TYMP

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): 549 total — 50 pathogenic, 46 likely-pathogenic (top 6% of genes corpus-wide)
• GTEx eGene: eQTL in 38 tissues, sQTL in 35 (q < 0.05)
• Phenotypes (HPO): 80
• Drug target: yes — 1 curated mechanism-of-action drug; 2 molecules with ChEMBL bioactivity
• Approved drugs (ChEMBL mechanism of action): 1 — Tipiracil Hydrochloride
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.52 (unconstrained)
• MANE Select transcript: NM_001953

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3148
Approved symbol	TYMP
Name	thymidine phosphorylase
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000025708
Ensembl biotype	protein_coding
OMIM	131222
Entrez	1890

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 37 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000252029

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 1, TSL 5: 2

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, ENST00001106447, ENST00001106448, ENST00001106449, ENST00001116113, ENST00001116114

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

Exon	Start	End
ENSE00000878931	50525752	50525918
ENSE00001356006	50529904	50530012
ENSE00003493281	50528512	50528610
ENSE00003499185	50529496	50529719
ENSE00003516855	50526576	50526738
ENSE00003530443	50526246	50526476
ENSE00003530451	50527165	50527283
ENSE00003551278	50526001	50526141
ENSE00003678267	50529136	50529338
ENSE00003690543	50527588	50527717

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.

Highest expression (Bgee): uterine tube, granulocyte, monocyte, mononuclear cell, leukocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TYMP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 38 tissues and its splicing (sQTL) in 35 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 73 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	sqtl	1.2e-59	-0.78	22:50525724:T:C
Whole Blood	eqtl	2.9e-45	+0.26	22:50532618:T:C
Cells Cultured fibroblasts	sqtl	2.5e-41	+1.19	22:50526017:A:T
Testis	sqtl	9.2e-39	+1.99	22:50531639:C:T
Cells EBV-transformed lymphocytes	sqtl	5.0e-38	+1.25	22:50526017:A:T
Adipose Subcutaneous	eqtl	1.0e-34	+0.42	22:50525724:T:C
Adipose Visceral Omentum	eqtl	9.3e-29	+0.41	22:50525724:T:C
Lung	sqtl	1.1e-28	-0.72	22:50525724:T:C
Thyroid	eqtl	1.1e-24	+0.34	22:50522740:A:G
Testis	eqtl	3.0e-24	+1.39	22:50531639:C:T
Skin Sun Exposed Lower leg	eqtl	1.8e-23	+0.32	22:50522740:A:G
Lung	eqtl	7.1e-23	+0.29	22:50525724:T:C
Esophagus Mucosa	eqtl	4.5e-22	+0.29	22:50532837:T:C
Colon Transverse	sqtl	5.8e-22	+0.96	22:50526017:A:T
Adipose Visceral Omentum	sqtl	1.4e-20	+0.77	22:50525724:T:C
Skin Not Sun Exposed Suprapubic	eqtl	5.8e-20	+0.30	22:50519091:G:A
Nerve Tibial	eqtl	1.5e-19	+0.25	22:50540091:C:T
Esophagus Mucosa	sqtl	1.1e-18	-0.82	22:50526017:A:T
Adipose Subcutaneous	sqtl	5.1e-18	+0.67	22:50525724:T:C
Muscle Skeletal	eqtl	5.2e-18	+0.36	22:50525724:T:C

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
194761	56.6001	1175
194762	0.1797	96
209536	0.1425	62
194759	0.1310	62
194760	0.1041	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.64	gold quality
granulocyte	CL:0000094	99.48	gold quality
monocyte	CL:0000576	99.43	gold quality
mononuclear cell	CL:0000842	99.13	gold quality
leukocyte	CL:0000738	99.09	gold quality
right lung	UBERON:0002167	98.29	gold quality
upper lobe of left lung	UBERON:0008952	98.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.75	gold quality
upper lobe of lung	UBERON:0008948	97.16	gold quality
spleen	UBERON:0002106	96.80	gold quality
apex of heart	UBERON:0002098	96.69	gold quality
omental fat pad	UBERON:0010414	96.47	gold quality
peritoneum	UBERON:0002358	96.41	gold quality
blood	UBERON:0000178	96.22	gold quality
right lobe of liver	UBERON:0001114	95.93	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.50	gold quality
gall bladder	UBERON:0002110	95.38	gold quality
minor salivary gland	UBERON:0001830	95.17	gold quality
right coronary artery	UBERON:0001625	95.01	gold quality
left uterine tube	UBERON:0001303	94.97	gold quality
lymph node	UBERON:0000029	94.56	gold quality
esophagus mucosa	UBERON:0002469	94.53	gold quality
vermiform appendix	UBERON:0001154	94.34	gold quality
right lobe of thyroid gland	UBERON:0001119	94.22	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.17	gold quality
lower esophagus mucosa	UBERON:0035834	94.14	gold quality
left adrenal gland cortex	UBERON:0035825	93.87	gold quality
left lobe of thyroid gland	UBERON:0001120	93.53	gold quality
left coronary artery	UBERON:0001626	93.42	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.29	gold quality
left adrenal gland	UBERON:0001234	93.17	gold quality
coronary artery	UBERON:0001621	92.89	gold quality
mucosa of stomach	UBERON:0001199	92.81	gold quality
esophagus	UBERON:0001043	92.60	gold quality
mucosa of transverse colon	UBERON:0004991	92.60	gold quality
right atrium auricular region	UBERON:0006631	92.36	gold quality
descending thoracic aorta	UBERON:0002345	92.28	gold quality
caecum	UBERON:0001153	92.25	gold quality
adrenal cortex	UBERON:0001235	92.21	gold quality
skin of abdomen	UBERON:0001416	92.13	gold quality
thyroid gland	UBERON:0002046	92.09	gold quality
small intestine	UBERON:0002108	92.05	gold quality
metanephros cortex	UBERON:0010533	91.94	gold quality
right adrenal gland	UBERON:0001233	91.79	gold quality
thoracic aorta	UBERON:0001515	91.79	gold quality
ascending aorta	UBERON:0001496	91.73	gold quality
mouth mucosa	UBERON:0003729	91.73	gold quality
saliva-secreting gland	UBERON:0001044	91.45	gold quality
transverse colon	UBERON:0001157	91.20	gold quality
skin of leg	UBERON:0001511	91.01	gold quality
tonsil	UBERON:0002372	90.77	gold quality
right adrenal gland cortex	UBERON:0035827	90.70	gold quality
lower esophagus	UBERON:0013473	90.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.56	gold quality
cardiac atrium	UBERON:0002081	90.47	gold quality
tibial nerve	UBERON:0001323	90.19	gold quality
colonic epithelium	UBERON:0000397	90.15	gold quality
body of stomach	UBERON:0001161	90.09	gold quality
endocervix	UBERON:0000458	89.87	gold quality
bone marrow cell	CL:0002092	89.85	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.74	gold quality
adrenal gland	UBERON:0002369	89.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.32	gold quality
adipose tissue	UBERON:0001013	88.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.75	gold quality
heart left ventricle	UBERON:0002084	88.20	gold quality
vagina	UBERON:0000996	88.09	gold quality
connective tissue	UBERON:0002384	88.03	gold quality
stomach	UBERON:0000945	87.89	gold quality
heart	UBERON:0000948	87.83	gold quality
ectocervix	UBERON:0012249	87.83	gold quality
aorta	UBERON:0000947	87.81	gold quality
cervix squamous epithelium	UBERON:0006922	87.81	gold quality
cardiac ventricle	UBERON:0002082	87.44	gold quality
spinal cord	UBERON:0002240	87.43	gold quality
zone of skin	UBERON:0000014	87.38	gold quality
penis	UBERON:0000989	87.26	gold quality
rectum	UBERON:0001052	87.24	gold quality
adenohypophysis	UBERON:0002196	86.99	gold quality
body of pancreas	UBERON:0001150	86.93	gold quality
intestine	UBERON:0000160	86.84	gold quality
nasal cavity mucosa	UBERON:0001826	86.75	gold quality
colon	UBERON:0001155	86.51	gold quality
nipple	UBERON:0002030	86.43	gold quality
lung	UBERON:0002048	86.42	gold quality
fundus of stomach	UBERON:0001160	86.12	gold quality
pericardium	UBERON:0002407	86.10	gold quality
sural nerve	UBERON:0015488	86.08	gold quality
trachea	UBERON:0003126	85.91	gold quality
large intestine	UBERON:0000059	85.66	gold quality
sigmoid colon	UBERON:0001159	85.59	gold quality
tibial artery	UBERON:0007610	84.95	gold quality
popliteal artery	UBERON:0002250	84.92	gold quality
gastrocnemius	UBERON:0001388	84.86	gold quality
liver	UBERON:0002107	84.86	gold quality
pancreas	UBERON:0001264	84.76	gold quality
decidua	UBERON:0002450	84.71	gold quality
body of uterus	UBERON:0009853	84.69	gold quality
lower lobe of lung	UBERON:0008949	84.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-149689	yes	2985.48
E-MTAB-8207	yes	2359.53
E-MTAB-8530	yes	2199.58
E-MTAB-9841	yes	2069.51
E-MTAB-6653	yes	1669.69
E-MTAB-8322	yes	1470.10
E-MTAB-6308	yes	1097.84
E-GEOD-84465	yes	1011.30
E-MTAB-8498	yes	963.33
E-MTAB-10662	yes	351.52
E-HCAD-4	yes	264.72
E-HCAD-1	yes	110.71
E-CURD-122	yes	90.68
E-MTAB-6701	yes	80.58
E-MTAB-8410	yes	56.85

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 64 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Appendix	tissue	73.3	medium
Medulla oblongata	tissue	50.2
Spleen	tissue	46.0	medium
Vagina	tissue	43.8	not detected
Salivary gland	tissue	33.5	not detected
Lung	tissue	30.2	medium
Lymph node	tissue	29.5	medium
Stomach 1	tissue	29.4	not detected
Choroid plexus	tissue	28.9
Spinal cord	tissue	25.8
Duodenum	tissue	24.6	not detected
Adipose tissue	tissue	22.5	not detected
Liver	tissue	22.3	not detected
Small intestine	tissue	21.5	not detected
Bone marrow	tissue	20.8	medium
Urinary bladder	tissue	18.1	low
Pituitary gland	tissue	17.8
Substantia nigra	tissue	17.7
Colon	tissue	17.3	not detected
Thymus	tissue	14.6
Placenta	tissue	14.4	not detected
Tonsil	tissue	14.4	medium
Locus coeruleus	tissue	14.2
Fallopian tube	tissue	12.6	not detected
Hippocampus	tissue	11.9	not detected
Skin 1	tissue	11.7	medium
Retrosplenial cortex	tissue	11.5
Esophagus	tissue	11.2	not detected
Skeletal muscle	tissue	10.1	not detected
Nucleus accumbens	tissue	9.8
Putamen	tissue	9.6
Smooth muscle	tissue	8.5	not detected
Gallbladder	tissue	6.8	not detected
Breast	tissue	6.6	not detected
Endometrium 1	tissue	6.5	low
Adrenal gland	tissue	6.2	not detected
Prostate	tissue	6.0	low
Seminal vesicle	tissue	5.3	low
Pancreas	tissue	5.0	not detected
Postcentral gyrus	tissue	4.6
Parathyroid gland	tissue	4.3	not detected
Cervix	tissue	4.2	not detected
Heart muscle	tissue	3.5	not detected
Kidney	tissue	3.5	low
Rectum	tissue	3.4	not detected
Thyroid gland	tissue	2.9	not detected
Testis	tissue	2.8	not detected
Tongue	tissue	1.5
Ovary	tissue	1.2	not detected
Pons	tissue	0.5
Epididymis	tissue	0.5	not detected
Cerebellum	tissue	0.4	not detected
Midbrain	tissue	0.3
Cerebral cortex	tissue	0.2	low
Frontal cortex	tissue	0.2
Amygdala	tissue	0.2
Thalamus	tissue	0.2
Corpus callosum	tissue	0.2
Retrosplenial and cingulate cortex	tissue	0.2
Basal ganglia	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 185; highest nTPM — Nucleus tractus solitarii (50.2), Blood vessel (50.1), Nucleus gracilis (49.6), Peritrigeminal nucleus (48.1), Anterior thalamic nucleus, ventral (41.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP3

Functional genomics

gnomAD constraint: pLI 7.12e-20, LOEUF 1.52, missense Z -3.44 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000252029 — one region, missense o/e 1.24. 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

Organism	Symbol	Gene ID
danio_rerio	tymp	ENSDARG00000099821
mus_musculus	Tymp	ENSMUSG00000022615
rattus_norvegicus	Tymp	ENSRNOG00000032394

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1920212) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal nucleotide metabolism	2
decreased liver enzyme/coenzyme activity	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Mycobacterium tuberculosis CDC1551	P9WFS0	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WFS1	100.0%	Diamond
Rhodopseudomonas palustris CGA009	Q6N2A3	99.6%	Diamond
Bradyrhizobium sp. ORS 278	A4YRL1	93.1%	Diamond
Bradyrhizobium sp. BTAi1	A5EG87	93.1%	Diamond
Methanosarcina mazei Go1	Q8Q0P9	91.5%	Diamond
Methanosarcina acetivorans C2A	Q8TL01	91.5%	Diamond
Rhodopseudomonas palustris BisA53	Q07J10	87.9%	Diamond
Rhodopseudomonas palustris BisB18	Q20Z21	87.9%	Diamond
Cupriavidus necator H16	Q0K3R9	84.7%	Diamond
Bradyrhizobium diazoefficiens USDA 110	Q89QK7	82.6%	Diamond
Cupriavidus pinatubonensis JMP134	Q46S32	76.4%	Diamond
Acidovorax sp. JS42	A1W631	76.3%	Diamond
Ralstonia pseudosolanacearum GMI1000	Q8Y2X7	74.6%	Diamond
Methanococcus aeolicus Nankai-3	A6UUN0	74.1%	Diamond
Polaromonas sp. JS666	Q12E97	70.5%	Diamond
Methanoculleus marisnigri JR1	A3CSY4	69.3%	Diamond
Methanoregula boonei 6A8	A7I5N0	69.3%	Diamond
Mycoplasmoides pneumoniae M129	P75052	67.5%	Diamond
Methanococcoides burtonii DSM 6242	Q12Z64	67.0%	Diamond
Archaeoglobus fulgidus DSM 4304	O28928	63.5%	Diamond
Methanothrix thermoacetophila PT	A0B6C9	62.9%	Diamond
Sphingopyxis alaskensis RB2256	Q1GQ92	59.8%	Diamond
Natronomonas pharaonis DSM 2160	Q3IP82	45.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
KLHDC7B-DT	ncRNA	105373098
KLHDC7B	protein-coding	113730
CIMAP1B	protein-coding	440836
SYCE3	protein-coding	644186
SCO2	protein-coding	9997
LINC03232	ncRNA	102724608
CPT1B	protein-coding	1375
CHKB-CPT1B	ncRNA	386593
NCAPH2	protein-coding	29781
MIOX	protein-coding	55586
LMF2	protein-coding	91289
ADM2	protein-coding	79924

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 ID	Names	Canonical?
P19971-1	1	yes
P19971-2	2

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

Domains & families (InterPro)

ID	Name	Type
IPR000053	Thymidine/pyrmidine_PPase	Family
IPR000312	Glycosyl_Trfase_fam3	Domain
IPR013102	PYNP_C	Domain
IPR017459	Glycosyl_Trfase_fam3_N_dom	Domain
IPR017872	Pyrmidine_PPase_CS	Conserved_site
IPR018090	Pyrmidine_PPas_bac/euk	Family
IPR035902	Nuc_phospho_transferase	Homologous_superfamily
IPR036320	Glycosyl_Trfase_fam3_N_dom_sf	Homologous_superfamily
IPR036566	PYNP-like_C_sf	Homologous_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.

Substrate	Km (mM)	Measurements
THYMIDINE	0.0017–9.3	23
PHOSPHATE	0.0006–2.3	7
THYMINE	0.0832–9.828	5
5-NITRO-2’-DEOXYURIDINE	0.16–0.23	4
1-(2’,6’-DIDEOXY-BETA-D-RIBOHEXAFURANOSYL)THYMIN	0.3–0.33	3
4-THIOTHYMIDINE	0.25–0.28	3
5’-DEOXYTHYMIDINE	0.4–32	3
2’-DEOXYURIDINE	0.32–0.735	2
3’-AMINO-3’-DEOXYTHYMIDINE	0.4	2
3’-DEOXY-2’,3’-DIDEHYDROTHYMIDINE	0.35	2
5’-AMINO-5’-DEOXYTHYMIDINE	0.4	2
5’-DEOXY-5-FLUOROURIDINE	0.2–1.72	2
URIDINE	0.275–47.6	2
1-(2’,6’-DIDEOXY-ALPHA-L-LYXO-HEXAFURANOSYL)THYM	0.35	1
1-(2’,6’-DIDEOXY-ALPHA-L-LYXOHEXAFURANOSYL)THYMI	0.35	1

Catalyzed reactions (Rhea)

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

UniProt features (64 total): helix 23, 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 by resolution:

PDB	Title	Method	Resolution (Å)
1UOU	Crystal structure of human thymidine phosphorylase in complex with a small molecule …	X-RAY DIFFRACTION	2.11
2J0F	Structural basis for non-competitive product inhibition in human thymidine phosphorylase: …	X-RAY DIFFRACTION	2.31
2WK6	Structural features of native human thymidine phosphorylase and in complex with …	X-RAY DIFFRACTION	2.5
2WK5	Structural features of native human thymidine phosphorylase and in complex with …	X-RAY DIFFRACTION	2.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19971-F1	92.82	0.90

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital disorders of metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; nuclear bodies; cytosol

Antibody reliability (HPA): IH enhanced · IF approved

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)

Position	Role
221	substrate
116	substrate
202	substrate
217	substrate

Post-translational modifications (1)

Type	Positions
Phosphothreonine	6

Mutagenesis-validated functional residues (3)

Position	Phenotype
199	abolishes catalytic activity.
199	reduced catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-1430728	Metabolism	—
R-HSA-15869	Metabolism of nucleotides	—
R-HSA-8956319	Nucleotide catabolism	—
R-HSA-8956321	Nucleotide salvage	—
R-HSA-73621	Pyrimidine catabolism	—
R-HSA-73614	Pyrimidine salvage	—

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 (10): 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), signal transduction (GO:0007165), nucleobase-containing small molecule metabolic process (GO:0055086), pyrimidine-containing compound metabolic process (GO:0072527), carbohydrate derivative metabolic process (GO:1901135)

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

4 top-level categories:

Category	Pathways
Metabolism of nucleotides	2
Nucleotide salvage	1
Nucleotide catabolism	1
Metabolism	1

GO top-level categories

31 GO namespaces:

Category	Terms
pyrimidine-containing compound metabolic process	2
metabolic process	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
nucleobase metabolic process	1
nucleoside metabolic process	1
response to chemical	1
taxis	1
cellular developmental process	1
pyrimidine deoxyribonucleoside monophosphate catabolic process	1
pyrimidine deoxyribonucleotide catabolic process	1
dTMP metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
nucleobase-containing compound metabolic process	1
small molecule metabolic process	1
hexosyltransferase activity	1
receptor ligand activity	1
pyrimidine-nucleoside phosphorylase activity	1
identical protein binding	1
protein dimerization activity	1
binding	1
pentosyltransferase activity	1
catalytic activity	1
transferase activity	1
glycosyltransferase activity	1
cytoplasm	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
pyrimidine nucleoside metabolic process	BP	direct assay
protein homodimerization activity	MF	direct assay
thymidine phosphorylase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,526 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TYMP	UPP1	Q16831	941
TYMP	TYMS	P04818	879
TYMP	POLG	P54098	814
TYMP	DGUOK	P78532	812
TYMP	NT5M	Q9NPB1	806
TYMP	TK2	O00142	798
TYMP	DPYD	Q12882	798
TYMP	UPP2	O95045	794
TYMP	RRM2B	Q7LG56	788
TYMP	SUCLA2	Q9P2R7	784
TYMP	UMPS	P11172	759
TYMP	MPV17	P39210	744
TYMP	TWNK	Q96RR1	737
TYMP	CDA	P32320	658
TYMP	TK1	P04183	630

IntAct

Human interaction partners of TYMP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
MESD	physical association	0.560	3
ZMYND12	physical association	0.560	3
KHDC4	association	0.530	1
ERBB2	physical association	0.370	1
CARD9	association	0.350	1
RPS6KL1	association	0.350	1

BioGRID (112 interactions; top human partners by supporting records): CCDC94 (Affinity Capture-MS; 3 records), GMCL1 (Affinity Capture-MS; 3 records), RBM24 (Affinity Capture-MS; 3 records), SUSD3 (Affinity Capture-MS; 3 records), ZSCAN20 (Affinity Capture-MS; 3 records), CDK15 (Affinity Capture-MS; 2 records), DDX19B (Affinity Capture-MS; 2 records), FAM60A (Affinity Capture-MS; 2 records), GPATCH2L (Affinity Capture-MS; 2 records), HSP90AA1 (Affinity Capture-Western; 2 records), KIAA0907 (Affinity Capture-MS; 2 records), PDE4DIP (Affinity Capture-MS; 2 records), TBC1D22B (Affinity Capture-MS; 2 records), AGPAT1 (Affinity Capture-MS), ANKRD36B (Affinity Capture-MS)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
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”

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ TYMP homodimer	1	TYMP

Disease & clinical

Genetic variants

Variant evidence for TYMP: 549 ClinVar records (96 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 23 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	50
Likely pathogenic	46
Uncertain significance	124
Likely benign	259
Benign	17

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 96 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
16653	NM_001953.5(TYMP):c.866A>C (p.Glu289Ala)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
223014	NM_001953.5(TYMP):c.112G>T (p.Glu38Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
964197	NM_001953.5(TYMP):c.417+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1407889	NM_001953.5(TYMP):c.199C>T (p.Gln67Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
16656	NM_001953.5(TYMP):c.665A>G (p.Lys222Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	5
223024	NM_001953.5(TYMP):c.340G>A (p.Asp114Asn)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	5
223031	NM_001953.5(TYMP):c.518T>G (p.Met173Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
223046	NM_001953.5(TYMP):c.893G>A (p.Gly298Asp)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
2679401	NM_001953.5(TYMP):c.418-1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
223004	NM_001953.5(TYMP):c.647C>T (p.Ala216Val)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
223071	NM_001953.5(TYMP):c.1301-1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1325321	NM_001953.5(TYMP):c.809T>C (p.Leu270Pro)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1509692	NM_001953.5(TYMP):c.214+1G>T	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2679397	NM_001953.5(TYMP):c.532_548dup (p.Cys183fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2901099	NM_001953.5(TYMP):c.391C>T (p.Pro131Ser)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2

Per-variant reference — Sugi Variant

Explore TYMP’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 15 predictions of 66):

Position(s)	Effect	Δscore	Sites
22:50529902–50529903	donor_loss	0.9000	5
22:50529902	donor_loss	0.8900
22:50529904	donor_loss	0.8700
22:50529904	donor_loss	0.8600
22:50529901	donor_loss	0.8100
22:50529904	donor_loss	0.7800
22:50529901	donor_loss	0.7600
22:50529905	donor_loss	0.6800	2
22:50529905	donor_loss	0.6200
22:50529742	acceptor_gain	0.6000

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Head and Neck Squamous Cell Carcinoma)

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
mitochondrial DNA depletion syndrome 1	Definitive	Autosomal recessive	3
mitochondrial neurogastrointestinal encephalomyopathy	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (19 panels, 19 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

19 panels:

Panel	Rating
Gastrointestinal neuromuscular disorders	green
Hereditary neuropathy	green
Hereditary neuropathy or pain disorder	green
Hypotonic infant	green
Inherited white matter disorders	green
Leukodystrophy, adult onset	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Mitochondrial DNA maintenance disorder	green
Mitochondrial disorders	green
Mitochondrial neurogastrointestinal encephalopathy	green
Other rare neuromuscular disorders	green
Paediatric disorders	green
Paediatric pseudo-obstruction syndrome	green
Possible mitochondrial disorder, nuclear genes	green
Rhabdomyolysis and metabolic muscle disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green
White matter disorders and cerebral calcification - childhood onset	green

Mondo (2): mitochondrial DNA depletion syndrome 1 (MONDO:0011283), mitochondrial neurogastrointestinal encephalomyopathy (MONDO:0017575)

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

HPO phenotypes

showing 60 of 80 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000044	Hypogonadotropic hypogonadism
HP:0000407	Sensorineural hearing impairment
HP:0000508	Ptosis
HP:0000544	External ophthalmoplegia
HP:0000590	Progressive external ophthalmoplegia
HP:0000597	Ophthalmoparesis
HP:0000651	Diplopia
HP:0000726	Dementia
HP:0000815	Hypergonadotropic hypogonadism
HP:0001155	Abnormality of the hand
HP:0001249	Intellectual disability
HP:0001284	Areflexia
HP:0001394	Cirrhosis
HP:0001403	Macrovesicular hepatic steatosis
HP:0001533	Slender build
HP:0001824	Weight loss
HP:0001903	Anemia
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002015	Dysphagia
HP:0002018	Nausea
HP:0002019	Constipation
HP:0002020	Gastroesophageal reflux
HP:0002024	Malabsorption
HP:0002027	Abdominal pain
HP:0002253	Colonic diverticula
HP:0002254	Intermittent diarrhea
HP:0002352	Leukoencephalopathy
HP:0002460	Distal muscle weakness
HP:0002500	Abnormal cerebral white matter morphology
HP:0002522	Areflexia of lower limbs
HP:0002578	Gastroparesis
HP:0002579	Gastrointestinal dysmotility
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0002922	Increased CSF protein concentration
HP:0002936	Distal sensory impairment
HP:0003128	Lactic acidosis
HP:0003199	Decreased muscle mass
HP:0003200	Ragged-red muscle fibers
HP:0003270	Abdominal distention
HP:0003348	Hyperalaninemia
HP:0003387	Decreased number of large peripheral myelinated nerve fibers
HP:0003388	Easy fatigability
HP:0003401	Paresthesia
HP:0003431	Decreased motor nerve conduction velocity
HP:0003448	Decreased sensory nerve conduction velocity
HP:0003477	Peripheral axonal neuropathy
HP:0003548	Subsarcolemmal accumulations of abnormally shaped mitochondria
HP:0003621	Juvenile onset
HP:0003676	Progressive
HP:0003688	Cytochrome C oxidase-negative muscle fibers
HP:0003689	Multiple mitochondrial DNA deletions
HP:0003693	Distal amyotrophy
HP:0003737	Mitochondrial myopathy
HP:0004326	Cachexia
HP:0004389	Intestinal pseudo-obstruction
HP:0004395	Malnutrition
HP:0004396	Poor appetite
HP:0007103	Hypointensity of cerebral white matter on MRI

GWAS associations

23 associations:

Study	Trait	p-value
GCST004602_155	Mean corpuscular volume	2e-129
GCST90002403_103	Red blood cell count	7e-102
GCST004630_174	Mean corpuscular hemoglobin	3e-94
GCST90002397_424	Mean spheric corpuscular volume	3e-93
GCST90002396_420	Mean reticulocyte volume	5e-76
GCST90002405_175	Reticulocyte count	1e-62
GCST90002392_731	Mean corpuscular volume	2e-57
GCST004601_212	Red blood cell count	2e-43
GCST005993_67	Mean corpuscular hemoglobin	1e-40
GCST90002390_78	Mean corpuscular hemoglobin	1e-35
GCST90002406_181	Reticulocyte fraction of red cells	1e-33
GCST90002385_119	High light scatter reticulocyte count	8e-29
GCST001765_11	Red blood cell traits	5e-23
GCST004621_111	Red cell distribution width	3e-19
GCST004622_108	Reticulocyte count	3e-16
GCST000503_14	Mean corpuscular volume	1e-15
GCST90002386_82	High light scatter reticulocyte percentage of red cells	1e-14
GCST90002394_13	Monocyte percentage of white cells	2e-13
GCST006585_889	Blood protein levels	2e-11
GCST004146_29	Chronic lymphocytic leukemia	3e-9
GCST90002397_423	Mean spheric corpuscular volume	3e-9
GCST90002396_419	Mean reticulocyte volume	6e-9
GCST000587_8	Mean corpuscular hemoglobin	4e-8

EFO canonical traits (from GWAS)

7 canonical traits:

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3106 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the TYMP protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
TIPIRACIL HYDROCHLORIDE	Small molecule	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,158 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL235668	TIPIRACIL	4	3,102
CHEMBL65375	TIPIRACIL HYDROCHLORIDE	4	1,056

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs11479	Toxicity	3	capecitabine;fluorouracil	Neoplasms

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11479	SCO2, TYMP	3	5.50	1	capecitabine;fluorouracil

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

2 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs11479	capecitabine, fluorouracil	Dosage	Genotypes AA + AG is associated with dose of capecitabine or fluorouracil in people with Colorectal Neoplasms as compared to genotype GG.	PMID:24167597
rs11479	capecitabine, fluorouracil	Toxicity	Genotypes AA + AG is associated with increased risk of Drug Toxicity when treated with capecitabine or fluorouracil in people with Colorectal Neoplasms as compared to genotype GG.	PMID:24167597

Binding affinities (BindingDB)

162 measured of 186 human assays (223 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
6-(4-Phenyl-butylamino)-1H-pyrimidine-2,4-dione	KI	0.58 nM
2-Amino-1-(5-bromo-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-ylmethyl)-3H-imidazol-1-ium; chloride	IC50	1.9 nM
6-Phenethylamino-1H-pyrimidine-2,4-dione	KI	11 nM
5-fluoro-6-[(2-aminoimidazol-1-yl)methyl]uracil	KI	17 nM
1-(5-Chloro-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-ylmethyl)-pyrrolidin-2-ylidene-ammonium	IC50	20 nM
CHEMBL4129617	IC50	20 nM
2-Amino-1-(5-chloro-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-ylmethyl)-3H-imidazol-1-ium; chloride	IC50	21 nM
MA-1	IC50	35 nM
CHEMBL4293861	IC50	120 nM
6-chloro-5-(cyclopent-1-en-1-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	200 nM
((2R,3aR,4R,6R,6aR)-4-(hydroxymethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-tetrahydrofuro[3,4-d][1,3]dioxol-2-yl)methylphosphonic acid	KI	236 nM
(1-fluoro-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propan-2-yloxy)methylphosphonic acid	KI	236 nM
(1-hydroxy-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propan-2-yloxy)methylphosphonic acid	KI	236 nM
(1-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propan-2-yloxy)methylphosphonic acid	KI	236 nM
(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy)methylphosphonic acid	KI	236 nM
8-(5-bromo-3-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2,6-dioxo-2,3-dihydropyrimidin-1(6H)-yl)octylphosphonic acid	KI	236 nM
6-chloro-5-(thiophen-2-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	280 nM
1,7-Dihydro-pyrrolo[2,3-d]pyrimidine-2,4-dione	IC50	300 nM
CHEMBL3087264	IC50	350 nM
6-chloro-5-phenyl-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	400 nM
6-chloro-5-[(1E)-pent-1-en-1-yl]-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	410 nM
6-chloro-5-(cyclohex-1-en-1-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	420 nM
6-chloro-5-[(2E)-pent-2-en-3-yl]-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	490 nM
6-fluoro-5-phenyl-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	500 nM
5-[(1E)-but-1-en-1-yl]-6-chloro-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	630 nM
6-chloro-5-(4-fluorophenyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	710 nM
CHEMBL4469338	IC50	1000 nM
5-butyl-6-chloro-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	1030 nM
((2S,3aR,4S,6R,6aR)-4-(hydroxymethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hexahydrofuro[3,4-b]furan-2-yl)methylphosphonic acid	KI	1050 nM
6-chloro-5-heptyl-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	1060 nM
6-chloro-5-[(1E)-prop-1-en-1-yl]-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	1170 nM
CHEMBL4468378	IC50	1200 nM
6-bromo-5-phenyl-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	1210 nM
6-amino-5-bromo-1,2,3,4-tetrahydropyrimidine-2,4-dione	IC50	1300 nM
CHEMBL4291353	IC50	1400 nM
6-chloro-5-(3,5-dimethylphenyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	1740 nM
6-chloro-5-hexyl-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	1830 nM
1-(cyclopropyl)methyl-5’-O-tritylinosine	IC50	2300 nM
CHEMBL4290057	IC50	2700 nM
CHEMBL2418061	IC50	2950 nM
6-chloro-5-(pyridin-3-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	3010 nM
6-chloro-5-(prop-1-en-2-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	3340 nM
CHEMBL4278709	IC50	3400 nM
6-chloro-5-pentyl-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	3670 nM
CHEMBL3233329	IC50	3820 nM
CHEMBL3233340	IC50	4290 nM
1-(cyclohexyl)methyl-5’-O-tritylinosine	IC50	4400 nM
CHEMBL3233339	IC50	4460 nM
5’-O-[(4-chlorophenyl)-1,1-(diphenyl)methyl]inosine	IC50	4500 nM
6-chloro-5-(naphthalen-1-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dione	KI	4590 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.89	Ki	1.3	nM	TIPIRACIL
8.72	IC50	1.9	nM	CHEMBL65986
8.68	Ki	2.1	nM	TIPIRACIL
8.30	Ki	5	nM	TIPIRACIL
7.77	Ki	17	nM	TIPIRACIL HYDROCHLORIDE
7.77	Ki	17	nM	CHEMBL1080896
7.77	Ki	17	nM	TIPIRACIL
7.72	IC50	19	nM	CHEMBL122679
7.70	Ki	20	nM	TIPIRACIL HYDROCHLORIDE
7.70	IC50	20	nM	CHEMBL4129617
7.70	Ki	20	nM	TIPIRACIL
7.70	IC50	20	nM	CHEMBL65986
7.70	IC50	20	nM	TIPIRACIL
7.70	IC50	20	nM	TIPIRACIL HYDROCHLORIDE
7.68	IC50	21	nM	CHEMBL66531
7.64	IC50	23	nM	TIPIRACIL HYDROCHLORIDE
7.52	IC50	30	nM	TIPIRACIL HYDROCHLORIDE
7.46	IC50	35	nM	TIPIRACIL HYDROCHLORIDE
7.46	IC50	35	nM	CHEMBL64909
7.46	IC50	35	nM	TIPIRACIL
7.31	IC50	49	nM	CHEMBL193667
7.00	IC50	100	nM	CHEMBL194335
6.92	IC50	120	nM	CHEMBL4293861
6.92	IC50	120	nM	CHEMBL4455140
6.70	Ki	200	nM	CHEMBL234998
6.63	Ki	236	nM	CHEMBL374140
6.63	Ki	236	nM	CHEMBL592394
6.63	Ki	236	nM	CHEMBL599022
6.63	Ki	236	nM	CHEMBL599755
6.63	Ki	236	nM	CHEMBL401998
6.63	Ki	236	nM	CHEMBL597717
6.55	Ki	280	nM	CHEMBL397364
6.54	Ki	290	nM	CHEMBL234998
6.46	IC50	350	nM	CHEMBL3087264
6.40	Ki	400	nM	CHEMBL235001
6.39	Ki	410	nM	CHEMBL238218
6.38	Ki	420	nM	CHEMBL234999
6.37	Ki	430	nM	CHEMBL235001
6.33	Ki	470	nM	CHEMBL395907
6.31	Ki	490	nM	CHEMBL394454
6.30	Ki	500	nM	CHEMBL395907
6.27	Ki	540	nM	CHEMBL397364
6.25	IC50	560	nM	CHEMBL303346
6.20	Ki	630	nM	CHEMBL396865
6.15	Ki	710	nM	CHEMBL235875
6.12	Ki	750	nM	CHEMBL234999
6.11	Ki	770	nM	CHEMBL87371
6.04	Ki	910	nM	CHEMBL238218
6.04	Ki	920	nM	CHEMBL396865
6.04	Ki	910	nM	CHEMBL394454

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.

Compound	Assay	Type	Value	Unit
5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	0.0013	uM
6-[(2-amino-1H-imidazol-3-ium-3-yl)methyl]-5-bromo-1H-pyrimidine-2,4-dione chloride	213303: Compound was evaluated for its inhibitory activity against recombinant purified Escherichia coli Thymidine Phosphorylase	ic50	0.0019	uM
6-[(2-aminoimidazol-1-yl)methyl]-5-fluoro-1H-pyrimidine-2,4-dione	465576: Inhibition of human thymidine phosphorylase	ki	0.0170	uM
5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]-1H-pyrimidine-2,4-dione;hydrochloride	456853: Inhibition of human recombinant thymidine phosphorylase	ki	0.0170	uM
6-[(2-amino-1H-imidazol-3-ium-3-yl)methyl]-5-bromo-1H-pyrimidine-2,4-dione	211058: Inhibitory activity against Escherichia coli thymidine phosphorylase	ic50	0.0190	uM
6-[(2-amino-4,5-dihydroimidazol-1-yl)methyl]-5-chloro-1H-pyrimidine-2,4-dione;hydrobromide	1497671: Inhibition of thymidine phosphorylase (unknown origin)	ic50	0.0200	uM
6-[(2-amino-1H-imidazol-3-ium-3-yl)methyl]-5-chloro-1H-pyrimidine-2,4-dione chloride	213303: Compound was evaluated for its inhibitory activity against recombinant purified Escherichia coli Thymidine Phosphorylase	ic50	0.0210	uM
6-amino-5-bromo-1H-pyrimidine-2,4-dione	1623806: Inhibition of thymidine phosphorylase (unknown origin)	ic50	0.0350	uM
6-[(2-amino-1H-imidazol-3-ium-3-yl)methyl]-5-chloro-1H-pyrimidine-2,4-dione	241061: Inhibitory concentration against human thymidine phosphorylase	ic50	0.0490	uM
6-[(2-amino-1H-imidazol-3-ium-3-yl)methyl]-1H-pyrimidine-2,4-dione	241061: Inhibitory concentration against human thymidine phosphorylase	ic50	0.1000	uM
1-[(Z)-C-(3,4-dichlorophenyl)-N-hydroxycarbonimidoyl]-6-methylpyrimidine-2,4-dione	1402656: Inhibition of thymidine phosphorylase (unknown origin) using thymidine as substrate after 1 hr by spectrophotometric analysis	ic50	0.1200	uM
6-[(1,3-dihydroxypropan-2-ylamino)methyl]-5-iodo-1H-pyrimidine-2,4-dione	1623718: Inhibition of recombinant human thymidine phosphorylase expressed in Escherichia coli Rosetta (DE3) cells using thymidine as substrate after 1 min by UV/visible spectrophotometry	ic50	0.1200	uM
6-chloro-5-(cyclopenten-1-yl)-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	0.2000	uM
[(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 acid	274782: Inhibition of human thymidine phosphorylase by continuous spectrophotometric assay	ki	0.2360	uM
2-(5-methyl-2,4-dioxopyrimidin-1-yl)ethoxymethylphosphonic acid	456853: Inhibition of human recombinant thymidine phosphorylase	ki	0.2360	uM
[1-fluoro-3-(5-methyl-2,4-dioxopyrimidin-1-yl)propan-2-yl]oxymethylphosphonic acid	456853: Inhibition of human recombinant thymidine phosphorylase	ki	0.2360	uM
1-(5-methyl-2,4-dioxopyrimidin-1-yl)propan-2-yloxymethylphosphonic acid	456853: Inhibition of human recombinant thymidine phosphorylase	ki	0.2360	uM
8-[5-bromo-3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,6-dioxopyrimidin-1-yl]octylphosphonic acid	456853: Inhibition of human recombinant thymidine phosphorylase	ki	0.2360	uM
[1-hydroxy-3-(5-methyl-2,4-dioxopyrimidin-1-yl)propan-2-yl]oxymethylphosphonic acid	456853: Inhibition of human recombinant thymidine phosphorylase	ki	0.2360	uM
6-chloro-5-thiophen-2-yl-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	0.2800	uM
(5-chloro-2,4-dioxo-1H-pyrimidin-6-yl)methyl carbamimidothioate;hydrochloride	1055575: Inhibition of human thymidine phosphorylase	ic50	0.3500	uM
6-chloro-5-phenyl-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	0.4000	uM
6-chloro-5-[(E)-pent-1-enyl]-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	0.4100	uM
6-chloro-5-(cyclohexen-1-yl)-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	0.4200	uM
6-fluoro-5-phenyl-1H-pyrimidine-2,4-dione	303487: Inhibition of human placental thymidine phosphorylase	ki	0.4700	uM
6-chloro-5-[(E)-pent-2-en-3-yl]-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	0.4900	uM
6-[(2-amino-1H-imidazol-3-ium-3-yl)methyl]-1H-pyrimidine-2,4-dione chloride	213303: Compound was evaluated for its inhibitory activity against recombinant purified Escherichia coli Thymidine Phosphorylase	ic50	0.5600	uM
5-[(E)-but-1-enyl]-6-chloro-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	0.6300	uM
6-chloro-5-(4-fluorophenyl)-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	0.7100	uM
(E)-3-[2-(3,4-dichlorophenyl)phenyl]-N-thiophen-2-ylsulfonylprop-2-enamide	161213: Inhibitory constant against Prostanoid TP receptor	ki	0.7700	uM
5-chloro-6-[(1,3-dihydroxypropan-2-ylamino)methyl]-1H-pyrimidine-2,4-dione	1623718: Inhibition of recombinant human thymidine phosphorylase expressed in Escherichia coli Rosetta (DE3) cells using thymidine as substrate after 1 min by UV/visible spectrophotometry	ic50	1.0000	uM
5-butyl-6-chloro-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	1.0300	uM
[(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 acid	274782: Inhibition of human thymidine phosphorylase by continuous spectrophotometric assay	ki	1.0500	uM
6-chloro-5-heptyl-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	1.0600	uM
6-chloro-5-[(E)-prop-1-enyl]-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	1.1700	uM
6-[(2-hydroxyethylamino)methyl]-5-iodo-1H-pyrimidine-2,4-dione	1623718: Inhibition of recombinant human thymidine phosphorylase expressed in Escherichia coli Rosetta (DE3) cells using thymidine as substrate after 1 min by UV/visible spectrophotometry	ic50	1.2000	uM
6-bromo-5-phenyl-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	1.2100	uM
6-chloro-5-(3,5-dimethylphenyl)-1H-pyrimidine-2,4-dione	303487: Inhibition of human placental thymidine phosphorylase	ki	1.2700	uM
1-[(Z)-C-(4-chlorophenyl)-N-hydroxycarbonimidoyl]-6-methylpyrimidine-2,4-dione	1402656: Inhibition of thymidine phosphorylase (unknown origin) using thymidine as substrate after 1 hr by spectrophotometric analysis	ic50	1.4000	uM
6-[(2-nitroimidazol-1-yl)methyl]-1H-pyrimidine-2,4-dione	213303: Compound was evaluated for its inhibitory activity against recombinant purified Escherichia coli Thymidine Phosphorylase	ic50	1.6000	uM
[4-oxo-2-sulfanylidene-8-[[4-(trifluoromethyl)phenyl]methyl]-6H-pyrazolo[1,5-a][1,3,5]triazin-7-yl]thiourea	1126859: Mixed-type inhibition of human recombinant thymidine phosphorylase expressed in Escherichia coli assessed as conversion of thymidide to thymine by Lineweaver-Burk plot analysis	ki	1.6500	uM
7-(3,4-dichlorophenyl)-2-sulfanylidene-6H-pyrazolo[1,5-a][1,3,5]triazin-4-one	1126859: Mixed-type inhibition of human recombinant thymidine phosphorylase expressed in Escherichia coli assessed as conversion of thymidide to thymine by Lineweaver-Burk plot analysis	ki	1.7700	uM
6-chloro-5-hexyl-1H-pyrimidine-2,4-dione	303487: Inhibition of human placental thymidine phosphorylase	ki	1.7900	uM
5-bromo-6-[2-[(5-bromo-2,4-dioxo-1H-pyrimidin-6-yl)amino]ethylamino]-1H-pyrimidine-2,4-dione;dihydrochloride	261612: Inhibition of human TP purified from placenta	ic50	2.2000	uM
1-(cyclopropylmethyl)-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(trityloxymethyl)oxolan-2-yl]purin-6-one	270128: Inhibition of human TPase in presence of 100 uM thymidine	ic50	2.3000	uM
1-[(Z)-C-(4-bromophenyl)-N-hydroxycarbonimidoyl]-6-methylpyrimidine-2,4-dione	1402656: Inhibition of thymidine phosphorylase (unknown origin) using thymidine as substrate after 1 hr by spectrophotometric analysis	ic50	2.7000	uM
2-[(3,4-dichlorophenyl)methyl]-5-sulfanylidene-1H-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-one	765733: Inhibition of human recombinant thymidine phosphorylase expressed in Escherichia coli using thymidine as substrate after 4 to 20 mins by spectrophotometry	ic50	2.9500	uM
6-chloro-5-pyridin-3-yl-1H-pyrimidine-2,4-dione	1797938: Enzyme Inhibition Assay from Article 10.1021/jm070644i: “Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase.”	ki	3.0100	uM
6-chloro-5-pyridin-3-yl-1H-pyrimidine-2,4-dione;hydrochloride	303486: Inhibition of human recombinant thymidine phosphorylase expressed in V79 cells	ki	3.0100	uM
6-chloro-5-pentyl-1H-pyrimidine-2,4-dione	303487: Inhibition of human placental thymidine phosphorylase	ki	3.0900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Fluorouracil	affects cotreatment, decreases reaction, decreases stability, decreases expression, increases expression (+2 more)	8
Cisplatin	affects cotreatment, decreases reaction, decreases degradation, decreases expression, increases activity (+4 more)	7
doxifluridine	affects cotreatment, decreases activity, affects expression, increases reaction, increases metabolic processing (+4 more)	6
bisphenol A	affects expression, decreases expression, increases expression	3
Air Pollutants	increases abundance, decreases expression, affects expression	3
Paclitaxel	increases expression, decreases reaction, increases cleavage, increases phosphorylation, increases reaction (+2 more)	3
sodium arsenite	increases expression	2
acetylleucyl-leucyl-norleucinal	affects cotreatment, decreases reaction, decreases stability, increases expression	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	affects cotreatment, decreases reaction, decreases stability, increases expression	2
Aspirin	increases expression, decreases expression, decreases reaction	2
Benzo(a)pyrene	increases expression, increases methylation	2
Dactinomycin	decreases reaction, increases expression, increases reaction	2
Formaldehyde	increases expression	2
Testosterone	affects cotreatment, increases expression, decreases expression	2
Thymidine	increases secretion, increases phosphorylation, affects cotreatment, decreases reaction, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Mitomycin	affects response to substance, decreases expression, affects cotreatment	2
Cadmium Chloride	decreases expression	2
GSK-J4	decreases expression	1
urushiol	increases expression	1
lasiocarpine	increases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
salinomycin	increases expression, increases reaction, affects cotreatment, decreases expression, decreases response to substance (+1 more)	1
ferrous chloride	decreases expression	1
nickel sulfate	affects cotreatment, decreases expression	1
2-deoxyribose 1-phosphate	increases abundance	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
FEC protocol	affects cotreatment, increases expression	1

ChEMBL screening assays

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

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1066239	Binding	Inhibition of human recombinant thymidine phosphorylase	Structural 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*
CHEMBL813688	Functional	In vitro percent of phosphorolysis after incubation with Escherichia coli thymidine phosphorylase for 10 min at 37 degree C; ND=Not determined	Synthesis, 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):

Cellosaurus	Name	Category	Sex
CVCL_9645	MKN45/TP	Cancer cell line	Female
CVCL_9659	YCC-3/TP	Cancer cell line	Male
CVCL_B2K2	Abcam HeLa TYMP KO	Cancer cell line	Female
CVCL_D2ZD	GM26124	Transformed cell line	Female
CVCL_S977	PC9-DPE2	Cancer cell line	Male
CVCL_W867	KU2-TP15	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

13 trials:

NCT	Phase	Status	Title
NCT02171104	Phase 2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT02427178	Phase 1	WITHDRAWN	MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study
NCT01694953	Not specified	RECRUITING	The Natural History Study of Mitochondrial NeuroGastroIntestinal Encephalopathy (MNGIE)
NCT01803906	Not specified	ENROLLING_BY_INVITATION	Tissue Sample Study for Mitochondrial Disorders
NCT04245917	Not specified	SUSPENDED	Natural History Study of MNGIE
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders
NCT05658822	Not specified	UNKNOWN	Digestive Dysmotility in Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT07627217	Not specified	RECRUITING	MNGIE Natural History Study
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT03662672	Not specified	COMPLETED	Rib Raising for Post-operative Ileus
NCT04981262	Not specified	COMPLETED	Improved Quality of Life in Children With Intestinal Failure
NCT06020365	Not specified	COMPLETED	Investigation of Fecal Microbiota Transplant in Chronic Intestinal Pseudo-obstruction Patients
NCT06711107	Not specified	ACTIVE_NOT_RECRUITING	Predicting NOM Failure in Bowel Obstruction

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TYMP across ~30M SureChEMBL compounds — explore on Sugi Predict.