ENTPD4

Summary

ENTPD4 (ectonucleoside triphosphate diphosphohydrolase 4, HGNC:14573) is a protein-coding gene on chromosome 8p21.3, encoding Ectonucleoside triphosphate diphosphohydrolase 4 (Q9Y227). Catalyzes the hydrolysis of nucleoside triphosphates and diphosphates in a calcium- or magnesium-dependent manner, with a preference for pyrimidines.

This gene encodes a member of the apyrase protein family. Apyrases are enzymes that catalyze the hydrolysis of nucleotide diphosphates and triphosphates in a calcium or magnesium-dependent manner. The encoded protein is an endo-apyrase and may play a role in salvaging nucleotides from lysosomes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and these isoforms may differ in divalent cation dependence and substrate specificity.

Source: NCBI Gene 9583 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 131 total
• Druggable target: yes
• MANE Select transcript: NM_004901

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14573
Approved symbol	ENTPD4
Name	ectonucleoside triphosphate diphosphohydrolase 4
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	LALP70, LAP70, KIAA0392, NTPDase-4, UDPase
Ensembl gene	ENSG00000197217
Ensembl biotype	protein_coding
OMIM	607577
Entrez	9583

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000356206, ENST00000358689, ENST00000417069, ENST00000518471, ENST00000518718, ENST00000519839, ENST00000520936, ENST00000521321, ENST00000522255, ENST00000522913, ENST00000523958, ENST00000854257, ENST00000854258, ENST00000912386, ENST00000912387, ENST00000912388, ENST00000912389, ENST00000961346, ENST00000961347, ENST00000961348

RefSeq mRNA: 2 — MANE Select: NM_004901 NM_001128930, NM_004901

CCDS: CCDS47827, CCDS6041

Canonical transcript exons

ENST00000358689 — 13 exons

Exon	Start	End
ENSE00001203350	23457557	23457647
ENSE00001822839	23429162	23433154
ENSE00003473340	23439749	23439915
ENSE00003485960	23449893	23449997
ENSE00003541728	23441569	23441723
ENSE00003546466	23434317	23434478
ENSE00003560374	23448742	23448939
ENSE00003579088	23436934	23437258
ENSE00003622125	23444456	23444606
ENSE00003622211	23443850	23443953
ENSE00003647317	23435392	23435477
ENSE00003657045	23447680	23447885
ENSE00003787187	23442007	23442066

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.9357 / max 297.4962, expressed in 1803 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92321	18.1909	1792
92322	4.7448	1584

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	97.75	gold quality
middle temporal gyrus	UBERON:0002771	97.08	gold quality
tibia	UBERON:0000979	97.00	gold quality
endothelial cell	CL:0000115	96.78	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.77	gold quality
postcentral gyrus	UBERON:0002581	95.39	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.12	gold quality
orbitofrontal cortex	UBERON:0004167	95.04	gold quality
tonsil	UBERON:0002372	94.98	gold quality
palpebral conjunctiva	UBERON:0001812	94.87	gold quality
parietal lobe	UBERON:0001872	94.84	gold quality
pigmented layer of retina	UBERON:0001782	94.78	gold quality
corpus epididymis	UBERON:0004359	94.76	gold quality
cauda epididymis	UBERON:0004360	94.74	gold quality
parotid gland	UBERON:0001831	94.63	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.59	gold quality
stromal cell of endometrium	CL:0002255	94.44	gold quality
visceral pleura	UBERON:0002401	94.34	gold quality
superior frontal gyrus	UBERON:0002661	94.17	gold quality
skin of hip	UBERON:0001554	93.90	gold quality
jejunal mucosa	UBERON:0000399	93.87	gold quality
primary visual cortex	UBERON:0002436	93.86	gold quality
colonic mucosa	UBERON:0000317	93.80	gold quality
vermiform appendix	UBERON:0001154	93.76	gold quality
lymph node	UBERON:0000029	93.75	gold quality
cartilage tissue	UBERON:0002418	93.69	gold quality
entorhinal cortex	UBERON:0002728	93.67	gold quality
upper leg skin	UBERON:0004262	93.43	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.28	gold quality
occipital lobe	UBERON:0002021	93.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.33
E-MTAB-9388	yes	6.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

110 targeting ENTPD4, 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-4692	100.00	67.32	2066
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-765	99.84	68.24	2442

Literature-anchored findings (GeneRIF, showing 4)

• The VSFASSQQ motif confers calcium sensitivity to LALP70 during UDP cleavage. (PMID:15200686)
• The present study fails to provide evidence for the contribution of ENTPD4 genes to the etiology of schizophrenia in the Japanese population. (PMID:20537721)
• NTPDASE4 gene products cooperate with the adenovirus E4orf4 protein through PP2A-dependent and -independent mechanisms and contribute to induction of cell death. (PMID:24672025)
• Crystal structure of the nucleotide-metabolizing enzyme NTPDase4. (PMID:32767432)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	entpd4	ENSDARG00000038422
mus_musculus	Entpd4b	ENSMUSG00000022066
mus_musculus	Entpd4	ENSMUSG00000095463
rattus_norvegicus	Entpd4	ENSRNOG00000016321
caenorhabditis_elegans		WBGENE00003254
caenorhabditis_elegans		WBGENE00016380

Paralogs (7): ENTPD2 (ENSG00000054179), ENTPD1 (ENSG00000138185), ENTPD3 (ENSG00000168032), ENTPD5 (ENSG00000187097), ENTPD8 (ENSG00000188833), ENTPD6 (ENSG00000197586), ENTPD7 (ENSG00000198018)

Protein

Protein identifiers

Ectonucleoside triphosphate diphosphohydrolase 4 — Q9Y227 (reviewed: Q9Y227)

Alternative names: Golgi UDPase, Lysosomal apyrase-like protein of 70 kDa, Uridine-diphosphatase

All UniProt accessions (5): E5RIB2, Q9Y227, H0YAN2, H0YBY8, Q8NE73

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of nucleoside triphosphates and diphosphates in a calcium- or magnesium-dependent manner, with a preference for pyrimidines. Preferentially hydrolyzes UTP and TTP. AMP, ADP, ATP and UMP are not substrates. Preferentially activated by Ca(2+) over Mg(2+). Has a broad substrate specificity with the ability of cleaving all nucleotide di- and triphosphates with the exception of adenosine di- and triphosphate (ADP and ATP). Preferentially hydrolyzes CTP, UDP, CDP, GTP and GDP. Can use either Ca(2+) or Mg(2+) equally.

Subcellular location. Cytoplasmic vesicle. Autophagosome membrane. Lysosome membrane Golgi apparatus membrane.

Tissue specificity. Ubiquitous. Highest expression in testis and lowest in bladder.

Similarity. Belongs to the GDA1/CD39 NTPase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y227-1	1, LALP70	yes
Q9Y227-2	2, LALP70V

RefSeq proteins (2): NP_001122402, NP_004892* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000407	GDA1_CD39_NTPase	Family

Pfam: PF01150

Catalyzed reactions (Rhea), 8 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)
• GDP + H2O = GMP + phosphate + H(+) (RHEA:22156)
• a ribonucleoside 5’-triphosphate + H2O = a ribonucleoside 5’-diphosphate + phosphate + H(+) (RHEA:23680)
• CTP + H2O = CDP + phosphate + H(+) (RHEA:29387)
• a ribonucleoside 5’-diphosphate + H2O = a ribonucleoside 5’-phosphate + phosphate + H(+) (RHEA:36799)
• UDP + H2O = UMP + phosphate + H(+) (RHEA:64876)
• UTP + H2O = UDP + phosphate + H(+) (RHEA:64900)
• 5-methyl-UTP + H2O = 5-methyl-UDP + phosphate + H(+) (RHEA:65580)

UniProt features (88 total): binding site 28, helix 25, strand 16, turn 4, topological domain 3, transmembrane region 2, glycosylation site 2, disulfide bond 2, sequence variant 2, chain 1, splice variant 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6WG5	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y227-F1	87.51	0.69

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): 222 (proton acceptor)

Ligand- & substrate-binding residues (28): 97; 97; 98; 98; 98; 98; 179; 179; 179; 179; 274; 274 …

Disulfide bonds (2): 368–395, 461–490

Glycosylation sites (2): 404, 407

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 217 (showing top): GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOCC_VACUOLAR_MEMBRANE, AAGCCAT_MIR135A_MIR135B, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, KEGG_LYSOSOME, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, chr8p21, GOBP_PYRIMIDINE_NUCLEOTIDE_CATABOLIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, HESS_TARGETS_OF_HOXA9_AND_MEIS1_UP

GO Biological Process (6): UDP catabolic process (GO:0006256), nucleobase-containing small molecule catabolic process (GO:0034656), CTP metabolic process (GO:0046036), GDP catabolic process (GO:0046712), purine ribonucleotide metabolic process (GO:0009150), pyrimidine ribonucleotide catabolic process (GO:0009222)

GO Molecular Function (11): GTPase activity (GO:0003924), GDP phosphatase activity (GO:0004382), nucleoside diphosphate phosphatase activity (GO:0017110), ribonucleoside triphosphate phosphatase activity (GO:0017111), CDP phosphatase activity (GO:0036384), CTPase activity (GO:0043273), UDP phosphatase activity (GO:0045134), nucleotide binding (GO:0000166), protein binding (GO:0005515), ATP binding (GO:0005524), hydrolase activity (GO:0016787)

GO Cellular Component (8): Golgi membrane (GO:0000139), autophagosome membrane (GO:0000421), lysosomal membrane (GO:0005765), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), lysosome (GO:0005764), cytoplasmic vesicle membrane (GO:0030659)

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
nucleoside diphosphate phosphatase activity	3
pyrimidine ribonucleotide metabolic process	2
ribonucleoside triphosphate phosphatase activity	2
pyrophosphatase activity	2
cytoplasm	2
pyrimidine ribonucleoside diphosphate catabolic process	1
pyrimidine ribonucleotide catabolic process	1
UDP metabolic process	1
nucleobase-containing compound catabolic process	1
small molecule catabolic process	1
nucleobase-containing small molecule metabolic process	1
pyrimidine ribonucleoside triphosphate metabolic process	1
purine ribonucleotide catabolic process	1
purine ribonucleoside diphosphate catabolic process	1
GDP metabolic process	1
purine nucleotide metabolic process	1
ribonucleotide metabolic process	1
pyrimidine nucleotide catabolic process	1
ribonucleotide catabolic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
vacuolar membrane	1
autophagosome	1
lysosome	1
lytic vacuole membrane	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular vesicle	1
lytic vacuole	1
vesicle membrane	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

698 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENTPD4	WDFY1	Q8IWB7	470
ENTPD4	XPO7	Q9UIA9	428
ENTPD4	STXBP6	Q8NFX7	425
ENTPD4	SYT17	Q9BSW7	425
ENTPD4	VGLL3	A8MV65	420
ENTPD4	KIF18B	Q86Y91	414
ENTPD4	NT5C1B	Q96P26	410
ENTPD4	UGP2	Q16851	400
ENTPD4	ENTPD5	O75356	396
ENTPD4	HHAT	Q5VTY9	388
ENTPD4	SLC25A37	Q9NYZ2	381
ENTPD4	ENTPD6	O75354	371
ENTPD4	ENTPD8	Q5MY95	365
ENTPD4	CMPK1	P30085	358
ENTPD4	ENPP4	Q9Y6X5	347

IntAct

34 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
GABRE	FZD6	psi-mi:“MI:0914”(association)	0.530
CCT8L2	ACSL4	psi-mi:“MI:0914”(association)	0.530
PCDHAC2	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
ENTPD4	PCYOX1	psi-mi:“MI:0915”(physical association)	0.500
RPS27	ENTPD4	psi-mi:“MI:0915”(physical association)	0.370
	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350
LRRC55	TMEM120B	psi-mi:“MI:0914”(association)	0.350
ATP2A1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
ATP13A3	GPR89A	psi-mi:“MI:0914”(association)	0.350
CD79B	GOLIM4	psi-mi:“MI:0914”(association)	0.350
HFE	PODXL	psi-mi:“MI:0914”(association)	0.350
ENTPD4	TYW1B	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
GP9	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATP2A3	UBXN8	psi-mi:“MI:0914”(association)	0.350
CHRNB1	CLGN	psi-mi:“MI:0914”(association)	0.350
PCDHGB4	AAMP	psi-mi:“MI:0914”(association)	0.350
SCN3B	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC1A1	SCD	psi-mi:“MI:0914”(association)	0.350
SLC30A1	PSMD11	psi-mi:“MI:0914”(association)	0.350
SLC39A11	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (35): ENTPD4 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), ENTPD4 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), TYW1B (Affinity Capture-MS), ENTPD4 (Affinity Capture-MS), ENTPD4 (Affinity Capture-MS), PDZD8 (Affinity Capture-MS), ENTPD4 (Affinity Capture-MS), ENTPD4 (Affinity Capture-MS), ENTPD4 (Affinity Capture-MS), ENTPD4 (Affinity Capture-MS), ENTPD4 (Affinity Capture-MS), TYW1B (Affinity Capture-MS), ENTPD4 (Affinity Capture-MS)

ESM2 similar proteins: A0A2D0TC04, A1A4K5, A7E2Z9, A8MWY0, F1QR43, J3SBP3, J3SEZ3, O14638, O15041, O18756, O94923, O95461, P06802, P0DQQ4, P15396, P22413, P79948, P97675, Q13219, Q13822, Q3UZV7, Q5M900, Q5NDE3, Q5NDE4, Q5NDE5, Q5NDE8, Q5R5M5, Q64610, Q66PG1, Q66PG2, Q66PG3, Q6DYE8, Q6FHJ7, Q6GMK0, Q6NRQ1, Q6P9A2, Q8C1F4, Q8JHF2, Q8K1B9, Q8N6G5

Diamond homologs: P40009, Q18411, Q21815, Q28CF8, Q3TCT4, Q5REF6, Q617Y0, Q9DBT4, Q9NQZ7, Q9USP2, Q9XU84, Q9Y227, P52914, P80595, Q9SPM5, Q9SQG2, O75354, Q8H7L6, Q6Z4P2, E1BPW0, Q2QYE1, D2GZV9, O55026, Q9Y5L3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 44 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.

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	5	92.4×	6e-07
intracellular calcium ion homeostasis	5	19.1×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	109
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2672 predictions. Top by Δscore:

Variant	Effect	Δscore
8:23403952:A:AC	donor_gain	1.0000
8:23403953:C:CC	donor_gain	1.0000
8:23433160:CA:C	acceptor_gain	1.0000
8:23434476:TACC:T	acceptor_loss	1.0000
8:23434478:CCTA:C	acceptor_loss	1.0000
8:23434479:CTA:C	acceptor_loss	1.0000
8:23434480:T:G	acceptor_loss	1.0000
8:23435387:CTT:C	donor_loss	1.0000
8:23435388:TTA:T	donor_loss	1.0000
8:23435390:A:AC	donor_gain	1.0000
8:23435390:A:T	donor_loss	1.0000
8:23435391:C:A	donor_loss	1.0000
8:23435391:C:CA	donor_gain	1.0000
8:23435394:AAG:A	donor_gain	1.0000
8:23435473:TAATC:T	acceptor_gain	1.0000
8:23435474:AATC:A	acceptor_gain	1.0000
8:23435476:TC:T	acceptor_gain	1.0000
8:23435476:TCCTG:T	acceptor_loss	1.0000
8:23435477:CC:C	acceptor_gain	1.0000
8:23435477:CCTGA:C	acceptor_loss	1.0000
8:23435478:C:CA	acceptor_loss	1.0000
8:23435478:C:CC	acceptor_gain	1.0000
8:23436989:T:TA	donor_gain	1.0000
8:23437973:A:AC	donor_gain	1.0000
8:23437974:T:C	donor_gain	1.0000
8:23437980:T:TA	donor_gain	1.0000
8:23439916:C:CG	acceptor_loss	1.0000
8:23439917:T:G	acceptor_loss	1.0000
8:23441403:G:C	donor_gain	1.0000
8:23441591:A:AC	donor_gain	1.0000

AlphaMissense

4044 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:23434353:C:T	G529E	1.000
8:23434354:C:G	G529R	1.000
8:23434354:C:T	G529R	1.000
8:23434361:C:A	W526C	1.000
8:23434361:C:G	W526C	1.000
8:23434363:A:G	W526R	1.000
8:23434363:A:T	W526R	1.000
8:23442041:A:C	N231K	1.000
8:23442041:A:T	N231K	1.000
8:23442053:C:A	W227C	1.000
8:23442053:C:G	W227C	1.000
8:23442055:A:G	W227R	1.000
8:23442055:A:T	W227R	1.000
8:23443850:C:G	G223R	1.000
8:23443851:T:A	E222D	1.000
8:23443851:T:G	E222D	1.000
8:23444471:C:G	R183T	1.000
8:23447773:A:G	W107R	1.000
8:23447773:A:T	W107R	1.000
8:23447781:A:T	V104D	1.000
8:23447790:C:G	R101P	1.000
8:23434344:A:G	L532P	0.999
8:23434350:G:T	A530D	0.999
8:23434351:C:G	A530P	0.999
8:23434353:C:A	G529V	0.999
8:23434362:C:G	W526S	0.999
8:23434456:A:G	W495R	0.999
8:23434456:A:T	W495R	0.999
8:23434471:A:G	C490R	0.999
8:23435469:A:C	C461W	0.999

dbSNP variants (sampled 300 via entrez): RS1000114003 (8:23457462 C>G), RS1000184773 (8:23455961 C>G), RS1000206855 (8:23438048 C>T), RS1000214253 (8:23443209 T>C), RS1000235128 (8:23457612 G>A,C,T), RS1000373777 (8:23449003 T>C), RS1000386174 (8:23454885 AT>A), RS1000487042 (8:23444892 C>A,G), RS1000547558 (8:23439660 T>C,G), RS1000733590 (8:23453459 C>G,T), RS1000755360 (8:23446107 T>C), RS1000817934 (8:23444666 T>A,C), RS1001124192 (8:23445731 C>T), RS1001124270 (8:23447616 A>G), RS1001287884 (8:23457744 G>C,T)

Disease associations

OMIM: gene MIM:607577 | disease phenotypes: MIM:217095

GenCC curated gene-disease

Mondo (1): conotruncal heart malformations (MONDO:0016581)

Orphanet (3): Conotruncal heart malformations (Orphanet:2445), Common arterial trunk (Orphanet:3384), Double outlet right ventricle (Orphanet:3426)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005051_19	Obstructive sleep apnea trait (apnea hypopnea index)	7.000000e-07
GCST008362_176	Birth weight	1.000000e-11
GCST008839_157	Height	4.000000e-10
GCST010653_31	Thyroid stimulating hormone levels	1.000000e-21

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007817	sleep apnea measurement
EFO:0004344	birth weight

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3313834 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
trichostatin A	affects cotreatment, decreases expression	3
bisphenol A	affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
nickel chloride	decreases expression	1
potassium chromate(VI)	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
PP242	decreases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diclofenac	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Oxygen	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3364112	ADMET	Stability assessed as human NTPDase4-mediated compound hydrolysis	2-Hexylthio-β,γ-CH2-ATP is an effective and selective NTPDase2 inhibitor. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004361	Not specified	COMPLETED	Study of the Relationship Between Calcium Levels and Intact Parathyroid Hormone (iPTH) in Adults With Repaired or Palliated Conotruncal Cardiac Defects
NCT00005102	Not specified	UNKNOWN	Immunologic Evaluation in Patients With DiGeorge Syndrome or Velocardiofacial Syndrome
NCT01460316	Not specified	COMPLETED	Conotruncal Cardiac Defects and Nutrigenetic Etiopathogeny