NPAS4

Summary

NPAS4 (neuronal PAS domain protein 4, HGNC:18983) is a protein-coding gene on chromosome 11q13.2, encoding Neuronal PAS domain-containing protein 4 (Q8IUM7). Transcription factor expressed in neurons of the brain that regulates the excitatory-inhibitory balance within neural circuits and is required for contextual memory in the hippocampus.

NXF is a member of the basic helix-loop-helix-PER (MIM 602260)-ARNT (MIM 126110)-SIM (see SIM2; MIM 600892) (bHLH-PAS) class of transcriptional regulators, which are involved in a wide range of physiologic and developmental events (Ooe et al., 2004 [PubMed 14701734]).

Source: NCBI Gene 266743 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 92 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_178864

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18983
Approved symbol	NPAS4
Name	neuronal PAS domain protein 4
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	PASD10, NXF, Le-PAS, bHLHe79
Ensembl gene	ENSG00000174576
Ensembl biotype	protein_coding
OMIM	608554
Entrez	266743

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000311034, ENST00000524617, ENST00000525148

RefSeq mRNA: 2 — MANE Select: NM_178864 NM_001318804, NM_178864

CCDS: CCDS8138

Canonical transcript exons

ENST00000311034 — 8 exons

Exon	Start	End
ENSE00001189009	66422674	66422941
ENSE00001189016	66422451	66422553
ENSE00001189021	66422120	66422271
ENSE00001263041	66423123	66423232
ENSE00001263062	66425961	66426707
ENSE00003475374	66423578	66423713
ENSE00003564388	66423835	66425270
ENSE00003850470	66421035	66421354

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 79.54.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9447 / max 211.3166, expressed in 125 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115341	0.9447	125

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	79.54	gold quality
adenohypophysis	UBERON:0002196	76.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.90	gold quality
left uterine tube	UBERON:0001303	73.47	gold quality
body of uterus	UBERON:0009853	72.17	gold quality
muscle layer of sigmoid colon	UBERON:0035805	71.12	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	70.54	gold quality
mucosa of stomach	UBERON:0001199	70.49	gold quality
lower esophagus muscularis layer	UBERON:0035833	69.88	gold quality
lower esophagus	UBERON:0013473	69.83	gold quality
smooth muscle tissue	UBERON:0001135	69.58	gold quality
popliteal artery	UBERON:0002250	62.67	gold quality
tibial artery	UBERON:0007610	62.66	gold quality
aorta	UBERON:0000947	62.37	gold quality
thoracic aorta	UBERON:0001515	62.28	gold quality
ascending aorta	UBERON:0001496	62.02	gold quality
myometrium	UBERON:0001296	61.14	gold quality
prefrontal cortex	UBERON:0000451	61.01	gold quality
right coronary artery	UBERON:0001625	60.89	gold quality
hypothalamus	UBERON:0001898	60.57	gold quality
right hemisphere of cerebellum	UBERON:0014890	60.49	gold quality
cerebellar cortex	UBERON:0002129	60.35	gold quality
cerebellar hemisphere	UBERON:0002245	60.18	gold quality
cerebellum	UBERON:0002037	58.92	gold quality
putamen	UBERON:0001874	58.65	gold quality
nucleus accumbens	UBERON:0001882	58.54	gold quality
anterior cingulate cortex	UBERON:0009835	58.43	gold quality
left coronary artery	UBERON:0001626	58.35	gold quality
right frontal lobe	UBERON:0002810	58.20	gold quality
islet of Langerhans	UBERON:0000006	57.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.63

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
CDK5
INS
MCU	Repression
NPAS4
RBFOX3
TRIB3

Upstream regulators (CollecTRI, top): ESR1, NPAS4, REST

miRNA regulators (miRDB)

40 targeting NPAS4, 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-340-5P	100.00	72.50	4437
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-5590-5P	98.81	68.78	969
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-378A-3P	98.43	66.10	548
HSA-MIR-378B	98.43	65.36	573
HSA-MIR-378C	98.43	66.10	548
HSA-MIR-378D	98.43	66.10	548
HSA-MIR-378E	98.43	65.99	551
HSA-MIR-378F	98.43	65.66	554
HSA-MIR-378H	98.43	66.16	545
HSA-MIR-378I	98.43	66.10	548
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359

Literature-anchored findings (GeneRIF, showing 9)

