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Aliases for MTHFD2L Gene

Aliases for MTHFD2L Gene

  • Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 2 Like 2 3 5
  • NADP-Dependent Methylenetetrahydrofolate Dehydrogenase 2-Like Protein 3 4
  • MTHFD2-Like 3 4
  • Probable Bifunctional Methylenetetrahydrofolate Dehydrogenase/Cyclohydrolase 2 3
  • Tetrahydrofolate Dehydrogenase/Cyclohydrolase 3

External Ids for MTHFD2L Gene

Previous GeneCards Identifiers for MTHFD2L Gene

  • GC04P075358
  • GC04P075207
  • GC04P074979
  • GC04P070834

Summaries for MTHFD2L Gene

GeneCards Summary for MTHFD2L Gene

MTHFD2L (Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 2 Like) is a Protein Coding gene. Among its related pathways are Metabolism and Metabolism of water-soluble vitamins and cofactors. Gene Ontology (GO) annotations related to this gene include formate-tetrahydrofolate ligase activity and methylenetetrahydrofolate dehydrogenase (NADP+) activity. An important paralog of this gene is MTHFD2.

Additional gene information for MTHFD2L Gene

No data available for Entrez Gene Summary , CIViC summary , UniProtKB/Swiss-Prot , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MTHFD2L Gene

Genomics for MTHFD2L Gene

GeneHancer (GH) Regulatory Elements for MTHFD2L Gene

Promoters and enhancers for MTHFD2L 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
GH04J074156 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 656.4 +43.8 43811 3.3 HDGF PKNOX1 SMAD1 MLX ARNT ZFP64 ARID4B SIN3A DMAP1 ZNF2 MTHFD2L ENSG00000269559 GC04P074159 LOC105377277
GH04J074107 Enhancer 1.6 FANTOM5 Ensembl ENCODE dbSUPER 654.4 -1.3 -1260 10.3 SIN3A BMI1 RFX5 YY1 ETS1 EGR1 SCRT2 FOS ZNF680 RXRA MTHFD2L CXCL2 EREG CXCL8 CXCL3 CXCL1 AREG LOC105377277
GH04J074123 Promoter/Enhancer 1.3 EPDnew dbSUPER 650.4 +9.1 9122 0.1 FOXA2 MZF1 FEZF1 RAD21 RARA YY1 EGR1 SCRT2 RXRA CEBPB MTHFD2L CXCL2 LOC105377277
GH04J074223 Promoter/Enhancer 1 EPDnew dbSUPER 650.1 +109.9 109851 0.1 JUND HLF CEBPB FOSL2 EP300 MTHFD2L GC04P074159 EPGN
GH04J074097 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE dbSUPER 10.4 -15.0 -14985 4 HDGF PKNOX1 FOXA2 ARNT SIN3A FEZF1 ZNF2 YY1 POLR2B ZNF766 CXCL2 ANKRD17 ENSG00000250220 CXCL3 AREG MTHFD2L LOC643014
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around MTHFD2L on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MTHFD2L gene promoter:
  • LHX3b
  • Lhx3a
  • Cart-1
  • p53
  • AML1a
  • AREB6
  • Pax-4a
  • FOXO3b

Genomic Locations for MTHFD2L Gene

Genomic Locations for MTHFD2L Gene
188,926 bases
Plus strand
188,926 bases
Plus strand

Genomic View for MTHFD2L Gene

Genes around MTHFD2L on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MTHFD2L Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MTHFD2L Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MTHFD2L Gene

Proteins for MTHFD2L Gene

  • Protein details for MTHFD2L Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Probable bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2
    Protein Accession:
    Secondary Accessions:
    • Q6P079
    • Q8N560

    Protein attributes for MTHFD2L Gene

    347 amino acids
    Molecular mass:
    37315 Da
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    No Data Available
    • Sequence=AAH32771.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAB14441.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};

    Alternative splice isoforms for MTHFD2L Gene


neXtProt entry for MTHFD2L Gene

Post-translational modifications for MTHFD2L Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for MTHFD2L Gene

Domains & Families for MTHFD2L Gene

Gene Families for MTHFD2L Gene

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

Suggested Antigen Peptide Sequences for MTHFD2L 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 MTHFD2L: view

Function for MTHFD2L Gene

Molecular function for MTHFD2L 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.

