Gene Report

Basic Information

Approved Symbol	MTHFR
Approved Name	methylenetetrahydrofolate reductase (NAD(P)H)
Previous Name	"5,10-methylenetetrahydrofolate reductase (NADPH)"
Location	1p36.3
Position	chr1:11865945-11865965 (-)
External Links	Entrez Gene: 4524 Ensembl: ENSG00000177000 UCSC: uc001atc.2 HGNC ID: 7436
No. of Studies (Positive/Negative)	5(1/4)
Type	Literature-origin; SNP mapped

Positive relationships between MTHFR and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
MTHFR	Shen, 2014	Patients and nomal controls	T allele (OR=1.81; CI95%=1.40¨C2.34, P<0.001); C/T genotype (OR=3.66; CI95% =2.53¨C5.28, P<0.001)	The T allele (OR=1.81; CI95%=1.40¨C2.34, P<0.001) and C/T ge...... The T allele (OR=1.81; CI95%=1.40¨C2.34, P<0.001) and C/T genotype (OR=3.66; CI95% =2.53¨C5.28, P<0.001) of MTHFR C677T were significantly different between case and control groups. More...

Positive relationships between MTHFR and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description	All
Name in Literature	Related Components
MTHFR		COMT(COMT)	gene	Gabriela Nielsen, 2015	Patients and nomal controls	p=0.005	Testing epistasis we found a positive interaction in case¨Cc...... Testing epistasis we found a positive interaction in case¨Ccontrol comparison between MTHFR A1298C and COMT Val158Met polymorphisms (p=0.005). In particular, the subjects that were homozygous for A1298C CC and carriers for the COMT Met allele had twice as much risk of developing depression (7.7% n=46 in MDD, 3.5% n=16 in controls; p=0.004, OR=2.29, 95%CI:1.28¨C4.10). This interaction increases considering only female subjects alone (8.6% n=36 in MDD, 2.7% n=7 in controls; p=0.002, OR=3.47, 95% CI:1.52¨C7.91). More...

Positive relationship network of MTHFR in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between MTHFR and MDD (count: 3)

Name in Literature	Reference	Research Type	Relation Description
MTHFR	Gaysina D, 2008	Patients and nomal controls	no significant differences in genotype or allele frequencies...... no significant differences in genotype or allele frequencies between depressive patients and controls were observed. More...
MTHFR	Evinova A, 2012	patients and normal controls	We found no significant association of either the BDNF G196A...... We found no significant association of either the BDNF G196A or MTHFR C677T polymorphisms with major depressive disorder neither in female nor male group of patients. More...
MTHFR	Gabriela Nielsen, 2015	Patients and nomal controls	For both SNPs of the MTHFR gene, the results did not show an...... For both SNPs of the MTHFR gene, the results did not show any differences in genotype and allele distributions between MDD and controls.However, for A1298C we found a significant interaction between gender and allele A carriers (F=4.84; p=0.03). Secondary analyses showed that A1298C CC homozygotes were more frequent in female MDD patients than female controls (F=6.50,p=0.01, OR=1.97, 95%CI:1.03¨C3.61; Table 4B). More...

Negative relationships between MTHFR and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description
Name in Literature	Related Components
MTHFR		cognition(cognition)	cognition and behavior	Wang X, 2014	Patients and nomal controls		Neither main effects of COMT genotype nor interactive effect...... Neither main effects of COMT genotype nor interactive effects of between COMT genotype and depression diagnosis were found to be significantly related to any neurocognitive task.In addition, we did not find a main effect of MTHFR genotype or MTHFR genotype by diagnosis interaction on each cognitive test performance in models.However,a significant interaction was found between COMT-MTHFR genotype and SDMT performance (F = 10.542, P = 0.001, ¦Ç2 = 0.076), which contributed to 7.6% of the variance in SDMT score adjusted by age, education, sex and depression diagnosis. More...

MTHFR related SNPs in MK4MDD (count: 2)

#rs	Location	Annotation	No. of Studies (Positive/Negative)
rs1801131	chr1:11794419(Forward)		1(1/0)
rs1801133	chr1:11796321(Forward)		2(1/1)

MTHFR related proteins in MK4MDD (count: 0)

MTHFR related GO terms (count: 26)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0005829	cytosol	cellular component	TAS
GO:0031060	regulation of histone methylation	biological process	IDA[24769206]
GO:0001666	response to hypoxia	biological process	IEA
GO:0044281	small molecule metabolic process	biological process	TAS
GO:0006767	water-soluble vitamin metabolic process	biological process	TAS
GO:0042493	response to drug	biological process	IEA
GO:0070555	response to interleukin-1	biological process	IEA
GO:0035999	tetrahydrofolate interconversion	biological process	IDA[12673793]; IEA; IGI[10551815]; IMP[12673793\|25736335]
GO:0046655	folic acid metabolic process	biological process	TAS
GO:0050661	NADP binding	molecular function	IEA
GO:0072341	modified amino acid binding	molecular function	IDA[20031578]
GO:0051593	response to folic acid	biological process	IEA
GO:0033274	response to vitamin B2	biological process	IEA
GO:0050660	flavin adenine dinucleotide binding	molecular function	IDA[12673793]
GO:0006766	vitamin metabolic process	biological process	TAS
GO:0032403	protein complex binding	molecular function	IPI[24769206]
GO:0004489	methylenetetrahydrofolate reductase (NAD(P)H) activity	molecular function	IDA[12673793\|24769206]; IGI[10551815]; IMP[12673793\|25736335]; TAS
GO:0006520	cellular amino acid metabolic process	biological process	TAS[7647779]
GO:0008015	blood circulation	biological process	TAS[7647779]
GO:0050667	homocysteine metabolic process	biological process	IDA[20031578]
GO:0070829	heterochromatin maintenance	biological process	IDA[24769206]
GO:0009086	methionine biosynthetic process	biological process	IEA
GO:0046500	S-adenosylmethionine metabolic process	biological process	IEA
GO:0006555	methionine metabolic process	biological process	IGI[10551815]
GO:0043005	neuron projection	cellular component	IEA
GO:0055114	oxidation-reduction process	biological process	IEA

MTHFR related KEGG pathways (count: 1)

Gene mapped KEGG pathways
ID	Name	Brief Description	Full Description
hsa00670	one carbon_pool_by_folate	One carbon pool by folate

MTHFR related BioCarta pathways (count: 0)

MTHFR related Reactome pathways (count: 1)

ID	Name	Description
Gene mapped Reactome pathways
REACT_11193	metabolism of_vitamins_and_cofactors	Vitamins are a diverse group of organic compounds, required ...... Vitamins are a diverse group of organic compounds, required in small amounts in the diet. They have distinct biochemical roles, often as coenzymes, and are either not synthesized or synthesized only in limited amounts by human cells. Vitamins are classified according to their solubility, either fat-soluble or water-soluble. The physiological processes dependent on vitamin-requiring reactions include many aspects of intermediary metabolism, vision, bone formation, and blood coagulation, and vitamin deficiencies are associated with a correspondingly diverse and severe group of diseases. More...

MTHFR related interactors from protein-protein interaction data in HPRD (count: 1)

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped Reactome pathways