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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

MTHFR Gene

protein-coding GIFtS: 64
GCID: GC01M011845

methylenetetrahydrofolate reductase (NAD(P)H)

(Previous name: 5,10-methylenetetrahydrofolate reductase (NADPH) )

Explore 339 diseases affiliated with
MTHFR via

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

Aliases
Methylenetetrahydrofolate Reductase (NAD(P)H)¹ ²
5,10-Methylenetetrahydrofolate Reductase (NADPH)¹ ²
EC 1.5.1.20³ ⁸
Methylenetetrahydrofolate Reductase²

External Ids:	HGNC: 7436¹	Entrez Gene: 4524²	Ensembl: ENSG00000177000⁷	OMIM: 607093⁵	UniProtKB: P42898³

Export aliases for MTHFR gene to outside databases

Previous GC identifers: GC01U990112 GC01M011694 GC01M011459 GC01M011556 GC01M011780 GC01M011000

(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 MTHFR:

The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to

5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene

influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and

mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.(provided by RefSeq, Oct

2009)

UniProtKB/Swiss-Prot: MTHR_HUMAN, P42898

Function: Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for

homocysteine remethylation to methionine

Gene Wiki entry for MTHFR (Methylenetetrahydrofolate reductase)

PharmGKB "VIP" summary for MTHFR

(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_000001.10 NC_018912.1 NT_021937.19

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the MTHFR gene promoter:
p53 AML1a MyoD
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: MTHFR promoter sequence

Search SABiosciences Chromatin IP Primers for MTHFR

Epigenetics:

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

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

Entrez Gene cytogenetic band: 1p36.3 Ensembl cytogenetic band: 1p36.22 HGNC cytogenetic band: 1p36.3

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

GeneLoc information about chromosome 1 GeneLoc Exon Structure

GeneLoc location for GC01M011845: view genomic region (about GC identifiers)

Start:	11,845,780 bp from pter	End:	11,866,977 bp from pter
Size:	21,198 bases	Orientation:	minus 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: MTHR_HUMAN, P42898 (See protein sequence)

Recommended Name: Methylenetetrahydrofolate reductase

Size: 656 amino acids; 74597 Da

Cofactor: FAD

Subunit: Homodimer

Secondary accessions: B2R7A6 Q5SNW9 Q7Z6M6 Q9UQR2

Explore the universe of human proteins at neXtProt for MTHFR: NX_P42898

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P42898

4/9 DME Specific Peptides for MTHFR (P42898) (see all 9)

DEFPNGR

EDVRPIFWA

GAVNLISRFDRM

GILTINSQPNIN

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

REFSEQ proteins: NP_005948.3

ENSEMBL proteins:

ENSP00000365777 ENSP00000365775 ENSP00000365770 ENSP00000405082 ENSP00000408307

ENSP00000398908 ENSP00000400460 ENSP00000365669 ENSP00000365767

Reactome Protein details: P42898
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	Uscn Proteins for MTHFR

Gene Ontology (GO): 1 cellular component term (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005829	cytosol	TAS	--

MTHFR for ontologies About GeneDecksing

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

MTHFR for domains About GeneDecksing

2 InterPro domains/families:

IPR003171 Mehydrof_redctse

IPR004621 Fadh2_euk

Graphical View of Domain Structure for InterPro Entry P42898

ProtoNet protein and cluster: P42898

1 Blocks protein family: IPB003171 Methylenetetrahydrofolate reductase

UniProtKB/Swiss-Prot: MTHR_HUMAN, P42898

Similarity: Belongs to the methylenetetrahydrofolate reductase family

(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: MTHR_HUMAN, P42898

Function: Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for

homocysteine remethylation to methionine

Catalytic activity: 5-methyltetrahydrofolate + NAD(P)(+) = 5,10-methylenetetrahydrofolate + NAD(P)H

Enzyme regulation: Allosterically regulated by S-adenosylmethionine

Genatlas biochemistry entry for MTHFR:

5-10 methylenetetrahydrofolate (THF) reductase,NADPH dependent,70kDa,reducing 5-10 methylene THF to,5 methyl-THF for

methionine biosynthesis,with a common variant putatively involved in occlusive vascular disease,neural tube

defects,colon cancer and adult akute leukemia. And a mutation responsible of increased mortality risk in men in middle

and old age

Enzyme Number (IUBMB): EC 1.5.1.20¹ ²

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		hsa-miR-3164 hsa-miR-26a-2* hsa-miR-4299 hsa-miR-764 hsa-miR-1205 hsa-miR-650 hsa-miR-4267 hsa-miR-3142

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In Situ Assay
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Gene Ontology (GO): 2 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004489	methylenetetrahydrofolate reductase (NADPH) activity	TAS	--
GO:0072341	modified amino acid binding	IDA	--

MTHFR for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for MTHFR:

Decreased Wnt reporter activit

Animal Models:
Mouse knock-out Mthfr^tm1Rzn for MTHFR
10 MGI mutant phenotypes (inferred from 3 alleles) (MGI details for Mthfr):

growth/size	homeostasis/metabolism	integument	limbs/digits/tail	mortality/aging
nervous system	no phenotypic analysis	reproductive system	skeleton	vision/eye

MTHFR 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

Fluoropyrimidine Activity

Fluoropyrimidine Activity

1.00

Fluoropyrimidine Pathway, Pharmacodynamics

0.30

One Carbon Metabolism

One Carbon Metabolism

1.00

One carbon pool by folate

0.52

Metabolism

Metabolism

1.00

Metabolic pathways

0.38

Vitamin B5 (pantothenate) metabolism

Metabolism of vitamins and cofactors

0.21

Metabolism of water-soluble vitamins and cofactors

0.21

Pathway sources
See GeneCards unified pathways
Show all pathways

4 BioSystems Pathways for MTHFR

	Fluoropyrimidine Activity
	One Carbon Metabolism
	Folate Metabolism
	Selenium Pathway

4 Reactome Pathways for MTHFR

	Metabolism of folate and pterines
	Metabolism
	Metabolism of vitamins and cofactors
	Metabolism of water-soluble vitamins and cofactors

4 PharmGKB Pathways for MTHFR

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

2 Kegg Pathways (Kegg details for MTHFR):

	One carbon pool by folate
	Metabolic pathways

UniProtKB/Swiss-Prot: MTHR_HUMAN, P42898

Pathway: One-carbon metabolism; tetrahydrofolate interconversion

MTHFR for pathways About GeneDecksing

Interactions:

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

STRING Interaction Network Preview (showing 5 interactants - click image to see 14)

5/40 Interacting proteins for MTHFR (P42898³ ENSP00000365775⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 40)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
PSMB1	P20618³, ENSP00000262193⁴	I2D: score=4 STRING: ENSP00000262193
NAA38	O95777³, ENSP00000249299⁴	I2D: score=4 STRING: ENSP00000249299
GGPS1	O95749³, ENSP00000282841⁴	I2D: score=1 STRING: ENSP00000282841
MAD2L1	Q13257³	I2D: score=4
PSMA1	P25786³	I2D: score=4

About this table

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

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006520	cellular amino acid metabolic process	TAS	7647779
GO:0006766	vitamin metabolic process	TAS	--
GO:0006767	water-soluble vitamin metabolic process	TAS	--
GO:0008015	blood circulation	TAS	7647779
GO:0009086	methionine biosynthetic process	IEA	--

MTHFR 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

MTHFR for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for MTHFR

10/13 HMDB Compounds for MTHFR (see all 13) About this table

Compound	Synonyms	CAS #	PubMed Ids
5,10-Methylene-THF	5,10-methylene-THF (see all 8)	31690-11-6	--
5-Methyltetrahydrofolic acid	5-Methyl tetrahydrofolate (see all 17)	134-35-0	--
Cyanocobalamin	Dimethylbenzimidazoylcobamide (see all 92)	68-19-9	--
FAD	1H-Purin-6-amine flavin dinucleotide (see all 21)	146-14-5	--
Menadione	Vitamin K3: 1,4-Dihydro-1,4-dioxo-2-methylnaphthalene (see all 49)	58-27-5	--
NAD	3-Carbamoyl-1-D-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate (see all 28)	53-84-9	--
NADH	1,4-Dihydronicotinamide adenine dinucleotide (see all 17)	58-68-4	--
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	--
Pyridoxal 5'-phosphate	Apolon B6 (see all 27)	54-47-7	--

1 DrugBank Compound for MTHFR About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Tetrahydrofolic acid	5,6,7,8-tetrahydrofolate (see all 3)	135-16-0	target	cofactor	12605391 10893069 11457468 11730351 10196703

10/84 Novoseek chemical compound relationships for MTHFR gene (see all 84) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
homocysteine	96.8	1798	11979347 (7), 9863549 (6), 11744407 (5), 15777550 (5) (see all 99)
folate	96.1	1642	11979347 (5), 16002818 (5), 11299748 (5), 16950805 (5) (see all 99)
5-methyltetrahydrofolate	91.6	218	19398669 (4), 12733064 (3), 12949355 (2), 9067278 (2) (see all 99)
vitamin b12	90.6	240	11979347 (5), 10780318 (5), 9264011 (3), 17295607 (3) (see all 99)
methionine	86.8	531	16024724 (4), 18351371 (3), 9587027 (3), 11730351 (3) (see all 99)
cystathionine	86.4	105	11216902 (2), 11292330 (2), 10517251 (2), 20160465 (2) (see all 66)
b vitamins	81.3	42	16379339 (2), 19180309 (2), 18053312 (2), 17332146 (2) (see all 22)
thymidylate	80.2	165	15510613 (2), 15598763 (2), 16045580 (2), 16920564 (2) (see all 91)
vitamin b6	79.5	53	19389261 (2), 17141597 (2), 19838916 (2), 17436239 (2) (see all 34)
5,10-methenyltetrahydrofolate	75	3	16712703 (1), 15503105 (1)

10/15 PharmGKB related drug/compound annotations for MTHFR gene (see all 15)

Drug/compound	PharmGKB Annotation
antipsychotics	CA
bevacizumab	CA
capecitabine	CA
carboplatin	CA
cisplatin	CA
cyanocobalamin	CA
cyclophosphamide	CA
fluorouracil	CA
folic acid	CA
leucovorin	CA

About this table

Search CenterWatch for drugs/clinical trials and news about MTHFR / MTHR

(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,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
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 MTHFR gene:

NM_005957.4

Unigene Clusters for MTHFR:

Methylenetetrahydrofolate reductase (NAD(P)H)

Hs.214142 [show with all ESTs], Hs.737916 [show with all ESTs]

Unigene Representative Sequences: NM_005957, AY046561

9 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000376592(uc001atb.1 uc001atc.2) ENST00000376590 ENST00000376585(uc001atd.1 uc009vnd.1)

ENST00000418034 ENST00000413656 ENST00000423400 ENST00000431243 ENST00000376486

ENST00000376583

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Additional cDNA sequence: AY046561.1

12 DOTS entries:

DT.87046276 DT.40285938 DT.100785174 DT.121440318 DT.100020900 DT.100785171 DT.121440369 DT.438299

DT.91685016 DT.95237745 DT.121440328 DT.121440354

24/121 AceView cDNA sequences (see all 121):

CB528721 AY046561 AY046564 AL048482 BM310814 BF724956 AI570123 AY046560

BE244583 AY046563 AY046565 C01118 AI358668 AY046562 BU501685 AI333711

CD251815 BF688893 BF993106 BM673336 CF121684 BV174002 BE513500 CF144282

GeneLoc Exon Structure

5/11 Alternative Splicing Database (ASD) splice patterns (SP) for MTHFR (see all 11) About this scheme

ExUns:	1a	·	1b	·	1c	·	1d	·	1e	^	2	^	3	^	4	^	5a	·	5b	·	5c	^	6a	·	6b	·	6c	·	6d	·	6e	·	6f	^	7	^	8a	·	8b	^	9a	·	9b	^	10a	·	10b	^	11a	·	11b	^
SP1:																							-										-				-
SP2:																																																	-
SP3:									-		-		-		-		-						-										-				-
SP4:									-		-		-		-		-						-										-
SP5:									-		-		-		-		-

ExUns:	12	^	13	^	14	^	15a	·	15b
SP1:
SP2:
SP3:
SP4:
SP5:

ECgene alternative splicing isoforms for MTHFR

(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

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

About this image
See MTHFR Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for MTHFR

SOURCE GeneReport for Unigene clusters: Hs.214142 Hs.737916

SABiosciences Expression via Pathway-Focused PCR Arrays including MTHFR:

Lung Cancer in human mouse rat

Drug Metabolism in human mouse rat

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In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MTHFR

(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)
About This Section

This gene was present in the last universal common ancestor (LUCA).

Orthologs for MTHFR gene from 11/37 species (see all 37) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Mthfr^{1 , 5}	5,10-methylenetetrahydrofolate reductase^{1, 5}	87.14(n)¹ 90.81(a)¹		4 (78.67 cM)⁵ 17769¹ NM_001161798.1¹ NP_001155270.1¹ 148039077⁵
chicken (Gallus gallus)	Aves	MTHFR¹	methylenetetrahydrofolate reductase (NAD(P)H)	77.98(n) 84.72(a)		419489 XM_417645.3 XP_417645.3
lizard (Anolis carolinensis)	Reptilia	--	--	20(a)	1 ↔ 1	AAWZ02037605(9764-12495)
African clawed frog (Xenopus laevis)	Amphibia	mthfr-prov²	5,10-methylenetetrahydrofolate reductase (NADPH)	76.22(n)		BC046708.1
zebrafish (Danio rerio)	Actinopterygii	mthfr¹	5,10-methylenetetrahydrofolate reductase (NADPH)	73.82(n) 79.81(a)		567547 NM_001128255.1 NP_001121727.1
fruit fly (Drosophila melanogaster)	Insecta	CG7560⁶	--	20(a)	1 ↔ 1	3L(11418250-11419495)
worm (Caenorhabditis elegans)	Secernentea	mthf-1¹	Protein MTHF-1	53.28(n) 49.26(a)		174254 NM_171025.5 NP_741028.1
baker's yeast (Saccharomyces cerevisiae)	Saccharomycetes	MET13(YGL125W)⁴ MET13¹	Major isozyme of methylenetetrahydrofolate reductase, more⁴ Met13p¹	51.38(n)¹ 44.11(a)¹		7(272520-274322)⁴ 852752^{1, 4} NP_011390.2^{1, 4}
thale cress (Arabidopsis thaliana)	eudicotyledons	MTHFR1¹	methylenetetrahydrofolate reductase 1	51.98(n) 45.49(a)		825167 NM_115860.3 NP_191556.1
rice (Oryza sativa)	Liliopsida	AK121351.1²	--	72.01(n)		AK121351.1

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

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for MTHFR gene

MTHFR for paralogs About GeneDecksing

1 Pseudogenes.org Pseudogene for MTHFR
PGOHUM00000251049

(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)
About This Section

UniProtKB/Swiss-Prot: MTHR_HUMAN, P42898

Polymorphism: Genetic variation in MTHFR influences susceptibility to occlusive vascular disease, neural tube defects

(NTD), colon cancer and acute leukemia

SNP ID	Valid	Clinical significance	Chr 1 pos	Sequence	#	AA Chg	Type	More	#	Pop	Total sample
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs1801133^1,2	C,F,O,A,H,	non-pathogenic	11011454(-)	`GGGAGA/C/G/T CGATT`	2	A V	mis¹ ese³		58	NA EA MN NS EU CSA WA	16646
rs45590836^1,2	C	pathogenic	11006360(-)	`TTCATG/ATTCTG`	2	/I /M	mis¹		1	--	480
rs121434296^1,2	C	pathogenic	11009899(-)	`TCTACC/TGTACC`	2	R C	mis¹		1	NA	4552
rs1801131^1,2	C,F,H,	other	11009552(-)	`TGAAGA/C/G/T AAGTG`	2	E A	mis¹		46	MN NA NS EA CSA WA EU	11558
rs74053317^1,2	C,	--	11000460(+)	`CCTCAC/TGCTCT`	2	--	ds500¹ int¹		2	WA	120
rs1057624^1,2	C,	--	11001356(-)	`AGGCTA/GTCAAC`	2	--	int¹ ut3¹ ese³		3	MN NA	306
rs2184226^1,2	C,F,O,H,	--	11002523(-)	`AAGGAA/GTAGCC`	2	--	int¹ ut3¹		21	EA NA NS CSA WA EU	2515
rs3820192^1,2	C,F,	--	11002859(-)	`CTCTCC/ACGGCT`	2	--	int¹ ut3¹ ese³		8	MN WA NA EA	718
rs41275468^1,2	C,F,	--	11003230(+)	`CGAGGG/AATGGG`	2	--	ut3¹ int¹		1	NA	120
rs114646114^1,2	C,F,	--	11004010(+)	`CCCTTC/TGTTTT`	2	--	int¹ ut3¹		1	WA	118

HapMap Linkage Disequilibrium report for MTHFR (11845780 - 11866977 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for MTHFR: --
Human Gene Mutation Database (HGMD): MTHFR

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing MTHFR

DNA2.0 Custom Variant and Variant Library Synthesis for MTHFR

(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

MTHFR for disorders           About GeneDecksing

OMIM gene information: 607093
OMIM disorders: 236250  181500  601634  188050
UniProtKB/Swiss-Prot: MTHR_HUMAN, P42898

Defects in MTHFR are the cause of methylenetetrahydrofolate reductase deficiency (MTHFRD) [MIM:236250]. MTHFRD

is autosomal recessive disorder with a wide range of features including homocysteinuria, homocysteinemia [MIM:603174],

developmental delay, severe mental retardation, perinatal death, psychiatric disturbances, and later-onset

neurodegenerative disorders

Defects in MTHFR may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:601367]; also known as

cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural

tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting

from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders

with multiple genetic and environmental risk factors

Defects in MTHFR 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

20/339 diseases for MTHFR (see all 339): About MalaCards

neural tube defect glycine n-methyltransferase deficiency mthfr thermolabile variant carotid intimal medial thickness

vascular disease open-angle glaucoma 5-fluorouracil toxicity retinal vein occlusion

acute leukemia central retinal vein occlusion antithrombin iii deficiency heparin-induced thrombocytopenia

deep vein thrombosis colon cancer homocystinuria due to mthfr deficiency homocysteine

limb reduction defect patent foramen ovale post-traumatic epilepsy spinal cord injury

20/26 diseases from the University of Copenhagen DISEASES database for MTHFR (see all 26):

Hyperhomocysteinemia Thrombophilia Homocystinuria Cerebrovascular accident

Placental abruption Hypertension Spina bifida Vitamin B12 deficiency

Colorectal cancer Heart disease Cleft lip Atherosclerosis

Protein C deficiency Down syndrome Migraine Pulmonary embolism

Antithrombin III deficiency Schizophrenia Portal vein thrombosis Antiphospholipid syndrome

10/94 Novoseek disease relationships for MTHFR gene (see all 94) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
hyperhomocysteinemia	95.5	343	16909866 (4), 18234410 (3), 11747974 (3), 19748043 (3) (see all 99)
methylenetetrahydrofolate reductase deficiency	93.1	51	10961793 (3), 12142069 (2), 18539994 (2), 18616155 (2) (see all 43)
thrombophilia	86.5	85	14691342 (2), 14747183 (2), 15834246 (2), 9890294 (1) (see all 51)
neural tube defects	86.2	119	12431255 (3), 10602111 (3), 10100053 (2), 10732818 (2) (see all 69)
folate deficiency	82.9	43	10452905 (2), 14734201 (2), 16950805 (2), 11440783 (2) (see all 28)
homocysteinemia	82	20	16055253 (2), 15834927 (2), 18220649 (1), 18328637 (1) (see all 13)
homocystinuria	81.1	50	9490685 (3), 8752689 (3), 15217352 (3), 8124871 (3) (see all 27)
venous thrombosis	75.3	75	9490685 (3), 10837091 (2), 18293456 (2), 17353498 (2) (see all 50)
vascular diseases	75.2	89	8989110 (3), 10477457 (2), 17099857 (2), 10318658 (2) (see all 61)
apc resistance	71.1	18	18191809 (1), 10847236 (1), 15609280 (1), 16797917 (1) (see all 16)

Genetic Association Database (GAD): MTHFR
Human Genome Epidemiology (HuGE) Navigator: MTHFR (2229 documents)

Export disorders for MTHFR 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)
About This Section

PubMed articles for MTHFR gene, integrated from 9 sources (see all 3302):
(articles sorted by number of sources associating them with MTHFR)

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

Mutations in the genes regulating methylene tetrahydrofolate reductase (MTHFR C-->T677) and cystathione beta-synthase (CBS G-->A919, CBS T-->c833) are not associated with myocardial infarction in African Americans. (PubMed id 11457468)^{1, 4, 7, 9} Dilley A....Evatt B.L. (2001)
Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults. (PubMed id 10536004)^{1, 2, 4, 9} Skibola C.F.... Morgan G. (1999)
Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. (PubMed id 7920641)^{1, 2, 3, 9} Goyette P.... Rozen R. (1994)
Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. (PubMed id 15534175)^{1, 2, 4} Casas J.P.... Sharma P. (2004)
An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and common carotid atherosclerosis. (PubMed id 11558898)^{1, 4, 9} Kawamoto R....Konishi I. (2001)
Severe and mild mutations in cis for the methylenetetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR. (PubMed id 8940272)^{1, 2, 9} Goyette P.... Rozen R. (1996)
Methylenetetrahydrofolate reductase polymorphism is associated with folate pool in gastrointestinal cancer tissue. (PubMed id 11299748)^{1, 4, 9} Kawakami K....Watanabe G. (2001)
Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR). (PubMed id 9680386)^{1, 2, 9} Goyette P....Rozen R. (1998)
Polymorphism of apoprotein E (APOE), methylenetetrahydrofolate reductase (MTHFR) and paraoxonase (PON1) genes in patients with cerebrovascular disease. (PubMed id 11388660)^{1, 4, 9} Topic E....Zuntar I. (2001)
Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency. (PubMed id 9781030)^{1, 2, 9} Kluijtmans L.A.J.... Blom H.J. (1998)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 4524	HGNC: 7436	AceView: MTHFR	Ensembl:ENSG00000177000	euGenes: HUgn4524
ECgene: MTHFR	Kegg: 4524	H-InvDB: MTHFR

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for MTHFR	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for MTHFR	Genetics and Cytogenetics in Oncology and Haematology
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MTHFR
NIEHS-SNPs	http://egp.gs.washington.edu/data/mthfr/
SHMPD	http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=MTHFR
Wikipedia	http://en.wikipedia.org/wiki/Methylenetetrahydrofolate_reductase

Intellectual Property for MTHFR gene
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Patent Information for MTHFR gene:
Search GeneIP for patents involving MTHFR

GeneCards and IP:
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MTHFR Gene

methylenetetrahydrofolate reductase (NAD(P)H)

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Pregnancy loss
Lymphoblastic Leukemia Acute Childhood
Down Syndrome
THROMBOTIC STROKE
Migraine
Vitamin Deficiency
Microsatellite Instability
Genetic Susceptibility
Myelomeningocele
Riboflavin Deficiency
coagulopathy
Antithrombin III Deficiency
Atherosclerosis
Breast Cancer
NAION
Deep vein thrombosis
Retinal Vein Occlusion
Schizophrenia
Antiphospholipid Syndrome
Cancer
methylmalonic aciduria
Cervical Intraepithelial Neoplasia
Brain Infarction
Coronary Atherosclerosis
Cerebral Thrombosis
Heart Defects Congenital
Miscarriage
RENAL DISEASE
Cerebral Infarction
ARTERIAL THROMBOSIS
Colorectal Cancer
Protein C Deficiency
Transient Ischemic Attack
Diabetic Nephropathies
Germ-Line Mutation
Microangiopathy Diabetic
Hyperhomocysteinemia
nutritional deficiency
Rheumatoid Arthritis
Cardiovascular Diseases
HELLP Syndrome
Thrombosis
Embryo Loss
Lymphoblastic Leukemia Acute
CEREBRAL VENOUS THROMBOSIS
Sinus Thrombosis
SMOKING HABIT
Carotid Atherosclerosis
Preeclampsia
Cleft Lip
Coronary Heart Disease
Budd-Chiari Syndrome
Gastric Cancer
Placental Diseases
APC Resistance
Anemia Megaloblastic
Colon Cancer
Venous Thrombosis
Abruptio Placentae
ACUTE LEUKEMIA
Eclampsia
Intrauterine death
Diabetes Mellitus
Arterial Occlusive Diseases
Miscarriage Recurrent
systemic hypertension
Neural Tube Defects
HOMOCYSTEINEMIA
Arteriosclerosis
Anencephaly
Intrauterine Growth Retardation
Cleft Palate
Vitamin B12 Deficiency
FOLATE DEFICIENCY
Myocardial Infarction
Vitamin B Deficiency
Coronary Artery Disease
Protein S Deficiency
Adenoma
Dementia Vascular
Homocystinuria
Infertility Male
Thrombophilia
STROKE
Spina Bifida
Vascular Diseases
Central retinal vein occlusion
Pulmonary Embolism
CEREBROVASCULAR DISEASE
NIDDM
METHYLENETETRAHYDROFOLATE REDUCTASE DEFICIENCY
Pregnancy Complications
Thromboembolism
Renal Failure Chronic

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MTHFR Gene

methylenetetrahydrofolate reductase (NAD(P)H)

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