MTHFD1
methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 | MTHFC, MTHFD

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]

Member of: DE-6 DE-6.18 Developmental clusters: GC3
Biological processes 47 terms
10-formyltetrahydrofolate biosynthetic process (GO:0009257)10-formyltetrahydrofolate biosynthetic process (GO:0009257)10-formyltetrahydrofolate biosynthetic process (GO:0009257)ATP binding (GO:0005524)L-methionine biosynthetic process (GO:0071265)L-methionine metabolic process (GO:0006555)catalytic activity (GO:0003824)cytoplasm (GO:0005737)cytosol (GO:0005829)cytosol (GO:0005829)cytosol (GO:0005829)cytosol (GO:0005829)cytosol (GO:0005829)embryonic neurocranium morphogenesis (GO:0048702)embryonic viscerocranium morphogenesis (GO:0048703)extracellular exosome (GO:0070062)folic acid metabolic process (GO:0046655)folic acid metabolic process (GO:0046655)folic acid metabolic process (GO:0046655)formate-tetrahydrofolate ligase activity (GO:0004329)formate-tetrahydrofolate ligase activity (GO:0004329)formate-tetrahydrofolate ligase activity (GO:0004329)formate-tetrahydrofolate ligase activity (GO:0004329)heart development (GO:0007507)heart development (GO:0007507)membrane (GO:0016020)methenyltetrahydrofolate cyclohydrolase activity (GO:0004477)methenyltetrahydrofolate cyclohydrolase activity (GO:0004477)methenyltetrahydrofolate cyclohydrolase activity (GO:0004477)methylenetetrahydrofolate dehydrogenase (NADP+) activity (GO:0004488)methylenetetrahydrofolate dehydrogenase (NADP+) activity (GO:0004488)methylenetetrahydrofolate dehydrogenase (NADP+) activity (GO:0004488)mitochondrion (GO:0005739)neural tube closure (GO:0001843)neural tube closure (GO:0001843)neutrophil homeostasis (GO:0001780)protein binding (GO:0005515)purine nucleotide biosynthetic process (GO:0006164)purine nucleotide biosynthetic process (GO:0006164)purine nucleotide biosynthetic process (GO:0006164)somite development (GO:0061053)somite development (GO:0061053)tetrahydrofolate interconversion (GO:0035999)tetrahydrofolate interconversion (GO:0035999)tetrahydrofolate interconversion (GO:0035999)tetrahydrofolate interconversion (GO:0035999)transsulfuration (GO:0019346)
Expression (TPM)
MTHFD1 — as a Regulated Gene

TFs regulating MTHFD1 0 TFs

Transcription factors with Perturb-seq knockdown data for MTHFD1. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = MTHFD1 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

Data: Effect:
TF Mean coef Binding Outlier TF→Gene link

Elements linked to MTHFD1

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of MTHFD1, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Accessibility Element Dist. to TSS Link type TFs
chr14:64,186,206–64,187,022 201.8 kb Distal (>10kb) Multiome 106
chr14:64,293,957–64,295,260 93.3 kb Distal (>10kb) Multiome 474
chr14:64,337,827–64,339,391 49.5 kb Distal (>10kb) Multiome 825
chr14:64,387,230–64,388,939 203 bp At TSS Multiome 902
chr14:64,391,271–64,391,891 3.3 kb Proximal (<10kb) Multiome 182
chr14:64,465,087–64,466,161 77.2 kb Distal (>10kb) Multiome 490
chr14:64,502,980–64,505,716 115.5 kb Distal (>10kb) Multiome 1045
chr14:64,508,924–64,509,409 120.9 kb Distal (>10kb) Multiome 117
chr14:64,539,520–64,541,644 152.2 kb Distal (>10kb) Multiome 722
chr14:64,549,785–64,550,422 161.7 kb Distal (>10kb) Multiome 234
chr14:64,645,238–64,645,989 257.4 kb Distal (>10kb) Multiome 252
chr14:64,657,975–64,659,082 270.3 kb Distal (>10kb) Multiome 104

Genome Browser

Genomic view of the MTHFD1 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.

chr14:64,176,206 – 64,669,082
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq