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Gene id

4524

Gene Summary SNPs Protein Summary Gene ontology KEGG pathways Diseases PubMed references

Gene Summary

Gene Symbol

MTHFR Gene UCSC Ensembl

Gene name

methylenetetrahydrofolate reductase

Alternate names

methylenetetrahydrofolate reductase, 5,10-methylenetetrahydrofolate reductase (NADPH), methylenetetrahydrofolate reductase (NAD(P)H),

Gene location

1p36.22 (11806102: 11785729) Exons: 13 NC_000001.11

Gene summary(Entrez)

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]

OMIM

607093

SNPs

rs1801133

Strand:    Allele origin: T(germline)/C(germline)   Allele change: C/T   Mutation type: snp

CM000663.2   g.11796321G>A
NC_000001.10   g.11856378G>A
NC_000001.11   g.11796321G>A
NG_013351.1   g.14783C>T
NM_001330358.1   c.788C>T
NM_005957.4   c.665C>T
NP_001317287.1   p.Ala263Val
NP_005948.3   p.Ala222Val
XP_005263515.1   p.Ala263Val
XP_005263516.1   p.Ala245Val
XP_005263517.1   p.Ala222Val
XP_005263518.1   p.Ala222Val
XP_005263519.1   p.Ala222Val
XP_005263520.1   p.Ala140Val
XP_011539797.1   p.Ala262Val
XP_011539798.1   p.Ala263Val
XP_016856817.1   p.Ala263Val
Clinical Significance: drug-response drug-response drug-response

rs1801133

Strand: -   Allele origin: germline,germline  Allele change: C/T   Mutation type: snp


NC_000001.11   g.11796321G>A
NC_000001.10   g.11856378G>A
NG_013351.1   g.14783C>T
NM_001330358.1   c.788C>T
NM_005957.4   c.665C>T
NP_001317287.1   p.Ala263Val
NP_005948.3   p.Ala222Val
XM_005263462.1   c.665C>T
XM_005263462.4   c.665C>T
XM_005263460.4   c.665C>T
XM_005263
Clinical Significance: drug-response

Protein Summary

Protein general information

P42898

Name: Methylenetetrahydrofolate reductase (EC 1.5.1.20)

Length: 656 Mass: 74,597

Sequence

MVNEARGNSSLNPCLEGSASSGSESSKDSSRCSTPGLDPERHERLREKMRRRLESGDKWFSLEFFPPRTAEGAVN
LISRFDRMAAGGPLYIDVTWHPAGDPGSDKETSSMMIASTAVNYCGLETILHMTCCRQRLEEITGHLHKAKQLGL
KNIMALRGDPIGDQWEEEEGGFNYAVDLVKHIRSEFGDYFDICVAGYPKGHPEAGSFEADLKHLKEKVSAGADFI
ITQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQGYHSLRQLVKLSKLEVPQEIKDVIEPIKDNDAAIRNYGIE
LAVSLCQELLASGLVPGLHFYTLNREMATTEVLKRLGMWTEDPRRPLPWALSAHPKRREEDVRPIFWASRPKSYI
YRTQEWDEFPNGRWGNSSSPAFGELKDYYLFYLKSKSPKEELLKMWGEELTSEESVFEVFVLYLSGEPNRNGHKV
TCLPWNDEPLAAETSLLKEELLRVNRQGILTINSQPNINGKPSSDPIVGWGPSGGYVFQKAYLEFFTSRETAEAL
LQVLKKYELRVNYHLVNVKGENITNAPELQPNAVTWGIFPGREIIQPTVVDPVSFMFWKDEAFALWIERWGKLYE
EESPSRTIIQYIHDNYFLVNLVDNDFPLDNCLWQVVEDTLELLNRPTQNARETEAP

Structural information

Interpro:	IPR029041 IPR004621 IPR003171
Pfam:	PF02219
CDD:	cd00537
STRING:	ENSP00000365775;

