MTHFD1 methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MTHFD1provided by HGNC
Official Full Name: methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1provided by HGNC
Primary source: HGNC:HGNC:7432
See related: Ensembl:ENSG00000100714 MIM:172460; AllianceGenome:HGNC:7432
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: CIMAH; 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]
Expression: Broad expression in liver (RPKM 96.4), fat (RPKM 36.5) and 22 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 14q23.3

Exon count:: 28

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (64388353..64460025)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (58596072..58667774)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (64855071..64926743)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

MTHFD1 regulates the NADPH redox homeostasis in MYCN-amplified neuroblastoma.
Title: MTHFD1 regulates the NADPH redox homeostasis in MYCN-amplified neuroblastoma.
The negative effect of G1958A polymorphism on MTHFD1 protein stability and HCC growth.
Title: The negative effect of G1958A polymorphism on MTHFD1 protein stability and HCC growth.
Association Between MTHFD1 1958G > A Variant and non-Syndromic Cleft lip and Palate: An Updated Meta-Analysis.
Title: Association Between MTHFD1 1958G > A Variant and non-Syndromic Cleft lip and Palate: An Updated Meta-Analysis.
[Association of maternal MTHFD1 and MTHFD2 gene polymorphisms with congenital heart disease in offspring].", trans "MTHFD1MTHFD2.
Title: [Association of maternal MTHFD1 and MTHFD2 gene polymorphisms with congenital heart disease in offspring].
Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.
Title: Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.
Association of methionine synthase (rs1805087), methionine synthase reductase (rs1801394), and methylenetetrahydrofolate dehydrogenase 1 (rs2236225) genetic polymorphisms with recurrent implantation failure.
Title: Association of methionine synthase (rs1805087), methionine synthase reductase (rs1801394), and methylenetetrahydrofolate dehydrogenase 1 (rs2236225) genetic polymorphisms with recurrent implantation failure.
A comprehensive association analysis between homocysteine metabolic pathway gene methylation and ischemic stroke in a Chinese hypertensive population.
Title: A comprehensive association analysis between homocysteine metabolic pathway gene methylation and ischemic stroke in a Chinese hypertensive population.
Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy.
Title: Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy.
Independent and Interactive Influences of Environmental UVR, Vitamin D Levels, and Folate Variant MTHFD1-rs2236225 on Homocysteine Levels.
Title: Independent and Interactive Influences of Environmental UVR, Vitamin D Levels, and Folate Variant MTHFD1-rs2236225 on Homocysteine Levels.
Biochemical analysis of patients with mutations in MTHFD1 and a diagnosis of methylenetetrahydrofolate dehydrogenase 1 deficiency.
Title: Biochemical analysis of patients with mutations in MTHFD1 and a diagnosis of methylenetetrahydrofolate dehydrogenase 1 deficiency.

Submit: New GeneRIF Correction See all GeneRIFs (92)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia MedGen: C4540434 OMIM: 617780 GeneReviews: Not available	Compare labs
Neural tube defects, folate-sensitive MedGen: C1866558 OMIM: 601634 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

G35893 (e-PCR)
- UniSTS:63241

RH66227 (e-PCR)
- UniSTS:9760

G17812 (e-PCR)
- UniSTS:79152

SHGC-8058 (e-PCR)
- UniSTS:4670

G35374 (e-PCR)
- UniSTS:51774

hummdmcs (e-PCR)
- UniSTS:88179

D14S1185 (e-PCR)
- UniSTS:68500

RH65696 (e-PCR)
- UniSTS:89786

G35987 (e-PCR)
- UniSTS:57066

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables formate-tetrahydrofolate ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables formate-tetrahydrofolate ligase activity	ISS Inferred from Sequence or Structural Similarity more info
enables methenyltetrahydrofolate cyclohydrolase activity	IBA Inferred from Biological aspect of Ancestor more info
enables methenyltetrahydrofolate cyclohydrolase activity	IDA Inferred from Direct Assay more info	PubMed
enables methylenetetrahydrofolate dehydrogenase (NAD+) activity	ISS Inferred from Sequence or Structural Similarity more info
enables methylenetetrahydrofolate dehydrogenase (NADP+) activity	IBA Inferred from Biological aspect of Ancestor more info
enables methylenetetrahydrofolate dehydrogenase (NADP+) activity	IDA Inferred from Direct Assay more info	PubMed
enables methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in 10-formyltetrahydrofolate biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in 10-formyltetrahydrofolate biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in embryonic neurocranium morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in embryonic viscerocranium morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in heart development	ISS Inferred from Sequence or Structural Similarity more info
involved_in methionine biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in methionine metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in neural tube closure	ISS Inferred from Sequence or Structural Similarity more info
involved_in neutrophil homeostasis	IEA Inferred from Electronic Annotation more info
involved_in one-carbon metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of purine nucleotide biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in purine nucleotide biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in purine ribonucleotide biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in serine family amino acid biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in serine family amino acid metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in somite development	ISS Inferred from Sequence or Structural Similarity more info
involved_in tetrahydrofolate interconversion	IBA Inferred from Biological aspect of Ancestor more info
involved_in tetrahydrofolate interconversion	IDA Inferred from Direct Assay more info	PubMed
involved_in tetrahydrofolate interconversion	IEA Inferred from Electronic Annotation more info
involved_in tetrahydrofolate interconversion	ISS Inferred from Sequence or Structural Similarity more info
involved_in transsulfuration	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in membrane	HDA more info	PubMed
located_in mitochondrion	TAS Traceable Author Statement more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: C-1-tetrahydrofolate synthase, cytoplasmic

Names: 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methylenetetrahydrofolate cyclohydrolase, 10-formyltetrahydrofolate synthetase; C1-THF synthase; cytoplasmic C-1-tetrahydrofolate synthase; epididymis secretory sperm binding protein; methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase

NP_001351766.1

EC 1.5.1.5

EC 3.5.4.9

EC 6.3.4.3

NP_005947.3

EC 1.5.1.5

EC 3.5.4.9

EC 6.3.4.3

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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_012450.2 RefSeqGene

Range

5313..76985

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1243

mRNA and Protein(s)

NM_001364837.1 → NP_001351766.1 C-1-tetrahydrofolate synthase, cytoplasmic isoform 2

Status: REVIEWED

Source sequence(s)

AK302747, AL122035

Consensus CDS

CCDS91885.1

UniProtKB/TrEMBL

B7Z809, F5H2F4

Related

ENSP00000438588.2, ENST00000545908.6

Conserved Domains (2) summary

PLN02759
Location:310 → 907

PLN02759; Formate--tetrahydrofolate ligase

COG0190
Location:6 → 294

FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme transport and metabolism]
NM_005956.4 → NP_005947.3 C-1-tetrahydrofolate synthase, cytoplasmic isoform 1

Status: REVIEWED

Source sequence(s)

AL122035, BQ959308, J04031

Consensus CDS

CCDS9763.1

UniProtKB/Swiss-Prot

A0A024R652, A0A384N5Y3, B2R5Y2, G3V2B8, P11586, Q86VC9, Q9BVP5

UniProtKB/TrEMBL

V9GYY3

Related

ENSP00000498336.1, ENST00000652337.1

Conserved Domains (2) summary

PLN02759
Location:310 → 935

PLN02759; Formate--tetrahydrofolate ligase

COG0190
Location:6 → 294

FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme transport and metabolism]