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FLASH GENE

Symbol

MTHFD1

contributors: mct/npt/pgu - updated : 19-09-2012

HGNC name	methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase
HGNC id	7432

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MTHFD1D MTHFD1 deficiency
Location	14q23.3      Physical location : 64.854.758 - 64.926.727
Synonym name	10-formyltetrahydrofolate synthetase
	C1-THF synthase
	NADP-dependent cyclohydrolase/formyltetrahydrofolate synthetase
	cytoplasmic C-1-tetrahydrofolate synthase
	5,10-methylenetetrahydrofolate cyclohydrolase,
	10-formyltetrahydrofolate synthetase
	C1-THF synthase
Synonym symbol(s)	MTHFC, TFD1, MTHFD, THFC, THFS, THFD1
EC.number	1.5.1.5, 3.5.4.9, 6.3.4.3

DNA

TYPE	functioning gene
STRUCTURE	71.97 kb     28 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
motif
text structure	controlled by a TATA-less, Initiator-less promoter and transcription is initiated at multiple start sites over a 126 bp region

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D14S63 - D14SD1026 - MTHFD1 - D14S982 - D14S271 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005956 28 - 3466 NP_005947 101 935 - 1998 9611072

EXPRESSION

Type	ubiquitous

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 liver       highly   stomach       highly Skin/Tegument skin       highly Visual eye       highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

the synthetase domain contains two regions that are homologous to consensus sequences for an ATP-binding site

mono polymer

homomer , dimer

HOMOLOGY

Homologene

FAMILY	in the N-terminal : tetrahydrofolate dehydrogenase cyclohydrolase family
	in the C-terminal : formate--tetrahydrofolate ligase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,cytosolic

basic FUNCTION	trifunctional enzyme catalyzing the second step in the oxidation of 5,10-methenyl THF to 10 formyl THF for use in purine biosynthesis
	possesses three distinct enzymatic activities, 5,10-methylenetetrahydrofolate dehydrogenase, cyclohydrolase and synthetase
	trifunctional enzyme involved in DNA synthesis and folate metabolism
	ssential for the generation of formyltetrahydrofolate and methylenetetrahydrofolate and important for nucleotide and homocysteine metabolism

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

aminoacid , purine/pyrimidine , other

signaling

biosynthesis of purines, thymydylate, methionine, histidine, pantothenate, and formyl tRNA-met

a component

INTERACTION

DNA

RNA

small molecule

protein

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

MTHFD1D

Susceptibility

to neural tube defect and spina bifida, folate-dependent to abdominal aortic aneurysm to congenital heart defects (CHD) to bipolar disorder and schizophrenia to early onset Alzheimer disease

Variant & Polymorphism other	maternal genotype QQ increasing the risk of neural tube defect-affected pregnancy
	R653Q increases the maternal risk for neural tube defects
	Arg653Gln polymorphism decreases enzyme stability and increases risk for CHD
	G1958A A allele might be a weak risk factor for early onset Alzheimer disease

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS