PNOC

Summary

PNOC (prepronociceptin, HGNC:9163) is a protein-coding gene on chromosome 8p21.1, encoding Prepronociceptin (Q13519). Ligand of the opioid receptor-like receptor OPRL1.

This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include nociceptin, nocistatin, and orphanin FQ2 (OFQ2). Nociceptin, also known as orphanin FQ, is a 17-amino acid neuropeptide that binds to the nociceptin receptor to induce increased pain sensitivity, and may additionally regulate body temperature, learning and memory, and hunger. Another product of the encoded preproprotein, nocistatin, may inhibit the effects of nociceptin.

Source: NCBI Gene 5368 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_006228

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9163
Approved symbol	PNOC
Name	prepronociceptin
Location	8p21.1
Locus type	gene with protein product
Status	Approved
Aliases	PPNOC, N/OFQ, NOP
Ensembl gene	ENSG00000168081
Ensembl biotype	protein_coding
OMIM	601459
Entrez	5368

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000301908, ENST00000518479, ENST00000519592, ENST00000522209, ENST00000923262

RefSeq mRNA: 2 — MANE Select: NM_006228 NM_001284244, NM_006228

CCDS: CCDS6066, CCDS64862

Canonical transcript exons

ENST00000301908 — 4 exons

Exon	Start	End
ENSE00001120173	28329135	28329283
ENSE00001335563	28317268	28317316
ENSE00003578608	28339040	28339491
ENSE00003842877	28342942	28343351

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 93.98.

FANTOM5 (CAGE): breadth broad, TPM avg 3.4313 / max 1212.6098, expressed in 250 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88191	2.4689	168
88193	0.8701	75
88190	0.0922	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.98	gold quality
germinal epithelium of ovary	UBERON:0001304	84.94	gold quality
lymph node	UBERON:0000029	84.00	gold quality
prefrontal cortex	UBERON:0000451	81.49	gold quality
spleen	UBERON:0002106	81.49	gold quality
granulocyte	CL:0000094	79.35	gold quality
vermiform appendix	UBERON:0001154	79.33	gold quality
epithelium of nasopharynx	UBERON:0001951	78.80	silver quality
bone marrow cell	CL:0002092	78.35	gold quality
cingulate cortex	UBERON:0003027	78.04	gold quality
anterior cingulate cortex	UBERON:0009835	77.91	gold quality
leukocyte	CL:0000738	76.41	gold quality
endothelial cell	CL:0000115	76.18	silver quality
monocyte	CL:0000576	75.98	gold quality
mononuclear cell	CL:0000842	75.95	gold quality
frontal cortex	UBERON:0001870	75.67	gold quality
neocortex	UBERON:0001950	75.65	gold quality
Brodmann (1909) area 46	UBERON:0006483	75.47	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	75.14	gold quality
frontal pole	UBERON:0002795	75.12	silver quality
blood	UBERON:0000178	74.02	gold quality
right frontal lobe	UBERON:0002810	73.66	gold quality
Brodmann (1909) area 10	UBERON:0013541	73.24	silver quality
bone marrow	UBERON:0002371	72.58	gold quality
caecum	UBERON:0001153	72.53	gold quality
cerebral cortex	UBERON:0000956	72.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.85	gold quality
ganglionic eminence	UBERON:0004023	71.40	gold quality
paraflocculus	UBERON:0005351	71.33	gold quality
primary visual cortex	UBERON:0002436	70.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	22.74
E-MTAB-8410	no	0.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, PTF1A, SP1

miRNA regulators (miRDB)

41 targeting PNOC, 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-4283	100.00	66.42	2097
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-936	98.87	70.51	1124

Literature-anchored findings (GeneRIF, showing 29)

• Peripheral blood levels are elevated in Wilson disease (PMID:12812047)
• results show that nociceptin/NociR is present and functional in human neutrophils, and the results identify a novel dialogue pathway between neural and immune tissues (PMID:12950177)
• The presence of two different forms of mature nocistatin (NST-17 and NST-30) and a possible N-terminal methionine cleaved NST-29 have been confirmed by both radioimmunoassay and mass spectrometry. (PMID:16043263)
• Two SNPs in PNOC showed marginal association with alcoholism and one with illicit drug dependence. (PMID:17910740)
• Peripheral blood mononuclear cells transcribe pre-pro-nociception/orphaninFQ. (PMID:18292431)
• Our results support the concept postulating that chronic ethanol consumption and withdrawal downregulate the PNOC/OPRL1 system, which critically controls alcohol intake. (PMID:19501074)
• Unstable angina is associated with a significant increase in circulating nociceptin/orphanin FQ levels unrelated to intervening transient myocardial ischemia or hemodynamic changes. (PMID:19560501)
• data obtained from neocortex of epileptic patients provide strong evidence that temporal lobe epilepsy is associated with alterations in mu opioid and nociceptin receptor binding and signal transduction mechanisms downstream of these receptors (PMID:19573600)
• Results showed that vigorous and prolonged hyperventilation changes plasma nociceptin/orphanin FQ levels due to the direct effects of hypocapnic alkalosis or to different sympatho-adrenergic system responses. (PMID:20100531)
• PNOC expression level was 2.99 times higher in vitiligo involved skin when compared to healthy control skin. (PMID:20888736)
• chronic ischemic conditions of atherosclerotic origin are associated with significantly lower plasma nociceptin levels (PMID:21310194)
• activation of NFkappaB by OFQ/Nociceptin suggests a likely mechanism for its modulation of the central nervous and immune systems. (PMID:21547539)
• A high expression of nociceptin in adenomyosis may be one of the casual factors of dysmenorrhea. The severity of dysmenorrhea is positively correlated with the expression of nociceptin in eutopic endometrial tissue. (PMID:21600132)
• The presence of Orphanin, Oxytocin, ANP, eNOS and iNOS proteins was identified in the human umbilical cord.[Orphanin] (PMID:21744319)
• Strong expression of PNOC was seen in neoplastic neurons of 7/7 brainstem gangliogliomas, but was significantly weaker in non-brainstem GGs. (PMID:22706982)
• REVIEW: intracellular localization and physiological role of nociceptin and nocistatin (PMID:23454174)
• Data suggest that nociceptin and nociceptin receptor evolved as one of 4 opioid receptor systems in vertebrates; this system exhibits both analgesic and hyperalgesic effects. [REVIEW] (PMID:25677768)
• Data suggest that nociceptin plays a crucial role in progress of meiosis during spermatogenesis. [REVIEW] (PMID:25677772)
• Opioid neuropeptide systems are important mediators of ovarian steroid signaling that regulate reproduction in female; data suggest that nociceptin and nociceptin receptor system in arcuate nucleus of hypothalamus is such a system. [REVIEW] (PMID:25677773)
• Data suggest that both nociceptin and nocistatin inhibit myometrial contractions and may play roles in perception of pain during delivery. [REVIEW] (PMID:25677774)
• Data suggest that the nociceptin/nociceptin receptor system is involved in modulation of the immune response and in pathogenesis of autoimmune diseases. [REVIEW] (PMID:25677775)
• Data suggest that the nociceptin/nociceptin receptor system is involved in modulation of psychological and inflammatory stress responses and in pathogenesis of anxiety. [REVIEW] (PMID:25677776)
• Data suggest that interaction between the nociceptin/nociceptin receptor system and the orexin/orexin receptor system in neurons of the hypothalamus positively and negatively modulate complex and integrated responses to stress. [REVIEW] (PMID:25677777)
• Data suggest that nociceptin/nociceptin receptor signaling in neurons of the hippocampus modulate learning and memory. [REVIEW] (PMID:25677778)
• findings suggest that SNPs in opioid receptors and the PNOC genes are associated with NAS severity. (PMID:26233486)
• Study presents evidence suggesting that the PNOC and OPRL1 are dysregulated in suicide completers, thereby potentially contributing to impaired emotional and behavioral control and, ultimately, to the suicidal crisis (PMID:26349406)
• The presence of the PNOC rs732636 A allele was associated with the worse Neonatal abstinence syndrome outcomes in infants. (PMID:26791055)
• found differences in Neonatal Abstinence Syndrome outcomes depending on PNOC and COMT SNP genotype. (PMID:27983768)
• PNOC Expressed by B Cells in Cholangiocarcinoma Was Survival Related and LAIR2 Could Be a T Cell Exhaustion Biomarker in Tumor Microenvironment: Characterization of Immune Microenvironment Combining Single-Cell and Bulk Sequencing Technology. (PMID:33841428)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pnocb	ENSDARG00000024189
danio_rerio	pnoca	ENSDARG00000025024
mus_musculus	Pnoc	ENSMUSG00000045731
rattus_norvegicus	Pnoc	ENSRNOG00000014231

Paralogs (2): PDYN (ENSG00000101327), PENK (ENSG00000181195)

Protein

Protein identifiers

Prepronociceptin — Q13519 (reviewed: Q13519)

All UniProt accessions (2): Q13519, E7EVP0

UniProt curated annotations — full annotation on UniProt →

Function. Ligand of the opioid receptor-like receptor OPRL1. It may act as a transmitter in the brain by modulating nociceptive and locomotor behavior. May be involved in neuronal differentiation and development. Blocks nociceptin action in pain transmission by inhibiting nociceptin-induced hyperalgesia and allodynia. Has potent analgesic activity.

Subcellular location. Secreted.

Tissue specificity. Predominantly expressed in the brain and spinal cord. Also expressed and secreted by peripheral blood neutrophils following degranulation.

Post-translational modifications. Specific enzymatic cleavages at paired basic residues probably yield other active peptides besides nociceptin. The N-terminal domain contains 6 conserved cysteines thought to be involved in disulfide bonding and/or processing.

Similarity. Belongs to the opioid neuropeptide precursor family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13519-1	1	yes
Q13519-2	2

RefSeq proteins (2): NP_001271173, NP_006219* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002367	Nociceptin	Family
IPR006024	Opioid_neupept	Family

Pfam: PF01160

UniProt features (9 total): peptide 3, propeptide 2, signal peptide 1, splice variant 1, strand 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8F7X	ELECTRON MICROSCOPY	3.28

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13519-F1	63.16	0.00

Antibody-complex structures (SAbDab): 1 — 8F7X

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 240 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, YAATNRNNNYNATT_UNKNOWN, GOBP_ACID_SECRETION, MODULE_274, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_COCAINE, NKX25_02, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, LFA1_Q6, GOBP_ADULT_BEHAVIOR, AREB6_03, GOBP_NEUROTRANSMITTER_TRANSPORT, TGACCTY_ERR1_Q2, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (7): signal transduction (GO:0007165), neuropeptide signaling pathway (GO:0007218), chemical synaptic transmission (GO:0007268), neuron-neuron synaptic transmission (GO:0007270), female pregnancy (GO:0007565), sensory perception (GO:0007600), sensory perception of pain (GO:0019233)

GO Molecular Function (4): opioid peptide activity (GO:0001515), neuropeptide hormone activity (GO:0005184), opioid receptor binding (GO:0031628), receptor ligand activity (GO:0048018)

GO Cellular Component (7): extracellular region (GO:0005576), plasma membrane (GO:0005886), dendrite (GO:0030425), neuronal cell body (GO:0043025), axon terminus (GO:0043679), synaptic membrane (GO:0097060), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor signaling pathway	1
anterograde trans-synaptic signaling	1
chemical synaptic transmission	1
multi-organism reproductive process	1
multi-multicellular organism process	1
nervous system process	1
sensory perception	1
receptor ligand activity	1
hormone activity	1
neuropeptide activity	1
G protein-coupled receptor binding	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
cellular anatomical structure	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
somatodendritic compartment	1
cell body	1
neuron projection terminus	1
presynapse	1
distal axon	1
synapse	1
plasma membrane region	1
cell junction	1

Protein interactions and networks

STRING

1334 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PNOC	PDYN	P01213	964
PNOC	POMC	P01189	822
PNOC	OPRM1	P35372	820
PNOC	NAT1	P18440	767
PNOC	CHRNA2	Q15822	757
PNOC	NPY	P01303	747
PNOC	CRH	P06850	743
PNOC	TAC1	P20366	741
PNOC	GAL	P22466	737
PNOC	SPINT2	O43291	720
PNOC	OPRD1	P41143	711
PNOC	HCRT	O43612	663
PNOC	PPP3CC	P48454	654
PNOC	PMCH	P20382	638
PNOC	NPFF	O15130	621

IntAct

5 interactions, top by confidence:

A	B	Type	Score
PNOC	CETN3	psi-mi:“MI:0914”(association)	0.530
PNOC	NUP155	psi-mi:“MI:0914”(association)	0.530
P		psi-mi:“MI:0914”(association)	0.350

BioGRID (16): PNOC (Biochemical Activity), PNOC (Reconstituted Complex), PNOC (Reconstituted Complex), PDP1 (Affinity Capture-MS), WDTC1 (Affinity Capture-MS), LNPEP (Affinity Capture-MS), FAM175B (Affinity Capture-MS), WDFY2 (Affinity Capture-MS), DCAF6 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), NUP155 (Affinity Capture-MS), BABAM1 (Affinity Capture-MS), CETN3 (Affinity Capture-MS), CDC26 (Affinity Capture-MS), TIMM10B (Affinity Capture-MS)

ESM2 similar proteins: A0A1L2F565, B3IWF7, B3IWF9, D3Z752, E2E4E4, F1QQI2, I7C2V3, M0R8L2, O46540, O62647, O73812, O93448, P01146, P01257, P01258, P07501, P0DQY8, P10093, P12272, P12969, P15743, P22858, P27104, P47851, P51918, P52211, P58073, P63152, P63292, P70160, P81564, P81872, Q0VBW8, Q0VC44, Q13519, Q5H8A3, Q60549, Q64387, Q75V94, Q75V95

Diamond homologs: O62647, Q13519, Q62923, Q64387, P55791

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

610 predictions. Top by Δscore:

Variant	Effect	Δscore
8:28339336:G:GT	donor_gain	1.0000
8:28317312:CTCAG:C	donor_loss	0.9900
8:28317313:TCAG:T	donor_loss	0.9900
8:28317314:CAGGT:C	donor_loss	0.9900
8:28317316:GGTA:G	donor_loss	0.9900
8:28317317:G:C	donor_loss	0.9900
8:28317318:T:G	donor_loss	0.9900
8:28339035:TGCA:T	acceptor_loss	0.9900
8:28339036:GCA:G	acceptor_loss	0.9900
8:28339039:G:GC	acceptor_loss	0.9900
8:28339324:G:GT	donor_gain	0.9900
8:28339362:G:GG	donor_gain	0.9900
8:28339429:GAATG:G	donor_gain	0.9900
8:28339492:G:GG	donor_gain	0.9900
8:28329127:T:G	acceptor_gain	0.9800
8:28329133:A:AG	acceptor_gain	0.9800
8:28329134:G:GG	acceptor_gain	0.9800
8:28339039:GGT:G	acceptor_gain	0.9800
8:28339039:GGTGT:G	acceptor_gain	0.9800
8:28339490:GA:G	donor_gain	0.9800
8:28329134:GCA:G	acceptor_gain	0.9700
8:28329134:GCAC:G	acceptor_gain	0.9700
8:28329279:TGGAG:T	donor_loss	0.9700
8:28329281:GAGGT:G	donor_loss	0.9700
8:28329282:AG:A	donor_loss	0.9700
8:28329283:GG:G	donor_loss	0.9700
8:28329284:G:GC	donor_loss	0.9700
8:28329285:TAGG:T	donor_loss	0.9700
8:28339038:A:AG	acceptor_gain	0.9700
8:28339038:AGGT:A	acceptor_gain	0.9700

AlphaMissense

1168 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:28339310:T:C	F133L	0.998
8:28339311:T:G	F133C	0.998
8:28339312:C:A	F133L	0.998
8:28339312:C:G	F133L	0.998
8:28339311:T:C	F133S	0.995
8:28339336:G:C	R141S	0.993
8:28339336:G:T	R141S	0.993
8:28339327:G:C	K138N	0.992
8:28339327:G:T	K138N	0.992
8:28339301:T:C	F130L	0.991
8:28339303:T:A	F130L	0.991
8:28339303:T:G	F130L	0.991
8:28339368:T:C	F152S	0.991
8:28339354:G:C	K147N	0.990
8:28339354:G:T	K147N	0.990
8:28339305:G:A	G131E	0.989
8:28339367:T:C	F152L	0.989
8:28339369:T:A	F152L	0.989
8:28339369:T:G	F152L	0.989
8:28339300:A:C	R129S	0.988
8:28339300:A:T	R129S	0.988
8:28339335:G:C	R141T	0.988
8:28339379:T:G	Y156D	0.987
8:28339339:G:C	K142N	0.986
8:28339339:G:T	K142N	0.986
8:28339358:T:C	F149L	0.986
8:28339360:C:A	F149L	0.986
8:28339360:C:G	F149L	0.986
8:28339361:A:C	S150R	0.986
8:28339363:T:A	S150R	0.986

dbSNP variants (sampled 300 via entrez): RS1000018752 (8:28341623 T>C), RS1000067654 (8:28320373 A>G), RS1000091992 (8:28341362 T>C), RS1000171890 (8:28318287 G>T), RS1000204714 (8:28318545 G>A,T), RS1000514750 (8:28330192 C>T), RS1000636613 (8:28339667 T>C), RS1000672155 (8:28324239 C>A,T), RS1000678888 (8:28324051 T>A), RS1000731690 (8:28330362 C>T), RS1001024104 (8:28343044 C>A), RS1001038913 (8:28333226 T>A), RS1001095919 (8:28342873 T>G), RS1001259058 (8:28333868 C>G,T), RS1001313146 (8:28336889 T>C)

Disease associations

OMIM: gene MIM:601459 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004904_78	Body mass index	4.000000e-08
GCST009391_1547	Metabolite levels	6.000000e-06
GCST011494_40	Daytime nap	2.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0010511	niacinamide measurement
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs351776	Toxicity	3	buprenorphine	Neonatal Abstinence Syndrome
rs351776	Toxicity	3	methadone	Neonatal Abstinence Syndrome
rs4732636	Toxicity	3	buprenorphine	Neonatal Abstinence Syndrome
rs4732636	Toxicity	3	methadone	Neonatal Abstinence Syndrome

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs351776	PNOC	3	0.00	2	buprenorphine;methadone
rs2614095	PNOC		0.00	0

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
bisphenol F	affects cotreatment, increases methylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, affects methylation, decreases methylation	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases methylation	1
Fulvestrant	increases methylation, affects cotreatment, affects methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Formaldehyde	decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	decreases expression	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1
Vincristine	decreases expression	1

Clinical trials (associated diseases)

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