MTRR Gene: Methionine Synthase Reductase – Function, Mutations, and Associated Diseases
Comprehensive guide to the MTRR gene, including genomic context, protein function, expression, disease associations, and clinical relevance.
Gene Information Card
| Symbol | MTRR |
|---|---|
| Full Name | Methionine synthase reductase |
| Gene Type | Protein coding |
| Chromosomal Location | 5p15.31 |
| NCBI Gene ID | 4552 ncbi.nlm.nih.gov/gene/4552 |
| Ensembl ID | ENSG00000124275 |
| UniProt ID | Q9UBK8 |
| OMIM ID | 602568 |
| HGNC ID | 7474 |
| Aliases | MSR, cblE, METHFR |
Description
The MTRR gene encodes methionine synthase reductase, a flavoprotein that catalyzes the reductive methylation of methionine synthase (MTR) using S-adenosylmethionine as a methyl donor. This reaction is essential for the regeneration of active methionine synthase, which converts homocysteine to methionine. MTRR is critical for folate and cobalamin metabolism, and its dysfunction leads to hyperhomocysteinemia and various clinical disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Methylcobalamin deficiency type cblE | Loss-of-function mutations in MTRR impair the reactivation of methionine synthase, leading to decreased methionine synthesis and accumulation of homocysteine. | OMIM 602568; ClinVar |
| Neural tube defects | MTRR polymorphisms (e.g., c.66A>G, p.Ile22Met) are associated with increased risk of neural tube defects due to altered homocysteine metabolism. | Case-control studies; ClinVar |
| Hyperhomocysteinemia | Reduced MTRR activity leads to elevated plasma homocysteine levels, a risk factor for cardiovascular disease. | OMIM; PubMed |
| Megaloblastic anemia | Impaired methionine synthesis affects DNA synthesis, leading to megaloblastic changes in bone marrow. | ClinVar; case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 10.2 | Medium |
| Kidney | 8.5 | Medium |
| Brain | 6.1 | Low |
| Heart | 5.4 | Low |
| Skeletal Muscle | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 12.3 | Liver cancer cell line |
| A549 | 9.7 | Lung carcinoma |
| HeLa | 7.8 | Cervical adenocarcinoma |
| K562 | 6.5 | Chronic myelogenous leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.66A>G (p.Ile22Met) | Missense | Common (allele frequency ~0.3-0.5) | Reduced enzyme activity; associated with neural tube defects and hyperhomocysteinemia |
| c.524C>T (p.Ala175Val) | Missense | Rare | Impaired flavin binding; may cause cblE deficiency |
| c.903+1G>A | Splice site | Rare | Splicing defect leading to loss of function; associated with cblE deficiency |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish MTRR enzymatic activity, leading to impaired methionine synthase reactivation and hyperhomocysteinemia.
Gain of Function (GOF)
No known gain-of-function mutations; MTRR activity is essential and typically not enhanced pathologically.
Dominant Negative (DN)
Not reported; MTRR mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 (GO:0005515) | • GO:0005524 (GO:0005524) |
| • GO:0005737 (GO:0005737) | • GO:0005829 (GO:0005829) |
| • GO:0008168 (GO:0008168) | • GO:0008705 (GO:0008705) |
| • GO:0016491 (GO:0016491) | • GO:0016651 (GO:0016651) |
| • GO:0031419 (GO:0031419) | • GO:0042803 (GO:0042803) |
| • GO:0046872 (GO:0046872) | • GO:0050660 (GO:0050660) |
| • GO:0050661 (GO:0050661) | • GO:0055114 (GO:0055114) |
| • GO:0009086 (GO:0009086) | • GO:0009100 (GO:0009100) |
| • GO:0009108 (GO:0009108) | • GO:0006730 (GO:0006730) |
| • GO:0006766 (GO:0006766) | • GO:0008652 (GO:0008652) |
Pathways
• Folate metabolism
• Methionine salvage pathway
• Cobalamin metabolism
• Homocysteine metabolism
• One-carbon metabolism
Protein Summary
Methionine synthase reductase (MTRR) is a 78 kDa flavoprotein that belongs to the family of diflavin oxidoreductases. It contains FAD and FMN binding domains and an NADPH binding domain. MTRR catalyzes the reductive methylation of methionine synthase (MTR) using S-adenosylmethionine as a methyl donor, regenerating the active form of MTR. This reaction is essential for the conversion of homocysteine to methionine, a key step in one-carbon metabolism. MTRR is localized in the cytoplasm and is ubiquitously expressed, with higher levels in liver and kidney. Defects in MTRR cause methylcobalamin deficiency type cblE, characterized by hyperhomocysteinemia, megaloblastic anemia, and neurological symptoms. Common polymorphisms like c.66A>G have been associated with increased risk of neural tube defects and cardiovascular disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MTRR Knockout HEK293 Cell Line | EDJ-KQ5269 | Human | 4552 | Details Get a Quote |
| MTRR Knockout A-549 Cell Line | EDJ-KQ28316 | Human | 4552 | Details Get a Quote |
| MTRR Knockout HCT 116 Cell Line | EDJ-KQ28317 | Human | 4552 | Details Get a Quote |
| MTRR Knockout HeLa Cell Line | EDJ-KQ28318 | Human | 4552 | Details Get a Quote |
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