TYMS
Function
Catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate (dUMP) to thymidine 5'-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Involvement in disease
Dyskeratosis congenita, digenic
DKCD
A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. DKCD transmission pattern is consistent with digenic inheritance.
None
The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. TYMS germline variants in the presence of a common ENOSF1 haplotype (defined by rs699517, rs2790 and rs1512643) result in severe thymidylate synthase deficiency and disease. The pathogenic mechanism involves increased expression of ENOSF1 relative to TYMS, and post-transcriptional inhibition of TYMS translation through ENOSF1-TYMS RNA-RNA interactions.
Pathway
Pyrimidine metabolism; dTTP biosynthesis.
Sequence Similarities
Belongs to the thymidylate synthase family.
Cellular localization
- Nucleus
- Cytoplasm
- Mitochondrion
- Mitochondrion matrix
- Mitochondrion inner membrane
Alternative names
TS, OK/SW-cl.29, TYMS, Thymidylate synthase, TSase