LPIN3

Summary

LPIN3 (lipin 3, HGNC:14451) is a protein-coding gene on chromosome 20q12, encoding Phosphatidate phosphatase LPIN3 (Q9BQK8). Magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis therefore regulates fatty acid metabolism.

The protein encoded by this gene is a member of the lipin family of proteins, and all family members share strong homology in their C-terminal region. This protein is thought to form hetero-oligomers with other lipin family members, while one family member, lipin 1, can also form homo-oligomers. This protein contains conserved motifs for phosphatidate phosphatase 1 (PAP1) activity as well as a domain that interacts with a transcriptional co-activator. Lipin complexes act in the cytoplasm to catalyze the dephosphorylation of phosphatidic acid to produce diacylglycerol, which is the precursor of both triglycerides and phospholipids. Lipin complexes are also thought to regulate gene expression as transcriptional co-activators in the nucleus. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 64900 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 158 total
• MANE Select transcript: NM_022896

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14451
Approved symbol	LPIN3
Name	lipin 3
Location	20q12
Locus type	gene with protein product
Status	Approved
Aliases	SMP2
Ensembl gene	ENSG00000132793
Ensembl biotype	protein_coding
OMIM	605520
Entrez	64900

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000373257, ENST00000445975, ENST00000491528, ENST00000496565, ENST00000632009, ENST00000884415, ENST00000884416, ENST00000884417

RefSeq mRNA: 2 — MANE Select: NM_022896 NM_001301860, NM_022896

CCDS: CCDS33469, CCDS93041

Canonical transcript exons

ENST00000373257 — 20 exons

Exon	Start	End
ENSE00000662075	41357040	41357188
ENSE00000991564	41352060	41352220
ENSE00000991565	41352606	41352699
ENSE00000991566	41352798	41352867
ENSE00000991567	41354645	41354737
ENSE00000991568	41355896	41356034
ENSE00001173305	41357882	41358034
ENSE00001173332	41351821	41351920
ENSE00001459888	41340821	41341002
ENSE00001459899	41354820	41354863
ENSE00001526786	41358722	41360582
ENSE00001623265	41349774	41349894
ENSE00001625607	41348619	41348887
ENSE00001736370	41349092	41349172
ENSE00001762461	41347552	41347647
ENSE00001792067	41350055	41350397
ENSE00002696163	41345796	41345995
ENSE00003469988	41357361	41357447
ENSE00003616618	41358237	41358351
ENSE00003647980	41358439	41358542

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 96.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.9410 / max 171.2711, expressed in 1266 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184643	4.3466	1235
184644	1.5943	502

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.20	gold quality
mucosa of transverse colon	UBERON:0004991	94.57	gold quality
right lobe of thyroid gland	UBERON:0001119	94.14	gold quality
skin of abdomen	UBERON:0001416	94.02	gold quality
apex of heart	UBERON:0002098	93.99	gold quality
metanephros cortex	UBERON:0010533	93.93	gold quality
skin of leg	UBERON:0001511	93.69	gold quality
left lobe of thyroid gland	UBERON:0001120	93.07	gold quality
transverse colon	UBERON:0001157	92.99	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.90	gold quality
esophagus mucosa	UBERON:0002469	91.86	gold quality
right lobe of liver	UBERON:0001114	91.51	gold quality
right uterine tube	UBERON:0001302	91.08	gold quality
thyroid gland	UBERON:0002046	90.96	gold quality
minor salivary gland	UBERON:0001830	90.03	gold quality
omental fat pad	UBERON:0010414	89.91	gold quality
body of uterus	UBERON:0009853	89.89	gold quality
peritoneum	UBERON:0002358	89.82	gold quality
ectocervix	UBERON:0012249	89.46	gold quality
esophagus	UBERON:0001043	89.12	gold quality
left uterine tube	UBERON:0001303	89.12	gold quality
ascending aorta	UBERON:0001496	88.92	gold quality
small intestine	UBERON:0002108	88.83	gold quality
thoracic aorta	UBERON:0001515	88.77	gold quality
zone of skin	UBERON:0000014	88.55	gold quality
right ovary	UBERON:0002118	88.42	gold quality
rectum	UBERON:0001052	88.36	gold quality
descending thoracic aorta	UBERON:0002345	88.06	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.99	gold quality
body of stomach	UBERON:0001161	87.80	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	29216.30
E-MTAB-7052	yes	451.79
E-ANND-3	yes	9.96
E-GEOD-100618	no	10.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

Literature-anchored findings (GeneRIF, showing 5)

• Data revealed that lipin 1 formed stable homo-oligomers with itself and hetero-oligomers with lipin 2/3. (PMID:20735359)
• LPIN1-related myolysis constitutes a major cause of early-onset rhabdomyolysis and occasionally in adults. Heterozygous LPIN1 mutations may cause mild muscular symptoms. No major defects of LPIN2 or LPIN3 genes were associated with muscle manifestations. (PMID:22481384)
• a newly identified novel cell-penetrating sequence (LPIN; RRKRRRRRK) from the nuclear localization sequence (NLS) of human nuclear phosphatase, LPIN3. (PMID:23263658)
• Identification of lipidomic profiles associated with drug-resistant prostate cancer cells. (PMID:33596934)
• Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and nucleocytoplasmic localization of Lipin1. (PMID:37776435)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:123305	ENSDARG00000015563
mus_musculus	Lpin3	ENSMUSG00000027412
rattus_norvegicus	Lpin3	ENSRNOG00000016636
drosophila_melanogaster	Lpin	FBGN0263593
caenorhabditis_elegans		WBGENE00010425

Paralogs (3): LPIN2 (ENSG00000101577), LPIN1 (ENSG00000134324), AP5Z1 (ENSG00000242802)

Protein

Protein identifiers

Phosphatidate phosphatase LPIN3 — Q9BQK8 (reviewed: Q9BQK8)

Alternative names: Lipin-3, Lipin-3-like

All UniProt accessions (2): Q9BQK8, H0Y5E1

UniProt curated annotations — full annotation on UniProt →

Function. Magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis therefore regulates fatty acid metabolism.

Subcellular location. Nucleus.

Tissue specificity. Significant expression in intestine and other regions of the gastrointestinal tract.

Activity regulation. Inhibited by N-ethylmaleimide.

Domain organisation. Contains 1 Asp-Xaa-Asp-Xaa-Thr (DXDXT) motif, a catalytic motif known to be essential for phosphatidate phosphatase activity. Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL) motif, a motif known to be a transcriptional binding motif.

Similarity. Belongs to the lipin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BQK8-1	1	yes
Q9BQK8-2	2

RefSeq proteins (2): NP_001288789, NP_075047* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007651	Lipin_N	Domain
IPR013209	LNS2	Domain
IPR026058	LIPIN	Family
IPR031315	LNS2/PITP	Domain
IPR031703	Lipin_mid	Domain
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF04571, PF08235, PF16876

Catalyzed reactions (Rhea), 1 shown:

• a 1,2-diacyl-sn-glycero-3-phosphate + H2O = a 1,2-diacyl-sn-glycerol + phosphate (RHEA:27429)

UniProt features (21 total): region of interest 5, compositionally biased region 5, modified residue 5, short sequence motif 3, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQK8-F1	61.59	0.25

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 159, 161, 162, 224, 463

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-1483191	Synthesis of PC
R-HSA-1483213	Synthesis of PE
R-HSA-4419969	Depolymerization of the Nuclear Lamina
R-HSA-75109	Triglyceride biosynthesis
R-HSA-1430728	Metabolism
R-HSA-1483206	Glycerophospholipid biosynthesis
R-HSA-1483257	Phospholipid metabolism
R-HSA-1640170	Cell Cycle
R-HSA-2980766	Nuclear Envelope Breakdown
R-HSA-556833	Metabolism of lipids
R-HSA-68875	Mitotic Prophase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-8979227	Triglyceride metabolism

MSigDB gene sets: 98 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_RESPONSE_TO_INSULIN, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_HORMONE, GOBP_NEUTRAL_LIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (6): fatty acid catabolic process (GO:0009062), triglyceride biosynthetic process (GO:0019432), cellular response to insulin stimulus (GO:0032869), positive regulation of transcription by RNA polymerase II (GO:0045944), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (3): transcription coactivator activity (GO:0003713), phosphatidate phosphatase activity (GO:0008195), hydrolase activity (GO:0016787)

GO Cellular Component (2): nucleus (GO:0005634), endoplasmic reticulum membrane (GO:0005789)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	2
Metabolism of lipids	2
Nuclear Envelope Breakdown	1
Triglyceride metabolism	1
Phospholipid metabolism	1
Mitotic Prophase	1
Metabolism	1
M Phase	1
Cell Cycle, Mitotic	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of DNA-templated transcription	2
fatty acid metabolic process	1
lipid catabolic process	1
monocarboxylic acid catabolic process	1
triglyceride metabolic process	1
acylglycerol biosynthetic process	1
response to insulin	1
cellular response to peptide hormone stimulus	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
transcription coregulator activity	1
lipid phosphatase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

896 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPIN3	PPARA	Q07869	699
LPIN3	PLPP2	O43688	661
LPIN3	CTDNEP1	O95476	649
LPIN3	PLPP3	O14495	613
LPIN3	GPAT4	Q86UL3	607
LPIN3	AGPAT2	O15120	590
LPIN3	PIGZ	Q86VD9	582
LPIN3	AGPAT4	Q9NRZ5	576
LPIN3	AGPAT3	Q9NRZ7	572
LPIN3	GPAT3	Q53EU6	541
LPIN3	DGAT1	O75907	521
LPIN3	AGPAT1	Q99943	503
LPIN3	NOC3L	Q8WTT2	483
LPIN3	PLPP1	O14494	471
LPIN3	MRTO4	Q9UKD2	454

IntAct

59 interactions, top by confidence:

A	B	Type	Score
LPIN3	CSNK2A2	psi-mi:“MI:0914”(association)	0.640
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
LPIN3	RTN4	psi-mi:“MI:0915”(physical association)	0.400
LPIN3	NOLC1	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAH	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAQ	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
LPIN3	VASP	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
LPIN3	DCLK1	psi-mi:“MI:0915”(physical association)	0.000
LPIN3	SIPA1L1	psi-mi:“MI:0915”(physical association)	0.000
LPIN3	MAST3	psi-mi:“MI:0915”(physical association)	0.000
LPIN3	SRGAP2	psi-mi:“MI:0915”(physical association)	0.000
LPIN3	GIGYF1	psi-mi:“MI:0915”(physical association)	0.000
LPIN3	NADK	psi-mi:“MI:0915”(physical association)	0.000
LPIN3	NF1	psi-mi:“MI:0915”(physical association)	0.000
LPIN3	HDAC4	psi-mi:“MI:0915”(physical association)	0.000
LPIN3	GIGYF2	psi-mi:“MI:0915”(physical association)	0.000
LPIN3	RALGPS2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (88): LPIN3 (Affinity Capture-MS), LPIN3 (Affinity Capture-MS), LPIN3 (Affinity Capture-MS), LPIN2 (Affinity Capture-MS), LPIN1 (Affinity Capture-MS), CAMKK1 (Affinity Capture-MS), BIRC2 (Affinity Capture-MS), HDAC6 (Affinity Capture-MS), SMG6 (Affinity Capture-MS), CSNK2A2 (Affinity Capture-MS), CSNK2A1 (Affinity Capture-MS), KCTD3 (Affinity Capture-MS), KIF13B (Affinity Capture-MS), CGN (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M9QN10, A0PK05, A2AHC3, D3Z8E6, D4AEC2, E9Q3C1, P28234, P29414, P55917, P59729, Q08AD1, Q08DM6, Q0VCR2, Q0VCT2, Q13009, Q14CH0, Q3MHM8, Q3V0J1, Q5EB20, Q5HZE8, Q5PQS0, Q5RD34, Q5T5Y3, Q5VUB5, Q60610, Q61194, Q6AYK4, Q6ZUJ8, Q7TNI2, Q7TNN8, Q7TSI1, Q8BGN6, Q8BJN4, Q8C1B1, Q8C3K5, Q8N6S5, Q8WYP3, Q924Y8, Q969M2, Q99PI4

Diamond homologs: P32567, Q14693, Q7TNN8, Q91ZP3, Q92539, Q99PI4, Q99PI5, Q9BQK8, Q9FMN2, Q9SF47, Q9UUJ6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	112.0×	2e-11
Activation of BAD and translocation to mitochondria	6	108.8×	7e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	96.0×	1e-09
Activation of BH3-only proteins	6	70.9×	7e-09
RHO GTPases activate PKNs	7	52.9×	2e-09
Intrinsic Pathway for Apoptosis	6	41.8×	1e-07
SARS-CoV-1-host interactions	6	25.1×	2e-06
Apoptosis	6	24.0×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	38.6×	4e-06
intracellular protein localization	7	12.8×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	123
Likely benign	13
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3229 predictions. Top by Δscore:

Variant	Effect	Δscore
20:41345993:GTG:G	donor_gain	1.0000
20:41347643:ATGAT:A	donor_gain	1.0000
20:41347644:TGAT:T	donor_gain	1.0000
20:41347644:TGATG:T	donor_loss	1.0000
20:41347645:GAT:G	donor_gain	1.0000
20:41347645:GATG:G	donor_gain	1.0000
20:41347646:AT:A	donor_gain	1.0000
20:41347647:TGT:T	donor_loss	1.0000
20:41347648:G:GG	donor_gain	1.0000
20:41347649:T:G	donor_loss	1.0000
20:41348843:GA:G	donor_gain	1.0000
20:41348868:C:G	donor_gain	1.0000
20:41349078:T:TA	acceptor_gain	1.0000
20:41349079:G:A	acceptor_gain	1.0000
20:41349087:A:AG	acceptor_gain	1.0000
20:41349088:G:GT	acceptor_gain	1.0000
20:41349088:GC:G	acceptor_gain	1.0000
20:41349088:GCA:G	acceptor_gain	1.0000
20:41349088:GCAGT:G	acceptor_gain	1.0000
20:41349170:CAGG:C	donor_loss	1.0000
20:41349171:AGGT:A	donor_loss	1.0000
20:41349172:GG:G	donor_loss	1.0000
20:41349772:A:AG	acceptor_gain	1.0000
20:41349773:G:GA	acceptor_gain	1.0000
20:41349773:GC:G	acceptor_gain	1.0000
20:41349773:GCC:G	acceptor_gain	1.0000
20:41349773:GCCT:G	acceptor_gain	1.0000
20:41352056:GCA:G	acceptor_loss	1.0000
20:41352057:CAGTG:C	acceptor_loss	1.0000
20:41352058:A:AG	acceptor_gain	1.0000

AlphaMissense

5524 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:41358270:G:C	K742N	0.997
20:41358270:G:T	K742N	0.997
20:41357080:T:C	F615S	0.996
20:41357167:A:C	D644A	0.995
20:41357167:A:T	D644V	0.995
20:41345946:T:C	F48S	0.994
20:41345957:T:C	F52L	0.994
20:41345959:T:A	F52L	0.994
20:41345959:T:G	F52L	0.994
20:41358265:T:C	F741L	0.994
20:41358267:C:A	F741L	0.994
20:41358267:C:G	F741L	0.994
20:41358281:T:C	L746P	0.994
20:41347618:T:C	F87L	0.993
20:41347620:C:A	F87L	0.993
20:41347620:C:G	F87L	0.993
20:41352818:C:A	A493D	0.993
20:41357163:T:C	S643P	0.993
20:41347592:T:C	M78T	0.992
20:41357079:T:C	F615L	0.992
20:41357081:C:A	F615L	0.992
20:41357081:C:G	F615L	0.992
20:41347622:T:C	F88S	0.991
20:41352808:T:A	W490R	0.991
20:41352808:T:C	W490R	0.991
20:41357136:T:A	W634R	0.991
20:41357136:T:C	W634R	0.991
20:41357362:T:C	S652P	0.991
20:41345958:T:C	F52S	0.990
20:41347622:T:G	F88C	0.989

dbSNP variants (sampled 300 via entrez): RS1000216539 (20:41360358 T>C), RS1000218981 (20:41343952 C>T), RS1000310712 (20:41355009 T>A,G), RS1000755049 (20:41356704 TTCCTGCCAACAGCAG>T), RS1000822648 (20:41342774 G>A), RS1000867208 (20:41354586 G>A), RS1000923589 (20:41359837 TC>T), RS1001089718 (20:41342494 A>G), RS1001190297 (20:41343267 T>A), RS1001669688 (20:41359635 G>C), RS1001697851 (20:41354414 G>A), RS1001803721 (20:41360763 A>T), RS1001963959 (20:41354077 T>G), RS1002144759 (20:41342020 G>A,T), RS1002165647 (20:41347877 G>A)

Disease associations

OMIM: gene MIM:605520 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005531_98	Multiple sclerosis	7.000000e-08
GCST006661_160	Male-pattern baldness	2.000000e-15
GCST008058_278	Estimated glomerular filtration rate	3.000000e-07
GCST008059_229	Estimated glomerular filtration rate	4.000000e-06
GCST010703_20	Brain morphology (MOSTest)	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Lipid phosphate phosphatases

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases abundance, increases expression	4
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol A	affects cotreatment, increases methylation	1
beta-lapachone	increases expression	1
cupric chloride	decreases expression	1
coumarin	increases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
GW 4064	affects cotreatment, decreases expression	1
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	affects cotreatment, decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	increases phosphorylation	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Farnesol	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Niclosamide	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1

Clinical trials (associated diseases)

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