The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylene... See more...

Aliases for MTHFR Gene

Aliases for MTHFR Gene

  • Methylenetetrahydrofolate Reductase 2 3 4 5
  • 5,10-Methylenetetrahydrofolate Reductase (NADPH) 2 3
  • Methylenetetrahydrofolate Reductase (NAD(P)H) 2 3
  • EC 1.5.1.20 4 52

External Ids for MTHFR Gene

Previous GeneCards Identifiers for MTHFR Gene

  • GC01U990112
  • GC01M011694
  • GC01M011459
  • GC01M011556
  • GC01M011780
  • GC01M011845
  • GC01M011000

Summaries for MTHFR Gene

Entrez Gene Summary for MTHFR Gene

  • The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.[provided by RefSeq, Oct 2009]

CIViC Summary for MTHFR Gene

GeneCards Summary for MTHFR Gene

MTHFR (Methylenetetrahydrofolate Reductase) is a Protein Coding gene. Diseases associated with MTHFR include Homocystinuria Due To Deficiency Of N -Methylenetetrahydrofolate Reductase Activity and Neural Tube Defects, Folate-Sensitive. Among its related pathways are Metabolism of water-soluble vitamins and cofactors and Carbon metabolism. Gene Ontology (GO) annotations related to this gene include NADP binding. An important paralog of this gene is MTR.

UniProtKB/Swiss-Prot Summary for MTHFR Gene

  • Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.

Gene Wiki entry for MTHFR Gene

PharmGKB "VIP" Summary for MTHFR Gene

Additional gene information for MTHFR Gene

No data available for Tocris Summary , Rfam classification and piRNA Summary for MTHFR Gene

Genomics for MTHFR Gene

GeneHancer (GH) Regulatory Elements for MTHFR Gene

Promoters and enhancers for MTHFR Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MTHFR on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MTHFR

Top Transcription factor binding sites by QIAGEN in the MTHFR gene promoter:
  • AML1a
  • MyoD
  • p53

Genomic Locations for MTHFR Gene

Genomic Locations for MTHFR Gene
chr1:11,785,723-11,806,920
(GRCh38/hg38)
Size:
21,198 bases
Orientation:
Minus strand
chr1:11,845,780-11,866,977
(GRCh37/hg19)
Size:
21,198 bases
Orientation:
Minus strand

Genomic View for MTHFR Gene

Genes around MTHFR on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for MTHFR Gene

Proteins for MTHFR Gene

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

    Protein Symbol:
    P42898-MTHR_HUMAN
    Recommended name:
    Methylenetetrahydrofolate reductase
    Protein Accession:
    P42898
    Secondary Accessions:
    • B2R7A6
    • Q5SNW6
    • Q5SNW9
    • Q7Z6M6
    • Q8IU73
    • Q9UQR2

    Protein attributes for MTHFR Gene

    Size:
    656 amino acids
    Molecular mass:
    74597 Da
    Cofactor:
    Name=FAD; Xref=ChEBI:CHEBI:57692;
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for MTHFR Gene

    Alternative splice isoforms for MTHFR Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MTHFR Gene

Selected DME Specific Peptides for MTHFR Gene

P42898:
  • EDVRPIFWA
  • GAVNLISRFDRM
  • FPNGRWGNSSSPAFG
  • NAVTWGIFPGREI
  • GILTINSQPNIN
  • IASTAVNYCGLETILHMTCC
  • EDPRRPLPWALSAHPKRR
  • DEFPNGR
  • IKDVIEPIKDNDAAIRNYGIE

Post-translational modifications for MTHFR Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for MTHFR Gene

Gene Families for MTHFR Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for MTHFR Gene

Blocks:
  • Methylenetetrahydrofolate reductase
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for MTHFR Gene

GenScript: Design optimal peptide antigens:
  • Methylenetetrahydrofolate reductase (A0MPA5_HUMAN)
  • Methylenetetrahydrofolate reductase (MTHR_HUMAN)
  • MTHF reductase (Q4FE54_HUMAN)
  • Methylenetetrahydrofolate reductase (Q5SNW5_HUMAN)
  • Methylenetetrahydrofolate reductase (Q5SNW6_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P42898

UniProtKB/Swiss-Prot:

MTHR_HUMAN :
  • Belongs to the methylenetetrahydrofolate reductase family.
Family:
  • Belongs to the methylenetetrahydrofolate reductase family.
genes like me logo Genes that share domains with MTHFR: view

Function for MTHFR Gene

Molecular function for MTHFR Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + NADP(+) = (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + H(+) + NADPH; Xref=Rhea:RHEA:19817, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636, ChEBI:CHEBI:18608, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.5.1.20; Evidence=. ;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + NAD(+) = (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + H(+) + NADH; Xref=Rhea:RHEA:19821, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636, ChEBI:CHEBI:18608, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.5.1.20; Evidence=. ;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Allosterically regulated by S-adenosylmethionine.
GENATLAS Biochemistry:
5-10 methylenetetrahydrofolate (THF) reductase,NADPH dependent,70kDa,reducing 5-10 methylene THF to,5 methyl-THF for methionine biosynthesis,with a common variant putatively involved in occlusive vascular disease,neural tube defects,colon cancer and adult akute leukemia. And a mutation responsible of increased mortality risk in men in middle and old age

Enzyme Numbers (IUBMB) for MTHFR Gene

Phenotypes From GWAS Catalog for MTHFR Gene

Gene Ontology (GO) - Molecular Function for MTHFR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0004489 methylenetetrahydrofolate reductase (NAD(P)H) activity IBA,IMP 12673793
GO:0016491 oxidoreductase activity IEA --
GO:0044877 protein-containing complex binding IPI 24769206
GO:0050660 flavin adenine dinucleotide binding IDA 12673793
genes like me logo Genes that share ontologies with MTHFR: view
genes like me logo Genes that share phenotypes with MTHFR: view

Human Phenotype Ontology for MTHFR Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MTHFR Gene

MGI Knock Outs for MTHFR:

Animal Model Products

CRISPR Products

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for MTHFR Gene

Localization for MTHFR Gene

Subcellular locations from

COMPARTMENTS
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 MTHFR gene
Compartment Confidence
cytosol 4
extracellular 3
nucleus 3
plasma membrane 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
peroxisome 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cell Junctions (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MTHFR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0045202 synapse IEA --
genes like me logo Genes that share ontologies with MTHFR: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for MTHFR Gene

Pathways & Interactions for MTHFR Gene

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

UniProtKB/Swiss-Prot P42898-MTHR_HUMAN

  • Pathway: One-carbon metabolism; tetrahydrofolate interconversion.

SIGNOR curated interactions for MTHFR Gene

Is activated by:

Gene Ontology (GO) - Biological Process for MTHFR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001666 response to hypoxia IEA --
GO:0001843 neural tube closure NAS 9349452
GO:0006555 methionine metabolic process IGI 10551815
GO:0008152 metabolic process IEA --
GO:0009086 methionine biosynthetic process IBA 21873635
genes like me logo Genes that share ontologies with MTHFR: view

Drugs & Compounds for MTHFR Gene

(87) Drugs for MTHFR Gene - From: DrugBank, PharmGKB, ClinicalTrials, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cyanocobalamin Approved Nutra Target, cofactor 410
Folic acid Approved, Vet_approved Nutra Enzyme, substrate 4724
Benazepril Approved, Investigational Pharma Enzyme, substrate 48
Methotrexate Approved Pharma Enzyme, substrate Folate antagonist,inhibits DFHR 1796
Riboflavin Approved, Investigational, Vet_approved Nutra Enzyme, cofactor 220

(37) Additional Compounds for MTHFR Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
5,10-Methylene-THF
  • (6R)-5,10-Methylenetetrahydrofolate
  • (6R)-5,10-Methylenetetrahydrofolic acid
  • 5,10-Methenyltetrahydropteroylglutamate
  • 5,10-Methylene-6-hydrofolate
  • 5,10-Methylene-6-hydrofolic acid
31690-11-6
Hydrogen Ion
  • H+
  • H(+)
  • Hydrogen cation
  • Hydron
  • Proton
nadph
  • 2'-(Dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide
  • 2'-(Dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) adenosine 5'-ester with 1,4-dihydro-1-beta-delta-ribofuranosylnicotinamide
  • Adenosine 5'-(trihydrogen diphosphate) 2'-(dihydrogen phosphate) p'-5'-ester with 1,4-dihydro-1-beta-D-ribofuranosyl-3-pyridinecarboxamide
  • Adenosine 5'-(trihydrogen diphosphate) 2'-(dihydrogen phosphate) p'-5'-ester with 1,4-dihydro-1-beta-delta-ribofuranosyl-3-pyridinecarboxamide
  • b-NADPH
53-57-6
genes like me logo Genes that share compounds with MTHFR: view

Transcripts for MTHFR Gene

mRNA/cDNA for MTHFR Gene

2 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
19 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

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

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6a · 6b · 6c · 6d · 6e · 6f ^ 7 ^ 8a · 8b ^ 9a · 9b ^ 10a · 10b ^ 11a · 11b ^
SP1: - - -
SP2: -
SP3: - - - - - - - -
SP4: - - - - - - -
SP5: - - - - -
SP6: - - - - - -
SP7: - -
SP8: - -
SP9:
SP10: - - - -
SP11: - - -

ExUns: 12 ^ 13 ^ 14 ^ 15a · 15b
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:

Relevant External Links for MTHFR Gene

GeneLoc Exon Structure for
MTHFR

Expression for MTHFR Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MTHFR Gene

This gene is overexpressed in Peripheral blood mononuclear cells (17.7), Lymph node (15.8), and Stomach (6.1).

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



Protein tissue co-expression partners for MTHFR Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MTHFR

SOURCE GeneReport for Unigene cluster for MTHFR Gene:

Hs.214142

Evidence on tissue expression from TISSUES for MTHFR Gene

  • Lung(4.7)
  • Nervous system(4.7)
  • Liver(4.5)
  • Blood(3.5)
  • Eye(2.8)
  • Intestine(2.4)
  • Heart(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for MTHFR Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • endocrine
  • integumentary
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • eye
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • skull
Thorax:
  • chest wall
  • clavicle
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • adrenal gland
Pelvis:
  • pelvis
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with MTHFR: view

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for MTHFR Gene

Orthologs for MTHFR Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MTHFR Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MTHFR 31 30
  • 99.54 (n)
OneToOne
dog
(Canis familiaris)
Mammalia MTHFR 31 30
  • 88.74 (n)
OneToOne
cow
(Bos Taurus)
Mammalia MTHFR 31 30
  • 88.53 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Mthfr 17 31 30
  • 86.78 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia MTHFR 31
  • 86 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MTHFR 31
  • 86 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Mthfr 30
  • 85.68 (n)
chicken
(Gallus gallus)
Aves MTHFR 31 30
  • 78.64 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MTHFR 31
  • 71 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia mthfr 30
  • 71.71 (n)
Str.513 30
African clawed frog
(Xenopus laevis)
Amphibia mthfr-prov 30
zebrafish
(Danio rerio)
Actinopterygii mthfr 31 30
  • 73.9 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG7560 31
  • 22 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea mthf-1 31 30
  • 53.28 (n)
OneToOne
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AAR170W 30
  • 54.56 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MET13 33 33 33 31 30
  • 51.55 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F09647g 30
  • 49.71 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons MTHFR1 30
  • 52.03 (n)
rice
(Oryza sativa)
Liliopsida Os03g0815200 30
  • 53.58 (n)
wheat
(Triticum aestivum)
Liliopsida Ta.1521 30
corn
(Zea mays)
Liliopsida Zm.475 30
barley
(Hordeum vulgare)
Liliopsida Hv.1973 30
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2215 31
  • 60 (a)
OneToOne
bread mold
(Neurospora crassa)
Ascomycetes NCU07690 30
  • 55.06 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes met9 30
  • 49.52 (n)
Species where no ortholog for MTHFR was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • 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 MTHFR Gene

ENSEMBL:
Gene Tree for MTHFR (if available)
TreeFam:
Gene Tree for MTHFR (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MTHFR: view image

Paralogs for MTHFR Gene

Paralogs for MTHFR Gene

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

Variants for MTHFR Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for MTHFR Gene

MTHR_HUMAN-P42898
Genetic variation in MTHFR influences susceptibility to occlusive vascular disease, neural tube defects (NTD), colon cancer and acute leukemia.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MTHFR Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
570071 Pathogenic: Homocysteinemia due to MTHFR deficiency 11,802,962(-) C/T MISSENSE_VARIANT
572237 Uncertain Significance: Homocysteinemia due to MTHFR deficiency 11,801,306(-) C/G MISSENSE_VARIANT
579195 Uncertain Significance: Homocysteinemia due to MTHFR deficiency 11,794,442(-) C/G MISSENSE_VARIANT
593575 Likely Benign: not specified 11,802,878(-) T/C INTRON_VARIANT
595780 Uncertain Significance: not provided 11,792,285(-) T/G MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for MTHFR Gene

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

Variant ID Type Subtype PubMed ID
nsv518652 CNV loss 19592680

Variation tolerance for MTHFR Gene

Residual Variation Intolerance Score: 60% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 13.52; 95.55% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MTHFR Gene

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

SNP Genotyping and Copy Number Assay Products

Disorders for MTHFR Gene

MalaCards: The human disease database

(190) MalaCards diseases for MTHFR Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards