NPAS3

Summary

NPAS3 (neuronal PAS domain protein 3, HGNC:19311) is a protein-coding gene on chromosome 14q13.1, encoding Neuronal PAS domain-containing protein 3 (Q8IXF0). May play a broad role in neurogenesis.

This gene encodes a member of the basic helix-loop-helix and PAS domain-containing family of transcription factors. The encoded protein is localized to the nucleus and may regulate genes involved in neurogenesis. Chromosomal abnormalities that affect the coding potential of this gene are associated with schizophrenia and cognitive disability. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 64067 — RefSeq curated summary.

At a glance

• GWAS associations: 37
• Clinical variants (ClinVar): 151 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001164749

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19311
Approved symbol	NPAS3
Name	neuronal PAS domain protein 3
Location	14q13.1
Locus type	gene with protein product
Status	Approved
Aliases	MOP6, PASD6, bHLHe12
Ensembl gene	ENSG00000151322
Ensembl biotype	protein_coding
OMIM	609430
Entrez	64067

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000346562, ENST00000356141, ENST00000357798, ENST00000546849, ENST00000547068, ENST00000548645, ENST00000549770, ENST00000550662, ENST00000551008, ENST00000551492, ENST00000551634, ENST00000552696, ENST00000552874, ENST00000680362, ENST00000681323, ENST00000681796

RefSeq mRNA: 6 — MANE Select: NM_001164749 NM_001164749, NM_001165893, NM_001394988, NM_001394989, NM_022123, NM_173159

CCDS: CCDS53891, CCDS53892, CCDS55912, CCDS9645

Canonical transcript exons

ENST00000356141 — 12 exons

Exon	Start	End
ENSE00000998919	33778466	33778572
ENSE00000998920	33676211	33676385
ENSE00000998924	33774337	33774530
ENSE00000998927	33735214	33735332
ENSE00001125141	33560121	33560210
ENSE00001283807	33797457	33797581
ENSE00001303918	33793897	33794044
ENSE00001433353	33055905	33055994
ENSE00003556720	33215182	33215426
ENSE00003651366	33367186	33367268
ENSE00003978116	33799734	33804173
ENSE00003978117	32938879	32939366

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 95.68.

FANTOM5 (CAGE): breadth broad, TPM avg 5.9737 / max 217.0966, expressed in 700 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139158	2.0742	240
139161	1.5662	510
139155	0.7952	133
139163	0.3347	132
139154	0.2749	106
139157	0.2437	110
139156	0.2313	106
139159	0.1903	97
139160	0.1215	56
139162	0.1135	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	95.68	gold quality
ventricular zone	UBERON:0003053	95.14	gold quality
corpus callosum	UBERON:0002336	94.92	gold quality
buccal mucosa cell	CL:0002336	94.52	gold quality
globus pallidus	UBERON:0001875	91.05	gold quality
medial globus pallidus	UBERON:0002477	90.92	gold quality
lateral globus pallidus	UBERON:0002476	90.82	gold quality
cranial nerve II	UBERON:0000941	89.51	gold quality
inferior vagus X ganglion	UBERON:0005363	88.89	gold quality
entorhinal cortex	UBERON:0002728	88.79	gold quality
ventral tegmental area	UBERON:0002691	88.71	gold quality
superior vestibular nucleus	UBERON:0007227	88.15	gold quality
subthalamic nucleus	UBERON:0001906	87.86	gold quality
diaphragm	UBERON:0001103	87.30	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.18	gold quality
medulla oblongata	UBERON:0001896	87.11	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.03	gold quality
temporal lobe	UBERON:0001871	86.73	gold quality
ganglionic eminence	UBERON:0004023	86.28	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	86.19	gold quality
amygdala	UBERON:0001876	85.62	gold quality
inferior olivary complex	UBERON:0002127	84.97	gold quality
middle temporal gyrus	UBERON:0002771	84.71	gold quality
dorsal plus ventral thalamus	UBERON:0001897	84.58	gold quality
primary visual cortex	UBERON:0002436	84.26	gold quality
postcentral gyrus	UBERON:0002581	84.24	gold quality
occipital lobe	UBERON:0002021	84.05	gold quality
substantia nigra pars compacta	UBERON:0001965	84.04	gold quality
Brodmann (1909) area 46	UBERON:0006483	83.88	gold quality
parietal lobe	UBERON:0001872	83.74	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	5937.73
E-HCAD-30	yes	5462.12
E-GEOD-131882	yes	3938.06
E-MTAB-10287	yes	48.64
E-CURD-119	yes	35.55
E-HCAD-25	yes	26.03
E-ANND-3	yes	6.02

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
VGF	Unknown

JASPAR motifs

Motif	Name	Family
MA2683.1	NPAS3	PAS

JASPAR matrix evidence (PMIDs): PMID:36044858

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

289 targeting NPAS3, 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-5011-5P	100.00	83.46	5820
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960

Literature-anchored findings (GeneRIF, showing 17)

• haploinsufficiency of NPAS3 contributes to the cause of schizophrenia (PMID:12746393)
• This study demonstrated that these risk and protective effects act combinatorially, potentially multiplicatively, to determine NPAS3 gene-wide susceptibility in bipolar disorder and schizophrenia. (PMID:18317462)
• This study identification of potentially defective NPAS3 variants supports recent studies that implicate perturbations in NPAS3 pathways in impaired neurogenesis and psychosis. (PMID:20466522)
• report of immunohistochemical findings on NPAS3 protein expression in the developing human fetal brain during the three trimesters (10-41 weeks) of gestational development (PMID:21306425)
• Loss of NPAS3 is associated with the progression of Astrocytomas. (PMID:21703424)
• In a HEK293 cell line over-expressing NPAS3, transcriptional targets varied with to circadian rhythm context & C-terminal deletion. NPAS3 contributes to neurodevelopmental transcription factor networks & the regulation of brain glucose metabolism. (PMID:21709683)
• During human postnatal cortical development, there was decreased NPAS3 mRNA yet increased NPAS3 protein expression, suggesting the involvement of posttranscriptional regulation, which results show is modified by miR-17. (PMID:22228753)
• Identification of NPAS3-V304I helps strengthen the hypothesis that NPAS3 is involved in schizophrenia pathogenesis (PMID:23337948)
• Results indicate that the high density of HAEs present in the human NPAS3 locus could have modified the spatiotemporal expression pattern of NPAS3 in the developing human brain and, therefore, contributed to human brain evolution. (PMID:23408798)
• The accelerated non-coding region 2xHAR142 of NPAS3 behaves as a developmental enhancer in the forebrain of transgenic mice. (PMID:24218632)
• Authors hypothesize that any nucleotide variant at the NPAS3 HAEs may lead to altered susceptibility to schizophrenia. (PMID:25982957)
• Here the authors examined the crystal structures of multi-domain NPAS1-ARNT and NPAS3-ARNT-DNA complexes, discovering each to contain four putative ligand-binding pockets. (PMID:27782878)
• Study provides a clear, unbiased view of the full spectrum of genes regulated by NPAS1 and NPAS3 and shows that these transcription factors are master regulators of neuropsychiatric function. These findings expose the molecular pathophysiology of NPAS1/3 mutations and provide a striking example of the shared, combinatorial nature of molecular pathways that underlie diagnostically distinct neuropsychiatric conditions. (PMID:28499489)
• NPAS3 is a true transcription factor capable of regulating expression of target genes through their promoters by directly cooperating with ARNT. (PMID:30509165)
• Molecular characterisation of rare loss-of-function NPAS3 and NPAS4 variants identified in individuals with neurodevelopmental disorders. (PMID:33758288)
• Npas3 deficiency impairs cortical astrogenesis and induces autistic-like behaviors. (PMID:36044858)
• SYMPTOM SEVERITY IN SCHIZOPHRENIA PATIENTS WITH NPAS3, DYSBINDIN-1 AND/OR TRIOBP PROTEIN PATHOLOGY IN THEIR BLOOD SERUM: A PANSS-BASED FOLLOW UP STUDY. (PMID:37480305)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	NPAS3	ENSDARG00000109820
mus_musculus	Npas3	ENSMUSG00000021010
rattus_norvegicus	Npas3	ENSRNOG00000068162
drosophila_melanogaster	trh	FBGN0262139
drosophila_melanogaster	sima	FBGN0266411
caenorhabditis_elegans		WBGENE00001851

Paralogs (7): HIF1A (ENSG00000100644), SIM1 (ENSG00000112246), EPAS1 (ENSG00000116016), HIF3A (ENSG00000124440), NPAS1 (ENSG00000130751), SIM2 (ENSG00000159263), NPAS4 (ENSG00000174576)

Protein

Protein identifiers

Neuronal PAS domain-containing protein 3 — Q8IXF0 (reviewed: Q8IXF0)

Alternative names: Basic-helix-loop-helix-PAS protein MOP6, Class E basic helix-loop-helix protein 12, Member of PAS protein 6, PAS domain-containing protein 6

All UniProt accessions (11): A0A7P0T8Q6, A0A7P0TA87, Q8IXF0, F8VR32, F8VS42, F8W0C2, H0YHB6, H0YHU7, H0YI42, X5D2Q4, X5D988

UniProt curated annotations — full annotation on UniProt →

Function. May play a broad role in neurogenesis. May control regulatory pathways relevant to schizophrenia and to psychotic illness.

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein. Interacts with ARNT; forms a heterodimer that binds core DNA sequence 5’-[AG]CGTG-3’ within the hypoxia response element (HRE) of target gene promoters.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed in the adult brain.

Disease relevance. A chromosomal aberration involving NPAS3 is found in a family with schizophrenia. Translocation t(9;14)(q34;q13).

Isoforms (6)

UniProt ID	Names	Canonical?
Q8IXF0-1	1, long form	yes
Q8IXF0-2	2
Q8IXF0-3	3, NPAS3v
Q8IXF0-4	4
Q8IXF0-5	5
Q8IXF0-6	6

RefSeq proteins (6): NP_001158221, NP_001159365, NP_001381917, NP_001381918, NP_071406, NP_775182 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000014	PAS	Domain
IPR011598	bHLH_dom	Domain
IPR013655	PAS_fold_3	Domain
IPR013767	PAS_fold	Domain
IPR035965	PAS-like_dom_sf	Homologous_superfamily
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00989, PF08447, PF23171

UniProt features (31 total): compositionally biased region 10, region of interest 7, splice variant 6, domain 4, sequence conflict 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXF0-F1	56.50	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 207 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, YAATNRNNNYNATT_UNKNOWN, LFA1_Q6, GOZGIT_ESR1_TARGETS_DN, EFC_Q6, BLALOCK_ALZHEIMERS_DISEASE_UP, CCTGTGA_MIR513, HFH4_01, HP1SITEFACTOR_Q6, TGACATY_UNKNOWN, AACTTT_UNKNOWN, MAF_Q6, FOXO4_02, chr14q13, ZHAN_MULTIPLE_MYELOMA_CD1_VS_CD2_UP

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of DNA-templated transcription (GO:0045893), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), protein heterodimerization activity (GO:0046982), DNA binding (GO:0003677), protein binding (GO:0005515), protein dimerization activity (GO:0046983)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
DNA-templated transcription	2
cellular anatomical structure	2
transcription by RNA polymerase II	1
positive regulation of RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription cis-regulatory region binding	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
protein dimerization activity	1
nucleic acid binding	1
binding	1
protein binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

1008 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPAS3	PRORP	O15091	766
NPAS3	HARS1	P12081	565
NPAS3	AKAP6	Q13023	560
NPAS3	AUTS2	Q8WXX7	543
NPAS3	RBFOX1	Q9NWB1	495
NPAS3	FOXP2	O15409	493
NPAS3	FBXW9	Q5XUX1	488
NPAS3	NPAS4	Q8IUM7	483
NPAS3	DISC1	Q9NRI5	481
NPAS3	SRGAP2	O75044	462
NPAS3	EGLN3	Q9H6Z9	450
NPAS3	SEMA5A	Q13591	450
NPAS3	TENM3	Q9P273	444
NPAS3	CLVS1	Q8IUQ0	437
NPAS3	NTN5	Q8WTR8	433

IntAct

8 interactions, top by confidence:

A	B	Type	Score
NPAS3	ARNT2	psi-mi:“MI:0915”(physical association)	0.550
NPAS3	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
NPAS3	ARNT2	psi-mi:“MI:0915”(physical association)	0.370
TP53	MDM2	psi-mi:“MI:0914”(association)	0.350
NPAS3	ARNT	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): NPAS3 (Affinity Capture-MS), NPAS3 (Two-hybrid), NPAS3 (Affinity Capture-RNA), ARNT (Affinity Capture-MS), ABCC12 (Affinity Capture-MS), ARNT2 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), NPAS3 (Two-hybrid), NPAS3 (Affinity Capture-MS), NPAS3 (Affinity Capture-RNA), ARNT2 (Two-hybrid)

ESM2 similar proteins: A0A0B4KGY6, A8MPH9, B4JYN3, B4K617, B4KXJ5, B4M5T7, B4MLR8, G5EFF1, G5EFL9, M9PH32, O01367, P12349, P17970, P21525, P34021, P34611, P49880, P51023, Q01295, Q01617, Q03297, Q24167, Q24767, Q29AP1, Q2LZ59, Q56R14, Q5U4T7, Q6E2N3, Q6YGZ4, Q7KVW5, Q7YU81, Q8IPW2, Q8IQG1, Q8IXF0, Q8MQJ9, Q8QGQ6, Q8T498, Q960C5, Q99MQ1, Q9BJZ5

Diamond homologs: A1YFY6, A2T6X9, A9YTQ3, O09000, O35800, P05709, P81133, P97459, P97481, Q0PGG7, Q0VBL6, Q14190, Q16665, Q24119, Q24167, Q309Z6, Q61045, Q61079, Q61221, Q8IXF0, Q98SJ5, Q98SW2, Q99742, Q99814, Q9I8A9, Q9JHS1, Q9JHS2, Q9QZQ0, Q9XTA5, Q9Y2N7, Q9YIB9, B5DE09, O02747, O15945, O57539, P30561, P35869, P41738, P70365, Q15596

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	122
Likely benign	11
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
545162	NC_000014.9:g.(?33318664)(33378429_?)del	Likely pathogenic

SpliceAI

6514 predictions. Top by Δscore:

Variant	Effect	Δscore
14:33215180:A:AG	acceptor_gain	1.0000
14:33215181:G:GA	acceptor_gain	1.0000
14:33215181:GT:G	acceptor_gain	1.0000
14:33215181:GTT:G	acceptor_gain	1.0000
14:33215181:GTTTA:G	acceptor_gain	1.0000
14:33215425:AGGT:A	donor_loss	1.0000
14:33215426:GGT:G	donor_loss	1.0000
14:33215427:G:GA	donor_loss	1.0000
14:33215520:T:G	acceptor_gain	1.0000
14:33241470:G:GT	donor_gain	1.0000
14:33367184:A:G	acceptor_gain	1.0000
14:33367185:G:GA	acceptor_gain	1.0000
14:33367264:TGCAG:T	donor_loss	1.0000
14:33367266:CAGGT:C	donor_loss	1.0000
14:33367267:AGGT:A	donor_loss	1.0000
14:33367268:GG:G	donor_loss	1.0000
14:33367269:G:GA	donor_loss	1.0000
14:33367270:T:A	donor_loss	1.0000
14:33560119:A:AG	acceptor_gain	1.0000
14:33560120:G:GG	acceptor_gain	1.0000
14:33560211:G:GG	donor_gain	1.0000
14:32939708:G:GT	donor_gain	0.9900
14:32957187:C:G	donor_gain	0.9900
14:32990230:A:T	donor_gain	0.9900
14:33055992:G:GT	donor_gain	0.9900
14:33055992:GAA:G	donor_gain	0.9900
14:33055995:G:GG	donor_gain	0.9900
14:33129124:TGGAA:T	donor_gain	0.9900
14:33197802:T:G	acceptor_gain	0.9900
14:33197813:T:A	acceptor_gain	0.9900

AlphaMissense

6117 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:33215196:G:C	R52T	1.000
14:33215197:A:C	R52S	1.000
14:33215197:A:T	R52S	1.000
14:33215200:G:C	K53N	1.000
14:33215200:G:T	K53N	1.000
14:33215206:A:C	K55N	1.000
14:33215206:A:T	K55N	1.000
14:33215207:T:C	S56P	1.000
14:33215208:C:T	S56F	1.000
14:33215211:G:C	R57P	1.000
14:33215216:G:C	A59P	1.000
14:33215217:C:A	A59D	1.000
14:33215219:G:C	A60P	1.000
14:33215220:C:A	A60D	1.000
14:33215220:C:T	A60V	1.000
14:33215222:C:A	R61S	1.000
14:33215222:C:T	R61C	1.000
14:33215223:G:C	R61P	1.000
14:33215225:T:C	S62P	1.000
14:33215228:C:A	R63S	1.000
14:33215228:C:G	R63G	1.000
14:33215228:C:T	R63C	1.000
14:33215229:G:A	R63H	1.000
14:33215229:G:C	R63P	1.000
14:33215232:G:C	R64P	1.000
14:33215234:G:A	G65R	1.000
14:33215234:G:C	G65R	1.000
14:33215237:A:G	K66E	1.000
14:33215238:A:T	K66I	1.000
14:33215239:A:C	K66N	1.000

dbSNP variants (sampled 300 via entrez): RS1000001865 (14:33527935 G>A,T), RS1000002420 (14:33021043 C>A,T), RS1000003520 (14:33309837 G>A), RS1000004943 (14:33736236 A>C,G), RS1000005566 (14:33696815 A>C,G), RS1000007463 (14:33239163 G>A), RS1000007928 (14:33001870 G>A), RS1000011889 (14:32953297 C>T), RS1000015296 (14:33347699 G>A,C,T), RS1000017296 (14:33067799 A>G), RS1000023548 (14:33117410 A>G), RS1000030944 (14:33625532 A>T), RS1000031270 (14:33402858 G>C), RS1000031800 (14:33503507 G>A,T), RS1000034199 (14:33602862 G>A)

Disease associations

OMIM: gene MIM:609430 | disease phenotypes: MIM:181500

GenCC curated gene-disease

Mondo (1): schizophrenia (MONDO:0005090)

Orphanet (1): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

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

HPO	Term
HP:0100753	Schizophrenia

GWAS associations

37 associations (top):

Study	Trait	p-value
GCST000774_2	Schizophrenia, bipolar disorder and depression (combined)	4.000000e-06
GCST001371_5	Inflammatory biomarkers	2.000000e-06
GCST002284_33	QRS duration in Tripanosoma cruzi seropositivity	8.000000e-07
GCST002360_3	Plasma amyloid beta peptide concentrations (ABx-40)	2.000000e-06
GCST002616_8	Mitochondrial DNA levels	4.000000e-06
GCST002875_136	Diisocyanate-induced asthma	2.000000e-06
GCST003208_2	Colorectal or endometrial cancer	6.000000e-06
GCST003542_58	Night sleep phenotypes	7.000000e-06
GCST003659_12	Modified Stumvoll Insulin Sensitivity Index (BMI interaction)	2.000000e-07
GCST004557_237	Body mass index	3.000000e-08
GCST004557_25	Body mass index	2.000000e-08
GCST004557_66	Body mass index	4.000000e-06
GCST004558_157	Body mass index (joint analysis main effects and physical activity interaction)	7.000000e-08
GCST004558_22	Body mass index (joint analysis main effects and physical activity interaction)	3.000000e-08
GCST004559_101	Body mass index in physically active individuals	6.000000e-08
GCST004559_18	Body mass index in physically active individuals	3.000000e-08
GCST004750_5	Squamous cell lung carcinoma	4.000000e-07
GCST004860_152	Alcoholic chronic pancreatitis	9.000000e-06
GCST004904_117	Body mass index	4.000000e-09
GCST004946_18	Schizophrenia	2.000000e-08
GCST005580_191	Intraocular pressure	3.000000e-08
GCST005580_192	Intraocular pressure	4.000000e-08
GCST005951_6	Body mass index	9.000000e-09
GCST006088_24	Familial squamous cell lung carcinoma	4.000000e-06
GCST006291_72	Spherical equivalent or myopia (age of diagnosis)	4.000000e-10
GCST008103_83	Bipolar disorder	1.000000e-06
GCST008153_20	Lean body mass	5.000000e-06
GCST008163_96	Height	6.000000e-06
GCST008179_22	Moderate-to-late spontaneous preterm birth	6.000000e-06
GCST008403_11	Arterial stiffness index	8.000000e-06

EFO canonical traits (18, from GWAS)

EFO ID	Trait name
EFO:0005659	plasma beta-amyloid 1-40 measurement
EFO:0006312	mitochondrial DNA measurement
EFO:0006995	response to diisocyanate
EFO:0004230	endometrial neoplasm
EFO:0004340	body mass index
EFO:0004471	insulin sensitivity measurement
EFO:0008002	physical activity measurement
EFO:0004695	intraocular pressure measurement
EFO:0006953	family history of lung cancer
EFO:0004847	age at onset
EFO:0004995	lean body mass
EFO:0006917	spontaneous preterm birth
EFO:0004517	arterial stiffness measurement
EFO:0006781	coffee consumption measurement
EFO:0010453	adenosine measurement
EFO:0004872	inflammatory biomarker measurement
EFO:0006527	smoking status measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1315115	NPAS3		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	7
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Resveratrol	affects cotreatment, decreases expression	2
Estradiol	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
FR900359	increases phosphorylation	1
methylmercuric chloride	increases expression	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
rofecoxib	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
Fulvestrant	increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Coal	increases abundance, increases expression	1
Coumestrol	decreases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Formaldehyde	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Nicotine	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silver	decreases expression	1
Smoke	increases abundance, increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety