NT5E

Summary

NT5E (5’-nucleotidase ecto, HGNC:8021) is a protein-coding gene on chromosome 6q14.3, encoding 5’-nucleotidase (P21589). Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside, with AMP being the preferred substrate. In precision oncology, NT5E Overexpression confers sensitivity to Cetuximab in Colorectal Cancer (CIViC Level B).

The protein encoded by this gene is a plasma membrane protein that catalyzes the conversion of extracellular nucleotides to membrane-permeable nucleosides. The encoded protein is used as a determinant of lymphocyte differentiation. Defects in this gene can lead to the calcification of joints and arteries. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4907 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary arterial and articular multiple calcification syndrome (Strong, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 125 total — 2 pathogenic, 3 likely-pathogenic
• GTEx eGene: eQTL in 38 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 15
• Drug target: yes — 1 curated mechanism-of-action drug; 7 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.25 (unconstrained)
• MANE Select transcript: NM_002526
• Interaction hub: 3,634 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8021
Approved symbol	NT5E
Name	5’-nucleotidase ecto
Location	6q14.3
Locus type	gene with protein product
Status	Approved
Aliases	CD73, eN, eNT, CALJA
Ensembl gene	ENSG00000135318
Ensembl biotype	protein_coding
OMIM	129190
Entrez	4907

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 14 protein_coding

MANE Select: ENST00000257770

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 2

ENST00000257770, ENST00000369646, ENST00000369651, ENST00000416334, ENST00000437581, ENST00000880505, ENST00000880506, ENST00000880507, ENST00000954716, ENST00000954717, ENST00001111673, ENST00001124157, ENST00001124158, ENST00001133660

RefSeq mRNA: 2 — MANE Select: NM_002526 NM_001204813, NM_002526

CCDS: CCDS5002, CCDS56439

Canonical transcript exons

ENST00000257770 — 9 exons

Exon	Start	End
ENSE00000918638	85485235	85485432
ENSE00000918639	85487335	85487489
ENSE00000918640	85489494	85489599
ENSE00000918641	85490508	85490657
ENSE00000918642	85491977	85492177
ENSE00001853124	85493841	85495784
ENSE00002430594	85467060	85467282
ENSE00002533809	85471237	85471425
ENSE00003847261	85450083	85450478

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 97.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 92.3698 / max 1223.7913, expressed in 1492 samples.

Highest expression (Bgee): stromal cell of endometrium, calcaneal tendon, jejunal mucosa, synovial joint, cartilage tissue.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NT5E is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 38 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 41 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	3.1e-73	+0.93	6:85459919:A:G
Whole Blood	eqtl	1.2e-39	-0.54	6:85436306:T:G
Cells EBV-transformed lymphocytes	eqtl	4.6e-32	-0.86	6:85436306:T:G
Spleen	eqtl	1.4e-18	-0.89	6:85422821:A:G
Nerve Tibial	eqtl	5.3e-17	-0.25	6:85496250:C:A
Adipose Subcutaneous	eqtl	1.3e-12	+0.25	6:85466238:A:G
Colon Transverse	eqtl	9.0e-12	-0.52	6:85377928:A:AC
Brain Nucleus accumbens basal ganglia	eqtl	5.8e-11	+0.33	6:85464326:C:T
Brain Cerebellum	eqtl	4.4e-10	+0.38	6:85401202:C:T
Liver	eqtl	6.0e-10	-0.56	6:85404773:C:T
Stomach	eqtl	2.2e-09	-0.31	6:85416962:C:T
Testis	eqtl	3.3e-09	-0.28	6:85406824:A:G
Skin Sun Exposed Lower leg	eqtl	5.1e-09	+0.22	6:85486588:G:T
Brain Cortex	eqtl	2.1e-08	+0.34	6:85464326:C:T
Brain Anterior cingulate cortex BA24	eqtl	2.4e-08	+0.30	6:85436306:T:G
Brain Caudate basal ganglia	eqtl	3.4e-07	+0.25	6:85436306:T:G
Brain Frontal Cortex BA9	eqtl	4.7e-07	+0.25	6:85459919:A:G
Esophagus Muscularis	eqtl	1.4e-06	-0.16	6:85437614:T:C
Artery Aorta	eqtl	4.5e-06	+0.28	6:85426715:T:C
Skin Not Sun Exposed Suprapubic	eqtl	6.3e-06	+0.19	6:85458547:G:A

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
68803	71.8965	1448
68804	10.0301	1098
68800	7.5798	956
68801	1.0244	469
68802	0.5795	379
68799	0.5131	326
68812	0.4441	247
68813	0.2140	74
68798	0.0885	25

Top tissues by expression

showing 100 of 289 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	97.96	gold quality
calcaneal tendon	UBERON:0003701	97.04	gold quality
jejunal mucosa	UBERON:0000399	96.12	gold quality
synovial joint	UBERON:0002217	95.99	gold quality
cartilage tissue	UBERON:0002418	94.82	gold quality
smooth muscle tissue	UBERON:0001135	94.50	gold quality
endocervix	UBERON:0000458	94.29	gold quality
tendon	UBERON:0000043	94.01	gold quality
endometrium	UBERON:0001295	93.76	gold quality
tendon of biceps brachii	UBERON:0008188	93.54	gold quality
germinal epithelium of ovary	UBERON:0001304	93.40	gold quality
endometrium epithelium	UBERON:0004811	93.32	gold quality
tibia	UBERON:0000979	92.85	gold quality
decidua	UBERON:0002450	92.69	gold quality
myometrium	UBERON:0001296	92.41	gold quality
popliteal artery	UBERON:0002250	92.19	gold quality
tibial artery	UBERON:0007610	92.19	gold quality
rectum	UBERON:0001052	92.17	gold quality
layer of synovial tissue	UBERON:0007616	92.17	gold quality
uterus	UBERON:0000995	92.14	gold quality
aorta	UBERON:0000947	91.97	gold quality
placenta	UBERON:0001987	91.88	gold quality
ascending aorta	UBERON:0001496	91.77	gold quality
thoracic aorta	UBERON:0001515	91.73	gold quality
descending thoracic aorta	UBERON:0002345	91.73	gold quality
artery	UBERON:0001637	91.71	gold quality
right coronary artery	UBERON:0001625	91.68	gold quality
body of uterus	UBERON:0009853	91.68	gold quality
duodenum	UBERON:0002114	91.58	gold quality
ectocervix	UBERON:0012249	91.19	gold quality
cauda epididymis	UBERON:0004360	90.10	gold quality
urethra	UBERON:0000057	89.78	gold quality
female reproductive system	UBERON:0000474	89.46	gold quality
left ovary	UBERON:0002119	89.45	gold quality
colonic mucosa	UBERON:0000317	89.24	gold quality
superficial temporal artery	UBERON:0001614	89.18	gold quality
right ovary	UBERON:0002118	89.12	gold quality
left coronary artery	UBERON:0001626	89.04	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.63	gold quality
left uterine tube	UBERON:0001303	88.58	gold quality
liver	UBERON:0002107	88.57	gold quality
coronary artery	UBERON:0001621	88.51	gold quality
mammalian vulva	UBERON:0000997	88.24	gold quality
saphenous vein	UBERON:0007318	88.05	gold quality
seminal vesicle	UBERON:0000998	87.85	gold quality
gall bladder	UBERON:0002110	87.55	gold quality
right lobe of liver	UBERON:0001114	87.36	gold quality
mucosa of stomach	UBERON:0001199	87.33	gold quality
ovary	UBERON:0000992	87.11	gold quality
left lobe of thyroid gland	UBERON:0001120	86.48	gold quality
vagina	UBERON:0000996	86.29	gold quality
uterine cervix	UBERON:0000002	86.27	gold quality
right lobe of thyroid gland	UBERON:0001119	86.26	gold quality
penis	UBERON:0000989	86.11	gold quality
sigmoid colon	UBERON:0001159	86.09	gold quality
large intestine	UBERON:0000059	86.02	gold quality
colon	UBERON:0001155	85.76	gold quality
thyroid gland	UBERON:0002046	85.76	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.52	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.46	gold quality
jejunum	UBERON:0002115	85.22	gold quality
intestine	UBERON:0000160	85.16	gold quality
blood vessel layer	UBERON:0004797	84.99	gold quality
urinary bladder	UBERON:0001255	84.97	gold quality
type B pancreatic cell	CL:0000169	84.77	gold quality
choroid plexus epithelium	UBERON:0003911	84.72	gold quality
olfactory bulb	UBERON:0002264	84.42	silver quality
tibial nerve	UBERON:0001323	84.37	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.35	gold quality
transverse colon	UBERON:0001157	84.30	gold quality
putamen	UBERON:0001874	84.17	gold quality
caudate nucleus	UBERON:0001873	84.14	gold quality
pericardium	UBERON:0002407	83.90	gold quality
mucosa of urinary bladder	UBERON:0001259	83.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.66	gold quality
mucosa of transverse colon	UBERON:0004991	83.41	gold quality
mammary duct	UBERON:0001765	83.38	gold quality
thoracic mammary gland	UBERON:0005200	83.21	gold quality
skin of hip	UBERON:0001554	82.88	gold quality
small intestine	UBERON:0002108	82.85	gold quality
peritoneum	UBERON:0002358	82.82	gold quality
caecum	UBERON:0001153	82.81	gold quality
omental fat pad	UBERON:0010414	82.80	gold quality
mammary gland	UBERON:0001911	82.75	gold quality
vermiform appendix	UBERON:0001154	82.73	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.70	gold quality
epithelium of bronchus	UBERON:0002031	82.45	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.28	gold quality
bronchus	UBERON:0002185	82.24	gold quality
islet of Langerhans	UBERON:0000006	82.20	gold quality
bronchial epithelial cell	CL:0002328	82.18	gold quality
amygdala	UBERON:0001876	82.15	gold quality
nucleus accumbens	UBERON:0001882	81.95	gold quality
colonic epithelium	UBERON:0000397	81.93	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.92	gold quality
connective tissue	UBERON:0002384	81.80	gold quality
epithelium of mammary gland	UBERON:0003244	81.53	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.47	gold quality
adenohypophysis	UBERON:0002196	81.44	gold quality
adipose tissue	UBERON:0001013	81.43	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	246.42
E-ANND-3	yes	13.59
E-GEOD-137537	no	602.75

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cervix	tissue	105.8	high
Retina	tissue	87.4
Smooth muscle	tissue	69.1	medium
Liver	tissue	51.2	medium
Endometrium 1	tissue	46.2	high
Duodenum	tissue	37.8	high
Ovary	tissue	34.3	high
Seminal vesicle	tissue	32.2	medium
Rectum	tissue	30.0	medium
Colon	tissue	27.5	high
Vagina	tissue	27.3	medium
Choroid plexus	tissue	27.0
Placenta	tissue	23.8	high
Locus coeruleus	tissue	23.4
Thyroid gland	tissue	22.3	medium
Small intestine	tissue	19.7	high
Fallopian tube	tissue	19.5	low
Adipose tissue	tissue	19.3	not detected
Nucleus accumbens	tissue	17.1
Gallbladder	tissue	16.1	high
Kidney	tissue	16.1	medium
Postcentral gyrus	tissue	15.8
Urinary bladder	tissue	14.8	high
Putamen	tissue	13.8
Spinal cord	tissue	13.2
Hippocampus	tissue	13.2	low
Prostate	tissue	12.5	low
Basal ganglia	tissue	12.4	medium
Spleen	tissue	12.2	high
Cerebral cortex	tissue	12.1	medium
Motor cortex	tissue	12.1
Prefrontal cortex	tissue	11.8
Ventral forebrain	tissue	11.8
Somatosensory cortex	tissue	11.7
Breast	tissue	11.5	medium
Occipital cortex	tissue	11.4
Caudate putamen	tissue	11.3
Appendix	tissue	11.2	high
Pituitary gland	tissue	10.9
Thalamus	tissue	10.9
Hippocampal formation	tissue	10.9
Entorhinal cortex	tissue	10.9
Temporal cortex	tissue	10.9
Tonsil	tissue	10.6	high
Retrosplenial and cingulate cortex	tissue	10.5
Midbrain	tissue	10.2
Insular cortex	tissue	10.1
Periaqueductal gray	tissue	10.0
Retrosplenial cortex	tissue	9.9
Testis	tissue	9.7	high
Tongue	tissue	9.4
Substantia nigra	tissue	9.4
Superior colliculi	tissue	9.2
Lymph node	tissue	9.0	medium
Medulla oblongata	tissue	8.7
Cerebellum	tissue	8.6	high
Septum	tissue	8.6
Pons	tissue	8.5
Corpus callosum	tissue	8.3
Esophagus	tissue	8.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (35.4), Cervical spinal cord, dorsal horn (27.0), Cervical spinal cord, central gray (25.9), Inferior colliculus (25.2), Cervical spinal cord, ventral horn (23.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, FOXO3, GFI1, HIF1A, HNF1A, JUN, LEF1, SP1, STAT3, TCF7, ZNF263

miRNA regulators (miRDB)

Targeting NT5E by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 118 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
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-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-22-3P	99.93	68.13	917

Functional genomics

gnomAD constraint: pLI 4.01e-18, LOEUF 1.25, missense Z 0.648 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000257770 — one region, missense o/e 0.94.

Literature-anchored findings (GeneRIF, showing 40)

• Review: Ecto-5’-nucleotidase in B-cell chronic lymphocytic leukemia (PMID:12000134)
• Regulation of ecto-5’-nucleotidase by TNF-alpha in human endothelial cells. (PMID:12030367)
• a critical enzyme responsible for the generation of adenosine (PMID:14578500)
• Review defines glycosylphosphatidylinositol-anchored 5’-nucleotidase as an extracellular, raft-associated enzyme responsible for conversion of extracellular adenosine triphosphate (ATP) into adenosine. (PMID:16709165)
• Expression of ecto-5’-nucleotidase in melanoma correlates with a number of metastasis-related markers and thus may have a function in this process. (PMID:16718268)
• Gliclazide inhibits the activity of lymphocyte ecto-5’-nucleotidase and decreases the concentration of adenosine at the cell surface. (PMID:16735966)
• CD73 is coexpressed with metastasis promoting antigens in human melanoma cells (PMID:17065075)
• CD73 may accelerate the growth of breast cancer by stimulating cell proliferation and tumor angiogenesis. (PMID:17487388)
• CD73 may facilitate the adhesion, migration and invasion of human breast cancer cells through its enzyme activity of generating adenosine (PMID:17671792)
• CD73 expression on central nervous system (CNS) microvasculature was confirmed with stainings of frozen tissue sections of multiple sclerosis brain samples taken at autopsy (PMID:17911479)
• eN is a novel and specific receptor for tenascin C (PMID:18062933)
• inhibition of TRAIL signaling works through interaction of CD73 with death receptor 5, as CD73 and death receptor 5 could be coimmunoprecipitated and were shown to be colocalized in the plasma membrane by confocal microscopy (PMID:18566412)
• Ecto-5’-nucleotidase/CD73 may regulate the extracellular adenosine 5’-monophosphate (AMP) and adenosine levels. (PMID:18636315)
• Data show that in varicocele patients, 5’-nucleotidase activity is decreased in seminal plasma and spermatozoa. (PMID:18787389)
• PMNs facilitate translocation across human epithelium and alter fluid homeostasis via epithelial cell-expressed NT5E. (PMID:18924612)
• CD73 plays a critical role by suppressing transendothelial leukocyte trafficking through its enzymatic activity and mitigates inflammatory and immune sequelae of cardiac transplantation via the adenosine 2B receptor. (PMID:19008478)
• CD73 expression can be modulated within minutes following exposure of HUVEC to lysophosphatidylcholine, and this response may be mediated by PKC (PMID:20476579)
• CD73 plays an important role in breast cancer growth by affecting cell cycle progression and apoptosis. (PMID:20874842)
• Studies indicate that it remains unclear whether interruption of IFNalphaA and IL-10 signaling in the absence of CD73 activity results from a deficiency of its product adenosine or an accumulation of its substrate nucleotides. (PMID:21057730)
• Abnormal expression of CD(73) in Treg cells may participate in the pathogenesis of systemic lupus erythematosus. (PMID:21092450)
• We identified mutations in NT5E in members of three families with symptomatic arterial and joint calcifications. This gene encodes CD73, which converts AMP to adenosine. (PMID:21288095)
• CD73 is expressed on a subpopulation of afferent lymph vessels but is absent on efferent lymphatics, unlike LYVE-1 and podoplanin, which are expressed on both types of lymphatics. (PMID:21346249)
• the ectonucleotidases CD39 and CD73 and ADORA2A appear as possible targets for novel treatments in ovarian cancer (PMID:21638125)
• Exosomes from diverse cancer cell types exhibit potent 5’AMP and ATP phosphohydrolytic activity, partly attributed to exosomally expressed CD73 and CD39, which contribute to extracellular adenosine production. (PMID:21677139)
• MSC migration is controlled by CD73 & CD29, which in turn are regulated by mechanical stimulation of cells (PMID:21732280)
• Sequence and structural analysis of H. influenzae NadN led to the discovery that human CD73 is capable of processing both NAD and NMN, therefore disclosing a possible novel function of human CD73 in systemic NAD metabolism. (PMID:21933152)
• CD73-generated extracellular adenosine activates type 1 purinergic A2A receptors that are constitutively expressed by chronic lymphocytic leukemia cells and that are further elevated in proliferating neoplastic cells. (PMID:21998208)
• The expression of CD73 is associated with leukemia subtype, differentiation and development. The higher differentiation of leukemia cells, the lower of CD73 expression in myeloid and B lymphoid leukemia. (PMID:22040959)
• Data show that the alterations in the CD39/CD73 adenosinergic machinery and loss of function in ADA-deficient Tregs provide insights into a predisposition to autoimmunity and the underlying mechanisms causing defective peripheral tolerance in ADA-SCID. (PMID:22184407)
• In multivariate Cox regression analysis, overexpression of CD73 was proven to be an independent prognostic biomarker for colorectal cancer. (PMID:22287455)
• deregulation of NT5E expression in melanoma occurs via epigenetic changes in the NT5E CpG island (PMID:22454080)
• Elevated CD73 expression in breast cancer can predict a good prognosis. However, the actual role of CD73 in cancerogenesis remains unclear and requires further analysis. (PMID:22553809)
• the activity of CD73 to trigger adenosine signaling sustains a chemoresistant phenotype in glioblastoma multiforme cells (PMID:22833450)
• The absence of ecto-5’NT/CD73 in the D283 cell line, a metastatic medulloblastoma phenotype, suggests that high expression levels of this ectonucleotidase could be correlated with a poor prognosis in patients with medulloblastoma. (PMID:23094051)
• Mutations in the underlying disease genes ENPP1, ABCC6, NT5E, and SLC20A2, respectively, lead to arterial media calcification. (PMID:23122642)
• Crystal structures of the dimeric human e5NT reveal an extensive conformational switch between the open and closed forms of the enzyme. (PMID:23142347)
• crystallization and preliminary X-ray crystallographic analysis of an open structural conformation of human e5NT are described. (PMID:23192044)
• Coronary vasodilation to adenine nucleotides is associated with endothelial CD73-dependent production of extracellular adenosine that acts as an endothelium-derived hyperpolarizing factor. (PMID:23288168)
• SNPs at the 5’-nucleotidase and xanthine oxidase genes influence the risk of noncirrhotic portal hypertension in HIV patients treated with didanosine. (PMID:23315321)
• Isoflurane causes TGF-beta1-dependent induction of renal tubular CD73 and adenosine generation to protect against renal ischemia and reperfusion injury. (PMID:23423261)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	nt5e	ENSDARG00000071017
mus_musculus	Nt5e	ENSMUSG00000032420
rattus_norvegicus	Nt5e	ENSRNOG00000011071
drosophila_melanogaster	veil	FBGN0034225
drosophila_melanogaster	CG30103	FBGN0050103
drosophila_melanogaster	NT5E-2	FBGN0050104
drosophila_melanogaster	CG42249	FBGN0259101

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:99782) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 27 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal response/metabolism to endogenous compounds	2
abnormal response to cardiac infarction	1
abnormal spleen morphology	1
enlarged spleen	1
abnormal testis morphology	1
enlarged testis	1
cataract	1
increased aggression towards humans	1
edema	1
abnormal eye morphology	1
abnormal kidney morphology	1
abnormal vitreous body morphology	1
increased circulating alkaline phosphatase level	1
small kidney	1
decreased coronary flow rate	1
increased myocardial infarct size	1
enlarged kidney	1
increased vascular permeability	1
calcinosis	1
calcified skin	1
lethargy	1
abnormal platelet physiology	1
abnormal renal vascular resistance	1
decreased bleeding time	1
urinary bladder obstruction	1

+2 more (showing top 25).

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
Gloydius brevicauda	B6EWW8	96.8%	Diamond
Crotalus adamanteus	F8S0Z7	96.8%	Diamond
Macrovipera lebetinus	W8EFS0	92.6%	Diamond
Bos taurus	Q05927	89.9%	Diamond
Naja atra	A0A2I4HXH5	89.4%	Diamond
Aedes albopictus	E0D877	83.0%	Diamond
Aedes aegypti	P50635	83.0%	Diamond
Anopheles gambiae	Q5TVM9	63.0%	Diamond
Diplobatis ommata	P29240	62.8%	Diamond
Treponema pallidum subsp. pallidum str. Nichols	O83142	50.1%	Diamond
Bacillus subtilis subsp. subtilis str. 168	O34313	46.3%	Diamond
Lutzomyia longipalpis	Q9XZ43	46.1%	Diamond
Tabanus yao	B3A0N5	40.5%	Diamond
Rhipicephalus microplus	P52307	40.5%	Diamond
Glossina morsitans morsitans	Q95P65	40.5%	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
LINC02535	ncRNA	101928820
SNORD50A	snoRNA	26799
SNHG5	ncRNA	387066
SNX14	protein-coding	57231
SYNCRIP	protein-coding	10492

Protein

Protein identifiers

5’-nucleotidase — P21589 (reviewed: P21589)

Alternative names: 5’-deoxynucleotidase, Ecto-5’-nucleotidase, IMP-specific 5’-nucleotidase, Thymidylate 5’-phosphatase

All UniProt accessions (4): P21589, H0Y3X5, H0Y7R7, Q96B60

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside, with AMP being the preferred substrate. Shows a preference for ribonucleotide monophosphates over their equivalent deoxyribose forms. Other substrates include IMP, UMP, GMP, CMP, dAMP, dCMP, dTMP, NAD and NMN.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane.

Disease relevance. Calcification of joints and arteries (CALJA) [MIM:211800] A condition characterized by adult-onset calcification of the lower extremity arteries, including the iliac, femoral and tibial arteries, and hand and foot capsule joints. Age of onset has been reported as early as the second decade of life, usually involving intense joint pain or calcification in the hands. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by adenosine 5’-(alpha,beta-methylene)-diphosphate (AMPCP).

Similarity. Belongs to the 5’-nucleotidase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P21589-1	1	yes
P21589-2	2

RefSeq proteins (2): NP_001191742, NP_002517* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004843	Calcineurin-like_PHP	Domain
IPR006146	5’-Nucleotdase_CS	Conserved_site
IPR006179	5_nucleotidase/apyrase	Family
IPR008334	5’-Nucleotdase_C	Domain
IPR029052	Metallo-depent_PP-like	Homologous_superfamily
IPR036907	5’-Nucleotdase_C_sf	Homologous_superfamily

Pfam: PF00149, PF02872

Enzyme classification (BRENDA)

• EC 3.1.3.5 — 5’-nucleotidase (BRENDA: 107 organisms, 375 substrates, 402 inhibitors, 307 Km, 66 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
5’-AMP	0.0003–23	73
5’-IMP	0.0071–18	49
5’-GMP	0.0064–7.2	29
5’-UMP	0.014–56	27
5’-CMP	0.002–100	19
INOSINE	0.25–10.2	13
5’-DAMP	0.012–35	9
AMP	0.0091–1.49	8
5’-DGMP	0.044–142	7
4-NITROPHENYL PHOSPHATE	0.224–21.78	6
5’-DCMP	0.023–0.75	6
DCMP	0.012–0.193	6
5’-TMP	0.008–0.73	5
5’-XMP	0.065–2.9	5
5’-DTMP	0.008–22	4

Catalyzed reactions (Rhea)

• dTMP + H2O = thymidine + phosphate (RHEA:11080)
• a ribonucleoside 5’-phosphate + H2O = a ribonucleoside + phosphate (RHEA:12484)
• GMP + H2O = guanosine + phosphate (RHEA:27714)
• IMP + H2O = inosine + phosphate (RHEA:27718)
• UMP + H2O = uridine + phosphate (RHEA:29359)
• dCMP + H2O = 2’-deoxycytidine + phosphate (RHEA:29363)
• CMP + H2O = cytidine + phosphate (RHEA:29367)
• dAMP + H2O = 2’-deoxyadenosine + phosphate (RHEA:29371)
• AMP + H2O = adenosine + phosphate (RHEA:29375)
• a 2’-deoxyribonucleoside 5’-phosphate + H2O = a 2’-deoxyribonucleoside + phosphate (RHEA:36167)

UniProt features (99 total): strand 31, helix 26, binding site 20, glycosylation site 4, disulfide bond 4, turn 4, sequence variant 3, site 2, signal peptide 1, chain 1, propeptide 1, lipid moiety-binding region 1, splice variant 1

Structure

Experimental structures (PDB)

showing 30 of 52 structures by resolution:

PDB	Title	Method	Resolution (Å)
6TVE	Unliganded human CD73 (5’-nucleotidase) in the open state	X-RAY DIFFRACTION	1.05
9HJ4	Crystal structure of CD73 (ecto-5’-nucleotidase) complexed to 8-butylthioadenosine …	X-RAY DIFFRACTION	1.06
7PBY	Crystal structure of CD73 in complex with 4-nitrocatechol in the open form	X-RAY DIFFRACTION	1.13
7PB5	Crystal structure of CD73 in complex with UMP in the open form	X-RAY DIFFRACTION	1.28
7PCP	Crystal structure of CD73 in complex with 5-iodouracil in the open form	X-RAY DIFFRACTION	1.38
7PD9	Crystal structure of CD73 in complex with riboflavin in the open form	X-RAY DIFFRACTION	1.39
7P9R	Crystal structure of CD73 in complex with GMP in the open form	X-RAY DIFFRACTION	1.41
7PBA	Crystal structure of CD73 in complex with IMP in the open form	X-RAY DIFFRACTION	1.42
7PA4	Crystal structure of CD73 in complex with CMP in the open form	X-RAY DIFFRACTION	1.45
7PBB	Crystal structure of CD73 in complex with caffeine in the open form	X-RAY DIFFRACTION	1.47
6TVG	Human CD73 (ecto 5’-nucleotidase) in complex with AMPCP in the open state	X-RAY DIFFRACTION	1.48
7QGA	Human CD73 (ecto 5’-nucleotidase) in complex with MRS4598 (a 3-methyl-CMPCP derivative …	X-RAY DIFFRACTION	1.5
7QGL	Human CD73 (ecto 5’-nucleotidase) in complex with MRS4602 (a 3-methyl-CMPCP derivative …	X-RAY DIFFRACTION	1.5
4H2G	Human ecto-5’-nucleotidase (CD73): crystal form II (open) in complex with adenosine	X-RAY DIFFRACTION	1.55
7P9N	Crystal structure of CD73 in complex with AMP in the open form	X-RAY DIFFRACTION	1.55
4H1Y	Human ecto-5’-nucleotidase (CD73): crystal form II (open) in complex with PSB11552	X-RAY DIFFRACTION	1.58
4H2B	Human ecto-5’-nucleotidase (CD73): crystal form II (open) in complex with Baicalin	X-RAY DIFFRACTION	1.7
7P9T	Crystal structure of CD73 in complex with dCMP in the open form	X-RAY DIFFRACTION	1.79
4H2F	Human ecto-5’-nucleotidase (CD73): crystal form I (open) in complex with adenosine	X-RAY DIFFRACTION	1.85
6S7H	Human CD73 (5’-nucleotidase) in complex with PSB12489 (an AOPCP derivative) in the closed …	X-RAY DIFFRACTION	1.85
6Z9D	Human Ecto-5’-nucleotidase (CD73) in complex with AOPCP derivative AB680 (compound 55 in …	X-RAY DIFFRACTION	1.9
6XUE	Human Ecto-5’-nucleotidase (CD73) in complex with A2396 (compound 74 in publication) in …	X-RAY DIFFRACTION	1.94
6XUQ	Human Ecto-5’-nucleotidase (CD73) in complex with A1618 (compound 1b in publication) in …	X-RAY DIFFRACTION	1.97
4H2I	Human ecto-5’-nucleotidase (CD73): crystal form III (closed) in complex with AMPCP	X-RAY DIFFRACTION	2
6TWA	Human CD73 (ecto 5’-nucleotidase) in complex with PSB12646 (an AOPCP derivative, compound …	X-RAY DIFFRACTION	2
6S7F	Human CD73 (5’-nucleotidase) in complex with PSB12379 (an AOPCP derivative) in the closed …	X-RAY DIFFRACTION	2.05
6XUG	Human Ecto-5’-nucleotidase (CD73) in complex with A2410 (compound 53 in publication) in …	X-RAY DIFFRACTION	2.09
6Z9B	Human Ecto-5’-nucleotidase (CD73) in complex with AOPCP derivative A830 (compound 16 in …	X-RAY DIFFRACTION	2.17
4H1S	Crystal Structure of a Truncated Soluble form of Human CD73 with Ecto-5’-Nucleotidase …	X-RAY DIFFRACTION	2.2
7QGO	Human CD73 (ecto 5’-nucleotidase) in complex with MRS4602 (a 3-methyl-CMPCP derivative …	X-RAY DIFFRACTION	2.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21589-F1	91.95	0.86

Antibody-complex structures (SAbDab)

5 antibodies co-crystallized with this protein: 6HXW, 6VC9, 6VCA, 7BBJ, 8ZNZ

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, CD markers, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; cytosol; nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

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 (2)

Position	Role
118	transition state stabilizer
121	transition state stabilizer

Ligand- & substrate-binding residues (20)

Position	Role
243	Zn(2+)
354	AMP
354	IMP
390	AMP
390	IMP
395	AMP
395	IMP
417	AMP
417	IMP
500	AMP
500	IMP
506	AMP
506	IMP
36	Zn(2+)
38	Zn(2+)
85	Zn(2+)
117	Zn(2+)
220	Zn(2+)

Post-translational modifications (1)

Type	Positions
Gpi-anchor amidated serine	549

Disulfide bonds (4)

Type	Positions
Disulfide bond	51–57, 353–358, 365–387, 476–479

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	53, 311, 333, 403

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 14; 6 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

14 pathways:

ID	Pathway	Evidence
R-HSA-9660826	Purinergic signaling in leishmaniasis infection ⚕	curated
R-HSA-196807	Nicotinate metabolism	curated
R-HSA-74259	Purine catabolism	curated
R-HSA-73621	Pyrimidine catabolism	curated
R-HSA-9664424	Cell recruitment (pro-inflammatory response) ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9658195	Leishmania infection ⚕	—
R-HSA-9824443	Parasitic Infection Pathways ⚕	—
R-HSA-1430728	Metabolism	—
R-HSA-15869	Metabolism of nucleotides	—
R-HSA-196854	Metabolism of vitamins and cofactors	—
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors	—
R-HSA-8956319	Nucleotide catabolism	—

MSigDB gene sets: 442 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, TSUNODA_CISPLATIN_RESISTANCE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_INFLAMMATORY_RESPONSE, REACTOME_PYRIMIDINE_CATABOLISM, AAGTCCA_MIR422B_MIR422A, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS

GO Biological Process (9): AMP catabolic process (GO:0006196), leukocyte cell-cell adhesion (GO:0007159), biomineral tissue development (GO:0031214), response to ATP (GO:0033198), ADP catabolic process (GO:0046032), ATP metabolic process (GO:0046034), calcium ion homeostasis (GO:0055074), inhibition of non-skeletal tissue mineralization (GO:0140928), nucleotide catabolic process (GO:0009166)

GO Molecular Function (9): nucleotide binding (GO:0000166), 5’-deoxynucleotidase activity (GO:0002953), 5’-nucleotidase activity (GO:0008253), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on ester bonds (GO:0016788), metal ion binding (GO:0046872)

GO Cellular Component (6): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), extracellular exosome (GO:0070062), side of membrane (GO:0098552)

Reactome top-level categories

10 top-level categories:

Category	Pathways
Nucleotide catabolism	2
Metabolism	2
Metabolism of water-soluble vitamins and cofactors	1
Cell recruitment (pro-inflammatory response)	1
Metabolism of vitamins and cofactors	1
Disease	1
Metabolism of nucleotides	1
Parasitic Infection Pathways	1
Leishmania infection	1
Infectious disease	1

GO top-level categories

37 GO namespaces:

Category	Terms
cellular anatomical structure	3
purine ribonucleotide catabolic process	2
membrane	2
purine ribonucleoside monophosphate catabolic process	1
AMP metabolic process	1
cell-cell adhesion	1
tissue development	1
animal organ development	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
purine ribonucleoside diphosphate catabolic process	1
ADP metabolic process	1
nucleoside triphosphate metabolic process	1
purine ribonucleotide metabolic process	1
purine ribonucleoside triphosphate metabolic process	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
tissue homeostasis	1
nucleotide metabolic process	1
nucleoside phosphate catabolic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
5’-nucleotidase activity	1
nucleotidase activity	1
transition metal ion binding	1
protein binding	1
binding	1
catalytic activity	1
hydrolase activity	1
cation binding	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
extracellular vesicle	1
leaflet of membrane bilayer	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 24 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
ATP metabolic process	BP	direct assay
biomineral tissue development	BP	direct assay
leukocyte cell-cell adhesion	BP	direct assay
response to ATP	BP	direct assay
cell surface	CC	high-throughput assay
extracellular exosome	CC	high-throughput assay
membrane	CC	direct assay
plasma membrane	CC	direct assay
5’-deoxynucleotidase activity	MF	direct assay
5’-nucleotidase activity	MF	direct assay
identical protein binding	MF	direct assay
zinc ion binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,634 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NT5E	ENTPD1	P49961	981
NT5E	ENG	P17813	930
NT5E	THY1	P04216	928
NT5E	CD34	P28906	892
NT5E	PTPRC	P08575	888
NT5E	ITGB1	P05556	886
NT5E	CD44	P16070	886
NT5E	ENPP1	P22413	884
NT5E	CD19	P15391	826
NT5E	PECAM1	P16284	812
NT5E	ALCAM	Q13740	807
NT5E	ITGAM	P11215	772
NT5E	MCAM	P43121	767
NT5E	ADORA2A	P29274	764
NT5E	ANPEP	P15144	734

IntAct

Human interaction partners of NT5E in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
RNF24	physical association	0.560	3
ZNRF4	physical association	0.560	3
SCAMP1	association	0.530	1
ARG2	physical association	0.400	1
IL13RA2	association	0.350	1
SCAMP3	association	0.350	1

BioGRID (161 interactions; top human partners by supporting records): USP22 (Affinity Capture-MS; 4 records), ADIPOR1 (Affinity Capture-MS; 3 records), ARF5 (Affinity Capture-MS; 3 records), ARL2 (Affinity Capture-MS; 3 records), CYP2S1 (Affinity Capture-MS; 3 records), DNAAF5 (Affinity Capture-MS; 3 records), FLVCR1 (Affinity Capture-MS; 3 records), GJA1 (Affinity Capture-MS; 3 records), GLMN (Affinity Capture-MS; 3 records), HSDL1 (Affinity Capture-MS; 3 records), MTOR (Affinity Capture-MS; 3 records), NR2F2 (Affinity Capture-MS; 3 records), PDS5A (Affinity Capture-MS; 3 records), RAB9A (Affinity Capture-MS; 3 records), RHOG (Affinity Capture-MS; 3 records)

SIGNOR signaling

4 signaling interactions:

A	Effect	B	Mechanism
HIF1A	“up-regulates quantity by expression”	NT5E	“transcriptional regulation”
TTK	“up-regulates activity”	NT5E	phosphorylation
NT5E	“up-regulates quantity”	adenosine	“chemical modification”
NT5E	“down-regulates quantity”	AMP	“chemical modification”

Ligand–receptor pairs (CellPhoneDB) (4)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

4 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
ADORA2B		Signaling by Adenosine
ADORA2A		Signaling by Adenosine
ADORA3		Signaling by Adenosine
ADORA1		Signaling by Adenosine

Disease & clinical

Genetic variants

Variant evidence for NT5E: 125 ClinVar records (5 pathogenic / likely pathogenic); 1 CIViC cancer variant; 7 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	88
Likely benign	16
Benign	8

Top pathogenic / likely-pathogenic (5)

Showing all 5 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
29689	NM_002526.4(NT5E):c.1608dup (p.Val537fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
2633543	NM_002526.4(NT5E):c.1428C>A (p.Cys476Ter)	Likely pathogenic	criteria provided, single submitter	1
4887735	NM_002526.4(NT5E):c.1104+2T>A	Likely pathogenic	criteria provided, single submitter	1
29687	NM_002526.4(NT5E):c.662C>A (p.Ser221Ter)	Pathogenic	no assertion criteria provided	1
29688	NM_002526.4(NT5E):c.1073G>A (p.Cys358Tyr)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore NT5E’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; 46 predictions of 606):

Position(s)	Effect	Δscore	Sites
6:85450479–85450480	donor_loss	1.0000	4
6:85467058–85467059	acceptor_loss	1.0000	6
6:85471235–85471236	acceptor_loss	1.0000	6
6:85471426–85471427	donor_loss	1.0000	5
6:85485433	donor_loss	1.0000	2
6:85487490–85487491	donor_loss	1.0000	5
6:85489492–85489493	acceptor_loss	1.0000	5
6:85450479	donor_loss	0.9900
6:85467283–85467284	donor_loss	0.9900	6
6:85485233–85485234	acceptor_loss	0.9900	6

AlphaMissense

1,251 missense substitutions predicted likely pathogenic (of 3,759 scored), across 337 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D36	8	0.993	0.998
H118	8	0.993	0.997
D85	8	0.990	0.999
H220	8	0.985	0.994
H38	8	0.980	0.994
D121	8	0.973	0.991
H243	8	0.972	0.988
N117	8	0.969	0.997
H33	8	0.962	0.988
D226	8	0.961	0.994
F120	8	0.949	0.993
D82	8	0.947	0.975
D506	8	0.908	0.971
F193	8	0.897	0.979
D422	8	0.895	0.928
D366	8	0.877	0.956
D237	8	0.869	0.953
D524	8	0.811	0.956
F435	8	0.810	0.967
F93	7	0.984	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (TCGA)	unfavorable	1.51e-07
Rectum Adenocarcinoma (validation)	unfavorable	2.06e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.14e-05
Stomach Adenocarcinoma (TCGA)	unfavorable	5.5e-05

Disease associations

OMIM: gene MIM:129190 | disease phenotypes: MIM:211800

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
hereditary arterial and articular multiple calcification syndrome	Strong	Autosomal recessive	4

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

Panel	Rating
Hypotonic infant	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Paediatric disorders	green
Skeletal dysplasia	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (1): hereditary arterial and articular multiple calcification syndrome (MONDO:0008895)

Orphanet (1): Hereditary arterial and articular multiple calcification syndrome (Orphanet:289601)

HPO phenotypes

15 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001717	Coronary artery calcification
HP:0003207	Arterial calcification
HP:0004417	Intermittent claudication
HP:0005116	Arterial tortuosity
HP:0005645	Intervertebral disk calcification
HP:0011025	Abnormal cardiovascular system physiology
HP:0011986	Ectopic ossification
HP:0012101	Decreased serum creatinine
HP:0025015	Abnormal vascular morphology
HP:0025324	Arterial occlusion
HP:0025477	Periarticular calcification
HP:0031303	Femoral arterial calcification
HP:0031304	Iliac arterial calcification
HP:0031305	Tibial arterial calcification

GWAS associations

7 associations:

Study	Trait	p-value
GCST012020_192	Serum metabolite levels	9e-15
GCST012020_193	Serum metabolite levels	9e-14
GCST012020_194	Serum metabolite levels	6e-13
GCST001217_27	Metabolic traits	7e-13
GCST012020_413	Serum metabolite levels	5e-11
GCST006993_12	Hippocampal volume in Alzheimer’s disease dementia	8e-7
GCST010057_7	Lung function	2e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004725	metabolite measurement
EFO:0005035	hippocampal volume
EFO:0004312	vital capacity

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C565891	Calcification of Joints and Arteries *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5957 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the NT5E 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
OLECLUMAB	Antibody	3

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 221,947 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

7 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1568	FLUDARABINE	3	101,644
CHEMBL50	QUERCETIN	3	75,572
CHEMBL6246	ELLAGIC ACID	2	23,439
CHEMBL2105120	FTIVAZIDE	2	118
CHEMBL4471306	QUEMLICLUSTAT	2	515
CHEMBL269277	BETULINIC ACID	1	20,637
CHEMBL4792487	LY-3475070	1	22

Clinical evidence (CIViC)

Drug × variant × indication, from 1 curated evidence items. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

1 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
NT5E Overexpression	Cetuximab	Colorectal Cancer	Sensitivity/Response	CIViC B	EID730

CIViC curated variants (1)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

Overexpression.

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

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

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs9450278			Allele A is associated with decreased expression of NT5E.	PMID:20855458

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Adenosine turnover

Most potent curated ligand interactions (11 total), top 11:

Ligand	Action	Affinity	Parameter
oleclumab	Binding	11.38	pKd
quemliclustat	Inhibition	11.3	pKi
dalutrafusp alfa	Binding	10.16	pKd
compound 49 [PMID: 36529947]	Inhibition	9.77	pIC50
αβ-methyleneADP	Inhibition	8.7	pIC50
compound 15 [PMID: 32045236]	Inhibition	8.44	pKi
mupadolimab	Inhibition	8.15	pKd
ORIC-533	Inhibition	8.0	pIC50
quercetin	Inhibition	7.34	pKi
PSB-0963	Inhibition	6.82	pKi
NUCC-0227579	Binding	6.04	pKd

Binding affinities (BindingDB)

1536 measured of 1992 human assays (2073 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4743437	IC50	0.0027 nM
CHEMBL5631165	KI	0.005 nM
CHEMBL4761506	IC50	0.01 nM
[(2R,3S,4R,5R)-5-(6-chloro-4-spiro[1,2-dihydroindene-3,3’-azetidine]-1’-ylpyrazolo[5,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxymethylphosphonic acid	IC50	0.013 nM	US-11332492: CD73 inhibitors and therapeutic uses thereof
CHEMBL6162112	IC50	0.02 nM
CHEMBL6152291	IC50	0.02 nM
CHEMBL4749428	IC50	0.027 nM
CHEMBL4776758	IC50	0.028 nM
CHEMBL4746184	IC50	0.031 nM
CHEMBL4740465	IC50	0.031 nM
CHEMBL4797225	IC50	0.032 nM
CHEMBL6150713	IC50	0.04 nM
CHEMBL6160794	IC50	0.04 nM
CHEMBL6167368	IC50	0.04 nM
CHEMBL6170363	IC50	0.05 nM
2-(((2R,3S,4R,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-3-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-2-(4-(2-oxo-3-propyltetrahydropyrimidin-1 (2H)-yl)benzyl)malonic acid	IC50	0.05 nM	US-11078228: Ectonucleotidase inhibitors and methods of use thereof
CHEMBL4790144	IC50	0.052 nM
CHEMBL4745002	IC50	0.058 nM
2-(((2R,3S,4R,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-3-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-2-(4-(1-(methoxymethyl)-2-oxo-1,2-dihydropyridin-3-yl)benzyl)malonic acid	IC50	0.06 nM	US-11078228: Ectonucleotidase inhibitors and methods of use thereof
[[(2R,3S,4R,5R)-5-[4-[(3aR,6aS)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-6-chloropyrazolo[5,4-d]pyrimidin-1-yl]-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	IC50	0.06 nM	US-20240368204: SMALL MOLECULAR CD73 ANTAGONIST AND USE THEREOF
CHEMBL4784155	IC50	0.07 nM
[(2R,3S,4R,5R)-5-[6-chloro-4-(6-chlorospiro[1H-2-benzofuran-3,3’-azetidine]-1’-yl)pyrazolo[5,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethylphosphonic acid	IC50	0.074 nM	US-11332492: CD73 inhibitors and therapeutic uses thereof
2-(((2R,3S,4R,5R)-5-(2-chloro-6-(methylamino)-9H-purin-9-yl)-3-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-2-(4-(3-methyl-2-oxotetrahydropyrimidin-1 (2H)-yl)benzyl)malonic acid	IC50	0.08 nM	US-11078228: Ectonucleotidase inhibitors and methods of use thereof
CHEMBL4777161	IC50	0.095 nM
2-(((2R,3S,4R,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-3-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-2-(4-(2-oxotetrahydropyrimidin-1 (2H)-yl)benzyl)malonic acid	IC50	0.1 nM
2-(((2R,3S,4R,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-3-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-2-(4-(2-oxo-1,2-dihydropyridin-3-yl)benzyl)malonic acid	IC50	0.1 nM	US-11078228: Ectonucleotidase inhibitors and methods of use thereof
5-[3-[(1R)-2,2-difluoro-1-(2-pyridyl)ethoxy]-1-methyl-pyrazolo[3,4-c]pyridazin-5-yl]-1H-pyrimidine-2,4-dione and 5-[3-[(1S)-2,2-difluoro-1-(2-pyridyl)ethoxy]-1-methyl-pyrazolo[3,4-c]pyridazin-5-yl]-1H-pyrimidine-2,4-dione	IC50	0.1 nM	US-20260055113: HETEROARYL COMPOUNDS FOR THE TREATMENT OF CANCER
2-(((2R,3S,4R,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-3-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-2-(4-(3-methyl-2-oxotetrahydropyrimidin-1 (2H)-yl)benzyl)malonic acid	IC50	0.11 nM	US-11078228: Ectonucleotidase inhibitors and methods of use thereof
[(2R,3S,4R,5R)-5-[4-(2-azaspiro[3.5]nonan-2-yl)-6-chloropyrazolo[5,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethylphosphonic acid	IC50	0.11 nM	US-11332492: CD73 inhibitors and therapeutic uses thereof
CHEMBL4753354	IC50	0.12 nM
2-(((2R,3S,4R,5R)-5-(2-chloro-6-(isopropylamino)-9H-purin-9-yl)-3-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-2-(4-(3-(2-hydroxyethyl)-2-oxotetrahydropyrimidin-1 (2H)-yl)benzyl)malonic acid	IC50	0.13 nM	US-11078228: Ectonucleotidase inhibitors and methods of use thereof
[(2R,3S,4R,5R)-5-[6-chloro-4-(6-methoxyspiro[1,2-dihydroindene-3,3’-azetidine]-1’-yl)pyrazolo[5,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethylphosphonic acid	IC50	0.13 nM	US-11332492: CD73 inhibitors and therapeutic uses thereof
US20240043427, Example 436	IC50	0.13 nM	US-20240043427: CD73 COMPOUNDS
5-[3-[(1R)-2,2-difluoro-1-(6-methyl-2-pyridyl)ethoxy]-1-methyl-pyrazolo[3,4-c]pyridazin-5-yl]-1H-pyrimidine-2,4-dione and 5-[3-[(1S)-2,2-difluoro-1-(6-methyl-2-pyridyl)ethoxy]-1-methyl-pyrazolo[3,4-c]pyridazin-5-yl]-1H-pyrimidine-2,4-dione	IC50	0.13 nM	US-20260055113: HETEROARYL COMPOUNDS FOR THE TREATMENT OF CANCER
2-(((2R,3S,4R,5R)-5-(5-chloro-7-((2,4-dimethoxybenzyl)amino)-3H-imidazo[4,5-b]pyridin-3-yl)-3-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-2-(4-(2-oxotetrahydropyrimidin-1 (2H)-yl)benzyl)malonic acid	IC50	0.14 nM	US-11078228: Ectonucleotidase inhibitors and methods of use thereof
US20240043427, Example 438	IC50	0.14 nM	US-20240043427: CD73 COMPOUNDS
CHEMBL4763896	IC50	0.15 nM
CHEMBL4758486	IC50	0.15 nM
2-(((2R,3S,4R,5R)-5-(2-chloro-6-((cyclopropylmethyl)amino)-9H-purin-9-yl)-3-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-2-(4-(3-(2-hydroxyethyl)-2-oxotetrahydropyrimidin-1 (2H)-yl)benzyl)malonic acid	IC50	0.15 nM	US-11078228: Ectonucleotidase inhibitors and methods of use thereof
US20240043427, Example 431	IC50	0.15 nM	US-20240043427: CD73 COMPOUNDS
US20240043427, Example 432	IC50	0.15 nM	US-20240043427: CD73 COMPOUNDS
5-[1-methyl-3-[(1S)-1-phenylethoxy]pyrazolo[3,4-c]pyridazin-5-yl]-1H-pyrimidine-2,4-dione	IC50	0.15 nM	US-20260055113: HETEROARYL COMPOUNDS FOR THE TREATMENT OF CANCER
5-[1-methyl-3-[(1R)-2,2,2-trifluoro-1-phenyl-ethoxy]pyrazolo[3,4-c]pyridazin-5-yl]-1H-pyrimidine-2,4-dione and 5-[1-methyl-3-[(1S)-2,2,2-trifluoro-1-phenyl-ethoxy]pyrazolo[3,4-c]pyridazin-5-yl]-1H-pyrimidine-2,4-dione	IC50	0.15 nM	US-20260055113: HETEROARYL COMPOUNDS FOR THE TREATMENT OF CANCER
5-[3-[(1R)-2,2-difluoro-1-(5-fluoro-2-pyridyl)ethoxy]-1-methyl-pyrazolo[3,4-c]pyridazin-5-yl]-1H-pyrimidine-2,4-dione and 5-[3-[(1S)-2,2-difluoro-1-(5-fluoro-2-pyridyl)ethoxy]-1-methyl-pyrazolo[3,4-c]pyridazin-5-yl]-1H-pyrimidine-2,4-dione	IC50	0.15 nM	US-20260055113: HETEROARYL COMPOUNDS FOR THE TREATMENT OF CANCER
2-(((2R,3S,4R,5R)-5-(2-chloro-6-((cyclopropylmethyl)amino)-9H-purin-9-yl)-3-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-2-(4-(3-methyl-2-oxotetrahydropyrimidin-1 (2H)-yl)benzyl)malonic acid	IC50	0.16 nM	US-11078228: Ectonucleotidase inhibitors and methods of use thereof
US20240043427, Example 430	IC50	0.18 nM	US-20240043427: CD73 COMPOUNDS
CHEMBL4744502	IC50	0.2 nM
2-(((2R,3S,4R,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-3-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-2-(4-(2-oxo-1-propy-1,2-dihydropyridin-3-yl)benzyl)malonic acid	IC50	0.2 nM	US-11078228: Ectonucleotidase inhibitors and methods of use thereof
2-(((2R,3S,4R,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-3-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-2-(4-(1-ethyl-2-oxo-1,2-dihydropyridin-3-yl)benzyl)malonic acid	IC50	0.2 nM	US-11078228: Ectonucleotidase inhibitors and methods of use thereof
2-(((2R,3S,4R,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-3-ethynyl-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-2-((2′-carboxy-[1,1′-biphenyl]-4-yl)methyl)malonic acid	IC50	0.2 nM	US-11078228: Ectonucleotidase inhibitors and methods of use thereof

ChEMBL bioactivities

1448 potent at pChembl≥5 of 1520 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL4761506
10.96	IC50	0.011	nM	QUEMLICLUSTAT
10.89	IC50	0.013	nM	CHEMBL5431118
10.70	IC50	0.02	nM	CHEMBL6162112
10.70	IC50	0.02	nM	CHEMBL6152291
10.68	IC50	0.021	nM	CHEMBL4761506
10.57	IC50	0.027	nM	CHEMBL4749428
10.55	IC50	0.028	nM	CHEMBL4776758
10.51	IC50	0.031	nM	CHEMBL4746184
10.51	IC50	0.031	nM	CHEMBL4740465
10.49	IC50	0.032	nM	CHEMBL4797225
10.42	Ki	0.038	nM	CHEMBL5423436
10.40	IC50	0.04	nM	CHEMBL6150713
10.40	IC50	0.04	nM	CHEMBL6160794
10.40	IC50	0.04	nM	CHEMBL6167368
10.39	IC50	0.041	nM	QUEMLICLUSTAT
10.37	IC50	0.043	nM	QUEMLICLUSTAT
10.35	IC50	0.045	nM	CHEMBL4743437
10.30	IC50	0.05	nM	CHEMBL5431118
10.30	IC50	0.05	nM	CHEMBL6035583
10.30	IC50	0.05	nM	CHEMBL6170363
10.29	IC50	0.051	nM	CHEMBL5431118
10.28	IC50	0.052	nM	CHEMBL4790144
10.28	IC50	0.053	nM	CHEMBL4743437
10.24	IC50	0.058	nM	CHEMBL4745002
10.22	IC50	0.06	nM	CHEMBL6026050
10.15	IC50	0.07	nM	CHEMBL4784155
10.13	IC50	0.074	nM	CHEMBL5984330
10.10	IC50	0.08	nM	CHEMBL6062089
10.02	IC50	0.095	nM	CHEMBL4777161
10.00	IC50	0.1	nM	CHEMBL5404625
10.00	IC50	0.1	nM	CHEMBL5423436
9.96	Ki	0.11	nM	CHEMBL5423436
9.96	IC50	0.11	nM	CHEMBL5899531
9.96	IC50	0.11	nM	CHEMBL5929751
9.94	IC50	0.115	nM	CHEMBL4761506
9.92	IC50	0.12	nM	CHEMBL4753354
9.89	IC50	0.13	nM	CHEMBL5827587
9.89	IC50	0.13	nM	CHEMBL5786397
9.85	IC50	0.14	nM	CHEMBL5923677
9.82	IC50	0.15	nM	CHEMBL4763896
9.82	IC50	0.15	nM	CHEMBL4758486
9.82	IC50	0.15	nM	CHEMBL5423436
9.82	IC50	0.15	nM	CHEMBL5809627
9.80	IC50	0.16	nM	CHEMBL5844303
9.77	IC50	0.17	nM	CHEMBL5423436
9.74	IC50	0.18	nM	CHEMBL5423436
9.70	IC50	0.2	nM	CHEMBL4744502
9.70	IC50	0.2	nM	CHEMBL5398484
9.70	IC50	0.2	nM	CHEMBL5828700

PubChem BioAssay actives

611 with measured affinity, of 981 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
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-1-(2-fluorophenyl)ethyl]amino]pyrazolo[5,4-b]pyridin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1605331: Inhibition of human CD73	ki	<0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-1-(3-fluorophenyl)ethyl]amino]pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-1-phenylethyl]amino]pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
[[(2R,3S,4R,5R)-5-[2-chloro-4-[[(1S)-1-(4-fluorophenyl)ethyl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-1-(4-fluorophenyl)ethyl]amino]pyrazolo[5,4-b]pyridin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674272: Inhibition of CD73 in human CD8-positive T cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 2.5 hrs by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
[[(2R,3S,4R,5R)-5-[2-chloro-4-[[(1S)-1-(2-fluorophenyl)ethyl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
[[(2R,3S,4R,5R)-5-[2-chloro-4-[[(1S)-1-(3-fluorophenyl)ethyl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]-2-[[4-(2-oxo-1,3-diazinan-1-yl)phenyl]methyl]propanedioic acid	1964441: Competitive inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells assessed as inhibition constant incubated for 1 hr by malachite green based spectrophotometer assay	ki	<0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1R)-1-(2-fluorophenyl)ethyl]amino]pyrazolo[5,4-b]pyridin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	2007820: Binding affinity to C-terminal His6-tagged human recombinant CD73 in HEK293 cells assessed as inhibition constant	ki	<0.0001	uM
6-[3-[(1R)-2,2-difluoro-1-[2-(2,2,2-trifluoroethoxy)-4-pyridinyl]ethoxy]-1-methylpyrazolo[3,4-c]pyridazin-5-yl]-2H-1,2,4-triazine-3,5-dione	2251198: Inhibition of recombinant human CD73 preincubated for 15 mins followed by AMP addition measured after 10 mins by LC/MS analysis	ic50	<0.0001	uM
6-[3-[(1R)-1-[2-(2,2-difluoroethoxy)-4-pyridinyl]-2,2-difluoroethoxy]-1-methylpyrazolo[3,4-c]pyridazin-5-yl]-2H-1,2,4-triazine-3,5-dione	2251198: Inhibition of recombinant human CD73 preincubated for 15 mins followed by AMP addition measured after 10 mins by LC/MS analysis	ic50	<0.0001	uM
[(2R,3S,4R,5R)-5-[5-chloro-7-[[(1S)-1-(2-fluorophenyl)ethyl]amino]imidazo[4,5-b]pyridin-3-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	2132855: Binding affinity to human recombinant CD73 assessed as inhibition constant	ki	<0.0001	uM
6-[3-[(1R)-2,2-difluoro-1-[2-[[(2S)-1,1,1-trifluoropropan-2-yl]amino]-4-pyridinyl]ethoxy]-1-methylpyrazolo[3,4-c]pyridazin-5-yl]-2H-1,2,4-triazine-3,5-dione	2251198: Inhibition of recombinant human CD73 preincubated for 15 mins followed by AMP addition measured after 10 mins by LC/MS analysis	ic50	<0.0001	uM
6-[3-[(1R)-1-[2-(2,2-difluoropropoxy)-4-pyridinyl]-2,2-difluoroethoxy]-1-methylpyrazolo[3,4-c]pyridazin-5-yl]-2H-1,2,4-triazine-3,5-dione	2251198: Inhibition of recombinant human CD73 preincubated for 15 mins followed by AMP addition measured after 10 mins by LC/MS analysis	ic50	<0.0001	uM
6-[3-[(1R)-2,2-difluoro-1-[2-[[(2R)-1,1,1-trifluoropropan-2-yl]amino]-4-pyridinyl]ethoxy]-1-methylpyrazolo[3,4-c]pyridazin-5-yl]-2H-1,2,4-triazine-3,5-dione	2251198: Inhibition of recombinant human CD73 preincubated for 15 mins followed by AMP addition measured after 10 mins by LC/MS analysis	ic50	<0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1R)-1-phenylethyl]amino]pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
[[(2R,3S,4R,5R)-5-[4-(benzylamino)-6-chloropyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-1-(2-fluorophenyl)ethyl]amino]pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
[[(2R,3R,4S,5R)-5-[2-chloro-6-[cyclopentyl(methyl)amino]purin-9-yl]-4-fluoro-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-1-(4-fluorophenyl)ethyl]amino]pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
[[(2R,3S,4R,5R)-5-[2-chloro-6-[cyclopentyl(methyl)amino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
[[(2R,3R,4S,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-4-fluoro-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]-2-[[4-(2-oxo-1H-pyridin-3-yl)phenyl]methyl]propanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0001	uM
[(2R,3S,4R,5R)-5-(6-chloro-4-spiro[1,2-dihydroindene-3,3’-azetidine]-1’-ylpyrazolo[5,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxymethylphosphonic acid	2007821: Inhibition of human CD73	ic50	0.0001	uM
6-[3-[(1R)-2,2-difluoro-1-[2-(2-methoxyethoxy)-4-pyridinyl]ethoxy]-1-methylpyrazolo[3,4-c]pyridazin-5-yl]-2H-1,2,4-triazine-3,5-dione	2251198: Inhibition of recombinant human CD73 preincubated for 15 mins followed by AMP addition measured after 10 mins by LC/MS analysis	ic50	0.0001	uM
[[(2R,3S,4R,5R)-5-[2-chloro-6-(cyclopentylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0002	uM
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]-2-[[4-(2-carboxyphenyl)phenyl]methyl]propanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0002	uM
[(2R)-2-[[(2R,3S,4R,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy]-1-hydroxy-3-methoxypropan-2-yl]phosphonic acid	1724305: Inhibition of CD73 in human CD8+ T-cells assessed as reduction in AMP-induced ADO expression preincubated for 15 mins followed by AMP addition and measured after 1 hr by LC-MS/MS analysis	ec50	0.0002	uM
[[(2R,3S,4R,5R)-5-[6-(benzylamino)-2-chloropurin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0003	uM
2-benzyl-2-[[(2R,3S,4R,5R)-5-(2-chloro-6-thiophen-2-ylpurin-9-yl)-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]propanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0003	uM
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]-2-[[4-(2-oxopiperidin-1-yl)phenyl]methyl]propanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0003	uM
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]-2-[(4-phenylphenyl)methyl]propanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0003	uM
[[(2R,3S,4R,5R)-5-[6-[benzyl(methyl)amino]-2-chloropurin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1605331: Inhibition of human CD73	ki	0.0003	uM
[[(2R,3S,4R,5R)-5-[2-chloro-6-[[(1S)-1-phenylethyl]amino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0003	uM
[(2R,3S,4R,5R)-5-[2-chloro-6-[(2-fluorophenyl)methyl-methylamino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	2132855: Binding affinity to human recombinant CD73 assessed as inhibition constant	ki	0.0003	uM
[[(2R,3R,4S,5R)-5-[2-chloro-6-(cyclopentylamino)purin-9-yl]-4-fluoro-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0004	uM
[(2R,3S,4R,5R)-5-[6-(benzylamino)-2-chloropurin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	1744449: Inhibition of human CD73 expressed in CHO cells incubated for 60 mins before addition of AMP and further incubated for 60 mins by colorimetric assay	ic50	0.0004	uM
bis(N,N-diethylethanamine);[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[(4Z)-4-[(4-iodophenyl)methoxyimino]-3-methyl-2-oxopyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1819263: Inhibition of human soluble CD73 assessed as inhibition constant	ki	0.0004	uM
[[(2R,3S,4R,5R)-5-[(4Z)-4-[(4-bromophenyl)methoxyimino]-3-methyl-2-oxopyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid;bis(N,N-diethylethanamine)	1819263: Inhibition of human soluble CD73 assessed as inhibition constant	ki	0.0004	uM
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3-(2-cyclopropylethynyl)-3,4-dihydroxyoxolan-2-yl]methoxy]-2-benzylpropanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0005	uM
[2-[[(2R,3S,4R,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy]-1-hydroxy-3-methoxypropan-2-yl]phosphonic acid	1724307: Inhibition of human C-terminal His6-tagged CD73 expressed in CHO cells preincubated for 15 mins followed by AMP addition and measured after 10 mins by malachite green reagent based assay	ic50	0.0005	uM
[(2R)-2-[[(2R,3S,4R,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy]-1-hydroxypropan-2-yl]phosphonic acid	1724307: Inhibition of human C-terminal His6-tagged CD73 expressed in CHO cells preincubated for 15 mins followed by AMP addition and measured after 10 mins by malachite green reagent based assay	ic50	0.0005	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-2,3-dihydro-1H-inden-1-yl]-methylamino]pyrazolo[5,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1724307: Inhibition of human C-terminal His6-tagged CD73 expressed in CHO cells preincubated for 15 mins followed by AMP addition and measured after 10 mins by malachite green reagent based assay	ic50	0.0005	uM
bis(N,N-diethylethanamine);[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[(4Z)-3-methyl-2-oxo-4-[[4-(pentafluoro-lambda6-sulfanyl)phenyl]methoxyimino]pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1819263: Inhibition of human soluble CD73 assessed as inhibition constant	ki	0.0005	uM
[[(2R,3R,4S,5R)-5-[6-(cyclopentylamino)-2-(methoxymethyl)purin-9-yl]-4-fluoro-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0006	uM
[(2R,3S,4R,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethylphosphonic acid	1744447: Inhibition of CD73 in human SK-OV-3 cells incubated for 60 mins before addition of AMP and further incubated for 60 mins by colorimetric assay	ic50	0.0006	uM
2-benzyl-2-[[(2R,3S,4R,5R)-5-[2-chloro-6-(3-hydroxyazetidin-1-yl)purin-9-yl]-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]propanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0006	uM
[2-[[(2R,3S,4R,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy]-1,3-dihydroxypropan-2-yl]phosphonic acid	1724307: Inhibition of human C-terminal His6-tagged CD73 expressed in CHO cells preincubated for 15 mins followed by AMP addition and measured after 10 mins by malachite green reagent based assay	ic50	0.0006	uM
[[(2R,3S,4R,5R)-5-[(4Z)-4-[[4-(2-aminoethylcarbamoyl)phenyl]methoxyimino]-3-methyl-2-oxopyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid;bis(N,N-diethylethanamine)	1819263: Inhibition of human soluble CD73 assessed as inhibition constant	ki	0.0006	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, decreases reaction, affects cotreatment, increases expression	5
Tetrachlorodibenzodioxin	decreases expression, affects expression	4
cobaltous chloride	decreases expression, increases expression	3
Tobacco Smoke Pollution	decreases expression, affects expression	3
Valproic Acid	decreases expression, decreases methylation, increases expression	3
Cyclosporine	affects expression, increases expression	3
bisphenol A	decreases expression, decreases methylation, increases expression	2
sodium arsenite	increases expression, decreases expression	2
chloropicrin	affects expression, decreases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	2
Formaldehyde	decreases expression, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	decreases activity, decreases expression	2
Medroxyprogesterone Acetate	affects cotreatment, increases expression, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
beta-Naphthoflavone	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
dicrotophos	decreases expression	1
urushiol	increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
deoxynivalenol	decreases expression	1
lead acetate	increases expression	1
sodium arsenate	increases abundance, increases expression	1

ChEMBL screening assays

181 unique, capped per target: 181 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1042900	Binding	Activity at ecto-5’-nucleotidase	Nucleoside-5’-monophosphates as prodrugs of adenosine A2A receptor agonists activated by ecto-5’-nucleotidase. — *J Med Chem*

Cellosaurus cell lines

5 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell, 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1CI	Abcam A-431 NT5E KO	Cancer cell line	Female
CVCL_B7V4	Abcam A-375 NT5E KO	Cancer cell line	Female
CVCL_C9M7	BFVSBi001-A	Induced pluripotent stem cell	Male
CVCL_E6RF	Genomeditech CHO-K1 H_NT5E(CD73)	Spontaneously immortalized cell line	Female
CVCL_E6UR	Genomeditech HEK-293 H_NT5E(CD73)	Transformed cell line	Female

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for NT5E across ~30M SureChEMBL compounds — explore on Sugi Predict.