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Aliases for MTHFD1L Gene

Aliases for MTHFD1L Gene

  • Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 1 Like 2 3 5
  • Monofunctional C1-Tetrahydrofolate Synthase, Mitochondrial 2 3
  • Formyltetrahydrofolate Synthetase Domain Containing 1 2 3
  • 10-Formyl-THF Synthetase 2 3
  • EC 4 56
  • FTHFSDC1 3 4
  • Mitochondrial C1-Tetrahydrofolate Synthase 2
  • Formyltetrahydrofolate Synthetase 4
  • DJ292B18.2 3
  • MTC1THFS 3

External Ids for MTHFD1L Gene

Previous HGNC Symbols for MTHFD1L Gene


Previous GeneCards Identifiers for MTHFD1L Gene

  • GC06P151279
  • GC06P151186
  • GC06P148750

Summaries for MTHFD1L Gene

Entrez Gene Summary for MTHFD1L Gene

  • The protein encoded by this gene is involved in the synthesis of tetrahydrofolate (THF) in the mitochondrion. THF is important in the de novo synthesis of purines and thymidylate and in the regeneration of methionine from homocysteine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2011]

GeneCards Summary for MTHFD1L Gene

MTHFD1L (Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 1 Like) is a Protein Coding gene. Diseases associated with MTHFD1L include Neural Tube Defects. Among its related pathways are One carbon pool by folate and Metabolism. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and methenyltetrahydrofolate cyclohydrolase activity. An important paralog of this gene is MTHFD1.

UniProtKB/Swiss-Prot for MTHFD1L Gene

  • May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism in embryonic an transformed cells complementing thus the enzymatic activities of MTHFD2.

Gene Wiki entry for MTHFD1L Gene

Additional gene information for MTHFD1L Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MTHFD1L Gene

Genomics for MTHFD1L Gene

GeneHancer (GH) Regulatory Elements for MTHFD1L Gene

Promoters and enhancers for MTHFD1L 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
GH06I150864 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 550.8 +0.9 912 4.1 HDGF CLOCK MLX ARNT ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 MTHFD1L AKAP12 ENSG00000216906 RAET1G ARL4AP5
GH06I150891 Enhancer 1 ENCODE dbSUPER 12.4 +26.9 26871 1.7 ARID4B DEAF1 RAD21 ARID2 ZNF143 CREM KLF11 ZNF654 MXD4 REST MTHFD1L AKAP12 ZBTB2 ARL4AP5
GH06I150817 Enhancer 0.7 ENCODE 11.6 -47.6 -47569 0.2 CTCF SAP130 ARID4B RAD21 TEAD3 CC2D1A ZNF121 GATA3 ZNF213 VEZF1 MTHFD1L AKAP12 PDCL3P5 ENSG00000226599 PLEKHG1
GH06I150004 Promoter/Enhancer 1.5 Ensembl ENCODE 4.8 -860.4 -860397 1.7 HDGF PKNOX1 SMAD1 ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF213 ZNF207 RAET1K LATS1 PPIL4 ENSG00000233330 RPS18P9 ULBP1 NUP43 KATNA1 GINM1 ENSG00000231760
GH06I150877 Enhancer 1 ENCODE dbSUPER 5.8 +13.0 12990 1.7 ELF3 FOXA2 ARID4B ZBTB40 DNMT3B ZSCAN9 RAD21 RARA ZNF143 CREM MTHFD1L ARL4AP5
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around MTHFD1L on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MTHFD1L gene promoter:

Genomic Locations for MTHFD1L Gene

Genomic Locations for MTHFD1L Gene
236,339 bases
Plus strand

Genomic View for MTHFD1L Gene

Genes around MTHFD1L on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MTHFD1L Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MTHFD1L Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MTHFD1L Gene

Proteins for MTHFD1L Gene

  • Protein details for MTHFD1L Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Monofunctional C1-tetrahydrofolate synthase, mitochondrial
    Protein Accession:
    Secondary Accessions:
    • Q2TBF3
    • Q8WVW0
    • Q96HG8
    • Q9H789
    • Q9UFU8

    Protein attributes for MTHFD1L Gene

    978 amino acids
    Molecular mass:
    105790 Da
    Quaternary structure:
    • Homodimer.
    • May participate in the progression of colorectal cancer by conferring growth advantage. Could be a new molecular target for cancer therapy.
    • Sequence=AAH08629.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB15009.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for MTHFD1L Gene


neXtProt entry for MTHFD1L Gene

Selected DME Specific Peptides for MTHFD1L Gene


Post-translational modifications for MTHFD1L Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for MTHFD1L Gene

Gene Families for MTHFD1L Gene

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

Graphical View of Domain Structure for InterPro Entry



  • This monofunctional enzyme consists of two major domains: an N-terminal inactive methylene-THF dehydrogenase and cyclohydrolase domain and an active larger formyl-THF synthetase C-terminal domain.
  • In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.
  • This monofunctional enzyme consists of two major domains: an N-terminal inactive methylene-THF dehydrogenase and cyclohydrolase domain and an active larger formyl-THF synthetase C-terminal domain.
  • 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 MTHFD1L: view

Function for MTHFD1L Gene

Molecular function for MTHFD1L Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=500 uM for THF monoglutamate {ECO:0000269 PubMed:16171773}; KM=16 uM for THF triglutamate {ECO:0000269 PubMed:16171773}; KM=3.6 uM for THF pentaglutamate {ECO:0000269 PubMed:16171773};
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate.
UniProtKB/Swiss-Prot Function:
May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism in embryonic an transformed cells complementing thus the enzymatic activities of MTHFD2.

Enzyme Numbers (IUBMB) for MTHFD1L Gene

Phenotypes From GWAS Catalog for MTHFD1L Gene

Gene Ontology (GO) - Molecular Function for MTHFD1L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004329 formate-tetrahydrofolate ligase activity TAS,IEA --
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity IBA --
GO:0004488 methylenetetrahydrofolate dehydrogenase (NADP+) activity IEA,IBA --
GO:0005524 ATP binding IEA,IDA 16171773
GO:0016874 ligase activity IEA --
genes like me logo Genes that share ontologies with MTHFD1L: view
genes like me logo Genes that share phenotypes with MTHFD1L: view

Animal Models for MTHFD1L Gene

MGI Knock Outs for MTHFD1L:

Animal Model Products

  • Taconic Biosciences Mouse Models for MTHFD1L

CRISPR Products

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MTHFD1L Gene

Localization for MTHFD1L Gene

Subcellular locations from UniProtKB/Swiss-Prot for MTHFD1L 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 MTHFD1L gene
Compartment Confidence
mitochondrion 5
nucleus 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for MTHFD1L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA,IEA 12937168
GO:0005759 mitochondrial matrix TAS --
GO:0016020 membrane HDA,IDA 19946888
genes like me logo Genes that share ontologies with MTHFD1L: view

Pathways & Interactions for MTHFD1L Gene

genes like me logo Genes that share pathways with MTHFD1L: view

Pathways by source for MTHFD1L Gene

UniProtKB/Swiss-Prot Q6UB35-C1TM_HUMAN

  • Pathway: One-carbon metabolism; tetrahydrofolate interconversion.

Gene Ontology (GO) - Biological Process for MTHFD1L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001843 neural tube closure ISS,IEA --
GO:0006730 one-carbon metabolic process IEA --
GO:0006760 folic acid-containing compound metabolic process IDA 12937168
GO:0009113 purine nucleobase biosynthetic process IBA --
GO:0009257 10-formyltetrahydrofolate biosynthetic process IBA --
genes like me logo Genes that share ontologies with MTHFD1L: view

No data available for SIGNOR curated interactions for MTHFD1L Gene

Drugs & Compounds for MTHFD1L Gene

(5) Drugs for MTHFD1L Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Formic acid Approved, Experimental, Investigational Pharma 0
Phosphoric acid Approved Pharma 0
Water Approved Pharma 0
ATP Investigational Nutra Agonist 0
Tetrahydrofolic acid Nutra 0

(7) Additional Compounds for MTHFD1L 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
  • Adenine-nicotinamide dinucleotide phosphate
  • b-NADP
  • b-Nicotinamide adenine dinucleotide phosphate
  • b-TPN
  • beta-NADP
genes like me logo Genes that share compounds with MTHFD1L: view

Transcripts for MTHFD1L Gene

Unigene Clusters for MTHFD1L Gene

Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like:
Representative Sequences:

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for MTHFD1L Gene

No ASD Table

Relevant External Links for MTHFD1L Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for MTHFD1L Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MTHFD1L Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MTHFD1L Gene

This gene is overexpressed in Artery - Coronary (x6.1).

Protein differential expression in normal tissues from HIPED for MTHFD1L Gene

This gene is overexpressed in Breast (42.7) and Testis (7.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for MTHFD1L Gene

Protein tissue co-expression partners for MTHFD1L Gene

NURSA nuclear receptor signaling pathways regulating expression of MTHFD1L Gene:


SOURCE GeneReport for Unigene cluster for MTHFD1L Gene:


mRNA Expression by UniProt/SwissProt for MTHFD1L Gene:

Tissue specificity: Detected in most tissues, highest expression found in placenta, thymus and brain. Low expression is found in liver and skeletal muscle. Up-regulated in colon adenocarcinoma.

Evidence on tissue expression from TISSUES for MTHFD1L Gene

  • Eye(4.3)
  • Muscle(4.1)
genes like me logo Genes that share expression patterns with MTHFD1L: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for MTHFD1L Gene

Orthologs for MTHFD1L Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MTHFD1L Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia MTHFD1L 33 34
  • 99.56 (n)
(Canis familiaris)
Mammalia MTHFD1L 33 34
  • 89.69 (n)
(Bos Taurus)
Mammalia MTHFD1L 33 34
  • 86.97 (n)
(Mus musculus)
Mammalia Mthfd1l 33 16 34
  • 84 (n)
(Rattus norvegicus)
Mammalia Mthfd1l 33
  • 83.9 (n)
(Monodelphis domestica)
Mammalia MTHFD1L 34
  • 83 (a)
(Ornithorhynchus anatinus)
Mammalia MTHFD1L 34
  • 80 (a)
(Gallus gallus)
Aves MTHFD1L 33 34
  • 74.02 (n)
(Anolis carolinensis)
Reptilia MTHFD1L 34
  • 68 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia mthfd1l 33
  • 72.9 (n)
(Danio rerio)
Actinopterygii mthfd1l 33 34
  • 67.71 (n)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.9251 33
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ADE3 34
  • 49 (a)
(Glycine max)
eudicotyledons Gma.5796 33
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.714 33
(Hordeum vulgare)
Liliopsida Hv.10671 33
(Oryza sativa)
Liliopsida Os.14842 33
Species where no ortholog for MTHFD1L was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • fruit fly (Drosophila melanogaster)
  • 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)
  • 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)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for MTHFD1L Gene

Gene Tree for MTHFD1L (if available)
Gene Tree for MTHFD1L (if available)

Paralogs for MTHFD1L Gene

Variants for MTHFD1L Gene

Sequence variations from dbSNP and Humsavar for MTHFD1L Gene

SNP ID Clin Chr 06 pos Variation AA Info Type
VAR_044346 A colorectal cancer sample p.Leu444Arg
rs1000021304 -- 150,975,512(+) A/G genic_downstream_transcript_variant, intron_variant
rs1000053936 -- 151,054,533(+) G/A genic_downstream_transcript_variant, intron_variant
rs1000062932 -- 151,014,121(+) C/T genic_downstream_transcript_variant, intron_variant
rs1000104241 -- 151,053,107(+) A/T genic_downstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for MTHFD1L Gene

Variant ID Type Subtype PubMed ID
dgv10964n54 CNV gain 21841781
dgv1229e214 CNV gain 21293372
dgv6162n100 CNV loss 25217958
esv1051422 CNV insertion 17803354
esv2669738 CNV deletion 23128226
esv2672856 CNV deletion 23128226
esv2732889 CNV deletion 23290073
esv2732890 CNV deletion 23290073
esv2759477 CNV gain 17122850
esv2762620 CNV loss 21179565
esv3540637 CNV deletion 23714750
esv3571467 CNV loss 25503493
esv3611239 CNV gain 21293372
esv3611241 CNV gain 21293372
esv3611242 CNV loss 21293372
esv3611243 CNV loss 21293372
esv3611246 CNV loss 21293372
esv3611249 CNV loss 21293372
esv5615 CNV loss 19470904
nsv1021285 CNV gain 25217958
nsv1121658 CNV deletion 24896259
nsv1124131 CNV deletion 24896259
nsv350123 CNV deletion 16902084
nsv464081 CNV loss 19166990
nsv472062 CNV novel sequence insertion 20440878
nsv478324 CNV novel sequence insertion 20440878
nsv518529 CNV loss 19592680
nsv519886 CNV loss 19592680
nsv523123 CNV loss 19592680
nsv525834 CNV loss 19592680
nsv5540 CNV deletion 18451855
nsv604854 CNV loss 21841781
nsv7978 CNV gain 18304495
nsv818460 CNV loss 17921354
nsv965779 CNV duplication 23825009
nsv969458 CNV duplication 23825009
nsv981196 CNV duplication 23825009

Variation tolerance for MTHFD1L Gene

Residual Variation Intolerance Score: 19.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.57; 56.02% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MTHFD1L Gene

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

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MTHFD1L Gene

Disorders for MTHFD1L Gene

MalaCards: The human disease database

(1) MalaCards diseases for MTHFD1L Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
neural tube defects
  • neural tube defects, susceptibility to
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for MTHFD1L

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with MTHFD1L: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MTHFD1L Gene

Publications for MTHFD1L Gene

  1. Mitochondrial methylenetetrahydrofolate dehydrogenase, methenyltetrahydrofolate cyclohydrolase, and formyltetrahydrofolate synthetases. (PMID: 18804703) Christensen KE … Mackenzie RE (Vitamins and hormones 2008) 2 3 22 58
  2. Enzymatic characterization of human mitochondrial C1-tetrahydrofolate synthase. (PMID: 16171773) Walkup AS … Appling DR (Archives of biochemistry and biophysics 2005) 3 4 22 58
  3. A novel mitochondrial C1-tetrahydrofolate synthetase is upregulated in human colon adenocarcinoma. (PMID: 15013446) Sugiura T … Hirotani K (Biochemical and biophysical research communications 2004) 3 4 22 58
  4. Human mitochondrial C1-tetrahydrofolate synthase: gene structure, tissue distribution of the mRNA, and immunolocalization in Chinese hamster ovary calls. (PMID: 12937168) Prasannan P … Appling DR (The Journal of biological chemistry 2003) 3 4 22 58
  5. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 44 58

Products for MTHFD1L Gene

Sources for MTHFD1L Gene

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