UPP1

Summary

UPP1 (uridine phosphorylase 1, HGNC:12576) is a protein-coding gene on chromosome 7p12.3, encoding Uridine phosphorylase 1 (Q16831). Catalyzes the reversible phosphorylytic cleavage of uridine to uracil and ribose-1-phosphate which can then be utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.

This gene encodes a uridine phosphorylase, an enzyme that catalyzes the reversible phosphorylation of uridine (or 2’- deoxyuridine) to uracil and ribose-1-phosphate (or deoxyribose-1-phosphate). The encoded enzyme functions in the degradation and salvage of pyrimidine ribonucleosides.

Source: NCBI Gene 7378 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 17 total
• Druggable target: yes
• MANE Select transcript: NM_003364

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12576
Approved symbol	UPP1
Name	uridine phosphorylase 1
Location	7p12.3
Locus type	gene with protein product
Status	Approved
Aliases	UPASE, UPP, UDRPASE
Ensembl gene	ENSG00000183696
Ensembl biotype	protein_coding
OMIM	191730
Entrez	7378

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 25 protein_coding, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000331803, ENST00000395560, ENST00000395564, ENST00000416681, ENST00000417464, ENST00000421046, ENST00000432131, ENST00000436673, ENST00000444999, ENST00000457596, ENST00000482015, ENST00000495446, ENST00000910222, ENST00000910224, ENST00000910226, ENST00000917355, ENST00000917356, ENST00000917357, ENST00000917358, ENST00000917359, ENST00000917360, ENST00000957590, ENST00000957591, ENST00000957592, ENST00000957593, ENST00000957594, ENST00000957595, ENST00000957596, ENST00000957597, ENST00000957598, ENST00000957599, ENST00000957600

RefSeq mRNA: 6 — MANE Select: NM_003364 NM_001287426, NM_001287428, NM_001287429, NM_001287430, NM_001362774, NM_003364

CCDS: CCDS5507

Canonical transcript exons

ENST00000395564 — 9 exons

Exon	Start	End
ENSE00001297074	48101824	48101982
ENSE00001319953	48099670	48099787
ENSE00001522110	48089265	48089418
ENSE00001522123	48090188	48090364
ENSE00003480520	48103297	48103411
ENSE00003494339	48106873	48107082
ENSE00003499625	48107361	48107507
ENSE00003520957	48108218	48108736
ENSE00003637773	48094763	48094827

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 60.4556 / max 2899.7764, expressed in 1739 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78589	39.9377	1598
78588	18.2353	1670
78584	0.9057	358
78585	0.4974	229
78586	0.3695	184
78590	0.3596	141
78583	0.1176	46
78587	0.0329	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.16	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.44	gold quality
cerebellar hemisphere	UBERON:0002245	97.29	gold quality
granulocyte	CL:0000094	97.19	gold quality
cerebellar cortex	UBERON:0002129	97.17	gold quality
esophagus mucosa	UBERON:0002469	96.98	gold quality
upper lobe of left lung	UBERON:0008952	95.70	gold quality
monocyte	CL:0000576	95.55	gold quality
mononuclear cell	CL:0000842	95.20	gold quality
leukocyte	CL:0000738	95.17	gold quality
cerebellum	UBERON:0002037	95.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.77	gold quality
upper lobe of lung	UBERON:0008948	94.59	gold quality
blood	UBERON:0000178	94.16	gold quality
buccal mucosa cell	CL:0002336	93.79	gold quality
mucosa of transverse colon	UBERON:0004991	93.39	gold quality
omental fat pad	UBERON:0010414	93.32	gold quality
metanephros cortex	UBERON:0010533	93.29	gold quality
peritoneum	UBERON:0002358	93.23	gold quality
right frontal lobe	UBERON:0002810	93.20	gold quality
right lung	UBERON:0002167	93.17	gold quality
apex of heart	UBERON:0002098	93.00	gold quality
esophagus squamous epithelium	UBERON:0006920	92.89	gold quality
ectocervix	UBERON:0012249	92.87	gold quality
right atrium auricular region	UBERON:0006631	92.64	gold quality
spleen	UBERON:0002106	92.54	gold quality
vagina	UBERON:0000996	92.48	gold quality
epithelium of esophagus	UBERON:0001976	92.18	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.17	gold quality
esophagus	UBERON:0001043	91.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	2623.18
E-MTAB-6819	yes	1830.78
E-MTAB-8142	yes	1579.18
E-MTAB-3929	yes	1443.62
E-ANND-3	yes	24.78
E-MTAB-5061	yes	5.91
E-MTAB-8060	no	480.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, EWSR1, FLI1, FOS, IRF1, JUN, NFKB1, NFKB, RELA, STAT1, TFE3, TP53

miRNA regulators (miRDB)

16 targeting UPP1, 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-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-6512-5P	98.76	69.29	1195
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-581	98.39	67.42	835
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-6771-3P	98.20	66.53	971
HSA-MIR-7850-5P	98.12	67.28	1111

Literature-anchored findings (GeneRIF, showing 13)

• The expression level of UPase gene may be an independent prognostic marker in human breast carcinoma (PMID:11807789)
• Characterization of the promoter region of UPase has indicated a direct regulation of its expression by the tumor suppressor gene p53. Review. (PMID:12084455)
• Uridine phosphorylase overexpression is associated with lymph node metastasis in oral neoplasms (PMID:12115385)
• Thymidine phosphorylase and uridine phosphorylase were both responsible for converting 5’dFUrd/5FU into 5FU/FUrd, respectively (PMID:16798057)
• The presented structures confirm that hUPP1 is dimeric. They also reveal the mechanism by which 5-benzylacyclouridine engages the active site of the protein and disables the enzyme by locking the protein in a closed conformation. (PMID:19291308)
• Data show that enhanced cytotoxicity of 5-FU by bFGF through modulating the expression of UPP1 at the transcription level. (PMID:19714313)
• The dimeric enzyme is capable of a large hinge motion facilitating ligand exchange. (PMID:20856879)
• there are inter-ethnic differences for uridine phosphorylase 1 (UPP1) and zinc finger-SWIM containing 4 (ZSWIM4) in response to 1alpha,25(OH)2D3 (PMID:28163244)
• Uridine phosphorylase 1 associates to biological and clinical significance in thyroid carcinoma cell lines. (PMID:31496029)
• Uridine phosphorylase 1 is a novel immune-related target and predicts worse survival in brain glioma. (PMID:32583596)
• Metabolites modulate the functional state of human uridine phosphorylase I. (PMID:32864839)
• UPP1 promotes lung adenocarcinoma progression through the induction of an immunosuppressive microenvironment. (PMID:38331898)
• Uridine phosphorylase-1 promotes cell viability and cell-cycle progression in human epidermal keratinocytes via the glycolytic pathway. (PMID:38797519)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	upp1	ENSDARG00000040869
mus_musculus	Upp1	ENSMUSG00000020407
rattus_norvegicus	Upp1	ENSRNOG00000004972
drosophila_melanogaster	CG12065	FBGN0030052
drosophila_melanogaster	CG17224	FBGN0031489
drosophila_melanogaster	CG3788	FBGN0034800
drosophila_melanogaster	CG6330	FBGN0039464
caenorhabditis_elegans		WBGENE00019199
caenorhabditis_elegans		WBGENE00022817

Paralogs (1): UPP2 (ENSG00000007001)

Protein

Protein identifiers

Uridine phosphorylase 1 — Q16831 (reviewed: Q16831)

All UniProt accessions (5): C9J486, C9JIP2, C9K0J2, F8WD51, Q16831

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible phosphorylytic cleavage of uridine to uracil and ribose-1-phosphate which can then be utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis. Shows broad substrate specificity and can also accept deoxyuridine and other analogous compounds.

Subunit / interactions. Homodimer.

Induction. By vitamin D3 and a mixture of inflammatory cytokines: TNF, IL1/interleukin-1 and IFNG/IFN-gamma.

Pathway. Pyrimidine metabolism; UMP biosynthesis via salvage pathway; uracil from uridine (phosphorylase route): step 1/1.

Miscellaneous. Inactive.

Similarity. Belongs to the PNP/UDP phosphorylase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16831-1	1	yes
Q16831-2	2, Truncated

RefSeq proteins (6): NP_001274355, NP_001274357, NP_001274358, NP_001274359, NP_001349703, NP_003355* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000845	Nucleoside_phosphorylase_d	Domain
IPR010059	Uridine_phosphorylase_euk	Family
IPR018016	Nucleoside_phosphorylase_CS	Conserved_site
IPR035994	Nucleoside_phosphorylase_sf	Homologous_superfamily

Pfam: PF01048

Enzyme classification (BRENDA):

• EC 2.4.2.3 — uridine phosphorylase (BRENDA: 34 organisms, 120 substrates, 109 inhibitors, 84 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
URIDINE	0.016–7.55	24
PHOSPHATE	0.076–16.1	16
URACIL	0.06–0.485	7
ALPHA-D-RIBOSE-1-PHOSPHATE	0.02–0.087	5
RIBOSE 1-PHOSPHATE	0.017–0.14	5
THYMIDINE	0.0489–0.215	5
5-METHYLURIDINE	0.065–4	4
5-FLUOROURACIL	0.036–0.06	3
2’-DEOXYURIDINE	0.121–0.13	2
DEOXYURIDINE	0.3–0.71	2
5’-DEOXY-5-FLUOROURIDINE	0.756	1
5-BROMODEOXYURIDINE	0.1	1
5-BROMOURIDINE	0.03	1
5-FLUORO-2’-DEOXYURIDINE	0.427	1
5-FLUOROURIDINE	0.024	1

Catalyzed reactions (Rhea), 2 shown:

• 2’-deoxyuridine + phosphate = 2-deoxy-alpha-D-ribose 1-phosphate + uracil (RHEA:22824)
• uridine + phosphate = alpha-D-ribose 1-phosphate + uracil (RHEA:24388)

UniProt features (34 total): strand 12, helix 11, binding site 5, turn 3, splice variant 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3EUF	X-RAY DIFFRACTION	1.9
3EUE	X-RAY DIFFRACTION	2.3
3NBQ	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16831-F1	94.68	0.92

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 (5): 60; 94; 138–141; 142–143; 217–219

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-73614	Pyrimidine salvage
R-HSA-73621	Pyrimidine catabolism

MSigDB gene sets: 408 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_PYRIMIDINE_CATABOLISM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, KENNY_CTNNB1_TARGETS_UP, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, PARK_TRETINOIN_RESPONSE_AND_RARA_PLZF_FUSION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, XU_HGF_SIGNALING_NOT_VIA_AKT1_48HR_UP, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, BILD_HRAS_ONCOGENIC_SIGNATURE

GO Biological Process (14): nucleobase-containing compound metabolic process (GO:0006139), uridine catabolic process (GO:0006218), CMP catabolic process (GO:0006248), dCMP catabolic process (GO:0006249), cellular response to glucose starvation (GO:0042149), UMP salvage (GO:0044206), UMP catabolic process (GO:0046050), dTMP catabolic process (GO:0046074), dUMP catabolic process (GO:0046079), pyrimidine nucleotide metabolic process (GO:0006220), nucleoside metabolic process (GO:0009116), nucleoside catabolic process (GO:0009164), nucleotide catabolic process (GO:0009166), uridine metabolic process (GO:0046108)

GO Molecular Function (8): uridine phosphorylase activity (GO:0004850), thymidine phosphorylase activity (GO:0009032), identical protein binding (GO:0042802), deoxyuridine phosphorylase activity (GO:0047847), catalytic activity (GO:0003824), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), pentosyltransferase activity (GO:0016763)

GO Cellular Component (3): nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Nucleotide salvage	1
Nucleotide catabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyrimidine deoxyribonucleoside monophosphate catabolic process	3
pyrimidine deoxyribonucleotide catabolic process	3
pyrimidine-nucleoside phosphorylase activity	3
cellular anatomical structure	3
pyrimidine ribonucleoside monophosphate catabolic process	2
pyrimidine ribonucleotide catabolic process	2
nucleotide metabolic process	2
primary metabolic process	1
uridine metabolic process	1
pyrimidine ribonucleoside catabolic process	1
CMP metabolic process	1
dCMP metabolic process	1
cellular response to starvation	1
UMP biosynthetic process	1
pyrimidine ribonucleotide salvage	1
UMP metabolic process	1
dTMP metabolic process	1
dUMP metabolic process	1
pyrimidine-containing compound metabolic process	1
nucleobase-containing small molecule metabolic process	1
carbohydrate derivative metabolic process	1
nucleoside metabolic process	1
nucleobase-containing small molecule catabolic process	1
glycosyl compound catabolic process	1
nucleoside phosphate catabolic process	1
pyrimidine ribonucleoside metabolic process	1
protein binding	1
molecular_function	1
catalytic activity	1
transferase activity	1
glycosyltransferase activity	1
nuclear lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1275 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UPP1	TYMP	P19971	963
UPP1	PNP	P00491	878
UPP1	UMPS	P11172	837
UPP1	UCKL1	Q9NWZ5	815
UPP1	UCK1	Q9HA47	808
UPP1	PGM2L1	Q6PCE3	788
UPP1	UCK2	Q9BZX2	754
UPP1	TYMS	P04818	748
UPP1	PGM2	Q96G03	724
UPP1	DPYD	Q12882	704
UPP1	CDA	P32320	665
UPP1	UPRT	Q96BW1	665
UPP1	UPB1	Q9UBR1	636
UPP1	RRM1	P23921	564
UPP1	DTYMK	P23919	554

IntAct

40 interactions, top by confidence:

A	B	Type	Score
CDA	LIN7A	psi-mi:“MI:0914”(association)	0.640
SLC31A1	PRORP	psi-mi:“MI:0914”(association)	0.530
LRRC45	UPP1	psi-mi:“MI:0915”(physical association)	0.400
UPP1	TBC1D4	psi-mi:“MI:0915”(physical association)	0.400
UPP1	E7	psi-mi:“MI:0915”(physical association)	0.370
Stmn1	FXR1	psi-mi:“MI:0914”(association)	0.350
VPS18	DNAJB5	psi-mi:“MI:0914”(association)	0.350
NUDCD1	APOBEC3B	psi-mi:“MI:0914”(association)	0.350
CUTA	UBB	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
E2F1	CLIC1	psi-mi:“MI:0914”(association)	0.350
HRAS	MET	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
FNDC5	A2ML1	psi-mi:“MI:0914”(association)	0.350
UPP1	A2ML1	psi-mi:“MI:0914”(association)	0.350
CHCHD4	PDHX	psi-mi:“MI:0914”(association)	0.350
CUTA	ERI3	psi-mi:“MI:0914”(association)	0.350

BioGRID (99): UPP1 (Co-fractionation), UPP1 (Co-fractionation), UPP1 (Affinity Capture-MS), UPP1 (Affinity Capture-MS), UPP1 (Affinity Capture-MS), UPP1 (Affinity Capture-MS), UPP1 (Affinity Capture-MS), UPP1 (Affinity Capture-MS), UPP1 (Proximity Label-MS), UPP1 (Affinity Capture-MS), UPP1 (Affinity Capture-MS), UPP1 (Proximity Label-MS), UPP1 (Proximity Label-MS), UPP1 (Affinity Capture-MS), UPP1 (Affinity Capture-MS)

ESM2 similar proteins: A5PK39, A7M6E7, A7M6E8, B4G0F3, B8BKI7, B9N1F9, B9SQI7, C6JS30, E0CSI1, F4JGR5, O80526, O95045, P11497, P28492, P29144, P52624, Q0J035, Q13085, Q16831, Q28559, Q28EN2, Q2QNG7, Q2QZ86, Q2R483, Q32LQ4, Q3T0V9, Q571F8, Q5M8Z0, Q5RAK7, Q5RF32, Q5RFG2, Q5SWU9, Q64514, Q64560, Q6P6M7, Q7SXM0, Q803A7, Q80YV4, Q8CGR7, Q91YP3

Diamond homologs: G4VGH9, G4VGI0, O95045, P52624, Q16831, Q23588, Q8CGR7, P12758, P43770, A1S477, A3D7J1, A4IN93, A5VHR2, A6WRB5, A7GN01, A8LJI8, B2G592, B3W8N4, B8E6P7, B9LS20, O08444, O32810, O83990, P0A1F6, P0A1F7, P50389, P52671, Q02ZT0, Q03CD2, Q169T2, Q1J733, Q28U96, Q5JJC1, Q5KZM1, Q8R973, Q9CH10

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
UPP1	“down-regulates quantity”	uracil	“chemical modification”
UPP1	“down-regulates quantity”	“alpha-D-ribose 1-phosphate(2-)”	“chemical modification”
UPP1	“up-regulates quantity”	uridine	“chemical modification”
UPP1	“down-regulates quantity”	“2-deoxy-D-ribofuranose 1-phosphate(2-)”	“chemical modification”
UPP1	“up-regulates quantity”	2’-deoxyuridine	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1487 predictions. Top by Δscore:

Variant	Effect	Δscore
7:48094822:TCAC:T	donor_gain	1.0000
7:48094827:AGT:A	donor_loss	1.0000
7:48094828:G:GC	donor_loss	1.0000
7:48094828:G:GG	donor_gain	1.0000
7:48094829:TAA:T	donor_loss	1.0000
7:48101822:A:AG	acceptor_gain	1.0000
7:48101823:G:GG	acceptor_gain	1.0000
7:48101823:GTTT:G	acceptor_gain	1.0000
7:48106868:CTCA:C	acceptor_loss	1.0000
7:48106871:A:AC	acceptor_loss	1.0000
7:48106871:A:AG	acceptor_gain	1.0000
7:48106871:AG:A	acceptor_gain	1.0000
7:48106872:G:GT	acceptor_gain	1.0000
7:48106872:GG:G	acceptor_gain	1.0000
7:48106872:GGT:G	acceptor_gain	1.0000
7:48106872:GGTC:G	acceptor_gain	1.0000
7:48106872:GGTCT:G	acceptor_gain	1.0000
7:48107080:AAG:A	donor_loss	1.0000
7:48107081:AG:A	donor_loss	1.0000
7:48107082:GG:G	donor_loss	1.0000
7:48107083:GTG:G	donor_loss	1.0000
7:48107084:T:A	donor_loss	1.0000
7:48107348:A:AG	acceptor_gain	1.0000
7:48107348:AT:A	acceptor_gain	1.0000
7:48107348:ATGT:A	acceptor_gain	1.0000
7:48107349:T:G	acceptor_gain	1.0000
7:48107349:T:TA	acceptor_gain	1.0000
7:48107351:T:TA	acceptor_gain	1.0000
7:48107353:T:TA	acceptor_gain	1.0000
7:48107358:CAGG:C	acceptor_loss	1.0000

AlphaMissense

2032 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:48107073:T:C	F213L	0.998
7:48107075:C:A	F213L	0.998
7:48107075:C:G	F213L	0.998
7:48107452:T:A	N246K	0.997
7:48107452:T:G	N246K	0.997
7:48106894:T:A	V153D	0.996
7:48107461:G:A	M249I	0.995
7:48107461:G:C	M249I	0.995
7:48107461:G:T	M249I	0.995
7:48108231:T:G	C269W	0.995
7:48101980:A:C	S107R	0.994
7:48101982:T:A	S107R	0.994
7:48101982:T:G	S107R	0.994
7:48107369:C:A	R219S	0.994
7:48108247:C:A	R275S	0.994
7:48101830:T:C	C57R	0.993
7:48103337:A:T	E121V	0.993
7:48103340:T:C	L122P	0.993
7:48103387:C:A	R138S	0.993
7:48101828:T:A	V56E	0.992
7:48101972:T:C	L104P	0.992
7:48103388:G:C	R138P	0.992
7:48103400:C:T	S142F	0.992
7:48103347:G:C	K124N	0.991
7:48103347:G:T	K124N	0.991
7:48103400:C:A	S142Y	0.991
7:48107370:G:C	R219P	0.991
7:48107430:C:A	A239D	0.991
7:48101978:T:A	V106D	0.990
7:48107365:A:C	Q217H	0.990

dbSNP variants (sampled 300 via entrez): RS1000112214 (7:48095885 G>A,C), RS1000224957 (7:48089450 C>T), RS1000333095 (7:48108048 C>T), RS1000514597 (7:48091933 A>C,G), RS1000527755 (7:48088448 T>C), RS1000542948 (7:48106568 C>A,G,T), RS1000565578 (7:48091716 A>C,G), RS1000838094 (7:48101017 T>C), RS1000876426 (7:48100670 A>G), RS1001017229 (7:48097799 C>T), RS1001471421 (7:48093930 C>A), RS1001510577 (7:48097475 C>A,G), RS1001514200 (7:48088880 C>G,T), RS1001572138 (7:48092895 A>G), RS1001829976 (7:48105311 G>A)

Disease associations

OMIM: gene MIM:191730 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): long QT syndrome (MONDO:0002442)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_1167	Metabolite levels	8.000000e-06
GCST010396_38	Gut microbiota (bacterial taxa, hurdle binary method)	7.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010460	anthranilic acid measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4811 (SINGLE PROTEIN)

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

ChEMBL bioactivities

27 potent at pChembl≥5 of 30 total, top 25 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.96	Ki	1.1	nM	CHEMBL1277898
7.70	Kd	20	nM	CHEMBL3086510
7.40	Kd	40	nM	CHEMBL3086510
6.97	Kd	108	nM	CHEMBL3086508
6.90	Kd	127	nM	CHEMBL3086508
6.82	Kd	151	nM	CHEMBL3086521
6.58	Kd	263	nM	CHEMBL3087492
6.51	Kd	312	nM	CHEMBL3087493
6.30	Kd	502	nM	CHEMBL3087491
5.92	Kd	1200	nM	CHEMBL17432
5.85	Kd	1400	nM	CHEMBL3086510
5.85	Kd	1400	nM	CHEMBL17432
5.70	Kd	2000	nM	CHEMBL3086521
5.64	Kd	2300	nM	CHEMBL3086521
5.64	Ki	2300	nM	CHEMBL37519
5.54	Kd	2900	nM	CHEMBL3086508
5.42	Kd	3800	nM	CHEMBL3086521
5.38	Kd	4200	nM	CHEMBL3087493
5.34	Kd	4600	nM	CHEMBL3087492
5.28	Kd	5300	nM	CHEMBL3087491
5.18	Kd	6600	nM	CHEMBL17432
5.16	Kd	7000	nM	CHEMBL3087491
5.13	Kd	7400	nM	CHEMBL3087493
5.03	Kd	9400	nM	CHEMBL3087492
5.00	Kd	1e+04	nM	CHEMBL3087493

PubChem BioAssay actives

27 with measured affinity, of 80 total; 9 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
1-(2-hydroxyethoxymethyl)-5-[(3-phenylmethoxyphenyl)methyl]-1,3-diazinane-2,4,6-trione	536623: Inhibition of human uridine phosphorylase	ki	0.0011	uM
2-hydroxy-4-methyl-6-oxo-1H-pyridine-3-carbonitrile	1054083: Binding affinity to human recombinant UP1-R1P binary complex expressed in Escherichia coli Rosetta (DE3) at 200 uM R1P by isothermal titration calorimetric analysis	kd	0.0200	uM
2-hydroxy-6-oxo-1H-pyridine-3-carbonitrile	1054085: Binding affinity to human recombinant UP1-R1P binary complex expressed in Escherichia coli Rosetta (DE3) at 50 uM R1P by isothermal titration calorimetric analysis	kd	0.1080	uM
6-hydroxy-5-[(2-hydroxyethylamino)methyl]-4-methyl-2-oxo-1H-pyridine-3-carbonitrile	1054086: Binding affinity to human recombinant UP1-inorganic phosphate binary complex expressed in Escherichia coli Rosetta (DE3) by isothermal titration calorimetric analysis	kd	0.1510	uM
5-[(2,3-dihydroxypropylamino)methyl]-6-hydroxy-4-methyl-2-oxo-1H-pyridine-3-carbonitrile	1054086: Binding affinity to human recombinant UP1-inorganic phosphate binary complex expressed in Escherichia coli Rosetta (DE3) by isothermal titration calorimetric analysis	kd	0.2630	uM
5-[(dimethylamino)methyl]-6-hydroxy-4-methyl-2-oxo-1H-pyridine-3-carbonitrile	1054086: Binding affinity to human recombinant UP1-inorganic phosphate binary complex expressed in Escherichia coli Rosetta (DE3) by isothermal titration calorimetric analysis	kd	0.3120	uM
5-[(1,3-dihydroxypropan-2-ylamino)methyl]-6-hydroxy-4-methyl-2-oxo-1H-pyridine-3-carbonitrile	1054086: Binding affinity to human recombinant UP1-inorganic phosphate binary complex expressed in Escherichia coli Rosetta (DE3) by isothermal titration calorimetric analysis	kd	0.5020	uM
5-benzyl-1-(2-hydroxyethoxymethyl)pyrimidine-2,4-dione	1054085: Binding affinity to human recombinant UP1-R1P binary complex expressed in Escherichia coli Rosetta (DE3) at 50 uM R1P by isothermal titration calorimetric analysis	kd	1.2000	uM
5-[(3-phenylmethoxyphenyl)methyl]-1,3-diazinane-2,4,6-trione	536623: Inhibition of human uridine phosphorylase	ki	2.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	5
bisphenol A	affects expression, decreases expression, affects cotreatment	4
Fluorouracil	increases expression, affects response to substance	4
Cyclosporine	increases expression	4
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
cobaltous chloride	increases expression	3
Benzo(a)pyrene	decreases methylation, increases expression	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Tetrachlorodibenzodioxin	decreases expression, increases expression	3
Tretinoin	increases expression	3
trichostatin A	affects cotreatment, decreases expression	2
Acetaminophen	affects cotreatment, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Doxorubicin	decreases expression, increases expression	2
Indomethacin	affects cotreatment, decreases expression, increases expression	2
Nickel	increases expression	2
Phenobarbital	affects expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Aflatoxin B1	affects expression, increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
2-butenal	increases expression	1
tris(2-butoxyethyl) phosphate	increases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1

ChEMBL screening assays

18 unique, capped per target: 18 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1287513	Binding	Inhibition of human uridine phosphorylase	Exploring new inhibitors of Plasmodium falciparum purine nucleoside phosphorylase. — Eur J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1RA	Abcam K-562 UPP1 KO	Cancer cell line	Female
CVCL_D2MX	Abcam Raji UPP1 KO	Cancer cell line	Male
CVCL_F1MG	HyCyte A-549 KO-hUPP1	Cancer cell line	Male
CVCL_WQ79	Abcam Jurkat UPP1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea