ENPP7

Summary

ENPP7 (ectonucleotide pyrophosphatase/phosphodiesterase 7, HGNC:23764) is a protein-coding gene on chromosome 17q25.3, encoding Ectonucleotide pyrophosphatase/phosphodiesterase family member 7 (Q6UWV6). Choline-specific phosphodiesterase that hydrolyzes sphingomyelin releasing the ceramide and phosphocholine and therefore is involved in sphingomyelin digestion, ceramide formation, and fatty acid (FA) absorption in the gastrointestinal tract.

The protein encoded by this gene is an intestinal alkaline sphingomyelin phosphodiesterase that converts sphingomyelin to ceramide and phosphocholine. The encoded protein is anchored in the cell membrane, and it may function to protect the intestinal mucosa from inflammation and tumorigenesis. This protein is glycosylated and also exhibits lysophosphatidylcholine hydrolase activity.

Source: NCBI Gene 339221 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 105 total
• Druggable target: yes
• MANE Select transcript: NM_178543

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23764
Approved symbol	ENPP7
Name	ectonucleotide pyrophosphatase/phosphodiesterase 7
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	alk-SMase, NPP7
Ensembl gene	ENSG00000182156
Ensembl biotype	protein_coding
OMIM	616997
Entrez	339221

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000328313, ENST00000576512, ENST00000864480, ENST00000864481, ENST00000864482

RefSeq mRNA: 1 — MANE Select: NM_178543 NM_178543

CCDS: CCDS11763

Canonical transcript exons

ENST00000328313 — 6 exons

Exon	Start	End
ENSE00001292940	79735043	79735669
ENSE00001296358	79737916	79738062
ENSE00001297319	79730943	79731392
ENSE00001310596	79737041	79737260
ENSE00001311948	79733508	79733653
ENSE00001337452	79741794	79742219

Expression profiles

Bgee: expression breadth broad, 91 present calls, max score 98.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2590 / max 149.9009, expressed in 13 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163179	0.1532	6
163180	0.0537	7
163181	0.0170	6
163183	0.0130	5
163182	0.0104	5
208433	0.0065	5
208432	0.0053	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.78	gold quality
duodenum	UBERON:0002114	93.37	gold quality
tendon of biceps brachii	UBERON:0008188	90.62	gold quality
kidney epithelium	UBERON:0004819	88.43	gold quality
jejunum	UBERON:0002115	85.77	gold quality
upper arm skin	UBERON:0004263	83.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.68	silver quality
left ventricle myocardium	UBERON:0006566	80.98	gold quality
epithelial cell of pancreas	CL:0000083	80.65	silver quality
vena cava	UBERON:0004087	77.80	silver quality
liver	UBERON:0002107	76.99	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	76.93	gold quality
right lobe of liver	UBERON:0001114	76.44	gold quality
trabecular bone tissue	UBERON:0002483	76.06	gold quality
nasal cavity epithelium	UBERON:0005384	74.99	gold quality
cerebellar vermis	UBERON:0004720	74.48	gold quality
epithelium of nasopharynx	UBERON:0001951	73.43	gold quality
pons	UBERON:0000988	73.03	gold quality
germinal epithelium of ovary	UBERON:0001304	72.89	silver quality
pericardium	UBERON:0002407	72.33	silver quality
gingival epithelium	UBERON:0001949	72.22	silver quality
thymus	UBERON:0002370	72.05	silver quality
saphenous vein	UBERON:0007318	72.02	gold quality
body of tongue	UBERON:0011876	71.99	silver quality
oocyte	CL:0000023	71.83	gold quality
pharyngeal mucosa	UBERON:0000355	71.73	silver quality
nipple	UBERON:0002030	71.68	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	71.63	silver quality
renal medulla	UBERON:0000362	71.52	gold quality
synovial joint	UBERON:0002217	71.44	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting ENPP7, 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-6825-5P	99.96	69.81	3431
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-634	97.74	67.11	818
HSA-MIR-320E	97.49	65.96	865
HSA-MIR-10397-5P	97.31	69.06	710

Literature-anchored findings (GeneRIF, showing 9)

• identified the amino acid and cDNA sequences of human intestinal alk-SMase, and found that it is a novel ecto-enzyme related to the ecto-nucleotide phosphodiesterase family with specific features essential for its SMase activity (PMID:12885774)
• intestinal alkaline sphingomyelinase may have a one-exon deletion in colon cancer cells (PMID:15016655)
• alk-SMase activity is severely affected by defective N-glycosylation at 5 sites and by structural alterations of the putative metal-binding sites and the predicted active core. (PMID:15458386)
• Results describe the cloning of rat alkaline sphingomyelinase from rat intestine, comparison to the human sequence, adjustment of the putative protein in GenBank, and confirmation of the specific expression of the gene in the small intestine. (PMID:15708357)
• Alkaline sphingomyelinase hydrolyses and inactivates PAF by a phospholipase C activity, a novel function by which it may counteract the development of intestinal inflammation and colon cancer. (PMID:16255717)
• predict the three-dimensional structure of NPP7 by homology modeling using a recently crystallized NPP from bacteria. Using the model, we studied the substrate specificity of the enzyme by docking. (PMID:20839774)
• The F275A mutation of NPP7 showed impaired catalytic function whereas L107F mutation showed enhanced catalytic activity. (PMID:22177013)
• NPP7 activity and the ratio of 1.4/1.2 kb products in bile are significantly decreased in malignancy, particularly in cholangiocarcinoma. (PMID:25100243)
• human alkaline sphingomyelinase crystal structure provides insights into substrate recognition (PMID:28292932)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	enpp7.2	ENSDARG00000053525
danio_rerio	enpp7.1	ENSDARG00000053526
mus_musculus	Enpp7	ENSMUSG00000046697
rattus_norvegicus	Enpp7	ENSRNOG00000081693
caenorhabditis_elegans		WBGENE00007753
caenorhabditis_elegans		WBGENE00007755

Paralogs (6): ENPP4 (ENSG00000001561), ENPP5 (ENSG00000112796), ENPP2 (ENSG00000136960), ENPP3 (ENSG00000154269), ENPP6 (ENSG00000164303), ENPP1 (ENSG00000197594)

Protein

Protein identifiers

Ectonucleotide pyrophosphatase/phosphodiesterase family member 7 — Q6UWV6 (reviewed: Q6UWV6)

Alternative names: Alkaline sphingomyelin phosphodiesterase, Intestinal alkaline sphingomyelinase

All UniProt accessions (2): Q6UWV6, I3L3G5

UniProt curated annotations — full annotation on UniProt →

Function. Choline-specific phosphodiesterase that hydrolyzes sphingomyelin releasing the ceramide and phosphocholine and therefore is involved in sphingomyelin digestion, ceramide formation, and fatty acid (FA) absorption in the gastrointestinal tract. Also has phospholipase C activity and can also cleave phosphocholine from palmitoyl lyso-phosphatidylcholine and platelet-activating factor (PAF) leading to its inactivation. Does not have nucleotide pyrophosphatase activity. May promote cholesterol absorption by affecting the levels of sphingomyelin derived from either diet or endogenous sources, in the intestinal lumen.

Subcellular location. Cell membrane.

Tissue specificity. Detected in the colon (at protein level). Expressed in the duodenum, jejunum and liver and at low levels in the ileum. Expression was very low in the esophagus, stomach and colon.

Post-translational modifications. N-glycosylated; required for activity and transport to the plasma membrane.

Activity regulation. Inhibited in a dose dependent manner by ATP, imidazole, orthovanadate and zinc ion. Not inhibited by ADP, AMP and EDTA.

Miscellaneous. Decreased levels of alkaline sphingomyelin phosphodiesterase may be associated with colon cancer.

Similarity. Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.

RefSeq proteins (1): NP_848638* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002591	Phosphodiest/P_Trfase	Family
IPR017850	Alkaline_phosphatase_core_sf	Homologous_superfamily

Pfam: PF01663

Enzyme classification (BRENDA):

• EC 3.1.4.12 — sphingomyelin phosphodiesterase (BRENDA: 30 organisms, 220 substrates, 319 inhibitors, 54 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
SPHINGOMYELIN	0.0006–13	30
2-N-HEXADECANOYLAMINO-4-NITROPHENYLPHOSPHORYLCHO	0.034–0.34	2
4-(4-NITROPHENOXY)-2-HYDROXY-BUTYL-1-PHOSPHORYLC	12.6–39.6	2
1-ALKYL-LYSO-PLATELET ACTIVATING FACTOR	0.048	1
2-(N-HEXADECANOYLAMINO)-4-NITROPHENYLPHOSPHORYLC	1.7	1
2N-HEXADECANOYLAMINO-4-NITROPHENYLPHOSPHORYLCHOL	0.027	1
4-NITROPHENYL PHOSPHORYLCHOLINE	11.6	1
ADP	0.306	1
ADP-RIBOSE	0.348	1
ATP	0.327	1
BIS-P-NITROPHENYL PHOSPHATE	14.5	1
BODIPYFL-C12-SPHINGOMYELIN	0.06	1
CDP-CHOLINE	0.262	1
CDP-ETHANOLAMINE	0.391	1
HEXADECANOYL-P-NITROPHENYL PHOSPHORYLCHOLINE	0.174	1

