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MTR 5-methyltetrahydrofolate-homocysteine methyltransferase [ Homo sapiens (human) ]

Gene ID: 4548, updated on 3-Apr-2024

Summary

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Official Symbol
MTRprovided by HGNC
Official Full Name
5-methyltetrahydrofolate-homocysteine methyltransferaseprovided by HGNC
Primary source
HGNC:HGNC:7468
See related
Ensembl:ENSG00000116984 MIM:156570; AllianceGenome:HGNC:7468
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
MS; HMAG; cblG
Summary
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]
Expression
Ubiquitous expression in kidney (RPKM 5.8), thyroid (RPKM 4.9) and 25 other tissues See more
Orthologs
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Genomic context

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See MTR in Genome Data Viewer
Location:
1q43
Exon count:
33
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (236795281..236903981)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (236206330..236315021)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (236958581..237067281)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene MPRA-validated peak785 silencer Neighboring gene galectin 8 Neighboring gene HEAT repeat containing 1 Neighboring gene MPRA-validated peak786 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2825 Neighboring gene MPRA-validated peak787 silencer Neighboring gene control region 3 heart enhancer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2005 Neighboring gene VISTA enhancer hs2135 Neighboring gene actinin alpha 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2826 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2827 Neighboring gene Sharpr-MPRA regulatory region 3741 Neighboring gene ribosomal protein SA pseudogene 21 Neighboring gene uncharacterized LOC105373218 Neighboring gene uncharacterized LOC124904563 Neighboring gene uncharacterized LOC124904564

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Assessment of MTR Rs1805087 SNP as Possible Modifier of Sickle Cell Disease Severity in a Nigerian Population. Osunkalu VO, et al. West Afr J Med, 2022 Nov 30. PMID 36455241
  2. Association between MTR A2756G polymorphism and susceptibility to congenital heart disease: A meta-analysis. Liu W, et al. PLoS One, 2022. PMID 35802641, Free PMC Article
  3. Methionine synthase is essential for cancer cell proliferation in physiological folate environments. Sullivan MR, et al. Nat Metab, 2021 Nov. PMID 34799701, Free PMC Article
  4. Methionine synthase supports tumour tetrahydrofolate pools. Ghergurovich JM, et al. Nat Metab, 2021 Nov. PMID 34799699, Free PMC Article
  5. The Mosaic mtr Locus as Major Genetic Determinant of Azithromycin Resistance of Neisseria gonorrhoeae-Germany, 2018. Banhart S, et al. J Infect Dis, 2021 Oct 28. PMID 33592101

See all (470) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Common Variants in One-Carbon Metabolism Genes (MTHFR, MTR, MTHFD1) and Depression in Gynecologic Cancers.
    Title: Common Variants in One-Carbon Metabolism Genes (MTHFR, MTR, MTHFD1) and Depression in Gynecologic Cancers.
  2. Association of MTR gene polymorphisms with the occurrence of non-syndromic congenital heart disease: a case-control study.
    Title: Association of MTR gene polymorphisms with the occurrence of non-syndromic congenital heart disease: a case-control study.
  3. Association of MTR and MTRR genes and oral health-related quality of life in children with dental caries.
    Title: Association of MTR and MTRR genes and oral health-related quality of life in children with dental caries.
  4. Association of MTR A2756G and MTRR A66G Polymorphisms With Male Infertility: An Updated Meta-Analysis.
    Title: Association of MTR A2756G and MTRR A66G Polymorphisms With Male Infertility: An Updated Meta-Analysis.
  5. Assessment of MTR Rs1805087 SNP as Possible Modifier of Sickle Cell Disease Severity in a Nigerian Population.
    Title: Assessment of MTR Rs1805087 SNP as Possible Modifier of Sickle Cell Disease Severity in a Nigerian Population.
  6. MTR-G is a high-risk allele for lower-extremity arteriosclerotic occlusion.
    Title: MTR-G is a high-risk allele for lower-extremity arteriosclerotic occlusion.
  7. Investigation of the relationship between MTRR A66G, MTR A2756G gene variations and cell anomalies in early diagnosis and progression of bladder cancer.
    Title: Investigation of the relationship between MTRR A66G, MTR A2756G gene variations and cell anomalies in early diagnosis and progression of bladder cancer.
  8. Association between MTR A2756G polymorphism and susceptibility to congenital heart disease: A meta-analysis.
    Title: Association between MTR A2756G polymorphism and susceptibility to congenital heart disease: A meta-analysis.
  9. ""Association of MTHFR and MS/MTR gene polymorphisms with congenital heart defects in North Indian population (Jammu and Kashmir): a case-control study encompassing meta-analysis and trial sequential analysis"".
    Title: "Association of MTHFR and MS/MTR gene polymorphisms with congenital heart defects in North Indian population (Jammu and Kashmir): a case-control study encompassing meta-analysis and trial sequential analysis".
  10. Folate metabolism abnormalities in infertile patients with endometriosis.
    Title: Folate metabolism abnormalities in infertile patients with endometriosis.
Submit: New GeneRIF Correction See all GeneRIFs (222)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Methylcobalamin deficiency type cblG
MedGen: C1855128 OMIM: 250940 GeneReviews: Disorders of Intracellular Cobalamin Metabolism
Compare labs
Neural tube defects, folate-sensitive
MedGen: C1866558 OMIM: 601634 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Vif vif HIV-1 Vif interacts with MTR; interaction predicted to be relevant to purine pyrimidine biosynthesis PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ33168, FLJ43216, FLJ45386

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables cobalamin binding IEA
Inferred from Electronic Annotation
more info
  
enables methionine synthase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables methionine synthase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables methionine synthase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables zinc ion binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in axon regeneration ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to nitric oxide ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cobalamin metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in homocysteine metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in methionine biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in methionine biosynthetic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in methylation IEA
Inferred from Electronic Annotation
more info
  
involved_in nervous system development TAS
Traceable Author Statement
more info
 PubMed 
involved_in response to axon injury ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in tetrahydrofolate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
methionine synthase
Names
5-methyltetrahydrofolate-homocysteine methyltransferase 1
cobalamin-dependent methionine synthase
vitamin-B12 dependent methionine synthase
NP_000245.2
NP_001278868.1
NP_001278869.1
NP_001397871.1
XP_005273198.1
XP_011542496.1
XP_016856818.1
XP_016856819.1
XP_047277138.1
XP_047277139.1
XP_047277141.1
XP_047277142.1
XP_047277143.1
XP_054192683.1
XP_054192684.1
XP_054192685.1
XP_054192686.1
XP_054192687.1
XP_054192688.1
XP_054192689.1
XP_054192690.1
XP_054192691.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008959.1 RefSeqGene

    Range
    5012..113701
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000254.3 → NP_000245.2  methionine synthase isoform 1

    See identical proteins and their annotated locations for NP_000245.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AL359185, AL359259
    Consensus CDS
    CCDS1614.1
    UniProtKB/Swiss-Prot
    A1L4N8, A9Z1W4, B7ZLW7, B9EGF7, Q99707, Q99713, Q99723
    UniProtKB/TrEMBL
    B7ZLW8
    Related
    ENSP00000355536.5, ENST00000366577.10
    Conserved Domains (5) summary
    COG0646
    Location:21 → 340
    MetH1; Methionine synthase I (cobalamin-dependent), methyltransferase domain [Amino acid transport and metabolism]
    PRK09490
    Location:19 → 1261
    metH; B12-dependent methionine synthase; Provisional
    cd00740
    Location:371 → 627
    MeTr; MeTr subgroup of pterin binding enzymes. This family includes cobalamin-dependent methyltransferases such as methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) and methionine synthase (MetH). Cobalamin-dependent ...
    cd02069
    Location:671 → 897
    methionine_synthase_B12_BD; B12 binding domain of methionine synthase. This domain binds methylcobalamin, which it uses as an intermediate methyl carrier from methyltetrahydrofolate (CH3H4folate) to homocysteine (Hcy).
    pfam02965
    Location:965 → 1246
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain

  2. NM_001291939.1 → NP_001278868.1  methionine synthase isoform 2

    See identical proteins and their annotated locations for NP_001278868.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame exon in the central coding region, compared to variant 1. The resulting isoform (2) lacks an internal segment, compared to isoform 1.
    Source sequence(s)
    AL359259, BC144095, CB241165, DC377743
    Consensus CDS
    CCDS73054.1
    UniProtKB/TrEMBL
    B7ZLW8
    Related
    ENSP00000441845.1, ENST00000535889.6
    Conserved Domains (5) summary
    COG0646
    Location:21 → 340
    MetH1; Methionine synthase I (cobalamin-dependent), methyltransferase domain [Amino acid transport and metabolism]
    PRK09490
    Location:19 → 1210
    metH; B12-dependent methionine synthase; Provisional
    cd00740
    Location:371 → 627
    MeTr; MeTr subgroup of pterin binding enzymes. This family includes cobalamin-dependent methyltransferases such as methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) and methionine synthase (MetH). Cobalamin-dependent ...
    pfam02965
    Location:914 → 1195
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain
    cl00293
    Location:679 → 846
    B12-binding_like; B12 binding domain (B12-BD). Most of the members bind different cobalamid derivates, like B12 (adenosylcobamide) or methylcobalamin or methyl-Co(III) 5-hydroxybenzimidazolylcobamide. This domain is found in several enzymes, such as glutamate mutase, ...

  3. NM_001291940.2 → NP_001278869.1  methionine synthase isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an internal exon, which causes translation initiation at a downstream AUG, compared to variant 1. The resulting isoform (3) has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AL359259, BC136440, BC144098, CB241165, DC377743
    UniProtKB/TrEMBL
    B1ANE3
    Conserved Domains (4) summary
    COG1410
    Location:2 → 823
    MetH2; Methionine synthase I, cobalamin-binding domain [Amino acid transport and metabolism]
    cd00740
    Location:1 → 220
    MeTr; MeTr subgroup of pterin binding enzymes. This family includes cobalamin-dependent methyltransferases such as methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) and methionine synthase (MetH). Cobalamin-dependent ...
    cd02069
    Location:264 → 490
    methionine_synthase_B12_BD; B12 binding domain of methionine synthase. This domain binds methylcobalamin, which it uses as an intermediate methyl carrier from methyltetrahydrofolate (CH3H4folate) to homocysteine (Hcy).
    pfam02965
    Location:558 → 839
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain

  4. NM_001410942.1 → NP_001397871.1  methionine synthase isoform 4

    Status: REVIEWED

    Source sequence(s)
    AL359185, AL359259
    Consensus CDS
    CCDS91175.1
    UniProtKB/TrEMBL
    A0A7P0TAJ0
    Related
    ENSP00000506109.1, ENST00000679842.1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    236795281..236903981
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047421186.1 → XP_047277142.1  methionine synthase isoform X8

  2. XM_005273141.6 → XP_005273198.1  methionine synthase isoform X3

    UniProtKB/TrEMBL
    B7ZLW8
    Conserved Domains (5) summary
    COG0646
    Location:20 → 339
    MetH1; Methionine synthase I (cobalamin-dependent), methyltransferase domain [Amino acid transport and metabolism]
    PRK09490
    Location:18 → 1260
    metH; B12-dependent methionine synthase; Provisional
    cd00740
    Location:370 → 626
    MeTr; MeTr subgroup of pterin binding enzymes. This family includes cobalamin-dependent methyltransferases such as methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) and methionine synthase (MetH). Cobalamin-dependent ...
    cd02069
    Location:670 → 896
    methionine_synthase_B12_BD; B12 binding domain of methionine synthase. This domain binds methylcobalamin, which it uses as an intermediate methyl carrier from methyltetrahydrofolate (CH3H4folate) to homocysteine (Hcy).
    pfam02965
    Location:964 → 1245
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain

  3. XM_047421185.1 → XP_047277141.1  methionine synthase isoform X7

  4. XM_047421182.1 → XP_047277138.1  methionine synthase isoform X5

  5. XM_011544194.4 → XP_011542496.1  methionine synthase isoform X1

    UniProtKB/TrEMBL
    A0A6Q8PGK3
    Related
    ENSP00000502299.2, ENST00000674797.2
    Conserved Domains (5) summary
    COG0646
    Location:140 → 396
    MetH1; Methionine synthase I (cobalamin-dependent), methyltransferase domain [Amino acid transport and metabolism]
    PRK09490
    Location:140 → 1317
    metH; B12-dependent methionine synthase; Provisional
    cd00740
    Location:427 → 683
    MeTr; MeTr subgroup of pterin binding enzymes. This family includes cobalamin-dependent methyltransferases such as methyltetrahydrofolate, corrinoid iron-sulfur protein methyltransferase (MeTr) and methionine synthase (MetH). Cobalamin-dependent ...
    cd02069
    Location:727 → 953
    methionine_synthase_B12_BD; B12 binding domain of methionine synthase. This domain binds methylcobalamin, which it uses as an intermediate methyl carrier from methyltetrahydrofolate (CH3H4folate) to homocysteine (Hcy).
    pfam02965
    Location:1021 → 1302
    Met_synt_B12; Vitamin B12 dependent methionine synthase, activation domain

  6. XM_017001330.3 → XP_016856819.1  methionine synthase isoform X4

    UniProtKB/TrEMBL
    A0A6Q8PGK3

  7. XM_017001329.3 → XP_016856818.1  methionine synthase isoform X2

    UniProtKB/TrEMBL
    A0A6Q8PGK3

  8. XM_047421183.1 → XP_047277139.1  methionine synthase isoform X6

  9. XM_047421187.1 → XP_047277143.1  methionine synthase isoform X9

    Related
    ENSP00000355535.3, ENST00000366576.3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    236206330..236315021
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054336715.1 → XP_054192690.1  methionine synthase isoform X8

  2. XM_054336710.1 → XP_054192685.1  methionine synthase isoform X3

  3. XM_054336714.1 → XP_054192689.1  methionine synthase isoform X7

  4. XM_054336712.1 → XP_054192687.1  methionine synthase isoform X5

  5. XM_054336708.1 → XP_054192683.1  methionine synthase isoform X1

  6. XM_054336711.1 → XP_054192686.1  methionine synthase isoform X4

  7. XM_054336709.1 → XP_054192684.1  methionine synthase isoform X2

  8. XM_054336713.1 → XP_054192688.1  methionine synthase isoform X6

  9. XM_054336716.1 → XP_054192691.1  methionine synthase isoform X9

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q99707.2 GenPept UniProtKB/Swiss-Prot:Q99707

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