ONECUT2

Summary

ONECUT2 (one cut homeobox 2, HGNC:8139) is a protein-coding gene on chromosome 18q21.31, encoding One cut domain family member 2 (O95948). Transcriptional activator.

This gene encodes a member of the onecut family of transcription factors, which are characterized by a cut domain and an atypical homeodomain. The protein binds to specific DNA sequences and stimulates expression of target genes, including genes involved in melanocyte and hepatocyte differentiation.

Source: NCBI Gene 9480 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 84 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_004852

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8139
Approved symbol	ONECUT2
Name	one cut homeobox 2
Location	18q21.31
Locus type	gene with protein product
Status	Approved
Aliases	OC-2
Ensembl gene	ENSG00000119547
Ensembl biotype	protein_coding
OMIM	604894
Entrez	9480

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000481727, ENST00000491143

RefSeq mRNA: 1 — MANE Select: NM_004852 NM_004852

CCDS: CCDS42440

Canonical transcript exons

ENST00000491143 — 2 exons

Exon	Start	End
ENSE00001231625	57435374	57436944
ENSE00001948155	57476437	57491298

Expression profiles

Bgee: expression breadth broad, 80 present calls, max score 96.65.

FANTOM5 (CAGE): breadth broad, TPM avg 6.2089 / max 478.4175, expressed in 663 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170360	3.3758	571
170361	2.4208	434
170362	0.2819	131
170363	0.1303	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	96.65	gold quality
pancreatic ductal cell	CL:0002079	89.46	gold quality
duodenum	UBERON:0002114	87.97	gold quality
jejunum	UBERON:0002115	85.47	gold quality
gall bladder	UBERON:0002110	82.72	gold quality
buccal mucosa cell	CL:0002336	79.25	gold quality
liver	UBERON:0002107	78.80	gold quality
islet of Langerhans	UBERON:0000006	76.48	gold quality
middle temporal gyrus	UBERON:0002771	75.89	gold quality
right lobe of liver	UBERON:0001114	75.33	gold quality
vastus lateralis	UBERON:0001379	74.66	gold quality
Brodmann (1909) area 23	UBERON:0013554	74.34	gold quality
epithelial cell of pancreas	CL:0000083	74.08	gold quality
triceps brachii	UBERON:0001509	73.91	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	73.72	gold quality
gluteal muscle	UBERON:0002000	73.50	gold quality
diaphragm	UBERON:0001103	73.24	gold quality
trigeminal ganglion	UBERON:0001675	73.04	gold quality
quadriceps femoris	UBERON:0001377	72.76	gold quality
olfactory bulb	UBERON:0002264	72.46	gold quality
type B pancreatic cell	CL:0000169	72.43	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	72.40	gold quality
dorsal root ganglion	UBERON:0000044	71.43	gold quality
putamen	UBERON:0001874	71.14	gold quality
mucosa of paranasal sinus	UBERON:0005030	70.30	gold quality
caudate nucleus	UBERON:0001873	70.21	gold quality
cerebellar vermis	UBERON:0004720	69.62	gold quality
endometrium epithelium	UBERON:0004811	69.29	gold quality
pancreas	UBERON:0001264	69.03	gold quality
frontal pole	UBERON:0002795	68.01	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	1852.77
E-GEOD-137537	yes	1081.65
E-MTAB-8495	yes	988.02
E-HCAD-56	yes	750.98
E-GEOD-75140	yes	285.68
E-GEOD-83139	yes	12.56
E-ANND-3	yes	9.39
E-CURD-53	no	1087.39

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
ADA	Unknown
MITF	Activation
SYTL4	Repression
TBX21

JASPAR motifs

Motif	Name	Family
MA0756.1	ONECUT2	HD-CUT
MA0756.2	ONECUT2	HD-CUT
MA0756.3	ONECUT2	HD-CUT

JASPAR matrix evidence (PMIDs): PMID:8887657

Upstream regulators (CollecTRI, top): TBX21

miRNA regulators (miRDB)

791 targeting ONECUT2, 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-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-200B-3P	100.00	73.31	2693

Literature-anchored findings (GeneRIF, showing 17)

• A CpG island proximal to ONECUT2 is frequently methylated in diffuse large B-cell lymphoma (DLBCL). (PMID:18288132)
• OC2 transcription factor is a direct target of T-bet in type-1 T-helper cells. (PMID:18418398)
• Mutations at the -5/-6 site of the F9 promotor account for the majority of hemophilia B Leyden cases and disrupt the binding of ONECUT1 and ONECUT2. (PMID:23472758)
• our data showed that transcript factor Onecut2 is involved in the EMT, migration and invasion of CRC cells; miR-429 inhibits the initiation of EMT and regulated expression of EMT-related markers (PMID:24402783)
• Data show that ONECUT2, IGF2BP1, and ANXA2 proteins were confirmed to be microRNA-9 (miR-9) targets and aberrantly upregulated in hepatocellular carcinoma (HCC). (PMID:26547929)
• Bioinformatics-based prediction, combined with qRT-PCR analysis and Western blotting, identified Onecut2 and SIRT1 as the 2 prominent miR-9 target genes under the conditions tested. In this study, Onecut2 and SIRT1 were confirmed as miR-9 target genes, which will help future investigations to probe in greater detail the role of miR-9 in Nonalcoholic Fatty Liver Disease. (PMID:27756894)
• Here we identify the transcription factor ONECUT2 (OC2) as a master regulator of AR networks in metastatic castration-resistant prostate cancer (mCRPC). OC2 acts as a survival factor in mCRPC models, suppresses the AR transcriptional program by direct regulation of AR target genes and the AR licensing factor FOXA1, and activates genes associated with neural differentiation and progression to lethal disease. (PMID:30478421)
• ONECUT2 activates SMAD3, which regulates hypoxia signaling through modulating HIF1alpha chromatin-binding, leading neuroendocrine prostate cancers to exhibit higher degrees of hypoxia compared to prostate adenocarcinomas. (PMID:30655535)
• Data show that chromatin regions that contain the ONECUT motif were in- or lowly accessible in fibroblasts and became accessible after the overexpression of ONECUT1, ONECUT2 or ONECUT3. (PMID:31049588)
• Chemotherapy induced breast cancer cells to secrete multiple EV miRNAs, including miR-9-5p, miR-195-5p, and miR-203a-3p, which simultaneously targeted the transcription factor One Cut Homeobox 2 (ONECUT2), leading to induction of CSC traits and expression of stemness-associated genes. (PMID:31118200)
• ONECUT2 overexpression promotes RAS-driven lung adenocarcinoma progression. (PMID:31882655)
• ONECUT2 upregulation is associated with CpG hypomethylation at promoter-proximal DNA in gastric cancer and triggers ACSL5. (PMID:32129880)
• Up-regulated ONECUT2 and down-regulated SST promote gastric cell migration, invasion, epithelial-mesenchymal transition and tumor growth in gastric cancer. (PMID:33015779)
• ONECUT2 which is targeted by hsa-miR-15a-5p enhances stemness maintenance of gastric cancer stem cells. (PMID:34365839)
• LncRNA TM1-3P Regulates Proliferation, Apoptosis and Inflammation of Fibroblasts in Osteoarthritis through miR-144-3p/ONECUT2 Axis. (PMID:36178080)
• MicroRNA-1298-3p induces tumor-suppressive effects in human cervical cancer cells via post-transcriptional suppression of ONECUT2. (PMID:36508388)
• Increased ONECUT2 induced by Helicobacter pylori promotes gastric cancer cell stemness via an AKT-related pathway. (PMID:38997271)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	onecut2	ENSDARG00000090387
mus_musculus	Onecut2	ENSMUSG00000045991
rattus_norvegicus	Onecut2	ENSRNOG00000052665
drosophila_melanogaster	onecut	FBGN0028996
caenorhabditis_elegans		WBGENE00000444
caenorhabditis_elegans		WBGENE00000459
caenorhabditis_elegans		WBGENE00000460
caenorhabditis_elegans		WBGENE00015934
caenorhabditis_elegans		WBGENE00017538

Paralogs (2): ONECUT1 (ENSG00000169856), ONECUT3 (ENSG00000205922)

Protein

Protein identifiers

One cut domain family member 2 — O95948 (reviewed: O95948)

Alternative names: Hepatocyte nuclear factor 6-beta, One cut homeobox 2, Transcription factor ONECUT-2

All UniProt accessions (1): O95948

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator. Activates the transcription of a number of liver genes such as HNF3B.

Subcellular location. Nucleus.

Similarity. Belongs to the CUT homeobox family.

RefSeq proteins (1): NP_004843* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR003350	CUT_dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR010982	Lambda_DNA-bd_dom_sf	Homologous_superfamily
IPR051649	CUT_Homeobox	Family

Pfam: PF00046, PF02376

UniProt features (26 total): helix 8, sequence conflict 4, region of interest 4, compositionally biased region 3, DNA-binding region 2, strand 2, turn 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8T0F	X-RAY DIFFRACTION	2.61
8T11	X-RAY DIFFRACTION	2.91

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95948-F1	58.97	0.27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 405 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, AHRARNT_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GAANYNYGACNY_UNKNOWN, RORA1_01, GOBP_EPITHELIAL_CELL_DEVELOPMENT, NKX25_02, GOBP_NEUROGENESIS, TAL1ALPHAE47_01, CAGCTG_AP4_Q5

GO Biological Process (17): liver development (GO:0001889), regulation of cell-matrix adhesion (GO:0001952), epithelial cell development (GO:0002064), regulation of transcription by RNA polymerase II (GO:0006357), transforming growth factor beta receptor signaling pathway (GO:0007179), animal organ morphogenesis (GO:0009887), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), endocrine pancreas development (GO:0031018), cell fate commitment (GO:0045165), positive regulation of transcription by RNA polymerase II (GO:0045944), peripheral nervous system neuron development (GO:0048935), cilium assembly (GO:0060271), mesenchymal stem cell migration (GO:1905319), positive regulation of mesenchymal stem cell migration (GO:1905322), anatomical structure morphogenesis (GO:0009653), cell migration (GO:0016477), pancreas development (GO:0031016)

GO Molecular Function (6): 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), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), actin cytoskeleton (GO:0015629)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
animal organ development	2
anatomical structure development	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
gland development	1
hepaticobiliary system development	1
cell-matrix adhesion	1
regulation of cell-substrate adhesion	1
epithelial cell differentiation	1
cell development	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
anatomical structure morphogenesis	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
pancreas development	1
endocrine system development	1
cell differentiation	1
cellular developmental process	1
positive regulation of DNA-templated transcription	1
neuron development	1
peripheral nervous system neuron differentiation	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cell migration	1
positive regulation of cell migration	1
mesenchymal stem cell migration	1
regulation of mesenchymal stem cell migration	1
developmental process	1
cell motility	1

Protein interactions and networks

STRING

1162 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ONECUT2	SYTL4	Q96C24	930
ONECUT2	FOXA2	Q9Y261	748
ONECUT2	RAB27A	P51159	687
ONECUT2	AR	P10275	634
ONECUT2	INS	P01308	533
ONECUT2	CTSK	P43235	525
ONECUT2	OTX1	P32242	521
ONECUT2	ACTL6B	O94805	520
ONECUT2	CTSL	P07711	511
ONECUT2	TCF15	Q12870	506
ONECUT2	DPF1	Q92782	501
ONECUT2	PHF10	Q8WUB8	496
ONECUT2	RFX6	Q8HWS3	472
ONECUT2	CACNA1F	O60840	457
ONECUT2	MTPN	P58546	457

IntAct

3 interactions, top by confidence:

A	B	Type	Score
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (19): ONECUT2 (Affinity Capture-MS), ONECUT2 (Affinity Capture-RNA), ONECUT2 (Affinity Capture-MS), ONECUT2 (Affinity Capture-MS), ONECUT2 (Affinity Capture-MS), ONECUT2 (Proximity Label-MS), ONECUT2 (Proximity Label-MS), ONECUT2 (Proximity Label-MS), ONECUT2 (Proximity Label-MS), ONECUT2 (Affinity Capture-MS), ONECUT2 (Cross-Linking-MS (XL-MS)), ONECUT2 (Affinity Capture-MS), ONECUT2 (Affinity Capture-MS), ONECUT2 (Affinity Capture-MS), ONECUT2 (Affinity Capture-MS)

ESM2 similar proteins: O08755, O16011, O43312, O60422, O77638, O88532, O88942, O95948, P0CL69, P17544, P54288, P70512, P98201, Q01826, Q02930, Q08289, Q08DV5, Q13469, Q3UR85, Q5R9C9, Q5REX3, Q5VTB9, Q60591, Q60611, Q6NT76, Q6P1E1, Q6P9S0, Q6PDX6, Q6UFS5, Q6UUV9, Q6XBJ3, Q765P7, Q7TMA2, Q8BIE6, Q8BJA3, Q8C0V0, Q8CIE2, Q8HXD5, Q8K557, Q8NF64

Diamond homologs: O08755, O14529, O60422, O95948, P70298, P70512, Q04650, Q19720, Q22811, Q22812, Q6XBJ3, Q8K557, Q8TE12, Q9BL02, Q9JKU8, Q9NJB5, Q9UBC0, P34237, P39880, P39881, P53564, P53565, P70403, Q13948, Q5R8V1, P10180, O42115, Q8IA98

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

503 predictions. Top by Δscore:

Variant	Effect	Δscore
18:57436942:CAGG:C	donor_loss	1.0000
18:57436943:AGG:A	donor_loss	1.0000
18:57436946:T:A	donor_loss	1.0000
18:57476435:A:G	acceptor_gain	1.0000
18:57436940:GGCAG:G	donor_gain	0.9900
18:57436941:GCAGG:G	donor_gain	0.9900
18:57476433:CAAGC:C	acceptor_loss	0.9900
18:57476434:A:AG	acceptor_gain	0.9900
18:57476434:AAGC:A	acceptor_gain	0.9900
18:57476435:AG:A	acceptor_loss	0.9900
18:57476435:AGC:A	acceptor_gain	0.9900
18:57476435:AGCGT:A	acceptor_gain	0.9900
18:57476436:G:GG	acceptor_gain	0.9900
18:57476436:GC:G	acceptor_gain	0.9900
18:57476436:GCG:G	acceptor_gain	0.9900
18:57476436:GCGT:G	acceptor_gain	0.9900
18:57476436:GCGTG:G	acceptor_gain	0.9900
18:57436941:GCAG:G	donor_gain	0.9800
18:57476792:G:GT	donor_gain	0.9800
18:57476793:A:T	donor_gain	0.9800
18:57483462:C:G	donor_gain	0.9800
18:57436945:G:GG	donor_gain	0.9700
18:57475489:G:GT	donor_gain	0.9700
18:57475554:G:GT	donor_gain	0.9700
18:57476834:T:G	donor_gain	0.9500
18:57476437:C:CA	acceptor_gain	0.9400
18:57436942:C:T	donor_gain	0.9300
18:57475597:GC:G	donor_gain	0.9300
18:57476726:G:GT	donor_gain	0.9000
18:57476833:A:AG	donor_gain	0.9000

