Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

TYMS

contributors: mct/npt/pgu - updated : 02-11-2022

HGNC name	thymidylate synthetase
HGNC id	12441

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	overlapping, gene in gene, opposite orientation
text	overlaps with ENOSF1
STRUCTURE	15.93 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

text structure

overlapping RTYMS in opposite orientation

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - CETN1 - CLUL1 /D18S1140 - TYMS /ENOSF1 - YES1 - D18S1231 - ADCYAP1 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001071 7 - 1613 NP_001062 35.6 313 - 2003 12706868 NM_001354867 6 - 1511 NP_001341796 - 279 - 2003 12706868 NM_001354868 5 - 1364 NP_001341797 - 230 - 2003 12706868

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Reproductive female system uterus cervix   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

mono polymer

homomer , dimer

HOMOLOGY

interspecies

homolog to murine Tyms

Homologene

FAMILY

thymidylate synthase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria,inner
	intracellular,cytoplasm,organelle,mitochondria,matrix
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,nucleolus
text	localized to mitochondrial matrix and inner membrane

basic FUNCTION	thymidylate synthetase, pyrimidine biosynthetic pathway
	catalyzing the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate
	primary site of action for 5-fluorouracil, 5-fluoro-2-prime-deoxyuridine, and some folate analogues
	play a role in DNA methylation, synthesis, and repair
	importance of the TYMS gene variants in response to 5-fluorouracil treatment
	catalyzes the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate, and is a central enzyme in the folate metabolic pathway
	may play a protective role against the development of childhood
	acute lymphoblastic leukemia

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

purine/pyrimidine

signaling

thymidylate biosynthesis pathway, composed of SHMT2, TYMS and DHFRL1 in mitochondria

a component

INTERACTION

DNA

RNA

small molecule	cofactor,
	methylenetetrahydrofolate (methylene-THF)

protein	CDKN1A (down regulation of CDKN1A)
	ENOSF1 modify TYMS expression at the RNA level by acting as an antisense molecule to TYMS

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

DKCD

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   amplification     and overexpressed in esophageal squamous cell carcinoma tumoral       gain of function protect against the development of hepatocellular carcinoma constitutional germinal mutation       digenic germline variants in both TYMS and ENOSF1 can generate disease features of dyskeratosis congenita tumoral       gain of function in pancreatic cancer and associated with poor overall survival (OS) and recurrence-free survival (RFS) tumoral     --over   in Retroperitoneal liposarcoma (RLPS) constitutional     --other   affected the balance between proliferation and apoptosis in neuroepithelial cells, which might shed some lights on the mechanisms involved in neural tube defects (NTDs)

Susceptibility

to cardiovascular disease to high red blood cell folate and homocysteine concentrations to abdominal aortic aneurysm (Giusti 2008) to gastric cancer to childhood acute lymphoblastic leukemia (ALL) to breast cancer

Variant & Polymorphism insertion/deletion	I/D polymorphism significantly associated to high red blood cell folate and homocysteine concentrations
	3G-del6 haplotype showed a significant association with the gastric cancer susceptibility
	TSER polymorphism may increase susceptibility to breast cancer in the Caucasian population
	TYMS 3R variant allele was significantly associated with a reduced risk of childhood ALL, represented by the sum of heterozygous and polymorphic homozygous genotypes

Candidate gene
Marker	upregulation of TYMS in pancreatic cancer represents a diagnostic and prognostic biomarker for patients with pancreatic cancer
	might serve as a potential biomarker for lymph node metastasis (LNM) and a prognostic factor in colorectal cancer (CRC)
Therapy target
	System Type Disorder Pubmed immunology infectious   may thus be considered as a potential therapeutic target for HIV-1 treatment

ANIMAL & CELL MODELS