CleftGeneDB-Search

Gene: MTHFR

Basic information

Tag	Content
Uniprot ID	P42898; B2R7A6; Q5SNW6; Q5SNW9; Q7Z6M6; Q8IU73; Q9UQR2;
Entrez ID	4524
Genbank protein ID	AAA74440.2; BAG35753.1; AAP88033.1; EAW71709.1; AAH53509.1; AAN40865.1; AAL17648.1; AAD17965.1; CAB41971.1;
Genbank nucleotide ID	XM_005263462.4; NM_001330358.1; XM_005263460.4; NM_005957.4;
Ensembl protein ID	ENSP00000365770; ENSP00000365775; ENSP00000365767; ENSP00000365777;
Ensembl nucleotide ID	ENSG00000177000
Gene name	Methylenetetrahydrofolate reductase
Gene symbol	MTHFR
Organism	Homo sapiens
NCBI taxa ID	9606
Cleft type	CPO,CL/P
Developmental stage
Data sources	Manually collected
Reference	20572854; 20082468; 27167580; 26110153; 23725631; 25745606; 24254627; 26236436; 18661527; 16470725; 15054400; 19419265; 12672677; 1159940; 20890936; 23787444; 25191068; 26540672; 15221800; 25219684; 26140186; 24460828; 27387868; 12796044; 21612398; 25808365;
Functional description	Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.
Sequence	MVNEARGNSS LNPCLEGSAS SGSESSKDSS RCSTPGLDPE RHERLREKMR RRLESGDKWF 60 SLEFFPPRTA EGAVNLISRF DRMAAGGPLY IDVTWHPAGD PGSDKETSSM MIASTAVNYC 120 GLETILHMTC CRQRLEEITG HLHKAKQLGL KNIMALRGDP IGDQWEEEEG GFNYAVDLVK 180 HIRSEFGDYF DICVAGYPKG HPEAGSFEAD LKHLKEKVSA GADFIITQLF FEADTFFRFV 240 KACTDMGITC PIVPGIFPIQ GYHSLRQLVK LSKLEVPQEI KDVIEPIKDN DAAIRNYGIE 300 LAVSLCQELL ASGLVPGLHF YTLNREMATT EVLKRLGMWT EDPRRPLPWA LSAHPKRREE 360 DVRPIFWASR PKSYIYRTQE WDEFPNGRWG NSSSPAFGEL KDYYLFYLKS KSPKEELLKM 420 WGEELTSEES VFEVFVLYLS GEPNRNGHKV TCLPWNDEPL AAETSLLKEE LLRVNRQGIL 480 TINSQPNING KPSSDPIVGW GPSGGYVFQK AYLEFFTSRE TAEALLQVLK KYELRVNYHL 540 VNVKGENITN APELQPNAVT WGIFPGREII QPTVVDPVSF MFWKDEAFAL WIERWGKLYE 600 EESPSRTIIQ YIHDNYFLVN LVDNDFPLDN CLWQVVEDTL ELLNRPTQNA RETEAP 656

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Gene expression information

Gene expression in different tissues (GTEx V7)

Gene expression in different tissues (ENCODE)

Protein structural annotations

3D structure in PDB database

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PDB ID
6FCX

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Protein disorder information

Orthologous information

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Relation	Gene symbol	Entrez ID	UniProt ID	Cleft type	Species	Evidence	Details
1:1 ortholog	MTHFR	4524	P42898	CPO,CL/P	Homo sapiens	Publication	More>>
1:1 ortholog		397180	F1RF82		Sus scrofa	Prediction	More>>
1:1 ortholog	MTHFR	497032	A0A3Q1M8J1		Bos taurus	Prediction	More>>
1:1 ortholog	MTHFR		E2QXW9		Canis lupus familiaris	Prediction	More>>
1:1 ortholog	MTHFR	102182523	A0A452G4N1		Capra hircus	Prediction	More>>
1:1 ortholog	MTHFR		A0A3Q2HUW6		Equus caballus	Prediction	More>>
1:1 ortholog	Mthfr		A2A7F9		Mus musculus	Prediction	More>>
1:1 ortholog	MTHFR	469800	H2PY11		Pan troglodytes	Prediction	More>>
1:1 ortholog	Mthfr	362657	D4A7E8		Rattus norvegicus	Prediction	More>>
1:1 ortholog	mthfr	567547	B0V153		Danio rerio	Prediction	More>>

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Identified variants/mutations related to cleft phenotype

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Gene symbol	Significant Variants/SNPS	Methods	PubMed ID
MTHFR	rs1801131; c.1298A>C	PCR�restriction fragment length polymorphism.	25219684
MTHFR	rs1801133; c.677C>T	PCR�restriction fragment length polymorphism.	25219684
MTHFR	c.1298A>C	PCR	26236436
MTHFR	c.677C>T	PCR	26236436
MTHFR	c.1298A>C	RFLP-PCR; ARMS_PCR	25745606
MTHFR	c.677C>T	RFLP-PCR; ARMS_PCR	25745606
MTHFR	c.1298A>C	RFLP-PCR;	26110153
MTHFR	rs1801133A>C	TDT	25808365
MTHFR	rs1801133; c.677C>T	TaqMan SNP Genotyping Assay	26540672
MTHFR	c.677C>T	Genotyping	24460828
MTHFR	rs2274976G>A	Genotyping; TDT	24254627
MTHFR	c.677C>T	PCR; RFLP	23787444
MTHFR	c.677C>T	Genotyping; TDT	16470725
MTHFR	c.677C>T	PCR; TDT	15221800
MTHFR	c.677C>T	Transmission disequilibrium test	1159940
MTHFR	rs2274976G>A	PCR-RFLP	20890936
MTHFR	c.665C>T; p.A222V	WES and Sanger sequencing	26449438
MTHFR	rs1801133; c.677C>T (increase risk)	meta analysis	32124929
MTHFR	rs1801133; c.677C>T	PCR-RFLP	27167580
MTHFR	c.677C>T	PCR-RFLP	18661527

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Other genetic variants/mutations

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ID	Variant	Type	Disease	Chromosome\Coordinate	Evidence
rs776483190	p.Arg46Gln	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11802980C>T	UniProt,dbSNP
rs201618781	p.Arg51Pro	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11802965C>G	UniProt,dbSNP
rs754980119	p.Arg52Gln	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11802962C>T	UniProt,dbSNP
rs786204007	p.Trp59Ser	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11802941C>G	UniProt,dbSNP
rs786204009	p.Arg82Trp	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11801392G>A	UniProt,dbSNP
rs147257424	p.Ala113Thr	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11801299C>T	UniProt,dbSNP
rs769381688	p.His127Tyr	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11801257G>A	UniProt,dbSNP
rs786204012	p.Cys130Arg	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11801248A>G	UniProt,dbSNP
rs786204013	p.Gln147Pro	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11801196T>G	UniProt,dbSNP
rs767890671	p.Ile153Met	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11801177G>C	UniProt,dbSNP
rs121434295	p.Arg157Gln	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11801166C>T	UniProt,dbSNP
rs574132670	p.Arg183Gln	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11800250C>T	UniProt,dbSNP
rs786204014	p.Gly196Asp	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11796399C>T	UniProt,dbSNP
rs200100285	p.Ile225Leu	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11796313T>G	UniProt,dbSNP
rs786204017	p.Pro254Ser	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11796226G>A	UniProt,dbSNP
rs786204018	p.Gly255Val	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11796222C>A	UniProt,dbSNP
rs373398993	p.Ile256Asn	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11796219A>T	UniProt,dbSNP
rs786204019	p.Phe257Val	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11796217A>C	UniProt,dbSNP
rs121434297	p.Leu323Pro	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11795161A>G	UniProt,dbSNP
rs267606887	p.Asn324Ser	missense variant	Methylenetetrahydrofolate reductase deficiency (MTHFRD)	NC_000001.11:g.11795158T>C	UniProt,dbSNP

Showing 1 to 20 of 750 entries

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Disease or phenotype associated information

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Disease ID	Disease Name	Disease Type	Source
C0000768	Congenital Abnormality	group	BEFREE;LHGDN
C0000786	Spontaneous abortion	phenotype	LHGDN
C0000809	Abortion, Habitual	disease	LHGDN
C0000832	Abruptio Placentae	phenotype	LHGDN
C0001206	Acromegaly	disease	BEFREE
C0001339	Acute pancreatitis	disease	BEFREE
C0001403	Addison Disease	disease	HPO
C0001418	Adenocarcinoma	group	BEFREE;LHGDN
C0001430	Adenoma	group	BEFREE;LHGDN
C0001723	Affective Disorders, Psychotic	group	BEFREE;PSYGENET
C0001787	Osteoporosis, Age-Related	disease	BEFREE
C0001857	AIDS related complex	disease	BEFREE
C0001956	Alcohol Use Disorder	disease	BEFREE
C0001969	Alcoholic Intoxication	disease	BEFREE;PSYGENET
C0001973	Alcoholic Intoxication, Chronic	disease	BEFREE;PSYGENET
C0002170	Alopecia	disease	BEFREE;CTD_human
C0002395	Alzheimer's Disease	disease	BEFREE;CTD_human;LHGDN
C0002622	Amnesia	disease	BEFREE
C0002871	Anemia	disease	BEFREE;CTD_human
C0002878	Anemia, Hemolytic	disease	BEFREE

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Gene Ontology (GO)/biological pathways

GO:Molecular Function

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GO ID	GO Term	Evidence
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) activity	IGI
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) activity	IDA
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) activity	IMP
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) activity	IBA
GO:0044877	protein-containing complex binding	IPI
GO:0050660	flavin adenine dinucleotide binding	IDA
GO:0050661	NADP binding	IEA
GO:0071949	FAD binding	IBA
GO:0072341	modified amino acid binding	IDA

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GO:Biological Process

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GO ID	GO Term	Evidence
GO:0001666	response to hypoxia	IEA
GO:0001843	neural tube closure	IMP
GO:0001843	neural tube closure	NAS
GO:0006555	methionine metabolic process	IGI
GO:0006730	one-carbon metabolic process	IBA
GO:0009086	methionine biosynthetic process	IBA
GO:0031060	regulation of histone methylation	IDA
GO:0033274	response to vitamin B2	IEA
GO:0035999	tetrahydrofolate interconversion	IEA
GO:0035999	tetrahydrofolate interconversion	IGI
GO:0035999	tetrahydrofolate interconversion	IDA
GO:0035999	tetrahydrofolate interconversion	IMP
GO:0035999	tetrahydrofolate interconversion	IBA
GO:0043200	response to amino acid	IEA
GO:0046500	S-adenosylmethionine metabolic process	IEA
GO:0046655	folic acid metabolic process	TAS
GO:0050667	homocysteine metabolic process	IDA
GO:0051593	response to folic acid	IEA
GO:0055114	oxidation-reduction process	IEA
GO:0070555	response to interleukin-1	IEA

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GO:Cellular Component

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GO ID	GO Term	Evidence
GO:0005829	cytosol	IBA
GO:0005829	cytosol	TAS
GO:0045202	synapse	IEA

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Reactome Pathway

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Reactome ID	Reactome Term	Evidence
R-HSA-1430728	Metabolism	TAS
R-HSA-196757	Metabolism of folate and pterines	TAS
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors	TAS
R-HSA-196854	Metabolism of vitamins and cofactors	TAS

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Drugs and compounds information

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ID	Drug Name	Action	PubMed
C000593030	GSK-J4	GSK-J4 results in decreased expression of MTHFR mRNA	29301935
C000593263	afuresertib	afuresertib results in increased expression of MTHFR mRNA	28960945
C005984	5-methyltetrahydrofolate	MTHFR protein results in increased chemical synthesis of 5-methyltetrahydrofolate	7647779; 9719624;
C005984	5-methyltetrahydrofolate	[MTHFR protein results in increased metabolism of 5,10-methylenetetrahydrofolic acid] which results in increased abundance of 5-methyltetrahydrofolate	30726997
C006253	pirinixic acid	pirinixic acid results in increased expression of MTHFR mRNA	18301758; 20813756; 23811191;
C006703	benzo(b)fluoranthene	benzo(b)fluoranthene results in decreased expression of MTHFR mRNA	26377693
C006780	bisphenol A	bisphenol A results in increased expression of MTHFR mRNA	29275510
C006780	bisphenol A	bisphenol A results in decreased expression of MTHFR mRNA	25181051
C009277	sodium arsenate	MTHFR gene mutant form results in increased susceptibility to sodium arsenate	24384392
C009407	2,5,2',5'-tetrachlorobiphenyl	[2,4,4'-trichlorobiphenyl co-treated with 2,5,2',5'-tetrachlorobiphenyl co-treated with 2,4,5,2',5'-pentachlorobiphenyl co-treated with 2,2',3',4,4',5-hexachlorobiphenyl co-treated with 2,4,5,2',4',5'-hexachlorobiphenyl co-treated with PCB 180] results in increased expression of MTHFR mRNA	25510870
C009828	2,4,5,2',5'-pentachlorobiphenyl	[2,4,4'-trichlorobiphenyl co-treated with 2,5,2',5'-tetrachlorobiphenyl co-treated with 2,4,5,2',5'-pentachlorobiphenyl co-treated with 2,2',3',4,4',5-hexachlorobiphenyl co-treated with 2,4,5,2',4',5'-hexachlorobiphenyl co-treated with PCB 180] results in increased expression of MTHFR mRNA	25510870
C011864	7-hydroxymethotrexate	MTHFR mRNA results in decreased susceptibility to 7-hydroxymethotrexate	19426680
C013123	5,10-methylenetetrahydrofolic acid	MTHFR protein results in increased metabolism of 5,10-methylenetetrahydrofolic acid	16187112
C013123	5,10-methylenetetrahydrofolic acid	MTHFR protein results in increased reduction of 5,10-methylenetetrahydrofolic acid	7647779
C013123	5,10-methylenetetrahydrofolic acid	[MTHFR protein results in increased metabolism of 5,10-methylenetetrahydrofolic acid] which results in increased abundance of 5-methyltetrahydrofolate	30726997
C013123	5,10-methylenetetrahydrofolic acid	MTHFR protein results in increased reduction of 5,10-methylenetetrahydrofolic acid	17387702
C014024	2,4,5,2',4',5'-hexachlorobiphenyl	[2,4,4'-trichlorobiphenyl co-treated with 2,5,2',5'-tetrachlorobiphenyl co-treated with 2,4,5,2',5'-pentachlorobiphenyl co-treated with 2,2',3',4,4',5-hexachlorobiphenyl co-treated with 2,4,5,2',4',5'-hexachlorobiphenyl co-treated with PCB 180] results in increased expression of MTHFR mRNA	25510870
C016517	indole-3-carbinol	[indole-3-carbinol co-treated with Diethylnitrosamine] results in increased expression of MTHFR mRNA	22129741
C016805	tris(1,3-dichloro-2-propyl)phosphate	tris(1,3-dichloro-2-propyl)phosphate results in decreased expression of MTHFR mRNA	26179874
C017096	n-butoxyethanol	n-butoxyethanol results in increased expression of MTHFR mRNA	19812364

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Functional annotations

Keywords

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Keyword ID	Keyword Term
KW-0002	3D-structure
KW-0021	Allosteric enzyme
KW-0025	Alternative splicing
KW-0225	Disease mutation
KW-0274	FAD
KW-0285	Flavoprotein
KW-0521	NADP
KW-0560	Oxidoreductase
KW-0621	Polymorphism
KW-1185	Reference proteome
KW-1211	Schizophrenia

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Interpro

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InterPro ID	InterPro Term
IPR003171	Mehydrof_redctse
IPR004621	Fadh2_euk
IPR029041	FAD-linked_oxidoreductase-like

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PROSITE

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Pfam

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Pfam ID	Pfam Term
PF02219	MTHFR

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Gene: MTHFR

Basic information

Gene expression information

Gene expression in different tissues (GTEx V7)

Gene expression in different tissues (ENCODE)

Protein structural annotations

3D structure in PDB database

Protein disorder information

Orthologous information

Identified variants/mutations related to cleft phenotype

Other genetic variants/mutations

Disease or phenotype associated information

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO:Biological Process

GO:Cellular Component

Reactome Pathway

Drugs and compounds information

Functional annotations

Keywords

Interpro

PROSITE

Pfam

Protein-protein interaction

Protein-miRNA interaction