• a novel NXF signaling system on neural gene promoter may be a molecular target of the adverse effects of Sim2 in the mental retardation of Down’s syndrome (PMID:14701734)
• These results provide insight into the mechanisms of NPAS4/ARNT dimerisation and transcriptional activation. (PMID:24465693)
• we provide the first evidence that Npas4 is expressed during embryonic development and that it may have a developmental role that is unrelated to its function in the adult brain (PMID:24887558)
• This review summarizes the current knowledge of the roles that Npas4 may play in neuroinflammation and ischemia. [review] (PMID:26690124)
• NPAS4 is expressed in endothelial cells, regulates VE-cadherin expression and regulates sprouting angiogenesis. (PMID:28082451)
• Circular RNA circ_0003420 mediates inflammation in sepsis-induced liver damage by downregulating neuronal PAS domain protein 4. (PMID:33719821)
• Molecular characterisation of rare loss-of-function NPAS3 and NPAS4 variants identified in individuals with neurodevelopmental disorders. (PMID:33758288)
• Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family. (PMID:36343253)
• Downregulated NPAS4 in multiple brain regions is associated with major depressive disorder. (PMID:38062059)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	npas4a	ENSDARG00000055752
danio_rerio	npas4b	ENSDARG00000087753
mus_musculus	Npas4	ENSMUSG00000045903
rattus_norvegicus	Npas4	ENSRNOG00000020009
drosophila_melanogaster	dysf	FBGN0039411
caenorhabditis_elegans		WBGENE00000521

Paralogs (7): HIF1A (ENSG00000100644), SIM1 (ENSG00000112246), EPAS1 (ENSG00000116016), HIF3A (ENSG00000124440), NPAS1 (ENSG00000130751), NPAS3 (ENSG00000151322), SIM2 (ENSG00000159263)

Protein

Protein identifiers

Neuronal PAS domain-containing protein 4 — Q8IUM7 (reviewed: Q8IUM7)

Alternative names: Class E basic helix-loop-helix protein 79, HLH-PAS transcription factor NXF, PAS domain-containing protein 10

All UniProt accessions (1): Q8IUM7

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor expressed in neurons of the brain that regulates the excitatory-inhibitory balance within neural circuits and is required for contextual memory in the hippocampus. Plays a key role in the structural and functional plasticity of neurons. Acts as an early-response transcription factor in both excitatory and inhibitory neurons, where it induces distinct but overlapping sets of late-response genes in these two types of neurons, allowing the synapses that form on inhibitory and excitatory neurons to be modified by neuronal activity in a manner specific to their function within a circuit, thereby facilitating appropriate circuit responses to sensory experience. In excitatory neurons, activates transcription of BDNF, which in turn controls the number of GABA-releasing synapses that form on excitatory neurons, thereby promoting an increased number of inhibitory synapses on excitatory neurons. In inhibitory neurons, regulates a distinct set of target genes that serve to increase excitatory input onto somatostatin neurons, probably resulting in enhanced feedback inhibition within cortical circuits. The excitatory and inhibitory balance in neurons affects a number of processes, such as short-term and long-term memory, acquisition of experience, fear memory, response to stress and social behavior. Acts as a regulator of dendritic spine development in olfactory bulb granule cells in a sensory-experience-dependent manner by regulating expression of MDM2. Efficient DNA binding requires dimerization with another bHLH protein, such as ARNT, ARNT2 or BMAL1. Can activate the CME (CNS midline enhancer) element.

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein. Heterodimer; forms a heterodimer with ARNT, ARNT2 or BMAL1.

Subcellular location. Nucleus.

Tissue specificity. Brain.

Post-translational modifications. Ubiquitinated, leading to degradation by the proteosome.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IUM7-1	1	yes
Q8IUM7-3	2

RefSeq proteins (2): NP_001305733, NP_849195* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000014	PAS	Domain
IPR011598	bHLH_dom	Domain
IPR013655	PAS_fold_3	Domain
IPR035965	PAS-like_dom_sf	Homologous_superfamily
IPR056192	bHLH_NPAS4	Domain

Pfam: PF08447, PF23183

UniProt features (38 total): sequence variant 14, sequence conflict 7, region of interest 5, domain 4, compositionally biased region 3, coiled-coil region 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUM7-F1	57.20	0.25

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9768778	Regulation of NPAS4 mRNA translation
R-HSA-9768919	NPAS4 regulates expression of target genes
R-HSA-9768777	Regulation of NPAS4 gene transcription

MSigDB gene sets: 156 (showing top): GOBP_MEMORY, TGGTGCT_MIR29A_MIR29B_MIR29C, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, WWTAAGGC_UNKNOWN, GOBP_BEHAVIOR, GOBP_SYNAPSE_ASSEMBLY, GOBP_CELLULAR_RESPONSE_TO_LIPID, AAGTCCA_MIR422B_MIR422A, GOBP_RESPONSE_TO_CORTICOSTEROID, TTTGTAG_MIR520D, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, chr11q13, SP1_Q2_01, GOBP_CELL_CELL_SIGNALING

GO Biological Process (16): regulation of transcription by RNA polymerase II (GO:0006357), learning (GO:0007612), short-term memory (GO:0007614), long-term memory (GO:0007616), cell differentiation (GO:0030154), regulation of synaptic transmission, GABAergic (GO:0032228), cellular response to stress (GO:0033554), social behavior (GO:0035176), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of synaptic plasticity (GO:0048167), excitatory postsynaptic potential (GO:0060079), inhibitory postsynaptic potential (GO:0060080), cellular response to corticosterone stimulus (GO:0071386), inhibitory synapse assembly (GO:1904862), nervous system development (GO:0007399), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (9): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), protein-containing complex binding (GO:0044877), protein heterodimerization activity (GO:0046982), DNA binding (GO:0003677), protein binding (GO:0005515), protein dimerization activity (GO:0046983)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytosol (GO:0005829), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Regulation of NPAS4 gene expression	2
Transcriptional Regulation by NPAS4	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
memory	2
modulation of chemical synaptic transmission	2
regulation of transcription by RNA polymerase II	2
regulation of postsynaptic membrane potential	2
chemical synaptic transmission, postsynaptic	2
binding	2
learning or memory	1
cellular developmental process	1
synaptic transmission, GABAergic	1
response to stress	1
cellular response to stimulus	1
behavior	1
biological process involved in intraspecies interaction between organisms	1
positive regulation of DNA-templated transcription	1
regulation of biological quality	1
response to corticosterone	1
cellular response to glucocorticoid stimulus	1
cellular response to mineralocorticoid stimulus	1
cellular response to alcohol	1
cellular response to ketone	1
synapse assembly	1
system development	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription cis-regulatory region binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
protein dimerization activity	1
nucleic acid binding	1
protein binding	1
chromosome	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1474 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPAS4	CSAG1	Q6PB30	818
NPAS4	DIPK2A	Q8NDZ4	817
NPAS4	ARNT2	Q9HBZ2	807
NPAS4	BMAL1	O00327	795
NPAS4	MAGEF1	Q9HAY2	782
NPAS4	NSMCE3	Q96MG7	771
NPAS4	SLC9A9	Q8IVB4	738
NPAS4	EGR1	P18146	733
NPAS4	NXT1	Q9UKK6	724
NPAS4	SLC9A6	Q92581	701
NPAS4	FOS	P01100	694
NPAS4	MAGEA1	P43355	655
NPAS4	MAGEL2	Q9UJ55	652
NPAS4	MAGED2	Q9UNF1	650
NPAS4	BDNF	P23560	640

IntAct

2 interactions, top by confidence:

A	B	Type	Score
NPAS4	TCP1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (8): NPAS4 (FRET), NPAS4 (Affinity Capture-Western), ARNT (Reconstituted Complex), ARNTL (Two-hybrid), ARNT2 (Affinity Capture-Western), NPAS4 (Proximity Label-MS), ARNT2 (Two-hybrid), ARNT (Two-hybrid)

ESM2 similar proteins: A0A0G2JTY4, A2A9T0, A2AHG0, A6NL88, A6QQJ8, A7MCY6, D3Z9H7, D3ZLB7, D3ZZN9, E9Q9M8, J3QNX5, O14529, O60299, O94983, O95153, P13346, P53539, P70298, P78524, P97305, P98152, Q0QWG9, Q12968, Q148V8, Q14934, Q15742, Q5BIM2, Q5D1E8, Q61127, Q62985, Q6DG50, Q6NUJ5, Q6PAJ3, Q6ZRV2, Q75VX8, Q80Y50, Q8BGD7, Q8IUM7, Q8K120, Q8K1Q4

Diamond homologs: A0MLS5, A6NFD8, O00327, O02219, O02748, O08785, O15516, O15945, O61734, O88529, P27540, P41739, P53762, P79832, P90953, P97460, Q2NL18, Q2VPD4, Q5R4T2, Q5RAK8, Q5ZQU2, Q61324, Q6YGZ4, Q6YGZ5, Q78E60, Q7TS99, Q8BGD7, Q8IUM7, Q8QGQ6, Q8QGQ7, Q8WYA1, Q91YA8, Q91YA9, Q91YB0, Q91YB2, Q99743, Q9BE97, Q9DBX7, Q9DG12, Q9EPW1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

677 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66421336:G:GT	donor_gain	1.0000
11:66421352:GTG:G	donor_gain	1.0000
11:66422271:GGT:G	donor_loss	1.0000
11:66422272:G:C	donor_loss	1.0000
11:66422272:G:GG	donor_gain	1.0000
11:66422273:T:A	donor_loss	1.0000
11:66422446:TCCA:T	acceptor_loss	1.0000
11:66422447:CCAG:C	acceptor_loss	1.0000
11:66422449:A:AC	acceptor_loss	1.0000
11:66422449:A:AG	acceptor_gain	1.0000
11:66422449:AG:A	acceptor_gain	1.0000
11:66422449:AGGT:A	acceptor_gain	1.0000
11:66422449:AGGTG:A	acceptor_gain	1.0000
11:66422450:G:A	acceptor_gain	1.0000
11:66422450:G:GA	acceptor_gain	1.0000
11:66422450:GGT:G	acceptor_gain	1.0000
11:66422450:GGTG:G	acceptor_gain	1.0000
11:66422450:GGTGG:G	acceptor_gain	1.0000
11:66422549:CACTG:C	donor_gain	1.0000
11:66422550:ACTG:A	donor_gain	1.0000
11:66422551:CTG:C	donor_gain	1.0000
11:66422552:TG:T	donor_gain	1.0000
11:66422552:TGGT:T	donor_loss	1.0000
11:66422553:GG:G	donor_gain	1.0000
11:66422553:GGT:G	donor_loss	1.0000
11:66422554:G:GG	donor_gain	1.0000
11:66422555:T:A	donor_loss	1.0000
11:66422664:A:AG	acceptor_gain	1.0000
11:66422665:T:G	acceptor_gain	1.0000
11:66422668:A:AG	acceptor_gain	1.0000

AlphaMissense

5213 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:66421197:G:C	K6N	1.000
11:66421197:G:T	K6N	1.000
11:66421205:C:T	S9F	1.000
11:66421207:A:G	K10E	1.000
11:66421209:G:C	K10N	1.000
11:66421209:G:T	K10N	1.000
11:66421213:C:A	R12S	1.000
11:66421217:G:C	R13P	1.000
11:66421223:A:C	Q15P	1.000
11:66421226:T:C	I16T	1.000
11:66421226:T:G	I16S	1.000
11:66421238:T:C	I20T	1.000
11:66421238:T:G	I20S	1.000
11:66421247:T:C	L23P	1.000
11:66421307:T:G	M43R	1.000
11:66422195:T:C	F84S	1.000
11:66422218:G:A	G92R	1.000
11:66422218:G:C	G92R	1.000
11:66422218:G:T	G92W	1.000
11:66422219:G:T	G92V	1.000
11:66422458:T:C	L112P	1.000
11:66421198:G:C	G7R	0.999
11:66421205:C:A	S9Y	0.999
11:66421207:A:C	K10Q	0.999
11:66421208:A:C	K10T	0.999
11:66421208:A:T	K10M	0.999
11:66421210:G:C	A11P	0.999
11:66421213:C:G	R12G	0.999
11:66421213:C:T	R12C	0.999
11:66421214:G:C	R12P	0.999

dbSNP variants (sampled 300 via entrez): RS1000024697 (11:66420964 C>A), RS1000366342 (11:66409005 C>A), RS1000438175 (11:66421179 C>A,T), RS1000973010 (11:66417203 C>A,T), RS1001100632 (11:66411758 C>T), RS1001229623 (11:66409737 G>A), RS1001297665 (11:66416996 G>A,C), RS1001347897 (11:66415733 G>A), RS1001403291 (11:66416023 G>A), RS1001413325 (11:66416443 G>A,C), RS1001413776 (11:66417517 A>T), RS1002619880 (11:66421612 G>A,T), RS1002642728 (11:66411785 C>T), RS1003075541 (11:66408293 C>G), RS1003107941 (11:66408583 C>T)

Disease associations

OMIM: gene MIM:608554 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (2): microcephaly (MONDO:0001149), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0000252	Microcephaly

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001241_12	Bipolar disorder	2.000000e-07
GCST007325_35	General risk tolerance (MTAG)	4.000000e-08
GCST90013421_7	Left-handedness	2.000000e-09
GCST90020029_338	Waist circumference adjusted for body mass index	2.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0009902	handedness
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	decreases expression, affects cotreatment	2
methylmercuric chloride	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
Decitabine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Dieldrin	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Niclosamide	increases expression	1
Phenylmercuric Acetate	decreases expression, affects cotreatment	1
Smoke	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
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