ENTPD2

Summary

ENTPD2 (ectonucleoside triphosphate diphosphohydrolase 2, HGNC:3364) is a protein-coding gene on chromosome 9q34.3, encoding Ectonucleoside triphosphate diphosphohydrolase 2 (Q9Y5L3). Catalyzes the hydrolysis of nucleoside triphosphates (NTPs) and diphosphates (NDPs), with a marked preference for triphosphonucleosides over diphosphonucleosides.

The protein encoded by this gene is the type 2 enzyme of the ecto-nucleoside triphosphate diphosphohydrolase family (E-NTPDase). E-NTPDases are a family of ecto-nucleosidases that hydrolyze 5’-triphosphates. This ecto-ATPase is an integral membrane protein. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 954 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 137 total — 1 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_203468

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3364
Approved symbol	ENTPD2
Name	ectonucleoside triphosphate diphosphohydrolase 2
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	NTPDase-2
Ensembl gene	ENSG00000054179
Ensembl biotype	protein_coding
OMIM	602012
Entrez	954

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000312665, ENST00000355097, ENST00000460614, ENST00000469106, ENST00000902978, ENST00000902979, ENST00000902980, ENST00000902981

RefSeq mRNA: 2 — MANE Select: NM_203468 NM_001246, NM_203468

CCDS: CCDS7025, CCDS7026

Canonical transcript exons

ENST00000355097 — 9 exons

Exon	Start	End
ENSE00001194447	137051211	137051370
ENSE00001244464	137049870	137049989
ENSE00001308239	137053881	137054061
ENSE00001310256	137050284	137050538
ENSE00001413449	137048941	137049075
ENSE00001880985	137048107	137048860
ENSE00003566021	137050902	137051129
ENSE00003755352	137052231	137052348
ENSE00003758755	137051510	137051660

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 91.33.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6367 / max 60.4142, expressed in 436 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103300	1.4730	420
103299	0.1636	93

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	91.33	gold quality
tibial nerve	UBERON:0001323	90.25	gold quality
pancreatic ductal cell	CL:0002079	88.40	silver quality
trigeminal ganglion	UBERON:0001675	86.91	gold quality
mucosa of transverse colon	UBERON:0004991	85.49	gold quality
epithelial cell of pancreas	CL:0000083	84.91	gold quality
lower esophagus mucosa	UBERON:0035834	83.84	gold quality
vena cava	UBERON:0004087	83.08	silver quality
right uterine tube	UBERON:0001302	82.65	gold quality
amygdala	UBERON:0001876	82.38	gold quality
ventral tegmental area	UBERON:0002691	82.31	gold quality
skin of abdomen	UBERON:0001416	82.26	gold quality
hypothalamus	UBERON:0001898	81.73	gold quality
left ventricle myocardium	UBERON:0006566	81.39	gold quality
cardiac muscle of right atrium	UBERON:0003379	81.27	gold quality
sural nerve	UBERON:0015488	81.21	gold quality
nucleus accumbens	UBERON:0001882	80.72	gold quality
transverse colon	UBERON:0001157	80.54	gold quality
skin of leg	UBERON:0001511	80.16	gold quality
lateral globus pallidus	UBERON:0002476	79.46	silver quality
right frontal lobe	UBERON:0002810	79.41	gold quality
caudate nucleus	UBERON:0001873	79.34	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.80	gold quality
cardia of stomach	UBERON:0001162	78.65	silver quality
dorsal plus ventral thalamus	UBERON:0001897	78.48	silver quality
subthalamic nucleus	UBERON:0001906	78.46	silver quality
zone of skin	UBERON:0000014	78.28	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.01	gold quality
superior vestibular nucleus	UBERON:0007227	77.74	silver quality
inferior vagus X ganglion	UBERON:0005363	77.66	silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	14.75
E-GEOD-83139	yes	4.47
E-ANND-3	yes	4.14
E-HCAD-31	no	3.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFATC2

miRNA regulators (miRDB)

73 targeting ENTPD2, 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-6748-5P	100.00	65.81	1057
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4516	99.61	67.78	3390

Literature-anchored findings (GeneRIF, showing 9)

• the lack of ecto-nucleotidase activity exhibited by NTPDase2 beta and -2 gamma and the C399S mutant, as well as the large reduction of activity in the N443D mutant are due to alterations in the folding/maturation of these proteins (PMID:12888562)
• NTPDase2 preferentially hydrolyzes nucleoside triphosphates. (PMID:15496502)
• down-regulation in biliary cirrhosis (PMID:15651265)
• NTPDase2 has a role in portal fibroblast regulation of bile duct epithelium proliferation (PMID:15799977)
• Mutagenesis study indicate the importance of K62 located in CR1, K182 downstream of ACR3, and R155. Mutation of Asp at the six potential glycosylation sites showed the importance of N64 in CR1 and N443 in ACR5 in protein function and expression (PMID:17489562)
• The role of cysteine 26 in the catalytic activity of NTPDase-2 and as the target of p-chloromercuriphenylsulfonate (pCMPS), a sulfhydryl reagent and NTPDase-2 inhibitor, is reported. (PMID:18656957)
• NTPDase2 and -3 are ecto-enzymes expressed in the enteric nervous system. Both enzymes confer protection against gut inflammation in experimental colitis and exhibit alterations in Crohn’s disease. These observations suggest that purinergic signalling modulated by E-NTPDases governs neuro-immune interactions that are relevant in Crohn’s disease. (PMID:28472257)
• Hypoxia upregulates ENTPD2 through HIF-1alpha in hepatocellular carcinoma and subsequently leading to the accumulation of extracellular 5’-AMP, which maintains myeloid-derived suppressor cells undifferentiated. (PMID:28894087)
• In oviducts, remarkably, ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2), with the ability to hydrolyze ATP to AMP, are expressed in ciliated epithelial cells but with different subcellular localization. (PMID:29273916)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	entpd2a.2	ENSDARG00000033953
danio_rerio	entpd2a.1	ENSDARG00000035506
danio_rerio	entpd2b	ENSDARG00000044795
mus_musculus	Entpd2	ENSMUSG00000015085
rattus_norvegicus	Entpd2	ENSRNOG00000013102

Paralogs (7): ENTPD1 (ENSG00000138185), ENTPD3 (ENSG00000168032), ENTPD5 (ENSG00000187097), ENTPD8 (ENSG00000188833), ENTPD4 (ENSG00000197217), ENTPD6 (ENSG00000197586), ENTPD7 (ENSG00000198018)

Protein

Protein identifiers

Ectonucleoside triphosphate diphosphohydrolase 2 — Q9Y5L3 (reviewed: Q9Y5L3)

Alternative names: CD39 antigen-like 1, Ecto-ATP diphosphohydrolase 2

All UniProt accessions (1): Q9Y5L3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of nucleoside triphosphates (NTPs) and diphosphates (NDPs), with a marked preference for triphosphonucleosides over diphosphonucleosides. The enzyme sequentially removes phosphate groups in two successive steps, converting NTPs to nucleoside monophosphates (NMPs) via NDP intermediates. This activity contributes to the regulation of extracellular nucleotides levels. ATP hydrolysis is characterized by fast ADP accumulation and delayed AMP formation, reflecting limited ADP hydrolase activity. Hydrolyzes ADP and UDP only to a marginal extent, and does not hydrolyze AMP. All nucleoside 5’-diphosphates are hydrolyzed at rates lower than those of their corresponding triphosphates. Catalytically inactive. Catalytically inactive.

Subcellular location. Cell membrane Endoplasmic reticulum membrane Endoplasmic reticulum membrane.

Tissue specificity. Brain, placenta, skeletal muscle, kidney, pancreas, heart, ovary, testis, colon, small intestine, prostate and pancreas. No expression in adult thymus, spleen, lung, liver and peripheral blood leukocytes.

Activity regulation. ATP hydrolysis activity is inhibited about 70% by 0.25 mM p-chloromercuri-phenylsulfonate (pCMPS) and >90% by 0.1% Nonidet P-40 (NP-40). ATP hydrolysis activity is markedly stimulated by concanavalin A, disuccinimidyl suberate (DSS) and glutaraldehyde; The stimulatory effects are greater at 55 degrees Celsius (6-10-fold) than at 37 degrees Celsius (about 2-fold). ATPase activity is decreased by about 50% at 55 degrees Celsius. ATPase activity increases from 15 to 37 degrees Celsius but declines at higher temperatures. ATPase activity is inhibited by 0.1% NP-40 at all temperatures.

Similarity. Belongs to the GDA1/CD39 NTPase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y5L3-1	Long, alpha	yes
Q9Y5L3-2	Short, beta
Q9Y5L3-3	gamma

RefSeq proteins (2): NP_001237, NP_982293* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000407	GDA1_CD39_NTPase	Family

Pfam: PF01150

Enzyme classification (BRENDA):

• EC 3.6.1.5 — apyrase (BRENDA: 66 organisms, 384 substrates, 230 inhibitors, 158 Km, 64 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ATP	0.0025–8.7	44
ADP	0.0025–5.3	42
UDP	0.0113–0.555	7
GDP	0.0114–0.357	6
UTP	0.01–0.207	5
N-[5-[4-CARBOXY-3-(3-OXO-9,9A-DIHYDRO-3H-XANTHEN	0.0133–0.105	4
DATP	0.018–0.89	3
DCTP	0.029–0.276	3
DGTP	0.028–0.16	3
IDP	0.0105–0.622	3
1,N6-ETHENO-ADP	0.073–0.114	2
1,N6-ETHENO-ATP	0.024–0.031	2
2’(3’)-O-(2,4,6-TRINITROPHENYL)ADENOSINE 5’-DIPH	0.009–0.019	2
2’(3’)-O-(2,4,6-TRINITROPHENYL)ADENOSINE 5’-TRIP	0.008–0.018	2
3’(2’)-O-(METHYLANTHRANOYL)ADENOSINE 5’-DIPHOSPH	0.014–0.017	2

Catalyzed reactions (Rhea), 12 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)
• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)
• ATP + 2 H2O = AMP + 2 phosphate + 2 H(+) (RHEA:20988)
• GDP + H2O = GMP + phosphate + H(+) (RHEA:22156)
• a ribonucleoside 5’-triphosphate + H2O = a ribonucleoside 5’-diphosphate + phosphate + H(+) (RHEA:23680)
• ITP + H2O = IDP + phosphate + H(+) (RHEA:28330)
• CTP + H2O = CDP + phosphate + H(+) (RHEA:29387)
• IDP + H2O = IMP + phosphate + H(+) (RHEA:35207)
• a ribonucleoside 5’-triphosphate + 2 H2O = a ribonucleoside 5’-phosphate + 2 phosphate + 2 H(+) (RHEA:36795)
• a ribonucleoside 5’-diphosphate + H2O = a ribonucleoside 5’-phosphate + phosphate + H(+) (RHEA:36799)
• ADP + H2O = AMP + phosphate + H(+) (RHEA:61436)
• UDP + H2O = UMP + phosphate + H(+) (RHEA:64876)

UniProt features (73 total): binding site 51, glycosylation site 5, disulfide bond 5, topological domain 3, transmembrane region 2, splice variant 2, mutagenesis site 2, chain 1, active site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5L3-F1	93.02	0.82

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 (1): 165 (proton acceptor)

Ligand- & substrate-binding residues (51): 48; 48; 48; 49; 49; 49; 49; 49; 50; 50; 50; 50 …

Disulfide bonds (5): 75–99, 242–284, 265–310, 323–328, 377–399

Glycosylation sites (5): 64, 129, 294, 378, 443

Mutagenesis-validated functional residues (2):

Position	Phenotype
399	abolishes ecto-atpase activity, accumulates intracellularly.
443	7% of wild-type atpase activity, accumulates intracellularly.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8850843	Phosphate bond hydrolysis by NTPDase proteins

MSigDB gene sets: 131 (showing top): GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_PLATELET_ACTIVATION, MODULE_45, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_WOUND_HEALING, MODULE_118, MODULE_379, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, KEGG_PURINE_METABOLISM

GO Biological Process (5): G protein-coupled receptor signaling pathway (GO:0007186), nucleoside diphosphate catabolic process (GO:0009134), purine ribonucleoside diphosphate catabolic process (GO:0009181), ribonucleoside triphosphate catabolic process (GO:0009203), platelet activation (GO:0030168)

GO Molecular Function (9): apyrase activity (GO:0004050), GDP phosphatase activity (GO:0004382), ATP binding (GO:0005524), ribonucleoside triphosphate phosphatase activity (GO:0017111), UDP phosphatase activity (GO:0045134), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787), nucleoside diphosphate phosphatase activity (GO:0017110)

GO Cellular Component (6): basement membrane (GO:0005604), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Nucleotide catabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyrophosphatase activity	3
nucleoside diphosphate phosphatase activity	2
G protein-coupled receptor activity	1
signal transduction	1
nucleoside diphosphate metabolic process	1
nucleoside phosphate catabolic process	1
purine nucleoside diphosphate catabolic process	1
purine ribonucleoside diphosphate metabolic process	1
ribonucleoside diphosphate catabolic process	1
nucleoside triphosphate catabolic process	1
cell activation	1
blood coagulation	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
extracellular matrix	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
extracellular vesicle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1228 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENTPD2	P2RY1	P47900	859
ENTPD2	CHMP3	Q9Y3E7	788
ENTPD2	A0A140T963	A0A140T963	781
ENTPD2	CHMP2A	O43633	777
ENTPD2	SIX3	O95343	773
ENTPD2	ATP6AP2	O75787	760
ENTPD2	VPS4B	O75351	672
ENTPD2	VPS4A	Q9UN37	671
ENTPD2	MITD1	Q8WV92	668
ENTPD2	P2RY2	P41231	648
ENTPD2	PAX6	P26367	635
ENTPD2	ATP12A	P54707	611
ENTPD2	ARID1A	O14497	600
ENTPD2	ATP7B	P35670	596
ENTPD2	ATP6V0D1	P12953	590

IntAct

32 interactions, top by confidence:

A	B	Type	Score
ENTPD2	OPTN	psi-mi:“MI:0915”(physical association)	0.560
HTT	ENTPD2	psi-mi:“MI:0915”(physical association)	0.560
DCT	CANX	psi-mi:“MI:0914”(association)	0.530
ENTPD2	HMBOX1	psi-mi:“MI:0915”(physical association)	0.370
ENTPD2	ATP2A1	psi-mi:“MI:0914”(association)	0.350
PCDHB3	ESYT2	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BRICD5	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-DQA1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-DRB3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ASIC4	TMEM131L	psi-mi:“MI:0914”(association)	0.350
DNAJB9	POTEF	psi-mi:“MI:0914”(association)	0.350
B3GALT4		psi-mi:“MI:0914”(association)	0.350
SPPL2B	HAS3	psi-mi:“MI:0914”(association)	0.350
PDGFRA	QSOX1	psi-mi:“MI:0914”(association)	0.350
ELSPBP1	QSOX1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
SLURP1	MAN2B1	psi-mi:“MI:0914”(association)	0.350
KLK15	APAF1	psi-mi:“MI:0914”(association)	0.350
ENTPD2	CLGN	psi-mi:“MI:0914”(association)	0.350
HTR1B	SCAMP2	psi-mi:“MI:0914”(association)	0.350
NCR1	ORC4	psi-mi:“MI:0914”(association)	0.350
HLA-DRA	MGRN1	psi-mi:“MI:0914”(association)	0.350
CD1A	FZD6	psi-mi:“MI:0914”(association)	0.350

BioGRID (96): ENTPD2 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), GOLGA5 (Affinity Capture-MS), LGALS1 (Affinity Capture-MS), PTPN1 (Affinity Capture-MS), PIGN (Affinity Capture-MS), HGSNAT (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), PREB (Affinity Capture-MS), B3GNT2 (Affinity Capture-MS), SLC39A11 (Affinity Capture-MS), ARL8B (Affinity Capture-MS), HLA-DRB1 (Affinity Capture-MS), HLA-G (Affinity Capture-MS), CERS6 (Affinity Capture-MS)

ESM2 similar proteins: A0JND9, E1BPW0, O14773, O18956, O35795, O55026, O75173, O75355, O75356, O75578, O89023, O93295, P08514, P08648, P11688, P17405, P49961, P55772, P56201, P79784, P97687, Q04519, Q0VD19, Q12794, Q32M88, Q49HH9, Q49KI5, Q5DRK1, Q5IS74, Q5MY95, Q5RFL1, Q5RFQ8, Q60HH1, Q6P3E7, Q6P6S9, Q717C1, Q717C2, Q7RTX0, Q8BFW6, Q8BNJ2

Diamond homologs: A0JND9, D2GZV9, O18956, O35795, O55026, O75354, O75355, O75356, O93295, P49961, P55772, P79784, P97687, Q3U0P5, Q5DRK1, Q5MY95, Q6NQA8, Q6P6S9, Q8BFW6, Q8H1D8, Q8H7L6, Q8K0L2, Q9ER31, Q9MYU4, Q9QYC8, Q9SQG2, Q9WUZ9, Q9XU84, Q9Y5L3, Q9XI62, E1BPW0, P32621, Q9HEM6, Q9USP2, E1C1L6, P80595, Q21815, Q6Z4P2, Q8TGG8, Q8TGH6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Adaptive Immune System	6	6.2×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
adaptive immune response	5	10.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	92
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3256927	NM_203468.3(ENTPD2):c.1170del (p.Gln391fs)	Likely pathogenic

SpliceAI

1609 predictions. Top by Δscore:

Variant	Effect	Δscore
9:137048857:CGGC:C	acceptor_gain	1.0000
9:137048859:GCC:G	acceptor_loss	1.0000
9:137048861:C:CC	acceptor_gain	1.0000
9:137048862:T:A	acceptor_loss	1.0000
9:137048936:CCCA:C	donor_loss	1.0000
9:137048937:CCA:C	donor_loss	1.0000
9:137048938:CACCT:C	donor_loss	1.0000
9:137048940:CCTT:C	donor_gain	1.0000
9:137048943:T:A	donor_gain	1.0000
9:137049073:CAG:C	acceptor_gain	1.0000
9:137049076:C:CC	acceptor_gain	1.0000
9:137049082:C:CT	acceptor_gain	1.0000
9:137049864:GCTCA:G	donor_loss	1.0000
9:137049865:CTCAC:C	donor_loss	1.0000
9:137049866:TCAC:T	donor_loss	1.0000
9:137049867:CACC:C	donor_loss	1.0000
9:137049868:A:C	donor_loss	1.0000
9:137049869:C:CA	donor_loss	1.0000
9:137049963:CACAG:C	acceptor_gain	1.0000
9:137049967:G:C	acceptor_gain	1.0000
9:137049967:G:GC	acceptor_gain	1.0000
9:137049969:G:GC	acceptor_gain	1.0000
9:137051366:TCAGG:T	acceptor_gain	1.0000
9:137051367:CAGG:C	acceptor_gain	1.0000
9:137051367:CAGGC:C	acceptor_gain	1.0000
9:137051508:A:AC	donor_gain	1.0000
9:137051509:C:CC	donor_gain	1.0000
9:137051525:CCCG:C	donor_gain	1.0000
9:137051579:T:TA	donor_gain	1.0000
9:137051656:CCCAC:C	acceptor_gain	1.0000

AlphaMissense

3181 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:137051249:A:G	W170R	0.993
9:137051249:A:T	W170R	0.993
9:137048837:C:A	W436C	0.992
9:137048837:C:G	W436C	0.992
9:137048839:A:G	W436R	0.991
9:137048839:A:T	W436R	0.991
9:137050945:C:A	G244V	0.991
9:137051247:C:A	W170C	0.991
9:137051247:C:G	W170C	0.991
9:137052294:A:G	W58R	0.991
9:137052294:A:T	W58R	0.991
9:137049889:C:T	C377Y	0.989
9:137050384:C:G	C310S	0.989
9:137050385:A:T	C310S	0.989
9:137051071:A:G	L202P	0.989
9:137050946:C:A	G244C	0.988
9:137050959:G:C	S239R	0.988
9:137050959:G:T	S239R	0.988
9:137050961:T:G	S239R	0.988
9:137051235:G:C	N174K	0.988
9:137051235:G:T	N174K	0.988
9:137052292:C:A	W58C	0.988
9:137052292:C:G	W58C	0.988
9:137050945:C:T	G244D	0.986
9:137050951:C:G	C242S	0.986
9:137050952:A:T	C242S	0.986
9:137049889:C:G	C377S	0.985
9:137049890:A:T	C377S	0.985
9:137050519:C:T	C265Y	0.984
9:137050383:G:C	C310W	0.983

dbSNP variants (sampled 300 via entrez): RS1000232900 (9:137051965 C>T), RS1000289239 (9:137055110 C>T), RS1000550387 (9:137055396 G>A), RS1000661676 (9:137051519 C>A,T), RS1000829072 (9:137055061 T>A,C), RS1000893265 (9:137056016 TG>T), RS1001245114 (9:137055920 C>G), RS1001367511 (9:137049704 G>A), RS1001375521 (9:137049817 G>C), RS1001488691 (9:137051464 G>A), RS1001558971 (9:137054206 A>G,T), RS1001565987 (9:137055918 G>A), RS1001598359 (9:137055739 G>A), RS1001930614 (9:137054800 A>G), RS1002379884 (9:137050694 G>A)

Disease associations

OMIM: gene MIM:602012 | 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: yes

ChEMBL targets (1): CHEMBL5049 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 36,848 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL265502	SURAMIN	3	36,848

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Hydrolases & Lipases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
PSB-6426	Inhibition	5.09	pKi

ChEMBL bioactivities

3 potent at pChembl≥5 of 10 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.52	IC50	3000	nM	CHEMBL597418
5.38	IC50	4200	nM	CHEMBL4787368
5.09	Ki	8200	nM	CHEMBL469212

PubChem BioAssay actives

3 with measured affinity, of 115 total; 3 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
sodium 1-amino-9,10-dioxo-4-(phenanthren-9-ylamino)anthracene-2-sulfonate	1312288: Inhibition of recombinant human NTPDase2 expressed in CHO cells using ADP as substrate incubated for 10 mins by capillary electrophoresis method	ic50	3.0000	uM
8-[3-[(5Z)-5-[(Z)-[5-[[5-[(4,6,8-trisulfo-2H-naphthalen-1-ylidene)carbamoyl]cyclohexa-2,4-dien-1-ylidene]carbamoyl]cyclohexa-2,4-dien-1-ylidene]carbamoyl]iminocyclohexa-1,3-diene-1-carbonyl]iminocyclohexa-1,4-diene-1-carbonyl]imino-7H-naphthalene-1,3,5-trisulfonic acid	1692619: Inhibition of human NTPDase2 expressed in green monkey Cos-7 cells using ATP as substrate preincubated for 3 mins followed by substrate addition by malachite green reagent based assay	ic50	4.2000	uM
(2S,3S,4R,5R)-N-[2-[4-(diethoxyphosphorylmethyl)anilino]-2-oxoethyl]-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolane-2-carboxamide	366263: Inhibition of human NTPDase 2 expressed in HEK293 cells	ki	8.2000	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	3
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	increases expression, decreases methylation	2
Tobacco Smoke Pollution	decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
lead acetate	decreases expression	1
sulforaphane	decreases expression	1
aflatoxin B2	affects methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Calcitriol	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Coumestrol	decreases expression	1
Demecolcine	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Lipopolysaccharides	increases expression, affects cotreatment, decreases reaction	1
Methyl Methanesulfonate	increases expression	1
Thiram	decreases expression	1
Vincristine	increases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	increases expression	1

ChEMBL screening assays

29 unique, capped per target: 24 binding, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001639	Binding	Activity of human NTPDase 2 expressed in human 293T cells assessed as drug hydrolysis at 100 uM after 20 mins relative to ATP	Identification of hydrolytically stable and selective P2Y(1) receptor agonists. — Eur J Med Chem
CHEMBL2390589	ADMET	Drug metabolism assessed as human nucleotide triphosphate diphosphohydrolase2-mediated compound hydrolysis at 4.24 mM after 1 hr by HPLC analysis relative to ADP	Highly efficient biocompatible neuroprotectants with dual activity as antioxidants and P2Y receptor agonists. — J Med Chem

Clinical trials (associated diseases)

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