ENPP6

Summary

ENPP6 (ectonucleotide pyrophosphatase/phosphodiesterase 6, HGNC:23409) is a protein-coding gene on chromosome 4q35.1, encoding Glycerophosphocholine cholinephosphodiesterase ENPP6 (Q6UWR7). Choline-specific glycerophosphodiesterase that hydrolyzes glycerophosphocholine (GPC) and lysophosphatidylcholine (LPC) and contributes to supplying choline to the cells.

Enables glycerophosphocholine cholinephosphodiesterase activity. Involved in choline metabolic process and lipid metabolic process. Located in extracellular region and plasma membrane.

Source: NCBI Gene 133121 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 90 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_153343

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23409
Approved symbol	ENPP6
Name	ectonucleotide pyrophosphatase/phosphodiesterase 6
Location	4q35.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC33971
Ensembl gene	ENSG00000164303
Ensembl biotype	protein_coding
OMIM	616983
Entrez	133121

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000296741, ENST00000505644, ENST00000510054, ENST00000512353, ENST00000952351

RefSeq mRNA: 1 — MANE Select: NM_153343 NM_153343

CCDS: CCDS3834

Canonical transcript exons

ENST00000296741 — 8 exons

Exon	Start	End
ENSE00001083233	184124161	184124272
ENSE00001083236	184117759	184117900
ENSE00001083239	184097245	184097368
ENSE00001083248	184112672	184112809
ENSE00001151533	184217579	184217873
ENSE00001218537	184088706	184091382
ENSE00003490717	184153554	184153733
ENSE00003608009	184116856	184117035

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 92.56.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.5942 / max 272.1425, expressed in 139 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55103	1.4644	137
55104	0.1298	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	92.56	gold quality
spinal cord	UBERON:0002240	91.57	gold quality
corpus callosum	UBERON:0002336	87.16	gold quality
kidney epithelium	UBERON:0004819	83.91	gold quality
inferior vagus X ganglion	UBERON:0005363	82.86	gold quality
trigeminal ganglion	UBERON:0001675	82.18	gold quality
peripheral nervous system	UBERON:0000010	82.10	gold quality
tibial nerve	UBERON:0001323	82.10	gold quality
substantia nigra	UBERON:0002038	79.47	gold quality
adult mammalian kidney	UBERON:0000082	78.52	gold quality
adrenal tissue	UBERON:0018303	77.88	gold quality
midbrain	UBERON:0001891	77.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.38	gold quality
kidney	UBERON:0002113	75.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.62	gold quality
prefrontal cortex	UBERON:0000451	74.23	gold quality
subthalamic nucleus	UBERON:0001906	73.94	gold quality
dorsal root ganglion	UBERON:0000044	73.91	gold quality
left ovary	UBERON:0002119	73.90	gold quality
pons	UBERON:0000988	72.52	gold quality
right ovary	UBERON:0002118	72.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.05	gold quality
Brodmann (1909) area 46	UBERON:0006483	69.87	gold quality
ovary	UBERON:0000992	69.32	gold quality
medulla oblongata	UBERON:0001896	69.20	gold quality
nucleus accumbens	UBERON:0001882	68.96	gold quality
frontal cortex	UBERON:0001870	68.88	gold quality
Ammon’s horn	UBERON:0001954	68.72	gold quality
hypothalamus	UBERON:0001898	67.18	gold quality
neocortex	UBERON:0001950	66.97	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.78
E-CURD-10	no	32.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting ENPP6, 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-3924	100.00	72.09	2394
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524

Literature-anchored findings (GeneRIF, showing 1)

• NPP6 has a specific role through the hydrolysis of polyunsaturated LPC, glycerophosphorylcholine, or sphingosylphosphorylcholine in kidney and brain (PMID:15788404)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	enpp6	ENSDARG00000040469
mus_musculus	Enpp6	ENSMUSG00000038173
rattus_norvegicus	Enpp6	ENSRNOG00000009660
caenorhabditis_elegans		WBGENE00007753
caenorhabditis_elegans		WBGENE00007755
caenorhabditis_elegans		WBGENE00015283

Paralogs (6): ENPP4 (ENSG00000001561), ENPP5 (ENSG00000112796), ENPP2 (ENSG00000136960), ENPP3 (ENSG00000154269), ENPP7 (ENSG00000182156), ENPP1 (ENSG00000197594)

Protein

Protein identifiers

Glycerophosphocholine cholinephosphodiesterase ENPP6 — Q6UWR7 (reviewed: Q6UWR7)

Alternative names: Choline-specific glycerophosphodiester phosphodiesterase, Ectonucleotide pyrophosphatase/phosphodiesterase family member 6

All UniProt accessions (2): Q6UWR7, D6R9P1

UniProt curated annotations — full annotation on UniProt →

Function. Choline-specific glycerophosphodiesterase that hydrolyzes glycerophosphocholine (GPC) and lysophosphatidylcholine (LPC) and contributes to supplying choline to the cells. Has a preference for LPC with short (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty acids. In vitro, hydrolyzes only choline-containing lysophospholipids, such as sphingosylphosphorylcholine (SPC), platelet-activating factor (PAF) and lysoPAF, but not other lysophospholipids.

