Gene-drug interactions (data source: DGIdb)
Gene Name Entrez ID Drug Name Chembl ID Interaction Types Sources publications
TYMS 7298 RALTITREXED CHEMBL225071 inhibitor PharmGKB, TdgClinicalTrial, GuideToPharmacologyInteractions, TEND, DrugBank 10047461, 11752352, 10499608, 18773878, 10482907, 10598555, 10592235, 10496350, 10430100
TYMS 7298 GEMCITABINE CHEMBL888 inhibitor DrugBank 16818276, 16818496, 11752352, 15795320, 17166391, 15655942, 16563096
TYMS 7298 CAPECITABINE CHEMBL1773 inhibitor ClearityFoundationBiomarkers, ClearityFoundationClinicalTrial, GuideToPharmacologyInteractions, ChemblInteractions, DrugBank 15134221, 15132128, 11752352, 15866500, 15709193, 16926630
TYMS 7298 DEOXYURIDINE MONOPHOSPHATE CHEMBL211312 DrugBank 17139284, 17016423, 10592235
TYMS 7298 PRALATREXATE CHEMBL1201746 inhibitor DrugBank 23409799
TYMS 7298 CHEMBL129788 CHEMBL129788 DrugBank 10592235
TYMS 7298 CYTARABINE CHEMBL803 PharmGKB
TYMS 7298 ETOPOSIDE CHEMBL44657 PharmGKB
TYMS 7298 LEUCOVORIN CHEMBL1679 TdgClinicalTrial, TEND
TYMS 7298 FOLIC ACID CHEMBL1622 PharmGKB
TYMS 7298 OXALIPLATIN CHEMBL414804 PharmGKB
TYMS 7298 METHOTREXATE CHEMBL34259 CIViC 23652803
TYMS 7298 FLOXURIDINE CHEMBL917 inhibitor TdgClinicalTrial, ClearityFoundationClinicalTrial, ChemblInteractions, TEND, DrugBank 10697523, 10697524, 10891536, 10482907, 10553409
TYMS 7298 FLUOROURACIL CHEMBL185 inhibitor ClearityFoundationClinicalTrial, ChemblInteractions, CIViC, DrugBank 15353299, 11752352, 16719540, 16538493, 16596248, 16609021, 16563096, 20628391
TYMS 7298 CHEMBL389051 CHEMBL389051 DrugBank 10592235
TYMS 7298 FOLITIXORIN CALCIUM CHEMBL2103811 DrugBank
TYMS 7298 CHEMBL169896 CHEMBL169896 TdgClinicalTrial, DrugBank
TYMS 7298 CHEMBL22148 CHEMBL22148 DrugBank 10592235
TYMS 7298 SODIUM beta-NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE CHEMBL295069 NCI 7790321
TYMS 7298 PEMETREXED DISODIUM CHEMBL1200373 inhibitor ChemblInteractions
TYMS 7298 CHEMBL219484 CHEMBL219484 DrugBank 10592235
TYMS 7298 CHEMBL1235693 CHEMBL1235693 DrugBank 10592235
TYMS 7298 PEMETREXED (CHEMBL1201258) CHEMBL1201258 inhibitor ClearityFoundationBiomarkers, TdgClinicalTrial, GuideToPharmacologyInteractions, CIViC, TEND 26502926, 23060591, 23645741, 21367480
TYMS 7298 PREDNISONE CHEMBL635 PharmGKB
TYMS 7298 TEGAFUR CHEMBL20883 TdgClinicalTrial
TYMS 7298 VINCRISTINE CHEMBL90555 NCI 2804079
TYMS 7298 TRIFLURIDINE CHEMBL1129 inhibitor DrugBank 16010590, 17179993, 6436227, 4719131, 11752352, 19886911, 18798063, 15571283, 18600528, 20372850, 6010427, 19816940, 16902987, 14719072, 15125867
TYMS 7298 TRIMETHOPRIM CHEMBL22 inhibitor DrugBank 17139284, 17016423, 19622858, 8920005, 10592235, 10090784, 8538681
TYMS 7298 THYMIDINE MONOPHOSPHATE CHEMBL394429 DrugBank 17139284, 17016423
TYMS 7298 ENILURACIL CHEMBL355200 NCI 10692560
TYMS 7298 ASPARAGINASE CHEMBL2108989 PharmGKB
TYMS 7298 SULFASALAZINE CHEMBL421 PharmGKB
TYMS 7298 DAUNORUBICIN CHEMBL178 NCI 2967076
TYMS 7298 INTERFERON GAMA-1B CHEMBL1201564 NCI 1557656
TYMS 7298 RESERPINE CHEMBL772 NCI 2866100
TYMS 7298 TAMOXIFEN CHEMBL83 NCI 9615734
TYMS 7298 DEXAMETHASONE CHEMBL384467 NCI 2707640, 3398844
TYMS 7298 HYDROCORTISONE CHEMBL389621 NCI 2707640
TYMS 7298 TOPOTECAN CHEMBL84 NCI 10803925
TYMS 7298 VERAPAMIL CHEMBL6966 NCI 3436366
TYMS 7298 ANTHRACENE-9-CARBOXYLIC ACID CHEMBL1513985 NCI 10803925
TYMS 7298 DOXIFLURIDINE CHEMBL1130 NCI 2972339
TYMS 7298 INDOMETHACIN CHEMBL6 NCI 2707640
TYMS 7298 MITOMYCIN CHEMBL105 NCI 15218314
TYMS 7298 PHENTOLAMINE CHEMBL597 NCI 2866100
TYMS 7298 IRINOTECAN CHEMBL481 CIViC 20628391

Variant-drug associations (data source: PharmGKB)
Gene Name Variant Alleles Chemical Phenotype Category Significance Notes Sentence Publications Annotation ID
TYMS rs11280056 del methotrexate toxicity no Discontinuation due to adverse effects. Allele described as TYMS rs34489327 Del/6bp. Authors state in discussion "In our study carriers of TYMS rs34489327, a 6-base pair (bp) sequence deletion, or TYMS rs34743033, a 28-bp variable number tandem repeat, experienced discontinuation because of AEs more frequently than noncarriers." But p value was not significant. Allele del is associated with increased discontinuation of methotrexate in people with Arthritis, Rheumatoid as compared to allele TTAAAGTTA. 27217051 1451161440
TYMS rs45445694 (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 fluorouracil efficacy not stated as measured by IC50 values in cell assays. Impact of additional SNP in the 3rd repeat is also measured but this SNP has no rs# so is not annotated. Genotype (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 is associated with decreased response to fluorouracil in people with as compared to genotype (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2. 15918040 769169217
TYMS rs45445694 (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 + (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 fluorouracil efficacy yes as measured by tumor reduction with preoperative chemoradiotherapy. Genotypes (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 + (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 is associated with increased response to fluorouracil in people with Rectal Neoplasms as compared to genotype (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2. 21167658 769165179
TYMS rs45445694 (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 fluorouracil efficacy no Allele (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 is not associated with response to fluorouracil in people with Colonic Neoplasms as compared to allele (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3. 20665215 827813447
TYMS rs45445694 (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 capecitabine efficacy yes "3R/3R genotype was preferentially found within the poor-response group of patients (p<0.01) while the 2R/2R genotype was more abundant in the good-response group." Genotype (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 is associated with decreased response to capecitabine and raltitrexed in people with Colorectal Neoplasms as compared to genotype (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2. 17203168 769166457
TYMS rs45445694 (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 fluorouracil efficacy yes Patients homozygous for the 2 tandem repeat genotype (*2/*2) had higher rate of progressive response (a decrease of >30% of the longest diameter of lesions) and a lower rate of stable disease (no change in lesion diameter) as compared to patients heterozygous for the 2 and 3 tandem repeat genotype (*2/*3). Overall survival (OS) and progression free survival (PFS) was different between the two groups but not in a statistically significant manner (*2/*2 OS 20.9 months, PFS 10.2 months and *2/*3 OS 11.4 months and PFS 6.0 months). Genotype (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 is associated with increased response to fluorouracil, leucovorin and oxaliplatin in people with Esophageal Neoplasms and Stomach Neoplasms as compared to genotype (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3. 25232828 1184886844
TYMS rs45445694 (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 + (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 FOLFIRI metabolism/PK no "Patients with favourable TS profile (i.e., genotype 2R/2R or 2R/3R) received either standard FOLFIRI or HD-FOLFIRI." Genotypes (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 + (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 is associated with increased dose of FOLFIRI in people with Colorectal Neoplasms as compared to genotype (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3. 21273624 769165161
TYMS rs2853542 GG methotrexate efficacy yes "when the TYMS gene was analysed with respect to VNTR and G to C substitution, the higher frequency 3 G/3 G genotype was found in the group of the non-responders when compared to all remaining genotypes" Genotype GG is associated with decreased response to methotrexate in people with Arthritis, Rheumatoid as compared to genotypes CC + CG. 22763757 1451239960
TYMS rs45445694 (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 fluorouracil efficacy yes Genotype (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 is associated with increased response to fluorouracil in people with Colorectal Neoplasms as compared to genotypes (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 + (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3. 11913730 769169082
TYMS rs2853542 C capecitabine efficacy no Meta-analysis with 6 studies. Preoperative fluorouracil-based chemoradiotherapy. Response was evaluated by tumor regression grade: responders were considered to be grade 1-2 and non-responders grade 3-5, or responders were considered to be grade 1 and non-responders grade 2-5. Allele C is not associated with response to capecitabine or fluorouracil in people with Rectal Neoplasms as compared to allele G. 27001118 1448426745
TYMS rs699517 T methotrexate efficacy no Allele T is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele C. 29743634 1449557975
TYMS rs45445694 (CCGCGCCACTTCGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTCGCCTGCCTCCGTCCCG)2 + (CCGCGCCACTTCGCCTGCCTCCGTCCCG)2/3 fluorouracil efficacy yes Increased response rate - pathological complete remission and microfoci residual tumor. Genotypes (CCGCGCCACTTCGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTCGCCTGCCTCCGTCCCG)2 + (CCGCGCCACTTCGCCTGCCTCCGTCCCG)2/3 is associated with increased response to fluorouracil in people with Rectal Neoplasms as compared to genotype 33. 20165956 1184468622
TYMS rs45445694 (CCGCGCCACTTCGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTCGCCTGCCTCCGTCCCG)2 fluorouracil efficacy no (CCGCGCCACTTCGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTCGCCTGCCTCCGTCCCG)2 is not associated with likelihood of tumor downstaging when treated with fluorouracil in people with Rectal Neoplasms, but the G>C SNP within the 3rd repeat (no rs#) was significantly associated with altered response. Genotype (CCGCGCCACTTCGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTCGCCTGCCTCCGTCCCG)2 is not associated with response to fluorouracil in people with Rectal Neoplasms. 20932673 1184469575
TYMS rs2244500 A methotrexate efficacy no Allele A is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele G. 29743634 1449558050
TYMS rs183205964 C capecitabine toxicity yes Discontinuation due to severe toxicity: gastrointestinal, hematological, and other treatment-related hospitalization. Allele C is associated with increased discontinuation of capecitabine, fluorouracil or tegafur in people with Neoplasms as compared to allele G. 26189437 1447944264
TYMS rs45445694 (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 + (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/CCGCGC(CACTTGGCCTGCCTCCGTCCCG)3 capecitabine efficacy yes Meta-analysis with 7 studies. Patients with the 2R/2R or 2R/3R genotypes had a greater response to preoperative fluorouracil-based chemoradiotherapy as compared to those with the 3R/3R genotype. Response was evaluated by tumor regression grade: responders were considered to be grade 1-2 and non-responders grade 3-5, or responders were considered to be grade 1 and non-responders grade 2-5. Genotypes (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 + (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/CCGCGC(CACTTGGCCTGCCTCCGTCCCG)3 is associated with increased response to capecitabine or fluorouracil in people with Rectal Neoplasms. 27001118 1448426721
TYMS rs2847153 A methotrexate efficacy no Allele A is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele G. 29743634 1449558056
TYMS rs45445694 (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 methotrexate toxicity no Discontinuation due to adverse effects. Please note that this variant was provided under the rsID rs34743033; this rsID has been updated to rs45445694. Allele (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 is not associated with discontinuation of methotrexate in people with Arthritis, Rheumatoid as compared to allele (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3. 27217051 1449164956
TYMS rs11280056 del methotrexate efficacy no Variant was originally mapped to TTAAAG allele of rs151264360, which has now been merged into rs11280056. This annotation replaces VA 827863352. Allele del is not associated with response to methotrexate in people with Arthritis, Rheumatoid. 22450926 1450821553
TYMS rs11280056 TTAAAGTTA capecitabine efficacy no Meta-analysis with 7 studies. Preoperative fluorouracil-based chemoradiotherapy. Referred to as "1494del6 polymorphism" in the study. Response was evaluated by tumor regression grade: responders were considered to be grade 1-2 and non-responders grade 3-5, or responders were considered to be grade 1 and non-responders grade 2-5. This variant was originally mapped to rs151264360, which has now been merged into rs11280056. This annotation replaces VA 1148426730. Allele TTAAAGTTA is not associated with response to capecitabine or fluorouracil in people with Rectal Neoplasms as compared to allele del. 27001118 1450821649
TYMS rs11280056 del fluorouracil efficacy no This association was originally mapped to rs34489327 and subsequently migrated to the analogous SNP rs151264360. rs151264360 has now been merged into rs11280056. This annotation replaces VA 1184886864. Allele del is not associated with response to fluorouracil, leucovorin and oxaliplatin in people with Esophageal Neoplasms and Stomach Neoplasms. 25232828 1450821634
TYMS rs11280056 TTAAAGTTA/del + del/del bevacizumab efficacy no No significant association with response, progression-free survival or overall survival was found for this variant. This variant was originally mapped to rs151264360, which has been merged into rs11280056. This annotation replaces VA 1448568367. Genotypes TTAAAGTTA/del + del/del are not associated with response to bevacizumab, capecitabine, cisplatin, docetaxel, epirubicin, oxaliplatin or trastuzumab in people with Stomach Neoplasms as compared to genotype del/del. 27995989 1450821655
TYMS rs11280056 TTAAAGTTA/del fluorouracil efficacy yes Significant only In patients also with the rs45445694 2R/2R genotype (diplotype analysis). As measured by disease-free survival and overall survival outcomes, which were decreased in patients with low-expression TYMS diplotypes. This association was originally mapped to rs34489327, then migrated to the analogous SNP rs151264360. rs151264360 has now been merged into rs11280056. This annotation replaces VA 827813357. Genotype TTAAAGTTA/del is associated with decreased response to fluorouracil in people with Colorectal Neoplasms as compared to genotype del/del. 21919605 1450821690
TYMS rs11280056 del folic acid efficacy no Is not significant alone but when considered as a haplotype with rs45445694 3R is highly significant. Reported in the paper as the del and TTAAAG alleles, which were initially mapped to rs151264360. rs151264360 was subsequently merged into rs11280056. This VA is an updated version of VA 769171248. Allele del is associated with increased response to folic acid, hydroxychloroquine, methotrexate and sulfasalazine in people with Arthritis, Rheumatoid as compared to allele TTAAAGTTA. 18322994 1450821537
TYMS rs2853539 AA methotrexate efficacy yes Genotype AA is associated with decreased response to methotrexate in people with Arthritis, Rheumatoid as compared to allele G. 19902562 655387811
TYMS rs45445694 (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 fluorouracil efficacy yes Significant only in patients also with TYMS rs34489327 del/del or del/ins genotypes (diplotype analysis). As measured by disease-free survival and overall survival outcomes, which were decreased in patients with low-expression TYMS diplotypes. Genotype (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 is associated with decreased response to fluorouracil in people with Colorectal Neoplasms. 21919605 827813351
TYMS rs45445694 (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 bevacizumab efficacy yes Patients with the 3R/3R genotype had a decreased likelihood of response to treatment as compared to those with the 2R/2R or 2R/3R genotypes in multivariable analysis. However, note that this was only a "nominally" significant association: formally significant was defined as p<0.0026, and nominally significant as p<0.05. No associations with progression-free survival or overall survival were found. Genotype (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 is associated with decreased response to bevacizumab, capecitabine, cisplatin, docetaxel, epirubicin, oxaliplatin or trastuzumab in people with Stomach Neoplasms as compared to genotypes (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 + (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3. 27995989 1448568253
TYMS rs45445694 (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 methotrexate efficacy yes Genotype (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 is associated with decreased response to methotrexate in people with Arthritis, Rheumatoid as compared to genotypes (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 + (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3. 27992285 1448589873