DPYD

Summary

DPYD (dihydropyrimidine dehydrogenase, HGNC:3012) is a protein-coding gene on chromosome 1p21.3, encoding Dihydropyrimidine dehydrogenase [NADP(+)] (Q12882). Involved in pyrimidine base degradation. In precision oncology, DPYD DPYD*13 HOMOZYGOSITY confers sensitivity to Capecitabine + Fluorouracil + Tegafur in Cancer (CIViC Level A); 3 further curated variant–drug associations are listed below.

The protein encoded by this gene is a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. Mutations in this gene result in dihydropyrimidine dehydrogenase deficiency, an error in pyrimidine metabolism associated with thymine-uraciluria and an increased risk of toxicity in cancer patients receiving 5-fluorouracil chemotherapy. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1806 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dihydropyrimidine dehydrogenase deficiency (Definitive, GenCC)
• GWAS associations: 44
• Clinical variants (ClinVar): 644 total — 14 pathogenic, 124 likely-pathogenic
• Phenotypes (HPO): 92
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 4 curated variant–drug associations
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000110

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3012
Approved symbol	DPYD
Name	dihydropyrimidine dehydrogenase
Location	1p21.3
Locus type	gene with protein product
Status	Approved
Aliases	DPD, DHPDHase
Ensembl gene	ENSG00000188641
Ensembl biotype	protein_coding
OMIM	612779
Entrez	1806

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000306031, ENST00000370192, ENST00000460019, ENST00000474241, ENST00000646851, ENST00000876334, ENST00000876335, ENST00000876336, ENST00000876337, ENST00000876338, ENST00000876339, ENST00000876340, ENST00000876341, ENST00000969914, ENST00000969915

RefSeq mRNA: 2 — MANE Select: NM_000110 NM_000110, NM_001160301

CCDS: CCDS30777, CCDS53346

Canonical transcript exons

ENST00000370192 — 23 exons

Exon	Start	End
ENSE00001003444	97098489	97098632
ENSE00001067062	97082330	97082470
ENSE00001067066	97450059	97450223
ENSE00001175939	97382393	97382461
ENSE00001175948	97515726	97515941
ENSE00001175981	97721510	97721671
ENSE00001179015	97193069	97193248
ENSE00001248261	97234852	97234994
ENSE00001293694	97373561	97373644
ENSE00001337292	97740392	97740479
ENSE00001401691	97306177	97306297
ENSE00001402719	97305259	97305378
ENSE00001416589	97549560	97549744
ENSE00001428755	97691717	97691798
ENSE00001429819	97679095	97679182
ENSE00001430871	97595059	97595166
ENSE00001431920	97593218	97593387
ENSE00001433514	97573760	97573970
ENSE00001761942	97828114	97828196
ENSE00001837520	97077743	97079146
ENSE00001844147	97920884	97921034
ENSE00003527026	97883264	97883374
ENSE00003676911	97699351	97699547

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 98.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.0316 / max 692.5421, expressed in 1666 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13455	40.7891	1660
13454	1.0883	527
13457	0.6579	372
13456	0.4963	258

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	98.84	gold quality
monocyte	CL:0000576	97.94	gold quality
mononuclear cell	CL:0000842	97.91	gold quality
leukocyte	CL:0000738	97.60	gold quality
parietal pleura	UBERON:0002400	97.43	gold quality
pleura	UBERON:0000977	96.76	gold quality
visceral pleura	UBERON:0002401	96.59	gold quality
palpebral conjunctiva	UBERON:0001812	95.39	gold quality
jejunal mucosa	UBERON:0000399	95.17	gold quality
lower lobe of lung	UBERON:0008949	94.35	gold quality
calcaneal tendon	UBERON:0003701	93.45	gold quality
esophagus squamous epithelium	UBERON:0006920	93.45	gold quality
superficial temporal artery	UBERON:0001614	93.36	gold quality
skin of hip	UBERON:0001554	92.83	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.53	gold quality
blood	UBERON:0000178	92.36	gold quality
epithelium of nasopharynx	UBERON:0001951	92.19	gold quality
nasopharynx	UBERON:0001728	92.17	gold quality
trabecular bone tissue	UBERON:0002483	91.74	gold quality
pericardium	UBERON:0002407	91.53	gold quality
cauda epididymis	UBERON:0004360	91.42	gold quality
liver	UBERON:0002107	91.28	gold quality
gall bladder	UBERON:0002110	91.25	gold quality
bone marrow cell	CL:0002092	91.11	gold quality
synovial joint	UBERON:0002217	91.11	gold quality
mammary duct	UBERON:0001765	90.71	gold quality
lung	UBERON:0002048	90.15	gold quality
oral cavity	UBERON:0000167	90.08	gold quality
thoracic mammary gland	UBERON:0005200	90.07	gold quality
epithelium of esophagus	UBERON:0001976	90.05	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	3003.05
E-HCAD-35	yes	83.23
E-HCAD-25	yes	62.70
E-ANND-3	yes	16.20
E-CURD-119	yes	8.86
E-MTAB-9801	yes	6.09
E-MTAB-6386	no	378.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CLOCK, PAX3, SP1, SP3

miRNA regulators (miRDB)

93 targeting DPYD, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-1271-5P	99.91	71.99	1972

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• circadian expression seen in leukocytes of healthy subjects, but rhythm disturbed in patients with advanced gastrointestinal carcinomas (PMID:11862480)
• DPD deficiency resulting from a compound heterozygote is seen in proband of breast cancer patients (PMID:11895907)
• Novel disease-causing mutations in the dihydropyrimidine dehydrogenase gene interpreted by analysis of the three-dimensional protein structure (PMID:11988088)
• 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)
• High prevalence of the IVS14 + 1G>A mutation is found in the gene of patients with severe 5-FU-associated toxicity. (PMID:12360106)
• Gene expression is a predictor for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer. (PMID:12576451)
• A deficiency or mutation in this gene in patients with epithelial neoplasms might be the cause of toxicity when administered 5-FU. (PMID:12844478)
• The DPYD mutation associated with lack of DPD activity, warrants genetic screening of these mutation before administration 5-FU for cancer patients. (PMID:12851836)
• TS and DPD quantitation may be helpful to evaluate prognosis of patients receiving adjuvant 5-FU and that patients with high TS and low DPD may benefit from adjuvant 5-FU chemotherapy in colorectal cancer. (PMID:14519634)
• high orotate phosphoribosyltransferase/dihydropyrimidine dehydrogenase ratio associated with longer survival in colorectal cancer patients treated with fluoropyrimidine-based chemotherapy (PMID:14562021)
• DPD expression may function as a marker of DPD activity and may be a prognostic indicator for patients with breast cancer. (PMID:14654904)
• There is no prognostic significance to DHP mRNA expression in breast neoplasms. (PMID:14702180)
• In stages I and II, DPD levels in the tumor specimens tended to be higher in the gastric cancer group than in the colorectal cancer group (PMID:15069545)
• Thymidine phosphorylase and dihydropyrimidine dehydrogenase have roles in progression of liver metastasis (PMID:15254700)
• DPD in differentiated type malignant tissue was statistically lower than in normal stromal tissue (p < 0.001), but no difference was seen in undifferentiated type cases. (PMID:15316940)
• Specific genetic polymorphisms in drug metabolizing enzymes (e.g., TPMT, UGT1A1, DPD), drug transporters (MDR1), and drug target enzymes (TS) are associated with clinical outcomes in patients treated with 5-fluorouracil and irinotecan. (PMID:15709212)
• This rate limiting enzyme of 5-fluorouracil whose activity in mononuclear cells shows circadian variation. (PMID:15939134)
• thymidylate synthase and dihydropyrimidine dehydrogenase are involved in resistance to 5-fluorouracil in human lung cancer cells (PMID:15993511)
• thymidylate synthase and orotate phosphoribosyl transferase, but not dihydropyrimidine dehydrogenase, are more highly expressed in prostate cancer than in benign prostatic hyperplasia (PMID:15999119)
• a newly described polymorphism of DPD gene might affect transcription of DPD and influence response to 5-FU (PMID:16021908)
• Association of mRNA expresion patterns with tumor stage and suggested new prognostic and predictive markers for patients with colorectal cancer. (PMID:16132996)
• Methylation of the DPYD promoter region is associated with down-regulation of DPD activity in clinical samples and should be considered as a potentially important regulatory mechanism of DPD activity and basis for 5-FU toxicity in cancer patients. (PMID:16361556)
• DPD may have a role in progression of colorectal cancer (PMID:16786143)
• Sp1 is a strong activator, while Sp3 by its own is a weak activator of the DPYD promoter. (PMID:16806531)
• DPD gene silencing is caused by epigenetic modification in biliary tract cancer cellsand has a role in sensitivity to 5-FU treatment (PMID:16820886)
• thymidine phosphorylase levels are more elevated relative to dihydropyrimidine dehydrogenase levels in squamous cell carcinoma than in adenocarcinoma (PMID:16969493)
• A novel mutation 464 T>A was identified in DPYD gene exon 5, resulting in the replacement of leucine 155 by a stop codon in the protein. (PMID:17046731)
• The mutation IVS14 + 1 G > A, DPYD*2A, is the most common mutation associated with DPD deficiency (PMID:17165084)
• thymidylate synthase and dihydropyrimidine dehydrogenase gene polymorphisms have a role in response and toxicity to capecitabine-raltitrexed treatment in colorectal cancer (PMID:17203168)
• study suggested that the influence of DPYD T85C posed only a limited risk for the six malignancies - esophageal, gastric, colon, lung, breast, and malignant lymphomas (PMID:17375478)
• Gene expression may be a response to fluorouracil sensitivity in stomach cancers of different histologic origin. (PMID:17377791)
• findings, from Korean patients with colon cancer, suggest that polymorphisms of the DPYD gene are not associated with an increased risk for toxic response to 5-fluorouracil (PMID:17417073)
• DPYD*5 gene mutation contributes to reduced DPYD enzyme activity and 5-FU metabolism, which is associated with accumulation of 5-FU and chemotherapeutic toxicity in patients with gastric and colonic carcinoma (PMID:17445431)
• Detection of DPD deficiency would avoid almost every early acute toxic side-effects of fluropyrimidnine treatment. (PMID:17582309)
• Assays to detect DPD deficiency should be but are not used as a screening test to prevent 5-FU toxicity in cancer treatment. (PMID:17582310)
• active transcription machinery for DPYD is present in RKO colorectal cancer cells, but promoter binding of Sp1, a transactivator of DPYD, was inhibited, which on subsequent examination was shown to be associated with dense promoter methylation (PMID:17612628)
• Results revealed a disturbed transcription of Per1 during tumor progression, which might be the cause for disrupted daily oscillation of DPD in undifferentiated colon carcinoma cells. (PMID:17699798)
• Nine novel nonsynonymous DPYD SNPs were found in Japanese associated with a risk for developing a severe or fatal toxicity to 5-FU. (PMID:17828463)
• study demonstrated relationship between DPYD gene polymorphism among 75 gastric & colon carcinoma patients & its impact on 5-FU pharmacokinetic & side effects; DPYD*5 gene mutation contributes to reduced DPYD enzyme activity & 5-FU dysmetabolism (PMID:17848752)
• 12 variants in the DPYD coding region & a new intronic polymorphism IVS 6-29 G>T were detected. (PMID:17905396)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dpydb	ENSDARG00000010267
danio_rerio	dpyda.3	ENSDARG00000086853
mus_musculus	Dpyd	ENSMUSG00000033308
rattus_norvegicus	Dpyd	ENSRNOG00000017105
drosophila_melanogaster	su(r)	FBGN0086450
caenorhabditis_elegans		WBGENE00016103

Paralogs (2): DHODH (ENSG00000102967), FDXR (ENSG00000161513)

Protein

Protein identifiers

Dihydropyrimidine dehydrogenase [NADP(+)] — Q12882 (reviewed: Q12882)

Alternative names: Dihydrothymine dehydrogenase, Dihydrouracil dehydrogenase

All UniProt accessions (1): Q12882

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Found in most tissues with greatest activity found in liver and peripheral blood mononuclear cells.

Disease relevance. Dihydropyrimidine dehydrogenase deficiency (DPYDD) [MIM:274270] A metabolic disorder with large phenotypic variability, ranging from no symptoms to a convulsive disorder with motor and intellectual disability. It is characterized by persistent urinary excretion of excessive amounts of uracil, thymine and 5-hydroxymethyluracil. Patients suffering from this disease show a severe reaction to the anticancer drug 5-fluorouracil. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inactivated by 5-iodouracil.

Cofactor. Binds 2 FAD. Binds 2 FMN. Binds 4 [4Fe-4S] clusters. Contains approximately 16 iron atoms per subunit.

Pathway. Amino-acid biosynthesis; beta-alanine biosynthesis.

Similarity. Belongs to the dihydropyrimidine dehydrogenase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12882-1	1	yes
Q12882-2	2

RefSeq proteins (2): NP_000101, NP_001153773 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005720	Dihydroorotate_DH_cat	Domain
IPR009051	Helical_ferredxn	Homologous_superfamily
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR017896	4Fe4S_Fe-S-bd	Domain
IPR017900	4Fe4S_Fe_S_CS	Conserved_site
IPR023753	FAD/NAD-binding_dom	Domain
IPR028261	DPD_II	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily

Pfam: PF01180, PF07992, PF14691, PF14697

Enzyme classification (BRENDA):

• EC 1.3.1.2 — dihydropyrimidine dehydrogenase (NADP+) (BRENDA: 9 organisms, 49 substrates, 49 inhibitors, 69 Km, 17 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NADPH	0.0001–0.0289	29
URACIL	0.0001–0.0366	20
THYMINE	0.0008–0.0068	7
5-FLUOROURACIL	0.0011–0.0089	4
NADP+	0.0004–0.0038	3
5,6-DIHYDROURACIL	0.24–2	2
DIHYDROTHYMINE	0.043–0.6	2
DIHYDROURACIL	0.193	1

Catalyzed reactions (Rhea), 2 shown:

• 5,6-dihydrouracil + NADP(+) = uracil + NADPH + H(+) (RHEA:18093)
• 5,6-dihydrothymine + NADP(+) = thymine + NADPH + H(+) (RHEA:58284)

UniProt features (58 total): binding site 36, sequence variant 8, sequence conflict 4, domain 3, modified residue 2, splice variant 2, propeptide 1, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12882-F1	96.23	0.95

Functional residue map

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

Catalytic / active sites (1): 671 (proton acceptor)

Ligand- & substrate-binding residues (36): 129; 130; 136; 140; 156; 194–198; 218–226; 235; 261; 340–343; 364–365; 371 …

Post-translational modifications (2): 384, 905

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-73621	Pyrimidine catabolism

MSigDB gene sets: 476 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, MODULE_93, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, KOBAYASHI_EGFR_SIGNALING_24HR_UP, ZHAN_MULTIPLE_MYELOMA_PR_DN, MODULE_255, REACTOME_PYRIMIDINE_CATABOLISM, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, MODULE_45, GOZGIT_ESR1_TARGETS_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, MODULE_317, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, HNF1_Q6

GO Biological Process (12): purine nucleobase catabolic process (GO:0006145), pyrimidine nucleobase catabolic process (GO:0006208), thymine catabolic process (GO:0006210), uracil catabolic process (GO:0006212), thymidine catabolic process (GO:0006214), CMP catabolic process (GO:0006248), dCMP catabolic process (GO:0006249), beta-alanine biosynthetic process (GO:0019483), xenobiotic catabolic process (GO:0042178), TMP catabolic process (GO:0046045), UMP catabolic process (GO:0046050), dUMP catabolic process (GO:0046079)

GO Molecular Function (12): uracil binding (GO:0002058), dihydropyrimidine dehydrogenase (NADP+) activity (GO:0017113), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), flavin adenine dinucleotide binding (GO:0050660), NADP binding (GO:0050661), 4 iron, 4 sulfur cluster binding (GO:0051539), nucleotide binding (GO:0000166), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-CH group of donors (GO:0016627), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Nucleotide catabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyrimidine ribonucleoside monophosphate catabolic process	3
pyrimidine ribonucleotide catabolic process	3
nucleobase catabolic process	2
pyrimidine nucleobase catabolic process	2
pyrimidine deoxyribonucleoside monophosphate catabolic process	2
pyrimidine deoxyribonucleotide catabolic process	2
cellular anatomical structure	2
purine nucleobase metabolic process	1
purine-containing compound catabolic process	1
pyrimidine nucleobase metabolic process	1
pyrimidine-containing compound catabolic process	1
thymine metabolic process	1
uracil metabolic process	1
thymidine metabolic process	1
pyrimidine deoxyribonucleoside catabolic process	1
CMP metabolic process	1
dCMP metabolic process	1
amino acid biosynthetic process	1
non-proteinogenic amino acid biosynthetic process	1
xenobiotic metabolic process	1
catabolic process	1
TMP metabolic process	1
UMP metabolic process	1
dUMP metabolic process	1
pyrimidine nucleobase binding	1
oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
nucleotide binding	1
anion binding	1
adenyl nucleotide binding	1
iron-sulfur cluster binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
oxidoreductase activity	1
metal cluster binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2545 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPYD	TYMS	P04818	978
DPYD	DPYS	Q14117	901
DPYD	UMPS	P11172	873
DPYD	TYMP	P19971	840
DPYD	MTDH	Q86UE4	820
DPYD	TFCP2	Q12800	818
DPYD	UPB1	Q9UBR1	793
DPYD	TPMT	P51580	782
DPYD	UGT1A1	P22309	763
DPYD	UGT1A7	Q9HAW7	730
DPYD	UGT1A8	Q9HAW9	728
DPYD	UPP2	O95045	727
DPYD	UGT1A10	Q9HAW8	726
DPYD	UGT1A4	P22310	726
DPYD	UGT1A6	P19224	720

IntAct

26 interactions, top by confidence:

A	B	Type	Score
GOPC	DPYD	psi-mi:“MI:0915”(physical association)	0.560
DPYD	LXN	psi-mi:“MI:0915”(physical association)	0.560
LXN	DPYD	psi-mi:“MI:0915”(physical association)	0.560
DPYD	GOPC	psi-mi:“MI:0915”(physical association)	0.560
FMR1	DPYD	psi-mi:“MI:0915”(physical association)	0.000
DPYD	tcaC1	psi-mi:“MI:0915”(physical association)	0.000
DPYD	xerC	psi-mi:“MI:0915”(physical association)	0.000
	DPYD	psi-mi:“MI:0915”(physical association)	0.000
DPYD		psi-mi:“MI:0915”(physical association)	0.000
gyrA	DPYD	psi-mi:“MI:0915”(physical association)	0.000
yapH	DPYD	psi-mi:“MI:0915”(physical association)	0.000
DPYD	clpA3	psi-mi:“MI:0915”(physical association)	0.000
rnr	DPYD	psi-mi:“MI:0915”(physical association)	0.000
DPYD	rpoB	psi-mi:“MI:0915”(physical association)	0.000
DPYD	phnK	psi-mi:“MI:0915”(physical association)	0.000
pelY	DPYD	psi-mi:“MI:0915”(physical association)	0.000
mntH	DPYD	psi-mi:“MI:0915”(physical association)	0.000
DPYD	glgX	psi-mi:“MI:0915”(physical association)	0.000
fyuA	DPYD	psi-mi:“MI:0915”(physical association)	0.000
arnB	DPYD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): LXN (Two-hybrid), GOPC (Two-hybrid), DPYD (Co-fractionation), DPYD (Co-fractionation), DPYD (Co-fractionation), DPYD (Co-fractionation), RPE (Co-fractionation), DPYD (Biochemical Activity), DPYD (Affinity Capture-RNA), DPYD (Affinity Capture-RNA), MICALL2 (Co-fractionation), NLN (Co-fractionation), STX18 (Co-fractionation), DPYD (Affinity Capture-MS), DPYD (Affinity Capture-MS)

ESM2 similar proteins: A2QGH7, B8BJ39, B9N1F9, C8VBV0, O04300, O04499, O09171, O22666, O22718, O23877, O35490, O54734, O80526, O89000, P11029, P11497, P21343, P41345, P50554, P55931, P61922, P80607, Q06364, Q12882, Q13085, Q16134, Q28007, Q28943, Q2KIG0, Q2QNG7, Q2QZ86, Q2RAK2, Q41141, Q4W1X2, Q4WU59, Q5FVD6, Q5R895, Q5RDD3, Q5SWU9, Q6NYG8

Diamond homologs: A0AJT8, A0RHQ6, A4IM35, A4J560, A4XKT6, A5VHS3, A6L5H1, A6TVS0, A7GRK9, A7Z4H4, A8FD19, A8MIU4, A8XKG6, A8YVZ9, A9KKR5, A9VTC4, B0TGQ8, B1I4M6, B1YIR7, B2G5A3, B2V726, B5YJH1, B7GFA1, B7H6M0, B7HLL8, B7IUP4, B7JJX1, B8DDR9, B9DPN4, B9IVW1, B9MS26, C0QYH6, C1EPP8, C1KWD2, C3L742, C3P654, C4XPD6, C5D8Q2, O29513, O59185

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
DPYD	“down-regulates quantity”	5-fluorouracil	“chemical modification”
CLOCK	“up-regulates quantity by expression”	DPYD	“transcriptional regulation”
DPYD	“down-regulates quantity”	uracil	“chemical modification”
DPYD	“down-regulates quantity”	thymine	“chemical modification”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	124
Uncertain significance	271
Likely benign	66
Benign	48

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1032888	NM_000110.4(DPYD):c.151-2A>C	Pathogenic
1192270	NM_000110.4(DPYD):c.464T>A (p.Leu155Ter)	Pathogenic
1805301	NM_000110.4(DPYD):c.2650G>T (p.Glu884Ter)	Pathogenic
2674913	NM_000110.4(DPYD):c.812del (p.Thr270_Leu271insTer)	Pathogenic
371160	NM_000110.4(DPYD):c.2003del (p.Asn668fs)	Pathogenic
4076028	GRCh37/hg19 1p21.3(chr1:97994374-98054281)x1	Pathogenic
4081632	NM_000110.4(DPYD):c.2202_2206dup (p.Asn736fs)	Pathogenic
4081633	NM_000110.4(DPYD):c.1820_1821del (p.Phe607fs)	Pathogenic
4279187	GRCh37/hg19 1p21.3(chr1:98109382-98199508)x1	Pathogenic
433	NM_000110.4(DPYD):c.2921A>T (p.Asp974Val)	Pathogenic
4536140	NM_000110.4(DPYD):c.12dup (p.Leu5fs)	Pathogenic
495550	NM_000110.4(DPYD):c.299_302del (p.Phe100fs)	Pathogenic
59973	GRCh38/hg38 1p21.3(chr1:96554406-97919058)x1	Pathogenic
686684	GRCh37/hg19 1p21.3(chr1:97757431-97798061)x1	Pathogenic
1335974	NM_000110.4(DPYD):c.895C>T (p.Gln299Ter)	Likely pathogenic
1722331	NM_000110.4(DPYD):c.2746del (p.Arg916fs)	Likely pathogenic
1723398	NM_000110.4(DPYD):c.1155_1156del (p.Cys385_Glu386delinsTer)	Likely pathogenic
188871	NM_000110.4(DPYD):c.2043_2058del (p.Leu682fs)	Likely pathogenic
2503882	NC_000001.10:g.(97658805_97700407)_(97700551_97770814)del	Likely pathogenic
2506136	NM_000110.4(DPYD):c.1A>C (p.Met1Leu)	Likely pathogenic
2573026	NM_000110.4(DPYD):c.508C>T (p.Gln170Ter)	Likely pathogenic
2581397	NM_000110.4(DPYD):c.2843T>C (p.Ile948Thr)	Likely pathogenic
2582686	NM_000110.4:c.850+23455_1128+8811del	Likely pathogenic
2633588	NM_000110.4(DPYD):c.1340-2A>C	Likely pathogenic
2634691	NM_000110.4(DPYD):c.1408C>T (p.Gln470Ter)	Likely pathogenic
2664661	NM_000110.4(DPYD):c.1072C>T (p.Arg358Cys)	Likely pathogenic
2674901	NM_000110.4(DPYD):c.1353_1360dup (p.Ile454fs)	Likely pathogenic
2674903	NM_000110.4(DPYD):c.601A>C (p.Ser201Arg)	Likely pathogenic
2674904	NM_000110.4(DPYD):c.2766+1G>A	Likely pathogenic
2674905	NM_000110.4(DPYD):c.40-6_42del	Likely pathogenic

SpliceAI

4636 predictions. Top by Δscore:

Variant	Effect	Δscore
1:97079143:TAGC:T	acceptor_gain	1.0000
1:97079145:GCCTG:G	acceptor_loss	1.0000
1:97079147:C:CG	acceptor_loss	1.0000
1:97098486:TACCT:T	donor_loss	1.0000
1:97098487:A:T	donor_loss	1.0000
1:97098488:C:CA	donor_loss	1.0000
1:97098628:AGTTT:A	acceptor_gain	1.0000
1:97098629:GTTT:G	acceptor_gain	1.0000
1:97098630:TTT:T	acceptor_gain	1.0000
1:97098631:TT:T	acceptor_gain	1.0000
1:97098631:TTCTA:T	acceptor_loss	1.0000
1:97098632:TCTAA:T	acceptor_loss	1.0000
1:97098633:C:CC	acceptor_gain	1.0000
1:97098633:CT:C	acceptor_loss	1.0000
1:97193064:CATA:C	donor_loss	1.0000
1:97193065:ATACC:A	donor_loss	1.0000
1:97193066:TACC:T	donor_loss	1.0000
1:97193068:C:T	donor_loss	1.0000
1:97193244:CATAC:C	acceptor_gain	1.0000
1:97193245:ATAC:A	acceptor_gain	1.0000
1:97193246:TAC:T	acceptor_gain	1.0000
1:97193247:AC:A	acceptor_gain	1.0000
1:97193248:CC:C	acceptor_gain	1.0000
1:97306171:TCTTA:T	donor_loss	1.0000
1:97306172:CTTA:C	donor_loss	1.0000
1:97306173:TTA:T	donor_loss	1.0000
1:97306174:TACC:T	donor_loss	1.0000
1:97306175:ACCT:A	donor_loss	1.0000
1:97306175:ACCTT:A	donor_gain	1.0000
1:97306176:C:A	donor_loss	1.0000

AlphaMissense

6741 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:97305350:G:C	N736K	0.999
1:97305350:G:T	N736K	0.999
1:97373615:A:C	N668K	0.999
1:97373615:A:T	N668K	0.999
1:97382447:G:C	S640R	0.999
1:97382447:G:T	S640R	0.999
1:97382449:T:G	S640R	0.999
1:97450122:A:C	S614R	0.999
1:97450122:A:T	S614R	0.999
1:97450124:T:G	S614R	0.999
1:97450137:A:C	N609K	0.999
1:97450137:A:T	N609K	0.999
1:97515745:T:A	K574I	0.999
1:97721575:A:G	C140R	0.999
1:97721587:A:G	C136R	0.999
1:97721605:A:G	C130R	0.999
1:97740442:A:G	C91R	0.999
1:97740454:A:G	C87R	0.999
1:97193240:A:C	S817R	0.998
1:97193240:A:T	S817R	0.998
1:97193242:T:G	S817R	0.998
1:97515764:A:G	W568R	0.998
1:97515764:A:T	W568R	0.998
1:97515816:G:C	S550R	0.998
1:97515816:G:T	S550R	0.998
1:97515818:T:G	S550R	0.998
1:97691772:A:G	L236P	0.998
1:97699428:A:C	S201R	0.998
1:97699428:A:T	S201R	0.998
1:97699430:T:G	S201R	0.998

dbSNP variants (sampled 300 via entrez): RS1000005289 (1:97116555 C>G), RS1000005804 (1:97659316 T>C,G), RS1000013481 (1:97661583 A>T), RS1000014061 (1:97848053 A>T), RS1000015053 (1:97412081 C>T), RS1000015599 (1:97453502 A>T), RS1000016265 (1:97109063 T>G), RS1000016925 (1:97577059 G>A), RS1000020249 (1:97615632 C>CA), RS1000023627 (1:97325757 G>T), RS1000032348 (1:97839510 G>C), RS1000033633 (1:97300921 C>T), RS1000034970 (1:97116295 C>T), RS1000041044 (1:97420020 T>C,G), RS1000057148 (1:97121681 C>G,T)

Disease associations

OMIM: gene MIM:612779 | disease phenotypes: MIM:274270, MIM:142623

GenCC curated gene-disease

Disease	Classification	Inheritance
dihydropyrimidine dehydrogenase deficiency	Definitive	Autosomal recessive

Mondo (4): dihydropyrimidine dehydrogenase deficiency (MONDO:0010130), prostate cancer (MONDO:0008315), Hirschsprung disease, susceptibility to, 1 (MONDO:0007723), 5-fluorouracil toxicity (MONDO:0027652)

Orphanet (4): Dihydropyrimidine dehydrogenase deficiency (Orphanet:1675), Familial prostate cancer (Orphanet:1331), Hirschsprung disease (Orphanet:388), (Orphanet:240839)

HPO phenotypes

92 total (30 of 92 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000478	Abnormality of the eye
HP:0000482	Microcornea
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000527	Long eyelashes
HP:0000545	Myopia
HP:0000568	Microphthalmia
HP:0000582	Upslanted palpebral fissure
HP:0000589	Coloboma
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000684	Delayed eruption of teeth
HP:0000708	Atypical behavior
HP:0000717	Autism

GWAS associations

44 associations (top):

Study	Trait	p-value
GCST001061_8	Platelet count	9.000000e-06
GCST001565_7	Schizophrenia	5.000000e-07
GCST001877_11	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	2.000000e-11
GCST002149_4	Schizophrenia	2.000000e-12
GCST002539_31	Schizophrenia	3.000000e-19
GCST002541_30	Menarche (age at onset)	2.000000e-09
GCST002783_190	Body mass index	4.000000e-06
GCST002783_344	Body mass index	2.000000e-06
GCST004136_5	Methadone dose in opioid dependence	3.000000e-06
GCST004521_145	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST004521_76	Autism spectrum disorder or schizophrenia	1.000000e-19
GCST004641_9	Borderline personality disorder	7.000000e-06
GCST005194_70	Coronary artery disease	6.000000e-06
GCST005316_305	Intelligence (MTAG)	1.000000e-08
GCST006803_3	Schizophrenia	2.000000e-18
GCST006803_43	Schizophrenia	4.000000e-08
GCST006914_25	Sleep duration	2.000000e-10
GCST006921_11	Regular attendance at a pub or social club	5.000000e-10
GCST006941_51	Irritable mood	5.000000e-09
GCST006948_9	Feeling nervous	2.000000e-08
GCST006979_993	Heel bone mineral density	5.000000e-11
GCST007044_3	Extremely high intelligence	4.000000e-08
GCST007201_171	Schizophrenia	3.000000e-10
GCST007201_51	Schizophrenia	2.000000e-06
GCST007490_7	Anthropometric traits (multi-trait analysis)	2.000000e-09
GCST007559_15	Sleep duration (short sleep)	4.000000e-09
GCST007576_306	Chronotype	2.000000e-11
GCST007710_20	Anxiety/tension (special factor of neuroticism)	4.000000e-09
GCST008129_4	Body mass index	9.000000e-10
GCST008159_33	Waist-to-hip ratio adjusted for BMI	7.000000e-06

EFO canonical traits (22, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004703	age at menarche
EFO:0004340	body mass index
EFO:0007907	methadone dose measurement
EFO:0004337	intelligence
EFO:0009592	social interaction measurement
EFO:0009594	irritability measurement
EFO:0009597	feeling nervous measurement
EFO:0009270	heel bone mineral density
EFO:0004324	body weights and measures
EFO:0008328	chronotype measurement
EFO:0009863	anxiety measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004784	self reported educational attainment
EFO:0009658	adverse effect
EFO:0004874	memory performance
EFO:0004761	uric acid measurement
EFO:0010416	triacylglycerol 52:4 measurement
EFO:0009695	household income
EFO:0004530	triglyceride measurement
EFO:0007874	gut microbiome measurement
EFO:0007828	daytime rest measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D054067	Dihydropyrimidine Dehydrogenase Deficiency	C16.320.565.798.183; C18.452.648.798.183
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3172 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 25,303 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL355200	ENILURACIL	3	25,303

Clinical evidence (CIViC)

Drug × variant × indication: 4 predictive associations from 4 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
DPYD DPYD*13 HOMOZYGOSITY	Capecitabine + Fluorouracil + Tegafur	Cancer	Adverse Response	CIViC A	EID1801
DPYD DPYD*2A HOMOZYGOSITY	Tegafur + Capecitabine + Fluorouracil	Cancer	Adverse Response	CIViC A	EID1800
DPYD RS67376798 HOMOZYGOSITY	Tegafur + Fluorouracil + Capecitabine	Cancer	Adverse Response	CIViC A	EID1803
DPYD EXON 11-19 DELETION	Leucovorin + Fluorouracil	Head And Neck Squamous Cell Carcinoma	Sensitivity/Response	CIViC C	EID7787

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

PharmGKB clinical annotations

82 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs115232898	Toxicity	1A	fluorouracil	Neoplasms
rs115232898	Other	1A	fluorouracil
rs115632870	Other	3	fluorouracil
rs1184321568	Other	3	fluorouracil
rs12022243	Toxicity	3	capecitabine	Colorectal Neoplasms
rs12119882	Toxicity	3	capecitabine	Hyperbilirubinemia;Neoplasms
rs1212037891	Other	3	fluorouracil
rs12132152	Toxicity	3	capecitabine	Colorectal Neoplasms
rs1335150891	Other	3	fluorouracil
rs140039091	Toxicity	3	fluorouracil	Drug Toxicity
rs140989814	Toxicity	3	fluorouracil	Drug Toxicity
rs143879757	Other	3	fluorouracil
rs148994843	Other	1A	fluorouracil
rs17376848	Toxicity	1A	capecitabine	Neoplasms
rs17376848	Toxicity	1A	fluorouracil	Neoplasms
rs1760217	Efficacy	3	antineoplastic agents	Pancreatic Neoplasms
rs1801158	Toxicity	1A	fluorouracil	Neoplasms
rs1801158	Toxicity	1A	capecitabine	Neoplasms
rs1801159	Toxicity	1A	capecitabine	Neoplasms
rs1801159	Toxicity	1A	fluorouracil	Neoplasms
rs1801160	Toxicity	1A	capecitabine	Neoplasms
rs1801160	Toxicity	1A	fluorouracil	Neoplasms
rs1801160	Other	1A	fluorouracil
rs1801265	Toxicity	1A	capecitabine	Neoplasms
rs1801265	Toxicity	1A	fluorouracil	Neoplasms
rs1801266	Other	1A	fluorouracil
rs1801268	Other	1A	fluorouracil
rs187713395	Toxicity	3	fluorouracil	Drug Toxicity
rs188052243	Other	3	fluorouracil
rs201268750	Toxicity	3	fluorouracil	Drug Toxicity
rs2297595	Toxicity	1A	capecitabine	Neoplasms
rs2297595	Toxicity	1A	fluorouracil	Neoplasms
rs367619008	Toxicity	3	capecitabine;fluorouracil;XELOX	Drug Toxicity
rs368146607	Toxicity	3	fluorouracil	Drug Toxicity
rs369103276	Toxicity	3	fluorouracil	Drug Toxicity
rs371258350	Toxicity	3	fluorouracil	Drug Toxicity
rs372307932	Toxicity	3	fluorouracil	Drug Toxicity
rs374527058	Toxicity	3	fluorouracil	Drug Toxicity
rs374825099	Toxicity	3	fluorouracil	Drug Toxicity
rs376073289	Toxicity	3	fluorouracil	Drug Toxicity

PharmGKB variants

207 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1760217	DPYD	3	2.50	1	antineoplastic agents
rs1801158	DPYD	1A	87.75	2	capecitabine;fluorouracil
rs1801159	DPYD	1A	86.75	2	capecitabine;fluorouracil
rs1801160	DPYD	1A	108.50	3	fluorouracil;capecitabine
rs1801265	DPYD	1A	93.75	2	fluorouracil;capecitabine
rs1801266	DPYD	1A	100.12	1	fluorouracil
rs1801267	DPYD		0.00	0
rs1801268	DPYD	1A	100.12	1	fluorouracil
rs2297595	DPYD	1A	84.00	2	fluorouracil;capecitabine
rs3918290	DPYD	1A	255.25	5	capecitabine;fluorouracil;tegafur
rs4970722	DPYD		0.00	0
rs7548189	DPYD		0.00	0
rs12022243	DPYD	3	3.00	1	capecitabine
rs12132152	DPYD	3	5.00	1	capecitabine
rs17116806	DPYD		0.00	0
rs17376848	DPYD	1A	95.75	2	capecitabine;fluorouracil
rs45589337	DPYD		0.00	0
rs55674432	DPYD		0.00	0
rs55886062	DPYD	1A	208.00	4	fluorouracil;capecitabine;tegafur
rs56038477	DPYD	1A	208.50	2	capecitabine;fluorouracil
rs56160474	DPYD		0.00	0
rs59086055	DPYD	1A	100.00	2	fluorouracil
rs60139309	DPYD		0.00	0
rs61757362	DPYD		0.00	0
rs67376798	DPYD	1A	233.75	4	fluorouracil;capecitabine;tegafur
rs72547601	DPYD		0.00	0
rs72549303	DPYD	1A	100.12	1	fluorouracil
rs72549304	DPYD		0.00	0
rs72549306	DPYD	1A	100.00	1	fluorouracil
rs72549307	DPYD		0.00	0
rs72549308	DPYD		0.00	0
rs72549309	DPYD	1A	100.12	1	fluorouracil
rs72728438	DPYD	3	1.25	1	fluorouracil
rs75017182	DPYD	1A	200.00	3	fluorouracil;capecitabine
rs76387818	DPYD	3	5.00	1	capecitabine
rs78060119	DPYD	1A	100.00	2	fluorouracil
rs80081766	DPYD		0.00	0
rs111858276	DPYD		0.00	0
rs112766203	DPYD		0.00	0
rs114096998	DPYD		0.00	0

PharmGKB dosing guidelines

10 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	capecitabine	Annotation of CPIC Guideline for capecitabine and DPYD	yes	yes
CPIC	fluorouracil	Annotation of CPIC Guideline for fluorouracil and DPYD	yes	yes
CPIC	tegafur	Annotation of CPIC Guideline for tegafur and DPYD
DPWG	capecitabine	Annotation of DPWG Guideline for capecitabine and DPYD	yes	yes
DPWG	flucytosine	Annotation of DPWG Guideline for flucytosine and DPYD		yes
DPWG	fluorouracil	Annotation of DPWG Guideline for fluorouracil and DPYD	yes	yes
DPWG	tegafur	Annotation of DPWG Guideline for tegafur and DPYD	yes	yes
RNPGx	capecitabine;fluorouracil	Annotation of RNPGx Guideline for capecitabine, fluorouracil and DPYD	yes	yes
SEFF/SEOM	capecitabine;fluorouracil;tegafur	Annotation of SEFF/SEOM Guideline for capecitabine, fluorouracil, tegafur and DPYD	yes	yes
AIOM	capecitabine;fluorouracil;tegafur	Annotation of AIOM Guideline for capecitabine, fluorouracil, tegafur and DPYD	yes	yes

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Nucleotide turnover

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.85	IC50	14	nM	ENILURACIL
7.37	IC50	43	nM	CHEMBL352944
7.05	IC50	89	nM	CHEMBL170188
7.01	IC50	97	nM	CHEMBL127691
6.70	IC50	200	nM	CHEMBL443038
6.66	IC50	220	nM	CHEMBL1173

PubChem BioAssay actives

6 with measured affinity, of 17 total; 6 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-ethynyl-1H-pyrimidine-2,4-dione	56039: Inhibitory activity against dihydropyrimidine dehydrogenase (DPD)	ic50	0.0140	uM
5-[(E)-2-phenylethenyl]-1H-pyrimidine-2,4-dione	56039: Inhibitory activity against dihydropyrimidine dehydrogenase (DPD)	ic50	0.0430	uM
5-ethenyl-1H-pyrimidine-2,4-dione	56039: Inhibitory activity against dihydropyrimidine dehydrogenase (DPD)	ic50	0.0890	uM
5-[(3-phenylmethoxyphenyl)methyl]-1H-pyrimidine-2,4-dione	56039: Inhibitory activity against dihydropyrimidine dehydrogenase (DPD)	ic50	0.0970	uM
2,4-dioxo-1H-pyrimidine-5-carbonitrile	56039: Inhibitory activity against dihydropyrimidine dehydrogenase (DPD)	ic50	0.2000	uM
5-iodo-1H-pyrimidine-2,4-dione	56039: Inhibitory activity against dihydropyrimidine dehydrogenase (DPD)	ic50	0.2200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Fluorouracil	decreases reaction, affects degradation, affects activity, decreases activity, increases activity (+11 more)	53
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
Cisplatin	increases expression, decreases activity, affects response to substance, affects reaction, affects cotreatment (+2 more)	6
gimeracil	decreases response to substance, increases degradation, increases metabolic processing, decreases activity, affects cotreatment (+3 more)	5
Benzo(a)pyrene	decreases expression	5
trichostatin A	increases expression, affects cotreatment	3
doxifluridine	affects expression, affects response to substance, decreases response to substance, affects cotreatment	3
Capecitabine	increases expression, affects response to substance, decreases response to substance	3
Air Pollutants	decreases expression, increases abundance	3
Aflatoxin B1	affects expression, decreases expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression, affects methylation	2
sodium arsenite	decreases expression, increases abundance	2
Irinotecan	decreases response to substance, decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Paclitaxel	affects expression, affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
propionaldehyde	increases expression	1
lead acetate	decreases expression	1
methylselenic acid	increases expression	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
heliotrine	decreases expression	1
tris(2-butoxyethyl) phosphate	decreases expression	1
sodium bichromate	decreases expression	1
sulforaphane	increases expression	1
cobaltous chloride	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 2 functional, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL664144	Functional	Stability to porcine renal DHP-I was determined	Synthesis and biological activity of 1beta-methyl-2-[5’-isoxazoloethenylpyrrolidin-3’-ylthio]carbapenems. — Bioorg Med Chem Lett
CHEMBL665825	Binding	Inhibitory activity against dihydropyrimidine dehydrogenase (DPD)	Design and synthesis of the tumor-activated prodrug of dihydropyrimidine dehydrogenase (DPD) inhibitor, RO0094889 for combination therapy with capecitabine. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer