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TYMP

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Summary

TYMP (thymidine phosphorylase, HGNC:3148) is a protein-coding gene on chromosome 22q13.33, encoding Thymidine phosphorylase (P19971). May have a role in maintaining the integrity of the blood vessels.

This gene encodes an angiogenic factor which promotes angiogenesis in vivo and stimulates the in vitro growth of a variety of endothelial cells. It has a highly restricted target cell specificity acting only on endothelial cells. Mutations in this gene have been associated with mitochondrial neurogastrointestinal encephalomyopathy. Multiple alternatively spliced transcript variants have been identified.

Source: NCBI Gene 1890 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +2 more curated relationships
  • GWAS associations: 23
  • Clinical variants (ClinVar): 547 total — 50 pathogenic, 45 likely-pathogenic
  • Phenotypes (HPO): 80
  • Druggable target: yes — 2 molecules with ChEMBL bioactivity
  • Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
  • MANE Select transcript: NM_001953

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:3148
Approved symbolTYMP
Namethymidine phosphorylase
Location22q13.33
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000025708
Ensembl biotypeprotein_coding
OMIM131222
Entrez1890

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 32 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000252029, ENST00000395678, ENST00000395680, ENST00000395681, ENST00000425169, ENST00000476284, ENST00000487162, ENST00000487577, ENST00000650719, ENST00000651095, ENST00000651196, ENST00000651401, ENST00000651490, ENST00000651906, ENST00000652237, ENST00000652352, ENST00000652401, ENST00000893015, ENST00000893016, ENST00000893017, ENST00000893018, ENST00000893019, ENST00000893020, ENST00000893021, ENST00000893022, ENST00000893023, ENST00000893024, ENST00000893025, ENST00000893026, ENST00000893027, ENST00000893028, ENST00000893029, ENST00000893030, ENST00000893031, ENST00000970788, ENST00000970789, ENST00000970790, ENST00000970791

RefSeq mRNA: 5 — MANE Select: NM_001953 NM_001113755, NM_001113756, NM_001257988, NM_001257989, NM_001953

CCDS: CCDS14096, CCDS58811

Canonical transcript exons

ENST00000252029 — 10 exons

ExonStartEnd
ENSE000008789315052575250525918
ENSE000013560065052990450530012
ENSE000034932815052851250528610
ENSE000034991855052949650529719
ENSE000035168555052657650526738
ENSE000035304435052624650526476
ENSE000035304515052716550527283
ENSE000035512785052600150526141
ENSE000036782675052913650529338
ENSE000036905435052758850527717

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 99.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.1574 / max 1949.0834, expressed in 1175 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
19476156.60011175
1947620.179796
2095360.142562
1947590.131062
1947600.104151

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
right uterine tubeUBERON:000130299.64gold quality
granulocyteCL:000009499.48gold quality
monocyteCL:000057699.43gold quality
mononuclear cellCL:000084299.13gold quality
leukocyteCL:000073899.09gold quality
right lungUBERON:000216798.29gold quality
upper lobe of left lungUBERON:000895298.16gold quality
olfactory segment of nasal mucosaUBERON:000538697.75gold quality
upper lobe of lungUBERON:000894897.16gold quality
spleenUBERON:000210696.80gold quality
apex of heartUBERON:000209896.69gold quality
omental fat padUBERON:001041496.47gold quality
peritoneumUBERON:000235896.41gold quality
bloodUBERON:000017896.22gold quality
right lobe of liverUBERON:000111495.93gold quality
adipose tissue of abdominal regionUBERON:000780895.50gold quality
gall bladderUBERON:000211095.38gold quality
minor salivary glandUBERON:000183095.17gold quality
right coronary arteryUBERON:000162595.01gold quality
left uterine tubeUBERON:000130394.97gold quality
lymph nodeUBERON:000002994.56gold quality
esophagus mucosaUBERON:000246994.53gold quality
vermiform appendixUBERON:000115494.34gold quality
right lobe of thyroid glandUBERON:000111994.22gold quality
small intestine Peyer’s patchUBERON:000345494.17gold quality
lower esophagus mucosaUBERON:003583494.14gold quality
left adrenal gland cortexUBERON:003582593.87gold quality
left lobe of thyroid glandUBERON:000112093.53gold quality
left coronary arteryUBERON:000162693.42gold quality
subcutaneous adipose tissueUBERON:000219093.29gold quality

Single-cell (SCXA)

Detected in 36 experiment(s), a significant marker in 32.

ExperimentMarker?Max mean expression
E-GEOD-149689yes2985.48
E-MTAB-8207yes2359.53
E-MTAB-8530yes2199.58
E-MTAB-9841yes2069.51
E-MTAB-6653yes1669.69
E-MTAB-8322yes1470.10
E-MTAB-6308yes1097.84
E-GEOD-84465yes1011.30
E-MTAB-8498yes963.33
E-MTAB-10662yes351.52
E-HCAD-4yes264.72
E-HCAD-1yes110.71
E-CURD-122yes90.68
E-MTAB-6701yes80.58
E-MTAB-8410yes56.85

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP3

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

  • induction in tumoral stroma, but not in tumor cells, may promote angiogenesis in adenocarcinoma of the lung; may be important prognostic factor in adenocarcinoma of the lung (PMID:11920479)
  • inhibits the intracellular apoptotic signal transduction in the Fas-induced apoptotic pathway (PMID:11925935)
  • COX-2 is upregulated in endometrial cancer and facilitates tumor growth via angiogenesis produced in associated with VEGF and TP. (PMID:11957147)
  • thymidine phosphorylase is a major angiogenic factor in prostate carcinoma and its upregulation is likely to occur in the context of host immune response (PMID:11986782)
  • TK1 gene expression together with TS, TP and DPD gene expression may play important roles in influencing the malignant behavior of epithelial ovarian cancer. (PMID:11992400)
  • summary of research advances concerning thymidine phosphorylase in breast carcinoma (review) (PMID:12174926)
  • Biochemical defects of thymidine phosphorylase (hPD-ECGF) and a pathogenic G-to-A transition mutation at nucleotide 435 in the hPD-ECGF gene have been identified in two affected siblings with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). (PMID:12177387)
  • Development of oral cancer epithelia is associated with a significant increase in thymidine phosphorylase expression (PMID:12429983)
  • Sp1 transcription factor contributes to its expression in human colon carcinoma cells. (PMID:12466967)
  • MCP-1-positive myxoma and stromal cells and TP-positive myxoma and stromal cells significantly correlated with increased microvessel count. In cardiac myxoma, MCP-1 and thymidine phosphorylase may be important angiogenic signals accompanying growth. (PMID:12520153)
  • These findings indicate that thymidine phosphorylase has cytoprotective functions against cytotoxic agents which are independent of its enzymatic activity. (PMID:12565868)
  • experiments are the first to demonstrate a direct effect of thymidine phosphorylase and 2-deoxyribose on signaling pathways associated with endothelial cell migration (PMID:12639965)
  • This enzyme is expressed and mediates angiogenesis regulated by enzyme inhibitors in human ovarian cancer cells in vivo. (PMID:12684660)
  • point mutations in mtDNA of tissues and cultured cells from patients with thymidine phosphorylase deficiency and mitochondrial neurogastrointestinal encephalomyopathy (PMID:12813027)
  • Overexpression of TP mRNA by stromal cells within tumors plays an important role in tumor angiogenesis of prostate cancer. (PMID:12820387)
  • overexpression of thymidine phosphorylase is associated with invasiveness and metastasis in lung adenocarcinoma (PMID:12918063)
  • There is no prognostic significance to TP mRNA expression in breast neoplasms. (PMID:14702180)
  • Activity of thymidine kinase, thymidine phosphorylase and thymidilate synthase in human cancer xenografts to investigate the contribution of these enzymes to the sensitivity of TAS-102. (PMID:14719072)
  • Tumor associated macrophages are the most important source of dThdPase in colorectal cancer tissues. (PMID:14966914)
  • There were no significant differences between TP levels in the tumor specimens of the two groups, whereas in stages III and IV, those of the gastric cancer group tended to be higher than those of colorectal cancer group (PMID:15069545)
  • Results describe the inhibitory activity of the purine riboside derivative KIN59 (5’-O-tritylinosine) against human and bacterial recombinant thymidine phosphorylase (TPase) and TPase-induced angiogenesis. (PMID:15123637)
  • Enzyme expression can precisely predict 5’-dFUR sensitivity in colorectal cancer. (PMID:15201953)
  • Thymidine phosphorylase and dihydropyrimidine dehydrogenase have roles in progression of liver metastasis (PMID:15254700)
  • Thymidine phsoporylase activity is significantly higher in more advanced neoplasmatic disease (FIGO III and IV) although no correlation between TP activity and grading or histopathological type of ovarian tumor was observed. (PMID:15262124)
  • TP expression in tumor tissue is high in proportion to TP expression in primary tissue (PMID:15289834)
  • We conclude that genetic approaches using PD-ECGF to target the myocardium are effective for alleviating chronic myocardial ischemia. (PMID:15374822)
  • vascular endothelial growth factor and TP expression was also associated with a significantly higher level of Cyclooxygenase-2, as well as greater intratumoral microvessel density (PMID:15375582)
  • Hypoxia increased both VEGF secretion and number of cells containing VEGF and thymidine phosphorylase. (PMID:15474072)
  • Thymidine phosphorylase deficiency has a role in causing MNGIE, an autosomal recessive mitochondrial disorder (PMID:15571233)
  • thymidine phosphorylase mRNA and activity expression is upregulated 2-3 fold after treatment with interferon alpha (PMID:15571260)
  • TP has no role in trifluorothymidine sensitivity, but activates 5’-deoxy-5-fluorouridine and to a lesser extent 5FU (PMID:15571282)
  • Genetic analysis revealed a novel 18-base pair (bp) duplication (5044-5061 dup) in exon 8 of the thymidine phosphorylase (TP) gene in the patient of mitochondrial neurogastrointestinal encephalomyopathy. (PMID:15607208)
  • TP/PD-ECGF may support or modify tumor growth through angiogenesis in cooperation with other factors (PMID:15756429)
  • thymidine phosphorylase may have a role in efficacy of adjuvant doxifluridine in advanced colorectal cancer (PMID:15756433)
  • TP overexpression upregulated HO-1 expression and consequently increased p27(KIP1) in cultured VSMCs, and inhibited VSMC migration and proliferation in vitro and in vivo (PMID:15879300)
  • an increased expression of mRNA, specific for thymidine kinase 1, deoxycytidine kinase, and thymidine phosphorylase, may be involved in carcinogenic processes in the human thyroid (PMID:15978330)
  • Association of mRNA expresion patterns with tumor stage and suggested new prognostic and predictive markers for patients with colorectal cancer. (PMID:16132996)
  • Increased muscle nucleoside levels associated with a novel frameshift mutation in the thymidine phosphorylase gene in a Spanish patient with MNGIE. (PMID:16198108)
  • TP expression significantly predicted metastasis-free survival, but not local control; this is consistent with role as tumor angiogenesis promotor (PMID:16317434)
  • results show a local increase in the expressions of IGF-1 and PDEGF in the muscularis propria of the pyloric muscle in children with IHPS, which may have implications to the pathogenesis of the disease (PMID:16369467)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriotympENSDARG00000099821
mus_musculusTympENSMUSG00000022615
rattus_norvegicusTympENSRNOG00000032394

Protein

Protein identifiers

Thymidine phosphorylase — P19971 (reviewed: P19971)

Alternative names: Gliostatin, Platelet-derived endothelial cell growth factor, TdRPase

All UniProt accessions (9): A0A494BZZ4, A0A494C0A4, A0A494C0L3, A0A494C0L6, A0A494C1L9, A0A494C1N7, C9JGI3, E5KRG5, P19971

UniProt curated annotations — full annotation on UniProt →

Function. May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro. Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.

Subunit / interactions. Homodimer.

Disease relevance. Mitochondrial DNA depletion syndrome 1, MNGIE type (MTDPS1) [MIM:603041] A multisystem disease associated with mitochondrial dysfunction. It is clinically characterized by onset between the second and fifth decades of life, ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility (often pseudoobstruction), diffuse leukoencephalopathy, cachexia, peripheral neuropathy, and myopathy. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Pyrimidine metabolism; dTMP biosynthesis via salvage pathway; dTMP from thymine: step 1/2.

Similarity. Belongs to the thymidine/pyrimidine-nucleoside phosphorylase family.

Isoforms (2)

UniProt IDNamesCanonical?
P19971-11yes
P19971-22

RefSeq proteins (5): NP_001107227, NP_001107228, NP_001244917, NP_001244918, NP_001944* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000053Thymidine/pyrmidine_PPaseFamily
IPR000312Glycosyl_Trfase_fam3Domain
IPR013102PYNP_CDomain
IPR017459Glycosyl_Trfase_fam3_N_domDomain
IPR017872Pyrmidine_PPase_CSConserved_site
IPR018090Pyrmidine_PPas_bac/eukFamily
IPR035902Nuc_phospho_transferaseHomologous_superfamily
IPR036320Glycosyl_Trfase_fam3_N_dom_sfHomologous_superfamily
IPR036566PYNP-like_C_sfHomologous_superfamily

Pfam: PF00591, PF02885, PF07831

Enzyme classification (BRENDA):

  • EC 2.4.2.4 — thymidine phosphorylase (BRENDA: 11 organisms, 141 substrates, 748 inhibitors, 74 Km, 34 kcat entries)

Substrate kinetics (BRENDA)

24 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
THYMIDINE0.0017–9.323
PHOSPHATE0.0006–2.37
THYMINE0.0832–9.8285
5-NITRO-2’-DEOXYURIDINE0.16–0.234
1-(2’,6’-DIDEOXY-BETA-D-RIBOHEXAFURANOSYL)THYMIN0.3–0.333
4-THIOTHYMIDINE0.25–0.283
5’-DEOXYTHYMIDINE0.4–323
2’-DEOXYURIDINE0.32–0.7352
3’-AMINO-3’-DEOXYTHYMIDINE0.42
3’-DEOXY-2’,3’-DIDEHYDROTHYMIDINE0.352
5’-AMINO-5’-DEOXYTHYMIDINE0.42
5’-DEOXY-5-FLUOROURIDINE0.2–1.722
URIDINE0.275–47.62
1-(2’,6’-DIDEOXY-ALPHA-L-LYXO-HEXAFURANOSYL)THYM0.351
1-(2’,6’-DIDEOXY-ALPHA-L-LYXOHEXAFURANOSYL)THYMI0.351

Catalyzed reactions (Rhea), 1 shown:

  • thymidine + phosphate = 2-deoxy-alpha-D-ribose 1-phosphate + thymine (RHEA:16037)

UniProt features (60 total): helix 19, strand 16, sequence variant 7, binding site 4, repeat 4, mutagenesis site 3, propeptide 1, chain 1, modified residue 1, splice variant 1, sequence conflict 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDBMethodResolution (Å)
1UOUX-RAY DIFFRACTION2.11
2J0FX-RAY DIFFRACTION2.31
2WK6X-RAY DIFFRACTION2.5
2WK5X-RAY DIFFRACTION2.99

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P19971-F192.820.90

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 221; 116; 202; 217

Post-translational modifications (1): 6

Mutagenesis-validated functional residues (3):

PositionPhenotype
199abolishes catalytic activity.
199reduced catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-73614Pyrimidine salvage
R-HSA-73621Pyrimidine catabolism

MSigDB gene sets: 401 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, MCLACHLAN_DENTAL_CARIES_UP, REACTOME_PYRIMIDINE_CATABOLISM, ZHAN_MULTIPLE_MYELOMA_MF_UP, MODULE_45, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOMF_GROWTH_FACTOR_ACTIVITY, MODULE_503, GOBP_PYRIMIDINE_NUCLEOBASE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS, GOBP_TAXIS, RICKMAN_METASTASIS_DN

GO Biological Process (14): angiogenesis (GO:0001525), pyrimidine nucleobase metabolic process (GO:0006206), pyrimidine nucleoside metabolic process (GO:0006213), chemotaxis (GO:0006935), cell differentiation (GO:0030154), dTMP catabolic process (GO:0046074), obsolete mitochondrial genome maintenance (GO:0000002), signal transduction (GO:0007165), regulation of myelination (GO:0031641), regulation of transmission of nerve impulse (GO:0051969), nucleobase-containing small molecule metabolic process (GO:0055086), pyrimidine-containing compound metabolic process (GO:0072527), carbohydrate derivative metabolic process (GO:1901135), regulation of gastric motility (GO:1905333)

GO Molecular Function (9): 1,4-alpha-oligoglucan phosphorylase activity (GO:0004645), growth factor activity (GO:0008083), thymidine phosphorylase activity (GO:0009032), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), pyrimidine-nucleoside phosphorylase activity (GO:0016154), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), pentosyltransferase activity (GO:0016763)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
Nucleotide salvage1
Nucleotide catabolism1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
pyrimidine-containing compound metabolic process2
regulation of cellular process2
metabolic process2
blood vessel morphogenesis1
anatomical structure formation involved in morphogenesis1
nucleobase metabolic process1
nucleoside metabolic process1
response to chemical1
taxis1
cellular developmental process1
pyrimidine deoxyribonucleoside monophosphate catabolic process1
pyrimidine deoxyribonucleotide catabolic process1
dTMP metabolic process1
cell communication1
cellular process1
signaling1
cellular response to stimulus1
myelination1
regulation of nervous system development1
regulation of cell communication1
transmission of nerve impulse1
regulation of nervous system process1
nucleobase-containing compound metabolic process1
small molecule metabolic process1
gastric motility1
regulation of digestive system process1
hexosyltransferase activity1
receptor ligand activity1
pyrimidine-nucleoside phosphorylase activity1
identical protein binding1
protein dimerization activity1
binding1
pentosyltransferase activity1
catalytic activity1
transferase activity1
glycosyltransferase activity1
cytoplasm1
cellular anatomical structure1

Protein interactions and networks

STRING

1764 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
TYMPUPP1Q16831963
TYMPTYMSP04818910
TYMPUPP2O95045851
TYMPDGUOKP78532844
TYMPDPYDQ12882840
TYMPPOLGP54098838
TYMPTK2O00142820
TYMPUMPSP11172815
TYMPRRM2BQ7LG56798
TYMPNT5MQ9NPB1797
TYMPSUCLA2Q9P2R7786
TYMPMPV17P39210784
TYMPTWNKQ96RR1753
TYMPCDAP32320718
TYMPTK1P04183717

IntAct

97 interactions, top by confidence:

ABTypeScore
SINHCAFTNRC18psi-mi:“MI:0914”(association)0.640
CCNCMED19psi-mi:“MI:0914”(association)0.640
TYMPZMYND12psi-mi:“MI:0915”(physical association)0.560
TYMPMESDpsi-mi:“MI:0915”(physical association)0.560
GMCL1A2ML1psi-mi:“MI:0914”(association)0.530
TBC1D22BA2ML1psi-mi:“MI:0914”(association)0.530
RBM24PPLpsi-mi:“MI:0914”(association)0.530
KHDC4TYMPpsi-mi:“MI:0914”(association)0.530
SSBP2CLEC18Apsi-mi:“MI:0914”(association)0.530
DHDHATRNpsi-mi:“MI:0914”(association)0.530
Cdk1psi-mi:“MI:0915”(physical association)0.400
TYMPTYMPpsi-mi:“MI:0915”(physical association)0.370
ERBB2TYMPpsi-mi:“MI:0915”(physical association)0.370
PI4KAA2ML1psi-mi:“MI:0914”(association)0.350
PDE4DIPA2ML1psi-mi:“MI:0914”(association)0.350
CDK15A2ML1psi-mi:“MI:0914”(association)0.350
GPATCH2LA2ML1psi-mi:“MI:0914”(association)0.350
SUSD3IGLL5psi-mi:“MI:0914”(association)0.350
DDX19BIGLL5psi-mi:“MI:0914”(association)0.350
ZSCAN20ZNF197psi-mi:“MI:0914”(association)0.350
YJU2PLRG1psi-mi:“MI:0914”(association)0.350
KHDC4IGKCpsi-mi:“MI:0914”(association)0.350
ATG16L1psi-mi:“MI:0914”(association)0.350
KLHL11PIPSLpsi-mi:“MI:0914”(association)0.350
STX17A2ML1psi-mi:“MI:0914”(association)0.350
PI4KAP1A2ML1psi-mi:“MI:0914”(association)0.350

BioGRID (111): TYMP (Two-hybrid), TYMP (Affinity Capture-MS), TYMP (Affinity Capture-MS), TYMP (Affinity Capture-MS), TYMP (Affinity Capture-MS), TYMP (Affinity Capture-MS), TYMP (Affinity Capture-MS), TYMP (Co-fractionation), TYMP (Affinity Capture-MS), TYMP (Affinity Capture-MS), TYMP (Affinity Capture-MS), TYMP (Affinity Capture-MS), TYMP (Affinity Capture-MS), TYMP (Affinity Capture-MS), TYMP (Affinity Capture-MS)

ESM2 similar proteins: A1A4L8, A2BDX3, A4RPM5, A5GFZ6, A6NK58, B4FAT0, B4NXF7, B6TNK6, O19179, O43323, O95396, O95571, P19971, P55203, P85971, Q02846, Q05922, Q08DH8, Q0VFH3, Q14BV6, Q17CA7, Q1WNP0, Q3KQV9, Q3TW96, Q3UQ84, Q561R2, Q58E95, Q5PQQ1, Q5ZKI2, Q61488, Q66JK4, Q6PAT0, Q7PY41, Q86U10, Q8AWD2, Q8NFV4, Q8VBZ0, Q8VDG5, Q923K4, Q96EY9

Diamond homologs: A0B6C9, A1RWC3, A1SYK5, A1W631, A1W9B0, A2BJU0, A2SPI9, A3CSY4, A4FZL0, A4VHV6, A4YRL1, A5EG87, A5IFN1, A6THZ7, A6URW3, A6UUN0, A6VIW6, A7HYS8, A7I5N0, A7ZVS5, A8A8B1, A8IA58, A9A6M7, A9MRA6, B1XFJ2, B2AIF3, B2VH51, B3QKL9, B4TH00, B5BAJ8, B5FA99, B5Y276, B5Z4R4, B6YWT7, B7LEM8, B7LNS2, B7LXU4, B7MNI9, B7NW62, C4LAA1

SIGNOR signaling

3 interactions.

AEffectBMechanism
TYMP“down-regulates quantity”thymine“chemical modification”
TYMP“down-regulates quantity”“2-deoxy-D-ribofuranose 1-phosphate(2-)”“chemical modification”
TYMP“up-regulates quantity”thymidine“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

547 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic50
Likely pathogenic45
Uncertain significance122
Likely benign260
Benign19

Top pathogenic / likely-pathogenic (30)

Variant IDHGVSClassification
1073039NM_001953.5(TYMP):c.317_330del (p.Glu106fs)Pathogenic
1395101NM_001953.5(TYMP):c.559C>T (p.Gln187Ter)Pathogenic
1407889NM_001953.5(TYMP):c.199C>T (p.Gln67Ter)Pathogenic
1416274NM_001953.5(TYMP):c.136G>T (p.Gly46Ter)Pathogenic
1451682NM_001953.5(TYMP):c.861_862dup (p.Glu288fs)Pathogenic
1455931NM_001953.5(TYMP):c.857_858insT (p.Glu286fs)Pathogenic
16653NM_001953.5(TYMP):c.866A>C (p.Glu289Ala)Pathogenic
16654NM_001953.5(TYMP):c.516+2T>CPathogenic
16660NM_001953.5(TYMP):c.457G>A (p.Gly153Ser)Pathogenic
16661NM_001953.5(TYMP):c.131G>A (p.Arg44Gln)Pathogenic
1802275NM_001953.5(TYMP):c.86dup (p.Ser30fs)Pathogenic
2004761NM_001953.5(TYMP):c.83_90dup (p.Pro31fs)Pathogenic
2064836NM_001953.5(TYMP):c.52_53del (p.Phe18fs)Pathogenic
2087234NM_001953.5(TYMP):c.133_152del (p.Asp45fs)Pathogenic
2123515NM_001953.5(TYMP):c.208_209del (p.Gln70fs)Pathogenic
215334NM_001953.5(TYMP):c.516+2T>APathogenic
223014NM_001953.5(TYMP):c.112G>T (p.Glu38Ter)Pathogenic
223017NM_001953.5(TYMP):c.146T>G (p.Leu49Arg)Pathogenic
223018NM_001953.5(TYMP):c.162C>G (p.Ile54Met)Pathogenic
223023NM_001953.5(TYMP):c.328C>T (p.Gln110Ter)Pathogenic
223025NM_001953.5(TYMP):c.398T>C (p.Leu133Pro)Pathogenic
223026NM_001953.5(TYMP):c.401C>A (p.Ala134Glu)Pathogenic
223029NM_001953.5(TYMP):c.467A>G (p.Asp156Gly)Pathogenic
223032NM_001953.5(TYMP):c.530T>C (p.Leu177Pro)Pathogenic
223033NM_001953.5(TYMP):c.605G>A (p.Arg202Lys)Pathogenic
223036NM_001953.5(TYMP):c.623T>G (p.Val208Gly)Pathogenic
223038NM_001953.5(TYMP):c.707T>C (p.Phe236Ser)Pathogenic
223040NM_001953.5(TYMP):c.760A>C (p.Thr254Pro)Pathogenic
223043NM_001953.5(TYMP):c.856G>A (p.Glu286Lys)Pathogenic
223063NM_001953.4(TYMP):c.929-3G>APathogenic

SpliceAI

1356 predictions. Top by Δscore:

VariantEffectΔscore
22:50526241:CTCA:Cdonor_loss1.0000
22:50526242:TCAC:Tdonor_loss1.0000
22:50526243:CACC:Cdonor_loss1.0000
22:50526245:C:CGdonor_loss1.0000
22:50526245:CCAT:Cdonor_gain1.0000
22:50526473:CCCC:Cacceptor_gain1.0000
22:50526474:CCCC:Cacceptor_gain1.0000
22:50526594:C:Adonor_gain1.0000
22:50525917:CC:Cacceptor_gain0.9900
22:50525917:CCCT:Cacceptor_loss0.9900
22:50525918:CC:Cacceptor_gain0.9900
22:50525920:T:Gacceptor_loss0.9900
22:50526232:C:CAdonor_gain0.9900
22:50526233:C:Adonor_gain0.9900
22:50526240:GCTCA:Gdonor_loss0.9900
22:50526244:A:ACdonor_gain0.9900
22:50526245:C:CCdonor_gain0.9900
22:50526269:T:TAdonor_gain0.9900
22:50526474:CCC:Cacceptor_gain0.9900
22:50526475:CC:Cacceptor_gain0.9900
22:50526475:CCC:Cacceptor_gain0.9900
22:50526476:CC:Cacceptor_gain0.9900
22:50526477:C:CCacceptor_gain0.9900
22:50526477:C:CGacceptor_loss0.9900
22:50526478:T:Cacceptor_loss0.9900
22:50526571:CTCA:Cdonor_loss0.9900
22:50526572:TCAC:Tdonor_loss0.9900
22:50526574:A:ACdonor_gain0.9900
22:50526574:A:AGdonor_loss0.9900
22:50526575:C:CCdonor_gain0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000474738 (22:50525566 G>A,C,T), RS1001277545 (22:50528375 A>G), RS1001517384 (22:50531172 T>A), RS1003394781 (22:50527512 A>G), RS1003426235 (22:50531345 G>A,T), RS1003738758 (22:50528992 C>A,G,T), RS1003999177 (22:50529828 C>G), RS1004654285 (22:50528126 C>T), RS1004918962 (22:50525810 G>A), RS1005674391 (22:50530803 G>A), RS1006008137 (22:50531960 C>G,T), RS1006214787 (22:50526771 T>C), RS1006645801 (22:50527810 T>C), RS1006891913 (22:50532001 G>A), RS1007113477 (22:50527797 AAG>A)

Disease associations

OMIM: gene MIM:131222 | disease phenotypes: MIM:603041

GenCC curated gene-disease

DiseaseClassificationInheritance
mitochondrial DNA depletion syndrome 1StrongAutosomal recessive
mitochondrial neurogastrointestinal encephalomyopathySupportiveAutosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

DiseaseClassificationInheritance
mitochondrial diseaseDefinitiveAR

Mondo (3): mitochondrial neurogastrointestinal encephalomyopathy (MONDO:0017575), mitochondrial DNA depletion syndrome 1 (MONDO:0011283), intestinal pseudo-obstruction (MONDO:0002803)

Orphanet (1): Mitochondrial neurogastrointestinal encephalomyopathy (Orphanet:298)

HPO phenotypes

80 total (30 of 80 shown, HPO-id order):

HPOTerm
HP:0000007Autosomal recessive inheritance
HP:0000044Hypogonadotropic hypogonadism
HP:0000407Sensorineural hearing impairment
HP:0000508Ptosis
HP:0000544External ophthalmoplegia
HP:0000590Progressive external ophthalmoplegia
HP:0000597Ophthalmoparesis
HP:0000651Diplopia
HP:0000726Dementia
HP:0000815Hypergonadotropic hypogonadism
HP:0001155Abnormality of the hand
HP:0001249Intellectual disability
HP:0001284Areflexia
HP:0001394Cirrhosis
HP:0001403Macrovesicular hepatic steatosis
HP:0001533Slender build
HP:0001824Weight loss
HP:0001903Anemia
HP:0002013Vomiting
HP:0002014Diarrhea
HP:0002015Dysphagia
HP:0002018Nausea
HP:0002019Constipation
HP:0002020Gastroesophageal reflux
HP:0002024Malabsorption
HP:0002027Abdominal pain
HP:0002253Colonic diverticula
HP:0002254Intermittent diarrhea
HP:0002352Leukoencephalopathy
HP:0002460Distal muscle weakness

GWAS associations

23 associations (top):

StudyTraitp-value
GCST000503_14Mean corpuscular volume1.000000e-15
GCST000587_8Mean corpuscular hemoglobin4.000000e-08
GCST001765_31Red blood cell traits5.000000e-23
GCST004146_29Chronic lymphocytic leukemia3.000000e-09
GCST004601_212Red blood cell count2.000000e-43
GCST004602_304Mean corpuscular volume2.000000e-129
GCST004621_211Red cell distribution width3.000000e-19
GCST004622_98Reticulocyte count3.000000e-16
GCST004630_49Mean corpuscular hemoglobin3.000000e-94
GCST005993_27Mean corpuscular hemoglobin1.000000e-40
GCST006585_1822Blood protein levels2.000000e-11
GCST90002385_586High light scatter reticulocyte count8.000000e-29
GCST90002386_498High light scatter reticulocyte percentage of red cells1.000000e-14
GCST90002390_286Mean corpuscular hemoglobin1.000000e-35
GCST90002392_232Mean corpuscular volume2.000000e-57
GCST90002394_213Monocyte percentage of white cells2.000000e-13
GCST90002396_95Mean reticulocyte volume6.000000e-09
GCST90002396_96Mean reticulocyte volume5.000000e-76
GCST90002397_613Mean spheric corpuscular volume3.000000e-09
GCST90002397_614Mean spheric corpuscular volume3.000000e-93
GCST90002403_710Red blood cell count7.000000e-102
GCST90002405_425Reticulocyte count1.000000e-62
GCST90002406_576Reticulocyte fraction of red cells1.000000e-33

EFO canonical traits (7, from GWAS)

EFO IDTrait name
EFO:0004509hemoglobin measurement
EFO:0004527mean corpuscular hemoglobin
EFO:0004305erythrocyte count
EFO:0009188Red cell distribution width
EFO:0007986reticulocyte count
EFO:0007989monocyte percentage of leukocytes
EFO:0010701mean reticulocyte volume

MeSH disease descriptors (1)

DescriptorNameTree numbers
D007418Intestinal Pseudo-ObstructionC06.405.469.531.492.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3106 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,952 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL235668TIPIRACIL42,948
CHEMBL65375TIPIRACIL HYDROCHLORIDE41,004

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

VariantTypeLevelDrugsPhenotypes
rs11479Toxicity3capecitabine;fluorouracilNeoplasms

PharmGKB variants

3 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs11479SCO2, TYMP35.501capecitabine;fluorouracil
rs470119IMPDH2, TYMP0.000
rs112723255SCO2, TYMP0.000

Binding affinities (BindingDB)

22 measured of 26 human assays (50 total across all organisms); most potent 22 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI1.3 nM
6-chloro-5-(cyclopent-1-en-1-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI200 nM
6-chloro-5-(thiophen-2-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI280 nM
6-chloro-5-phenyl-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI400 nM
6-chloro-5-[(1E)-pent-1-en-1-yl]-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI410 nM
6-chloro-5-(cyclohex-1-en-1-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI420 nM
6-chloro-5-[(2E)-pent-2-en-3-yl]-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI490 nM
6-fluoro-5-phenyl-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI500 nM
5-[(1E)-but-1-en-1-yl]-6-chloro-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI630 nM
6-chloro-5-(4-fluorophenyl)-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI710 nM
5-butyl-6-chloro-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI1030 nM
6-chloro-5-heptyl-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI1060 nM
6-chloro-5-[(1E)-prop-1-en-1-yl]-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI1170 nM
6-bromo-5-phenyl-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI1210 nM
6-chloro-5-(3,5-dimethylphenyl)-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI1740 nM
6-chloro-5-hexyl-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI1830 nM
6-chloro-5-(pyridin-3-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI3010 nM
6-chloro-5-(prop-1-en-2-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI3340 nM
6-chloro-5-pentyl-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI3670 nM
6-chloro-5-(naphthalen-1-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI4590 nM
5-benzyl-6-chloro-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI4650 nM
6-chloro-5-propyl-1,2,3,4-tetrahydropyrimidine-2,4-dioneKI5810 nM

ChEMBL bioactivities

163 potent at pChembl≥5 of 304 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.89Ki1.3nMTIPIRACIL
8.72IC501.9nMCHEMBL65986
8.68Ki2.1nMTIPIRACIL
8.30Ki5nMTIPIRACIL
7.77Ki17nMTIPIRACIL HYDROCHLORIDE
7.77Ki17nMCHEMBL1080896
7.77Ki17nMTIPIRACIL
7.72IC5019nMCHEMBL122679
7.70Ki20nMTIPIRACIL HYDROCHLORIDE
7.70IC5020nMCHEMBL4129617
7.70Ki20nMTIPIRACIL
7.70IC5020nMCHEMBL65986
7.70IC5020nMTIPIRACIL
7.70IC5020nMTIPIRACIL HYDROCHLORIDE
7.68IC5021nMCHEMBL66531
7.64IC5023nMTIPIRACIL HYDROCHLORIDE
7.52IC5030nMTIPIRACIL HYDROCHLORIDE
7.46IC5035nMTIPIRACIL HYDROCHLORIDE
7.46IC5035nMCHEMBL64909
7.46IC5035nMTIPIRACIL
7.31IC5049nMCHEMBL193667
7.00IC50100nMCHEMBL194335
6.92IC50120nMCHEMBL4293861
6.92IC50120nMCHEMBL4455140
6.70Ki200nMCHEMBL234998
6.63Ki236nMCHEMBL374140
6.63Ki236nMCHEMBL592394
6.63Ki236nMCHEMBL599022
6.63Ki236nMCHEMBL599755
6.63Ki236nMCHEMBL401998
6.63Ki236nMCHEMBL597717
6.55Ki280nMCHEMBL397364
6.54Ki290nMCHEMBL234998
6.46IC50350nMCHEMBL3087264
6.40Ki400nMCHEMBL235001
6.39Ki410nMCHEMBL238218
6.38Ki420nMCHEMBL234999
6.37Ki430nMCHEMBL235001
6.33Ki470nMCHEMBL395907
6.31Ki490nMCHEMBL394454
6.30Ki500nMCHEMBL395907
6.27Ki540nMCHEMBL397364
6.25IC50560nMCHEMBL303346
6.20Ki630nMCHEMBL396865
6.15Ki710nMCHEMBL235875
6.12Ki750nMCHEMBL234999
6.11Ki770nMCHEMBL87371
6.04Ki910nMCHEMBL238218
6.04Ki920nMCHEMBL396865
6.04Ki910nMCHEMBL394454

PubChem BioAssay actives

206 with measured affinity, of 554 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki0.0013uM
6-[(2-amino-1H-imidazol-3-ium-3-yl)methyl]-5-bromo-1H-pyrimidine-2,4-dione chloride213303: Compound was evaluated for its inhibitory activity against recombinant purified Escherichia coli Thymidine Phosphorylaseic500.0019uM
6-[(2-aminoimidazol-1-yl)methyl]-5-fluoro-1H-pyrimidine-2,4-dione465576: Inhibition of human thymidine phosphorylaseki0.0170uM
5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]-1H-pyrimidine-2,4-dione;hydrochloride456853: Inhibition of human recombinant thymidine phosphorylaseki0.0170uM
6-[(2-amino-1H-imidazol-3-ium-3-yl)methyl]-5-bromo-1H-pyrimidine-2,4-dione211058: Inhibitory activity against Escherichia coli thymidine phosphorylaseic500.0190uM
6-[(2-amino-4,5-dihydroimidazol-1-yl)methyl]-5-chloro-1H-pyrimidine-2,4-dione;hydrobromide1497671: Inhibition of thymidine phosphorylase (unknown origin)ic500.0200uM
6-[(2-amino-1H-imidazol-3-ium-3-yl)methyl]-5-chloro-1H-pyrimidine-2,4-dione chloride213303: Compound was evaluated for its inhibitory activity against recombinant purified Escherichia coli Thymidine Phosphorylaseic500.0210uM
6-amino-5-bromo-1H-pyrimidine-2,4-dione1623806: Inhibition of thymidine phosphorylase (unknown origin)ic500.0350uM
6-[(2-amino-1H-imidazol-3-ium-3-yl)methyl]-5-chloro-1H-pyrimidine-2,4-dione241061: Inhibitory concentration against human thymidine phosphorylaseic500.0490uM
6-[(2-amino-1H-imidazol-3-ium-3-yl)methyl]-1H-pyrimidine-2,4-dione241061: Inhibitory concentration against human thymidine phosphorylaseic500.1000uM
1-[(Z)-C-(3,4-dichlorophenyl)-N-hydroxycarbonimidoyl]-6-methylpyrimidine-2,4-dione1402656: Inhibition of thymidine phosphorylase (unknown origin) using thymidine as substrate after 1 hr by spectrophotometric analysisic500.1200uM
6-[(1,3-dihydroxypropan-2-ylamino)methyl]-5-iodo-1H-pyrimidine-2,4-dione1623718: Inhibition of recombinant human thymidine phosphorylase expressed in Escherichia coli Rosetta (DE3) cells using thymidine as substrate after 1 min by UV/visible spectrophotometryic500.1200uM
6-chloro-5-(cyclopenten-1-yl)-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki0.2000uM
[(2R,3aR,4R,6R,6aR)-6-(hydroxymethyl)-4-(5-methyl-2,4-dioxopyrimidin-1-yl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-2-yl]methylphosphonic acid274782: Inhibition of human thymidine phosphorylase by continuous spectrophotometric assayki0.2360uM
2-(5-methyl-2,4-dioxopyrimidin-1-yl)ethoxymethylphosphonic acid456853: Inhibition of human recombinant thymidine phosphorylaseki0.2360uM
[1-fluoro-3-(5-methyl-2,4-dioxopyrimidin-1-yl)propan-2-yl]oxymethylphosphonic acid456853: Inhibition of human recombinant thymidine phosphorylaseki0.2360uM
1-(5-methyl-2,4-dioxopyrimidin-1-yl)propan-2-yloxymethylphosphonic acid456853: Inhibition of human recombinant thymidine phosphorylaseki0.2360uM
8-[5-bromo-3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,6-dioxopyrimidin-1-yl]octylphosphonic acid456853: Inhibition of human recombinant thymidine phosphorylaseki0.2360uM
[1-hydroxy-3-(5-methyl-2,4-dioxopyrimidin-1-yl)propan-2-yl]oxymethylphosphonic acid456853: Inhibition of human recombinant thymidine phosphorylaseki0.2360uM
6-chloro-5-thiophen-2-yl-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki0.2800uM
(5-chloro-2,4-dioxo-1H-pyrimidin-6-yl)methyl carbamimidothioate;hydrochloride1055575: Inhibition of human thymidine phosphorylaseic500.3500uM
6-chloro-5-phenyl-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki0.4000uM
6-chloro-5-[(E)-pent-1-enyl]-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki0.4100uM
6-chloro-5-(cyclohexen-1-yl)-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki0.4200uM
6-fluoro-5-phenyl-1H-pyrimidine-2,4-dione303487: Inhibition of human placental thymidine phosphorylaseki0.4700uM
6-chloro-5-[(E)-pent-2-en-3-yl]-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki0.4900uM
6-[(2-amino-1H-imidazol-3-ium-3-yl)methyl]-1H-pyrimidine-2,4-dione chloride213303: Compound was evaluated for its inhibitory activity against recombinant purified Escherichia coli Thymidine Phosphorylaseic500.5600uM
5-[(E)-but-1-enyl]-6-chloro-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki0.6300uM
6-chloro-5-(4-fluorophenyl)-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki0.7100uM
(E)-3-[2-(3,4-dichlorophenyl)phenyl]-N-thiophen-2-ylsulfonylprop-2-enamide161213: Inhibitory constant against Prostanoid TP receptorki0.7700uM
5-chloro-6-[(1,3-dihydroxypropan-2-ylamino)methyl]-1H-pyrimidine-2,4-dione1623718: Inhibition of recombinant human thymidine phosphorylase expressed in Escherichia coli Rosetta (DE3) cells using thymidine as substrate after 1 min by UV/visible spectrophotometryic501.0000uM
5-butyl-6-chloro-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki1.0300uM
[(2S,3aR,4S,6R,6aR)-4-(hydroxymethyl)-6-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,3,3a,4,6,6a-hexahydrofuro[2,3-c]furan-2-yl]methylphosphonic acid274782: Inhibition of human thymidine phosphorylase by continuous spectrophotometric assayki1.0500uM
6-chloro-5-heptyl-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki1.0600uM
6-chloro-5-[(E)-prop-1-enyl]-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki1.1700uM
6-[(2-hydroxyethylamino)methyl]-5-iodo-1H-pyrimidine-2,4-dione1623718: Inhibition of recombinant human thymidine phosphorylase expressed in Escherichia coli Rosetta (DE3) cells using thymidine as substrate after 1 min by UV/visible spectrophotometryic501.2000uM
6-bromo-5-phenyl-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki1.2100uM
6-chloro-5-(3,5-dimethylphenyl)-1H-pyrimidine-2,4-dione303487: Inhibition of human placental thymidine phosphorylaseki1.2700uM
1-[(Z)-C-(4-chlorophenyl)-N-hydroxycarbonimidoyl]-6-methylpyrimidine-2,4-dione1402656: Inhibition of thymidine phosphorylase (unknown origin) using thymidine as substrate after 1 hr by spectrophotometric analysisic501.4000uM
6-[(2-nitroimidazol-1-yl)methyl]-1H-pyrimidine-2,4-dione213303: Compound was evaluated for its inhibitory activity against recombinant purified Escherichia coli Thymidine Phosphorylaseic501.6000uM
[4-oxo-2-sulfanylidene-8-[[4-(trifluoromethyl)phenyl]methyl]-6H-pyrazolo[1,5-a][1,3,5]triazin-7-yl]thiourea1126859: Mixed-type inhibition of human recombinant thymidine phosphorylase expressed in Escherichia coli assessed as conversion of thymidide to thymine by Lineweaver-Burk plot analysiski1.6500uM
7-(3,4-dichlorophenyl)-2-sulfanylidene-6H-pyrazolo[1,5-a][1,3,5]triazin-4-one1126859: Mixed-type inhibition of human recombinant thymidine phosphorylase expressed in Escherichia coli assessed as conversion of thymidide to thymine by Lineweaver-Burk plot analysiski1.7700uM
6-chloro-5-hexyl-1H-pyrimidine-2,4-dione303487: Inhibition of human placental thymidine phosphorylaseki1.7900uM
5-bromo-6-[2-[(5-bromo-2,4-dioxo-1H-pyrimidin-6-yl)amino]ethylamino]-1H-pyrimidine-2,4-dione;dihydrochloride261612: Inhibition of human TP purified from placentaic502.2000uM
1-(cyclopropylmethyl)-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(trityloxymethyl)oxolan-2-yl]purin-6-one270128: Inhibition of human TPase in presence of 100 uM thymidineic502.3000uM
1-[(Z)-C-(4-bromophenyl)-N-hydroxycarbonimidoyl]-6-methylpyrimidine-2,4-dione1402656: Inhibition of thymidine phosphorylase (unknown origin) using thymidine as substrate after 1 hr by spectrophotometric analysisic502.7000uM
2-[(3,4-dichlorophenyl)methyl]-5-sulfanylidene-1H-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-one765733: Inhibition of human recombinant thymidine phosphorylase expressed in Escherichia coli using thymidine as substrate after 4 to 20 mins by spectrophotometryic502.9500uM
6-chloro-5-pyridin-3-yl-1H-pyrimidine-2,4-dione1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”ki3.0100uM
6-chloro-5-pyridin-3-yl-1H-pyrimidine-2,4-dione;hydrochloride303486: Inhibition of human recombinant thymidine phosphorylase expressed in V79 cellski3.0100uM
6-chloro-5-pentyl-1H-pyrimidine-2,4-dione303487: Inhibition of human placental thymidine phosphorylaseki3.0900uM

CTD chemical–gene interactions

93 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Fluorouracildecreases expression, increases expression, increases response to substance, affects response to substance, affects cotreatment (+2 more)8
Cisplatindecreases degradation, decreases expression, increases activity, decreases reaction, increases response to substance (+4 more)7
doxifluridineaffects expression, increases expression, increases response to substance, increases metabolic processing, affects cotreatment (+4 more)6
bisphenol Aaffects expression, decreases expression, increases expression3
Air Pollutantsdecreases expression, affects expression, increases abundance3
Paclitaxelaffects cotreatment, affects expression, increases expression, decreases reaction, increases cleavage (+2 more)3
sodium arseniteincreases expression2
acetylleucyl-leucyl-norleucinaldecreases reaction, decreases stability, increases expression, affects cotreatment2
benzyloxycarbonylleucyl-leucyl-leucine aldehydeaffects cotreatment, decreases reaction, decreases stability, increases expression2
Aspirinincreases expression, decreases expression, decreases reaction2
Benzo(a)pyreneincreases expression, increases methylation2
Dactinomycindecreases reaction, increases expression, increases reaction2
Formaldehydeincreases expression2
Testosteroneaffects cotreatment, increases expression, decreases expression2
Thymidineincreases phosphorylation, affects cotreatment, decreases reaction, increases expression, increases secretion2
Tobacco Smoke Pollutionaffects expression, decreases expression2
Mitomycindecreases expression, affects cotreatment, affects response to substance2
Cadmium Chloridedecreases expression2
GSK-J4decreases expression1
urushiolincreases expression1
lasiocarpineincreases expression1
triphenyl phosphateaffects expression1
pyrogallol 1,3-dimethyl etheraffects cotreatment, affects localization, increases expression, decreases expression1
salinomycindecreases expression, decreases response to substance, decreases reaction, increases expression, increases reaction (+1 more)1
ferrous chloridedecreases expression1
nickel sulfatedecreases expression, affects cotreatment1
2-deoxyribose 1-phosphateincreases abundance1
4-aminophenylarsenoxideaffects binding, decreases reaction1
S-(1,2-dichlorovinyl)cysteineincreases expression, decreases reaction1
FEC protocolaffects cotreatment, increases expression1

ChEMBL screening assays

94 unique, capped per target: 91 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1066239BindingInhibition of human recombinant thymidine phosphorylaseStructural diversity of nucleoside phosphonic acids as a key factor in the discovery of potent inhibitors of rat T-cell lymphoma thymidine phosphorylase. — Bioorg Med Chem Lett
CHEMBL813688FunctionalIn vitro percent of phosphorolysis after incubation with Escherichia coli thymidine phosphorylase for 10 min at 37 degree C; ND=Not determinedSynthesis, in vitro biological stability, and anti-HIV activity of 5-halo-6-alkoxy(or azido)-5,6-dihydro-3’-azido-3’-deoxythymidine diastereomers as potential prodrugs to 3’-azido-3’-deoxythymidine (AZT). — J Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_9645MKN45/TPCancer cell lineFemale
CVCL_9659YCC-3/TPCancer cell lineMale
CVCL_B2K2Abcam HeLa TYMP KOCancer cell lineFemale
CVCL_D2ZDGM26124Transformed cell lineFemale
CVCL_S977PC9-DPE2Cancer cell lineMale
CVCL_W867KU2-TP15Cancer cell lineMale

Clinical trials (associated diseases)

12 trials via MONDO — disease-level, not drug-specific.

TrialPhaseStatusTitle
NCT02171104PHASE2ACTIVE_NOT_RECRUITINGMT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT02427178PHASE1WITHDRAWNMNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study
NCT01694953Not specifiedRECRUITINGThe Natural History Study of Mitochondrial NeuroGastroIntestinal Encephalopathy (MNGIE)
NCT01803906Not specifiedENROLLING_BY_INVITATIONTissue Sample Study for Mitochondrial Disorders
NCT04245917Not specifiedSUSPENDEDNatural History Study of MNGIE
NCT05554835Not specifiedRECRUITINGGlobal Registry and Natural History Study for Mitochondrial Disorders
NCT05658822Not specifiedUNKNOWNDigestive Dysmotility in Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT01793168Not specifiedRECRUITINGRare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT03662672Not specifiedCOMPLETEDRib Raising for Post-operative Ileus
NCT04981262Not specifiedCOMPLETEDImproved Quality of Life in Children With Intestinal Failure
NCT06020365Not specifiedCOMPLETEDInvestigation of Fecal Microbiota Transplant in Chronic Intestinal Pseudo-obstruction Patients
NCT06711107Not specifiedACTIVE_NOT_RECRUITINGPredicting NOM Failure in Bowel Obstruction

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
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Sources 79

This page pulls from 79 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot