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FLASH GENE

Symbol

MTHFR

contributors: SGE - updated : 29-07-2010

HGNC name	methylenetetrahydrofolate reductase (NAD(P)H)
HGNC id	7436

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MTHFR developmental delay NTDS1 neural tube defects, folate- sensitive
Location	1p36.22      Physical location : 11.845.786 - 11.866.160
Synonym name	5,10-methylenetetrahydrofolate reductase (NADPH)
EC.number	1.5.1.20

DNA

TYPE	functioning gene
STRUCTURE	20.33 kb     12 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	cytosine-phosphate-guanine/HTF
	Binding site   transcription factor
text structure	CpG islands, numerous consensus sequences transcription factor binding sites (SP1 binding sites) (Gaughan 2000)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

text	three major transcripts different initiation sites, two additional spliced variants of form 1

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005957 12 - 7150 NP_005948 - 656 - Goyette (1998) MTHFRS variant 2 - polyA site 9800 isoform 2 - - - Gaughan (2000) also called MTHFRL variant 3 - polyA site 7200 isoform 3 - - - Gaughan (2000) also called MTHFRM

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive stomach         Lymphoid/Immune lymph node       highly   spleen       highly Nervous brain         Reproductive female system placenta

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

N terminal catalytic domain

secondary structure

FAD moncovalently bound

conjugated

FlavoP

mono polymer

homomer , dimer

HOMOLOGY

interspecies	homolog to murine Mthfr (90.8pc)
	homolog to rattus Mthfr (89.1pc)

Homologene

FAMILY

methylenetetrahydrofolate reductase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic

basic FUNCTION	reducing 5-10 methylene THF to 5 methyl-THF for methionine biosynthesis (oxydoreductase)
	playing a role in DNA methylation, synthesis, and repair (Yuan 2007)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

aminoacid

signaling

folate metabolism, methionine biosynthesis

a component

INTERACTION

DNA

RNA

small molecule	cofactor, nucleotide,
	NADPH
	FAD

protein

cell & other

REGULATION

Other

allosterically regulated by S-adenosylmethionine

ASSOCIATED DISORDERS

corresponding disease(s)

MTHFR , NTDS1

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       loss of function may protect against the development of hepatocellular carcinoma (Yuan 2008)

Susceptibility

to schizophrenia (rs801131) to increased mortality risk in men in middle and old age to recurrent abortus in early pregnancy to cardiovascular disease (CAD)

Variant & Polymorphism SNP , other	common variant putatively involved in occlusive vascular disease, neural tube defects, colon cancer and adult acute leukemia, cardiovascular disease, 677CT/1298CC or 677TT/1298CC genotypes, 677CT/1298AC
	polymorphisms increasing mortality risk in men in middle and old age
	maternal polymorphisms 677C-T and 1298A-C of MTHFR and risk for Down syndrome
	TT genotype was associated with an increased risk of CAD
	polymorphism associated with risk of metabolic syndrome in patients with schizophrenia (Van Winkel 2010)
	SNp is associated with blood pressure and/or hypertension in the Japanese (Takeuchi 2010)

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS