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    TYMS thymidylate synthetase [ Homo sapiens (human) ]

    Gene ID: 7298, updated on 27-Nov-2024

    Summary

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    Official Symbol
    TYMSprovided by HGNC
    Official Full Name
    thymidylate synthetaseprovided by HGNC
    Primary source
    HGNC:HGNC:12441
    See related
    Ensembl:ENSG00000176890 MIM:188350; AllianceGenome:HGNC:12441
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    TS; TMS; DKCD; HST422
    Summary
    Thymidylate synthase catalyzes the methylation of deoxyuridylate to deoxythymidylate using, 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 occurring antisense transcript, mitochondrial enolase superfamily member 1 (GeneID:55556), vary inversely when cell-growth progresses from late-log to plateau phase. Polymorphisms in this gene may be associated with etiology of neoplasia, including breast cancer, and response to chemotherapy. [provided by RefSeq, Aug 2017]
    Expression
    Broad expression in bone marrow (RPKM 46.3), testis (RPKM 32.5) and 21 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TYMS in Genome Data Viewer
    Location:
    18p11.32
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (657653..673578)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (811985..827856)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (657653..673578)

    Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene ReSE screen-validated silencer GRCh37_chr18:596737-596866 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9239 Neighboring gene RN7SK pseudogene 146 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:597469-597968 Neighboring gene Sharpr-MPRA regulatory region 12053 Neighboring gene clusterin like 1 Neighboring gene uncharacterized LOC105371952 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr18:641155-642354 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:657377-657878 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:657879-658378 Neighboring gene TYMS opposite strand RNA Neighboring gene enolase superfamily member 1 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr18:686134-686722 Neighboring gene ReSE screen-validated silencer GRCh37_chr18:697612-697744 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9242 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:712826-713405 Neighboring gene Sharpr-MPRA regulatory region 6782 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13022 Neighboring gene YES proto-oncogene 1, Src family tyrosine kinase Neighboring gene RNA, U1 small nuclear 109, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9243 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9244 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:812361-812903 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:812904-813445 Neighboring gene NANOG hESC enhancer GRCh37_chr18:830325-830891 Neighboring gene bolA family member 2 pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Identification of thymidylate synthase as a potential therapeutic target for lung cancer. Takezawa K, et al. Br J Cancer, 2010 Jul 27. PMID 20628382, Free PMC Article
    2. Expression of thymidylate synthase determines the response of gastric cancer patients undergoing gastrectomy to 5-fluorouracil-based adjuvant chemotherapy. Yeh CN, et al. Langenbecks Arch Surg, 2010 Mar. PMID 20012317
    3. The efficacy of pemetrexed as a third- or fourth-line therapy and the significance of thymidylate synthase expression in patients with advanced non-small cell lung cancer. Chang MH, et al. Lung Cancer, 2010 Sep. PMID 20061047
    4. Replacement of Val3 in human thymidylate synthase affects its kinetic properties and intracellular stability . Huang X, et al. Biochemistry, 2010 Mar 23. PMID 20151707, Free PMC Article
    5. Thymidylate synthase germline polymorphisms in rectal cancer patients treated with neoadjuvant chemoradiotherapy based on 5-fluorouracil. Páez D, et al. J Cancer Res Clin Oncol, 2010 Nov. PMID 20165956

    See all (623) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. LncRNA BC200 promotes the development of EBV-associated nasopharyngeal carcinoma by competitively binding to miR-6834-5p to upregulate TYMS expression.
      Title: LncRNA BC200 promotes the development of EBV-associated nasopharyngeal carcinoma by competitively binding to miR-6834-5p to upregulate TYMS expression.
    2. Association of Thymidylate Synthase (TS) Gene Polymorphisms with Incidence and Prognosis of Coronary Artery Disease.
      Title: Association of Thymidylate Synthase (TS) Gene Polymorphisms with Incidence and Prognosis of Coronary Artery Disease.
    3. DPYD and TYMS polymorphisms as predictors of 5 fluorouracil toxicity in colorectal cancer patients.
      Title: DPYD and TYMS polymorphisms as predictors of 5 fluorouracil toxicity in colorectal cancer patients.
    4. TYMS promotes genomic instability and tumor progression in Ink4a/Arf null background.
      Title: TYMS promotes genomic instability and tumor progression in Ink4a/Arf null background.
    5. Analysis of the TSER and G>C variants in the TYMS gene: a high frequency of low expression genotypes predicted in the Mexican population.
      Title: Analysis of the TSER and G>C variants in the TYMS gene: a high frequency of low expression genotypes predicted in the Mexican population.
    6. Significance of microRNA-330-5p/TYMS Expression Axis in the Pathogenesis of Colorectal Tumorigenesis.
      Title: Significance of microRNA-330-5p/TYMS Expression Axis in the Pathogenesis of Colorectal Tumorigenesis.
    7. Evaluation of TS and ENOSF1 Variants as a Biomarker in Response to Neoadjuvant Chemotherapy based on 5FU in Gastric Cancer Patients.
      Title: Evaluation of TS and ENOSF1 Variants as a Biomarker in Response to Neoadjuvant Chemotherapy based on 5FU in Gastric Cancer Patients.
    8. Investigation of DPYD, MTHFR and TYMS polymorphisms on 5-fluorouracil related toxicities in colorectal cancer.
      Title: Investigation of DPYD, MTHFR and TYMS polymorphisms on 5-fluorouracil related toxicities in colorectal cancer.
    9. Germline thymidylate synthase deficiency impacts nucleotide metabolism and causes dyskeratosis congenita.
      Title: Germline thymidylate synthase deficiency impacts nucleotide metabolism and causes dyskeratosis congenita.
    10. Association of MTHFR and TYMS gene polymorphisms with the susceptibility to HCC in Egyptian HCV cirrhotic patients.
      Title: Association of MTHFR and TYMS gene polymorphisms with the susceptibility to HCC in Egyptian HCV cirrhotic patients.
    Submit: New GeneRIF Correction See all GeneRIFs (413)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Dyskeratosis congenita, digenic
    MedGen: C5774217 OMIM: 620040 GeneReviews: Not available
    		not available

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC88736

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables folic acid binding IC
    Inferred by Curator
    more info
    		 PubMed 
    enables mRNA regulatory element binding translation repressor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein homodimerization activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables sequence-specific mRNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables thymidylate synthase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables thymidylate synthase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables thymidylate synthase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA biosynthetic process IC
    Inferred by Curator
    more info
    		 PubMed 
    involved_in cartilage development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in circadian rhythm IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in dTMP biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in dTMP biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in dTTP biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in developmental growth IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intestinal epithelial cell maturation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in liver regeneration IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in methylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of translation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to cytokine IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to ethanol IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to folic acid IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to glucocorticoid IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to organophosphorus IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in response to progesterone IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to toxic substance IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to vitamin A IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to xenobiotic stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in tetrahydrofolate interconversion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in uracil metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrial inner membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial matrix IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    thymidylate synthase
    Names
    TSase
    NP_001062.1
    NP_001341796.1
    NP_001341797.1
    XP_024307010.1
    XP_054175017.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_028255.1 RefSeqGene

      Range
      5001..20896
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_783

    mRNA and Protein(s)

    1. NM_001071.4 → NP_001062.1  thymidylate synthase isoform 1

      See identical proteins and their annotated locations for NP_001062.1

      Status: REVIEWED

      Source sequence(s)
      AK223372, BC018858, BC083512, HY016886, HY269620
      Consensus CDS
      CCDS11821.1
      UniProtKB/Swiss-Prot
      P04818, Q8WYK3, Q8WYK4
      UniProtKB/TrEMBL
      A8K9A5, Q53FB7, Q53Y97
      Related
      ENSP00000315644.10, ENST00000323274.15
      Conserved Domains (1) summary
      pfam00303
      Location:32 → 313
      Thymidylat_synt; Thymidylate synthase

    2. NM_001354867.2 → NP_001341796.1  thymidylate synthase isoform 2

      Status: REVIEWED

      Source sequence(s)
      AB077208, AK223372, BC083512, HY016886, HY269620
      Consensus CDS
      CCDS86658.1
      UniProtKB/TrEMBL
      A8K9A5, Q53FB7
      Related
      ENSP00000314727.7, ENST00000323224.7
      Conserved Domains (1) summary
      cl19097
      Location:27 → 279
      TS_Pyrimidine_HMase; Thymidylate synthase and pyrimidine hydroxymethylase: Thymidylate synthase (TS) and deoxycytidylate hydroxymethylase (dCMP-HMase) are homologs that catalyze analogous alkylation of C5 of pyrimidine nucleotides. Both enzymes are involved in the ...

    3. NM_001354868.2 → NP_001341797.1  thymidylate synthase isoform 3

      Status: REVIEWED

      Source sequence(s)
      AB077207, AK223372, BC083512, HY016886, HY269620
      Consensus CDS
      CCDS86659.1
      Related
      ENSP00000314902.5, ENST00000323250.9
      Conserved Domains (1) summary
      pfam00303
      Location:32 → 230
      Thymidylat_synt; Thymidylate synthase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000018.10 Reference GRCh38.p14 Primary Assembly

      Range
      657653..673578
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024451242.2 → XP_024307010.1  thymidylate synthase isoform X1

      Conserved Domains (1) summary
      pfam00303
      Location:26 → 186
      Thymidylat_synt; Thymidylate synthase

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060942.1 Alternate T2T-CHM13v2.0

      Range
      811985..827856
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054319042.1 → XP_054175017.1  thymidylate synthase isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P04818.3 GenPept UniProtKB/Swiss-Prot:P04818

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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