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

Summary

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: mouse all
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Genomic context

Location:: 1q43

Exon count:: 33

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (236795281..236903981)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (236206330..236315021)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (236958581..237067281)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Genetic Association between the Risk of Dental Caries and MTR Gene Polymorphism in Chinese Children.
Title: Genetic Association between the Risk of Dental Caries and MTR Gene Polymorphism in Chinese Children.
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.
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.
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.
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.
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.
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.
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.
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.
""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".

Submit: New GeneRIF Correction See all GeneRIFs (223)

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	not available
Neural tube defects, folate-sensitive MedGen: C1866558 OMIM: 601634 GeneReviews: Not available	not available

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G32413 (e-PCR)
- UniSTS:117000

SHGC-76575 (e-PCR)
- UniSTS:56075

A009C16 (e-PCR)
- UniSTS:80670

STS-U73338 (e-PCR)
- UniSTS:45953

SHGC-141923 (e-PCR)
- UniSTS:171141

SHGC-76574 (e-PCR)
- UniSTS:60045

RH70474 (e-PCR)
- UniSTS:49808

D1S1568 (e-PCR)
- UniSTS:20369

AL009990 (e-PCR)
- UniSTS:11970

SHGC-76580 (e-PCR)
- UniSTS:25801

SHGC-145811 (e-PCR)
- UniSTS:174806

SHGC-142509 (e-PCR)
- UniSTS:171498

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 methionine synthase activity	TAS Traceable Author Statement more info
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 cobalamin metabolic process	TAS Traceable Author Statement more info
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	TAS Traceable Author Statement 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 sulfur amino acid metabolic process	TAS Traceable Author Statement 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

EC 2.1.1.13

NP_001278868.1

EC 2.1.1.13

NP_001278869.1

EC 2.1.1.13

NP_001397871.1

EC 2.1.1.13

XP_005273198.1

EC 2.1.1.13

XP_011542496.1

EC 2.1.1.13

XP_016856818.1

EC 2.1.1.13

XP_016856819.1

EC 2.1.1.13

XP_047277138.1

EC 2.1.1.13

XP_047277139.1

EC 2.1.1.13

XP_047277141.1

EC 2.1.1.13

XP_047277142.1

EC 2.1.1.13

XP_047277143.1

EC 2.1.1.13

XP_054192683.1

EC 2.1.1.13

XP_054192684.1

EC 2.1.1.13

XP_054192685.1

EC 2.1.1.13

XP_054192686.1

EC 2.1.1.13

XP_054192687.1

EC 2.1.1.13

XP_054192688.1

EC 2.1.1.13

XP_054192689.1

EC 2.1.1.13

XP_054192690.1

EC 2.1.1.13

XP_054192691.1

EC 2.1.1.13

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

NG_008959.1 RefSeqGene

Range

5012..113701

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Status: REVIEWED

Source sequence(s)

AL359185, AL359259

Consensus CDS

CCDS91175.1

UniProtKB/TrEMBL

A0A7P0TAJ0, B7ZLW8

Related

ENSP00000506109.1, ENST00000679842.1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

236795281..236903981

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047421186.1 → XP_047277142.1 methionine synthase isoform X8

UniProtKB/TrEMBL

B7ZLW8
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
XM_047421185.1 → XP_047277141.1 methionine synthase isoform X7

UniProtKB/TrEMBL

B7ZLW8
XM_047421182.1 → XP_047277138.1 methionine synthase isoform X5

UniProtKB/TrEMBL

B7ZLW8
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
XM_017001330.3 → XP_016856819.1 methionine synthase isoform X4

UniProtKB/TrEMBL

A0A6Q8PGK3
XM_017001329.3 → XP_016856818.1 methionine synthase isoform X2

UniProtKB/TrEMBL

A0A6Q8PGK3
XM_047421183.1 → XP_047277139.1 methionine synthase isoform X6

UniProtKB/TrEMBL

A0A6Q8PGK3
XM_047421187.1 → XP_047277143.1 methionine synthase isoform X9

UniProtKB/TrEMBL

B1ANE3

Related

ENSP00000355535.3, ENST00000366576.3

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

236206330..236315021

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054336715.1 → XP_054192690.1 methionine synthase isoform X8

UniProtKB/TrEMBL

B7ZLW8
XM_054336710.1 → XP_054192685.1 methionine synthase isoform X3

UniProtKB/TrEMBL

B7ZLW8
XM_054336714.1 → XP_054192689.1 methionine synthase isoform X7

UniProtKB/TrEMBL

B7ZLW8
XM_054336712.1 → XP_054192687.1 methionine synthase isoform X5

UniProtKB/TrEMBL

B7ZLW8
XM_054336708.1 → XP_054192683.1 methionine synthase isoform X1

UniProtKB/TrEMBL

A0A6Q8PGK3
XM_054336711.1 → XP_054192686.1 methionine synthase isoform X4

UniProtKB/TrEMBL

A0A6Q8PGK3
XM_054336709.1 → XP_054192684.1 methionine synthase isoform X2

UniProtKB/TrEMBL

A0A6Q8PGK3
XM_054336713.1 → XP_054192688.1 methionine synthase isoform X6

UniProtKB/TrEMBL

A0A6Q8PGK3
XM_054336716.1 → XP_054192691.1 methionine synthase isoform X9

UniProtKB/TrEMBL

B1ANE3