ENTPD1

Summary

ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1, HGNC:3363) is a protein-coding gene on chromosome 10q24.1, encoding Ectonucleoside triphosphate diphosphohydrolase 1 (P49961). Catalyzes the hydrolysis of nucleoside triphosphates (NTPs) and diphosphates (NDPs).

The protein encoded by this gene is a plasma membrane protein that hydrolyzes extracellular ATP and ADP to AMP. Inhibition of this protein’s activity may confer anticancer benefits. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 953 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex hereditary spastic paraplegia (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 13
• Clinical variants (ClinVar): 251 total — 8 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 16
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001776

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3363
Approved symbol	ENTPD1
Name	ectonucleoside triphosphate diphosphohydrolase 1
Location	10q24.1
Locus type	gene with protein product
Status	Approved
Aliases	NTPDase-1, ATPDase, SPG64
Ensembl gene	ENSG00000138185
Ensembl biotype	protein_coding
OMIM	601752
Entrez	953

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 12 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000371205, ENST00000371206, ENST00000371207, ENST00000422161, ENST00000453258, ENST00000461927, ENST00000483213, ENST00000490659, ENST00000494070, ENST00000543964, ENST00000635076, ENST00000635677, ENST00000639992, ENST00000859523, ENST00000859524, ENST00000859525, ENST00000859526, ENST00000859527, ENST00000953039, ENST00000953040, ENST00000953041

RefSeq mRNA: 9 — MANE Select: NM_001776 NM_001098175, NM_001164178, NM_001164179, NM_001164181, NM_001164182, NM_001164183, NM_001312654, NM_001320916, NM_001776

CCDS: CCDS41554, CCDS53556, CCDS53557, CCDS7444

Canonical transcript exons

ENST00000371205 — 10 exons

Exon	Start	End
ENSE00001454616	95756163	95756255
ENSE00001811430	95866177	95877266
ENSE00003533158	95842344	95842494
ENSE00003546647	95844476	95844635
ENSE00003651981	95823237	95823364
ENSE00003679002	95839691	95839808
ENSE00003803333	95847446	95847706
ENSE00003804982	95845357	95845596
ENSE00003809905	95864724	95864861
ENSE00003810859	95860469	95860582

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 96.37.

FANTOM5 (CAGE): breadth broad, TPM avg 10.1353 / max 621.2268, expressed in 683 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106364	6.3649	554
106362	1.3312	282
106363	0.8787	354
106360	0.8524	337
106361	0.2620	127
106365	0.2590	95
106358	0.1228	33
106366	0.0643	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	96.37	gold quality
monocyte	CL:0000576	95.63	gold quality
mononuclear cell	CL:0000842	95.33	gold quality
blood vessel layer	UBERON:0004797	95.03	gold quality
leukocyte	CL:0000738	94.93	gold quality
popliteal artery	UBERON:0002250	94.72	gold quality
tibial artery	UBERON:0007610	94.70	gold quality
tendon of biceps brachii	UBERON:0008188	94.49	gold quality
gall bladder	UBERON:0002110	93.89	gold quality
right coronary artery	UBERON:0001625	93.74	gold quality
urethra	UBERON:0000057	93.16	gold quality
blood	UBERON:0000178	92.84	gold quality
vermiform appendix	UBERON:0001154	92.60	gold quality
bone marrow cell	CL:0002092	92.43	gold quality
smooth muscle tissue	UBERON:0001135	92.42	gold quality
visceral pleura	UBERON:0002401	92.24	gold quality
left coronary artery	UBERON:0001626	91.74	gold quality
bone marrow	UBERON:0002371	91.72	gold quality
coronary artery	UBERON:0001621	91.67	gold quality
aorta	UBERON:0000947	91.50	gold quality
superficial temporal artery	UBERON:0001614	91.34	gold quality
caecum	UBERON:0001153	91.02	gold quality
mucosa of urinary bladder	UBERON:0001259	90.96	gold quality
periodontal ligament	UBERON:0008266	90.57	gold quality
trabecular bone tissue	UBERON:0002483	90.50	gold quality
myometrium	UBERON:0001296	90.32	gold quality
urinary bladder	UBERON:0001255	90.28	gold quality
skin of hip	UBERON:0001554	90.07	gold quality
descending thoracic aorta	UBERON:0002345	89.60	gold quality
lymph node	UBERON:0000029	89.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-88	yes	17.41
E-HCAD-25	yes	15.96
E-ANND-3	yes	12.90
E-CURD-112	no	3.56

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2, CREB1, GFI1, STAT3

miRNA regulators (miRDB)

410 targeting ENTPD1, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-12136	99.98	72.81	5713

Literature-anchored findings (GeneRIF, showing 40)

• NTPDase/E-ATPDase activity was demonstrated on cryosections of human pancreas.Significantly diminished activity of NTPDase1 in the tissues surrounding the ducts was detected (PMID:11897808)
• Thrombin-induced deactivation of CD39 in endothelial cells is reversed by HMG-CoA reductase inhibitors and preservation of ATP and ADP metabolism. (PMID:12067895)
• Roles of Asp54 and Asp213 in Ca2+ utilization by soluble enzymes (PMID:12234494)
• Depolarization causes the endothelial production of superoxide, which inhibits the activity of endothelial NTPDase-1 and enhances platelet aggregation. (PMID:12482826)
• Correlation was observed between ATP hydrolysis and triglycerides in patients with chronic heart disease, suggesting a relationship between ATP diphosphohydrolase and thrombogenesis. (PMID:12623446)
• hCD39 transgenic mice exhibit impaired platelet aggregation, prolonged bleeding times, and resistance to systemic thromboembolism (PMID:15146241)
• capacity of NTPDase1 to hydrolyze both nucleoside triphosphates and diphosphates. (PMID:15496502)
• The NTPDase1/CD39 is the dominant ecto-nucleotidase of vascular and placental trophoblastic tissues and appears to modulate the functional expression of type-2 purinergic (P2) G-protein coupled receptors (GPCRs). (PMID:15590415)
• After exercise, all subjects showed a significant reduction of CD39 expression in platelet and an increase of CD39 expression in B lymphocytes. (PMID:15772061)
• there is a functional link between the localization of CD39 in cholesterol-rich domains of the membrane and its role in thromboregulation (PMID:15890655)
• leukocyte NTPDase1 provides means of dephosphorylating ATP which enables ATP-induced platelet aggregation via conversion to ADP, but also converts ADP to AMP and adenosine. (PMID:16011960)
• Changes in the expression of NTPDase1 and caveolins seem to be independent of human cardiovascular disease (PMID:16028070)
• CD39 associations with RanBPM have the potential to regulate NTPDase catalytic activity. This intermolecular interaction may have important implications for the regulation of extracellular nucleotide-mediated signalling. (PMID:16478441)
• Distinct roles for CD39 and P2-purinergic signaling in both tissue remodeling and fibrogenesis with respect to human pancreatic diseases. (PMID:16920697)
• Composition of the active site of wild-type CD39 appears optimized for ADPase function in the context of the transmembrane domains. (PMID:17374358)
• Patients with the remitting/relapsing form of multiple sclerosis have strikingly reduced numbers of CD39(+) Treg cells in the blood (PMID:17449799)
• Data show that host-derived CD39 is acquired by both laboratory-adapted and clinical variants of HIV-1 produced in cellular reservoirs of the virus. (PMID:17560607)
• the effect of overexpressed CD39/NTPDase-1 in injured aorta (PMID:18485080)
• Prolonged exposure to endogenous ATP related to decreased NTPDase1/CD39 activity leads to P2-purinoceptor desensitization in impotent men (PMID:18600538)
• E-NTPDase1 plays an important role in regulating neutrophil chemotaxis by facilitating the hydrolysis of extracellular ATP (PMID:18713747)
• a novel Sp1-dependent regulatory pathway for CD39 indicate the likelihood that CD39 is central to protective responses to hypoxia/ischemia (PMID:18812468)
• stable oxidants present in diluted aqueous cigarette smoke extract (aCSE) are responsible for platelet NTPDase inhibition induced by aCSE. (PMID:18979366)
• Studies in human cell lines and in vivo mouse data support a potential role for ENTPD1 genetic variation in susceptibility to type 2 diabetes. (PMID:19095759)
• Isolation of functional human regulatory T cells (Treg) from the peripheral blood based on the CD39 expression. (PMID:19450601)
• report that the ectoenzyme CD39/NTPDase1 helps to delineate a novel population of human “inducer” CD4+ T cells (Tind) that significantly increases the proliferation and cytokine production of responder T cells in a dose-dependent manner. (PMID:19877008)
• The NTPDase activity and expression were increased in lymphocytes from RRMS patients when compared with the control group. (PMID:19914228)
• 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)
• CD39(+);Fxop3(+);Treg subset may play an essential role in immune regulation of Treg, and CD39 can be used as a surface marker to identify the functional Treg cells. (PMID:20487644)
• Increased expression of CD39 is restricted to the CD4-expressing T cell population from the inflamed joint in juvenile idiopathic arthritis. (PMID:20498355)
• reduced expression by CD8-positive Treg populations from primary biliary cirrhosis patients (PMID:20638239)
• CD39 is expressed at high levels in clinical inflammatory bowel disease tissues. (PMID:20936356)
• We conclude that the ectonucleotidase CD39 is a useful and dynamic lymphocytes surface marker that can be used to identify different peripheral blood T cell-populations to allow tracking of these in health and disease, as in renal allograft rejection. (PMID:20977632)
• In type 2 diabetes (T2D) patients, the percentages of CD39+ cells and CD39+CD19+ cells were significantly associated with HbA1c and fasting plasma glucose levels. Enhanced CD39 enzyme activity and low serum levels of IL-17 were detected in T2D patients. (PMID:21492831)
• the ectonucleotidases CD39 and CD73 and ADORA2A appear as possible targets for novel treatments in ovarian cancer (PMID:21638125)
• CD39(+)Tregs inhibit generation and differentiation of Th17 cells via a latency-associated peptide-dependent mechanism in malignant pleural effusion. (PMID:21663645)
• Extracellular nucleotides, whose levels are tightly controlled by endogenously expressed NTPDase1, induce interleukin (IL)-8 production by human neutrophils. (PMID:21670316)
• Exosomes from diverse cancer cell types exhibit potent ATP and 5’AMP phosphohydrolytic activity, partly attributed to exosomally expressed CD39 and CD73, which contribute to extracellular adenosine production. (PMID:21677139)
• Data indicate that CD39-expressing T(regs) comprised 37+/-13% of the T(reg) population in healthy controls and 36+/-21% in lupus subjects. (PMID:21763644)
• transgenic ENTPDase-1 expression preferentially conveys myocardial protection from ischemic injury via adenosine A(2B) receptor engagement (PMID:21939667)
• 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)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	entpd1	ENSDARG00000045066
mus_musculus	Entpd1	ENSMUSG00000048120
rattus_norvegicus	Entpd1	ENSRNOG00000014574

Paralogs (7): ENTPD2 (ENSG00000054179), ENTPD3 (ENSG00000168032), ENTPD5 (ENSG00000187097), ENTPD8 (ENSG00000188833), ENTPD4 (ENSG00000197217), ENTPD6 (ENSG00000197586), ENTPD7 (ENSG00000198018)

Protein

Protein identifiers

Ectonucleoside triphosphate diphosphohydrolase 1 — P49961 (reviewed: P49961)

Alternative names: ATP diphosphohydrolase, Ecto-ATP diphosphohydrolase 1, Ecto-apyrase, Lymphoid cell activation antigen, Nucleoside triphosphate diphosphohydrolase 1

All UniProt accessions (4): P49961, A0A0U1RQZ5, A0A0U1RR44, A0A1W2PQK8

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. By hydrolyzing proinflammatory ATP and platelet-activating ADP to AMP, it blocks platelet aggregation and supports blood flow.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Membrane. Caveola.

Tissue specificity. Expressed primarily on activated lymphoid cells. Also expressed in endothelial tissues. Highly expressed in placenta, lung, skeletal muscle, kidney.

Post-translational modifications. N-glycosylated. The N-terminus is blocked. Palmitoylated on Cys-13; which is required for caveola targeting.

Disease relevance. Spastic paraplegia 64, autosomal recessive (SPG64) [MIM:615683] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The ADP and ATP diphosphohydrolase activities are decreased by half by sodium azide. The ADP diphosphohydrolase activity is inhibited by EDTA. The ATP and ADP diphosphohydrolase activities are inhibited by sodium fluoride. The ADP diphosphohydrolase activity is inhibited to a less extend by adenosine 5’-[alpha,beta-methylene]triphosphate and of about 80% by AMP-PNP.

Similarity. Belongs to the GDA1/CD39 NTPase family.

Isoforms (6)

UniProt ID	Names	Canonical?
P49961-1	1, Vascular	yes
P49961-2	2, Placental I
P49961-3	3, Placental II
P49961-4	4
P49961-5	5
P49961-6	6

RefSeq proteins (9): NP_001091645, NP_001157650, NP_001157651, NP_001157653, NP_001157654, NP_001157655, NP_001299583, NP_001307845, NP_001767* (*=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 (79 total): binding site 47, glycosylation site 6, splice variant 6, disulfide bond 5, sequence conflict 5, topological domain 3, transmembrane region 2, sequence variant 2, chain 1, lipid moiety-binding region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49961-F1	90.85	0.78

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): 174 (proton acceptor)

Ligand- & substrate-binding residues (47): 57; 57; 57; 58; 58; 58; 58; 58; 59; 59; 59; 59 …

Post-translational modifications (1): 13

Disulfide bonds (5): 84–108, 255–301, 282–325, 338–343, 390–413

Glycosylation sites (6): 73, 227, 292, 334, 371, 457

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8850843	Phosphate bond hydrolysis by NTPDase proteins
R-HSA-9660826	Purinergic signaling in leishmaniasis infection

MSigDB gene sets: 437 (showing top): GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_PLATELET_ACTIVATION, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GGGTGGRR_PAX4_03, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_WOUND_HEALING, GOBP_CELL_CELL_ADHESION, WTGAAAT_UNKNOWN, CASORELLI_APL_SECONDARY_VS_DE_NOVO_UP, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN

GO Biological Process (9): AMP catabolic process (GO:0006196), cell adhesion (GO:0007155), G protein-coupled receptor signaling pathway (GO:0007186), blood coagulation (GO:0007596), nucleoside diphosphate catabolic process (GO:0009134), ADP catabolic process (GO:0046032), platelet aggregation (GO:0070527), purine ribonucleoside diphosphate catabolic process (GO:0009181), platelet activation (GO:0030168)

GO Molecular Function (16): GTPase activity (GO:0003924), apyrase activity (GO:0004050), GDP phosphatase activity (GO:0004382), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nucleoside diphosphate phosphatase activity (GO:0017110), ribonucleoside triphosphate phosphatase activity (GO:0017111), CDP phosphatase activity (GO:0036384), ADP phosphatase activity (GO:0043262), CTPase activity (GO:0043273), UDP phosphatase activity (GO:0045134), ITPase activity (GO:0103023), IDP phosphatase activity (GO:1990003), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): basement membrane (GO:0005604), plasma membrane (GO:0005886), caveola (GO:0005901), external side of plasma membrane (GO:0009897), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Nucleotide catabolism	1
Cell recruitment (pro-inflammatory response)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleoside diphosphate phosphatase activity	5
ribonucleoside triphosphate phosphatase activity	4
pyrophosphatase activity	3
purine ribonucleotide catabolic process	2
purine ribonucleoside monophosphate catabolic process	1
AMP metabolic process	1
cellular process	1
G protein-coupled receptor activity	1
signal transduction	1
hemostasis	1
wound healing	1
coagulation	1
nucleoside diphosphate metabolic process	1
nucleoside phosphate catabolic process	1
purine ribonucleoside diphosphate catabolic process	1
ADP metabolic process	1
platelet activation	1
homotypic cell-cell adhesion	1
purine nucleoside diphosphate catabolic process	1
purine ribonucleoside diphosphate metabolic process	1
ribonucleoside diphosphate catabolic process	1
cell activation	1
blood coagulation	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ATP-dependent activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
extracellular matrix	1
membrane	1
cell periphery	1
plasma membrane raft	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

2598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENTPD1	NT5E	P21589	998
ENTPD1	P2RY2	P41231	935
ENTPD1	ADORA2A	P29274	862
ENTPD1	P2RY1	P47900	820
ENTPD1	TNFRSF18	Q9Y5U5	800
ENTPD1	CTLA4	P16410	782
ENTPD1	FOXP3	Q9BZS1	778
ENTPD1	CD4	P01730	768
ENTPD1	CD8A	P01732	760
ENTPD1	ADORA2B	P29275	752
ENTPD1	LAG3	P18627	720
ENTPD1	HAVCR2	Q8TDQ0	713
ENTPD1	ADA	P00813	704
ENTPD1	IL10	P22301	697
ENTPD1	TIGIT	Q495A1	692

IntAct

7 interactions, top by confidence:

A	B	Type	Score
ENTPD1	RANBP9	psi-mi:“MI:0915”(physical association)	0.580
RANBP9	ENTPD1	psi-mi:“MI:0915”(physical association)	0.580
ENTPD1	APC	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): ENTPD1 (Affinity Capture-RNA), PJA1 (Affinity Capture-MS), ANKRD50 (Affinity Capture-MS), ANKRD40 (Affinity Capture-MS), WDR60 (Affinity Capture-MS), ANKRD52 (Affinity Capture-MS), ASCC3 (Affinity Capture-MS), ANKRD44 (Affinity Capture-MS), PEX5 (Affinity Capture-MS), USP34 (Affinity Capture-MS), PDE4DIP (Affinity Capture-MS), APC (Affinity Capture-MS), PACSIN2 (Affinity Capture-MS), ENTPD2 (Negative Genetic), ENTPD1 (Affinity Capture-RNA)

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, E1BPW0, E1C1L6, O80612, P32621, P52914, P80595, Q2QYE1, Q6Z4P2, Q8TGG8, Q8TGH6, Q9HEM6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	6
Uncertain significance	100
Likely benign	84
Benign	25

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
101076	NM_001776.6(ENTPD1):c.628G>A (p.Gly210Arg)	Pathogenic
101077	NM_001776.6(ENTPD1):c.520G>T (p.Glu174Ter)	Pathogenic
2129367	NM_001776.6(ENTPD1):c.1020C>G (p.Tyr340Ter)	Pathogenic
2443792	NM_001776.6(ENTPD1):c.1109T>A (p.Leu370Ter)	Pathogenic
2443794	NM_001776.6(ENTPD1):c.640del (p.Gly216fs)	Pathogenic
2784423	NM_001776.6(ENTPD1):c.861T>A (p.Tyr287Ter)	Pathogenic
3775363	NM_001776.6(ENTPD1):c.967C>T (p.Gln323Ter)	Pathogenic
802625	NM_001776.6(ENTPD1):c.770_771del (p.Gly257fs)	Pathogenic
3345590	NM_001776.6(ENTPD1):c.1018_1021del (p.Tyr340fs)	Likely pathogenic
3638856	NM_001776.6(ENTPD1):c.813+2C>G	Likely pathogenic
3775912	NM_001776.6(ENTPD1):c.262+1G>T	Likely pathogenic
3776000	NM_001776.6(ENTPD1):c.144+1G>A	Likely pathogenic
3779615	NM_001776.6(ENTPD1):c.17-2A>G	Likely pathogenic
802624	NM_001776.6(ENTPD1):c.574-6_574-3del	Likely pathogenic

SpliceAI

2586 predictions. Top by Δscore:

Variant	Effect	Δscore
10:95823235:A:AG	acceptor_gain	1.0000
10:95823236:G:GG	acceptor_gain	1.0000
10:95823236:GA:G	acceptor_gain	1.0000
10:95823361:TAAGG:T	donor_loss	1.0000
10:95823364:GGT:G	donor_loss	1.0000
10:95823365:G:GC	donor_loss	1.0000
10:95823365:G:GG	donor_gain	1.0000
10:95823366:TAAG:T	donor_loss	1.0000
10:95839689:A:AG	acceptor_gain	1.0000
10:95839689:AGTAT:A	acceptor_gain	1.0000
10:95839690:G:GG	acceptor_gain	1.0000
10:95839690:GT:G	acceptor_gain	1.0000
10:95839690:GTAT:G	acceptor_gain	1.0000
10:95839690:GTATG:G	acceptor_gain	1.0000
10:95844631:GTCAG:G	donor_gain	1.0000
10:95820994:G:GT	donor_gain	0.9900
10:95823222:T:TA	acceptor_gain	0.9900
10:95823228:T:TA	acceptor_gain	0.9900
10:95823229:G:A	acceptor_gain	0.9900
10:95823231:TTTTA:T	acceptor_loss	0.9900
10:95823235:A:C	acceptor_loss	0.9900
10:95823236:G:GA	acceptor_loss	0.9900
10:95823236:GAGT:G	acceptor_gain	0.9900
10:95823360:TTAAG:T	donor_gain	0.9900
10:95839677:T:TA	acceptor_loss	0.9900
10:95839682:T:A	acceptor_loss	0.9900
10:95839685:TTTCA:T	acceptor_loss	0.9900
10:95839686:TTCA:T	acceptor_loss	0.9900
10:95839687:TCAG:T	acceptor_loss	0.9900
10:95839688:CAGT:C	acceptor_loss	0.9900

AlphaMissense

3396 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:95866198:T:A	W450R	1.000
10:95866198:T:C	W450R	1.000
10:95839745:T:A	W67R	0.999
10:95839745:T:C	W67R	0.999
10:95839747:G:C	W67C	0.999
10:95839747:G:T	W67C	0.999
10:95844597:T:A	W179R	0.999
10:95844597:T:C	W179R	0.999
10:95844599:G:C	W179C	0.999
10:95844599:G:T	W179C	0.999
10:95866200:G:C	W450C	0.999
10:95866200:G:T	W450C	0.999
10:95866207:G:C	G453R	0.999
10:95866208:G:A	G453D	0.999
10:95866208:G:T	G453V	0.999
10:95839709:G:C	A55P	0.998
10:95844611:C:A	N183K	0.998
10:95844611:C:G	N183K	0.998
10:95866207:G:T	G453C	0.998
10:95866217:T:C	L456P	0.998
10:95866223:T:C	L458P	0.998
10:95839739:T:G	Y65D	0.997
10:95844584:A:C	E174D	0.997
10:95844584:A:T	E174D	0.997
10:95845424:T:C	L214P	0.997
10:95845537:A:C	S252R	0.997
10:95845539:C:A	S252R	0.997
10:95845539:C:G	S252R	0.997
10:95839694:G:T	G50W	0.996
10:95839704:T:C	L53P	0.996

dbSNP variants (sampled 300 via entrez): RS1000017855 (10:95854104 T>C), RS1000019824 (10:95832461 T>C), RS1000041087 (10:95768496 TTTTC>T,TTTTCTTTC), RS1000060246 (10:95814698 C>T), RS1000112958 (10:95858298 C>G), RS1000144594 (10:95760293 G>T), RS1000147428 (10:95825639 A>G), RS1000151373 (10:95777339 T>A,C), RS1000154129 (10:95729784 A>G), RS1000159684 (10:95741806 T>G), RS1000163833 (10:95769355 G>A), RS1000218599 (10:95722296 T>A), RS1000225804 (10:95789075 A>G), RS1000257555 (10:95769972 G>A), RS1000275153 (10:95815540 A>G)

Disease associations

OMIM: gene MIM:601752 | disease phenotypes: MIM:615683, MIM:303350, MIM:258860, MIM:614815

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary spastic paraplegia 64	Definitive	Autosomal recessive
complex hereditary spastic paraplegia	Definitive	Autosomal recessive
neurodevelopmental disorder	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex hereditary spastic paraplegia	Definitive	AR

Mondo (8): hereditary spastic paraplegia 64 (MONDO:0014303), hereditary spastic paraplegia (MONDO:0019064), orofaciodigital syndrome IV (MONDO:0009794), Joubert syndrome 18 (MONDO:0013896), polymicrogyria (MONDO:0000087), microcephaly (MONDO:0001149), complex hereditary spastic paraplegia (MONDO:0015150), neurodevelopmental disorder (MONDO:0700092)

Orphanet (5): Autosomal recessive spastic paraplegia type 64 (Orphanet:401810), Hereditary spastic paraplegia (Orphanet:685), Orofaciodigital syndrome type 4 (Orphanet:2753), Orofaciodigital syndrome type 6 (Orphanet:2754), Polymicrogyria (Orphanet:35981)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000519	Developmental cataract
HP:0000718	Aggressive behavior
HP:0000823	Delayed puberty
HP:0001249	Intellectual disability
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001762	Talipes equinovarus
HP:0002342	Moderate intellectual disability
HP:0002500	Abnormal cerebral white matter morphology
HP:0003202	Skeletal muscle atrophy
HP:0006889	Borderline intellectual disability

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST006585_2586	Blood protein levels	2.000000e-08
GCST010796_5375	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-15
GCST010796_5376	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-14
GCST010796_5377	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-14
GCST010796_5378	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-12
GCST010796_5379	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-12
GCST010796_5380	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-11
GCST010796_5381	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-10
GCST010796_5382	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-10
GCST010796_5383	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST90002400_717	Plateletcrit	1.000000e-11
GCST90002401_218	Platelet distribution width	8.000000e-12
GCST90002402_126	Platelet count	1.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D065706	Polymicrogyria	C10.500.507.500.500; C16.131.666.507.500.500
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C537133	Orofaciodigital syndrome 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5722 (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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
PSB-0963	Inhibition	5.59	pKi
ARL 67156	Inhibition	4.57	pKi

ChEMBL bioactivities

8 potent at pChembl≥5 of 16 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	IC50	50	nM	CHEMBL5277365
6.30	IC50	500	nM	CHEMBL5283491
6.10	Ki	800	nM	CHEMBL4750781
6.10	Ki	800	nM	CHEMBL2364580
6.05	Ki	900	nM	CHEMBL4797422
5.59	Ki	2590	nM	CHEMBL608559
5.28	IC50	5200	nM	CHEMBL4787368
5.25	IC50	5600	nM	CHEMBL2364580

PubChem BioAssay actives

8 with measured affinity, of 115 total; 7 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
3-[2-[(E)-(3,4,5-trimethoxyphenyl)methylideneamino]-1,3-thiazol-4-yl]chromen-2-one	1960114: Inhibition of human NTPDase1	ic50	0.0500	uM
[[(2R,3S,4R,5R)-5-(6-amino-8-butan-2-ylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	1960114: Inhibition of human NTPDase1	ic50	0.5000	uM
[(2R,3S,4R,5R)-5-(6-amino-8-butylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate	1692611: Inhibition of human CD39 using ATP as substrate preincubated for 3 mins followed by substrate addition and measured after 10 to 15 mins by Dixon and Cornish-Bowden plot analysis	ki	0.8000	uM
[[(2R,3S,4R,5R)-5-(6-amino-8-butylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	1692612: Inhibition of human CD39 using ATP as substrate preincubated for 3 mins followed by substrate addition and measured after 10 to 15 mins by Cheng-Prusoff analysis	ki	0.8000	uM
[(2R,3S,4R,5R)-5-(6-amino-8-butylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	1692611: Inhibition of human CD39 using ATP as substrate preincubated for 3 mins followed by substrate addition and measured after 10 to 15 mins by Dixon and Cornish-Bowden plot analysis	ki	0.9000	uM
sodium 1-amino-4-(anthracen-2-ylamino)-9,10-dioxoanthracene-2-sulfonate	461580: Inhibition of human NTPdase1 by capillary electrophoresis method	ki	2.5900	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	1692618: Inhibition of human CD39 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	5.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, decreases expression, affects cotreatment	3
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	3
bisphenol A	decreases methylation, increases expression	2
entinostat	increases expression, affects cotreatment	2
Nickel	increases expression	2
Valproic Acid	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
testosterone enanthate	affects expression	1
ethylbenzene	affects cotreatment, decreases methylation, increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases methylation	1
cobaltous chloride	increases expression	1
nickel sulfate	increases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
cerivastatin	decreases expression, decreases reaction	1
deguelin	increases expression, decreases reaction	1
17-(dimethylaminoethylamino)-17-demethoxygeldanamycin	decreases reaction, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
2-(1’H-indole-3’-carbonyl)thiazole-4-carboxylic acid methyl ester	increases expression	1
Air Pollutants, Occupational	decreases methylation, increases expression	1
Arsenic	affects methylation	1
Azacitidine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Cytarabine	increases expression	1

ChEMBL screening assays

32 unique, capped per target: 27 binding, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001638	Binding	Activity of human NTPDase 1 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
CHEMBL2390590	ADMET	Drug metabolism assessed as human nucleotide triphosphate diphosphohydrolase1-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

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8F9	Abcam HCT 116 ENTPD1 KO	Cancer cell line	Male
CVCL_B9HH	Abcam A-549 ENTPD1 KO	Cancer cell line	Male
CVCL_D2F1	Abcam MCF-7 ENTPD1 KO	Cancer cell line	Female
CVCL_D8KT	Ubigene HCT 116 ENTPD1 KO	Cancer cell line	Male
CVCL_E0CL	Ubigene HeLa ENTPD1 KO	Cancer cell line	Female
CVCL_SM09	HAP1 ENTPD1 (-) 1	Cancer cell line	Male
CVCL_XN46	HAP1 ENTPD1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase