TYMS: Thymidylate Synthetase Gene
Key enzyme in nucleotide metabolism and target of fluoropyrimidine chemotherapy
Gene Information Card
| Symbol | TYMS |
|---|---|
| Full Name | Thymidylate Synthetase |
| Gene Type | Protein coding |
| Chromosomal Location | 18p11.32 |
| NCBI Gene ID | 7298 ncbi.nlm.nih.gov/gene/7298 |
| Ensembl ID | ENSG00000176890 |
| UniProt ID | P04818 |
| OMIM ID | 188350 |
| HGNC ID | 12441 |
| Aliases | TS, TMS, TYMS, HsT422 |
Description
The TYMS gene encodes thymidylate synthetase, an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), a critical step in de novo pyrimidine biosynthesis. This reaction provides the sole de novo source of thymidylate, essential for DNA replication and repair. TYMS is a target of fluoropyrimidine chemotherapeutic agents such as 5-fluorouracil (5-FU) and capecitabine. Polymorphisms and expression levels of TYMS are associated with response and toxicity to these drugs.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | Overexpression of TYMS leads to resistance to 5-FU-based chemotherapy; low expression correlates with better response. | ClinVar, COSMIC |
| Breast Cancer | TYMS expression levels predict response to capecitabine and 5-FU; high expression associated with poor prognosis. | ClinVar, PubMed |
| Gastric Cancer | TYMS polymorphisms (e.g., 2R/3R VNTR) influence 5-FU efficacy and toxicity. | ClinVar, OMIM |
| Head and Neck Cancer | TYMS expression is a biomarker for response to cisplatin and 5-FU combination therapy. | COSMIC, PubMed |
| Thymidylate Synthase Deficiency | Rare autosomal recessive disorder causing megaloblastic anemia, intellectual disability, and homocystinuria. | OMIM #188350 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Colon | 18.3 | High |
| Small Intestine | 15.2 | High |
| Liver | 8.1 | Medium |
| Lung | 6.4 | Low |
| Breast | 5.9 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical) | 14.7 | High expression |
| MCF7 (breast) | 9.2 | Medium expression |
| A549 (lung) | 7.8 | Medium expression |
| HCT116 (colon) | 22.1 | Very high expression |
| K562 (leukemia) | 11.3 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs34743033 (2R/3R VNTR) | Promoter polymorphism | Common (allele frequency varies by population) | Affects TYMS expression; 3R allele associated with higher expression and reduced 5-FU response |
| rs11280056 (3'-UTR 6bp del) | Deletion | Common | Associated with decreased TYMS mRNA stability and improved 5-FU response |
| c.742A>G (p.Ile248Val) | Missense | Rare | Reduced enzyme activity; linked to thymidylate synthase deficiency |
| c.113G>A (p.Arg38His) | Missense | Rare | Loss of function; causes thymidylate synthase deficiency |
Mutation functional classification
Loss of Function (LOF)
Rare missense mutations (e.g., p.Arg38His, p.Ile248Val) reduce or abolish enzyme activity, leading to thymidylate synthase deficiency.
Gain of Function (GOF)
Not well documented; promoter polymorphisms (e.g., 3R VNTR) increase expression but are not considered gain-of-function mutations.
Dominant Negative (DN)
No dominant-negative mutations reported for TYMS.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Pyrimidine metabolism (KEGG: hsa00240)
• One carbon pool by folate (KEGG: hsa00670)
• 5-Fluorouracil mechanism of action (Reactome: R-HSA-975110)
Protein Summary
Thymidylate synthetase (TS) is a homodimeric enzyme of approximately 36 kDa per subunit. It catalyzes the reductive methylation of dUMP to dTMP using methylenetetrahydrofolate as a cofactor. TS is essential for DNA synthesis and repair, making it a critical target for cancer chemotherapy. The enzyme is inhibited by fluoropyrimidine metabolites (e.g., FdUMP), leading to thymineless death. TS expression is regulated by a polymorphic tandem repeat in the 5'-UTR and by microRNAs. Elevated TS levels are associated with resistance to 5-FU and other antifolates.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TYMS Knockout HEK293 Cell Line | EDJ-KQ17847 | Human | 7298 | Details Get a Quote |
| TYMS Knockout A-549 Cell Line | EDJ-KQ29560 | Human | 7298 | Details Get a Quote |
| TYMS Knockout HCT 116 Cell Line | EDJ-KQ29561 | Human | 7298 | Details Get a Quote |
| TYMS Knockout HeLa Cell Line | EDJ-KQ29562 | Human | 7298 | Details Get a Quote |
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