MTR (5-Methyltetrahydrofolate-Homocysteine Methyltransferase)
Key enzyme in homocysteine metabolism and folate cycle; associated with megaloblastic anemia and neurological disorders.
Gene Information Card
| Symbol | MTR |
|---|---|
| Full Name | 5-methyltetrahydrofolate-homocysteine methyltransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 1q43 |
| NCBI Gene ID | 4548 ncbi.nlm.nih.gov/gene/4548 |
| Ensembl ID | ENSG00000116984 |
| UniProt ID | Q99707 |
| OMIM ID | 156570 |
| HGNC ID | 7461 |
| Aliases | MS, cblG, methionine synthase |
Description
The MTR gene encodes methionine synthase, a cobalamin-dependent enzyme that catalyzes the remethylation of homocysteine to methionine using 5-methyltetrahydrofolate as a methyl donor. This reaction is essential for homocysteine homeostasis, methionine synthesis, and the regeneration of tetrahydrofolate for nucleotide biosynthesis. Mutations in MTR cause methylcobalamin deficiency type G (cblG), leading to homocystinuria and megaloblastic anemia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Methylcobalamin deficiency type G (cblG) | Loss-of-function mutations impair homocysteine remethylation, causing homocystinuria, megaloblastic anemia, and neurological deficits. | ClinVar, OMIM |
| Homocystinuria due to MTR deficiency | Deficient methionine synthase activity leads to elevated homocysteine and low methionine. | OMIM |
| Megaloblastic anemia | Impaired folate metabolism due to MTR dysfunction disrupts DNA synthesis. | ClinVar |
| Neural tube defects | Polymorphisms in MTR may influence folate metabolism and risk. | NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 9.8 | Medium |
| Brain | 7.2 | Medium |
| Heart | 6.1 | Low |
| Lung | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.3 | Hepatocellular carcinoma cell line |
| K-562 | 11.0 | Chronic myeloid leukemia |
| HeLa | 9.5 | Cervical carcinoma |
| A549 | 7.8 | Lung carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2756A>G (p.Asp919Gly) | SNP | Common | Reduced enzyme activity; associated with homocysteine levels |
| c.3518C>T (p.Pro1173Leu) | Missense | Rare | Loss of function; cblG disease |
| c.3233G>A (p.Arg1078His) | Missense | Rare | Impaired cobalamin binding |
| c.1465C>T (p.Arg489*) | Nonsense | Rare | Premature truncation; severe cblG |
Mutation functional classification
Loss of Function (LOF)
Most MTR mutations cause loss of enzyme activity, leading to homocystinuria and megaloblastic anemia.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Not described; MTR deficiency is typically recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Homocysteine remethylation cycle
• Folate metabolism
• Methionine cycle
• Sulfur amino acid metabolism
Protein Summary
Methionine synthase (UniProt Q99707) is a 140 kDa cytoplasmic enzyme that requires cobalamin (vitamin B12) as a cofactor and S-adenosylmethionine as a methyl donor. It catalyzes the transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine, producing methionine and tetrahydrofolate. The protein contains a cobalamin-binding domain and a catalytic domain. Defects in this enzyme disrupt one-carbon metabolism and are linked to inherited metabolic disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MTR Knockout HEK293 Cell Line | EDJ-KQ5268 | Human | 4548 | Details Get a Quote |
| MTRR Knockout HEK293 Cell Line | EDJ-KQ5269 | Human | 4552 | Details Get a Quote |
| MTRF1 Knockout HEK293 Cell Line | EDJ-KQ6667 | Human | 9617 | Details Get a Quote |
| MTRES1 Knockout HEK293 Cell Line | EDJ-KQ10997 | Human | 51250 | Details Get a Quote |
| MTRF1L Knockout HEK293 Cell Line | EDJ-KQ11449 | Human | 54516 | Details Get a Quote |
| MTRFR Knockout HEK293 Cell Line | EDJ-KQ14334 | Human | 91574 | Details Get a Quote |
| MTR Knockout A-549 Cell Line | EDJ-KQ27076 | Human | 4548 | Details Get a Quote |
| MTRF1 Knockout A-549 Cell Line | EDJ-KQ30973 | Human | 9617 | Details Get a Quote |
| MTRF1 Knockout HCT 116 Cell Line | EDJ-KQ30974 | Human | 9617 | Details Get a Quote |
| MTRF1 Knockout HeLa Cell Line | EDJ-KQ30975 | Human | 9617 | Details Get a Quote |
| MTRFR Knockout A-549 Cell Line | EDJ-KQ43205 | Human | 91574 | Details Get a Quote |
| MTRFR Knockout HCT 116 Cell Line | EDJ-KQ44442 | Human | 91574 | Details Get a Quote |
| MTRFR Knockout HeLa Cell Line | EDJ-KQ44443 | Human | 91574 | Details Get a Quote |
| MTR Knockout HCT 116 Cell Line | EDJ-KQ28314 | Human | 4548 | Details Get a Quote |
| MTR Knockout HeLa Cell Line | EDJ-KQ28315 | Human | 4548 | Details Get a Quote |
