UPRT

Summary

UPRT (uracil phosphoribosyltransferase homolog, HGNC:28334) is a protein-coding gene on chromosome Xq13.3, encoding Uracil phosphoribosyltransferase homolog (Q96BW1).

This gene encodes uracil phosphoribosyltransferase, which catalyzes the conversion of uracil and 5-phosphoribosyl-1-R-diphosphate to uridine monophosphate (UMP). This reaction is an important part of nucleotide metabolism, specifically the pyrimidine salvage pathway. The enzyme localizes to the nucleus and cytoplasm. The protein is a potential target for rational design of drugs to treat parasitic infections and cancer.

Source: NCBI Gene 139596 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 84 total
• MANE Select transcript: NM_145052

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28334
Approved symbol	UPRT
Name	uracil phosphoribosyltransferase homolog
Location	Xq13.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp781E1243, MGC23937, FUR1, RP11-311P8.3
Ensembl gene	ENSG00000094841
Ensembl biotype	protein_coding
OMIM	300656
Entrez	139596

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000373373, ENST00000373379, ENST00000373383, ENST00000462237, ENST00000474175, ENST00000526850, ENST00000530743, ENST00000531704, ENST00000652605, ENST00000924922, ENST00000966884

RefSeq mRNA: 3 — MANE Select: NM_145052 NM_001307944, NM_001363821, NM_145052

CCDS: CCDS14429, CCDS78494, CCDS87767

Canonical transcript exons

ENST00000373383 — 7 exons

Exon	Start	End
ENSE00001810166	75274085	75274640
ENSE00003470127	75303405	75304885
ENSE00003497105	75297491	75297553
ENSE00003526233	75293472	75293514
ENSE00003581179	75300867	75300965
ENSE00003586816	75299735	75299896
ENSE00003657789	75296342	75296411

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 86.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.2699 / max 75.1101, expressed in 1746 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196759	4.3843	1648
196760	1.8856	809

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	86.62	gold quality
left ventricle myocardium	UBERON:0006566	86.04	gold quality
islet of Langerhans	UBERON:0000006	85.83	gold quality
calcaneal tendon	UBERON:0003701	84.92	gold quality
monocyte	CL:0000576	84.44	gold quality
leukocyte	CL:0000738	84.28	gold quality
duodenum	UBERON:0002114	84.27	gold quality
palpebral conjunctiva	UBERON:0001812	84.05	gold quality
right adrenal gland cortex	UBERON:0035827	83.97	gold quality
esophagus squamous epithelium	UBERON:0006920	83.70	gold quality
right adrenal gland	UBERON:0001233	83.56	gold quality
cardiac muscle of right atrium	UBERON:0003379	83.41	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	83.33	gold quality
nasal cavity epithelium	UBERON:0005384	83.25	gold quality
lower esophagus mucosa	UBERON:0035834	83.02	gold quality
muscle of leg	UBERON:0001383	82.89	gold quality
gastrocnemius	UBERON:0001388	82.80	gold quality
left adrenal gland	UBERON:0001234	82.74	gold quality
adrenal tissue	UBERON:0018303	82.70	gold quality
adrenal gland	UBERON:0002369	82.54	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.36	gold quality
left adrenal gland cortex	UBERON:0035825	82.34	gold quality
body of stomach	UBERON:0001161	82.32	gold quality
bone marrow cell	CL:0002092	82.25	gold quality
prefrontal cortex	UBERON:0000451	82.23	gold quality
adrenal cortex	UBERON:0001235	81.77	gold quality
oviduct epithelium	UBERON:0004804	81.74	gold quality
jejunal mucosa	UBERON:0000399	81.70	gold quality
bone marrow	UBERON:0002371	81.64	gold quality
stomach	UBERON:0000945	81.59	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	398.42
E-ANND-3	no	5.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

87 targeting UPRT, 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-126-5P	100.00	72.71	3180
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-1323	99.83	69.89	2471

Literature-anchored findings (GeneRIF, showing 2)

• isolation, expression, purification, and characterization of human uracil phosphoribosyltransferase (PMID:17384901)
• the efficacy of 5-FU-based chemotherapy in prostate cancers can be significantly improved by targeted expression of the suicide gene UPRT under the control of prostate-specific membrane antigen promoter/enhancer (PMID:18626508)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	uprt	ENSDARG00000035549
mus_musculus	Uprt	ENSMUSG00000073016
rattus_norvegicus	Uprt	ENSRNOG00000063275
drosophila_melanogaster	kri	FBGN0035639
caenorhabditis_elegans	C47B2.2	WBGENE00008131

Paralogs (3): UCK1 (ENSG00000130717), UCK2 (ENSG00000143179), UCKL1 (ENSG00000198276)

Protein

Protein identifiers

Uracil phosphoribosyltransferase homolog — Q96BW1 (reviewed: Q96BW1)

All UniProt accessions (6): Q96BW1, A0A0A0MRR5, A0A494C0H3, A8KAF9, E9PSD7, F8W6E9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in leukocytes, liver, spleen and thymus, with lower expression in brain, lung and skeletal muscle.

Similarity. Belongs to the UPRTase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96BW1-1	1	yes
Q96BW1-2	2
Q96BW1-3	3

RefSeq proteins (3): NP_001294873, NP_001350750, NP_659489* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000836	PRTase_dom	Domain
IPR029057	PRTase-like	Homologous_superfamily

Pfam: PF14681

Enzyme classification (BRENDA):

• EC 2.4.2.9 — uracil phosphoribosyltransferase (BRENDA: 24 organisms, 60 substrates, 47 inhibitors, 46 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
5-PHOSPHO-ALPHA-D-RIBOSE 1-DIPHOSPHATE	0.0069–0.3	18
URACIL	0.0004–0.159	18
2-THIOURACIL	0.67	1
4-THIOURACIL	0.0071	1
5-FLUOROURACIL	0.0064	1
DIPHOSPHATE	1	1
UMP	0.13	1

UniProt features (18 total): binding site 8, splice variant 5, chain 1, region of interest 1, modified residue 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BW1-F1	76.74	0.62

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 (8): 299–301; 133; 142; 176–179; 186; 203; 232; 238–246

Post-translational modifications (1): 25

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, GOBP_RESPONSE_TO_INSULIN, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, WTGAAAT_UNKNOWN, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SECRETION, GOBP_MAMMARY_GLAND_DEVELOPMENT, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS

GO Biological Process (4): UMP biosynthetic process (GO:0006222), female pregnancy (GO:0007565), lactation (GO:0007595), response to insulin (GO:0032868)

GO Molecular Function (5): GTP binding (GO:0005525), ribosylnicotinamide kinase activity (GO:0050262), nicotinate riboside kinase activity (GO:0061769), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (3): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
kinase activity	2
phosphotransferase activity, alcohol group as acceptor	2
cellular anatomical structure	2
pyrimidine ribonucleoside monophosphate biosynthetic process	1
pyrimidine ribonucleotide biosynthetic process	1
UMP metabolic process	1
multi-organism reproductive process	1
multi-multicellular organism process	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
response to peptide hormone	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UPRT	UMPS	P11172	724
UPRT	UCK1	Q9HA47	714
UPRT	DHFR	P00374	694
UPRT	UCK2	Q9BZX2	683
UPRT	TYMS	P04818	682
UPRT	UPP2	O95045	670
UPRT	UPP1	Q16831	665
UPRT	TK2	O00142	636
UPRT	PNP	P00491	604
UPRT	CDA	P32320	591
UPRT	DHODH	Q02127	572
UPRT	APRT	P07741	566
UPRT	TYMP	P19971	533
UPRT	DTYMK	P23919	532
UPRT	ADSL	P30566	531

IntAct

46 interactions, top by confidence:

A	B	Type	Score
PYROXD1	UPRT	psi-mi:“MI:0915”(physical association)	0.830
UPRT	PYROXD1	psi-mi:“MI:0915”(physical association)	0.830
MPPED1	TXNDC9	psi-mi:“MI:0914”(association)	0.640
HSF2BP	UPRT	psi-mi:“MI:0915”(physical association)	0.560
UPRT	GGA3	psi-mi:“MI:0915”(physical association)	0.560
ERH	UPRT	psi-mi:“MI:0915”(physical association)	0.560
COMMD1	UPRT	psi-mi:“MI:0915”(physical association)	0.560
KAT5	UPRT	psi-mi:“MI:0915”(physical association)	0.560
PPL	UPRT	psi-mi:“MI:0915”(physical association)	0.560
NPM3	UPRT	psi-mi:“MI:0915”(physical association)	0.560
POLR2G	UPRT	psi-mi:“MI:0915”(physical association)	0.560
UPRT	SERPINB4	psi-mi:“MI:0914”(association)	0.530
POLR3H	POLR3A	psi-mi:“MI:0914”(association)	0.530
UPRT	UCK2	psi-mi:“MI:0914”(association)	0.530
KLHL2	DCTN6	psi-mi:“MI:0914”(association)	0.350
TLK2	IGKV1D-13	psi-mi:“MI:0914”(association)	0.350
EFNA4	NBAS	psi-mi:“MI:0914”(association)	0.350
UPRT	HSF2BP	psi-mi:“MI:0915”(physical association)	0.000
UPRT	PYROXD1	psi-mi:“MI:0915”(physical association)	0.000
UPRT	GGA3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): UPRT (Two-hybrid), UCK1 (Affinity Capture-MS), UCK2 (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS), UCKL1 (Affinity Capture-MS), UPRT (Affinity Capture-MS), UPRT (Two-hybrid), PYROXD1 (Two-hybrid), UCK2 (Affinity Capture-MS), UCKL1 (Affinity Capture-MS), UCK1 (Affinity Capture-MS), UPRT (Affinity Capture-MS), UPRT (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS)

ESM2 similar proteins: A1L0Y2, A2ALK8, A2ARP1, A2Z8S0, A4IFG2, A8XT88, B1AVZ0, B3M1E1, B3P4N5, B4GZ20, B4HJC0, B4KA23, B4LVS8, B4NKI9, B4PVH6, B4QVW6, M9MRI4, O35242, O76050, P0C644, P26045, Q18223, Q29B63, Q29RQ5, Q3MHZ2, Q3UJK4, Q571F5, Q5M870, Q5NCX5, Q5PQR3, Q5R881, Q6PFW1, Q6PJ21, Q75G68, Q8BVR6, Q8C726, Q8CJC5, Q8R516, Q91YL3, Q91ZY8

Diamond homologs: A0ALM3, A2RG73, A3CPK9, A4VWM9, A5H0J4, A5IE48, A5N3J1, A5VIQ0, A5VVW9, A6UET4, A8AYQ0, A8FIC0, A9KIB0, A9MCZ3, A9WW75, B0K1G2, B0K7G1, B1AVZ0, B2G680, B2GAT5, B2SC51, B2U8Z0, B3PXN0, B3WDL1, B5XJZ7, B5YDB8, B5ZXI2, B6IW12, B7GMG3, B8DBH1, B8E009, B9DX75, B9J6V7, C0RMK4, C0Z818, C1KYV5, C3MBH2, C4Z9S1, C5D9M4, O13867

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1472 predictions. Top by Δscore:

Variant	Effect	Δscore
X:75274636:GACAA:G	donor_gain	1.0000
X:75274641:G:GG	donor_gain	1.0000
X:75296341:GATCA:G	acceptor_gain	1.0000
X:75297117:G:GT	donor_gain	1.0000
X:75299730:TCAA:T	acceptor_loss	1.0000
X:75299732:A:AG	acceptor_gain	1.0000
X:75299732:AAG:A	acceptor_gain	1.0000
X:75299732:AAGGT:A	acceptor_gain	1.0000
X:75299733:A:G	acceptor_gain	1.0000
X:75299733:AG:A	acceptor_gain	1.0000
X:75299733:AGGTG:A	acceptor_gain	1.0000
X:75299734:G:C	acceptor_loss	1.0000
X:75299734:G:GA	acceptor_gain	1.0000
X:75299734:GG:G	acceptor_gain	1.0000
X:75299734:GGT:G	acceptor_gain	1.0000
X:75299734:GGTGA:G	acceptor_gain	1.0000
X:75299892:TCTCA:T	donor_gain	1.0000
X:75299893:CTCA:C	donor_gain	1.0000
X:75299894:TCA:T	donor_gain	1.0000
X:75299895:CA:C	donor_gain	1.0000
X:75299895:CAGTG:C	donor_loss	1.0000
X:75299896:AGTGA:A	donor_loss	1.0000
X:75299897:G:GG	donor_gain	1.0000
X:75299897:GTGAG:G	donor_loss	1.0000
X:75299898:T:G	donor_loss	1.0000
X:75299899:GAGTG:G	donor_loss	1.0000
X:75300858:T:TA	acceptor_gain	1.0000
X:75300861:TTTCA:T	acceptor_loss	1.0000
X:75300862:TTCA:T	acceptor_loss	1.0000
X:75300863:TCA:T	acceptor_loss	1.0000

AlphaMissense

2019 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:75274619:T:C	L122P	1.000
X:75274634:G:C	R127P	1.000
X:75293503:G:C	A140P	1.000
X:75293509:C:A	R142S	1.000
X:75293510:G:C	R142P	1.000
X:75297533:G:A	G181E	1.000
X:75297536:T:A	V182D	1.000
X:75297538:A:C	S183R	1.000
X:75297540:C:A	S183R	1.000
X:75297540:C:G	S183R	1.000
X:75297542:T:A	I184K	1.000
X:75297542:T:G	I184R	1.000
X:75297548:G:C	R186T	1.000
X:75297549:A:C	R186S	1.000
X:75297549:A:T	R186S	1.000
X:75297553:G:C	G188R	1.000
X:75299735:G:A	G188D	1.000
X:75299735:G:T	G188V	1.000
X:75299759:G:C	R196P	1.000
X:75299785:G:A	G205R	1.000
X:75299785:G:C	G205R	1.000
X:75299786:G:A	G205E	1.000
X:75299795:T:C	L208P	1.000
X:75299879:T:C	L236P	1.000
X:75299888:C:A	P239Q	1.000
X:75300873:G:A	G244E	1.000
X:75300890:G:C	A250P	1.000
X:75300944:A:C	S268R	1.000
X:75300946:T:A	S268R	1.000
X:75300946:T:G	S268R	1.000

dbSNP variants (sampled 300 via entrez): RS1000006702 (X:75262582 G>A), RS1000020686 (X:75189336 A>G), RS1000035601 (X:75230203 T>C), RS1000086104 (X:75181904 G>A), RS1000107811 (X:75246610 G>A,T), RS1000181837 (X:75252908 G>A,T), RS1000195987 (X:75180697 T>G), RS1000235710 (X:75252690 G>A,T), RS1000239685 (X:75211179 G>A), RS1000273481 (X:75271699 T>C), RS1000293480 (X:75204678 G>A), RS1000324143 (X:75204268 T>C), RS1000354832 (X:75228227 G>C), RS1000387853 (X:75223140 C>G), RS1000391902 (X:75155733 A>C)

Disease associations

OMIM: gene MIM:300656 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Calcitriol	increases expression	1
Doxorubicin	decreases expression	1
Fluorouracil	increases metabolic processing	1
Hydrogen Peroxide	affects expression	1
Oxygen	increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Extracts	increases expression, affects cotreatment	1
Tretinoin	increases expression	1
Valproic Acid	affects expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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