MTHFD2 (Methylenetetrahydrofolate Dehydrogenase, Cyclohydrolase, and Formyltetrahydrofolate Synthetase 2)
A mitochondrial bifunctional enzyme involved in one-carbon metabolism, implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | MTHFD2 |
|---|---|
| Full Name | Methylenetetrahydrofolate Dehydrogenase, Cyclohydrolase, and Formyltetrahydrofolate Synthetase 2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 2p13.1 |
| NCBI Gene ID | 10797 ncbi.nlm.nih.gov/gene/10797 |
| Ensembl ID | ENSG00000165997 |
| UniProt ID | P13995 |
| OMIM ID | 604887 |
| HGNC ID | 7434 |
| Aliases | MTHFD2, NMDMC, MTHFD2L |
Description
MTHFD2 encodes a mitochondrial bifunctional enzyme that catalyzes the interconversion of methylenetetrahydrofolate to methenyltetrahydrofolate and then to formyltetrahydrofolate, playing a critical role in one-carbon metabolism essential for nucleotide synthesis and cellular proliferation. It is highly expressed in embryonic tissues and many cancers, where it supports rapid cell division. Mutations in MTHFD2 are associated with a rare neurometabolic disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| MTHFD2 deficiency (NMDMC) | Loss-of-function mutations impair mitochondrial folate metabolism, leading to developmental delay, microcephaly, and leukoencephalopathy. | ClinVar, OMIM |
| Cancer (various types) | Overexpression in tumors promotes proliferation and metastasis via enhanced nucleotide biosynthesis and redox balance. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 10.2 | Moderate |
| Liver | 8.5 | Moderate |
| Testis | 7.3 | Low |
| Brain | 2.1 | Low |
| Heart | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.4 | High expression |
| MCF7 | 12.8 | High expression |
| A549 | 11.2 | High expression |
| HepG2 | 9.6 | Moderate expression |
| K562 | 6.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.940C>T (p.Arg314Ter) | Nonsense | Rare | Loss of function, associated with NMDMC |
| c.1A>G (p.Met1Val) | Missense | Rare | Loss of function, associated with NMDMC |
| c.742G>A (p.Gly248Ser) | Missense | Rare | Loss of function, associated with NMDMC |
Mutation functional classification
Loss of Function (LOF)
Mutations leading to reduced or absent enzymatic activity, causing MTHFD2 deficiency.
Gain of Function (GOF)
No known gain-of-function mutations; overexpression is observed in cancer but not due to mutations.
Dominant Negative (DN)
No evidence for dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • methylenetetrahydrofolate dehydrogenase (NADP+) activity | • methenyltetrahydrofolate cyclohydrolase activity |
| • formyltetrahydrofolate synthetase activity | • mitochondrion |
| • one-carbon metabolic process | • tetrahydrofolate interconversion |
Pathways
• One-carbon metabolism
• Folate metabolism
• Purine biosynthesis
• Thymidylate biosynthesis
Protein Summary
MTHFD2 is a mitochondrial bifunctional enzyme with dehydrogenase and cyclohydrolase activities, but lacks the synthetase domain present in the cytoplasmic isoform. It is a homodimer that uses NADP+ as cofactor. The protein is essential for embryonic development and is highly expressed in proliferating cells, making it a potential therapeutic target in cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MTHFD2 Knockout HEK293 Cell Line | EDJ-KQ3010 | Human | 10797 | Details Get a Quote |
| MTHFD2L Knockout HEK293 Cell Line | EDJ-KQ11886 | Human | 441024 | Details Get a Quote |
| MTHFD2L Knockout HeLa Cell Line | EDJ-KQ39093 | Human | 441024 | Details Get a Quote |
| MTHFD2 Knockout A-549 Cell Line | EDJ-KQ25588 | Human | 10797 | Details Get a Quote |
| MTHFD2 Knockout HCT 116 Cell Line | EDJ-KQ25590 | Human | 10797 | Details Get a Quote |
| MTHFD2 Knockout HeLa Cell Line | EDJ-KQ25591 | Human | 10797 | Details Get a Quote |
| MTHFD2L Knockout A-549 Cell Line | EDJ-KQ40329 | Human | 441024 | Details Get a Quote |
| MTHFD2L Knockout HCT 116 Cell Line | EDJ-KQ40330 | Human | 441024 | Details Get a Quote |
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