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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

MTRR Gene

protein-coding GIFtS: 64
GCID: GC05P007851

5-methyltetrahydrofolate-homocysteine methyltransferase...

Explore 101 diseases affiliated with
MTRR via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase¹ ²		Methionine Synthase Reductase²
CblE¹		Methionine Synthase Reductase, Mitochondrial²
MSR² ³		EC 1.16.1.8³
[Methionine Synthase]-Cobalamin Methyltransferase (Cob(II)Alamin Reducing)²

External Ids:	HGNC: 7473¹	Entrez Gene: 4552²	Ensembl: ENSG00000124275⁷	OMIM: 602568⁵	UniProtKB: Q9UBK8³

Export aliases for MTRR gene to outside databases

Previous GC identifers: GC05P008057 GC05P007901 GC05P007921 GC05P007922

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for MTRR:

Methionine is an essential amino acid required for protein synthesis and one-carbon metabolism. Its synthesis is

catalyzed by the enzyme methionine synthase. Methionine synthase eventually becomes inactive due to the oxidation of

its cob(I)alamin cofactor. The protein encoded by this gene regenerates a functional methionine synthase via reductive

methylation. It is a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. Patients of the

cbl-E complementation group of disorders of folate/cobalamin metabolism are defective in reductive activation of

methionine synthase. Alternative splicing of this gene results in multiple transcript variants encoding distinct

isoforms. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: MTRR_HUMAN, Q9UBK8

Function: Involved in the reductive regeneration of cob(I)alamin cofactor required for the maintenance of methionine

synthase in a functional state

Gene Wiki entry for MTRR

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000005.9 NC_018916.1 NT_006576.16

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the MTRR gene promoter:
Nkx3-1 TBP COUP-TF1 COUP Nkx3-1 v1 HNF-4alpha2 HNF-4alpha1 COUP-TF POU2F1 POU2F1a
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: MTRR promoter sequence

Search SABiosciences Chromatin IP Primers for MTRR

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat MTRR

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 5p15.31 Ensembl cytogenetic band: 5p15.31 HGNC cytogenetic band: 5p15.31

MTRR Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
MTRR gene location

GeneLoc information about chromosome 5 GeneLoc Exon Structure

GeneLoc location for GC05P007851: view genomic region (about GC identifiers)

Start:	7,851,299 bp from pter	End:	7,906,138 bp from pter
Size:	54,840 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: MTRR_HUMAN, Q9UBK8 (See protein sequence)

Recommended Name: Methionine synthase reductase

Size: 725 amino acids; 80410 Da

Cofactor: FAD

Cofactor: FMN

Subcellular location: Isoform B: Cytoplasm

Subcellular location: Isoform C: Cytoplasm

Subcellular location: Isoform A: Cytoplasm

2 PDB 3D structures from and Proteopedia for MTRR:

2QTL (3D)

2QTZ (3D)

Secondary accessions: O60471 Q32MA9 Q7Z4M8

Alternative splicing: 3 isoforms: Q9UBK8-1 Q9UBK8-2 Q9UBK8-3

Explore the universe of human proteins at neXtProt for MTRR: NX_Q9UBK8

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q9UBK8

MTRR Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_002445.2 NP_076915.2

ENSEMBL proteins:

ENSP00000426710 ENSP00000264668 ENSP00000423139 ENSP00000427200 ENSP00000423863

ENSP00000424719 ENSP00000424644 ENSP00000402510 ENSP00000426132 ENSP00000424599

ENSP00000427416 ENSP00000421318 ENSP00000421991 ENSP00000341918

Reactome Protein details: Q9UBK8
Human Recombinant Protein Products:

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	Uscn Proteins for MTRR

Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IDA	--
GO:0005730	NOT nucleolus	IDA	--
GO:0005737	cytoplasm	IDA	--
GO:0005829	cytosol	TAS	9501215
GO:0045111	intermediate filament cytoskeleton	IDA	--

MTRR for ontologies About GeneDecksing

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	Uscn ELISAs and CLIAs for MTRR

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

MTRR for domains About GeneDecksing

5/8 InterPro domains/families (see all 8):

IPR017927 Fd_Rdtase_FAD-bd

IPR001094 Flavdoxin

IPR008254 Flavodoxin/NO_synth

IPR001433 OxRdtase_FAD/NAD-bd

IPR017938 Riboflavin_synthase-like_b-brl

Graphical View of Domain Structure for InterPro Entry Q9UBK8

ProtoNet protein and cluster: Q9UBK8

4 Blocks protein families:

IPB001094 Flavodoxin signature

IPB001433 Oxidoreductase FAD/NAD(P)-binding

IPB001709 Flavoprotein pyridine nucleotide cytochrome reductase signature

IPB008254 Flavodoxin/nitric oxide synthase

UniProtKB/Swiss-Prot: MTRR_HUMAN, Q9UBK8

Similarity: Contains 1 FAD-binding FR-type domain

Similarity: Contains 1 flavodoxin-like domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: MTRR_HUMAN, Q9UBK8

Function: Involved in the reductive regeneration of cob(I)alamin cofactor required for the maintenance of methionine

synthase in a functional state

Catalytic activity: 2 [methionine synthase]-methylcob(I)alamin + 2 S-adenosylhomocysteine + NADP(+) = 2 [methionine

synthase]-cob(II)alamin + NADPH + 2 S-adenosyl-L-methionine

Biophysicochemical properties: Kinetic parameters: KM=2.89 uM for NADPH; KM=3540 uM for NADH;

Genatlas biochemistry entry for MTRR:

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 Number (IUBMB): EC 1.16.1.8¹

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		hsa-miR-374a* hsa-miR-361-5p
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MTRR

Gene Ontology (GO): 5/9 molecular function terms (GO ID links to tree view) (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003958	NOT NADPH-hemoprotein reductase activity	IBA	--
GO:0005506	iron ion binding	IEA	--
GO:0010181	FMN binding	TAS	9501215
GO:0016491	oxidoreductase activity	--	--
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	--

MTRR for ontologies About GeneDecksing

Animal Models:
2 MGI mutant phenotypes (inferred from 1 allele) (MGI details for Mtrr):

growth/size

homeostasis/metabolism

MTRR for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/8 super-pathways (see all 8) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Antimetabolite Pathway - Folate Cycle, Pharmacodynamics

	Antimetabolite Pathway - Folate Cycle, Pharmacodynamics	1.00			Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics	0.36
	Methotrexate Pathway (Cancer Cell), Pharmacodynamics	0.45

Biological oxidations

Biological oxidations

1.00

Phase II conjugation

0.52

Metabolism of amino acids and derivatives

Metabolism of amino acids and derivatives

1.00

Sulfur amino acid metabolism

Sulfur amino acid metabolism

1.00

Metabolism

Metabolism

1.00

Pathway sources
See GeneCards unified pathways
Show all pathways

2 BioSystems Pathways for MTRR

	One Carbon Metabolism
	Folate Metabolism

5/6 Reactome Pathways for MTRR (see all 6)

	Metabolism
	Sulfur amino acid metabolism
	Biological oxidations
	Metabolism of amino acids and derivatives
	Phase II conjugation

3 PharmGKB Pathways for MTRR

	Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
	Methotrexate Pathway (Cancer Cell), Pharmacodynamics
	Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics

MTRR for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for MTRR

STRING Interaction Network Preview (showing 3 interactants - click image to see more details)

3 Interacting proteins for MTRR (Q9UBK8³ ENSP00000264668⁴) via UniProtKB, MINT, STRING, and/or I2D

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
MMAB	Q96EY8³, ENSP00000266839⁴	I2D: score=1 STRING: ENSP00000266839
UBC	ENSP00000344818⁴	STRING: ENSP00000344818
ELAVL1	ENSP00000385269⁴	STRING: ENSP00000385269

About this table

Gene Ontology (GO): 3 biological process terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006555	methionine metabolic process	TAS	9501215
GO:0009086	methionine biosynthetic process	IEA	--
GO:0055114	oxidation-reduction process	TAS	9501215

MTRR for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

MTRR for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for MTRR

9 HMDB Compounds for MTRR About this table

Compound	Synonyms	CAS #	PubMed Ids
Cob(I)alamin	Vitamin B12s (see all 5)	18534-66-2	--
Cob(II)alamin	Vitamin B12r (see all 5)	14463-33-3	--
Cyanocobalamin	Dimethylbenzimidazoylcobamide (see all 92)	68-19-9	--
FAD	1H-Purin-6-amine flavin dinucleotide (see all 21)	146-14-5	--
Flavin Mononucleotide	FMN (see all 19)	146-17-8	--
NADP	Adenine-nicotinamide dinucleotide phosphate (see all 18)	53-59-8	--
NADPH	2'-(dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide (see all 23)	53-57-6	--
S-Adenosylhomocysteine	(S)-5'-(S)-(3-Amino-3-carboxypropyl)-5'-thioadenosine (see all 19)	979-92-0	--
S-Adenosylmethionine	(3S)-5'-[(3-amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine (see all 16)	29908-03-0	--

3 DrugBank Compounds for MTRR About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Cyanocobalamin	Cyanocob(III)alamin (see all 3)	68-19-9	target	cofactor	17024475 15979034 16268464 15612980 17611986
L-Methionine	(S)-2-amino-4-(methylthio)butanoic acid (see all 6)	63-68-3	target	product of	17101561 17079868 17369066
Hydroxocobalamin	Hydroxomin (see all 2)	13422-51-0	target	other	17139284 17016423

10/29 Novoseek chemical compound relationships for MTRR gene (see all 29) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
methionine	91	469	11466310 (5), 12416982 (5), 12871938 (5), 12482550 (4) (see all 99)
folate	88.9	79	10484769 (2), 15797993 (2), 14632302 (2), 17220339 (2) (see all 54)
homocysteine	87.9	98	12482550 (6), 15514263 (3), 12801615 (3), 11472746 (2) (see all 44)
cob(ii)alamin	85.7	27	19243433 (3), 14717604 (3), 15347655 (3), 17477549 (2) (see all 8)
cystathionine	85.3	25	17937607 (2), 17553479 (1), 17993766 (1), 14977639 (1) (see all 16)
cobalamin	82.4	34	10484769 (3), 15347655 (3), 19243433 (2), 17113603 (2) (see all 11)
vitamin b12	78.4	16	14656028 (2), 12807760 (1), 18226574 (1), 15135249 (1) (see all 13)
methylmalonic acid	73.9	4	20082058 (1), 17522601 (1)
5-methyltetrahydrofolate	69.6	6	16047261 (1), 15354395 (1), 17937607 (1)
methylcobalamin	68.9	4	11006889 (1), 16769880 (1), 12971424 (1)

1 PharmGKB related drug/compound annotation for MTRR gene

Drug/compound	PharmGKB Annotation
methotrexate	CA

About this table

Search CenterWatch for drugs/clinical trials and news about MTRR

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for MTRR gene (2 alternative transcripts):

NM_002454.2 NM_024010.2

Unigene Cluster for MTRR:

5-methyltetrahydrofolate-homocysteine methyltransferase reductase

Hs.481551 [show with all ESTs]

Unigene Representative Sequence: NM_002454

18/26 Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 26):

ENST00000507837 ENST00000502509 ENST00000511639 ENST00000513439(uc010itn.1)

ENST00000264668(uc003jed.3 uc003jee.4 uc003jef.4 uc003jeg.4 uc010ito.3)

ENST00000508047 ENST00000510279 ENST00000514220 ENST00000511461 ENST00000503550

ENST00000440940 ENST00000514369 ENST00000502550 ENST00000506877 ENST00000512217

ENST00000510525 ENST00000508890 ENST00000508101

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		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat MTRR

Additional cDNA sequence:

AF025794.1 AF121214.1 AK308442.1 AK311663.1 BC035977.1 BC054816.1 BC062577.1 BC109216.1

BC109217.1

17 DOTS entries:

DT.316433 DT.101981916 DT.100764835 DT.75144196 DT.92437944 DT.120815985 DT.100764831 DT.100031973

DT.100764837 DT.120815957 DT.120815978 DT.120815993 DT.92437947 DT.120816016 DT.412474 DT.92039497

DT.99978919

24/165 AceView cDNA sequences (see all 165):

BQ431497 AU124440 BI772430 AA279726 BX093000 AI276625 AI373715 AU279788

AI016080 BC062577 BC035977 AL079567 BC054816 BM468590 AA252150 BX348674

CB997527 AA451664 AI758177 AL600207 Z38251 AA085543 N36383 T26679

GeneLoc Exon Structure

5/14 Alternative Splicing Database (ASD) splice patterns (SP) for MTRR (see all 14) About this scheme

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:																																							-				-		-

ExUns:	13a	·	13b	·	13c	^	14	^	15	^	16	^	17a	·	17b
SP1:
SP2:
SP3:
SP4:
SP5:

ECgene alternative splicing isoforms for MTRR

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

MTRR expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: AAGACAGCGG

About this image

MTRR expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

1 LifeMap In Vivo Development Anatomical Compartment/Cell

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Head Mesenchyme

Branchial Arch 1

Paraxial Mesoderm Cells

Bone, Skeletal Muscle

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See MTRR Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for MTRR

SOURCE GeneReport for Unigene cluster: Hs.481551

UniProtKB/Swiss-Prot: MTRR_HUMAN, Q9UBK8

Tissue specificity: Found in all tissues tested, particularly abundant in skeletal muscle

SABiosciences Custom PCR Arrays for MTRR

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the last universal common ancestor (LUCA).

Orthologs for MTRR gene from 10/29 species (see all 29) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Mtrr^{1 , 5}	5-methyltetrahydrofolate-homocysteine methyltransferase more^{1, 5}	78.88(n)¹ 78.74(a)¹		13 (35.54 cM)⁵ 210009¹ NM_172480.2¹ NP_766068.1¹ 68560780⁵
chicken (Gallus gallus)	Aves	MTRR¹	5-methyltetrahydrofolate-homocysteine methyltransferase more	66.57(n) 61.27(a)		428502 XM_426057.3 XP_426057.3
lizard (Anolis carolinensis)	Reptilia	MTRR⁶ NDOR1⁶	--	62(a) 28(a)	1 ↔ 1 possible ortholog	4(82510544-82538382) GL344097.1(1892-21914)
African clawed frog (Xenopus laevis)	Amphibia	Xl.9723²	Xenopus laevis transcribed sequence with weak similarity more	72(n)		BX845943.1
zebrafish (Danio rerio)	Actinopterygii	mtrr¹	5-methyltetrahydrofolate-homocysteine methyltransferase more	58.44(n) 56.02(a)		560667 XM_684065.2 XP_689157.2
fruit fly (Drosophila melanogaster)	Insecta	CG14882³	[methionine synthase]-cobalamin methyltransferase more	31(a)		--
worm (Caenorhabditis elegans)	Secernentea	mtrr-1¹	Protein MTRR-1	45.15(n) 35.16(a)		174471 NM_063577.3 NP_495978.1
thale cress (Arabidopsis thaliana)	eudicotyledons	AT3G02280⁶ ATLFNR1⁶ (see all 5)	ferredoxin--NADP+ reductase (see all 5)	28(a) 20(a) (see all 5)	possible ortholog possible ortholog (see all 5)	3(453421-457841) 5(26450964-26453199)
rice (Oryza sativa)	Liliopsida	-- -- (see all 5)	NADPH reductase, putative, expressed ferredoxin--NADP reductase, chloroplast precursor,... (see all 5)	26(a) 19(a) (see all 5)	possible ortholog possible ortholog (see all 5)	1(30592390-30597478) 2(183601-185327)
E. coli (Escherichia coli)	Gamma proteobacteria	cysJ⁶	sulfite reductase, alpha subunit, flavoprotein	26(a)	possible ortholog	Chromosome(2888121-2889920)

ENSEMBL Gene Tree for MTRR (if available)
TreeFam Gene Tree for MTRR (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for MTRR gene

NOS3² POR² NOS2² NOS1²

MTRR for paralogs About GeneDecksing

1 Pseudogenes.org Pseudogene for MTRR
PGOHUM00000232597

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
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UniProtKB/Swiss-Prot: MTRR_HUMAN, Q9UBK8

Polymorphism: Variant Met-49 has been associated with an increased risk for spina bifida and may be associated with

chromosomal non-disjunction and Down syndrome

SNP ID	Valid	Clinical significance	Chr 5 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs1801394^1,2	C,F,H,	other	7852709(+)	`GAAATA/GTGTGA`	4	I M	mis¹		35		EA MN NS NA WA CSA EU	10160
rs201464747^1,2	C	--	7850052(+)	`TATCTA/GGAAAA`	2	--	us2k¹		0	--	--	--	--
rs145393069^1,2	F	--	7850630(+)	`GTGTGTGG/-CAAGA`	2	--	us2k¹		1		--	576
rs141755990^1,2	F	--	7851123(+)	`AATCTCCTCT/- GGGAG`	2	--	int¹		1		--	574
rs73032346^1,2	C,	--	7851344(+)	`CTTTGG/TTTCTA`	2	--	int¹		1		WA	2
rs75772655^1,2		--	7851439(+)	`ACCCGG/AGACGT`	2	--	int¹		4		CSA WA NA EA	360
rs149786347^1,2	C,	--	7851838(+)	`TTCAGT/CTTAAA`	2	--	int¹		1		--	576
rs111592503^1,2	C,	--	7852385(+)	`CGAGCC/GGATCA`	2	--	int¹		2		CSA	578
rs6413427^1,2	C,F	--	7852782(+)	`GAGCCG/ATTACA`	2	--	int¹		6		MN	984
rs7722483^1,2	C,	--	7852924(+)	`TATCAC/GCAGCA`	2	--	int¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for MTRR (7851299 - 7906138 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for MTRR: --
Human Gene Mutation Database (HGMD): MTRR

Locus Specific Mutation Databases (LSDB): MTRR

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

MTRR for disorders           About GeneDecksing

OMIM gene information: 602568
OMIM disorders: 236270  601634
UniProtKB/Swiss-Prot: MTRR_HUMAN, Q9UBK8

Defects in MTRR are the cause of methylcobalamin deficiency type E (cblE) [MIM:236270]; also known as vitamin

B12-responsive homocystinuria or homocystinuria-megaloblastic anemia complementation type E. Patients who are

defective in reductive activation of methionine synthase exhibit megaloblastic anemia, developmental delay,

hypomethioninemia, and hyperhomocysteinemia, a risk factor in cardiovascular disease and neural tube defects. It is an

autosomal recessive disease

Defects in MTRR may be a cause of susceptibility to folate-sensitive neural tube defects (FS-NTD)

[MIM:601634]. The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. Genetic defects in MTRR

may affect the risk of spina bifida via the maternal rather than the embryonic genotype

20/101 diseases for MTRR (see all 101): About MalaCards

homocystinuria-megaloblastic anemia, cbl e type neural tube defects, folate-sensitive homocystinuria-megaloblastic anemia neural tube defect

cble disorders of intracellular cobalamin metabolism megaloblastic anemia homocysteine

diffuse large b-cell lymphoma homocysteine plasma level cleft lip/palate age related macular degeneration

deep vein thrombosis homocystinuria patent ductus arteriosus spina bifida

cleft lip b-cell lymphomas methylcobalamin deficiency abdominal aortic aneurysm

4 diseases from the University of Copenhagen DISEASES database for MTRR:

Hyperhomocysteinemia Down syndrome Spina bifida Homocystinuria

10/17 Novoseek disease relationships for MTRR gene (see all 17) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
hyperhomocysteinemia	84.3	12	15866085 (1), 10484769 (1), 11006889 (1), 17079868 (1) (see all 7)
neural tube defects	77.4	9	12812837 (2), 15979034 (2), 18413293 (1), 17101561 (1) (see all 7)
homocystinuria	73.1	11	12555939 (2), 20120036 (2), 15714522 (1), 9501215 (1) (see all 8)
anemia megaloblastic	70.4	4	10484769 (1), 17554763 (1)
spina bifida	60.3	7	12375236 (2), 12812837 (1), 12649067 (1), 10444342 (1) (see all 5)
down syndrome	59.1	25	11807890 (4), 18257130 (2), 11443546 (2), 16115349 (1) (see all 12)
gonorrhea	51.7	1	10837198 (1)
cleft lip	36.5	1	17581676 (1)
vascular diseases	36.1	1	19348062 (1)
coronary artery disease	24.2	5	12801615 (2), 11006889 (1), 15612980 (1), 16485733 (1)

Genatlas disease: MTRR

megaloblastic anemia,developmental delay,hyperhomocysteinemia and hypomathioninemia,cblE complementation group of

disorders in folate/cobalamin metabolism

GeneTests: MTRR

Disorders of Intracellular Cobalamin Metabolism

Genetic Association Database (GAD): MTRR
Human Genome Epidemiology (HuGE) Navigator: MTRR (220 documents)

Export disorders for MTRR gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for MTRR gene, integrated from 9 sources (see all 326):
(articles sorted by number of sources associating them with MTRR)

Utopia: connect your pdf to the dynamic
world of online information

Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. (PubMed id 15979034)^{1, 2, 4, 7, 9} O'Leary V.B.... Brody L.C. (2005)
Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria. (PubMed id 9501215)^{1, 2, 3, 9} Leclerc D.... Gravel R.A. (1998)
Association of MTRRA66G polymorphism (but not of MTHFR C677T and A1298C, MTRA2756G, TCN C776G) with homocysteine and coronary artery disease in the French population. (PubMed id 16268464)^{1, 4, 7, 9} Gueant-Rodriguez R.M....Gueant J.L. (2005)
Genetic polymorphisms predisposing to hyperhomocysteinemia in cardiac transplant patients. (PubMed id 15612980)^{1, 4, 7, 9} Miriuka S.G....Cole D.E. (2005)
Restricted role for methionine synthase reductase defined by subcellular localization. (PubMed id 18221906)^{1, 2, 9} Froese D.S....Gravel R.A. (2008)
Mechanism of coenzyme binding to human methionine synthase reductase revealed through the crystal structure of the FNR-like module and isothermal titration calorimetry. (PubMed id 17892308)^{1, 2, 9} Wolthers K.R....Scrutton N.S. (2007)
Effects of polymorphisms of methionine synthase and methionine synthase reductase on total plasma homocysteine in the NHLBI Family Heart Study. (PubMed id 12482550)^{1, 4, 9} Jacques P.F....Rozen R. (2003)
Molecular basis for methionine synthase reductase deficiency in patients belonging to the cblE complementation group of disorders in folate/cobalamin metabolism. (PubMed id 10484769)^{1, 2, 9} Wilson A.... Gravel R.A. (1999)
Methionine synthase reductase polymorphisms are associated with serum osteocalcin levels in postmenopausal women. (PubMed id 17079868)^{1, 7, 9} Kim D.J....Kim S.Y. (2006)
Homocysteine remethylation enzyme polymorphisms and increased risks for neural tube defects. (PubMed id 12649067)^{1, 4, 9} Zhu H....Finnell R.H. (2003)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 4552	HGNC: 7473	AceView: MTRR	Ensembl:ENSG00000124275	euGenes: HUgn4552
ECgene: MTRR	H-InvDB: MTRR

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for MTRR	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MTRR

Intellectual Property for MTRR gene
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Patent Information for MTRR gene:
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GeneCards and IP:
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