Phenotypes From GWAS Catalog for MTHFD2L Gene

Gene Ontology (GO) - Molecular Function for MTHFD2L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity TAS --
GO:0004487 methylenetetrahydrofolate dehydrogenase (NAD+) activity IBA,TAS --
GO:0004488 methylenetetrahydrofolate dehydrogenase (NADP+) activity IEA,IBA --
GO:0016491 oxidoreductase activity IEA --
genes like me logo Genes that share ontologies with MTHFD2L: view
genes like me logo Genes that share phenotypes with MTHFD2L: view

Animal Models for MTHFD2L Gene

MGI Knock Outs for MTHFD2L:
  • Mthfd2l Mthfd2l<tm1b(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

miRNA for MTHFD2L Gene

miRTarBase miRNAs that target MTHFD2L

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MTHFD2L

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MTHFD2L Gene

Localization for MTHFD2L Gene

Subcellular locations from UniProtKB/Swiss-Prot for MTHFD2L Gene

Mitochondrion inner membrane; Peripheral membrane protein; Matrix side.

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 MTHFD2L gene
Compartment Confidence
mitochondrion 5
nucleus 2
cytosol 2

Gene Ontology (GO) - Cellular Components for MTHFD2L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IBA --
GO:0005743 mitochondrial inner membrane IEA --
GO:0005759 mitochondrial matrix TAS,IEA --
GO:0005829 NOT cytosol IBA --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with MTHFD2L: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for MTHFD2L Gene

Pathways & Interactions for MTHFD2L Gene

genes like me logo Genes that share pathways with MTHFD2L: view

Pathways by source for MTHFD2L Gene

UniProtKB/Swiss-Prot Q9H903-MTD2L_HUMAN

  • Pathway: One-carbon metabolism; tetrahydrofolate interconversion.

Gene Ontology (GO) - Biological Process for MTHFD2L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000105 histidine biosynthetic process IEA --
GO:0006164 purine nucleotide biosynthetic process IEA --
GO:0006730 one-carbon metabolic process IBA --
GO:0008152 metabolic process IEA --
GO:0008652 cellular amino acid biosynthetic process IEA --
genes like me logo Genes that share ontologies with MTHFD2L: view

No data available for SIGNOR curated interactions for MTHFD2L Gene

Drugs & Compounds for MTHFD2L Gene

(4) Drugs for MTHFD2L Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Water Approved Pharma 0
Magnesium Approved Nutra 0
NADH Approved Nutra 0
NAD Pharma Full agonist, Agonist, Activator 0

(4) Additional Compounds for MTHFD2L Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • 10-Formyl-THF
  • 10-Formyltetrahydrofolic acid
  • 10-Formyl-(6Rs)-tetrahydrofolic acid
  • 10-Formyl-H4pteglu1
  • 10-Formyl-tetrahydrofolate
5,10-Methenyltetrahydrofolic acid
  • 5,10-Methenyl-THF
  • 5,10-Methenyltetrahydrofolate
  • anhydro-Leucovorin
  • anhydro-Leucovorin a
  • Anhydroleucovorin
  • (6R)-5,10-Methylenetetrahydrofolate
  • (6R)-5,10-Methylenetetrahydrofolic acid
  • 5,10-Methenyltetrahydropteroylglutamate
  • 5,10-Methylene-6-hydrofolate
  • 5,10-Methylene-6-hydrofolic acid
Hydrogen Ion
  • H+
  • H(+)
  • Hydrogen cation
  • Hydron
  • Proton
genes like me logo Genes that share compounds with MTHFD2L: view

Transcripts for MTHFD2L Gene

Unigene Clusters for MTHFD2L Gene

Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2-like:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MTHFD2L

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for MTHFD2L Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b · 4c ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14a · 14b
SP1: - - -
SP2: - -
SP5: -

Relevant External Links for MTHFD2L Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for MTHFD2L Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MTHFD2L Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MTHFD2L Gene

This gene is overexpressed in Amniocyte (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for MTHFD2L Gene

Protein tissue co-expression partners for MTHFD2L Gene

NURSA nuclear receptor signaling pathways regulating expression of MTHFD2L Gene:


SOURCE GeneReport for Unigene cluster for MTHFD2L Gene:


mRNA Expression by UniProt/SwissProt for MTHFD2L Gene:

Tissue specificity: Isoform 1, isoform 4 and isoform 5 are expressed in brain and placenta.

Evidence on tissue expression from TISSUES for MTHFD2L Gene

  • Lung(4.1)
genes like me logo Genes that share expression patterns with MTHFD2L: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for MTHFD2L Gene

Orthologs for MTHFD2L Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for MTHFD2L Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia MTHFD2L 34 33
  • 99.51 (n)
(Canis familiaris)
Mammalia MTHFD2L 34
  • 97 (a)
LOC482197 33
  • 93.44 (n)
(Monodelphis domestica)
Mammalia MTHFD2L 34
  • 88 (a)
(Bos Taurus)
Mammalia MTHFD2L 34 33
  • 87.99 (n)
(Mus musculus)
Mammalia Mthfd2l 16 34 33
  • 83.93 (n)
(Rattus norvegicus)
Mammalia Mthfd2l 33
  • 83.43 (n)
(Ornithorhynchus anatinus)
Mammalia MTHFD2L 34
  • 75 (a)
(Gallus gallus)
Aves MTHFD2L 34 33
  • 74.9 (n)
(Anolis carolinensis)
Reptilia MTHFD2L 34
  • 80 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia mthfd2l 33
  • 74.44 (n)
(Danio rerio)
Actinopterygii mthfd2l 34
  • 60 (a)
fruit fly
(Drosophila melanogaster)
Insecta Nmdmc 34
  • 52 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ADE3 34
  • 13 (a)
MTD1 36
Species where no ortholog for MTHFD2L 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)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • 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 (Oryza sativa)
  • 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)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for MTHFD2L Gene

Gene Tree for MTHFD2L (if available)
Gene Tree for MTHFD2L (if available)
Evolutionary constrained regions (ECRs) for MTHFD2L: view image

Paralogs for MTHFD2L Gene

Paralogs for MTHFD2L Gene

(4) SIMAP similar genes for MTHFD2L Gene using alignment to 3 proteins:

  • F8W7P9_HUMAN
  • Q8IY64_HUMAN
genes like me logo Genes that share paralogs with MTHFD2L: view

Variants for MTHFD2L Gene

Sequence variations from dbSNP and Humsavar for MTHFD2L Gene

SNP ID Clin Chr 04 pos Variation AA Info Type
rs1000012892 -- 74,177,749(+) A/G genic_upstream_transcript_variant, intron_variant
rs1000032595 -- 74,187,564(+) A/G genic_downstream_transcript_variant, intron_variant
rs1000046553 -- 74,198,005(+) C/G genic_downstream_transcript_variant, intron_variant
rs1000091544 -- 74,262,576(+) C/A genic_downstream_transcript_variant, intron_variant
rs1000108080 -- 74,183,419(+) T/G downstream_transcript_variant, genic_downstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for MTHFD2L Gene

Variant ID Type Subtype PubMed ID
nsv967763 CNV duplication 23825009
nsv525980 CNV gain 19592680
nsv509908 OTHER sequence alteration 20534489
nsv441890 CNV loss 18776908
nsv437397 CNV loss 16327808
nsv1143096 CNV tandem duplication 24896259
nsv1136876 CNV deletion 24896259
nsv1111274 CNV tandem duplication 24896259
nsv1009099 CNV gain 25217958
nsv1004768 CNV gain 25217958
esv998628 CNV insertion 20482838
esv8809 CNV gain 19470904
esv3601012 CNV loss 21293372
esv3601011 CNV loss 21293372
esv3569519 CNV loss 25503493
esv3360374 CNV insertion 20981092
esv29295 CNV loss 19812545
esv2760892 CNV loss 21179565
esv2662787 CNV deletion 23128226
esv2421669 CNV deletion 20811451
dgv9134n54 CNV loss 21841781
dgv5320n100 CNV loss 25217958

Variation tolerance for MTHFD2L Gene

Residual Variation Intolerance Score: 62% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.08; 21.97% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MTHFD2L Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MTHFD2L Gene

Disorders for MTHFD2L Gene

Additional Disease Information for MTHFD2L

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

No disorders were found for MTHFD2L Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for MTHFD2L Gene

Publications for MTHFD2L Gene

  1. Mammalian MTHFD2L encodes a mitochondrial methylenetetrahydrofolate dehydrogenase isozyme expressed in adult tissues. (PMID: 21163947) Bolusani S … Appling DR (The Journal of biological chemistry 2011) 2 3 4 58
  2. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 44 58
  3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 58
  4. Architecture of the human interactome defines protein communities and disease networks. (PMID: 28514442) Huttlin EL … Harper JW (Nature 2017) 3 58
  5. Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. (PMID: 22610502) Kennedy RB … Poland GA (Human genetics 2012) 3 58

Products for MTHFD2L Gene

Sources for MTHFD2L Gene

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