ENTPD3

Summary

ENTPD3 (ectonucleoside triphosphate diphosphohydrolase 3, HGNC:3365) is a protein-coding gene on chromosome 3p22.1, encoding Ectonucleoside triphosphate diphosphohydrolase 3 (O75355). Catalyzes the hydrolysis of nucleoside triphosphates (NTPs) and diphosphates (NDPs).

This gene encodes a plasma membrane-bound divalent cation-dependent E-type nucleotidase. The encoded protein is involved in the regulation of extracellular levels of ATP by hydrolysis of it and other nucleotides. Multiple transcript variants have been described.

Source: NCBI Gene 956 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 73 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001248

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3365
Approved symbol	ENTPD3
Name	ectonucleoside triphosphate diphosphohydrolase 3
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	NTPDase-3, HB6
Ensembl gene	ENSG00000168032
Ensembl biotype	protein_coding
OMIM	603161
Entrez	956

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000301825, ENST00000439533, ENST00000445129, ENST00000456402, ENST00000647765, ENST00000900100

RefSeq mRNA: 3 — MANE Select: NM_001248 NM_001248, NM_001291960, NM_001291961

CCDS: CCDS2691, CCDS74919

Canonical transcript exons

ENST00000301825 — 11 exons

Exon	Start	End
ENSE00001119542	40400894	40401011
ENSE00001119544	40423826	40423963
ENSE00001119545	40414681	40414840
ENSE00001119547	40427272	40428744
ENSE00001119548	40415840	40416073
ENSE00001119549	40411812	40411962
ENSE00001119550	40422850	40423122
ENSE00001119551	40392023	40392150
ENSE00001119552	40423291	40423401
ENSE00001266997	40387184	40387261
ENSE00001267071	40388046	40388097

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 92.53.

FANTOM5 (CAGE): breadth broad, TPM avg 3.4939 / max 136.0167, expressed in 518 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36178	3.4116	515
202732	0.0823	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	92.53	gold quality
periodontal ligament	UBERON:0008266	90.23	gold quality
middle temporal gyrus	UBERON:0002771	88.90	gold quality
parotid gland	UBERON:0001831	87.88	gold quality
putamen	UBERON:0001874	87.14	gold quality
nasal cavity epithelium	UBERON:0005384	86.66	silver quality
tibia	UBERON:0000979	86.51	gold quality
tongue squamous epithelium	UBERON:0006919	86.20	gold quality
pancreas	UBERON:0001264	86.09	gold quality
caudate nucleus	UBERON:0001873	85.61	gold quality
minor salivary gland	UBERON:0001830	85.58	gold quality
saliva-secreting gland	UBERON:0001044	85.56	gold quality
nasal cavity mucosa	UBERON:0001826	85.19	gold quality
decidua	UBERON:0002450	84.80	gold quality
mouth mucosa	UBERON:0003729	84.80	gold quality
cervix squamous epithelium	UBERON:0006922	84.60	silver quality
type B pancreatic cell	CL:0000169	84.54	gold quality
mucosa of urinary bladder	UBERON:0001259	84.53	gold quality
body of pancreas	UBERON:0001150	83.74	gold quality
gingival epithelium	UBERON:0001949	83.46	gold quality
gingiva	UBERON:0001828	83.24	gold quality
squamous epithelium	UBERON:0006914	83.23	gold quality
lateral globus pallidus	UBERON:0002476	83.13	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.81	gold quality
primary visual cortex	UBERON:0002436	82.77	gold quality
Brodmann (1909) area 10	UBERON:0013541	82.73	gold quality
prefrontal cortex	UBERON:0000451	82.45	gold quality
mucosa of paranasal sinus	UBERON:0005030	82.33	gold quality
CA1 field of hippocampus	UBERON:0003881	82.25	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	82.11	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	474.24
E-HCAD-25	yes	39.79
E-MTAB-5061	yes	17.10
E-GEOD-81608	yes	16.82
E-GEOD-81547	yes	10.85
E-GEOD-83139	yes	9.89
E-ANND-3	yes	7.01
E-GEOD-84465	yes	6.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting ENTPD3, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-5584-3P	99.23	68.79	1351

Literature-anchored findings (GeneRIF, showing 9)

• NTPDase3 sequence revealed a high degree of structural fold similarity with a bacterial exopolyphosphatase (PMID:15966724)
• efficiently inhibit the NTPDase3expressed in insulin secreting human pancreatic islet cells in situ (PMID:19120451)
• Generation of a helical model for NTPDase3 suggests the importance of putative hydrogen bond interactions of conserved polar residues which are critical for enzyme expression, activity, and its susceptibility to membrane perturbations. (PMID:19743837)
• Cystic fibrosis epithelia exhibit >50% lower NTPDase1 activity, protein, and mRNA levels than normal epithelia, whereas these parameters are threefold higher for NTPDase3. (PMID:20190036)
• NTPDase3 is the major ectonucleotidase in pancreatic beta-cells in multiple species and modulates insulin secretion by controlling activation of purinergic receptors. (PMID:24085034)
• Despite the increased level of NTPDase1 and NTPDase3 mRNA expression in chondrogenically induced MSCs, their activity toward ATP remains quite low. (PMID:26018728)
• 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)
• ENTPD3 Marks Mature Stem Cell-Derived beta-Cells Formed by Self-Aggregation In Vitro. (PMID:34380694)
• Silencing NTPDase3 activity rehabilitates the osteogenic commitment of post-menopausal stem cell bone progenitors. (PMID:37076930)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	entpd3	ENSDARG00000035309
mus_musculus	Entpd3	ENSMUSG00000041608
rattus_norvegicus	Entpd3	ENSRNOG00000018982

Paralogs (7): ENTPD2 (ENSG00000054179), ENTPD1 (ENSG00000138185), ENTPD5 (ENSG00000187097), ENTPD8 (ENSG00000188833), ENTPD4 (ENSG00000197217), ENTPD6 (ENSG00000197586), ENTPD7 (ENSG00000198018)

Protein

Protein identifiers

Ectonucleoside triphosphate diphosphohydrolase 3 — O75355 (reviewed: O75355)

Alternative names: CD39 antigen-like 3, Ecto-ATP diphosphohydrolase 3, Ecto-apyrase 3, HB6

All UniProt accessions (3): A0A3B3IT06, C9J0J3, O75355

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of nucleoside triphosphates (NTPs) and diphosphates (NDPs). 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 levels of nucleotides. Has a preference for the hydrolysis of ATP. Does not hydrolyzes AMP.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in adult brain, pancreas, spleen and prostate. Moderate or low expression is seen in most tissues. Not expressed in liver and peripheral blood leukocytes.

Post-translational modifications. N-glycosylated.

Activity regulation. ADP hydrolase activity is lost of about 50% with 1 mM NaN3, and 75% with 20 mM. The ATP hydrolase activity is slightly less sensitive to inhibition at all azide concentrations tested. ADP hydrolase activity is inhibited by cibacron blue with an IC(50) value of 1.5 uM. Approximately 30% of the ATP hydrolase activity and 50% of the ADP hydrolase activity are inhibited by 1 mM azide.

Similarity. Belongs to the GDA1/CD39 NTPase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75355-1	1	yes
O75355-2	2

RefSeq proteins (3): NP_001239, NP_001278889, NP_001278890 (=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 (78 total): binding site 39, mutagenesis site 14, glycosylation site 7, disulfide bond 5, sequence variant 5, topological domain 3, transmembrane region 2, chain 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75355-F1	90.79	0.77

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): 182 (proton acceptor)

Ligand- & substrate-binding residues (39): 65; 65; 65; 66; 66; 66; 66; 66; 139; 139; 139; 139 …

Disulfide bonds (5): 92–116, 261–308, 289–334, 347–353, 399–422

Glycosylation sites (7): 81, 149, 238, 381, 392, 402, 454

Mutagenesis-validated functional residues (14):

Position	Phenotype
67	increase of activity.
143	loss of activity.
143	increase of activity.
146	no effect.
146	increase of atpase activity, decrease of adpase activity.
146	increase of activity.
182	complete loss of activity.
187	complete loss of activity.
191	loss of atpase activity, increase of adpase activity.
219	increase of activity.
224	complete loss of activity.
226	loss of activity.
459	increase of activity, especially the atp hydrolysis.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 116 (showing top): GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, RACCACAR_AML_Q6, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, CHANG_IMMORTALIZED_BY_HPV31_DN, AML_Q6, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, chr3p22, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, KEGG_PURINE_METABOLISM, GOBP_NUCLEOSIDE_PHOSPHATE_CATABOLIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_CATABOLIC_PROCESS, VECCHI_GASTRIC_CANCER_EARLY_DN, RICKMAN_TUMOR_DIFFERENTIATED_MODERATELY_VS_POORLY_UP

GO Biological Process (4): nucleoside diphosphate catabolic process (GO:0009134), ribonucleoside diphosphate catabolic process (GO:0009191), ribonucleoside triphosphate catabolic process (GO:0009203), nucleoside triphosphate catabolic process (GO:0009143)

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

GO Cellular Component (2): plasma membrane (GO:0005886), 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 phosphate catabolic process	2
nucleoside diphosphate phosphatase activity	2
nucleoside diphosphate metabolic process	1
nucleoside diphosphate catabolic process	1
ribonucleoside diphosphate metabolic process	1
nucleoside triphosphate catabolic process	1
nucleoside triphosphate metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

968 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENTPD3	ITGA2B	P08514	728
ENTPD3	CMPK1	P30085	717
ENTPD3	P2RY2	P41231	713
ENTPD3	ENPP3	O14638	704
ENTPD3	PAPSS1	O43252	702
ENTPD3	PANX1	Q96RD7	677
ENTPD3	PAPSS2	O95340	667
ENTPD3	P2RY12	Q9H244	662
ENTPD3	P2RY1	P47900	658
ENTPD3	AK1	P00568	649
ENTPD3	P2RX1	P51575	634
ENTPD3	GP6	Q9HCN6	620
ENTPD3	P2RY6	Q15077	594
ENTPD3	P2RX7	Q99572	594
ENTPD3	SELP	P16109	582

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SYNE4	ENTPD3	psi-mi:“MI:0915”(physical association)	0.560
ENTPD3	SYNE4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (16): SYNE4 (Two-hybrid), ENTPD3 (Two-hybrid), ENTPD3 (Two-hybrid), ENTPD3 (Two-hybrid), ENTPD3 (Two-hybrid), ENTPD3 (Two-hybrid), ENTPD3 (Two-hybrid), ENTPD3 (Two-hybrid), ENTPD3 (Two-hybrid), ENTPD3 (Two-hybrid), ARL13B (Two-hybrid), FNDC9 (Two-hybrid), TMEM106A (Two-hybrid), MUC1 (Two-hybrid), LHFPL5 (Two-hybrid)

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, Q6Z4P2, E1C1L6, O80612, Q9SPM5, P52914, P80595

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2285 predictions. Top by Δscore:

Variant	Effect	Δscore
3:40400892:A:AG	acceptor_gain	1.0000
3:40400892:AGTAT:A	acceptor_gain	1.0000
3:40400893:G:GG	acceptor_gain	1.0000
3:40400893:GT:G	acceptor_gain	1.0000
3:40400893:GTATG:G	acceptor_gain	1.0000
3:40422848:A:AG	acceptor_gain	1.0000
3:40422849:G:GG	acceptor_gain	1.0000
3:40422849:GA:G	acceptor_gain	1.0000
3:40387259:CAGG:C	donor_loss	0.9900
3:40387260:AGGTA:A	donor_loss	0.9900
3:40387263:T:A	donor_loss	0.9900
3:40388044:A:AG	acceptor_gain	0.9900
3:40388045:G:GG	acceptor_gain	0.9900
3:40388045:GCTA:G	acceptor_gain	0.9900
3:40392021:A:AG	acceptor_gain	0.9900
3:40392022:G:GG	acceptor_gain	0.9900
3:40392148:AAGGT:A	donor_loss	0.9900
3:40392151:GTA:G	donor_loss	0.9900
3:40392152:T:G	donor_loss	0.9900
3:40400467:G:GT	donor_gain	0.9900
3:40400506:G:GT	donor_gain	0.9900
3:40400527:GC:G	donor_gain	0.9900
3:40411969:GC:G	donor_gain	0.9900
3:40411970:C:G	donor_gain	0.9900
3:40414583:G:GT	donor_gain	0.9900
3:40414791:GGGTA:G	donor_gain	0.9900
3:40414827:G:T	donor_gain	0.9900
3:40415838:A:AG	acceptor_gain	0.9900
3:40415839:G:GG	acceptor_gain	0.9900
3:40416041:GC:G	donor_gain	0.9900

AlphaMissense

3493 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:40414802:T:A	W187R	0.994
3:40414802:T:C	W187R	0.994
3:40423018:T:A	C334S	0.993
3:40423019:G:C	C334S	0.993
3:40427293:T:A	W459R	0.993
3:40427293:T:C	W459R	0.993
3:40400948:T:A	W75R	0.992
3:40400948:T:C	W75R	0.992
3:40415895:T:C	L218P	0.992
3:40422883:T:A	C289S	0.991
3:40422884:G:C	C289S	0.991
3:40422885:T:G	C289W	0.991
3:40427295:G:C	W459C	0.991
3:40427295:G:T	W459C	0.991
3:40422883:T:C	C289R	0.990
3:40400912:G:C	A63P	0.989
3:40414816:C:A	N191K	0.989
3:40414816:C:G	N191K	0.989
3:40422884:G:A	C289Y	0.989
3:40423876:C:G	C422W	0.989
3:40392079:A:C	S33R	0.988
3:40392081:T:A	S33R	0.988
3:40392081:T:G	S33R	0.988
3:40422940:T:A	C308S	0.988
3:40422941:G:C	C308S	0.988
3:40423019:G:A	C334Y	0.988
3:40423381:T:A	C399S	0.988
3:40423382:G:C	C399S	0.988
3:40423874:T:C	C422R	0.988
3:40423382:G:A	C399Y	0.987

dbSNP variants (sampled 300 via entrez): RS1000012181 (3:40427114 G>A), RS1000019235 (3:40407201 G>A), RS1000035189 (3:40423739 A>T), RS1000075095 (3:40393239 T>C), RS1000108548 (3:40423484 G>A), RS1000302418 (3:40417660 C>T), RS1000359170 (3:40404160 A>G), RS1000413919 (3:40410468 A>G), RS1000437475 (3:40389133 G>A), RS1000555314 (3:40387927 G>A,C), RS1000674079 (3:40394790 G>A,C), RS1000709196 (3:40404534 G>A), RS1000738643 (3:40396290 G>A), RS1000775554 (3:40387689 GA>G,GAA), RS1000828817 (3:40386271 T>C)

Disease associations

OMIM: gene MIM:603161 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005232_29	Neuroticism	2.000000e-08
GCST90002382_561	Eosinophil percentage of white cells	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5897 (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)

ChEMBL bioactivities

3 potent at pChembl≥5 of 4 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.22	IC50	600	nM	CHEMBL4787368
5.37	IC50	4310	nM	SURAMIN
5.37	IC50	4300	nM	SURAMIN

PubChem BioAssay actives

3 with measured affinity, of 106 total; 2 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
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	1692620: Inhibition of human NTPDase3 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	0.6000	uM
8-[4-methyl-3-[(5Z)-5-[(Z)-[5-[[2-methyl-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	1692620: Inhibition of human NTPDase3 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	4.3000	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Tobacco Smoke Pollution	affects expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
3,4-dichloroaniline	increases expression	1
sodium arsenite	increases expression	1
chloroquine diphosphate	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Azathioprine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Calcitriol	increases expression	1
Diuron	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Gold Sodium Thiomalate	increases expression	1
Methapyrilene	increases methylation	1
Methotrexate	increases expression	1
Nicotine	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Triclosan	increases expression	1
Antirheumatic Agents	increases expression	1

ChEMBL screening assays

26 unique, capped per target: 21 binding, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001640	Binding	Activity of human NTPDase 3 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
CHEMBL2390588	ADMET	Drug metabolism assessed as human nucleotide triphosphate diphosphohydrolase3-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.