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TYMS thymidylate synthetase [ Homo sapiens (human) ]

Gene ID: 7298, updated on 7-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (657653..673578)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (811985..827856)
105.20220307 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. Analysis of the TSER and G>C variants in the TYMS gene: a high frequency of low expression genotypes predicted in the Mexican population. Favela-Mendoza AF, et al. Ann Hum Biol, 2023 Feb. PMID 36789646
  2. Germline thymidylate synthase deficiency impacts nucleotide metabolism and causes dyskeratosis congenita. Tummala H, et al. Am J Hum Genet, 2022 Aug 4. PMID 35931051, Free PMC Article
  3. Thymidylate synthase is essential for efficient HIV-1 replication in macrophages. Desrosiers V, et al. Virology, 2021 Sep. PMID 34146963
  4. Gender-dependent association of TYMS-TSER polymorphism with 5-fluorouracil or capecitabine-based chemotherapy toxicity. Ioannou C, et al. Pharmacogenomics, 2021 Jul. PMID 34100299
  5. Association between 5'-UTR and 3'-UTR Polymorphisms of the TYMS Gene and Breast Cancer in Kurdish Women of Iraq. Mohamad KS. Asian Pac J Cancer Prev, 2021 May 1. PMID 34048185, Free PMC Article

See all (609) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Germline thymidylate synthase deficiency impacts nucleotide metabolism and causes dyskeratosis congenita.
    Title: Germline thymidylate synthase deficiency impacts nucleotide metabolism and causes dyskeratosis congenita.
  9. 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.
  10. MicroRNA-140-3p represses the proliferation, migration, invasion and angiogenesis of lung adenocarcinoma cells via targeting TYMS (thymidylate synthetase).
    Title: MicroRNA-140-3p represses the proliferation, migration, invasion and angiogenesis of lung adenocarcinoma cells via targeting TYMS (thymidylate synthetase).
Submit: New GeneRIF Correction See all GeneRIFs (412)

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)

Genotypes

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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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_2023_10

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

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