Catalyzed reactions (Rhea), 4 shown:

• a sphingomyelin + H2O = phosphocholine + an N-acylsphing-4-enine + H(+) (RHEA:19253)
• 1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycerol + phosphocholine + H(+) (RHEA:41119)
• a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = a 1-O-alkyl-2-acetyl-sn-glycerol + phosphocholine + H(+) (RHEA:63380)
• 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-octadecyl-2-acetyl-sn-glycerol + phosphocholine + H(+) (RHEA:63384)

UniProt features (76 total): helix 19, strand 15, mutagenesis site 14, binding site 8, glycosylation site 5, turn 5, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, sequence variant 1, transmembrane region 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5TCD	X-RAY DIFFRACTION	2.4
5UDY	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWV6-F1	91.15	0.85

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): 75 (nucleophile)

Ligand- & substrate-binding residues (8): 199; 203; 246; 247; 353; 39; 75; 96

Glycosylation sites (5): 100, 121, 146, 168, 267

Mutagenesis-validated functional residues (14):

Position	Phenotype
76	loss of activity.
78	strongly reduces activity.
100	strongly reduces n-glycosylation and enzyme activity; when associated with q-121; q-146; q-168 and q-267.
109	decreased enzyme activity with sphingomyelin and para-nitrophenylphosphorylcholine.
121	strongly reduces n-glycosylation and enzyme activity; when associated with q-100; q-146; q-168 and q-267.
146	strongly reduces n-glycosylation and enzyme activity; when associated with q-100; q-146; q-168 and q-267.
166	decreased enzyme activity with sphingomyelin and para-nitrophenylphosphorylcholine.
168	strongly reduces n-glycosylation and enzyme activity; when associated with q-100; q-121; q-168 and q-267.
267	strongly reduces n-glycosylation and enzyme activity; when associated with q-100; q-121; q-146 and q-168.
271	decreased enzyme activity; when associated with e-343.
343	decreased enzyme activity; when associated with e-271.
344–348	loss of enzyme activity with sphingomyelin.
353	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9840310	Glycosphingolipid catabolism

MSigDB gene sets: 101 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_DIGESTION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_AMIDE_METABOLIC_PROCESS, GOBP_SPHINGOMYELIN_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_DIGESTIVE_SYSTEM_PROCESS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_DIGESTION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, GOBP_LIPID_HOMEOSTASIS

GO Biological Process (11): sphingomyelin metabolic process (GO:0006684), negative regulation of DNA replication (GO:0008156), negative regulation of cell population proliferation (GO:0008285), lipid digestion (GO:0044241), positive regulation of intestinal cholesterol absorption (GO:0045797), glycosphingolipid catabolic process (GO:0046479), fatty acid homeostasis (GO:0055089), regulation of intestinal lipid absorption (GO:1904729), positive regulation of ceramide biosynthetic process (GO:2000304), positive regulation of sphingomyelin catabolic process (GO:2000755), lipid metabolic process (GO:0006629)

GO Molecular Function (6): sphingomyelin phosphodiesterase activity (GO:0004767), phosphoric diester hydrolase activity (GO:0008081), zinc ion binding (GO:0008270), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (4): Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), microvillus (GO:0005902), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycosphingolipid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phospholipid metabolic process	1
sphingolipid metabolic process	1
DNA replication	1
regulation of DNA replication	1
negative regulation of DNA metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
digestion	1
intestinal cholesterol absorption	1
regulation of intestinal cholesterol absorption	1
positive regulation of intestinal lipid absorption	1
glycosphingolipid metabolic process	1
glycolipid catabolic process	1
sphingolipid catabolic process	1
lipid homeostasis	1
intestinal lipid absorption	1
regulation of intestinal absorption	1
ceramide biosynthetic process	1
positive regulation of sphingolipid biosynthetic process	1
regulation of ceramide biosynthetic process	1
sphingomyelin catabolic process	1
positive regulation of phospholipid catabolic process	1
regulation of sphingomyelin catabolic process	1
primary metabolic process	1
phosphoric diester hydrolase activity	1
sphingophospholipase activity	1
phosphoric ester hydrolase activity	1
transition metal ion binding	1
binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
actin filament bundle	1
actin-based cell projection	1
cellular anatomical structure	1

Protein interactions and networks

STRING

846 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENPP7	ASAH2	Q9NR71	695
ENPP7	SMPD2	O60906	667
ENPP7	SMPD1	P17405	664
ENPP7	SMPD4	Q9NXE4	609
ENPP7	SPTLC2	O15270	542
ENPP7	ZNF705G	A8MUZ8	541
ENPP7	SPTLC3	Q9NUV7	540
ENPP7	SPTLC1	O15269	529
ENPP7	SMPD3	Q9NY59	512
ENPP7	ASAH1	Q13510	491
ENPP7	CERS6	Q6ZMG9	480
ENPP7	ACER1	Q8TDN7	470
ENPP7	FAT4	Q6V0I7	453
ENPP7	CERS4	Q9HA82	452
ENPP7	ALB	P02768	450

IntAct

20 interactions, top by confidence:

A	B	Type	Score
GOLGA2	ENPP7	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	ENPP7	psi-mi:“MI:0915”(physical association)	0.560
LRRC73	ENPP7	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	ENPP7	psi-mi:“MI:0915”(physical association)	0.560
ENPP7	BACH2	psi-mi:“MI:0915”(physical association)	0.560
ENPP7	TUBB3	psi-mi:“MI:0914”(association)	0.530
ARHGAP26	ARHGAP10	psi-mi:“MI:0914”(association)	0.510
ENPP7	PDIA4	psi-mi:“MI:0914”(association)	0.350
ENPP7	GOLGA2	psi-mi:“MI:0915”(physical association)	0.000
ENPP7	MTUS2	psi-mi:“MI:0915”(physical association)	0.000
ENPP7	BACH2	psi-mi:“MI:0915”(physical association)	0.000
ENPP7	LRRC73	psi-mi:“MI:0915”(physical association)	0.000
ENPP7	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): TUBB1 (Affinity Capture-MS), EPDR1 (Affinity Capture-MS), CD109 (Affinity Capture-MS), ERGIC2 (Affinity Capture-MS), RHEB (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), MKS1 (Affinity Capture-MS), TTC17 (Affinity Capture-MS), PDF (Affinity Capture-MS), ENPP7 (Two-hybrid), ENPP7 (Two-hybrid), ENPP7 (Two-hybrid), LRRC73 (Two-hybrid), KRTAP5-9 (Two-hybrid), TUBB8 (Affinity Capture-MS)

ESM2 similar proteins: A7MB73, F1NPQ2, O09009, O09010, O12971, O43272, O60568, O97583, P11117, P17405, P52849, P52850, P58242, P97812, Q04519, Q0V8G3, Q13641, Q14623, Q2KJ92, Q32NY4, Q504Y2, Q5NDE9, Q5QQ49, Q5QQ50, Q5QQ51, Q5R6K5, Q5RJI4, Q5T4B2, Q5U367, Q5ZIW1, Q62226, Q63673, Q6PCX7, Q6PZ03, Q6UWV6, Q8IZ52, Q8NE01, Q8NES3, Q92485, Q924T4

Diamond homologs: A0A2D0TC04, A1A4K5, A2VDP5, J3SBP3, J3SEZ3, O14638, O94323, P06802, P0DQQ4, P15396, P22413, P84039, P97675, Q0VA77, Q13822, Q3TIW9, Q566N0, Q5EZ72, Q5R5M5, Q5RAC0, Q64610, Q6AX80, Q6DYE8, Q6UWV6, Q8BTJ4, Q924C3, Q9EQG7, Q9R1E6, Q9UJA9, Q9Y6X5, W8E7D1, P90754, A1YYW7, B0BND0, F1N5C8, P90755, Q58D68, Q5BKW7, Q5RB45, Q6DDP3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1056 predictions. Top by Δscore:

Variant	Effect	Δscore
17:79731390:CCG:C	donor_gain	1.0000
17:79731391:CG:C	donor_gain	1.0000
17:79731391:CGG:C	donor_loss	1.0000
17:79731392:GG:G	donor_gain	1.0000
17:79731393:G:GG	donor_gain	1.0000
17:79731393:GTG:G	donor_loss	1.0000
17:79735033:T:TA	acceptor_gain	1.0000
17:79735037:T:TA	acceptor_gain	1.0000
17:79735038:G:A	acceptor_gain	1.0000
17:79735041:AG:A	acceptor_gain	1.0000
17:79735042:GG:G	acceptor_gain	1.0000
17:79735068:ACCC:A	acceptor_gain	1.0000
17:79735666:TGGG:T	donor_gain	1.0000
17:79735667:GGG:G	donor_gain	1.0000
17:79735667:GGGG:G	donor_gain	1.0000
17:79735668:GG:G	donor_gain	1.0000
17:79735668:GGG:G	donor_gain	1.0000
17:79735668:GGGT:G	donor_loss	1.0000
17:79735669:GG:G	donor_gain	1.0000
17:79735669:GGT:G	donor_loss	1.0000
17:79735670:G:GA	donor_loss	1.0000
17:79735670:G:GG	donor_gain	1.0000
17:79735671:TGAGT:T	donor_loss	1.0000
17:79735672:GA:G	donor_loss	1.0000
17:79731388:CACCG:C	donor_gain	0.9900
17:79731394:T:A	donor_loss	0.9900
17:79733651:CAG:C	donor_loss	0.9900
17:79733652:AG:A	donor_loss	0.9900
17:79733653:GG:G	donor_loss	0.9900
17:79733654:GT:G	donor_loss	0.9900

AlphaMissense

3020 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:79731255:A:T	D39V	0.998
17:79735377:C:T	S245F	0.998
17:79731365:A:C	S76R	0.997
17:79731367:C:A	S76R	0.997
17:79731367:C:G	S76R	0.997
17:79733542:C:A	N96K	0.997
17:79733542:C:G	N96K	0.997
17:79733633:T:A	W127R	0.997
17:79733633:T:C	W127R	0.997
17:79735250:C:G	H203D	0.997
17:79735377:C:A	S245Y	0.997
17:79731256:C:A	D39E	0.996
17:79731256:C:G	D39E	0.996
17:79733611:G:C	W119C	0.996
17:79733611:G:T	W119C	0.996
17:79735239:A:T	D199V	0.996
17:79735240:C:A	D199E	0.996
17:79735240:C:G	D199E	0.996
17:79735380:A:T	D246V	0.996
17:79733508:G:T	G85V	0.995
17:79733609:T:A	W119R	0.995
17:79733609:T:C	W119R	0.995
17:79735238:G:C	D199H	0.995
17:79735252:C:A	H203Q	0.995
17:79735252:C:G	H203Q	0.995
17:79735382:C:G	H247D	0.995
17:79735383:A:C	H247P	0.995
17:79735384:C:A	H247Q	0.995
17:79735384:C:G	H247Q	0.995
17:79735386:G:A	G248D	0.995

dbSNP variants (sampled 300 via entrez): RS1000148964 (17:79739658 C>T), RS1000338634 (17:79740083 T>A), RS1000490194 (17:79735289 G>T), RS1001536163 (17:79735432 C>T), RS1002539066 (17:79736536 C>A,G,T), RS1002978282 (17:79741597 G>A), RS1003685356 (17:79737800 G>A), RS1003838788 (17:79733221 G>A,C), RS1004107906 (17:79733041 A>G), RS1004274200 (17:79734905 C>A,T), RS1004383116 (17:79739341 A>T), RS1004435406 (17:79739631 C>G), RS1004872537 (17:79735625 A>C,G), RS1005385244 (17:79740422 C>T), RS1005415129 (17:79735948 C>T)

Disease associations

OMIM: gene MIM:616997 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003805_8	Diastolic blood pressure response to hydrochlorothiazide in hypertension	5.000000e-06
GCST006585_451	Blood protein levels	0.000000e+00

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006945	diastolic blood pressure change measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6058 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	2
OTX015	decreases expression	1
dicrotophos	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	decreases methylation	1
imidazole	decreases activity	1
trans-10,cis-12-conjugated linoleic acid	increases expression	1
Acetaminophen	decreases expression	1
Adenosine Triphosphate	decreases activity	1
Amiodarone	increases expression	1
Edetic Acid	decreases activity, decreases reaction	1
Lysophosphatidylcholines	increases hydrolysis	1
Methapyrilene	decreases methylation	1
Phosphatidylcholines	increases hydrolysis	1
Sphingomyelins	increases hydrolysis	1
Valproic Acid	increases methylation	1
Vanadates	decreases activity	1
Zinc	decreases activity, decreases reaction	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases expression, decreases methylation	1
Fluorescein-5-isothiocyanate	affects binding	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1048410	Binding	Inhibition of NPP7 expressed in HEK293 cells assessed as para-nitrophenylphosphoryl choline hydrolysis	Optimization of a pipemidic acid autotaxin inhibitor. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer