MTAP Gene (Methylthioadenosine Phosphorylase)
A key enzyme in polyamine metabolism and a tumor suppressor frequently deleted in cancers.
Gene Information Card
| Symbol | MTAP |
|---|---|
| Full Name | Methylthioadenosine phosphorylase |
| Gene Type | Protein-coding |
| Chromosomal Location | 9p21.3 |
| NCBI Gene ID | 4507 ncbi.nlm.nih.gov/gene/4507 |
| Ensembl ID | ENSG00000133318 |
| UniProt ID | Q13126 |
| OMIM ID | 156540 |
| HGNC ID | 7413 |
| Aliases | DMSFH, LGMBF, MSAP |
Description
The MTAP gene encodes methylthioadenosine phosphorylase, an enzyme that catalyzes the reversible phosphorolysis of 5'-methylthioadenosine (MTA) into adenine and 5-methylthioribose-1-phosphate. This reaction is crucial for the salvage of adenine and methionine, and for the regulation of polyamine metabolism. MTAP is located on chromosome 9p21.3, a region frequently deleted in various cancers, making it a potential tumor suppressor and a target for cancer therapy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Homozygous deletion of MTAP leads to loss of enzyme activity, disrupting polyamine metabolism and potentially promoting tumorigenesis. MTAP deletion is often co-deleted with CDKN2A, a well-known tumor suppressor. | COSMIC, ClinVar, multiple studies |
| Methylthioadenosine phosphorylase deficiency | Loss-of-function mutations or deletions in MTAP result in enzyme deficiency, leading to accumulation of MTA and altered methionine salvage, which may contribute to metabolic dysregulation. | OMIM, ClinVar |
| Glioblastoma | MTAP deletion is common in glioblastoma and is associated with poor prognosis. Loss of MTAP may confer sensitivity to certain chemotherapeutic agents. | COSMIC, literature |
| Mesothelioma | MTAP deletion is frequently observed in malignant mesothelioma, and MTAP immunohistochemistry is used as a diagnostic marker to detect 9p21 deletion. | COSMIC, literature |
| Pancreatic cancer | MTAP deletion occurs in a subset of pancreatic cancers and may be a therapeutic target for drugs exploiting the methionine salvage pathway. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | Not available | Not available |
| Adrenal gland | Not available | Not available |
| Appendix | Not available | Not available |
| Blood | Not available | Not available |
| Bone marrow | Not available | Not available |
| Brain | Not available | Not available |
| Breast | Not available | Not available |
| Colon | Not available | Not available |
| Esophagus | Not available | Not available |
| Fallopian tube | Not available | Not available |
| Gallbladder | Not available | Not available |
| Heart | Not available | Not available |
| Kidney | Not available | Not available |
| Liver | Not available | Not available |
| Lung | Not available | Not available |
| Lymph node | Not available | Not available |
| Muscle | Not available | Not available |
| Ovary | Not available | Not available |
| Pancreas | Not available | Not available |
| Pituitary | Not available | Not available |
| Prostate | Not available | Not available |
| Salivary gland | Not available | Not available |
| Skin | Not available | Not available |
| Small intestine | Not available | Not available |
| Spleen | Not available | Not available |
| Stomach | Not available | Not available |
| Testis | Not available | Not available |
| Thymus | Not available | Not available |
| Thyroid | Not available | Not available |
| Tonsil | Not available | Not available |
| Urinary bladder | Not available | Not available |
| Uterus | Not available | Not available |
| Vagina | Not available | Not available |
| White blood cells | Not available | Not available |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | Not available | Cervical cancer cell line; MTAP expression may be variable. |
| MCF7 | Not available | Breast cancer cell line; MTAP expression may be reduced. |
| A549 | Not available | Lung cancer cell line; MTAP expression may be present. |
| HCT116 | Not available | Colon cancer cell line; MTAP expression may be present. |
| U87MG | Not available | Glioblastoma cell line; MTAP deletion is common. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Homozygous deletion | Copy number loss | Frequent in cancers (e.g., ~10-30% of many solid tumors) | Loss of MTAP protein expression and enzyme activity. |
| Missense mutations | Point mutation | Rare | May impair enzyme function or stability. |
| Frameshift mutations | Insertion/deletion | Rare | Likely loss-of-function. |
| Splice-site mutations | Splice variant | Rare | May lead to aberrant splicing and loss of function. |
Mutation functional classification
Loss of Function (LOF)
Homozygous deletions and loss-of-function mutations in MTAP result in complete loss of enzyme activity, leading to MTA accumulation and disruption of polyamine metabolism. This is the most common mechanism in cancer.
Gain of Function (GOF)
No gain-of-function mutations have been reported for MTAP. The gene acts as a tumor suppressor, and its loss is associated with malignancy.
Dominant Negative (DN)
No dominant-negative mutations have been described for MTAP. The enzyme functions as a homotrimer, but loss of one allele is typically compensated by the remaining allele; complete loss requires biallelic inactivation.
View complete mutation data：
Gene Ontology (GO)
| • magnesium ion binding (GO:0000287) | • catalytic activity (GO:0003824) |
| • protein binding (GO:0005515) | • cytoplasm (GO:0005737) |
| • cytosol (GO:0005829) | • purine nucleotide metabolic process (GO:0006163) |
| • nucleoside metabolic process (GO:0009116) | • methionine salvage pathway (GO:0019281) |
| • adenine salvage (GO:0019282) | • metal ion binding (GO:0046872) |
| • protein homooligomerization (GO:0051260) |
Pathways
• Methionine salvage pathway
• Polyamine metabolism
• Adenine salvage
• Purine metabolism
Protein Summary
Methylthioadenosine phosphorylase (MTAP) is a 283-amino acid protein that forms a homotrimer. It catalyzes the phosphorolysis of 5'-methylthioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. The enzyme requires a metal ion (likely magnesium) for activity. MTAP is ubiquitously expressed in normal tissues but is often lost in cancers due to homozygous deletion of 9p21.3. Loss of MTAP leads to MTA accumulation, which can inhibit protein arginine methyltransferases (PRMTs) and affect gene expression. MTAP deficiency also creates a dependency on de novo adenine synthesis, providing a therapeutic window for drugs like L-alanosine or PRMT inhibitors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MTAP Knockout HEK293 Cell Line | EDJ-KQ50457 | Human | 4507 | Details Get a Quote |
| MTAP Knockout HeLa Cell Line | EDJ-KQ53916 | Human | 4507 | Details Get a Quote |
| MTAP Knockout A-549 Cell Line | EDJ-KQ62409 | Human | 4507 | Details Get a Quote |
| MTAP Knockout HCT 116 Cell Line | EDJ-KQ70876 | Human | 4507 | Details Get a Quote |
