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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

MTHFD1 Gene

protein-coding GIFtS: 65
GCID: GC14P064854

methylenetetrahydrofolate dehydrogenase (NADP+ dependent)...

(Previous symbols: MTHFC, MTHFD)

Explore 57 diseases affiliated with
MTHFD1 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 1, Methenyltetrahydrofolate Cyclohydrolase, Formyltetrahydrofolate Synthetase¹ ²		5,10-Methylenetetrahydrofolate Dehydrogenase, 5,10-Methylenetetrahydrofolate Cyclohydrolase, 10-Formyltetrahydrofolate Synthetase²
MTHFC¹ ² ³ ⁵		C-1-Tetrahydrofolate Synthase, Cytoplasmic²
MTHFD¹ ² ³ ⁵		Cytoplasmic C-1-Tetrahydrofolate Synthase²
C1-THF Synthase² ³		EC 6.3.4.3⁸

External Ids:	HGNC: 7432¹	Entrez Gene: 4522²	Ensembl: ENSG00000100714⁷	OMIM: 172460⁵	UniProtKB: P11586³

Export aliases for MTHFD1 gene to outside databases

Previous GC identifers: GC14P062182 GC14P058648 GC14P062845 GC14P063924 GC14P045027

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for MTHFD1:

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)

Gene Wiki entry for MTHFD1

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000014.8 NC_018925.1 NT_026437.12

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the MTHFD1 gene promoter:
RFX1 NF-YA NF-YC STAT5A CBF-C NF-YB HOXA5 CP1A CP1C NF-Y
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: MTHFD1 promoter sequence

Search SABiosciences Chromatin IP Primers for MTHFD1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat MTHFD1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 14q24 Ensembl cytogenetic band: 14q23.3 HGNC cytogenetic band: 14q24

MTHFD1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
MTHFD1 gene location

GeneLoc information about chromosome 14 GeneLoc Exon Structure

GeneLoc location for GC14P064854: view genomic region (about GC identifiers)

Start:	64,854,749 bp from pter	End:	64,926,725 bp from pter
Size:	71,977 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: C1TC_HUMAN, P11586 (See protein sequence)

Recommended Name: C-1-tetrahydrofolate synthase, cytoplasmic

Size: 935 amino acids; 101559 Da

Subunit: Homodimer

Subcellular location: Cytoplasm

4 PDB 3D structures from and Proteopedia for MTHFD1:

1A4I (3D)

1DIA (3D)

1DIB (3D)

1DIG (3D)

Secondary accessions: B2R5Y2 Q86VC9 Q9BVP5

Explore the universe of human proteins at neXtProt for MTHFD1: NX_P11586

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P11586

4/21 DME Specific Peptides for MTHFD1 (P11586) (see all 21)

PICMAKT

GGGYSQV

LMQTLEG

NLHLTGD

MTHFD1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_005947.3

ENSEMBL proteins:

ENSP00000438588 ENSP00000216605 ENSP00000451309 ENSP00000450560

Reactome Protein details: P11586
Human Recombinant Protein Products:

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	Uscn Proteins for MTHFD1

Gene Ontology (GO): 3 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005737	cytoplasm	IDA	--
GO:0005739	mitochondrion	TAS	3528153
GO:0005829	cytosol	TAS	--

MTHFD1 for ontologies About GeneDecksing

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	Uscn ELISAs and CLIAs for MTHFD1

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

MTHFD1 for domains About GeneDecksing

5/7 InterPro domains/families (see all 7):

IPR020631 THF_DH/CycHdrlase_NAD-bd_dom

IPR020628 Formate_THF_ligase_CS

IPR016040 NAD(P)-bd_dom

IPR000672 THF_DH/CycHdrlase

IPR020630 THF_DH/CycHdrlase_cat_dom

Graphical View of Domain Structure for InterPro Entry P11586

ProtoNet protein and cluster: P11586

2 Blocks protein families:

IPB000559 Formate-tetrahydrofolate ligase

IPB000672 Tetrahydrofolate dehydrogenase/cyclohydrolase

UniProtKB/Swiss-Prot: C1TC_HUMAN, P11586

Domain: This trifunctional enzyme consists of two major domains: an N-terminal part containing the methylene-THF

dehydrogenase and cyclohydrolase activities and a larger C-terminal part containing formyl-THF synthetase activity

Similarity: In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family

Similarity: In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: C1TC_HUMAN, P11586

Catalytic activity: 5,10-methylenetetrahydrofolate + NADP(+) = 5,10-methenyltetrahydrofolate + NADPH

Catalytic activity: 5,10-methenyltetrahydrofolate + H(2)O = 10-formyltetrahydrofolate

Catalytic activity: ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate

Genatlas biochemistry entry for MTHFD1:

folate dependent,trifunctional enzyme catalyzing the oxidation of 5 methy THF for use in purine biosynthesis(see

THFC,THFD,THFS)

Enzyme Number (IUBMB): EC 6.3.4.3²

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		hsa-miR-942 hsa-miR-32* hsa-miR-1207-5p
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Gene Editing
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MTHFD1

Gene Ontology (GO): 5/6 molecular function terms (GO ID links to tree view) (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004329	formate-tetrahydrofolate ligase activity	TAS	--
GO:0004477	methenyltetrahydrofolate cyclohydrolase activity	TAS	--
GO:0004486	methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity	TAS	--
GO:0004488	methylenetetrahydrofolate dehydrogenase (NADP+) activity	IBA	--
GO:0005524	ATP binding	IEA	--

MTHFD1 for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for MTHFD1:

Increased gamma-H2AX phosphory

Animal Models:
3 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Mthfd1):

growth/size

homeostasis/metabolism

mortality/aging

MTHFD1 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/7 super-pathways (see all 7) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Antimetabolite Pathway - Folate Cycle, Pharmacodynamics

	Antimetabolite Pathway - Folate Cycle, Pharmacodynamics	1.00			Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics	0.36
	Methotrexate Pathway (Cancer Cell), Pharmacodynamics	0.45

glycine biosynthesis I

	folate polyglutamylation	0.50			Metabolism of folate and pterines	0.10
	folate transformations I	0.33

Metabolism

Metabolism

1.00

Metabolic pathways

0.38

One Carbon Metabolism

One Carbon Metabolism

1.00

One carbon pool by folate

0.52

Vitamin B5 (pantothenate) metabolism

Metabolism of vitamins and cofactors

0.21

Metabolism of water-soluble vitamins and cofactors

0.21

Pathway sources
See GeneCards unified pathways
Show all pathways

5 BioSystems Pathways for MTHFD1

	One Carbon Metabolism
	histidine degradation III
	tetrahydrofolate salvage from 5,10-methenyltetrahydrofolate
	folate polyglutamylation
	folate transformations I

4 Reactome Pathways for MTHFD1

	Metabolism of folate and pterines
	Metabolism
	Metabolism of vitamins and cofactors
	Metabolism of water-soluble vitamins and cofactors

3 PharmGKB Pathways for MTHFD1

	Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
	Methotrexate Pathway (Cancer Cell), Pharmacodynamics
	Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics

2 Kegg Pathways (Kegg details for MTHFD1):

	One carbon pool by folate
	Metabolic pathways

UniProtKB/Swiss-Prot: C1TC_HUMAN, P11586

Pathway: One-carbon metabolism; tetrahydrofolate interconversion

MTHFD1 for pathways About GeneDecksing

Interactions:

Search SABiosciences Gene Network Central^TM Interacting Genes and Proteins Networks for MTHFD1

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/198 Interacting proteins for MTHFD1 (P11586^{1, 2, 3} ENSP00000216605⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 198)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
WRAP73	Q9P2S5¹^,³, ENSP00000270708⁴	EBI-709638,EBI-1054904 I2D: score=2 STRING: ENSP00000270708
HSP90AB1	P08238²^,³	MINT-72655 I2D: score=3
PRPF6	O94906²^,³	MINT-8173832 I2D: score=3
MCC	P23508¹^,³	EBI-709638,EBI-307531 I2D: score=2
TRAF6	Q9Y4K3¹^,³	EBI-709638,EBI-359276 I2D: score=2

About this table

Gene Ontology (GO): 5/11 biological process terms (GO ID links to tree view) (see all 11): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000105	histidine biosynthetic process	IEA	--
GO:0006164	purine nucleotide biosynthetic process	IEA	--
GO:0006548	histidine catabolic process	--	--
GO:0006730	one-carbon metabolic process	IBA	--
GO:0006766	vitamin metabolic process	TAS	--

MTHFD1 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

MTHFD1 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for MTHFD1

10/12 HMDB Compounds for MTHFD1 (see all 12) About this table

Compound	Synonyms	CAS #	PubMed Ids
5,10-Methenyltetrahydrofolic acid	5,10-Methenyltetrahydrofolate (see all 13)	7444-29-3	--
5,10-Methylene-THF	5,10-methylene-THF (see all 8)	31690-11-6	--
ADP	adenosindiphosphorsaeure (see all 8)	58-64-0	--
Adenosine triphosphate	5'-(tetrahydrogen triphosphate) Adenosine (see all 24)	56-65-5	--
Formic acid	Add-F (see all 21)	64-18-6	--
NAD	3-Carbamoyl-1-D-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate (see all 28)	53-84-9	--
NADH	1,4-Dihydronicotinamide adenine dinucleotide (see all 17)	58-68-4	--
NADP	Adenine-nicotinamide dinucleotide phosphate (see all 18)	53-59-8	--
NADPH	2'-(dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide (see all 23)	53-57-6	--
Phosphate	NFB Orthophosphate (see all 13)	14265-44-2	--

5 DrugBank Compounds for MTHFD1 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Tetrahydrofolic acid	5,6,7,8-tetrahydrofolate (see all 3)	135-16-0	target	cofactor	12937168 12949177 11323021 16171773 17533396
2'-Monophosphoadenosine 5'-Diphosphoribose	--	--	target	--	17139284 17016423
LY249543	--	--	target	--	17139284 17016423
LY374571	--	--	target	--	17139284 17016423
NADH	beta-DPNH (see all 18)	606-68-8	target	--	17139284 17016423

10/13 Novoseek chemical compound relationships for MTHFD1 gene (see all 13) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
5,10-methenyltetrahydrofolate	96.5	20	9701462 (1), 18801628 (1), 18804703 (1), 19649727 (1) (see all 16)
10-formyltetrahydrofolate	91.7	8	16171773 (1), 18801628 (1), 19649727 (1), 16712703 (1) (see all 7)
folate	81.5	43	17438114 (2), 19167960 (2), 12482398 (1), 19020309 (1) (see all 15)
ch2h4folate	76.8	1	16171773 (1)
cystathionine	74.4	3	15503105 (1), 19112534 (1)
homocysteine	71.1	19	17438114 (4), 9701462 (1), 20374669 (1), 15503105 (1) (see all 6)
methionine	70.9	19	19020309 (1), 16712703 (1), 17449906 (1), 20209990 (1) (see all 9)
purine	57.8	2	18767138 (1)
thymidylate	54.9	5	19020309 (1), 17449906 (1), 15797993 (1), 15953655 (1)
cobalamin	51.3	1	2335231 (1)

1 PharmGKB related drug/compound annotation for MTHFD1 gene

Drug/compound	PharmGKB Annotation
methotrexate	CA

About this table

Search CenterWatch for drugs/clinical trials and news about MTHFD1 / C1TC

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for MTHFD1 gene:

NM_005956.3

Unigene Cluster for MTHFD1:

Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase

Hs.652308 [show with all ESTs]

Unigene Representative Sequence: NM_005956

17 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000545908(uc010aqe.2) ENST00000216605 ENST00000554739 ENST00000554768

ENST00000555252 ENST00000557539 ENST00000554057 ENST00000553391 ENST00000556025

ENST00000554677 ENST00000555858 ENST00000556771 ENST00000553405 ENST00000556284

ENST00000557370 ENST00000554353 ENST00000555709(uc001xhb.3 uc010aqf.3)

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		SwitchGear 3'UTR luciferase reporter plasmid: MTHFD1 3' UTR sequence

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		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat MTHFD1

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for MTHFD1 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for MTHFD1 OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: MTHFD1 (NM_005956)
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		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat MTHFD1
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat MTHFD1

Additional cDNA sequence:

AK095514.1 AK097323.1 AK302747.1 AK309266.1 AK312361.1 BC001014.2 BC009806.2 BC050420.1

J04031.1

22 DOTS entries:

DT.447175 DT.100884819 DT.40278922 DT.75113598 DT.102843121 DT.95076849 DT.100758571 DT.120751953

DT.98082896 DT.100030488 DT.100884815 DT.121299659 DT.121299672 DT.121299676 DT.100659065 DT.100884822

DT.120752066 DT.40210775 DT.95076882 DT.75104387 DT.92450985 DT.95295841

24/389 AceView cDNA sequences (see all 389):

AI308940 BE873526 BU521318 CK825448 CB149881 BQ921397 BE906447 CB124895

BM765529 AI262978 BE741343 BC050420 BM833899 CR613709 BU619641 BG675843

AU134663 BQ267460 BQ430626 CR619741 BM549962 CR601328 J04031 BU150148

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

MTHFD1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TCTGTTTACT

About this image

MTHFD1 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

1 LifeMap In Vivo Development Anatomical Compartment/Cell

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Neural Tube

Mesencephalic Ventricular Zone

Neural Tube

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See MTHFD1 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for MTHFD1

SOURCE GeneReport for Unigene cluster: Hs.652308

UniProtKB/Swiss-Prot: C1TC_HUMAN, P11586

Tissue specificity: Ubiquitous

SABiosciences Custom PCR Arrays for MTHFD1

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		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat MTHFD1

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MTHFD1

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of eukaryotes.

Orthologs for MTHFD1 gene from 10/38 species (see all 38) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Mthfd1^{1 , 5}	methylenetetrahydrofolate dehydrogenase (NADP+ dependent), more^{1, 5}	87.27(n)¹ 93.16(a)¹		12 (33.52 cM)⁵ 108156¹ NM_138745.2¹ NP_620084.2¹ 76255232⁵
chicken (Gallus gallus)	Aves	MTHFD1¹	methylenetetrahydrofolate dehydrogenase (NADP+ dependent) more	75.83(n) 80.86(a)		423508 NM_001039303.1 NP_001034392.1
lizard (Anolis carolinensis)	Reptilia	MTHFD1⁶	--	80(a)	1 ↔ 1	1(1506235-1557831)
African clawed frog (Xenopus laevis)	Amphibia	mthfd1-prov²	C1-tetrahydrofolate synthase	76.07(n)		BC045019.1
zebrafish (Danio rerio)	Actinopterygii	mthfd1²	methylenetetrahydrofolate dehydrogenase (NADP+ dependent), more	74.63(n)		260441 BC045396.1
fruit fly (Drosophila melanogaster)	Insecta	pug^{1 , 3}	methylenetetrahydrofolate dehydrogenase (NADP+)³ pugilist¹	61(a)³ 60.06(n)¹ 61.35(a)¹		86C4³ 41279¹ NM_169350.2¹ NP_731489.2¹
worm (Caenorhabditis elegans)	Secernentea	K07E3.4a³ K07E3.4¹	tetrahydrofolate synthase³ Protein K07E3.4¹	70(a) (best of 3)³ 64.14(n)¹ 70.62(a)¹		X(8116261-8118592)³ 181064¹ NM_076960.2¹ NP_509361.1¹
baker's yeast (Saccharomyces cerevisiae)	Saccharomycetes	MIS1(YBR084W)⁴ ADE3¹	Mitochondrial C1-tetrahydrofolate synthase, involved more⁴ Ade3p¹	58.28(n)¹ 59.18(a)¹		2(411054-413981)⁴ 853118¹ NP_011720.3¹ 852378⁴ NP_009640.1⁴
thale cress (Arabidopsis thaliana)	eudicotyledons	THFS¹	Formate--tetrahydrofolate ligase	61.54(n) 67.63(a)		841470 NM_103931.3 NP_564571.1
rice (Oryza sativa)	Liliopsida	Os09g0446800¹	hypothetical protein	60.42(n) 68.27(a)		4347204 NM_001069845.1 NP_001063310.1

ENSEMBL Gene Tree for MTHFD1 (if available)
TreeFam Gene Tree for MTHFD1 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for MTHFD1 gene

MTHFD1L² LOC100996643²

5 SIMAP similar genes for MTHFD1 using alignment to 4 protein entries: C1TC_HUMAN (see all proteins):

LOC100996643 bA251O17.4 MTHFD1L MTHFD2 MTHFD2L

MTHFD1 for paralogs About GeneDecksing

2 Pseudogenes.org Pseudogenes for MTHFD1
PGOHUM00000245259 PGOHUM00000261943

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 14 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs34181110^1,2	C,F	other	64892470(+)	`CAAGCG/ATTTCC`	2	/H /R	mis¹		5		NA EU	5607
rs2236225^1,2	C,F,O,A,H,	other	64908845(-)	`CGATCC/TGGTCT`	2	Q R	mis¹ ese³		31		EA NA NS CSA WA EU	8917
rs183699854^1,2		--	64852762(+)	`CAACTC/TATACA`	1	--	us2k¹		0	--	--	--	--
rs1956545^1,2	C,F,A,H,	--	64852905(-)	`ATCCCA/GTTTTA`	1	--	us2k¹		33		NS EA NA WA CSA	2988
rs187878745^1,2		--	64853017(+)	`CCTTCA/CATTTT`	1	--	us2k¹		0	--	--	--	--
rs191474062^1,2		--	64853051(+)	`TACAAC/TACAAT`	1	--	us2k¹		0	--	--	--	--
rs141622461^1,2		--	64853067(+)	`ACAATA/GTGTTT`	1	--	us2k¹		0	--	--	--	--
rs182232887^1,2		--	64853161(+)	`TAAGGC/TCACGC`	1	--	us2k¹		0	--	--	--	--
rs115723765^1,2		--	64853185(+)	`CCCATT/CATCCC`	1	--	us2k¹		1		WA	118
rs73271875^1,2	C,	--	64853368(+)	`CAGAGG/CCTACA`	1	--	us2k¹		1		WA	2

HapMap Linkage Disequilibrium report for MTHFD1 (64854749 - 64926725 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for MTHFD1: --
Human Gene Mutation Database (HGMD): MTHFD1

SABiosciences Cancer Mutation PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

MTHFD1 for disorders           About GeneDecksing

OMIM gene information: 172460
OMIM disorders: 601634
UniProtKB/Swiss-Prot: C1TC_HUMAN, P11586

Defects in MTHFD1 may be a cause of susceptibility to folate-sensitive neural tube defects (FS-NTD)

[MIM:601634]. The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. Genetic defects in MTHFD1

may affect the risk of spina bifida via the maternal rather than the embryonic genotype

Genetic variation in MTHFD1 could be associated with susceptibility to colorectal cancer (CRC) [MIM:114500]

20/57 diseases for MTHFD1 (see all 57): About MalaCards

spina bifida, folate-sensitive neural tube defect spina bifida cleft lip/palate

patent ductus arteriosus abdominal aortic aneurysm placental abruption cleft lip

non-hodgkin lymphoma type 2 diabetes mellitus aortic aneurysm birth defects

orofacial cleft congenital heart defect leukemia/lymphoma lymphoblastic leukemia

systemic lupus erythematosus leukemia/lymphoma, t-cell myelomeningocele anencephaly

3 Novoseek disease relationships for MTHFD1 gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
neural tube defects	75.9	6	19130090 (2), 9611072 (1), 18767138 (1)
lymphoblastic leukemia acute childhood	56.8	1	14647408 (1)
spina bifida	44.4	1	17894836 (1)

Genetic Association Database (GAD): MTHFD1
Human Genome Epidemiology (HuGE) Navigator: MTHFD1 (94 documents)

Export disorders for MTHFD1 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for MTHFD1 gene, integrated from 9 sources (see all 166):
(articles sorted by number of sources associating them with MTHFD1)

Utopia: connect your pdf to the dynamic
world of online information

A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group. (PubMed id 12384833)^{1, 2, 4, 9} Brody L.C....Swanson D.A. (2002)
Primary structure of a human trifunctional enzyme. Isolation of a cDNA encoding methylenetetrahydrofolate dehydrogenase- methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase. (PubMed id 3053686)^{1, 2, 3} Hum D.W.... Mackenzie R.E. (1988)
Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects. (PubMed id 9611072)^{1, 2, 9} Hol F.A.... Blom H.J. (1998)
The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects. (PubMed id 18767138)^{1, 2, 9} Christensen K.E.... Rozen R. (2009)
Relationship between polymorphism of methylenetetrahydrofolate dehydrogenase and congenital heart defect. (PubMed id 15861780)^{1, 4, 9} Cheng J....Li Y. (2005)
Role of polymorphisms in MTHFR and MTHFD1 genes in the outcome of childhood acute lymphoblastic leukemia. (PubMed id 14647408)^{1, 4, 9} Krajinovic M....Moghrabi A. (2004)
Confirmation of the R653Q polymorphism of the trifunctional C1- synthase enzyme as a maternal risk for neural tube defects in the Irish population. (PubMed id 16552426)^{1, 2, 9} Parle-McDermott A....Scott J.M. (2006)
Thymidylate synthase promoter tandem repeat and MTHFD1 R653Q polymorphisms modulate the risk for migraine conferred by the MTHFR T677 allele. (PubMed id 15953655)^{1, 4, 9} Oterino A....Cid C. (2005)
Polymorphisms in the one-carbon metabolic pathway, plasma folate levels and colorectal cancer in a prospective study. (PubMed id 15122597)^{1, 4, 9} Chen J....Ma J. (2004)
Prognostic significance of folate metabolism polymorphisms for lung cancer. (PubMed id 17533396)^{1, 7, 9} Matakidou A....Houlston R.S. (2007)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 4522	HGNC: 7432	AceView: MTHFD1	Ensembl:ENSG00000100714	euGenes: HUgn4522
ECgene: MTHFD1	Kegg: 4522	H-InvDB: MTHFD1

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for MTHFD1	Pharmacogenomics, SNPs, Pathways

Intellectual Property for MTHFD1 gene
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Patent Information for MTHFD1 gene:
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