This gene encodes a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. This protein functions in the synthesis of methionine by regenerating methionine synthase to a functional state. Because methionine synthesis requires methyl-group transfer by a folate donor, activity of the encoded enzyme is important for folate metabolism and cellular methyla... See more...

Aliases for MTRR Gene

Aliases for MTRR Gene

  • 5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase 2 3 5
  • Methionine Synthase Reductase 2 3 4
  • Aquacobalamin Reductase 3 4
  • AqCbl Reductase 3 4
  • CblE 2 3
  • MSR 3 4
  • [Methionine Synthase]-Cobalamin Methyltransferase (Cob(II)Alamin Reducing) 3
  • Methionine Synthase Reductase, Mitochondrial 3
  • EC 1.16.1.8 4
  • EC 1.16.1.- 4
  • MTRR 5

External Ids for MTRR Gene

Previous GeneCards Identifiers for MTRR Gene

  • GC05P008057
  • GC05P007901
  • GC05P007921
  • GC05P007922

Summaries for MTRR Gene

Entrez Gene Summary for MTRR Gene

  • This gene encodes a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. This protein functions in the synthesis of methionine by regenerating methionine synthase to a functional state. Because methionine synthesis requires methyl-group transfer by a folate donor, activity of the encoded enzyme is important for folate metabolism and cellular methylation. Mutations in this gene can cause homocystinuria-megaloblastic anemia, cbl E type. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]

GeneCards Summary for MTRR Gene

MTRR (5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase) is a Protein Coding gene. Diseases associated with MTRR include Homocystinuria-Megaloblastic Anemia, Cble Complementation Type and Neural Tube Defects, Folate-Sensitive. Among its related pathways are Metabolism of water-soluble vitamins and cofactors and Cytochrome P450 - arranged by substrate type. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and flavin adenine dinucleotide binding. An important paralog of this gene is NOS2.

UniProtKB/Swiss-Prot Summary for MTRR Gene

  • Key enzyme in methionine and folate homeostasis responsible for the reactivation of methionine synthase (MTR/MS) activity by catalyzing the reductive methylation of MTR-bound cob(II)alamin (PubMed:17892308). Cobalamin (vitamin B12) forms a complex with MTR to serve as an intermediary in methyl transfer reactions that cycles between MTR-bound methylcob(III)alamin and MTR bound-cob(I)alamin forms, and occasional oxidative escape of the cob(I)alamin intermediate during the catalytic cycle leads to the inactive cob(II)alamin species (Probable). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:27771510). Also necessary for the utilization of methyl groups from the folate cycle, thereby affecting transgenerational epigenetic inheritance (By similarity). Also acts as a molecular chaperone for methionine synthase by stabilizing apoMTR and incorporating methylcob(III)alamin into apoMTR to form the holoenzyme (PubMed:16769880). Also serves as an aquacobalamin reductase by reducing aquacobalamin to cob(II)alamin in the presence of NADPH; this reduction leads to stimulation of the conversion of apoMTR and aquacobalamin to MTR holoenzyme (PubMed:16769880).

Gene Wiki entry for MTRR Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MTRR Gene

Genomics for MTRR Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MTRR 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 MTRR on the GeneHancer Hub at the UCSC Golden Path

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

Top Transcription factor binding sites by QIAGEN in the MTRR gene promoter:
  • COUP
  • COUP-TF
  • COUP-TF1
  • HNF-4alpha1
  • HNF-4alpha2
  • Nkx3-1
  • Nkx3-1 v1
  • POU2F1
  • POU2F1a
  • TBP

Genomic Locations for MTRR Gene

Latest Assembly
chr5:7,851,186-7,906,025
(GRCh38/hg38)
Size:
54,840 bases
Orientation:
Plus strand

Previous Assembly
chr5:7,869,261-7,901,226
(GRCh37/hg19 by Entrez Gene)
Size:
31,966 bases
Orientation:
Plus strand

chr5:7,851,299-7,906,138
(GRCh37/hg19 by Ensembl)
Size:
54,840 bases
Orientation:
Plus strand

Genomic View for MTRR Gene

Genes around MTRR on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for MTRR Gene

Proteins for MTRR Gene

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

    Protein Symbol:
    Q9UBK8-MTRR_HUMAN
    Recommended name:
    Methionine synthase reductase
    Protein Accession:
    Q9UBK8
    Secondary Accessions:
    • O60471
    • Q32MA9
    • Q7Z4M8

    Protein attributes for MTRR Gene

    Size:
    698 amino acids
    Molecular mass:
    77674 Da
    Cofactor:
    Name=FAD; Xref=ChEBI:CHEBI:57692;
    Cofactor:
    Name=FMN; Xref=ChEBI:CHEBI:58210;
    Quaternary structure:
    • Forms a multiprotein complex with MMACHC, MMADHC AND MTR.
    Miscellaneous:
    • It is debated whether the reaction of cob(II)alamin and NADP(+) occurs spontaneously or is enzyme catalyzed.

    Three dimensional structures from OCA and Proteopedia for MTRR Gene

    Alternative splice isoforms for MTRR Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MTRR Gene

Post-translational modifications for MTRR Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for MTRR Gene

Domains & Families for MTRR Gene

Gene Families for MTRR Gene

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

Protein Domains for MTRR Gene

InterPro:
Blocks:
  • Oxidoreductase FAD/NAD(P)-binding
  • Flavoprotein pyridine nucleotide cytochrome reductase signature
  • Flavodoxin signature
  • Flavodoxin/nitric oxide synthase

Suggested Antigen Peptide Sequences for MTRR Gene

GenScript: Design optimal peptide antigens:
  • Methionine synthase reductase (MTRR_HUMAN)
genes like me logo Genes that share domains with MTRR: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for MTRR Gene

Function for MTRR Gene

Molecular function for MTRR Gene

UniProtKB/Swiss-Prot Function:
Key enzyme in methionine and folate homeostasis responsible for the reactivation of methionine synthase (MTR/MS) activity by catalyzing the reductive methylation of MTR-bound cob(II)alamin (PubMed:17892308). Cobalamin (vitamin B12) forms a complex with MTR to serve as an intermediary in methyl transfer reactions that cycles between MTR-bound methylcob(III)alamin and MTR bound-cob(I)alamin forms, and occasional oxidative escape of the cob(I)alamin intermediate during the catalytic cycle leads to the inactive cob(II)alamin species (Probable). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:27771510). Also necessary for the utilization of methyl groups from the folate cycle, thereby affecting transgenerational epigenetic inheritance (By similarity). Also acts as a molecular chaperone for methionine synthase by stabilizing apoMTR and incorporating methylcob(III)alamin into apoMTR to form the holoenzyme (PubMed:16769880). Also serves as an aquacobalamin reductase by reducing aquacobalamin to cob(II)alamin in the presence of NADPH; this reduction leads to stimulation of the conversion of apoMTR and aquacobalamin to MTR holoenzyme (PubMed:16769880).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=2 [methionine synthase]-methylcob(III)alamin + H(+) + NADP(+) + 2 S-adenosyl-L-homocysteine = 2 [methionine synthase]-cob(II)alamin + NADPH + 2 S-adenosyl-L-methionine; Xref=Rhea:RHEA:23908, Rhea:RHEA-COMP:14714, Rhea:RHEA-COMP:14715, ChEBI:CHEBI:15378, ChEBI:CHEBI:16304, ChEBI:CHEBI:28115, ChEBI:CHEBI:57783, ChEBI:CHEBI:57856, ChEBI:CHEBI:58349, ChEBI:CHEBI:59789; EC=1.16.1.8; Evidence={ECO:0000269|PubMed:17892308};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=2 cob(II)alamin + H(+) + 2 H2O + NADP(+) = 2 aquacob(III)alamin + NADPH; Xref=Rhea:RHEA:20752, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15852, ChEBI:CHEBI:16304, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:16769880};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=2.89 uM for NADPH {ECO:0000269|PubMed:17892308}; KM=3540 uM for NADH {ECO:0000269|PubMed:17892308}; KM=3.7 uM for aquacobalamin (at 37 degrees Celsius, pH 7.2) {ECO:0000269|PubMed:16769880}; Note=kcat is 3.92 s(-1) for the reduction of cytochrome c3 with NADPH (PubMed:17892308). kcat is 0.24 s(-1) for the reduction of cytochrome c3 with NADH (PubMed:17892308). kcat is 220 min(-1) for aquacobalamin reduction (PubMed:16769880). {ECO:0000269|PubMed:16769880, ECO:0000269|PubMed:17892308};
GENATLAS Biochemistry:
5-methyltetrahydrofolate-homocysteine methyltransferase reductase,77kDa,sulfur aminoacid metabolism,with homology to cytochrome p450 reductase and C elegans methionine synthase reductase,activating cobalamin-dependent methionine synthase,risk factor for neural tube defect (combined with low cobalamin)

Enzyme Numbers (IUBMB) for MTRR Gene

Phenotypes From GWAS Catalog for MTRR Gene

Gene Ontology (GO) - Molecular Function for MTRR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003958 NADPH-hemoprotein reductase activity IBA,IDA 11466310
GO:0005515 protein binding IPI 17288554
GO:0010181 FMN binding IEA,TAS 9501215
GO:0016491 oxidoreductase activity IEA,IBA 21873635
GO:0016709 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen IBA 21873635
genes like me logo Genes that share ontologies with MTRR: view
genes like me logo Genes that share phenotypes with MTRR: view

Human Phenotype Ontology for MTRR Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Inhibitory RNAs for research

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

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for MTRR Gene

Localization for MTRR Gene

Subcellular locations from UniProtKB/Swiss-Prot for MTRR Gene

[Isoform B]: Cytoplasm.
[Isoform A]: Cytoplasm.

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

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Intermediate filaments (1)
  • Nucleoplasm (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MTRR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol IBA,TAS 9501215
GO:0045111 intermediate filament cytoskeleton IDA --
genes like me logo Genes that share ontologies with MTRR: view

Pathways & Interactions for MTRR Gene

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

Gene Ontology (GO) - Biological Process for MTRR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000096 sulfur amino acid metabolic process TAS --
GO:0006306 DNA methylation ISS --
GO:0006555 methionine metabolic process TAS 9501215
GO:0008652 cellular amino acid biosynthetic process IEA --
GO:0009086 methionine biosynthetic process IBA,IDA 11466310
genes like me logo Genes that share ontologies with MTRR: view

No data available for SIGNOR curated interactions for MTRR Gene

Drugs & Compounds for MTRR Gene

(23) Drugs for MTRR Gene - From: DrugBank, PharmGKB, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Methionine Approved Nutra Target, product of 125
Cyanocobalamin Approved Nutra Target, cofactor 465
Methotrexate Approved Pharma Folate antagonist,inhibits DFHR 1884
Folic acid Approved, Vet_approved Nutra 5007
FAD Approved Pharma 0

(15) Additional Compounds for MTRR Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
cob(ii)alamin
  • Co(I)-cobalamine
  • Cob(2)alamin
  • Cobinamide-co(1+)
  • Vitamin b12R
  • B12r
14463-33-3
s-adenosylmethionine
  • (3S)-5'-[(3-Amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine, inner salt
  • [1-(Adenin-9-yl)-1,5-dideoxy-beta-D-ribofuranos-5-yl][(3S)-3-amino-3-carboxypropyl](methyl)sulfonium
  • Acylcarnitine
  • AdoMet
  • S-(5'-Deoxyadenosin-5'-yl)-L-methionine
485-80-3
Cob(I)alamin
  • Vitamin b-12S
  • Vitamin b12S
  • Cyanocobalamin
  • Hydrido-cobalamin
  • Hydridocobalamin
18534-66-2
genes like me logo Genes that share compounds with MTRR: view

Transcripts for MTRR Gene

mRNA/cDNA for MTRR Gene

5 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
25 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

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

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

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b · 5c · 5d · 5e ^ 6a · 6b · 6c ^ 7 ^ 8a · 8b ^ 9a · 9b · 9c ^ 10a · 10b ^ 11 ^ 12 ^
SP1: - - - - - -
SP2: - - - - -
SP3: - - - - - -
SP4: - - - -
SP5: - - -
SP6: - - -
SP7: - - -
SP8: - - -
SP9: - -
SP10: - -
SP11: -
SP12: -
SP13: - - -
SP14: - -

ExUns: 13a · 13b · 13c ^ 14 ^ 15 ^ 16 ^ 17a · 17b
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:

Relevant External Links for MTRR Gene

GeneLoc Exon Structure for
MTRR

Expression for MTRR Gene

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

Protein differential expression in normal tissues from HIPED for MTRR Gene

This gene is overexpressed in Adrenal (59.6).

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



Protein tissue co-expression partners for MTRR Gene

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

SOURCE GeneReport for Unigene cluster for MTRR Gene:

Hs.481551

mRNA Expression by UniProt/SwissProt for MTRR Gene:

Q9UBK8-MTRR_HUMAN
Tissue specificity: Found in all tissues tested, particularly abundant in skeletal muscle.

Evidence on tissue expression from TISSUES for MTRR Gene

  • Liver(4.5)
  • Lung(4.4)
  • Nervous system(4)
  • Intestine(2.4)
  • Blood(2.4)
  • Skin(2.3)
  • Kidney(2.2)
  • Heart(2)

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

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • eye
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • skull
Thorax:
  • chest wall
  • clavicle
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • kidney
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
  • red blood cell
  • spinal column
  • vertebrae
genes like me logo Genes that share expression patterns with MTRR: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for MTRR Gene

Orthologs for MTRR Gene

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

Orthologs for MTRR Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia MTRR 29 30
  • 99.03 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia MTRR 29 30
  • 84.36 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia MTRR 29 30
  • 81.39 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Mtrr 29
  • 80.18 (n)
Mouse
(Mus musculus)
Mammalia Mtrr 29 16 30
  • 78.88 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia MTRR 30
  • 72 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia MTRR 30
  • 70 (a)
OneToOne
Chicken
(Gallus gallus)
Aves MTRR 29 30
  • 66.52 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia MTRR 30
  • 63 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia mtrr 29
  • 59.62 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.9723 29
Zebrafish
(Danio rerio)
Actinopterygii mtrr 29 30
  • 58.49 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta CG14882 30 31
  • 30 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea mtrr-1 29 30
  • 44.58 (n)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes NCP1 30
  • 25 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 39 (a)
OneToOne
Species where no ortholog for MTRR was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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 Vase (Ciona intestinalis)
  • 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 MTRR Gene

ENSEMBL:
Gene Tree for MTRR (if available)
TreeFam:
Gene Tree for MTRR (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MTRR: view image
Alliance of Genome Resources:
Additional Orthologs for MTRR

Paralogs for MTRR Gene

Paralogs for MTRR Gene

Pseudogenes.org Pseudogenes for MTRR Gene

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

Variants for MTRR Gene

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

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
1008396 Uncertain Significance: Homocystinuria-Megaloblastic anemia due to defect in cobalamin metabolism, cblE complementation type 7,892,786(+) C/G
NM_002454.3(MTRR):c.1430C>G (p.Ser477Cys)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
1009244 Uncertain Significance: Homocystinuria-Megaloblastic anemia due to defect in cobalamin metabolism, cblE complementation type 7,899,931(+) C/T
NM_002454.3(MTRR):c.1970C>T (p.Ala657Val)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
1019355 Uncertain Significance: Homocystinuria-Megaloblastic anemia due to defect in cobalamin metabolism, cblE complementation type 7,889,201(+) G/A
NM_002454.3(MTRR):c.1253G>A (p.Arg418Gln)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
1023313 Uncertain Significance: Homocystinuria-Megaloblastic anemia due to defect in cobalamin metabolism, cblE complementation type 7,895,855(+) A/G
NM_002454.3(MTRR):c.1676+3A>G
INTRON
1033921 Uncertain Significance: Homocystinuria-Megaloblastic anemia due to defect in cobalamin metabolism, cblE complementation type 7,895,818(+) G/A
NM_002454.3(MTRR):c.1642G>A (p.Gly548Ser)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for MTRR Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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

Variant ID Type Subtype PubMed ID
dgv334n21 CNV gain 19592680
esv2663385 CNV deletion 23128226
esv2729709 CNV deletion 23290073
esv2729710 CNV deletion 23290073
esv3064921 CNV deletion 24192839
nsv4705 CNV insertion 18451855
nsv508345 CNV deletion 20534489
nsv597003 CNV gain 21841781
nsv597005 CNV gain 21841781

Variation tolerance for MTRR Gene

Residual Variation Intolerance Score: 59.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 16.52; 97.77% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MTRR Gene

Human Gene Mutation Database (HGMD)
MTRR
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MTRR
Leiden Open Variation Database (LOVD)
MTRR

SNP Genotyping and Copy Number Assays for research

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

Disorders for MTRR Gene

MalaCards: The human disease database

(42) MalaCards diseases for MTRR Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
homocystinuria-megaloblastic anemia, cble complementation type
  • hmae
neural tube defects, folate-sensitive
  • ntdfs
methylmalonic acidemia without homocystinuria
  • methylmalonic aciduria without homocystinuria
homocystinuria
  • cbs deficiency
megaloblastic anemia
  • grasbeck-imerslund syndrome
- elite association - COSMIC cancer census association via MalaCards
Search MTRR in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

MTRR_HUMAN
  • Homocystinuria-megaloblastic anemia, cblE complementation type (HMAE) [MIM:236270]: 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. Cells from patients with HMAE fail to incorporate methyltetrahydrofolate into methionine in whole cells, but cell extracts show normal methionine synthase activity in the presence of a reducing agent. {ECO:0000269 PubMed:10484769, ECO:0000269 PubMed:9501215}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Neural tube defects, folate-sensitive (NTDFS) [MIM:601634]: The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. {ECO:0000269 PubMed:10444342, ECO:0000269 PubMed:12375236}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Genatlas disease for MTRR Gene

megaloblastic anemia,developmental delay,hyperhomocysteinemia and hypomathioninemia,cblE complementation group of disorders in folate/cobalamin metabolism

Additional Disease Information for MTRR

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Publications for MTRR Gene

  1. Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. (PMID: 15979034) O'Leary VB … Members of the Birth Defects Research Group (Molecular genetics and metabolism 2005) 3 4 22 25 40 72
  2. Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria. (PMID: 9501215) Leclerc D … Gravel RA (Proceedings of the National Academy of Sciences of the United States of America 1998) 2 3 4 22 72
  3. The methionine synthase reductase 66A>G polymorphism is a maternal risk factor for spina bifida. (PMID: 17024475) van der Linden IJ … Blom HJ (Journal of molecular medicine (Berlin, Germany) 2006) 3 22 25 40
  4. Genetic polymorphisms predisposing to hyperhomocysteinemia in cardiac transplant patients. (PMID: 15612980) Miriuka SG … Cole DE (Transplant international : official journal of the European Society for Organ Transplantation 2005) 3 22 25 40
  5. Association of MTRRA66G polymorphism (but not of MTHFR C677T and A1298C, MTRA2756G, TCN C776G) with homocysteine and coronary artery disease in the French population. (PMID: 16268464) Guéant-Rodriguez RM … Gueánt JL (Thrombosis and haemostasis 2005) 3 22 25 40

Products for MTRR Gene

Sources for MTRR Gene