Subunit / interactions. Homodimer; disulfide-linked. Homotetramer.

Subcellular location. Cell membrane.

Tissue specificity. Predominantly expressed in kidney and brain. In the kidney, expressed specifically in the proximal tubules and thin descending limbs of Henle (at protein level).

Activity regulation. Inhibited by EDTA and EGTA in vitro.

Cofactor. Binds 2 Zn(2+) ions per subunit.

Similarity. Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.

RefSeq proteins (1): NP_699174* (*=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 3.1.4.3 — phospholipase C (BRENDA: 61 organisms, 196 substrates, 182 inhibitors, 46 Km, 17 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
1,2-DIPALMITOYLPHOSPHATIDYLCHOLINE	0.166–0.6	3
4-NITROPHENYLPHOSPHORYLCHOLINE	14.8–39.5	3
P-NITROPHENYLPHOSPHORYLCHOLINE	14.1–200	3
1,2-DIHEXANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	2.4–2.8	2
1-PALMITOYL-LYSOPHOSPHATIDYLCHOLINE	0.025–0.165	2
4-NITROPHENYLPHOSPHORYCHOLINE	0.32–0.76	2
DIHEPTANOYLPHOSPHATIDYLCHOLINE	0.03–1.09	2
DIHEXANOYLPHOSPHATIDIC ACID	4.2–9	2
DIHEXANOYLPHOSPHATIDYLCHOLINE	0.19–1.12	2
PHOSPHATIDYLCHOLINE	0.38–0.9	2
PHOSPHATIDYLINOSITOL	0.087–0.369	2
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE	0.137–0.571	2
SPHINGOMYELIN	0.09–0.8	2
1,2-DIBUTYRYL-SN-GLYCERO-3-PHOSPHOCHOLINE	43.5	1
1,2-DIHEPTANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	8.5	1

Catalyzed reactions (Rhea), 11 shown:

• sn-glycerol 3-phosphocholine + H2O = phosphocholine + glycerol + H(+) (RHEA:19545)
• a 1-O-alkyl-sn-glycero-3-phosphocholine + H2O = a 1-O-alkyl-sn-glycerol + phosphocholine + H(+) (RHEA:36083)
• 1-tetradecanoyl-sn-glycero-3-phosphocholine + H2O = 1-tetradecanoyl-sn-glycerol + phosphocholine + H(+) (RHEA:40999)
• 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + phosphocholine + H(+) (RHEA:41003)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-(9Z-octadecenoyl)-sn-glycerol + phosphocholine + H(+) (RHEA:41091)
• sphing-4-enine-phosphocholine + H2O = sphing-4-enine + phosphocholine + H(+) (RHEA:41095)
• 1-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphocholine + H2O = 1-(9Z,12Z-octadecadienoyl)-sn-glycerol + phosphocholine + H(+) (RHEA:41115)
• 1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycerol + phosphocholine + H(+) (RHEA:41119)
• 1-dodecanoyl-sn-glycero-3-phosphocholine + H2O = 1-dodecanoyl-sn-glycerol + phosphocholine + H(+) (RHEA:41127)
• a 1-acyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycerol + phosphocholine + H(+) (RHEA:44720)
• glycero-2-phosphocholine + H2O = phosphocholine + glycerol + H(+) (RHEA:61684)

UniProt features (27 total): binding site 13, glycosylation site 4, disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, modified residue 1, lipid moiety-binding region 1, propeptide 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWR7-F1	93.06	0.90

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): 71 (nucleophile)

Ligand- & substrate-binding residues (13): 193; 197; 240; 241; 241; 354; 354; 32; 32; 71; 71; 92 …

Post-translational modifications (2): 71, 419

Disulfide bonds (2): 142–154, 412

Glycosylation sites (4): 100, 118, 341, 404

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6814848	Glycerophospholipid catabolism

MSigDB gene sets: 88 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, USF_C, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, IRF1_Q6, chr4q35, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_CATABOLIC_PROCESS, SABATES_COLORECTAL_ADENOMA_DN, GOBP_GLYCEROLIPID_CATABOLIC_PROCESS, GOBP_LIPID_CATABOLIC_PROCESS

GO Biological Process (4): lipid metabolic process (GO:0006629), choline metabolic process (GO:0019695), glycerophospholipid catabolic process (GO:0046475), lipid catabolic process (GO:0016042)

GO Molecular Function (6): phosphoric diester hydrolase activity (GO:0008081), glycerophosphodiester phosphodiesterase activity (GO:0008889), metal ion binding (GO:0046872), glycerophosphocholine cholinephosphodiesterase activity (GO:0047390), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
PI Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
phosphoric diester hydrolase activity	2
membrane	2
primary metabolic process	1
metabolic process	1
glycerophospholipid metabolic process	1
phospholipid catabolic process	1
glycerolipid catabolic process	1
lipid metabolic process	1
catabolic process	1
phosphoric ester hydrolase activity	1
cation binding	1
binding	1
catalytic activity	1
cell periphery	1
extracellular vesicle	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENPP6	BCAS1	O75363	564
ENPP6	MYRF	Q9Y2G1	546
ENPP6	OPALIN	Q96PE5	520
ENPP6	OLIG2	Q13516	456
ENPP6	FBXL15	Q9H469	455
ENPP6	PDGFRA	P16234	444
ENPP6	AHCTF1	Q8WYP5	441
ENPP6	SOX10	P56693	414
ENPP6	CSPG4	Q6UVK1	408
ENPP6	PLP1	P04400	405
ENPP6	GPR17	Q13304	405
ENPP6	GDPD1	Q8N9F7	403
ENPP6	CNP	P09543	396
ENPP6	FBXW2	Q9UKT8	395
ENPP6	OLIG1	Q8TAK6	385

IntAct

9 interactions, top by confidence:

A	B	Type	Score
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
ASPH	ENPP6	psi-mi:“MI:0915”(physical association)	0.560
ENPP6	CRLF3	psi-mi:“MI:0914”(association)	0.530
TRIM10	WIZ	psi-mi:“MI:0914”(association)	0.530
ASPH	ENPP6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (99): CTPS2 (Affinity Capture-MS), OCRL (Affinity Capture-MS), MEX3B (Affinity Capture-MS), DIAPH3 (Affinity Capture-MS), SACS (Affinity Capture-MS), NDUFA7 (Affinity Capture-MS), SCAMP1 (Affinity Capture-MS), PIGS (Affinity Capture-MS), EMC3 (Affinity Capture-MS), NDUFB9 (Affinity Capture-MS), STX7 (Affinity Capture-MS), NUP85 (Affinity Capture-MS), ZBTB33 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), PTPN1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2D0TC04, A2VDP5, B0BND0, F1N5C8, J3SBP3, J3SEZ3, O14638, O62806, O94323, P06802, P0DQQ4, P23188, P23377, P29119, P54793, P70699, P84039, P97675, Q0VA77, Q29444, Q32KH8, Q4FZV0, Q566N0, Q58D68, Q5BKW7, Q5FYA8, Q5R5M5, Q5RAC0, Q5RB45, Q6AX80, Q6DDP3, Q6DYE8, Q6P179, Q6P7A9, Q6UVY6, Q6UWR7, Q8BGN3, Q8BTJ4, Q8C129, Q8IVL8

Diamond homologs: A0A2D0TC04, A1A4K5, A1YYW7, A2VDP5, B0BND0, F1N5C8, J3SBP3, J3SEZ3, O14638, O94323, P06802, P0DQQ4, P15396, P22413, P84039, P90755, P97675, Q0VA77, Q13822, Q3TIW9, Q566N0, Q58D68, Q5BKW7, Q5EZ72, Q5R5M5, Q5RAC0, Q5RB45, Q64610, Q6AX80, Q6DDP3, Q6DYE8, Q6UWR7, Q6UWV6, Q8BGN3, Q8BTJ4, Q924C3, Q9EQG7, Q9R1E6, Q9UJA9, Q9Y6X5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	83
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
809725	GRCh37/hg19 4q35.1-35.2(chr4:183245174-190948359)x1	Likely pathogenic

SpliceAI

1774 predictions. Top by Δscore:

Variant	Effect	Δscore
4:184094863:T:A	donor_gain	1.0000
4:184094878:T:TA	donor_gain	1.0000
4:184094879:C:A	donor_gain	1.0000
4:184097199:T:TA	donor_gain	1.0000
4:184112667:ATTAC:A	donor_loss	1.0000
4:184112668:TTAC:T	donor_loss	1.0000
4:184112669:TA:T	donor_loss	1.0000
4:184112671:C:CA	donor_loss	1.0000
4:184112726:T:A	donor_gain	1.0000
4:184112805:TATAT:T	acceptor_gain	1.0000
4:184112806:ATAT:A	acceptor_gain	1.0000
4:184112806:ATATC:A	acceptor_loss	1.0000
4:184112807:TAT:T	acceptor_gain	1.0000
4:184112807:TATC:T	acceptor_loss	1.0000
4:184112808:ATCTG:A	acceptor_loss	1.0000
4:184112809:TCTGC:T	acceptor_loss	1.0000
4:184112810:C:CC	acceptor_gain	1.0000
4:184112810:CT:C	acceptor_loss	1.0000
4:184112811:T:G	acceptor_loss	1.0000
4:184116905:T:TA	donor_gain	1.0000
4:184116915:G:A	donor_gain	1.0000
4:184116943:A:AC	donor_gain	1.0000
4:184116943:ATT:A	donor_gain	1.0000
4:184117031:CGCTC:C	acceptor_gain	1.0000
4:184117033:CTC:C	acceptor_gain	1.0000
4:184117034:TC:T	acceptor_gain	1.0000
4:184117035:CCTG:C	acceptor_gain	1.0000
4:184117036:C:A	acceptor_loss	1.0000
4:184117036:C:CC	acceptor_gain	1.0000
4:184117782:T:TA	donor_gain	1.0000

AlphaMissense

2906 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:184116992:T:A	D240V	0.999
4:184217725:T:A	D32V	0.999
4:184116992:T:G	D240A	0.998
4:184117855:G:C	D193E	0.998
4:184117855:G:T	D193E	0.998
4:184117856:T:A	D193V	0.998
4:184153560:A:G	W139R	0.998
4:184153560:A:T	W139R	0.998
4:184153605:A:G	W124R	0.998
4:184153605:A:T	W124R	0.998
4:184153624:C:A	W117C	0.998
4:184153624:C:G	W117C	0.998
4:184153666:A:C	F103L	0.998
4:184153666:A:T	F103L	0.998
4:184153668:A:G	F103L	0.998
4:184153699:G:C	N92K	0.998
4:184153699:G:T	N92K	0.998
4:184217613:A:C	S69R	0.998
4:184217613:A:T	S69R	0.998
4:184217615:T:G	S69R	0.998
4:184217724:A:C	D32E	0.998
4:184217724:A:T	D32E	0.998
4:184116986:C:A	G242V	0.997
4:184116986:C:T	G242E	0.997
4:184116992:T:C	D240G	0.997
4:184116993:C:G	D240H	0.997
4:184116995:G:C	S239W	0.997
4:184117848:C:G	G196R	0.997
4:184117856:T:G	D193A	0.997
4:184153558:C:A	W139C	0.997

dbSNP variants (sampled 300 via entrez): RS1000049854 (4:184176414 GAAGTT>G), RS1000050911 (4:184137911 G>A,T), RS1000080292 (4:184100582 C>A,T), RS1000080694 (4:184176116 A>G), RS1000095011 (4:184094928 G>A), RS1000106929 (4:184219249 A>C,T), RS1000126306 (4:184115577 C>T), RS1000142508 (4:184208718 C>A,G,T), RS1000174413 (4:184154152 C>A,T), RS1000198376 (4:184208604 C>G,T), RS1000210321 (4:184170423 C>G), RS1000212574 (4:184201452 C>T), RS1000242606 (4:184115801 C>T), RS1000263676 (4:184132426 C>T), RS1000279240 (4:184154663 A>G)

Disease associations

OMIM: gene MIM:616983 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003123_14	Severe influenza A (H1N1) infection	4.000000e-10
GCST003542_88	Night sleep phenotypes	8.000000e-06
GCST003806_5	Response to bupropion and depression	6.000000e-07
GCST005566_7	Insomnia	2.000000e-07
GCST006445_5	Femoral neck bone mineral density	3.000000e-06
GCST012291_2	Schizophrenia, bipolar disorder or recurrent major depressive disorder	7.000000e-06
GCST012292_8	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	6.000000e-06
GCST012302_4	Recurrent major depressive disorder	5.000000e-06
GCST90014243_12	Kawasaki disease	2.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0007785	femoral neck bone mineral density
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6033 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, affects methylation	1
methyleugenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects methylation, affects cotreatment, decreases methylation	1
entinostat	increases expression	1
abrine	increases expression	1
bisphenol S	increases methylation	1
Resveratrol	affects cotreatment, increases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects methylation, affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Copper	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Valproic Acid	affects expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1048409	Binding	Inhibition of NPP6 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
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms