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MTHFR Gene

protein-coding GIFtS: 69

GC01M011780

5,10-methylenetetrahydrofolate reductase (NADPH)
Symbol approved by the HUGO Gene Nomenclature Committee (HGNC) database

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc , and/or ⁷Ensembl, ⁸miRBase)
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Aliases
EC 1.5.1.20 ^³
OTTHUMP00000002367 ^²
OTTHUMP00000002368 ^²

Descriptions
5,10-methylenetetrahydrofolate reductase ^²
5,10-methylenetetrahydrofolate reductase (NADPH) ^²
methylenetetrahydrofolate reductase intermediate form ^²

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

Search outside databases for aliases for MTHFR gene

Previous GC identifers: GC01U990112 GC01M011694 GC01M011459 GC01M011556

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

EntrezGene summary for MTHFR:

Methylenetetrahydrofolate reductase (EC 1.5.1.20) catalyzes the conversion of

5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine

remethylation to methionine.[supplied by OMIM]

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)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 36),
and/or miRBase,
Genomic Views according to UCSC and Ensembl, Transcription factor binding sites according to SABiosciences)
About This Section

Genomic View:

UCSC Golden Path with GeneCards custom track

Transcription factor binding sites upstream to the MTHFR gene

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)

GeneLoc gene densities for chromosome 1 GeneLoc Exon Structure

GeneLoc location for GC01M011780: (about GC identifiers)

Start:	11,768,367 bp from pter
End:	11,788,702 bp from pter
Size:	20,336 bases
Orientation:	minus strand

RefSeq DNA sequence:

NC_000001.9 NT_021937.18

(According to ¹UniProtKB, and/or Ensembl, Phosphorylation sites according to ²Phosphosite, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Enzo Life Sciences, Abnova, OriGene and/or, Abcam,
Biochemical Assays by Invitrogen, Millipore, R&D Systems, Cell Signaling Technology, and/or Enzo Life Sciences, Ontologies according to Gene Ontology Consortium 01 Apr 2009 and Entrez Gene, Antibodies by Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Cell Signaling Technology, Abcam, Abnova, and/or Novus Biologicals)
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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: Q7Z6M6 Q9UQR2

Post-translational modifications:

View phosphorylation sites using PhosphoSite²

REFSEQ proteins: NP_005948.3

ENSEMBL proteins:

ENSP00000365777 ENSP00000365775 ENSP00000365770 ENSP00000365767

Human Recombinant Proteins

	Browse Drug Discovery Central at Invitrogen for human recombinant proteins
	Browse Purified and Recombinant Proteins at Millipore
	Browse Human Recombinant Proteins at Sigma-Aldrich
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Recombinant Proteins from Abcam (MTHFR)
	Human Recombinant Proteins from Abnova (MTHFR)

Browse Origene for full length recombinant human proteins expressed in human HEK293 cells

1 Gene Ontology (GO) cellular component term (links to tree view):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005829	cytosol	EXP	7726158

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Antibodies for MTHFR:

	Browse Antibodies Central at Invitrogen
	Browse Millipore's Extensive Line of Mono- and Polyclonal Antibodies
	Sigma-Aldrich Antibodies for MTHFR
	Browse R&D Systems for Antibodies
	Antibodies from Abcam (MTHFR), each with their Abpromise^SM
	Monoclonal and Polyclonal Antibodies from Abnova (MTHFR)
	Novus Biologicals Antibodies for MTHFR

Assays for MTHFR:

	Browse Invitrogen for biochemical assays
	Browse Kits and Assays available from Millipore
	Browse R&D Systems for biochemical assays
	Browse biochemical assays available from Enzo Life Sciences

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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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 MGI Jun 06 2009, UniProtKB, IUBMB,and/or Genatlas,
shRNA from OriGene, Sigma-Aldrich, RNAi from Sigma-Aldrich,
RNAi Products, Clones, and Q-PCR Products from Invitrogen, Millipore, OriGene, and/or Abnova, siRNAs from Applied Biosystems, SYBR primers from OriGene, Cell-based Assays from Millipore, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
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Inhib. RNA:		Invitrogen RNAi Products for gene knock-down (MTHFR)
		Browse for Gene Knock-down Tools from Millipore
		Abnova Chimera RNAi Products for Gene knock-down (MTHFR)

OriGene 29mer shRNA kit in GFP-retroviral vector: NM_005957

Applied Biosystems Silencer® siRNAs for MTHFR

Sigma-Aldrich siRNA and siRNA Panels for MTHFR

Sigma-Aldrich shRNA for MTHFR

Explore Sigma-Aldrich super-pooled esiRNAs

Clones:		Invitrogen Clones for MTHFR
		Browse Clones for the Expression of Recombinant Proteins Available from Millipore

OriGene GFP tagged cDNA clone in CMV expression vector: NM_005957
Myc/DDK tagged cDNA clone in CMV expression vector: NM_005957
untagged cDNA clone in CMV expression vector: NM_005957

Primers:

Browse Quantitative PCR Central at Invitrogen for Q-PCR LUX™ Primers

OriGene genome-wide validated SYBR primer pairs: NM_005957

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

Enzyme Number (IUBMB): EC 1.5.1.20

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

9 MGI mutant phenotypes (inferred from 1 allele) (MGI details for Mthfr):

growth/size	homeostasis/metabolism	life span-post-weaning/aging	limbs/digits/tail	nervous system
reproductive system	skeleton	skin/coat/nails	vision/eye

3 Gene Ontology (GO) molecular function terms (links to tree view):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004489	methylenetetrahydrofolate reductase (NADPH) activity	TAS	7647779
GO:0005515	protein binding	IPI	15231747
GO:0016491	oxidoreductase activity	IEA	--

About this table

(Pathways according to Invitrogen (maps by GeneGo), Millipore, Cell Signaling Technology, Sigma-Aldrich, KEGG and/or UniProtKB,
Sets of similar genes according to GeneDecks, Proteins Network according to SABiosciences, Interactions according to ¹UniProtKB, ²MINT, and/or ³STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
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2 Sigma-Aldrich "Your Favorite Gene" Pathways for MTHFR (Your Favorite Gene powered by Ingenuity)

One Carbon Pool by Folate
Methane Metabolism

GeneDecks MTHFR for the pathways selected above

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UniProtKB/Swiss-Prot: MTHR_HUMAN, P42898

Pathway: One-carbon metabolism; tetrahydrofolate pathway

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

5/58 Interacting proteins for MTHFR (ENSP00000365767³ P42898¹) via UniProtKB, MINT, and/or STRING (see all 58 )

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
LSM8	O95777¹	EBI-372435, EBI-347779
MTR	ENSP00000355535³	STRING (score=.997)
MTHFD1	ENSP00000216605³	STRING (score=.983)
SHMT1	ENSP00000318868³	STRING (score=.983)
TYMS	ENSP00000315644³	STRING (score=.981)

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4 Gene Ontology (GO) biological process terms (links to tree view):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006520	amino acid metabolic process	TAS	7647779
GO:0008015	blood circulation	TAS	7647779
GO:0009086	methionine biosynthetic process	IEA	--
GO:0055114	oxidation reduction	IEA	--

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, Sigma-Aldrich, Tocris Bioscience, and/or Novoseek and Drugs according to Enzo Life Sciences and/or PharmGKB)
About This Section

Browse drugs & compounds from Enzo Life Sciences

Browse Small Molecules at Sigma-Aldrich

Browse Tocris compounds for MTHFR
10/28 Novoseek chemical compound relationships for MTHFR gene (see all 28 )

Compound	Score	Articles	PubMed IDs for Articles with Shared Sentences (# sentences)
homocysteine	96.82	1637	11979347 (7), 9863549 (6), 11744407 (5), 10229729 (5) (see all 99)
5-methyltetrahydrofolate	91.78	204	19398669 (4), 12733064 (3), 12949355 (2), 9067278 (2) (see all 99)
methionine	86.77	489	16024724 (4), 18351371 (3), 9587027 (3), 11730351 (3) (see all 99)
cystathionine	86.52	99	11216902 (2), 11292330 (2), 10517251 (2), 17327360 (2) (see all 63)
5,10-methenyltetrahydrofolate	73.80	3	16712703 (1), 15503105 (1)
hinfi	73.04	18	11427218 (1), 14560345 (1), 15764293 (1), 9133512 (1) (see all 16)
sele	65.15	3	11341749 (1), 11714857 (1), 15076187 (1)
riboflavin	63.72	49	17303386 (5), 12145019 (4), 12560354 (3), 15454103 (3) (see all 22)
s-adenosylmethionine	61.61	54	16024724 (4), 11555831 (3), 11508552 (2), 17457696 (2) (see all 23)
s-adenosylhomocysteine	60.56	19	11555831 (2), 16024724 (1), 15122759 (1), 18823966 (1) (see all 9)

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10/14 PharmGKB drug compound relationships for MTHFR gene (see all 14 )

Drug compound	PharmGKB Relations	PubMed IDs for articles supporting these relationships
5-fluorouracil	CO FA GN	14740638 14734703 12738713 10462625 15608557
asparaginase	CO	15713801
cytarabine	CO	15713801
daunorubicin	CO	15713801
etoposide	CO	15713801
folic acid	CO PD GN	8542260 12384833 14744749 12215845 14656021
irinotecan	CO PD GN	14740638 14962716
mercaptopurine	CO	15713801
methotrexate	CO PD GN	14647408 12453860 11418485 12471611 14740638 12915598 15361376 15713801
prednisone	CO	15713801

About this table

(GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 219 Homo sapiens; Jun 2 2009) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView,
non coding RNAs according to RNAdb,
ESTs according to GeneTide,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from Invitrogen, Millipore, and/or Abnova,
siRNAs from Applied Biosystems, Sigma-Aldrich,
shRNA from Sigma-Aldrich, OriGene,
Tagged/untagged cDNA clones from OriGene,
Expression Assays from Applied Biosystems)
About This Section

Inhib. RNA:		Invitrogen RNAi Products for gene knock-down (MTHFR)
		Browse for Gene Knock-down Tools from Millipore
		Abnova Chimera RNAi Products for Gene knock-down (MTHFR)

OriGene 29mer shRNA kit in GFP-retroviral vector: NM_005957

Sigma-Aldrich siRNA and siRNA Panels for MTHFR

Sigma-Aldrich shRNA for MTHFR

Explore Sigma-Aldrich super-pooled esiRNAs

Applied Biosystems Silencer® siRNAs:

NM_005957

REFSEQ mRNAs for MTHFR gene:

NM_005957.3

Applied Biosystems TaqMan ® Gene Expression Assays:

NM_005957

              OriGene GFP tagged cDNA clone in CMV expression vector: NM_005957
                                 Myc/DDK tagged cDNA clone in CMV expression vector: NM_005957
                                 untagged cDNA clone in CMV expression vector: NM_005957

Additional cDNA sequence:

AB209113.1 AJ237672.1 AK312907.1 AY046560.1 AY046561.1 AY046562.1 AY046563.1 AY046564.1

AY046565.1 BC011614.2 BC018766.1 BC053509.1

12 DOTS entries:

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

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

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

AY046565 AL048482 BE244583 AY046561 BU501685 AY046564 CB528721 AY046563

AI358668 C01118 BM310814 AI570123 AY046562 BF724956 AY046560 AI333711

BI014733 BQ707098 CF122109 BG683043 AA309849 BU633781 BM662260 BQ940401

highest scoring ESTs for MTHFR:

AA494230 AJ237672 AU129663 AW502770 AY046560 AY046564 BC053509 BQ924752 BX339167 BX424988

Unigene Cluster for MTHFR:

5,10-methylenetetrahydrofolate reductase (NADPH)

Hs.214142 [show with all ESTs]

Unigene Representative Sequence: NM_005957

GeneLoc Exon Structure

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

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:

About this scheme

ECgene alternative splicing isoforms for MTHFR

4 Ensembl transcripts including schematic representations:

ENST00000376592 ENST00000376590 ENST00000376585 ENST00000376583

(Experimental results according to ¹GeneNote and GNF BioGPS,
probe sets-to-genes annotations according to ²GeneAnnot , ³GeneTide , Sets of similar genes according to GeneDecks, Electronic Northern calculations according to data from UniGene (Build 219 Homo sapiens), SAGE tags according to CGAP, plus additional links to SOURCE, and/or GNF BioGPS, and/or EXPOLDB, and/or UniProtKB,
Expression Assays from Applied Biosystems )
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MTHFR expression in normal and diseased human tissues

Applied Biosystems TaqMan ® Gene Expression Assays for MTHFR

¹ / ² / ³

15 probe-sets matching MTHFR gene

Affymetrix probe-set	Array	# genes	Sensitivity	Specificity	Correlation	Length	Gb_Accession	Consensus	Uniqueness	Score	Rank
Affymetrix probe-set	Array	GeneAnnot data			GeneNote data		GeneTide data
32897_at²^{, 3}	U95-A	1	1.00	1.00	0.19	1.26	AJ237672	0.80	1.00	0.91	1
705_at²^{, 3}	U95-A	1	1.00	1.00	0.29	0.67	HG4234-HT4504	0.20	1.00	0.72	1
80086_at²^{, 3}	U95-E	1	1.00	1.00	0.75	0.96	F23245	0.80	0.80	0.80	1
84134_at²^{, 3}	U95-E	1	1.00	1.00	0.83	1.35	AI435368	0.40	1.00	0.76	1
56892_at²^{, 3}	U95-B	1	0.94	1.00	0.83	0.80	AA494230	0.80	1.00	0.91	1
226929_at²^{, 3}	U133-B	1	1.00	1.00	--	--	AA524272	0.60	1.00	0.82	1
217071_s_at²	U133-A	1	1.00	1.00	--	--	--	--	--	--	--
206800_at²^{, 3}	U133-A	1	1.00	1.00	--	--	NM_005957	0.60	1.00	0.82	1
239035_at²^{, 3}	U133-B	1	1.00	1.00	--	--	AL138431	0.40	1.00	0.76	1
217070_at²	U133-A	1	1.00	1.00	--	--	--	--	--	--	--
226929_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--
217071_s_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--
206800_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--
239035_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--
217070_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--

GeneDecks MTHFR for binary patterns associated with the probe-sets selected above

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Data from

(Publications) and GNF BioGPS
About these images
About these images

CGAP SAGE TAG: GCGTAATGGG

SOURCE GeneReport for Unigene cluster: Hs.214142
Expression variation in blood from EXPOLDB for MTHFR

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD and/or ⁵MGI Jun 06 2009, with possible further links to Flybase and/or WormBase, Gene Trees according to Ensembl)
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Orthologs for MTHFR gene from 5/21 species (see all 21 )

Organism	Gene	Locus	Description	Human Similarity	NCBI accessions
dog (Canis familiaris)	MTHFR¹	--	5,10-methylenetetrahydrofolate reductase (NADPH)	89.28(n) 91.04(a)	478230 XM_535405.2 XP_535405.2
chimpanzee (Pan troglodytes)	MTHFR¹	--	5,10-methylenetetrahydrofolate reductase (NADPH)	99.54(n) 99.85(a)	469800 XM_001141362.1 XP_001141362.1
cow (Bos taurus)	MTHFR¹	--	5,10-methylenetetrahydrofolate reductase (NADPH)	88.69(n) 90.67(a)	497032 NM_001011685.1 NP_001011685.1
rat (Rattus norvegicus)	Mthfr¹	--	5,10-methylenetetrahydrofolate reductase (NADPH)	86.03(n) 89.14(a)	362657 XM_342975.2 XP_342976.2
mouse (Mus musculus)	Mthfr^{1, 5}	4 (76.40 cM)⁵	5,10-methylenetetrahydrofolate reductase^{1, 5}	87.14(n)¹ 90.81(a)¹	17769¹ NM_010840.2¹ NP_034970.2¹ AF105988⁵ AF105989⁵ (see all 35)

About this table Species with no ortholog for MTHFR

ENSEMBL Gene Tree for MTHFR

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

(According to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, and UniProtKB, Linkage Disequilibrium by HapMap, Genotyping Reagents from Applied Biosystems)
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

10/158 NCBI SNPs in MTHFR are shown (see all 158 )
(Click for Applied Biosystems TaqMan ® Genotyping Assay) (see all 129)

AB	SNP ID	Valid	Chr 1 pos	Sequence	Recs	AA Chg	Type	More	Recs	Pop	Total sample	More
AB	Genomic Data				Transcription Data				Allele Frequencies
				--	--	--		--	--			--
	rs1801133^1,2	A,C,F,H,O	11778965(-)	`GGGAGC/TCGATT`	1	A/V	mis¹ ese³		35	NA EA MN CSAM NS EU WA	5398
	rs1801131^1,2	C,F,H	11777063(-)	`TGAAGA/CAAGTG`	1	E/A	mis¹		25	MN CSAM EA NA EU WA NS	3280
--	rs45571736^1,2	C,F	11777085(-)	`TGTGGG/AGGGAG`	1	R/G	mis¹		2	NS	656
	rs2274974^1,2	C,H	11773906(-)	`CCCTGG/AGCGAG`	1	E/G	mis¹ ese³		4	EU EA WA	406
	rs2066472^1,2	C,H	11785558(-)	`TCCTCG/AAACTG`	1	Q/R	mis¹ ese³		12	NA MN CSAM EA EU WA NS	1234
--	rs45449298^1,2	F	11774998(-)	`TTCCCG/ACGAGA`	1	H/R	mis¹		1	--	480
--	rs3927589^1,2	C	11777080(-)	`GGAG/TGAGCT`	1	E/D	mis¹		5	MN CSAM EA	404
	rs2066470^1,2	C,F,H,O	11785644(-)	`GACCCC/TGAGCG`	1	P/P	syn¹ ese³		23	NA MN EA EU WA CSAM NS	2684
	rs2066462^1,2	C,F,H	11777483(-)	`CTCAGC/TGCCCA`	1	S/S	syn¹ ese³		11	NA EU EA WA NS	1454
	rs2066466^1,2	C,F,O	11783863(-)	`ATCACG/AGGCCA`	1	T/T	syn¹ ese³		3	NA NS	730

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HapMap Linkage Disequilibrium images for MTHFR (up to first 250kb)

(in which this Gene is Involved, According to OMIM, UniProtKB, Novoseek, PharmGKB, Genatlas, GeneTests, Blood group antigen gene mutations by BGMUT, HGMD, GAD, HuGE Navigator, BCGD, and/or TGDB.)
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OMIM: 607093

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 [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

(folate-sensitive NTD) [MIM:601634]. The most common NTDs are open spina bifida (myelomeningocele)

and anencephaly

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

Disease	Score	Articles	PubMed IDs for Articles with Shared Sentences (# sentences)
hyperhomocysteinemia	95.51	327	16909866 (4), 18234410 (3), 11747974 (3), 16917400 (3) (see all 99)
methylenetetrahydrofolate reductase deficiency	93.50	50	10961793 (3), 12142069 (2), 18539994 (2), 18616155 (2) (see all 42)
thrombophilia	86.49	60	14691342 (2), 14747183 (2), 15834246 (2), 9890294 (1) (see all 44)
neural tube defects	86.44	115	12431255 (3), 10602111 (3), 10100053 (2), 10732818 (2) (see all 65)
folate deficiency	83.30	42	10452905 (2), 14734201 (2), 16950805 (2), 11440783 (2) (see all 27)
homocysteinemia	82.86	20	16055253 (2), 15834927 (2), 18220649 (1), 18328637 (1) (see all 13)
homocystinuria	81.15	49	9490685 (3), 8752689 (3), 15217352 (3), 8124871 (3) (see all 26)
vascular diseases	76.32	88	8989110 (3), 10477457 (2), 17099857 (2), 7647779 (2) (see all 60)
venous thrombosis	75.30	74	9490685 (3), 10837091 (2), 18293456 (2), 17353498 (2) (see all 49)
thrombosis	71.02	82	12469051 (4), 10634828 (2), 9054653 (2), 11896528 (2) (see all 54)

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10/15 PharmGKB disease relationships for MTHFR gene (see all 15 )

Disease	PharmGKB Relations	PubMed IDs for articles supporting these relationships
ALL (acute lymphoblastic leukemia)	PD GN	12915598
Adenoma	CO GN	14744749
Arthritis, Rheumatoid	PD GN	15361376
Colonic Neoplasms	CO GN	12738713 10462625
Colorectal Neoplasms	CO GN	14744749 15608557
Hyperhomocysteinemia	PD GN	12471611 10704624 12215845 14656021
Leukemia	PD GN	12453860 11418485
Leukemia, Lymphocytic, Acute	CO GN	11986237 14647408
Leukemia, Lymphocytic, Acute, L1	CO	15713801
Marfan Syndrome	CO PD GN	14613740

About this table

Human Gene Mutation Database: MTHFR
Genetic Association Database: MTHFR
Human Genome Epidemiology Navigator: MTHFR (1679 documents)

(Possibly Related Articles in Doctor's Guide)
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(in PubMed. Associations of this gene to articles via ¹Novoseek, ²HGNC, ³Entrez Gene, ⁴UniProtKB/Swiss-Prot, ⁵UniProtKB/TrEMBL, ⁶GAD, and/or ⁷PharmGKB)
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10/2433 PubMed articles for MTHFR gene (see all 2433 ):

Role of polymorphisms in MTHFR and MTHFD1 genes in the outcome of childhood acute lymphoblastic leukemia. (PubMed id 14647408)^{1, 3, 6, 7} Krajinovic M....Moghrabi A. (2004)
Methylenetetrahydrofolate reductase gene polymorphisms in black South Africans and the association with preeclampsia. (PubMed id 15059157)^{1, 3, 6, 7} Pegoraro R.J....Moodley J. (2004)
The role of genetic factors in the development of hyperhomocysteinemia. (PubMed id 14656021)^{1, 3, 6, 7} Geisel J....Herrmann W. (2003)
Thymidylate synthase: a novel genetic determinant of plasma homocysteine and folate levels. (PubMed id 12215845)^{1, 3, 6, 7} Trinh B.N....Laird P.W. (2002)
Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults. (PubMed id 10536004)^{1, 3, 4, 6} Skibola C.F.... Morgan G. (1999)
Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. (PubMed id 7920641)^{1, 2, 3, 4} 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)^{3, 4, 6} Casas J.P.... Sharma P. (2004)
Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene. (PubMed id 15361376)^{1, 3, 7} Berkun Y....Ben-Yehuda A. (2004)
Methylenetetrahydrofolate reductase gene polymorphisms and response to fluorouracil-based treatment in advanced colorectal cancer patients. (PubMed id 15608557)^{1, 3, 7} Etienne M.C....Milano G. (2004)
Methylenetetrahydrofolate reductase polymorphism in advanced colorectal cancer: a novel genomic predictor of clinical response to fluoropyrimidine-based chemotherapy. (PubMed id 12738713)^{1, 3, 7} Cohen V....Rozen R. (2003)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, and/or H-InvDB)
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Entrez Gene: 4524	HGNC: 7436	AceView: MTHFR	Ensembl:ENSG00000177000	euGenes: HUgn4524
ECgene: MTHFR	H-InvDB: MTHFR

(According to HUGE)
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(According to ATLAS, HORDE, IMGT, MTDB, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
ATLAS Chromosomes in Cancer entry for MTHFR	Genetics and Cytogenetics in Oncology and Haematology
GeneReviews	http://www.genetests.org/query?gene=MTHFR
NIEHS-SNPs	http://egp.gs.washington.edu/data/mthfr/

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(Reagents available from Applied Biosystems, Antibodies and assays by Cell Signaling Technology, Abcam, Novus Biologicals,
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MTHFR Gene

protein-coding GIFtS: 69

Aliases &
Descriptions
for MTHFR

Summaries
for MTHFR

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for MTHFR

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for MTHFR

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for MTHFR

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for MTHFR

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Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

MTHFR Gene

protein-coding GIFtS: 69

Aliases & Descriptionsfor MTHFR

Summariesfor MTHFR

Genomic Locationfor MTHFR

Proteinsfor MTHFR

Protein Domains/Familiesfor MTHFR

Gene Functionfor MTHFR

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Other Databases showing MTHFR

Specialized Databases showing MTHFR

Licensable Technologiesfor MTHFR

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Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Aliases &
Descriptions
for MTHFR

Summaries
for MTHFR

Genomic Location
for MTHFR

Proteins
for MTHFR

Protein Domains/
Families
for MTHFR

Gene Function
for MTHFR

Pathways & Interactions
for MTHFR

Drugs & Compounds
for MTHFR

Transcripts
for MTHFR

Expression
for MTHFR

Orthologs
for MTHFR

Paralogs
for MTHFR

SNPs/Variants
for MTHFR

Disorders & Mutations
for MTHFR

Medical News
for MTHFR

Publications
for MTHFR

Licensable Technologies
for MTHFR

Services
for MTHFR