UMPS

Summary

UMPS (uridine monophosphate synthetase, HGNC:12563) is a protein-coding gene on chromosome 3q21.2, encoding Uridine 5’-monophosphate synthase (P11172). Bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT), which converts orotate to orotidine-5’-monophosphate (OMP), and orotidine-5’-monophosphate decarboxylase (ODC), the terminal enzymatic reaction that de…. It is a selective cancer dependency (DepMap: 45.9% of cell lines).

This gene encodes a uridine 5’-monophosphate synthase. The encoded protein is a bifunctional enzyme that catalyzes the final two steps of the de novo pyrimidine biosynthetic pathway. The first reaction is carried out by the N-terminal enzyme orotate phosphoribosyltransferase which converts orotic acid to orotidine-5’-monophosphate. The terminal reaction is carried out by the C-terminal enzyme OMP decarboxylase which converts orotidine-5’-monophosphate to uridine monophosphate. Defects in this gene are the cause of hereditary orotic aciduria. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 7372 — RefSeq curated summary.

At a glance

• Gene–disease (curated): orotic aciduria (Definitive, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 293 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 27
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 45.9% of screened cell lines
• MANE Select transcript: NM_000373

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12563
Approved symbol	UMPS
Name	uridine monophosphate synthetase
Location	3q21.2
Locus type	gene with protein product
Status	Approved
Aliases	OPRT, ODC
Ensembl gene	ENSG00000114491
Ensembl biotype	protein_coding
OMIM	613891
Entrez	7372

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 8 protein_coding, 6 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000232607, ENST00000460034, ENST00000462091, ENST00000467167, ENST00000474588, ENST00000479719, ENST00000487622, ENST00000495751, ENST00000497791, ENST00000498715, ENST00000628619, ENST00000876661, ENST00000876662, ENST00000876663, ENST00000876664, ENST00000924427, ENST00000947786

RefSeq mRNA: 1 — MANE Select: NM_000373 NM_000373

CCDS: CCDS3029

Canonical transcript exons

ENST00000232607 — 6 exons

Exon	Start	End
ENSE00001382696	124743915	124749273
ENSE00003478708	124740024	124740199
ENSE00003566655	124735093	124735246
ENSE00003635320	124742152	124742266
ENSE00003663863	124737568	124738239
ENSE00003693247	124730452	124730627

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 91.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.7133 / max 509.6753, expressed in 1794 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38325	23.7133	1794

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	91.23	gold quality
ventricular zone	UBERON:0003053	89.34	gold quality
ganglionic eminence	UBERON:0004023	89.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.24	gold quality
islet of Langerhans	UBERON:0000006	89.07	gold quality
calcaneal tendon	UBERON:0003701	88.80	gold quality
right lobe of liver	UBERON:0001114	88.69	gold quality
embryo	UBERON:0000922	88.47	gold quality
mucosa of transverse colon	UBERON:0004991	88.42	gold quality
gingival epithelium	UBERON:0001949	88.08	gold quality
stromal cell of endometrium	CL:0002255	87.98	gold quality
gingiva	UBERON:0001828	87.56	gold quality
liver	UBERON:0002107	87.13	gold quality
esophagus mucosa	UBERON:0002469	87.02	gold quality
right adrenal gland	UBERON:0001233	86.99	gold quality
esophagus squamous epithelium	UBERON:0006920	86.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.67	gold quality
squamous epithelium	UBERON:0006914	86.40	gold quality
left adrenal gland	UBERON:0001234	86.33	gold quality
rectum	UBERON:0001052	86.32	gold quality
right adrenal gland cortex	UBERON:0035827	86.32	gold quality
hair follicle	UBERON:0002073	86.26	gold quality
left adrenal gland cortex	UBERON:0035825	85.98	gold quality
adrenal gland	UBERON:0002369	85.93	gold quality
pancreas	UBERON:0001264	85.81	gold quality
tendon	UBERON:0000043	85.48	gold quality
placenta	UBERON:0001987	85.27	gold quality
body of pancreas	UBERON:0001150	84.87	gold quality
colonic epithelium	UBERON:0000397	84.85	gold quality
palpebral conjunctiva	UBERON:0001812	84.83	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.92
E-MTAB-4850	no	545.18
E-MTAB-6142	no	291.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

149 targeting UMPS, 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-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 45.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 30)

• expression of OPRT gene and the OPRT/dihydropyrimidine dehydrogenase ratio might be useful as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer (PMID:14562021)
• thymidylate synthase and orotate phosphoribosyl transferase, but not dihydropyrimidine dehydrogenase, are more highly expressed in prostate cancer than in benign prostatic hyperplasia (PMID:15999119)
• orotate phosphoribosyl transferase has a role in lymph node metastasis of gastric cancer (PMID:16142362)
• The investigated SNPs of OPRT may have no major influence on 5-FU sensitivity. (PMID:16328050)
• The OPRT Gly213Ala polymorphism seems to be a useful marker for predicting toxicity to bolus 5-FU chemotherapy. (PMID:16818689)
• Overexpression of the OPRT gene plays an important role in the antiproliferative effect of 5-FU. (PMID:17237621)
• High expression of OPRT is associated with the response to adjuvant chemotherapy in human pancreatic cancer (PMID:17549346)
• data suggest that OPRT is involved in early events of pancreatic and gallbladder carcinogenesis and invasion of hepatocellular carcinomas (PMID:17607371)
• decreased the sensitivities of the cultured tumor cells to 5-FU. These results suggest that the OPRT expression level in tumors is an additional determinant of the efficacy of 5-FU. (PMID:17854773)
• OPRT activity levels in tumor tissue may be prognostic factor for survival in colorectal carcinoma with radical resection and 5-FU chemotherapy;postoperative survival was significantly better in patients with high OPRT activity (PMID:18597678)
• determination of OPRT levels in gastric carcinoma tissue enables to predict the response to S-1-based neoadjuvant/adjuvant chemotherapy (PMID:18633253)
• orotate phosphoribosyltransferase is involved in the invasion and metastasis of colorectal carcinoma (PMID:18949394)
• decreased activity of OPRT plays an important role in the acquired resistance of gastric cancer cells towards 5-FU (PMID:19020740)
• head & neck, gastric, colorectal, breast, lung & pancreatic cancer were examined; findings show mRNA expression & protein level of thymidylate synthase, dihydropyrimidine dehydrogenase & orotate phosphoribosyltransferase differed according to cancer type (PMID:19020767)
• Immunohistochemical staining for Orotate phosphoribosyl transferase (OPRT)revealed strong expression of OPRT in prostate cancer cells. There was a significant correlation between OPRT mRNA expression levels and the tumor pathological grade (PMID:19082440)
• High orotate phosphoribosyltransferase gene expression is associated with complete response to chemoradiotherapy in patients with squamous cell carcinoma of the esophagus (PMID:19307741)
• [review] It is confirmed that the type I defect in hereditary orotic aciduria is caused by loss of uridine monophosphate (UMP)synthase activity (PMID:19562503)
• patients who developed distant recurrence of rectal cancer were found to have significantly higher intratumoral thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT) (PMID:19724871)
• Increased orotate phosphoribosyltransferase expression is associated with bladder cancers. (PMID:20112501)
• novel phosphoribosyltransferase transition states (PMID:20527751)
• orotate phosphoribosyl transferase/DPD ratio has a relation to cancer staging and survival rate. (PMID:20647710)
• Although no association was detected between UMPS variants and gastrointestinal cancer risk in Caucasians, polymerase chain reaction-RFLP with BsrI digestion and DHPLC set up at 59 degrees C are reliable and cost-effective methods to genotype UMPS. (PMID:21631301)
• The observed mutations, aberrant splicing and downregulation of UMPS represent novel mechanisms for acquired 5-FU resistance in colorectal cancer (PMID:22249354)
• High expression levels of orotate phosphoribosyl transferase and thymidylate synthase in colorectal cancer appear to be significantly involved in metastasis after curative surgery (PMID:22641663)
• OPRT expression in colorectal carcinoma tissues is not correlated with the toxicity of 5-FU, but OPRT expression in the normal tissues can help predict the toxicity associated with 5-FU. (PMID:22931617)
• OPRT transition state analogues identify crucial components of potent inhibitors targeting OPRT enzymes. (PMID:24158442)
• Partial UMPS-deficiency should be included in the differential diagnosis of mild orotic aciduria. (PMID:28205048)
• The UMPS 638 CC genotype might be a candidate biomarker predicting toxicity in patients receiving tegafur-uracil/leucovorin-based preoperative chemoradiation for locally advanced rectal cancer (PMID:28347333)
• LncRNA SNORD3A specifically sensitizes breast cancer cells to 5-FU by sponging miR-185-5p to enhance UMPS expression. (PMID:32382150)
• Human uridine 5’-monophosphate synthase stores metabolic potential in inactive biomolecular condensates. (PMID:36708921)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	umps	ENSDARG00000012215
mus_musculus	Umps	ENSMUSG00000022814
rattus_norvegicus	Umps	ENSRNOG00000001797
drosophila_melanogaster	r-l	FBGN0003257
caenorhabditis_elegans		WBGENE00011559

Protein

Protein identifiers

Uridine 5’-monophosphate synthase — P11172 (reviewed: P11172)

All UniProt accessions (6): A8K5J1, E9PFD2, P11172, F2Z303, F2Z3P2, F8WDG4

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT), which converts orotate to orotidine-5’-monophosphate (OMP), and orotidine-5’-monophosphate decarboxylase (ODC), the terminal enzymatic reaction that decarboxylates OMP to uridine monophosphate (UMP).

Subunit / interactions. Homodimer; dimerization is required for enzymatic activity.

Disease relevance. Orotic aciduria 1 (ORAC1) [MIM:258900] A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and intellectual disability. A minority of cases have additional features, particularly congenital malformations and immune deficiencies. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Pyrimidine metabolism; UMP biosynthesis via de novo pathway; UMP from orotate: step 1/2. Pyrimidine metabolism; UMP biosynthesis via de novo pathway; UMP from orotate: step 2/2.

Similarity. In the N-terminal section; belongs to the purine/pyrimidine phosphoribosyltransferase family. In the C-terminal section; belongs to the OMP decarboxylase family.

Isoforms (4)

UniProt ID	Names	Canonical?
P11172-1	1	yes
P11172-2	2
P11172-3	3
P11172-4	4

RefSeq proteins (1): NP_000364* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000836	PRTase_dom	Domain
IPR001754	OMPdeCOase_dom	Domain
IPR004467	Or_phspho_trans_dom	Domain
IPR011060	RibuloseP-bd_barrel	Homologous_superfamily
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR014732	OMPdecase	Family
IPR018089	OMPdecase_AS	Active_site
IPR023031	OPRT	Family
IPR029057	PRTase-like	Homologous_superfamily

Pfam: PF00156, PF00215

Enzyme classification (BRENDA):

• EC 4.1.1.23 — orotidine-5’-phosphate decarboxylase (BRENDA: 27 organisms, 122 substrates, 165 inhibitors, 129 Km, 109 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
OROTIDINE 5’-PHOSPHATE	0.0002–30	82
5-FLUOROOROTIDINE 5’-PHOSPHATE	0.0008–1.1	17
2’-DEOXYOROTIDINE 5’-PHOSPHATE	0.0052–0.01	4
OROTIDINE 5’-MONOPHOSPHATE	0.0016–0.13	4
4-THIOOROTIDINE 5’-PHOSPHATE	0.02	1
5-AZAOROTIDINE 5’-PHOSPHATE	0.03	1
OROTIDINE	0.0007	1

Catalyzed reactions (Rhea), 2 shown:

• orotidine 5’-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate (RHEA:10380)
• orotidine 5’-phosphate + H(+) = UMP + CO2 (RHEA:11596)

UniProt features (88 total): helix 21, strand 20, binding site 16, turn 8, sequence variant 6, region of interest 3, modified residue 3, splice variant 3, active site 3, sequence conflict 2, initiator methionine 1, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

72 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9HDW	X-RAY DIFFRACTION	0.83
9HDS	X-RAY DIFFRACTION	0.86
7OUZ	X-RAY DIFFRACTION	0.9
7ASQ	X-RAY DIFFRACTION	0.95
7OTU	X-RAY DIFFRACTION	0.95
7OV0	X-RAY DIFFRACTION	0.95
9HY0	X-RAY DIFFRACTION	0.95
7AM9	X-RAY DIFFRACTION	0.99
6ZWY	X-RAY DIFFRACTION	1
6ZX1	X-RAY DIFFRACTION	1
9HDU	X-RAY DIFFRACTION	1
6YWT	X-RAY DIFFRACTION	1.05
7OQF	X-RAY DIFFRACTION	1.05
7OQM	X-RAY DIFFRACTION	1.05
9HDX	X-RAY DIFFRACTION	1.05
3EWW	X-RAY DIFFRACTION	1.1
3EWY	X-RAY DIFFRACTION	1.1
6YWU	X-RAY DIFFRACTION	1.1
7OQK	X-RAY DIFFRACTION	1.1
7OQN	X-RAY DIFFRACTION	1.1
6ZX3	X-RAY DIFFRACTION	1.15
7OQI	X-RAY DIFFRACTION	1.15
3MI2	X-RAY DIFFRACTION	1.2
6ZWZ	X-RAY DIFFRACTION	1.2
6ZX2	X-RAY DIFFRACTION	1.2
2QCF	X-RAY DIFFRACTION	1.22
3EX4	X-RAY DIFFRACTION	1.24
6YVK	X-RAY DIFFRACTION	1.25
6YVL	X-RAY DIFFRACTION	1.25
6YVM	X-RAY DIFFRACTION	1.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11172-F1	92.36	0.84

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 (3): 312 (for ompdecase activity); 314 (for ompdecase activity); 317 (for ompdecase activity)

Ligand- & substrate-binding residues (16): 259; 281–283; 281; 314; 317; 317; 321; 321; 372; 372; 430–432; 430–432 …

Post-translational modifications (3): 2, 37, 214

Mutagenesis-validated functional residues (1):

Position	Phenotype
312	loss of ompdecase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-500753	Pyrimidine biosynthesis

MSigDB gene sets: 322 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, MODULE_52, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, MODULE_56, CGGAARNGGCNG_UNKNOWN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOBASE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, KOKKINAKIS_METHIONINE_DEPRIVATION_96HR_UP, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, MODULE_272

GO Biological Process (6): ‘de novo’ pyrimidine nucleobase biosynthetic process (GO:0006207), UMP biosynthetic process (GO:0006222), UDP biosynthetic process (GO:0006225), pyrimidine nucleobase biosynthetic process (GO:0019856), ‘de novo’ UMP biosynthetic process (GO:0044205), pyrimidine nucleotide biosynthetic process (GO:0006221)

GO Molecular Function (9): orotate phosphoribosyltransferase activity (GO:0004588), orotidine-5’-phosphate decarboxylase activity (GO:0004590), identical protein binding (GO:0042802), catalytic activity (GO:0003824), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), lyase activity (GO:0016829), carboxy-lyase activity (GO:0016831)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Nucleotide biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyrimidine ribonucleotide biosynthetic process	2
pyrimidine-containing compound biosynthetic process	2
catalytic activity	2
cellular anatomical structure	2
pyrimidine nucleobase biosynthetic process	1
pyrimidine ribonucleoside monophosphate biosynthetic process	1
UMP metabolic process	1
pyrimidine ribonucleoside diphosphate biosynthetic process	1
UDP metabolic process	1
pyrimidine nucleobase metabolic process	1
nucleobase biosynthetic process	1
UMP biosynthetic process	1
pyrimidine nucleotide metabolic process	1
nucleotide biosynthetic process	1
pentosyltransferase activity	1
carboxy-lyase activity	1
protein binding	1
molecular_function	1
binding	1
transferase activity	1
carbon-carbon lyase activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

4539 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UMPS	DHODH	Q02127	978
UMPS	DPYD	Q12882	873
UMPS	UPP2	O95045	845
UMPS	UPP1	Q16831	837
UMPS	TYMS	P04818	816
UMPS	TYMP	P19971	815
UMPS	UCK1	Q9HA47	811
UMPS	UCKL1	Q9NWZ5	811
UMPS	CAD	P27708	805
UMPS	UCK2	Q9BZX2	768
UMPS	PRPS1L1	P21108	763
UMPS	F10	P00742	761
UMPS	PRPS1	P09329	751
UMPS	UPRT	Q96BW1	724
UMPS	CTPS1	P17812	721

IntAct

77 interactions, top by confidence:

A	B	Type	Score
HRAS	RAF1	psi-mi:“MI:0914”(association)	0.980
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
UMPS	EPHA4	psi-mi:“MI:0915”(physical association)	0.560
EPPIN	UMPS	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
S100A4	OIP5	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
	TK2	psi-mi:“MI:0915”(physical association)	0.400
A2M	UMPS	psi-mi:“MI:0915”(physical association)	0.370
UMPS	NOS3	psi-mi:“MI:0915”(physical association)	0.370
PAXIP1	UMPS	psi-mi:“MI:0915”(physical association)	0.370
PSEN1	UMPS	psi-mi:“MI:0915”(physical association)	0.370
UMPS	CALU	psi-mi:“MI:0915”(physical association)	0.370
UMPS	ZNF227	psi-mi:“MI:0915”(physical association)	0.370
PLA2G12A	UMPS	psi-mi:“MI:0915”(physical association)	0.370
UMPS	RPS29	psi-mi:“MI:0915”(physical association)	0.370
CASP8	UMPS	psi-mi:“MI:0915”(physical association)	0.370
PIK3CA	UMPS	psi-mi:“MI:0915”(physical association)	0.370
UMPS	RAD51	psi-mi:“MI:0915”(physical association)	0.370
UMPS	RB1CC1	psi-mi:“MI:0915”(physical association)	0.370
Nup98	POM121C	psi-mi:“MI:0914”(association)	0.350
Kif4	UMPS	psi-mi:“MI:0914”(association)	0.350
KLC4	PUF60	psi-mi:“MI:0914”(association)	0.350
MYH6	ELOC	psi-mi:“MI:0914”(association)	0.350

BioGRID (144): UMPS (Affinity Capture-RNA), UMPS (Affinity Capture-RNA), UMPS (Affinity Capture-MS), AASDHPPT (Co-fractionation), ALDH16A1 (Co-fractionation), ALDH5A1 (Co-fractionation), APRT (Co-fractionation), DUT (Co-fractionation), GBE1 (Co-fractionation), GLO1 (Co-fractionation), GNPDA1 (Co-fractionation), GNPDA2 (Co-fractionation), HMBS (Co-fractionation), ITPA (Co-fractionation), PGAM1 (Co-fractionation)

ESM2 similar proteins: A0A1J6KGJ9, A0A314KSQ4, A2RU49, A4IF87, A5PJU6, B4G0F3, B8BKI7, B9SQI7, C6JS30, E0CSI1, E0CTF3, G1SPE9, O08848, O15228, O22190, O23732, O43929, O82333, O88708, P11172, P31531, P37821, P42700, P46416, Q05B63, Q10D00, Q28DB5, Q2R483, Q2YDI2, Q3T067, Q3U1V6, Q4U3P8, Q5R514, Q5R6Z7, Q5R962, Q6GM82, Q6I581, Q6YJI5, Q7TNK6, Q7Z4G4

Diamond homologs: A0RY85, A1RRV2, A1SPW6, A2BJ25, A2CCL7, A2SQ87, A3CU84, A3DM49, A3MX27, A4QHG9, A4WLH7, A4YL97, A5EST0, A6KYP1, A6SUD4, A6U5N7, A8LRS7, A9VTC2, B0SCV6, B0SL24, B7IUP2, B7JJW9, B9JQW1, C3L744, C3MF81, C3P652, C5A1Y3, C6BW21, D4GZW2, G5EDZ2, O08359, O27888, O28533, O58855, O61790, O67742, P09556, P0CL78, P0CL79, P11172

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
UMPS	“down-regulates quantity”	“orotic acid”	“chemical modification”
UMPS	“down-regulates quantity”	“orotidine 5’-phosphate(3-)”	“chemical modification”
UMPS	“down-regulates quantity”	orotate	“chemical modification”
UMPS	“down-regulates quantity”	“5-phospho-α-D-ribose 1-diphosphate”	“chemical modification”
UMPS	“up-regulates quantity”	“orotidine 5’-phosphate(3-)”	“chemical modification”
UMPS	“up-regulates quantity”	UMP	“chemical modification”
UMPS	up-regulates	Pyrimidine_nucleotide_metabolic_process

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	166
Likely benign	44
Benign	53

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
11907	NM_000373.4(UMPS):c.326T>G (p.Val109Gly)	Pathogenic
3233632	NM_000373.4(UMPS):c.188del (p.Asn63fs)	Pathogenic
620432	NM_000373.4(UMPS):c.670G>T (p.Glu224Ter)	Pathogenic
523038	NM_000373.4(UMPS):c.1123G>A (p.Gly375Ser)	Likely pathogenic
810716	NM_000373.4(UMPS):c.870dup (p.Thr291fs)	Likely pathogenic

SpliceAI

1132 predictions. Top by Δscore:

Variant	Effect	Δscore
3:124735227:G:GT	donor_gain	1.0000
3:124735228:A:T	donor_gain	1.0000
3:124735240:GAT:G	donor_gain	1.0000
3:124735258:G:GG	donor_gain	1.0000
3:124737562:TTCTA:T	acceptor_loss	1.0000
3:124737563:TCTA:T	acceptor_loss	1.0000
3:124737564:CTA:C	acceptor_loss	1.0000
3:124737565:TAGG:T	acceptor_loss	1.0000
3:124737566:A:AC	acceptor_loss	1.0000
3:124737566:A:AG	acceptor_gain	1.0000
3:124737567:G:GG	acceptor_gain	1.0000
3:124740020:TTA:T	acceptor_loss	1.0000
3:124740021:TA:T	acceptor_loss	1.0000
3:124740022:A:AC	acceptor_loss	1.0000
3:124740023:G:GT	acceptor_loss	1.0000
3:124740197:GCG:G	donor_gain	1.0000
3:124740197:GCGGT:G	donor_loss	1.0000
3:124740199:GGTA:G	donor_loss	1.0000
3:124740200:G:GA	donor_loss	1.0000
3:124740200:G:GG	donor_gain	1.0000
3:124740201:T:A	donor_loss	1.0000
3:124744055:G:GT	donor_gain	1.0000
3:124744055:G:T	donor_gain	1.0000
3:124730623:G:GG	donor_gain	0.9900
3:124730623:GTCAG:G	donor_loss	0.9900
3:124730624:TCAG:T	donor_loss	0.9900
3:124730625:CAGG:C	donor_loss	0.9900
3:124730627:GGTGC:G	donor_loss	0.9900
3:124730629:T:G	donor_loss	0.9900
3:124730640:G:GT	donor_gain	0.9900

AlphaMissense

3115 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:124735227:G:C	R97S	0.992
3:124735227:G:T	R97S	0.992
3:124735226:G:C	R97T	0.991
3:124738195:G:C	R313P	0.990
3:124738192:A:C	D312A	0.989
3:124735226:G:T	R97M	0.988
3:124737627:G:C	D124H	0.987
3:124738192:A:T	D312V	0.987
3:124738193:C:A	D312E	0.986
3:124738193:C:G	D312E	0.986
3:124740155:A:C	S372R	0.986
3:124740157:C:A	S372R	0.986
3:124740157:C:G	S372R	0.986
3:124738191:G:C	D312H	0.985
3:124737628:A:C	D124A	0.984
3:124737648:A:C	S131R	0.983
3:124737650:T:A	S131R	0.983
3:124737650:T:G	S131R	0.983
3:124738100:G:C	K281N	0.983
3:124738100:G:T	K281N	0.983
3:124737629:T:A	D124E	0.982
3:124737629:T:G	D124E	0.982
3:124740047:T:A	W336R	0.981
3:124740047:T:C	W336R	0.981
3:124740147:C:A	A369E	0.981
3:124735169:C:A	A78D	0.980
3:124735181:C:A	A82D	0.979
3:124738020:T:C	C255R	0.979
3:124740134:T:C	C365R	0.979
3:124742189:G:A	G399D	0.979

dbSNP variants (sampled 300 via entrez): RS1000036185 (3:124732429 G>A,T), RS1000051300 (3:124735891 C>G,T), RS1000103349 (3:124736421 A>G), RS1000219177 (3:124748604 C>A,G,T), RS1000392371 (3:124730003 T>C), RS1000462391 (3:124745508 C>A), RS1000535212 (3:124744312 C>T), RS1000600087 (3:124745776 C>G,T), RS1001157148 (3:124731980 T>G), RS1001354922 (3:124738421 T>C), RS1001663653 (3:124728620 C>T), RS1001726209 (3:124734037 A>G), RS1001778418 (3:124734438 T>C), RS1001878572 (3:124738678 A>G), RS1001965594 (3:124743603 A>T)

Disease associations

OMIM: gene MIM:613891 | disease phenotypes: MIM:258900

GenCC curated gene-disease

Disease	Classification	Inheritance
orotic aciduria	Definitive	Autosomal recessive

Mondo (2): orotic aciduria (MONDO:0009797), cardiomyopathy (MONDO:0004994)

Orphanet (2): Hereditary orotic aciduria (Orphanet:30), Rare cardiomyopathy (Orphanet:167848)

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000069	Abnormality of the ureter
HP:0000316	Hypertelorism
HP:0000358	Posteriorly rotated ears
HP:0000431	Wide nasal bridge
HP:0000494	Downslanted palpebral fissures
HP:0000790	Hematuria
HP:0001263	Global developmental delay
HP:0001385	Hip dysplasia
HP:0001508	Failure to thrive
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001643	Patent ductus arteriosus
HP:0001744	Splenomegaly
HP:0001903	Anemia
HP:0002205	Recurrent respiratory infections
HP:0003218	Oroticaciduria
HP:0003267	Reduced orotidine 5-prime phosphate decarboxylase level
HP:0003339	Pyrimidine-responsive megaloblastic anemia
HP:0003355	Aminoaciduria
HP:0003526	Orotic acid crystalluria
HP:0004447	Poikilocytosis
HP:0004826	Folate-unresponsive megaloblastic anemia
HP:0008388	Abnormal toenail morphology
HP:0011273	Anisocytosis
HP:0011840	Abnormal T cell physiology
HP:0032231	Hypochromia

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004787_30	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	2.000000e-09
GCST005194_107	Coronary artery disease	2.000000e-13
GCST005195_46	Coronary artery disease	1.000000e-14
GCST005196_108	Coronary artery disease	2.000000e-13
GCST007990_6	Coronary artery disease	2.000000e-08
GCST010566_2	Benign childhood epilepsy with centro-temporal spikes	2.000000e-06
GCST010866_9	Coronary artery disease	4.000000e-13
GCST012020_96	Serum metabolite levels	6.000000e-123
GCST012020_97	Serum metabolite levels	9.000000e-163
GCST90002400_396	Plateletcrit	1.000000e-31

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5216 (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: 11,438 (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
CHEMBL2105330	PYRAZOFURIN	2	11,438

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

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1801019	Toxicity	3	tegafur	Drug Toxicity
rs2279199	Toxicity	3	capecitabine	Nausea;Vomiting
rs2291078	Efficacy	3	capecitabine;fluorouracil	Metastatic neoplasm
rs3772809	Efficacy	3	capecitabine;fluorouracil	Metastatic neoplasm
rs3772810	Efficacy	3	capecitabine;fluorouracil	Metastatic neoplasm
rs4678145	Toxicity	3	capecitabine	Asthenia;Neoplasms

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1801019	UMPS	3	5.00	1	tegafur
rs2291078	UMPS	3	0.00	1	capecitabine;fluorouracil
rs3772809	UMPS	3	0.00	1	capecitabine;fluorouracil
rs3772810	UMPS	3	0.00	1	capecitabine;fluorouracil
rs10049380	ITGB5, UMPS		0.00	0
rs2279199	UMPS	3	2.75	1	capecitabine
rs4678145	MIR544B, UMPS	3	3.25	1	capecitabine

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.77	Ki	17	nM	PYRAZOFURIN
7.77	Ki	17	nM	CHEMBL1164953
7.10	Kd	79.06	nM	CHEMBL5653589
7.10	ED50	79.06	nM	CHEMBL5653589
6.46	Ki	350	nM	CHEMBL473587
5.96	Ki	1100	nM	CHEMBL474164

PubChem BioAssay actives

26 with measured affinity, of 51 total; 25 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
3-[(2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1H-pyrazole-5-carboxamide	1388714: Inhibition of human ODCase	ki	0.0170	uM
[(2R,3S,4R,5S)-5-(5-carbamoyl-4-hydroxy-1H-pyrazol-3-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate	488222: Inhibition of human uridine 5’-monophosphate synthase after overnight incubation at room temperature by UV spectroscopy	ki	0.0170	uM
[(2R,5S)-3,4-dihydroxy-5-(4-nitrophenoxy)oxolan-2-yl]methyl dihydrogen phosphate	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.0410	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149731: Binding affinity to human UMPS incubated for 45 mins by Kinobead based pull down assay	kd	0.0791	uM
5-bromo-1-[2-[(2R)-3,4-dihydroxy-2-(hydroxymethyl)pyrrolidin-1-ium-1-yl]ethyl]-1,3-diazinane-2,4-dione	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.0800	uM
5-[[(4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidin-1-ium-1-yl]methyl]-2,6-dioxo-1,3-diazinane-4-carboxylic acid	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.0830	uM
[(3S,6R)-4,5-dihydroxy-8,11,13-trioxo-1,7,12-triazatricyclo[7.4.0.03,7]tridecan-6-yl]methyl dihydrogen phosphate	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.0900	uM
(3S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-1,7,12-triazatricyclo[7.4.0.03,7]tridecane-8,11,13-trione	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.1100	uM
(2R,5S)-2-(hydroxymethyl)-5-(4-nitrophenoxy)oxolane-3,4-diol	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.1200	uM
1,3-dihydroxypropan-2-yl-[2-(4-nitrophenyl)ethyl]azanium	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.1200	uM
[(2R,5S)-5-[(6-cyano-2,4-dioxo-1,3-diazinan-1-yl)methyl]-3,4-dihydroxypyrrolidin-1-ium-2-yl]methyl dihydrogen phosphate	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.1400	uM
1,3-dihydroxypropan-2-yl-[(4-nitrophenyl)methyl]azanium	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.1500	uM
[(2R,5S)-5-[(5-bromo-2,4-dioxo-1,3-diazinan-1-yl)methyl]-3,4-dihydroxypyrrolidin-1-ium-2-yl]methyl dihydrogen phosphate	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.2000	uM
(4R)-4-(hydroxymethyl)-1-[(4-nitrophenyl)methyl]pyrrolidin-1-ium-3-ol	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.2000	uM
(2R,5S)-2-(hydroxymethyl)-5-(4-nitrophenyl)pyrrolidin-1-ium-3,4-diol	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.2300	uM
(4R)-4-(hydroxymethyl)-1-[2-(4-nitrophenyl)ethyl]pyrrolidin-1-ium-3-ol	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.2300	uM
5-[[(4R)-3-hydroxy-4-(phosphonooxymethyl)pyrrolidin-1-ium-1-yl]methyl]-2,6-dioxo-1,3-diazinane-4-carboxylic acid	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.2400	uM
2,6-dioxo-5-(pyrrolidin-1-ium-1-ylmethyl)-1,3-diazinane-4-carboxylic acid	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.2500	uM
3-[2-[(2R)-3,4-dihydroxy-2-(hydroxymethyl)pyrrolidin-1-ium-1-yl]ethyl]-2,6-dioxo-1,3-diazinane-4-carboxylic acid	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.2900	uM
[(2R,3S,4R,5R)-5-(6-ethyl-5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate	1798852: Enzyme Inhibition Assay from Article 10.1021/jm801224t: “Structure-activity relationships of orotidine-5’-monophosphate decarboxylase inhibitors as anticancer agents.”	ki	0.3500	uM
3-[[(2S,5R)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidin-1-ium-2-yl]methyl]-2,6-dioxo-1,3-diazinane-4-carbonitrile	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.3600	uM
5-bromo-1-[2-[(4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidin-1-ium-1-yl]ethyl]-1,3-diazinane-2,4-dione	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.5200	uM
5-bromo-1-[[(2S,5R)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidin-1-ium-2-yl]methyl]-1,3-diazinane-2,4-dione	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	0.5300	uM
[(2R,3S,4R,5R)-5-(5-fluoro-6-iodo-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate	393540: Irreversible inhibition of human ODCase	ki	1.1000	uM
3-[(2S,5R)-3,4-dihydroxy-5-(phosphonooxymethyl)pyrrolidin-1-ium-2-yl]pyridine-4-carboxylic acid	1802454: Inhibition Assay from Article 10.1074/jbc.M113.521955: “Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.”	ki	4.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Fluorouracil	decreases reaction, increases reaction, increases response to substance, affects response to substance, decreases response to substance (+3 more)	12
bisphenol A	decreases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
cobaltous chloride	decreases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Plant Extracts	affects cotreatment, increases expression, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, increases reaction	1
afimoxifene	decreases reaction, increases expression	1
nickel chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
gambogic acid	increases expression, increases reaction	1
di-n-butylphosphoric acid	affects expression	1
wogonin	decreases expression, decreases reaction	1
cylindrospermopsin	increases expression	1
azaribine	increases activity	1
K 7174	decreases expression	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
NSC 689534	decreases expression, affects binding	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1010812	Binding	Irreversible inhibition of human ODCase	Structure-activity relationships of orotidine-5’-monophosphate decarboxylase inhibitors as anticancer agents. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT02110147	PHASE3	COMPLETED	Open-Label Study of Uridine Triacetate in Pediatric Patients With Hereditary Orotic Aciduria
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	PHASE3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	PHASE3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	PHASE3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	PHASE3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	PHASE3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	PHASE3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	PHASE3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT06158698	PHASE3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06563895	PHASE3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
NCT06846086	PHASE3	RECRUITING	Cardioprotective Effects of Melatonin in Patients With Cardiomyopathy
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