This gene encodes a nuclear-encoded mitochondrial bifunctional enzyme with methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities. The enzyme functions as a homodimer and is unique in its absolute requirement for magnesium and inorganic phosphate. Formation of the enzyme-magnesium complex allows binding of NAD. Alternative splicing results in two different transcripts, one protein-coding and the other not protein-coding. This gene has a pseudogene on chromosome 7. [provided by RefSeq, Mar 2009]
Transcription factors with Perturb-seq knockdown data for MTHFD2. 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 = MTHFD2 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.
| TF | Mean coef | Binding | Outlier | TF→Gene link |
|---|
Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of MTHFD2, 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 |
|---|---|---|---|---|
| chr2:73,921,096–73,921,666 | 277.2 kb | Distal (>10kb) Multiome | 284 | |
| chr2:73,926,648–73,927,193 | 271.7 kb | Distal (>10kb) Multiome | 961 | |
| chr2:73,981,145–73,981,910 | 217.0 kb | Distal (>10kb) Multiome | 483 | |
| chr2:73,983,451–73,985,871 | 213.3 kb | Distal (>10kb) Multiome | 821 | |
| chr2:74,002,059–74,003,348 | 195.9 kb | Distal (>10kb) Multiome | 514 | |
| chr2:74,008,705–74,009,321 | 189.6 kb | Distal (>10kb) Multiome | 142 | |
| chr2:74,026,198–74,026,578 | 172.2 kb | Distal (>10kb) Multiome | 88 | |
| chr2:74,119,987–74,120,643 | 78.2 kb | Distal (>10kb) Multiome | 969 | |
| chr2:74,147,573–74,148,843 | 50.6 kb | Distal (>10kb) Multiome | 884 | |
| chr2:74,178,147–74,179,324 | 19.7 kb | Distal (>10kb) Multiome | 869 | |
| chr2:74,187,993–74,188,519 | 10.4 kb | Distal (>10kb) Multiome | 192 | |
| chr2:74,198,074–74,199,486 | 66 bp | At TSS Multiome | 1098 | |
| chr2:74,261,293–74,261,813 | 63.0 kb | Distal (>10kb) Multiome | 184 | |
| chr2:74,374,253–74,375,246 | 176.1 kb | Distal (>10kb) Multiome | 158 | |
| chr2:74,379,653–74,380,438 | 181.4 kb | Distal (>10kb) Multiome | 229 | |
| chr2:74,391,129–74,392,484 | 193.3 kb | Distal (>10kb) Multiome | 876 | |
| chr2:74,421,273–74,422,464 | 223.1 kb | Distal (>10kb) Multiome | 756 | |
| chr2:74,426,172–74,426,842 | 228.0 kb | Distal (>10kb) Multiome | 88 | |
| chr2:74,440,246–74,442,723 | 243.5 kb | Distal (>10kb) Multiome | 1050 | |
| chr2:74,454,612–74,455,413 | 256.4 kb | Distal (>10kb) Multiome | 982 | |
| chr2:74,457,177–74,459,169 | 259.7 kb | Distal (>10kb) Multiome | 934 | |
| chr2:74,464,912–74,465,776 | 266.8 kb | Distal (>10kb) Multiome | 842 | |
| chr2:74,472,106–74,473,059 | 274.0 kb | Distal (>10kb) Multiome | 1071 | |
| chr2:74,481,955–74,483,673 | 284.5 kb | Distal (>10kb) Multiome | 1031 | |
| chr2:74,497,707–74,500,027 | 299.6 kb | Distal (>10kb) Multiome | 553 |
Genomic view of the MTHFD2 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.