• Gene id: 4522

Gene Summary

• Gene Symbol: MTHFD1   Gene   UCSC   Ensembl
• Aliases: CIMAH, MTHFC, MTHFD
• Gene name: methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1
• Alternate names: C-1-tetrahydrofolate synthase, cytoplasmic, 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methylenetetrahydrofolate cyclohydrolase, 10-formyltetrahydrofolate synthetase, C1-THF synthase, cytoplasmic C-1-tetrahydrofolate synthase, methylenetetrahydrof,
• Gene location: 14q23.3 (64388040: 64460006)     Exons: 28     NC_000014.9
• Gene summary(Entrez): 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
• OMIM: 172460

Protein Summary

• Protein general information: P11586  
  • Name: C 1 tetrahydrofolate synthase, cytoplasmic (C1 THF synthase) [Cleaved into: C 1 tetrahydrofolate synthase, cytoplasmic, N terminally processed] [Includes: Methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5); Methenyltetrahydrofolate cyclohydrolase (EC 3.
  • Length: 935  
  • Mass: 101,559
• Sequence:

  MAPAEILNGKEISAQIRARLKNQVTQLKEQVPGFTPRLAILQVGNRDDSNLYINVKLKAAEEIGIKATHIKLPRT
  TTESEVMKYITSLNEDSTVHGFLVQLPLDSENSINTEEVINAIAPEKDVDGLTSINAGRLARGDLNDCFIPCTPK
  GCLELIKETGVPIAGRHAVVVGRSKIVGAPMHDLLLWNNATVTTCHSKTAHLDEEVNKGDILVVATGQPEMVKGE
  WIKPGAIVIDCGINYVPDDKKPNGRKVVGDVAYDEAKERASFITPVPGGVGPMTVAMLMQSTVESAKRFLEKFKP
  GKWMIQYNNLNLKTPVPSDIDISRSCKPKPIGKLAREIGLLSEEVELYGETKAKVLLSALERLKHRPDGKYVVVT
  GITPTPLGEGKSTTTIGLVQALGAHLYQNVFACVRQPSQGPTFGIKGGAAGGGYSQVIPMEEFNLHLTGDIHAIT
  AANNLVAAAIDARIFHELTQTDKALFNRLVPSVNGVRRFSDIQIRRLKRLGIEKTDPTTLTDEEINRFARLDIDP
  ETITWQRVLDTNDRFLRKITIGQAPTEKGHTRTAQFDISVASEIMAVLALTTSLEDMRERLGKMVVASSKKGEPV
  SAEDLGVSGALTVLMKDAIKPNLMQTLEGTPVFVHAGPFANIAHGNSSIIADRIALKLVGPEGFVVTEAGFGADI
  GMEKFFNIKCRYSGLCPHVVVLVATVRALKMHGGGPTVTAGLPLPKAYIQENLELVEKGFSNLKKQIENARMFGI
  PVVVAVNAFKTDTESELDLISRLSREHGAFDAVKCTHWAEGGKGALALAQAVQRAAQAPSSFQLLYDLKLPVEDK
  IRIIAQKIYGADDIELLPEAQHKAEVYTKQGFGNLPICMAKTHLSLSHNPEQKGVPTGFILPIRDIRASVGAGFL
  YPLVGTMSTMPGLPTRPCFYDIDLDPETEQVNGLF

• Structural information:
  • Interpro: IPR000559  IPR020628  IPR036291  IPR027417  IPR000672   IPR020630  IPR020867  IPR020631  
  • Prosite: PS00721 PS00722 PS00766 PS00767
  • CDD: cd00477
  • PDB: 1A4I 1DIA 1DIB 1DIG
  • PDBsum: 1A4I 1DIA 1DIB 1DIG
  • DIP: 33682
  • STRING: ENSP00000450560
• Other Databases: GeneCards:  MTHFD1  Malacards:  MTHFD1

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0000105	histidine biosynthetic process	IEA	biological process
GO:0001780	neutrophil homeostasis	IEA	biological process
GO:0001843	neural tube closure	ISS	biological process
GO:0001843	neural tube closure	ISS	biological process
GO:0004329	formate-tetrahydrofolate ligase activity	ISS	molecular function
GO:0004329	formate-tetrahydrofolate ligase activity	TAS	molecular function
GO:0004477	methenyltetrahydrofolate cyclohydrolase activity	TAS	molecular function
GO:0004477	methenyltetrahydrofolate cyclohydrolase activity	TAS	molecular function
GO:0004486	methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity	TAS	molecular function
GO:0004486	methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity	TAS	molecular function
GO:0004487	methylenetetrahydrofolate dehydrogenase (NAD+) activity	ISS	molecular function
GO:0004488	methylenetetrahydrofolate dehydrogenase (NADP+) activity	IBA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0005739	mitochondrion	IEA	cellular component
GO:0005829	cytosol	IBA	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0006164	purine nucleotide biosynthetic process	ISS	biological process
GO:0006555	methionine metabolic process	ISS	biological process
GO:0006730	one-carbon metabolic process	IMP	biological process
GO:0007507	heart development	ISS	biological process
GO:0009069	serine family amino acid metabolic process	ISS	biological process
GO:0009070	serine family amino acid biosynthetic process	IMP	biological process
GO:0009086	methionine biosynthetic process	IMP	biological process
GO:0009257	10-formyltetrahydrofolate biosynthetic process	ISS	biological process
GO:0016020	membrane	IDA	cellular component
GO:0019346	transsulfuration	IEA	biological process
GO:0035999	tetrahydrofolate interconversion	ISS	biological process
GO:0035999	tetrahydrofolate interconversion	IEA	biological process
GO:0046655	folic acid metabolic process	TAS	biological process
GO:0048702	embryonic neurocranium morphogenesis	ISS	biological process
GO:0048703	embryonic viscerocranium morphogenesis	ISS	biological process
GO:0055114	oxidation-reduction process	IEA	biological process
GO:0061053	somite development	ISS	biological process
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0000105	histidine biosynthetic process	IEA	biological process
GO:0000166	nucleotide binding	IEA	molecular function
GO:0001780	neutrophil homeostasis	IEA	biological process
GO:0001843	neural tube closure	IEA	biological process
GO:0001843	neural tube closure	ISS	biological process
GO:0001843	neural tube closure	ISS	biological process
GO:0003824	catalytic activity	IEA	molecular function
GO:0003824	catalytic activity	IEA	molecular function
GO:0004329	formate-tetrahydrofolate ligase activity	IEA	molecular function
GO:0004329	formate-tetrahydrofolate ligase activity	IEA	molecular function
GO:0004329	formate-tetrahydrofolate ligase activity	IEA	molecular function
GO:0004329	formate-tetrahydrofolate ligase activity	ISS	molecular function
GO:0004329	formate-tetrahydrofolate ligase activity	TAS	molecular function
GO:0004329	formate-tetrahydrofolate ligase activity	TAS	molecular function
GO:0004477	methenyltetrahydrofolate cyclohydrolase activity	IEA	molecular function
GO:0004477	methenyltetrahydrofolate cyclohydrolase activity	TAS	molecular function
GO:0004477	methenyltetrahydrofolate cyclohydrolase activity	TAS	molecular function
GO:0004477	methenyltetrahydrofolate cyclohydrolase activity	TAS	molecular function
GO:0004486	methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity	TAS	molecular function
GO:0004486	methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity	TAS	molecular function
GO:0004486	methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity	TAS	molecular function
GO:0004487	methylenetetrahydrofolate dehydrogenase (NAD+) activity	IEA	molecular function
GO:0004487	methylenetetrahydrofolate dehydrogenase (NAD+) activity	ISS	molecular function
GO:0004488	methylenetetrahydrofolate dehydrogenase (NADP+) activity	IEA	molecular function
GO:0004488	methylenetetrahydrofolate dehydrogenase (NADP+) activity	IEA	molecular function
GO:0004488	methylenetetrahydrofolate dehydrogenase (NADP+) activity	IBA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0005737	cytoplasm	IEA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0005739	mitochondrion	IEA	cellular component
GO:0005739	mitochondrion	TAS	cellular component
GO:0005829	cytosol	IBA	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0006164	purine nucleotide biosynthetic process	IEA	biological process
GO:0006164	purine nucleotide biosynthetic process	ISS	biological process
GO:0006164	purine nucleotide biosynthetic process	IEA	biological process
GO:0006555	methionine metabolic process	IEA	biological process
GO:0006555	methionine metabolic process	ISS	biological process
GO:0006730	one-carbon metabolic process	IEA	biological process
GO:0006730	one-carbon metabolic process	IMP	biological process
GO:0007507	heart development	IEA	biological process
GO:0007507	heart development	ISS	biological process
GO:0008152	metabolic process	IEA	biological process
GO:0008652	cellular amino acid biosynthetic process	IEA	biological process
GO:0009069	serine family amino acid metabolic process	IEA	biological process
GO:0009069	serine family amino acid metabolic process	ISS	biological process
GO:0009070	serine family amino acid biosynthetic process	IMP	biological process
GO:0009086	methionine biosynthetic process	IEA	biological process
GO:0009086	methionine biosynthetic process	IMP	biological process
GO:0009257	10-formyltetrahydrofolate biosynthetic process	IEA	biological process
GO:0009257	10-formyltetrahydrofolate biosynthetic process	ISS	biological process
GO:0009396	folic acid-containing compound biosynthetic process	IEA	biological process
GO:0016020	membrane	IDA	cellular component
GO:0016491	oxidoreductase activity	IEA	molecular function
GO:0016787	hydrolase activity	IEA	molecular function
GO:0016874	ligase activity	IEA	molecular function
GO:0019346	transsulfuration	IEA	biological process
GO:0035999	tetrahydrofolate interconversion	IEA	biological process
GO:0035999	tetrahydrofolate interconversion	ISS	biological process
GO:0035999	tetrahydrofolate interconversion	IEA	biological process
GO:0046655	folic acid metabolic process	TAS	biological process
GO:0048702	embryonic neurocranium morphogenesis	ISS	biological process
GO:0048703	embryonic viscerocranium morphogenesis	ISS	biological process
GO:0055114	oxidation-reduction process	IEA	biological process
GO:0055114	oxidation-reduction process	IEA	biological process
GO:0061053	somite development	IEA	biological process
GO:0061053	somite development	ISS	biological process
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0001843	neural tube closure	ISS	biological process
GO:0001843	neural tube closure	ISS	biological process
GO:0004329	formate-tetrahydrofolate ligase activity	ISS	molecular function
GO:0004329	formate-tetrahydrofolate ligase activity	TAS	molecular function
GO:0004329	formate-tetrahydrofolate ligase activity	TAS	molecular function
GO:0004477	methenyltetrahydrofolate cyclohydrolase activity	TAS	molecular function
GO:0004477	methenyltetrahydrofolate cyclohydrolase activity	TAS	molecular function
GO:0004477	methenyltetrahydrofolate cyclohydrolase activity	TAS	molecular function
GO:0004486	methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity	TAS	molecular function
GO:0004486	methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity	TAS	molecular function
GO:0004486	methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity	TAS	molecular function
GO:0004487	methylenetetrahydrofolate dehydrogenase (NAD+) activity	ISS	molecular function
GO:0004488	methylenetetrahydrofolate dehydrogenase (NADP+) activity	IBA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005739	mitochondrion	TAS	cellular component
GO:0005829	cytosol	IBA	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0006164	purine nucleotide biosynthetic process	ISS	biological process
GO:0006555	methionine metabolic process	ISS	biological process
GO:0006730	one-carbon metabolic process	IMP	biological process
GO:0007507	heart development	ISS	biological process
GO:0009069	serine family amino acid metabolic process	ISS	biological process
GO:0009070	serine family amino acid biosynthetic process	IMP	biological process
GO:0009086	methionine biosynthetic process	IMP	biological process
GO:0009257	10-formyltetrahydrofolate biosynthetic process	ISS	biological process
GO:0016020	membrane	IDA	cellular component
GO:0035999	tetrahydrofolate interconversion	ISS	biological process
GO:0046655	folic acid metabolic process	TAS	biological process
GO:0048702	embryonic neurocranium morphogenesis	ISS	biological process
GO:0048703	embryonic viscerocranium morphogenesis	ISS	biological process
GO:0061053	somite development	ISS	biological process
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0070062	extracellular exosome	IDA	cellular component

KEGG pathways

Pathway id	Pathway name
hsa01100	Metabolic pathways

Diseases

Associated diseases	References
Cancer	GAD: 14647408
Cancer (Adenocarcinoma)	GAD: 20056620
Cancer (colorectal)	GAD: 17449906
Cancer (esophageal)	GAD: 20453000
Cancer (leukemia)	GAD: 14647408
Cancer (lung)	GAD: 17533396
Cancer (ovarian)	GAD: 20570913
Cancer (prostate)	GAD: 19064578
Cancer (stomach)	GAD: 17438114
Cancer (breast)	GAD: 16328059
Aortic aneurysm	GAD: 15719048
Aneurysm	GAD: 18635682
Apoplexy	GAD: 20458436
Atherosclerosis	GAD: 20209990
Cardiovascular disease	GAD: 15861780
Congenital abnormalities	GAD: 20374669
Hyperhomocysteinemia	GAD: 18427977
Spinal dysraphism	GAD: 19161160
Spina bifida	KEGG: H00262
Down syndrome	GAD: 21254748
Cleft defects	GAD: 16712703
Neural tube defects	GAD: 19533788
Exfoliation syndrome	GAD: 19112534
Arthritis	GAD: 20386493
Folic acid deficiency	GAD: 19167960
Migraine disorder	GAD: 15953655
Alzheimer's disease	GAD: 20217437
Bipolar disorder	GAD: 17417062
Psychological disorders	GAD: 18801628
Bipolar disorder	GAD: 19328558
Cognitive function	GAD: 19734545
Depression	GAD: 18801628
Abortion	GAD: 20334533
Abruptio placentae	GAD: 15633187
Pregnancy loss	GAD: 16051678
Male factor infertility	MIK: 24268703
Azoospermia	MIK: 24268703
Connective tissue diseases	GAD: 19527514
Omphalocele	GAD: 15937947
Male infertility	MIK: 24268703
Azoospermia	MIK: 24268703

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
24268703	Idiopathic male infertility, azoospermia	MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G, SHMT1 C1420T, MTHFD1 G1958A, and CBS 844ins68	Russian	624 (275 men with idiopathic male infertility, 349 controls)	Male infertility	MTHFD1 G1958A MTR A2756G MTHFR C677T