
(Gallus gallus)
Aves MTHFD1 35
  • 75.83 (n)
  • 80.86 (a)
MTHFD1 36
  • 81 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MTHFD1 36
  • 81 (a)
OneToOne
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
zebrafish
(Danio rerio)
Actinopterygii mthfd1 35
mthfd1b 35
  • 70.35 (n)
  • 77.06 (a)
mthfd1a 36
  • 57 (a)
OneToMany
mthfd1b 36
  • 77 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta pug 37
  • 61 (a)
pug 35
  • 60.06 (n)
  • 61.35 (a)
pug 36
  • 59 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002830 35
  • 59.36 (n)
  • 62.73 (a)
worm
(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)
OneToMany
K07E3.4 36
  • 70 (a)
OneToMany
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)
OneToMany
MIS1 38
thale cress
(Arabidopsis thaliana)
eudicotyledons THFS 35
  • 61.49 (n)
  • 67.63 (a)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.7494 35
rice
(Oryza sativa)
Liliopsida Os09g0446800 35
  • 60.42 (n)
  • 68.27 (a)
wheat
(Triticum aestivum)
Liliopsida Ta.14577 35
corn
(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)
OneToOne
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

ENSEMBL:
Gene Tree for MTHFD1 (if available)
TreeFam:
Gene Tree for MTHFD1 (if available)

Paralogs for MTHFD1 Gene

Paralogs for MTHFD1 Gene

(4) SIMAP similar genes for MTHFD1 Gene using alignment to 6 proteins:

Pseudogenes.org 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
rs34181110 Neural tube defects, folate-sensitive (NTDFS) 64,425,752(+) CAAGC(A/G)TTTCC reference, missense
rs2236225 Neural tube defects, folate-sensitive (NTDFS) 64,442,127(-) CGATC(C/T)GGTCT reference, missense
rs1950902 - 64,415,662(-) CAAGT(C/T)TCCCA reference, missense
VAR_032789 -
VAR_032790 -

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

Variation tolerance for MTHFD1 Gene

Residual Variation Intolerance Score: 5.65% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.17; 90.38% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for MTHFD1 Gene

HapMap Linkage Disequilibrium report
MTHFD1
Human Gene Mutation Database (HGMD)
MTHFD1

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

Disorders for MTHFD1 Gene

MalaCards: The human disease database

(21) MalaCards diseases for MTHFD1 Gene - From: OMIM, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

C1TC_HUMAN
  • 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.
  • Neural tube defects, folate-sensitive (NTDFS) [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.
  • Note=MTHFD1 deficiency, due to mutation in this gene, can cause a metabolic syndrome with variable features including hyperhomocysteinemia, megaloblastic anemia, hemolytic uremic syndrome (HUS), severe combined immunodeficiency, microangiopathy and retinopathy. Symptoms improve after treatment with hydroxocobalamin, betaine and folinic acid. {ECO:0000269 PubMed:21813566, ECO:0000269 PubMed:25633902}.

Relevant External Links for MTHFD1

Genetic Association Database (GAD)
MTHFD1
Human Genome Epidemiology (HuGE) Navigator
MTHFD1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
MTHFD1
genes like me logo Genes that share disorders with MTHFD1: view

No data available for Genatlas for MTHFD1 Gene

Publications for MTHFD1 Gene

  1. 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 67
  2. Prognostic significance of folate metabolism polymorphisms for lung cancer. (PMID: 17533396) Matakidou A. … Houlston R.S. (Br. J. Cancer 2007) 3 23 25
  3. Polymorphic variants of folate metabolism genes and the risk of laryngeal cancer. (PMID: 19649727) Kruszyna A.8. … JagodziA8ski P.P. (Mol. Biol. Rep. 2010) 3 23
  4. MTHFR c.1793G>A polymorphism is associated with congenital cardiac disease in a Chinese population. (PMID: 20374669) Xu J. … Chen Y. (Cardiol Young 2010) 3 23
  5. Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia. (PMID: 19020309) de Jonge R. … Pieters R. (Blood 2009) 3 23

Products for MTHFD1 Gene

Sources for MTHFD1 Gene

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