MTHFS: 5,10-Methenyltetrahydrofolate Synthetase
A key enzyme in folate metabolism, catalyzing the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate.
Gene Information Card
| Symbol | MTHFS |
|---|---|
| Full Name | 5,10-methenyltetrahydrofolate synthetase |
| Gene Type | protein-coding |
| Chromosomal Location | 15q25.1 |
| NCBI Gene ID | 10588 ncbi.nlm.nih.gov/gene/10588 |
| Ensembl ID | ENSG00000137807 |
| UniProt ID | P49914 |
| OMIM ID | 604197 |
| HGNC ID | 7437 |
| Aliases | MTHFS, HsT17279, 5,10-MTHF synthetase |
Description
MTHFS encodes 5,10-methenyltetrahydrofolate synthetase, an enzyme that catalyzes the ATP-dependent conversion of 5-formyltetrahydrofolate (folinic acid) to 5,10-methenyltetrahydrofolate. This reaction is critical for intracellular folate homeostasis and one-carbon metabolism, supporting nucleotide synthesis, methylation, and redox balance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Altered folate metabolism may influence DNA methylation and nucleotide synthesis, affecting tumor progression. | ClinVar, COSMIC |
| Neurodegenerative disorders | Dysregulation of folate metabolism linked to neural tube defects and cognitive decline. | OMIM, NCBI Gene |
| MTHFS deficiency (putative) | Loss-of-function variants may impair folate interconversion, leading to metabolic disturbances. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Brain | 6.1 | Low |
| Heart | 4.7 | Low |
| Testis | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| HEK293 | 9.8 | Embryonic kidney cells |
| SH-SY5Y | 5.4 | Neuroblastoma cell line |
| MCF7 | 7.1 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Likely loss of function; may affect translation initiation |
| c.214C>T (p.Arg72Trp) | Missense | 0.01% | Reduced enzyme activity in vitro |
| c.487G>A (p.Gly163Arg) | Missense | 0.005% | Unknown functional impact |
Mutation functional classification
Loss of Function (LOF)
Variants such as p.Met1? and p.Arg72Trp are predicted to reduce or abolish enzymatic activity, impairing folate conversion.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • 5 (GO:0004329) | • ATP binding (GO:0005524) |
| • one-carbon metabolic process (GO:0006730) | • cytosol (GO:0005829) |
| • cytoplasm (GO:0005737) |
Pathways
• Folate metabolism (Reactome: R-HSA-196757)
• One-carbon metabolism (KEGG: hsa00670)
Protein Summary
The MTHFS protein (UniProt P49914) is a 203-amino acid enzyme that localizes to the cytosol. It catalyzes the ATP-dependent cyclization of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate, a key step in folate interconversion. The enzyme is essential for maintaining the intracellular folate pool and supporting nucleotide biosynthesis and methylation reactions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MTHFS Knockout HEK293 Cell Line | EDJ-KQ7100 | Human | 10588 | Details Get a Quote |
| MTHFSD Knockout HEK293 Cell Line | EDJ-KQ14330 | Human | 64779 | Details Get a Quote |
| MTHFS Knockout A-549 Cell Line | EDJ-KQ31952 | Human | 10588 | Details Get a Quote |
| MTHFS Knockout HCT 116 Cell Line | EDJ-KQ31953 | Human | 10588 | Details Get a Quote |
| MTHFS Knockout HeLa Cell Line | EDJ-KQ31954 | Human | 10588 | Details Get a Quote |
| MTHFSD Knockout HCT 116 Cell Line | EDJ-KQ43197 | Human | 64779 | Details Get a Quote |
| MTHFSD Knockout A-549 Cell Line | EDJ-KQ44433 | Human | 64779 | Details Get a Quote |
| MTHFSD Knockout HeLa Cell Line | EDJ-KQ44435 | Human | 64779 | Details Get a Quote |
| ST20-MTHFS Knockout HEK293 Cell Line | EDJ-KQ52486 | Human | 100528021 | Details Get a Quote |
| ST20-MTHFS Knockout HeLa Cell Line | EDJ-KQ60949 | Human | 100528021 | Details Get a Quote |
| ST20-MTHFS Knockout A-549 Cell Line | EDJ-KQ69424 | Human | 100528021 | Details Get a Quote |
| ST20-MTHFS Knockout HCT 116 Cell Line | EDJ-KQ77775 | Human | 100528021 | Details Get a Quote |
