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Aliases for MTR Gene

Aliases for MTR Gene

  • 5-Methyltetrahydrofolate-Homocysteine Methyltransferase 2 3
  • Vitamin-B12 Dependent Methionine Synthase 3 4
  • EC 4 63
  • HMAG 3 6
  • MS 3 4
  • 5-Methyltetrahydrofolate-Homocysteine Methyltransferase 1 3
  • 5-Methyltetrahydrofolate--Homocysteine Methyltransferase 4
  • Cobalamin-Dependent Methionine Synthase 3
  • Methionine Synthase 3
  • CblG 3

External Ids for MTR Gene

Previous GeneCards Identifiers for MTR Gene

  • GC01P235091
  • GC01P232412
  • GC01P233255
  • GC01P233999
  • GC01P233284
  • GC01P235025
  • GC01P236958
  • GC01P207414

Summaries for MTR Gene

Entrez Gene Summary for MTR Gene

  • This gene encodes the 5-methyltetrahydrofolate-homocysteine methyltransferase. This enzyme, also known as cobalamin-dependent methionine synthase, catalyzes the final step in methionine biosynthesis. Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency complementation group G. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

GeneCards Summary for MTR Gene

MTR (5-Methyltetrahydrofolate-Homocysteine Methyltransferase) is a Protein Coding gene. Diseases associated with MTR include homocystinuria-megaloblastic anemia, cblg complementation type and neural tube defects, folate-sensitive. Among its related pathways are Disease and Metabolism. GO annotations related to this gene include cobalamin binding and methionine synthase activity.

UniProtKB/Swiss-Prot for MTR Gene

  • Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity).

Gene Wiki entry for MTR Gene

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

Genomics for MTR Gene

Regulatory Elements for MTR Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for MTR Gene

236,795,281 bp from pter
236,903,981 bp from pter
108,701 bases
Plus strand

Genomic View for MTR Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for MTR Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MTR Gene

Proteins for MTR Gene

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

    Protein Symbol:
    Recommended name:
    Methionine synthase
    Protein Accession:
    Secondary Accessions:
    • A1L4N8
    • A9Z1W4
    • B7ZLW7
    • B9EGF7
    • Q99713
    • Q99723

    Protein attributes for MTR Gene

    1265 amino acids
    Molecular mass:
    140527 Da
    Name=methyl(III)cobalamin; Xref=ChEBI:CHEBI:28115;
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.;
    Quaternary structure:
    No Data Available
    • L-homocysteine is bound via the zinc atom.

    Three dimensional structures from OCA and Proteopedia for MTR Gene

    Alternative splice isoforms for MTR Gene


neXtProt entry for MTR Gene

Proteomics data for MTR Gene at MOPED

Post-translational modifications for MTR Gene

  • Ubiquitination at Lys16, Lys28, Lys127, Lys151, Lys216, Lys231, Lys685, Lys727, Lys735, Lys753, Lys781, Lys789, Lys814, Lys817, Lys823, Lys865, Lys1000, Lys1127, and Lys1169
  • Modification sites at PhosphoSitePlus

Other Protein References for MTR Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for MTR Gene

Graphical View of Domain Structure for InterPro Entry



  • Q99707
  • Modular enzyme with four functionally distinct domains. The isolated Hcy-binding domain catalyzes methyl transfer from free methylcobalamin to homocysteine. The Hcy-binding domain in association with the pterin-binding domain catalyzes the methylation of cob(I)alamin by methyltetrahydrofolate and the methylation of homocysteine. The B12-binding domain binds the cofactor. The AdoMet activation domain binds S-adenosyl-L-methionine. Under aerobic conditions cob(I)alamin can be converted to inactive cob(II)alamin. Reductive methylation by S-adenosyl-L-methionine and flavodoxin regenerates methylcobalamin (By similarity).
  • Contains 1 AdoMet activation domain.
  • Contains 1 B12-binding domain.
  • Contains 1 B12-binding N-terminal domain.
  • Contains 1 Hcy-binding domain.
  • Contains 1 pterin-binding domain.
  • Belongs to the vitamin-B12 dependent methionine synthase family.
genes like me logo Genes that share domains with MTR: view

No data available for Gene Families for MTR Gene

Function for MTR Gene

Molecular function for MTR Gene

GENATLAS Biochemistry:
5-methyl tetrahydrofolate (THF),homocysteine methyltransferase,methionine synthase,140kDa,methylcobolamin dependent,sulfur aminoacid metabolism,no evidence of association with neural tube defects (NTD) in Netherlands and U.K.
UniProtKB/Swiss-Prot CatalyticActivity:
5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
UniProtKB/Swiss-Prot Function:
Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity).

Enzyme Numbers (IUBMB) for MTR Gene

Gene Ontology (GO) - Molecular Function for MTR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 23825108
GO:0008270 zinc ion binding IEA --
GO:0008705 methionine synthase activity IMP 23825108
GO:0008898 S-adenosylmethionine-homocysteine S-methyltransferase activity IEA --
GO:0031419 cobalamin binding IEA --
genes like me logo Genes that share ontologies with MTR: view

Phenotypes for MTR Gene

MGI mutant phenotypes for MTR:
inferred from 1 alleles
GenomeRNAi human phenotypes for MTR:
genes like me logo Genes that share phenotypes with MTR: view

Animal Models for MTR Gene

MGI Knock Outs for MTR:

Animal Model Products

miRNA for MTR Gene

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for MTR

In Situ Assay Products

Flow Cytometry Products

No data available for Transcription Factor Targeting and HOMER Transcription for MTR Gene

Localization for MTR Gene

Subcellular locations from UniProtKB/Swiss-Prot for MTR Gene


Subcellular locations from

Jensen Localization Image for MTR Gene COMPARTMENTS Subcellular localization image for MTR gene
Compartment Confidence
cytosol 4
mitochondrion 2
nucleus 2
chloroplast 1
extracellular 1
lysosome 1
peroxisome 1
plasma membrane 1
vacuole 1

Gene Ontology (GO) - Cellular Components for MTR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular --
GO:0005737 cytoplasm IDA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with MTR: view

Pathways for MTR Gene

SuperPathways for MTR Gene

Superpath Contained pathways
1 Defective BTD causes biotidinase deficiency
2 One carbon pool by folate
3 Biological oxidations
4 Metabolism
5 Sulfur amino acid metabolism
genes like me logo Genes that share pathways with MTR: view

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

UniProtKB/Swiss-Prot Q99707-METH_HUMAN

  • Pathway: Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-methionine from L-homocysteine (MetH route): step 1/1

Gene Ontology (GO) - Biological Process for MTR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000096 sulfur amino acid metabolic process TAS --
GO:0006766 vitamin metabolic process TAS --
GO:0006767 water-soluble vitamin metabolic process TAS --
GO:0006805 xenobiotic metabolic process TAS --
GO:0007399 nervous system development TAS 8968737
genes like me logo Genes that share ontologies with MTR: view

Compounds for MTR Gene

(13) HMDB Compounds for MTR Gene

Compound Synonyms Cas Number PubMed IDs
5-Methyltetrahydrofolic acid
  • 5-Methyl tetrahydrofolate
  • Vitamin B12s
  • Vitamin B12r
  • 5,6-dimethyl-1-a-D-ribofuranosylbenzimidazole
  • Co

(4) Drugbank Compounds for MTR Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
  • Cyanocob(III)alamin
68-19-9 target cofactor
  • Hydroxomin
13422-51-0 target cofactor
  • (S)-2-amino-4-(methylthio)butanoic acid
63-68-3 target product of
Tetrahydrofolic acid
  • 5,6,7,8-tetrahydrofolate
135-16-0 target cofactor

(60) Novoseek inferred chemical compound relationships for MTR Gene

Compound -log(P) Hits PubMed IDs
methionine 95.4 288
methylcobalamin 93.6 38
5-methyltetrahydrofolate 92.7 39
homocysteine 92.7 140
cobalamin 92.6 73

(7) PharmGKB related drug/compound annotations for MTR Gene

Drug/compound Annotation
benazepril CA
cisplatin CA
cyclophosphamide CA
dactinomycin CA
doxorubicin CA
methotrexate CA
vincristine CA
genes like me logo Genes that share compounds with MTR: view

Transcripts for MTR Gene

Unigene Clusters for MTR Gene

5-methyltetrahydrofolate-homocysteine methyltransferase:
Representative Sequences:

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for MTR

Primer Products

Flow Cytometry Products

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

No ASD Table

Relevant External Links for MTR Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for MTR Gene

mRNA expression in normal human tissues for MTR Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues for MTR Gene

This gene is overexpressed in Ovary (10.9).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for MTR Gene

SOURCE GeneReport for Unigene cluster for MTR Gene Hs.498187

mRNA Expression by UniProt/SwissProt for MTR Gene

Tissue specificity: Widely expressed. Expressed at the highest levels in pancreas, heart, brain, skeletal muscle and placenta. Expressed at lower levels in lung, liver and kidney
genes like me logo Genes that share expressions with MTR: view

Expression partners for MTR Gene

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for MTR Gene

Orthologs for MTR Gene

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

Orthologs for MTR Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia MTR 35
  • 89.62 (n)
  • 92.09 (a)
MTR 36
  • 92 (a)
(Canis familiaris)
Mammalia MTR 35
  • 89.14 (n)
  • 90.91 (a)
MTR 36
  • 91 (a)
(Mus musculus)
Mammalia Mtr 35
  • 88.55 (n)
  • 92.09 (a)
Mtr 16
Mtr 36
  • 92 (a)
(Pan troglodytes)
Mammalia MTR 35
  • 99.55 (n)
  • 99.84 (a)
MTR 36
  • 100 (a)
(Rattus norvegicus)
Mammalia Mtr 35
  • 88.63 (n)
  • 92.49 (a)
(Monodelphis domestica)
Mammalia MTR 36
  • 88 (a)
(Ornithorhynchus anatinus)
Mammalia MTR 36
  • 50 (a)
(Gallus gallus)
Aves MTR 35
  • 78.69 (n)
  • 84.1 (a)
MTR 36
  • 84 (a)
(Anolis carolinensis)
Reptilia MTR 36
  • 81 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100488827 35
  • 74.83 (n)
  • 81.3 (a)
(Danio rerio)
Actinopterygii mtr 35
  • 70.65 (n)
  • 77.91 (a)
MTR 36
  • 73 (a)
(Caenorhabditis elegans)
Secernentea R03D7.1 37
  • 63 (a)
metr-1 35
  • 61.95 (n)
  • 64.36 (a)
metr-1 36
  • 64 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MHT1 38
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.1103 35
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 68 (a)
Species with no ortholog for MTR:
  • 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)
  • 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)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • 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)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MTR Gene

Gene Tree for MTR (if available)
Gene Tree for MTR (if available)

Paralogs for MTR Gene

Selected SIMAP similar genes for MTR Gene using alignment to 5 proteins:

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

No data available for Paralogs for MTR Gene

Variants for MTR Gene

Sequence variations from dbSNP and Humsavar for MTR Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type MAF
rs9779 -- 236,900,204(+) tatat(A/G)tattc utr-variant-3-prime
rs14354 -- 236,903,553(+) TCGCC(C/T)AGGAA utr-variant-3-prime
rs883395 -- 236,833,075(+) ATTCC(A/G)TCCTC intron-variant
rs883396 -- 236,833,090(+) CTTAG(A/G)TATTA intron-variant
rs946403 -- 236,832,817(+) TTTAT(C/T)CCCCT intron-variant

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

Variant ID Type Subtype PubMed ID
nsv428335 CNV Gain 18775914
nsv5010 CNV Insertion 18451855
nsv5021 CNV Loss 18451855

Relevant External Links for MTR Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)
Locus Specific Mutation Databases (LSDB)

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

Disorders for MTR Gene

(2) OMIM Diseases for MTR Gene (156570)


  • Homocystinuria-megaloblastic anemia, cblG complementation type (HMAG) [MIM:250940]: An autosomal recessive inborn error of metabolism resulting from defects in the cobalamin-dependent pathway that converts homocysteine to methionine. It causes delayed psychomotor development, megaloblastic anemia, homocystinuria, and hypomethioninemia. {ECO:0000269 PubMed:8968736, ECO:0000269 PubMed:8968737}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Folate-sensitive neural tube defects (FS-NTD) [MIM:601634]: The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. {ECO:0000269 PubMed:12375236}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

(52) Novoseek inferred disease relationships for MTR Gene

Disease -log(P) Hits PubMed IDs
hyperhomocysteinemia 82.9 9
homocystinuria 82.3 8
anemia megaloblastic 82 7
methylenetetrahydrofolate reductase deficiency 81.4 2
subacute combined degeneration 80.7 2

Genatlas disease for MTR Gene

methylmalonic acidemia and homocystinuria,megaloblastic anemia with/without the cblG variant,characterized by neonatal seizures,severe developmental delay and hyperhomocysteinemia,cblG complementation groups no evidence of association with neural tube defects (NTD) in Netherlands and U.K.

Relevant External Links for MTR

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with MTR: view

Publications for MTR Gene

  1. Cloning, mapping and RNA analysis of the human methionine synthase gene. (PMID: 8968735) Li Y.N. … Kruger W.D. (Hum. Mol. Genet. 1996) 2 3 4 23
  2. Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. (PMID: 15979034) O'Leary V.B. … Brody L.C. (Mol. Genet. Metab. 2005) 3 4 23 48
  3. Polymorphisms of genes controlling homocysteine levels and IQ score following the treatment for childhood ALL. (PMID: 16013960) Krajinovic M. … Moghrabi A. (Pharmacogenomics 2005) 3 23 48
  4. No association between common polymorphisms in genes of folate and homocysteine metabolism and the risk of Down's syndrome among French mothers. (PMID: 16115349) Chango A. … Nicolas J.P. (Br. J. Nutr. 2005) 3 23 48
  5. Methyltetrahydrofolate reductase polymorphism influences onset of Huntington's disease. (PMID: 15354395) Brune N. … Epplen J.T. (J. Neural Transm. Suppl. 2004) 3 23 48

Products for MTR Gene

Sources for MTR Gene

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