MGMT (O-6-Methylguanine-DNA Methyltransferase)
A DNA repair protein that directly reverses alkylation damage at the O6 position of guanine, a key determinant of resistance to alkylating chemotherapies and a biomarker in glioblastoma.
Gene Information Card
| Symbol | MGMT |
|---|---|
| Full Name | O-6-methylguanine-DNA methyltransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 10q26.3 |
| NCBI Gene ID | 4255 ncbi.nlm.nih.gov/gene/4255 |
| Ensembl ID | ENSG00000170430 |
| UniProt ID | P16455 |
| OMIM ID | 156569 |
| HGNC ID | 7059 |
| Aliases | AGT, ACP, MGMT, O6-methylguanine-DNA methyltransferase |
Description
The MGMT gene encodes a DNA repair protein that removes alkyl groups from the O6 position of guanine, a mutagenic and cytotoxic lesion induced by alkylating agents. This direct reversal repair mechanism is crucial for maintaining genomic stability. MGMT expression is frequently silenced by promoter methylation in various cancers, particularly glioblastoma, leading to increased sensitivity to alkylating chemotherapy. Conversely, high MGMT expression is associated with resistance to such treatments.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glioblastoma | MGMT promoter methylation reduces MGMT expression, impairing DNA repair and increasing sensitivity to temozolomide. | ClinVar, COSMIC, multiple clinical studies |
| Colorectal cancer | MGMT promoter methylation is associated with G>A mutations in KRAS and TP53, contributing to tumorigenesis. | COSMIC, literature |
| Lung cancer | MGMT promoter methylation is observed in non-small cell lung cancer and may influence response to alkylating agents. | COSMIC, literature |
| Lymphoma | MGMT expression levels affect resistance to alkylating chemotherapy in some lymphomas. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Kidney | 8.7 | Low |
| Brain | 5.2 | Low |
| Colon | 4.1 | Low |
| Lung | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line; moderate expression |
| A549 | 8.4 | Lung carcinoma; low expression |
| U87MG | 2.1 | Glioblastoma; low expression due to promoter methylation |
| MCF7 | 6.7 | Breast cancer; low expression |
| HepG2 | 18.9 | Liver cancer; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.250A>G (p.Ile84Val) | Missense | Rare (<0.1%) | May affect protein stability or activity; clinical significance uncertain |
| c.533A>G (p.Asn178Ser) | Missense | Rare (<0.1%) | Reported in cancer; functional impact unknown |
| c.1A>G (p.Met1?) | Start codon loss | Very rare | Loss of protein expression; likely pathogenic |
| Promoter methylation | Epigenetic | Common in cancers (e.g., glioblastoma ~40-50%) | Silences gene expression; associated with better response to alkylating agents |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations or promoter methylation reduce MGMT activity, impairing DNA repair and increasing sensitivity to alkylating agents.
Gain of Function (GOF)
Gain-of-function mutations are rare; overexpression of wild-type MGMT is more common and confers chemoresistance.
Dominant Negative (DN)
No dominant-negative mutations have been reported for MGMT.
View complete mutation data：
Gene Ontology (GO)
| • methylated-DNA-[protein]-cysteine S-methyltransferase activity (GO:0003908) | • DNA repair (GO:0006281) |
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
| • cytosol (GO:0005829) |
Pathways
• Direct DNA repair pathway
• Alkylation damage repair
• O6-methylguanine repair
Protein Summary
The MGMT protein is a 207-amino acid enzyme that transfers the alkyl group from O6-methylguanine to a cysteine residue in its active site, irreversibly inactivating itself. This stoichiometric reaction repairs the DNA lesion in a single step without requiring a template. The protein is predominantly nuclear but can also be found in mitochondria. Its expression is regulated by promoter methylation, transcription factors, and post-translational modifications. MGMT is a key factor in resistance to alkylating chemotherapy, and its promoter methylation status is a predictive biomarker in glioblastoma.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MGMT Knockout HEK293 Cell Line | EDJ-KQ3115 | Human | 4255 | Details Get a Quote |
| MGMT Knockout A-549 Cell Line | EDJ-KQ24460 | Human | 4255 | Details Get a Quote |
| MGMT Knockout HCT 116 Cell Line | EDJ-KQ24461 | Human | 4255 | Details Get a Quote |
| MGMT Knockout HeLa Cell Line | EDJ-KQ24462 | Human | 4255 | Details Get a Quote |
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