MTHFD1 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase [Homo sapiens] - Gene

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Summary

Official Symbol: MTHFD1provided by HGNC
Official Full Name: methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetaseprovided by HGNC
Primary source: HGNC:7432
See related: Ensembl:ENSG00000100714; HPRD:01403; MIM:172460; Vega:OTTHUMG00000141309
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MTHFC; MTHFD
Summary: This gene encodes a protein that possesses three distinct enzymatic activities, 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase. Each of these activities catalyzes one of three sequential reactions in the interconversion of 1-carbon derivatives of tetrahydrofolate, which are substrates for methionine, thymidylate, and de novo purine syntheses. The trifunctional enzymatic activities are conferred by two major domains, an aminoterminal portion containing the dehydrogenase and cyclohydrolase activities and a larger synthetase domain. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 14q24

Sequence :: Chromosome: 14; NC_000014.8 (64854759..64926725)

See MTHFD1 in Epigenomics, MapViewer

Chromosome 14 - NC_000014.8 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

MTHFD1 1958GA or AA genotypes were associated with smoking (p = 0.04) and alcoholism (p = 0.03) and were more often found in more advanced stage tumors (p = 0.04) and in patients with a shorter survival (p = 0.03).
Title: Head and neck carconogenesis: impact of MTHFD1 G1958A polymorphism.
This is the first implication of chr14q23.2-23.3 in the etiology of autism and points to MTHFD1, PLEKHG3, and CHURC1 as potential candidate genes contributing to autism risk.
Title: A de novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis.
The genotype and allele frequencies of the MTR Asp919Gly, MTHFR Ala222Val, MTHFD1 Arg653Gln and MTRR Ile22Met gene variants did not display statistical differences between patients with cervical cancer and controls.
Title: Folate and choline metabolism gene variants and development of uterine cervical carcinoma.
Mutation in Methylenetetrahydrofolate Dehydrogenase gene is associated with thrombosis.
Title: A neonate with antiphospholipid syndrome and inherited thrombophilia.
Data show that a significant association with NHL was observed only for MTHFD1 G1958A.
Title: Polymorphisms in folate-metabolizing genes and risk of non-Hodgkin's lymphoma.
c.1958 G>A polymorphism unlikely to play a major role in recurrent spontaneous abortion
Title: The MTHFD1 c.1958 G>A polymorphism and recurrent spontaneous abortions.
the frequencies of MTHFD1 alleles, as well as the frequencies of MTHFD11958 genotypes (GG, GA, AA, GA+AA) do not correlate with Down syndrome pregnancies
Title: Methylenetetrahydrofolate dehydrogenase (MTHFD) enzyme polymorphism as a maternal risk factor for trisomy 21: a clinical study.
Polymorphic variants of folate metabolizing genes (C677T and A1298C MTHFR, C1420T SHMT1 and G1958A MTHFD) are not associated with the risk of breast cancer in West Siberian Region of Russia
Title: [Polymorphic variants of folate metabolizing genes (C677T and A1298C MTHFR, C1420T SHMT1 and G1958A MTHFD) are not associated with the risk of breast cancer in West Siberian Region of Russia].
Observational study and meta-analysis of gene-disease association. (HuGE Navigator)
Title: Polymorphisms in folate-metabolizing genes and risk of non-Hodgkin's lymphoma.
G1793A gene polymorphism, HHcy, folate deficiency and low vitamin B(12) concentration were associated with ulcerative colitis in central China.
Title: Genetic polymorphism of methylenetetrahydrofolate reductase G1793A, hyperhomocysteinemia, and folate deficiency correlate with ulcerative colitis in central China.

Submit: New GeneRIF Correction See all (40)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.

Abruptio placentae, susceptibility to

MIM: 172460

Spina bifida, folate-sensitive, susceptibility to

MIM: 601634

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Products	Interactant	Other Gene	Source	Pubs	Description
P11586	P11586	MTHFD1	HPRD	PubMed
BioGRID:110622	BioGRID:115331	HDAC5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110622	BioGRID:110333	MCC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110622	BioGRID:110455	MME	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110622	BioGRID:111657	PSMA3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110622	BioGRID:112497	SUMO2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110622	BioGRID:113041	TRAF6	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110622	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110622	BioGRID:119068	WRAP73	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
formate-tetrahydrofolate ligase activity	TAS Traceable Author Statement more info
hydrolase activity	IEA Inferred from Electronic Annotation more info
ligase activity	IEA Inferred from Electronic Annotation more info
methenyltetrahydrofolate cyclohydrolase activity	TAS Traceable Author Statement more info
methylenetetrahydrofolate dehydrogenase (NADP+) activity	IEA Inferred from Electronic Annotation more info
methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity	TAS Traceable Author Statement more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
oxidoreductase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cellular amino acid biosynthetic process	IEA Inferred from Electronic Annotation more info
folic acid metabolic process	TAS Traceable Author Statement more info
folic acid-containing compound biosynthetic process	IEA Inferred from Electronic Annotation more info
histidine biosynthetic process	IEA Inferred from Electronic Annotation more info
methionine biosynthetic process	IEA Inferred from Electronic Annotation more info
one-carbon metabolic process	IEA Inferred from Electronic Annotation more info
purine nucleotide biosynthetic process	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info
vitamin metabolic process	TAS Traceable Author Statement more info
water-soluble vitamin metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
mitochondrion	TAS Traceable Author Statement more info	PubMed

General protein information

Preferred Names: C-1-tetrahydrofolate synthase, cytoplasmic

Names: C-1-tetrahydrofolate synthase, cytoplasmic; C1-THF synthase; cytoplasmic C-1-tetrahydrofolate synthase; 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methylenetetrahydrofolate cyclohydrolase, 10-formyltetrahydrofolate synthetase

NP_005947.3

EC 1.5.1.5

EC 3.5.4.9

EC 6.3.4.3

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012450.1 RefSeqGene

Range

5001..76967

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005956.3 → NP_005947.3 C-1-tetrahydrofolate synthase, cytoplasmic

Status: REVIEWED

Source sequence(s)

AL122035, BQ959308, CA446032, DC368835, J04031

Consensus CDS

CCDS9763.1

UniProtKB/TrEMBL

G3V2B8

UniProtKB/Swiss-Prot

P11586

Related

ENSP00000450560, ENST00000555709

Conserved Domains (5) summary

cd00477
Location:333 – 918
Blast Score: 2118

FTHFS; Formyltetrahydrofolate synthetase (FTHFS) catalyzes the ATP-dependent activation of formate ion via its addition to the N10 position of tetrahydrofolate. FTHFS is a highly expressed key enzyme in both the Wood-Ljungdahl pathway of autotrophic CO2 ...

cd01080
Location:120 – 292
Blast Score: 743

NAD_bind_m-THF_DH_Cyclohyd; NADP binding domain of methylene-tetrahydrofolate dehydrogenase/cyclohydrolase

PLN02759
Location:310 – 935
Blast Score: 2623

PLN02759; Formate--tetrahydrofolate ligase

PRK14190
Location:4 – 293
Blast Score: 890

PRK14190; bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase/ 5,10-methylene-tetrahydrofolate cyclohydrolase; Provisional

pfam00763
Location:5 – 125
Blast Score: 413

THF_DHG_CYH; Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000014.8 Reference GRCh37.p5 Primary Assembly

Range

64854759..64926725

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000146.1 Alternate HuRef

Range

45027910..45099523

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AL122035.6 (26632..98260)	None
genomic	CH471061.1	EAW80857.1
		EAW80858.1
mRNA	AK302747.1	BAH13795.1
mRNA	AK309266.1	None
mRNA	AK312361.1	BAG35279.1
mRNA	BC001014.2	AAH01014.2
mRNA	BC009806.2	AAH09806.1
mRNA	BC050420.1	AAH50420.1
mRNA	BQ959308.1	None
mRNA	CA446032.1	None
mRNA	DC368835.1	None
mRNA	J04031.1	AAA59574.1
other-genetic	DQ893634.2	ABM84560.1
other-genetic	DQ896853.2	ABM87852.1