Other Databases

GeneCards: MTHFR; Malacards: MTHFR

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0001666	response to hypoxia	IEA	biological_process
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IGI	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IDA	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IMP	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IDA	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IMP	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	TAS	molecular_function
GO:0005829	cytosol	IBA	cellular_component
GO:0005829	cytosol	TAS	cellular_component
GO:0006520	cellular amino acid metab olic process	TAS	biological_process
GO:0006555	methionine metabolic proc ess	IGI	biological_process
GO:0008015	blood circulation	TAS	biological_process
GO:0031060	regulation of histone met hylation	IDA	biological_process
GO:0032403	protein complex binding	IPI	molecular_function
GO:0033274	response to vitamin B2	IEA	biological_process
GO:0035999	tetrahydrofolate intercon version	IEA	biological_process
GO:0035999	tetrahydrofolate intercon version	IGI	biological_process
GO:0035999	tetrahydrofolate intercon version	IDA	biological_process
GO:0035999	tetrahydrofolate intercon version	IMP	biological_process
GO:0035999	tetrahydrofolate intercon version	IMP	biological_process
GO:0042493	response to drug	IEA	biological_process
GO:0043005	neuron projection	IEA	cellular_component
GO:0046500	S-adenosylmethionine meta bolic process	IEA	biological_process
GO:0046655	folic acid metabolic proc ess	TAS	biological_process
GO:0050660	flavin adenine dinucleoti de binding	IDA	molecular_function
GO:0050661	NADP binding	IEA	molecular_function
GO:0050667	homocysteine metabolic pr ocess	IDA	biological_process
GO:0051593	response to folic acid	IEA	biological_process
GO:0055114	oxidation-reduction proce ss	IEA	biological_process
GO:0070555	response to interleukin-1	IEA	biological_process
GO:0070829	heterochromatin maintenan ce	IDA	biological_process
GO:0072341	modified amino acid bindi ng	IDA	molecular_function
GO:0001666	response to hypoxia	IEA	biological_process
GO:0003824	catalytic activity	IEA	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IEA	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IEA	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IEA	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IGI	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IDA	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IMP	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IDA	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IMP	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	TAS	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	TAS	molecular_function
GO:0005829	cytosol	IEA	cellular_component
GO:0005829	cytosol	IBA	cellular_component
GO:0005829	cytosol	TAS	cellular_component
GO:0006520	cellular amino acid metab olic process	TAS	biological_process
GO:0006555	methionine metabolic proc ess	IEA	biological_process
GO:0006555	methionine metabolic proc ess	IGI	biological_process
GO:0008015	blood circulation	TAS	biological_process
GO:0008152	metabolic process	IEA	biological_process
GO:0016491	oxidoreductase activity	IEA	molecular_function
GO:0031060	regulation of histone met hylation	IDA	biological_process
GO:0032403	protein complex binding	IPI	molecular_function
GO:0033274	response to vitamin B2	IEA	biological_process
GO:0035999	tetrahydrofolate intercon version	IEA	biological_process
GO:0035999	tetrahydrofolate intercon version	IGI	biological_process
GO:0035999	tetrahydrofolate intercon version	IDA	biological_process
GO:0035999	tetrahydrofolate intercon version	IMP	biological_process
GO:0035999	tetrahydrofolate intercon version	IMP	biological_process
GO:0042493	response to drug	IEA	biological_process
GO:0043005	neuron projection	IEA	cellular_component
GO:0043200	response to amino acid	IEA	biological_process
GO:0046500	S-adenosylmethionine meta bolic process	IEA	biological_process
GO:0046653	tetrahydrofolate metaboli c process	IEA	biological_process
GO:0046655	folic acid metabolic proc ess	TAS	biological_process
GO:0050660	flavin adenine dinucleoti de binding	IEA	molecular_function
GO:0050660	flavin adenine dinucleoti de binding	IDA	molecular_function
GO:0050661	NADP binding	IEA	molecular_function
GO:0050667	homocysteine metabolic pr ocess	IEA	biological_process
GO:0050667	homocysteine metabolic pr ocess	IDA	biological_process
GO:0051593	response to folic acid	IEA	biological_process
GO:0055114	oxidation-reduction proce ss	IEA	biological_process
GO:0055114	oxidation-reduction proce ss	IEA	biological_process
GO:0070555	response to interleukin-1	IEA	biological_process
GO:0070829	heterochromatin maintenan ce	IDA	biological_process
GO:0072341	modified amino acid bindi ng	IDA	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IGI	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IDA	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IMP	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IDA	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	IMP	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	TAS	molecular_function
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) acti vity	TAS	molecular_function
GO:0005829	cytosol	IBA	cellular_component
GO:0005829	cytosol	TAS	cellular_component
GO:0006520	cellular amino acid metab olic process	TAS	biological_process
GO:0006555	methionine metabolic proc ess	IGI	biological_process
GO:0008015	blood circulation	TAS	biological_process
GO:0031060	regulation of histone met hylation	IDA	biological_process
GO:0032403	protein complex binding	IPI	molecular_function
GO:0035999	tetrahydrofolate intercon version	IGI	biological_process
GO:0035999	tetrahydrofolate intercon version	IDA	biological_process
GO:0035999	tetrahydrofolate intercon version	IMP	biological_process
GO:0035999	tetrahydrofolate intercon version	IMP	biological_process
GO:0046655	folic acid metabolic proc ess	TAS	biological_process
GO:0050660	flavin adenine dinucleoti de binding	IDA	molecular_function
GO:0050667	homocysteine metabolic pr ocess	IDA	biological_process
GO:0070829	heterochromatin maintenan ce	IDA	biological_process
GO:0072341	modified amino acid bindi ng	IDA	molecular_function

KEGG pathways

hsa01100  Metabolic pathways
hsa01200  Carbon metabolism
hsa01523  Antifolate resistance
hsa00670  One carbon pool by folate

Diseases

Associated diseases	References
Abruptio placentae	PMID: 11451544
Adrenoleukodystrophy	PMID: 19353223
Alzheimer's disease	PMID: 11711225
Amyotrophic lateral sclerosis (ALS)	PMID: 18513389
Anemia	PMID: 19521764
Antiphospholipid syndrome	PMID: 11454529
Aortic aneurysm	PMID: 11568114
Asthma	PMID: 11471199
Autism	PMID: 19267885
Azoospermia	PMID: 22175540
Beta thalassemia	PMID: 15073633
Bipolar disorder	PMID: 18513846
Blindness	PMID: 19421414
Blood coagulation disorders	PMID: 19133039
Cancer	PMID: 20056627
Celiac disease	PMID: 19248194
Cerebral palsy	PMID: 19238444
Cerebrovascular disease	PMID: 18545917
Chondrosarcoma	PMID: 18498722
Chronic obstructive pulmonary disease (COPD)	PMID: 19625176
Cleft lip	PMID: 16712703
Congenital abnormalities	PMID: 18435414
Crohn's disease	PMID: 16141796
Deep vein thrombophilia	PMID: 12170465
Dementia	PMID: 19716217
Depression	PMID: 18801628
Diabetes	PMID: 19937354
Diabetic nephropathy	PMID: 12897091
Diabetic retinopathy	PMID: 10765003
Down syndrome	PMID: 15834031
Endometriosis	PMID: 21429654
Epistaxis	PMID: 19245802
Erectile dysfunction	PMID: 19694922
Exfoliation syndrome	PMID: 19112534
Female infertility	PMID: 18930220
Femoral Neck Fractures	PMID: 19225709
Fetal growth retardation	PMID: 19461414
Gaucher Disease	PMID: 18978274
Genital diseases	PMID: 19799358
Glaucoma	PMID: 18385801
Glomerulonephritis	PMID: 19420105
Hearing loss	PMID: 19898482
HELLP Syndrome	PMID: 18568463
Hemifacial Spasm	PMID: 18642643
Hemolytic uremic syndrome	PMID: 19110485
Hemophilia A	PMID: 18459951
Homocystinuria	KEGG: H00183, OMIM: 607093
Hyperhomocysteinemia	PMID: 18511109
Implantation failure	PMID: 27068821
Inflammatory bowel disease	PMID: 17111197
Intrauterine growth retardation	PMID: 16192348
Isolated orofacial clefts	KEGG: H00516
Kidney disease	PMID: 19520069
Leukemia	PMID: 12958073
Liver disease	PMID: 18495456
Macular degeneration	PMID: 18378576
Male infertility	PMID: 21775772
Mental retardation	PMID: 18510799
Metabolic syndrome	PMID: 19083485
Migraine disorders	PMID: 15953655
Multiple sclerosis	PMID: 19854238
Neural tube defects	OMIM: 607093
Neutropenia	PMID: 19074750
Non-obstructive azoospermia (NOA)	PMID: 19477879
Non-symdromic cleft lip	PMID: 19727233
Obesity	PMID: 12518110
Oligoasthenoteratozoospermia	PMID: 26549413
Oligoasthenozoospermia	PMID: 25966116
Oligozoospermia	PMID: 25428700
Oocyte maturation	PMID: 24746944
Osteonecrosis	PMID: 14742985
Osteoporosis	PMID: 12674333
Ovarian responsiveness	PMID: 16533336
Ovarian hyperstimulation syndrome(OHSS)	PMID: 16128122
Parkinson's disease	PMID: 19452554
Endometriosis associated infertility	INFBASE21429654
Endometriosis	INFBASE21429654
Placenta diseases	PMID: 19070828
Polycystic ovary syndrome (PCOS)	PMID: 22882325
Preeclampsia	PMID: 10869114
Premature ovarian failure ( POF)	PMID: 22713864
Recurrent miscarriage	PMID: 22047507
Renal disease	PMID: 12180000
Retinal vein occlusion	PMID: 19729099
Retinal vein thrombosis	PMID: 19825913
Rheumatoid arthritis	PMID: 11927833
Schizophrenia	OMIM: 607093
Secondary infertility	PMID: 23234018
Sickle cell anemia	PMID: 15481892
Spermatogenetic defects	PMID: 23117460
Spina bifida	KEGG: H00262
Spinal dysraphism	PMID: 19161160
Systemic lupus erythematosus	PMID: 12027572
Thrombocytopenia	PMID: 12724616
Thromboembolism	OMIM: 607093
Thrombophilia	PMID: 18583164
Turner Syndrome (TS)	PMID: 19169497
Ulcerative colitis	PMID: 18787277
Unexplained azoospermia	PMID: 19657388
Unexplained female infertility	PMID: 19324355
Unexplained pregnancy loss	PMID: 23539766
Unexplained recurrent pregnancy loss (RPL)	PMID: 21815801
Unexplained severe male infertility	PMID: 22457816
Unexplained infertility	PMID: 24265582
Varicocele	PMID: 24456105
Vascular disease	OMIM: 607093
von Willebrand Disease	PMID: 19959486

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes	Abstract
21429654	Endometrio sis	rs1801133 of MTHFR and rs4244593 of PEMT		313 (163 women with endometrio sis, 150 contro ls)	Female infertility	BHMT BHMT2 CBS CHDH CHKA MTHFD1 MTHFR MTR MTRR PCYT1A PEMT TCN	Show abstract
21429654	Endometrio sis	BHMT (rs7356530 and rs3733890), BHMT2 (rs625879), CBS (844ins68), CHDH (rs893363 and rs2289205), CHKA (rs7928739), MTHFD1 (rs2236225), MTHFR (rs1801133), MTR (rs1805087), MTRR (rs1801394), PCYT1A (rs712012 and rs7639752),�PEMT�(rs4244593 and rs4646406) an		310(163 women w ith endometrios is, 150 control s)		BHMT BHMT2 CBS CHDH CHKA MTHFD1 MTHFR MTR MTRR PCYT1A �PEMT TCN	Show abstract