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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

TYMS Gene

protein-coding GIFtS: 76
GCID: GC18P000657

thymidylate synthetase

(Previous symbol: TS)

Explore 135 diseases affiliated with
TYMS via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Thymidylate Synthetase¹ ²		HsT422¹
TS¹ ² ³ ⁵		Tsase¹
TMS¹ ² ⁵		HST422²
TSase² ³		Thymidylate Synthase²
EC 2.1.1.45³ ⁸

External Ids:	HGNC: 12441¹	Entrez Gene: 7298²	Ensembl: ENSG00000176890⁷	OMIM: 188350⁵	UniProtKB: P04818³

Export aliases for TYMS gene to outside databases

Previous GC identifers: GC18U990034 GC18P000645 GC18P000647

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for TYMS:

Thymidylate synthase catalyzes the methylation of deoxyuridylate to deoxythymidylate using

5,10-methylenetetrahydrofolate (methylene-THF) as a cofactor. This function maintains the dTMP (thymidine-5-prime

monophosphate) pool critical for DNA replication and repair. The enzyme has been of interest as a target for cancer

chemotherapeutic agents. It is considered to be the primary site of action for 5-fluorouracil,

5-fluoro-2-prime-deoxyuridine, and some folate analogs. Expression of this gene and that of a naturally occuring

antisense transcript rTSalpha (GeneID:55556) vary inversely when cell-growth progresses from late-log to plateau

phase. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: TYSY_HUMAN, P04818

Function: Contributes to the de novo mitochondrial thymidylate biosynthesis pathway

Gene Wiki entry for TYMS (Thymidylate synthase)

PharmGKB "VIP" summary for TYMS

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000018.9 NC_018929.1 NT_010859.14

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the TYMS gene promoter:
AML1a p53 ATF-2 Egr-1 RREB-1 FAC1 POU2F1 POU2F1a ARP-1 MRF-2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: TYMS promoter sequence

Search SABiosciences Chromatin IP Primers for TYMS

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TYMS

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 18p11.32 Ensembl cytogenetic band: 18p11.32 HGNC cytogenetic band: 18p11.31-p11.21

TYMS Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TYMS gene location

GeneLoc information about chromosome 18 GeneLoc Exon Structure

GeneLoc location for GC18P000657: view genomic region (about GC identifiers)

Start:	657,604 bp from pter	End:	673,578 bp from pter
Size:	15,975 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: TYSY_HUMAN, P04818 (See protein sequence)

Recommended Name: Thymidylate synthase

Size: 313 amino acids; 35716 Da

Subunit: Homodimer

Subcellular location: Nucleus. Cytoplasm. Mitochondrion. Mitochondrion matrix. Mitochondrion inner membrane

6/30 PDB 3D structures from and Proteopedia for TYMS (see all 30):

1HVY (3D)

1HW3 (3D)

1HW4 (3D)

1HZW (3D)

1I00 (3D)

1JU6 (3D)

Explore the universe of human proteins at neXtProt for TYMS: NX_P04818

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P04818

4/19 DME Specific Peptides for TYMS (P04818) (see all 19)

FGMQARY

MALPPCH

DRTGTGT

LLTYMIA

TYMS Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_001062.1

ENSEMBL proteins:

ENSP00000315644 ENSP00000314902 ENSP00000314727

Reactome Protein details: P04818
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Proteins (see all 2): TYMS OriGene Protein Over-expression Lysate: TYMS OriGene Custom Protein Services for TYMS
	GenScript Custom Purified and Recombinant Proteins Services for TYMS
	Novus Biologicals TYMS Proteins Novus Biologicals TYMS Lysates
	Browse Sino Biological Recombinant Proteins
	ProSpec Recombinant Protein for TYMS
	Uscn Proteins for TYMS

Gene Ontology (GO): 5/9 cellular component terms (GO ID links to tree view) (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005625	soluble fraction	--	--
GO:0005634	nucleus	IDA	--
GO:0005654	nucleoplasm	TAS	--
GO:0005730	nucleolus	IEA	--
GO:0005737	cytoplasm	IDA	--

TYMS for ontologies About GeneDecksing

TYMS Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of TYMS
	Browse R&D Systems for Antibodies
	Cell Signaling Technology (CST) Antibodies for TYMS
	OriGene Antibodies (see all 13): TYMS OriGene Custom Antibody Services for TYMS
	GenScript Custom Superior Antibodies Services for TYMS
	Novus Biologicals TYMS Antibodies
	Abcam antibodies for TYMS
	Uscn Antibodies for TYMS
	ThermoFisher Antibodies for TYMS

Assay Products for TYMS:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for TYMS
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for TYMS

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

TYMS for domains About GeneDecksing

3 InterPro domains/families:

IPR023451 Thymidate_synth/dCMP_Mease

IPR020940 Thymidylate_synthase_AS

IPR000398 Thymidylate_synthase

Graphical View of Domain Structure for InterPro Entry P04818

ProtoNet protein and cluster: P04818

1 Blocks protein family: IPB000398 Thymidylate synthase

UniProtKB/Swiss-Prot: TYSY_HUMAN, P04818

Similarity: Belongs to the thymidylate synthase family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: TYSY_HUMAN, P04818

Function: Contributes to the de novo mitochondrial thymidylate biosynthesis pathway

Catalytic activity: 5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP

Genatlas biochemistry entry for TYMS:

thymidylate synthetase,pyrimidine biosynthetic pathway

Enzyme Number (IUBMB): EC 2.1.1.45¹ ²

miRNA Products:		miRTarBase miRNAs that target TYMS: hsa-let-7b (MIRT001582)

		OriGene 3'-UTR Clone: TYMS Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TYMS
		4 QIAGEN miScript miRNA Assays for microRNAs that regulate TYMS:
		hsa-miR-3163 hsa-miR-196a* hsa-miR-215 hsa-miR-192
		SwitchGear 3'UTR luciferase reporter plasmid: TYMS 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for TYMS (see all 7) OriGene shRNA RFP: TYMS OriGene siRNA: TYMS
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TYMS

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for TYMS

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for TYMS (see all 4) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for TYMS OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: TYMS (NM_001071)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TYMS
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TYMS

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for TYMS
		Search LifeMap BioReagents cell lines for TYMS

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TYMS

Gene Ontology (GO): 5/7 molecular function terms (GO ID links to tree view) (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000166	nucleotide binding	IEA	--
GO:0003729	mRNA binding	IEA	--
GO:0004799	thymidylate synthase activity	TAS	--
GO:0005542	folic acid binding	IEA	--
GO:0008144	drug binding	IEA	--

TYMS for ontologies About GeneDecksing

2 GenomeRNAi human phenotypes for TYMS:

Decreased viability of wild-ty

Increased S DNA content

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/18 super-pathways (see all 18) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

G1/S-Specific Transcription

	G1/S-Specific Transcription	1.00			E2F mediated regulation of DNA replication	0.45
	Activation of E2F target genes at G1/S	1.00

Antimetabolite Pathway - Folate Cycle, Pharmacodynamics

	Antimetabolite Pathway - Folate Cycle, Pharmacodynamics	1.00			Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics	0.36
	Methotrexate Pathway (Cancer Cell), Pharmacodynamics	0.45

Fluoropyrimidine Activity

	Fluoropyrimidine Activity	1.00			Fluoropyrimidine Pathway, Pharmacodynamics	0.30
	Fluoropyrimidine Pathway, Pharmacokinetics	0.73

Cell Cycle

Cell Cycle

1.00

Cell Cycle, Mitotic

0.84

Metabolism

Metabolism

1.00

Metabolic pathways

0.38

Pathway sources
See GeneCards unified pathways
Show all pathways

1 EMD Millipore Pathway for TYMS

Transcription Ligand-dependent activation of the ESR1/SP pathway

2 Cell Signaling Technology (CST) Pathways for TYMS

	Cell Cycle / Checkpoint Control
	DNA Damage

1 GeneGo (Thomson Reuters) Pathway for TYMS

Transcription Ligand-dependent activation of the ESR1/SP pathway

5/7 BioSystems Pathways for TYMS (see all 7)

	Fluoropyrimidine Activity
	One Carbon Metabolism
	dTMP de novo biosynthesis
	Integrated Pancreatic Cancer Pathway
	Integrated Pancreatic Cancer Pathway

5/11 Reactome Pathways for TYMS (see all 11)

	Metabolism of nucleotides
	Mitotic G1-G1/S phases
	Metabolism
	Cell Cycle
	E2F mediated regulation of DNA replication

5 PharmGKB Pathways for TYMS

	Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
	Fluoropyrimidine Pathway, Pharmacodynamics
	Fluoropyrimidine Pathway, Pharmacokinetics
	Methotrexate Pathway (Cancer Cell), Pharmacodynamics
	Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics

3 Kegg Pathways (Kegg details for TYMS):

	Pyrimidine metabolism
	One carbon pool by folate
	Metabolic pathways

UniProtKB/Swiss-Prot: TYSY_HUMAN, P04818

Pathway: Pyrimidine metabolism; dTTP biosynthesis

TYMS for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for TYMS

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/65 Interacting proteins for TYMS (P04818^{2, 3} ENSP00000315644⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 65)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
SH3GL2	Q99962²^,³, ENSP00000369981⁴	MINT-8270616 I2D: score=2 STRING: ENSP00000369981
GTPBP4	Q9BZE4³, ENSP00000354040⁴	I2D: score=2 STRING: ENSP00000354040
PCNA	P12004³, ENSP00000368438⁴	I2D: score=1 STRING: ENSP00000368438
UNG	P13051³, ENSP00000242576⁴	I2D: score=1 STRING: ENSP00000242576
UBC	P0CG48³, ENSP00000344818⁴	I2D: score=1 STRING: ENSP00000344818

About this table

Gene Ontology (GO): 5/34 biological process terms (GO ID links to tree view) (see all 34): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000082	G1/S transition of mitotic cell cycle	TAS	--
GO:0000083	regulation of transcription involved in G1/S phase of mitotic cell cycle	TAS	--
GO:0000278	mitotic cell cycle	TAS	--
GO:0005976	polysaccharide metabolic process	IEA	--
GO:0006139	nucleobase-containing compound metabolic process	TAS	2987839

TYMS for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

TYMS for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Enzo Life Sciences drugs & compounds for TYMS

Compounds for TYMS available from Tocris Bioscience About this table

Compound	Action	CAS #
Trifluorothymidine	Thymidylate synthase inhibitor; induces DNA fragmentation	[70-00-08]

5 HMDB Compounds for TYMS About this table

Compound	Synonyms	CAS #	PubMed Ids
5,10-Methylene-THF	5,10-methylene-THF (see all 8)	31690-11-6	--
5-Thymidylic acid	2'-Deoxythymidine 5'-monophosphate (see all 28)	365-07-1	--
Dihydrofolic acid	7,8-Dihydro-L-folic acid (see all 13)	4033-27-6	--
Thymidine 3',5'-cyclic monophosphate	3',5'-Cyclic TMP (see all 14)	6453-60-7	--
dUMP	2'-Deoxy-5'-uridylate (see all 12)	964-26-1	--

10/18 DrugBank Compounds for TYMS (see all 18) About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Trifluridine	--	70-00-8	target	inhibitor	18600528 18798063 15571283 20372850 16010590 17179993 14719072 19886911 6010427 15125867 11752352 19816940 4719131 16902987 6436227
Pemetrexed	LY231514 (see all 2)	150399-23-8	target	inhibitor	15795320 11742712 14596699 11763166 12571811 11752352 11252887 11531245 12023793 11524555 11848474
Raltitrexed	ZD-1694 (see all 2)	112887-68-0	target	inhibitor	10499608 10598555 10496350 10047461 10430100 10482907 11752352 10592235 18773878
Fluorouracil	--	51-21-8	target	other/unknown	16609021 16719540 15353299 16596248 11752352 16563096 16538493
Fluorouracil	--	51-21-8	enzyme	substrate	16609021 16719540 15353299 16596248 11752352 16563096 16538493 21332317
Trimethoprim	--	738-70-5	target	inhibitor	8920005 10090784 8538681 19622858 17139284 17016423 10592235
Capecitabine	--	154361-50-9	target	inhibitor	15866500 16926630 15132128 11752352 15709193 15134221
Floxuridine	5 Fluorodeoxyuridine (see all 10)	50-91-9	target	inhibitor	10697524 10482907 10553409 11752352 10697523 10891536
Gemcitabine	--	95058-81-4	target	inhibitor	15795320 16818496 11752352 16563096 15655942 17166391
Leucovorin	Calcium folinate (see all 7)	1492-18-8	target	inhibitor	16251201 11752352 15025795 12453856
2'-deoxyuridylic acid	--	--	target	--	17139284 17016423 10592235

10/123 Novoseek chemical compound relationships for TYMS gene (see all 123) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
thymidylate	99.5	4891	18443433 (10), 1505078 (8), 7518280 (7), 8869745 (7) (see all 99)
tomudex	96.2	303	8325888 (6), 8939755 (5), 7646540 (5), 10047461 (4) (see all 99)
5fluorouracil	94.4	2323	7779703 (9), 15355920 (9), 7833111 (8), 11501504 (7) (see all 99)
5-fluoro-2'-deoxyuridine-5'-monophosphate	94.2	133	12167486 (10), 1557655 (4), 16550002 (3), 7556218 (3) (see all 50)
ag 337	93.7	103	9413945 (4), 8612303 (4), 9565579 (4), 12734319 (4) (see all 35)
zd9331	93.2	72	9654109 (5), 9815766 (4), 10952785 (3), 15342418 (3) (see all 33)
2'-deoxyuridine-5-monophosphate	93	111	15068368 (4), 8939755 (3), 8399157 (2), 9053905 (2) (see all 46)
1843u89	92.7	43	8764125 (5), 16010590 (4), 9596684 (3), 8805515 (3) (see all 19)
glycinamide ribonucleotide	92.1	87	15655941 (2), 10739873 (2), 2106831 (2), 9420020 (1) (see all 63)
fudr	91.7	233	15918040 (4), 10975679 (4), 20079039 (4), 10891536 (3) (see all 81)

9 PharmGKB related drug/compound annotations for TYMS gene

Drug/compound	PharmGKB Annotation
Pyrimidine analogues	CA
capecitabine	CA
fluorouracil	CA
irinotecan	CA
leucovorin	CA
methotrexate	CA
pemetrexed	CA
raltitrexed	CA
tegafur	CA

About this table

Search CenterWatch for drugs/clinical trials and news about TYMS / TYSY

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for TYMS gene:

NM_001071.2

Unigene Cluster for TYMS:

Thymidylate synthetase

Hs.369762 [show with all ESTs]

Unigene Representative Sequence: BQ056428

6 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000323274(uc010dka.1 uc010dkb.1 uc010dkc.1) ENST00000579128

ENST00000323250 ENST00000323224 ENST00000584122 ENST00000581920

miRNA Products:		OriGene 3'-UTR Clone: TYMS Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TYMS
		4 QIAGEN miScript miRNA Assays for microRNAs that regulate TYMS:
		hsa-miR-3163 hsa-miR-196a* hsa-miR-215 hsa-miR-192
		SwitchGear 3'UTR luciferase reporter plasmid: TYMS 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for TYMS (see all 7) OriGene shRNA RFP: TYMS OriGene siRNA: TYMS
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TYMS

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for TYMS (see all 4) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for TYMS OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: TYMS (NM_001071)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TYMS
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TYMS

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for TYMS Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat TYMS
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat TYMS
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat TYMS

Additional cDNA sequence:

AB062290.1 AB077207.1 AB077208.1 AK223372.1 AK292620.1 AK314140.1 BC002567.2 BC013919.1

BC018858.2 BC083512.1 BT006811.1 X02308.1

24/25 DOTS entries (see all 25):

DT.91987769 DT.95139599 DT.91940417 DT.100887990 DT.121095554 DT.121095683 DT.121095715 DT.100887966

DT.75149969 DT.121095704 DT.92454718 DT.95249706 DT.95263539 DT.100805334 DT.100887972 DT.100887984

DT.100887988 DT.100887995 DT.121095691 DT.100887973 DT.108596 DT.121095668 DT.209162 DT.91833876

24/409 AceView cDNA sequences (see all 409):

CR617715 BM843120 BG107998 BM478045 BF970938 BC013919 CR605696 AL551990

CB127815 AI539850 BM904778 BU632016 AB077208 BQ642223 BE464920 BE797177

CR612901 BQ223405 BG575942 AL556369 AI368057 BM928567 BU170603 BU170619

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

TYMS expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: ATGTAGAGTG

About this image

TYMS expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

1 LifeMap In Vivo Development Anatomical Compartment/Cell

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Bone

Mandibular Process

Bone

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 2 LifeMap Cells

Name

Category

PureStem™ progenitor E68 (Embryonic Progenitor Cell)

PureStem™ progenitor E44 (Embryonic Progenitor Cell)

See TYMS Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for TYMS

SOURCE GeneReport for Unigene cluster: Hs.369762

SABiosciences Custom PCR Arrays for TYMS

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for TYMS Browse OriGene validated miRNA SYBR primer pairs
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the last universal common ancestor (LUCA).

Orthologs for TYMS gene from 11/43 species (see all 43) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Tyms^{1 , 5}	thymidylate synthase^{1, 5}	86.97(n)¹ 90.55(a)¹		5 (15.81 cM)⁵ 22171¹ NM_021288.4¹ NP_067263.1¹ 30058202⁵
chicken (Gallus gallus)	Aves	TYMS¹	thymidylate synthetase	79.35(n) 84.51(a)		421060 XM_419147.3 XP_419147.2
lizard (Anolis carolinensis)	Reptilia	TYMS⁶	--	84(a)	1 ↔ 1	4(39515293-39527499)
African clawed frog (Xenopus laevis)	Amphibia	Xl.17306²	Xenopus laevis transcribed sequence with moderate similarity to protein pdb1HVY (H.sapiens) A Chain A, Human Thymidylate Synthase Complexed With Dump And Raltitrexed, An Antifolate Drug, Is In The Closed Conformation less	78.12(n)		BX845600.1
zebrafish (Danio rerio)	Actinopterygii	tyms²	thymidylate synthase	77.62(n)		81540 AY005804.1
fruit fly (Drosophila melanogaster)	Insecta	Ts^{1 , 3}	deoxyribonucleotide biosynthesis thymidylate synthase less³ CG3181-PA¹	63(a)³ 64.62(n)¹ 64.72(a)¹		23C3³ 33499¹ NM_058019.3¹ NP_477367.1¹
worm (Caenorhabditis elegans)	Secernentea	Y110A7A.4^{1 , 3}	thymidylate synthase³ Protein Y110A7A.4¹	68(a)³ 62.91(n)¹ 68.31(a)¹		I(5138274-5139312)³ 172149¹ NM_059131.4¹ NP_491532.3¹
baker's yeast (Saccharomyces cerevisiae)	Saccharomycetes	CDC21(YOR074C)⁴ CDC21¹	Thymidylate synthase, required for de novo biosynthesis of pyrimidine deoxyribonucleotides; expression is induced at G1/S less⁴ Cdc21p¹	60.8(n)¹ 64.79(a)¹		15(467589-466675)⁴ 854241^{1, 4} NP_014717.2^{1, 4}
thale cress (Arabidopsis thaliana)	eudicotyledons	THY-2¹	thymidylate synthase	61.54(n) 65.73(a)		829609 NM_119623.4 NP_195183.2
rice (Oryza sativa)	Liliopsida	Os.8307²	Transcribed sequence with moderate similarity to protein refNP_179230.1 (A.thaliana) dihydrofolate reductase-thymidylate synthase [Arabidopsis thaliana] less	71.27(n)		CB631384.1

ENSEMBL Gene Tree for TYMS (if available)
TreeFam Gene Tree for TYMS (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for TYMS gene

1 SIMAP similar gene for TYMS using alignment to 2 protein entries: TYSY_HUMAN (see all proteins):

TYMS for paralogs About GeneDecksing

2 Pseudogenes.org Pseudogenes for TYMS
PGOHUM00000234291 PGOHUM00000243716

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 18 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs149617693^1,2		--	655632(+)	`TGCTTA/GCAAGT`	2	--	int¹ us2k¹		0	--	--	--	--
rs145030965^1,2		--	655768(+)	`CACAAA/GAACTA`	2	--	us2k¹ int¹		0	--	--	--	--
rs58808873^1,2	C,	--	655875(+)	`GGCCTC/TAAGAC`	2	--	int¹ us2k¹		4		WA NA EA	360
rs9967368^1,2	C,F,A,H,	--	656020(+)	`CTATTG/CATTCA`	2	--	us2k¹ int¹		23		NS EA NA WA CSA	2338
rs73366457^1,2		--	656043(+)	`TTTTTC/TCCCCA`	2	--	int¹ us2k¹		0	--	--	--	--
rs138860805^1,2		--	656096(+)	`AGCTAC/GTGCAA`	2	--	int¹ us2k¹		0	--	--	--	--
rs181416102^1,2		--	656170(+)	`CAGGCC/GTGTGC`	2	--	us2k¹ int¹		0	--	--	--	--
rs142073147^1,2		--	656174(+)	`CGTGTA/GCCACC`	2	--	us2k¹ int¹		0	--	--	--	--
rs114903712^1,2	F,	--	656178(+)	`TGCCAC/TCTCGC`	2	--	us2k¹ int¹		1		WA	118
rs146294848^1,2		--	656205(+)	`TTTTCA/GGTAGA`	2	--	us2k¹ int¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for TYMS (657604 - 673578 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 6 variations for TYMS
2 CNVs: 5044 102568
4 Indels: 61594 45680 45679 41819
Human Gene Mutation Database (HGMD): TYMS

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

TYMS for disorders           About GeneDecksing

OMIM gene information: 188350    OMIM disorders: --

20/135 diseases for TYMS (see all 135):    About MalaCards

5-fluorouracil toxicity neural tube defect diffuse large b-cell lymphoma hemifacial spasm

adult acute lymphocytic leukemia gastroesophageal junction adenocarcinoma graft versus host disease squamous cell carcinoma

non-small cell lung carcinoma biliary tract cancer b-cell lymphomas abdominal aortic aneurysm

acute lymphocytic leukemia malignant mesothelioma gastroesophageal reflux disease malignant pleural mesothelioma

sigmoid colon cancer non-hodgkin lymphoma soft tissue sarcoma fragile x syndrome

1 disease from the University of Copenhagen DISEASES database for TYMS:

Colorectal cancer

10/95 Novoseek disease relationships for TYMS gene (see all 95) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
colorectal cancer	84.5	548	12022983 (5), 15197779 (5), 15770397 (5), 9951876 (4) (see all 99)
colon cancer	75.8	162	10914714 (5), 17934851 (4), 10100718 (3), 16284371 (3) (see all 87)
gastric cancer	70.1	233	11161374 (4), 17854149 (4), 19102414 (4), 10965817 (4) (see all 80)
tumors	69	962	9048835 (10), 11179438 (8), 15309465 (7), 14576935 (6) (see all 99)
colon carcinoma	69	55	12525515 (3), 10791849 (3), 19621386 (3), 16609021 (2) (see all 29)
colorectal carcinoma	68.1	77	11832164 (4), 15500737 (4), 11131679 (4), 15751630 (3) (see all 34)
colorectal tumors	64.7	27	16391809 (3), 12576451 (2), 10778957 (2), 11249590 (1) (see all 17)
cancer	63.3	409	9126308 (5), 7647337 (5), 19155291 (5), 11410778 (4) (see all 99)
solid tumor	61	30	14612954 (2), 19047127 (2), 11249590 (1), 15359285 (1) (see all 23)
nsclc	59	82	15868929 (5), 10853017 (5), 14612954 (4), 17695427 (4) (see all 26)

Genetic Association Database (GAD): TYMS
Human Genome Epidemiology (HuGE) Navigator: TYMS (281 documents)

Export disorders for TYMS gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for TYMS gene, integrated from 9 sources (see all 1865):
(articles sorted by number of sources associating them with TYMS)

Utopia: connect your pdf to the dynamic
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Association of thymidylate synthase gene polymorphism with its mRNA and protein expression and with prognosis in gastric cancer. (PubMed id 12530000)^{1, 4, 9} Ishida Y....Watanabe G. (2002)
Thymidylate synthase gene polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy. (PubMed id 15355920)^{1, 4, 9} Lecomte T....Laurent-Puig P. (2004)
Polymorphism in the thymidylate synthase promoter enhancer region in colorectal cancer. (PubMed id 11445856)^{1, 4, 9} Marsh S....McLeod H.L. (2001)
Intracellular thymidylate synthase inhibition by trifluorothymidine in FM3A cells. (PubMed id 15571283)^{1, 7, 9} Temmink O.H....Peters G.J. (2004)
Genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase and risk of pancreatic cancer. (PubMed id 16234002)^{1, 4, 9} Wang L....Lin D. (2005)
Single nucleotide polymorphism in the 5' tandem repeat sequences of thymidylate synthase gene predicts for response to fluorouracil-based chemotherapy in advanced colorectal cancer patients. (PubMed id 15386371)^{1, 4, 9} Marcuello E....Baiget M. (2004)
Association of thymidylate synthase polymorphisms with gastric cancer susceptibility. (PubMed id 15386366)^{1, 4, 9} Graziano F....Magnani M. (2004)
Immunohistochemical characterization of pyrimidine sy nthetic enzymes, thymidine kinase-1 and thymidylate synthase, in various types of cancer. (PubMed id 20372850)^{1, 7, 9} Shintani M....Kamoshida S. (2010)
Thymidylate synthase expression pattern, expression level and single nucleotide polymorphism are predictors for disease-free survival in patients of colorectal cancer treated with 5-fluorouracil. (PubMed id 16596248)^{1, 7, 9} Fernandez-Contreras M.E....Gamallo C. (2006)
Prognostic role of thymidylate synthase polymorphisms in gastric cancer patients treated with surgery and adjuvant chemotherapy. (PubMed id 15897576)^{1, 4, 9} Kawakami K....Magnani M. (2005)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 7298	HGNC: 12441	AceView: TYMS	Ensembl:ENSG00000176890	euGenes: HUgn7298
ECgene: TYMS	Kegg: 7298	H-InvDB: TYMS

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for TYMS	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for TYMS	Genetics and Cytogenetics in Oncology and Haematology
SHMPD	http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=TYMS

Intellectual Property for TYMS gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for TYMS gene:
Search GeneIP for patents involving TYMS

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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thymidylate synthetase

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TYMS Gene

thymidylate synthetase

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