AlphaMissense

3300 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:57436720:C:T	T335I	1.000
18:57436731:G:C	A339P	1.000
18:57436732:C:A	A339D	1.000
18:57436738:G:C	R341P	1.000
18:57436740:A:T	I342F	1.000
18:57436741:T:A	I342N	1.000
18:57436741:T:C	I342T	1.000
18:57436741:T:G	I342S	1.000
18:57436746:G:C	A344P	1.000
18:57436749:G:A	E345K	1.000
18:57436751:G:C	E345D	1.000
18:57436751:G:T	E345D	1.000
18:57436753:T:A	L346Q	1.000
18:57436753:T:C	L346P	1.000
18:57436753:T:G	L346R	1.000
18:57436755:A:G	K347E	1.000
18:57436757:G:C	K347N	1.000
18:57436757:G:T	K347N	1.000
18:57436758:C:A	R348S	1.000
18:57436759:G:C	R348P	1.000
18:57436761:T:G	Y349D	1.000
18:57436764:A:C	S350R	1.000
18:57436766:T:A	S350R	1.000
18:57436766:T:G	S350R	1.000
18:57436767:A:T	I351F	1.000
18:57436768:T:A	I351N	1.000
18:57436768:T:C	I351T	1.000
18:57436768:T:G	I351S	1.000
18:57436770:C:A	P352T	1.000
18:57436770:C:G	P352A	1.000

dbSNP variants (sampled 300 via entrez): RS1000004692 (18:57434927 G>C), RS1000141172 (18:57468289 C>T), RS1000216654 (18:57459836 G>A), RS1000238353 (18:57484371 C>T), RS1000273246 (18:57444158 A>C), RS1000286055 (18:57433699 G>A,T), RS1000349451 (18:57480406 A>G), RS1000440230 (18:57455852 T>C), RS1000444651 (18:57461895 A>G), RS1000453475 (18:57472753 G>A,C), RS1000552359 (18:57440145 T>G), RS1000628589 (18:57448736 A>G), RS1000638317 (18:57472518 A>T), RS1000663926 (18:57443938 A>G), RS1000664144 (18:57490832 T>G)

Disease associations

OMIM: gene MIM:604894 | disease phenotypes: MIM:174050

GenCC curated gene-disease

Mondo (2): autosomal dominant polycystic kidney disease (MONDO:0004691), autosomal dominant polycystic liver disease (MONDO:0000447)

Orphanet (2): Autosomal dominant polycystic kidney disease (Orphanet:730), Isolated polycystic liver disease (Orphanet:2924)

HPO phenotypes

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

HPO	Term
HP:0006557	Polycystic liver disease

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003986_23	Migraine	6.000000e-08
GCST007614_3	C-reactive protein levels	3.000000e-10
GCST90011899_170	Aspartate aminotransferase levels	4.000000e-45
GCST90013406_188	Liver enzyme levels (alkaline phosphatase)	2.000000e-20

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016891	Polycystic Kidney, Autosomal Dominant	C12.050.351.968.419.403.875.500; C12.200.777.419.403.875.500; C12.950.419.403.875.500; C16.131.077.717.500; C16.320.184.625.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	6
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression, decreases expression	2
Estradiol	affects binding, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	affects cotreatment, decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
bisphenol A	increases expression	1
trichostatin A	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation	1
Leflunomide	increases expression	1
Panobinostat	affects cotreatment, affects expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Quercetin	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00414440	PHASE4	COMPLETED	Efficacy, Safety and Tolerability of Everolimus in Preventing End-stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease
NCT03273413	PHASE4	ACTIVE_NOT_RECRUITING	Statin Therapy in Patients With Early Stage ADPKD
NCT03949894	PHASE4	COMPLETED	Evaluating the Safety and effectivenesS in Adult KorEaN Patients Treated With Tolvaptan for Management of Autosomal domInAnt poLycystic Kidney Disease
NCT00309283	PHASE3	COMPLETED	Somatostatin in Polycystic Kidney: a Long-term Three Year Follow up Study
NCT00346918	PHASE3	COMPLETED	Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT00428948	PHASE3	COMPLETED	Tolvaptan Phase 3 Efficacy and Safety Study in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT01022424	PHASE3	COMPLETED	A Long-term Administration Study of OPC-41061 in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) (2) [Extension of Study 156-05-002]
NCT01214421	PHASE3	COMPLETED	Tolvaptan Extension Study in Participants With ADPKD
NCT01377246	PHASE3	COMPLETED	Somatostatin In Patients With Autosomal Dominant Polycystic Kidney Disease And Moderate To Severe Renal Insufficiency
NCT01616927	PHASE3	UNKNOWN	Study of Lanreotide to Treat Polycystic Kidney Disease
NCT01853553	PHASE3	COMPLETED	Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT02115659	PHASE3	UNKNOWN	Triptolide-Containing Formulation as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT02134899	PHASE3	COMPLETED	The Efficacy of Everolimus in Reducing Total Native Kidney Volume in Polycystic Kidney Disease Transplanted Recipients
NCT02160145	PHASE3	COMPLETED	Efficacy and Safety of Tolvaptan in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease
NCT02964273	PHASE3	COMPLETED	Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease)
NCT03764605	PHASE3	UNKNOWN	Metformin vs Tolvaptan for Treatment of Autosomal Dominant Polycystic Kidney Disease
NCT03918447	PHASE3	TERMINATED	A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON
NCT04064346	PHASE3	TERMINATED	Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease
NCT04152837	PHASE3	TERMINATED	Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease
NCT04939935	PHASE3	RECRUITING	Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD)
NCT05373264	PHASE3	RECRUITING	HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life
NCT00841568	PHASE2	COMPLETED	A Long-term Administration Study of OPC-41061 in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) [Extension of Study 156-04-001]
NCT01210560	PHASE2	COMPLETED	Dose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD
NCT01336972	PHASE2	COMPLETED	Short-term Renal Hemodynamic Effects of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT01451827	PHASE2	COMPLETED	8-Week Study of Tolvaptan Dose Forms in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT01670110	PHASE2	COMPLETED	Pasireotide LAR in Severe Polycystic Liver Disease
NCT01932450	PHASE2	UNKNOWN	Radiofrequency Ablation for ADPKD Blood Pressure and Disease Progression Control
NCT02527863	PHASE2	COMPLETED	Effect of the Aquaretic Tolvaptan on Nitric Oxide System
NCT02616055	PHASE2	TERMINATED	Long-Term Treatment and Follow up of Subjects Completing 24 Months of Treatment With Tesevatinib on Study KD019-101
NCT03203642	PHASE2	COMPLETED	Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD
NCT03487913	PHASE2	COMPLETED	The ELiSA Study - Evaluation of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease
NCT03541447	PHASE2	COMPLETED	Tolvaptan-Octreotide LAR Combination in ADPKD
NCT04284657	PHASE2	COMPLETED	Pravastatin and Alkali Therapy in Patients With Autosomal Dominant Polycystic Kidney Disease
NCT04578548	PHASE2	TERMINATED	A Study to Evaluate the Effects of GLPG2737 in Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT05190744	PHASE2	COMPLETED	Probenecid (PB) to Treat Hereditary Nephrogenic Diabetes Insipidus (NDI), ADPKD Treated With Tolvaptan, and Severely Polyuric Patients With Previous Lithium Administration
NCT05870007	PHASE2	ENROLLING_BY_INVITATION	Atorvastatin and Alkali Therapy in Patients With Autosomal Dominant Polycystic Kidney Disease
NCT06100133	PHASE2	UNKNOWN	Treat Autosomal Dominant Polycystic Kidney Disease With Oral Ketone Ester?
NCT06289998	PHASE2	ACTIVE_NOT_RECRUITING	Study of Tamibarotene in Patients With ADPKD
NCT06435858	PHASE2	RECRUITING	Short-term Effects of an SGLT2 Inhibitor on Divalent Ions in Autosomal Dominant Polycystic Kidney Disease
NCT06800651	PHASE2	RECRUITING	Trial of JMKX003142 in Participants With Rapidly Progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD)