ATOH8

Summary

ATOH8 (atonal bHLH transcription factor 8, HGNC:24126) is a protein-coding gene on chromosome 2p11.2, encoding Transcription factor ATOH8 (Q96SQ7). Transcription factor that binds a palindromic (canonical) core consensus DNA sequence 5’-CANNTG- 3’ known as an E-box element, possibly as a heterodimer with other bHLH proteins.

Enables DNA-binding transcription factor activity and E-box binding activity. Involved in several processes, including positive regulation of SMAD protein signal transduction; positive regulation of endothelial cell differentiation; and regulation of gene expression. Located in nucleoplasm.

Source: NCBI Gene 84913 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 71 total — 4 pathogenic
• MANE Select transcript: NM_032827

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24126
Approved symbol	ATOH8
Name	atonal bHLH transcription factor 8
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	HATH6, FLJ14708, bHLHa21
Ensembl gene	ENSG00000168874
Ensembl biotype	protein_coding
OMIM	619820
Entrez	84913

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000306279, ENST00000463422, ENST00000469442, ENST00000473116, ENST00000489682, ENST00000716557, ENST00000881377, ENST00000881378

RefSeq mRNA: 1 — MANE Select: NM_032827 NM_032827

CCDS: CCDS1985

Canonical transcript exons

ENST00000306279 — 3 exons

Exon	Start	End
ENSE00003482799	85763991	85764182
ENSE00003593928	85786885	85791383
ENSE00004030097	85753991	85754957

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 97.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.4154 / max 162.3307, expressed in 1106 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21267	1.5675	740
21262	1.5023	696
21266	0.8303	330
21261	0.6090	345
21269	0.4708	283
21265	0.4657	213
21272	0.3806	119
21264	0.3681	205
21263	0.3563	201
21268	0.2774	173

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	97.14	gold quality
left lobe of thyroid gland	UBERON:0001120	96.94	gold quality
right lung	UBERON:0002167	96.58	gold quality
tibial nerve	UBERON:0001323	96.32	gold quality
thyroid gland	UBERON:0002046	96.17	gold quality
popliteal artery	UBERON:0002250	95.72	gold quality
tibial artery	UBERON:0007610	95.69	gold quality
aorta	UBERON:0000947	95.27	gold quality
thoracic aorta	UBERON:0001515	94.89	gold quality
right atrium auricular region	UBERON:0006631	94.88	gold quality
ascending aorta	UBERON:0001496	94.85	gold quality
apex of heart	UBERON:0002098	94.45	gold quality
left coronary artery	UBERON:0001626	94.42	gold quality
cardiac atrium	UBERON:0002081	94.33	gold quality
decidua	UBERON:0002450	94.05	gold quality
descending thoracic aorta	UBERON:0002345	94.02	gold quality
coronary artery	UBERON:0001621	93.96	gold quality
gastrocnemius	UBERON:0001388	93.93	gold quality
upper lobe of left lung	UBERON:0008952	93.83	gold quality
right coronary artery	UBERON:0001625	93.77	gold quality
upper lobe of lung	UBERON:0008948	93.20	gold quality
muscle of leg	UBERON:0001383	92.68	gold quality
omental fat pad	UBERON:0010414	92.28	gold quality
peritoneum	UBERON:0002358	92.21	gold quality
endocervix	UBERON:0000458	92.11	gold quality
pancreatic ductal cell	CL:0002079	92.03	silver quality
adipose tissue of abdominal region	UBERON:0007808	91.43	gold quality
sural nerve	UBERON:0015488	91.27	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.20	silver quality
hindlimb stylopod muscle	UBERON:0004252	90.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.74

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
FGFR1
HAMP
KRT27
ME3

Upstream regulators (CollecTRI, top): BMP6, HAMP, NEUROG3, SMAD4

miRNA regulators (miRDB)

120 targeting ATOH8, 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-9-5P	100.00	72.28	2361
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-548AZ-5P	99.83	69.94	3230

Literature-anchored findings (GeneRIF, showing 12)

• Data show that in ATOH8 was hosted in one chromosome which is a fusion product of two orthologous chromosomes in non-human. primates. (PMID:21857980)
• Regeneration marker ATOH8 contributes to muscle cell differentiation in healthy and diseased human muscle tissue. (PMID:25514850)
• ATOH8 appears to be a tumor suppressor that induces stem-cell features and chemoresistance in HCC cells. (PMID:26099525)
• calcineurin mediates the subcellular localization of ATOH8, which reveals the regulation of ATOH8 transcriptional activity by calcium signaling via calcineurin. (PMID:26496921)
• These findings raise the possibility that ATOH8 is a pivotal regulator in nasopharyngeal carcinoma tumorigenesis (PMID:27049918)
• Data demonstrated that ATOH8 expression was upregulated in colorectal cancer (CRC) patients, and seems to increase the malignancy potential of CRC. (PMID:28393252)
• Shear stress activates ATOH8 via autocrine VEGF promoting glycolysis dependent-survival of colorectal cancer cells in the circulation. (PMID:32000836)
• A novel isoform of ATOH8 promotes the metastasis of breast cancer by regulating RhoC. (PMID:33049034)
• Long non-coding RNA CIR inhibits chondrogenic differentiation of mesenchymal stem cells by epigenetically suppressing ATOH8 via methyltransferase EZH2. (PMID:33546582)
• ATOH8 binds SMAD3 to induce cellular senescence and prevent Ras-driven malignant transformation. (PMID:36626550)
• ATOH8 promotes HBV immune tolerance by inhibiting the pyroptotic pathway in hepatocytes. (PMID:37232357)
• ATOH8 Expression Is Regulated by BMP2 and Plays a Key Role in Human Endometrial Stromal Cell Decidualization. (PMID:38060684)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	atoh8	ENSDARG00000037555
mus_musculus	Atoh8	ENSMUSG00000037621
rattus_norvegicus	Atoh8	ENSRNOG00000010716
drosophila_melanogaster	net	FBGN0002931

Paralogs (15): NEUROG3 (ENSG00000122859), NEUROD4 (ENSG00000123307), BHLHE23 (ENSG00000125533), NEUROD1 (ENSG00000162992), NEUROD6 (ENSG00000164600), NEUROD2 (ENSG00000171532), ATOH1 (ENSG00000172238), OLIG3 (ENSG00000177468), NEUROG2 (ENSG00000178403), ATOH7 (ENSG00000179774), BHLHA15 (ENSG00000180535), BHLHE22 (ENSG00000180828), NEUROG1 (ENSG00000181965), OLIG1 (ENSG00000184221), OLIG2 (ENSG00000205927)

Protein

Protein identifiers

Transcription factor ATOH8 — Q96SQ7 (reviewed: Q96SQ7)

Alternative names: Class A basic helix-loop-helix protein 21, Helix-loop-helix protein hATH-6, Protein atonal homolog 8

All UniProt accessions (1): Q96SQ7

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that binds a palindromic (canonical) core consensus DNA sequence 5’-CANNTG- 3’ known as an E-box element, possibly as a heterodimer with other bHLH proteins. Regulates endothelial cell proliferation, migration and tube-like structures formation. Modulates endothelial cell differentiation through NOS3. May be implicated in specification and differentiation of neuronal cell lineages in the brain. May participate in kidney development and may be involved in podocyte differentiation. During early embryonic development is involved in tissue-specific differentiation processes that are dependent on class II bHLH factors and namely modulates the differentiation program initiated by the pro-endocrine factor NEUROG3. During myogenesis, may play a role during the transition of myoblasts from the proliferative phase to the differentiation phase. Positively regulates HAMP transcription in two ways, firstly by acting directly on the HAMP promoter via E-boxes binding and indirectly through increased phosphorylation of SMAD protein complex. Repress NEUROG3-dependent gene activation in a gene-specific manner through at least two mechanisms; requires only either the sequestering of a general partner such as TCF3 through heterodimerization, either also requires binding of the bHLH domain to DNA via a basic motif.

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein. Interacts with NEUROG3 and NEUROD1. Interacts with ZFPM2; mediates indirect interaction with GATA4. Forms a heterodimer with TCF3; repress transcription of TCF3 and TCF3/NEUROG3 dimer-induced transactivation of E box-dependent promoters.

Subcellular location. Nucleus. Nucleus speckle. Cytoplasm.

Tissue specificity. Expressed in lung, liver, kidney, heart and pancreas. Expressed in endothel of umbilical vessels.

Domain organisation. The bHLH domain mediates transcriptional repression by inhibiting TCF3 transcriptional activity through heterodimerization.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96SQ7-1	1	yes
Q96SQ7-2	2

RefSeq proteins (1): NP_116216* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR032660	ATOH8_bHLH	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR050359	bHLH_transcription_factors	Family

Pfam: PF00010

UniProt features (13 total): compositionally biased region 5, region of interest 4, chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96SQ7-F1	65.44	0.25

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 172 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GGGACCA_MIR133A_MIR133B, AAGCAAT_MIR137, GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, MYOGENIN_Q6, HNF3ALPHA_Q6, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_DIFFERENTIATION, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GCANCTGNY_MYOD_Q6

GO Biological Process (16): formation of primary germ layer (GO:0001704), negative regulation of endothelial cell proliferation (GO:0001937), nervous system development (GO:0007399), anatomical structure morphogenesis (GO:0009653), positive regulation of endothelial cell migration (GO:0010595), negative regulation of gene expression (GO:0010629), cell differentiation (GO:0030154), tube formation (GO:0035148), positive regulation of endothelial cell differentiation (GO:0045603), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), myoblast proliferation (GO:0051450), positive regulation of SMAD protein signal transduction (GO:0060391), positive regulation of miRNA transcription (GO:1902895), anatomical structure formation involved in morphogenesis (GO:0048646)

GO Molecular Function (8): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription factor activity (GO:0003700), protein dimerization activity (GO:0046983), E-box binding (GO:0070888), DNA-binding transcription factor binding (GO:0140297), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear speck (GO:0016607)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
cellular anatomical structure	3
anatomical structure formation involved in morphogenesis	2
developmental process	2
DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
gastrulation	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
system development	1
anatomical structure development	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
cellular developmental process	1
tube morphogenesis	1
positive regulation of epithelial cell differentiation	1
endothelial cell differentiation	1
regulation of endothelial cell differentiation	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
cell population proliferation	1
regulation of SMAD protein signal transduction	1
SMAD protein signal transduction	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of intracellular signal transduction	1
miRNA transcription	1
regulation of miRNA transcription	1
positive regulation of miRNA metabolic process	1
anatomical structure morphogenesis	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
transcription cis-regulatory region binding	1

Protein interactions and networks

STRING

816 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATOH8	PPP3CB	P16298	512
ATOH8	NEUROD1	Q13562	485
ATOH8	VGLL3	A8MV65	474
ATOH8	OLFML1	Q6UWY5	443
ATOH8	PRRX2	Q99811	437
ATOH8	MRGPRF	Q96AM1	421
ATOH8	COPZ2	Q9P299	421
ATOH8	HES6	Q96HZ4	388
ATOH8	DHRSX	Q8N5I4	384
ATOH8	SRPX2	O60687	373
ATOH8	EFEMP2	O95967	372
ATOH8	FKBP10	Q96AY3	369
ATOH8	TGFB1I1	O43294	368
ATOH8	FEM1B	Q9UK73	360
ATOH8	PTGIS	Q16647	359

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CYP3A5	ATOH8	psi-mi:“MI:0915”(physical association)	0.370
ATOH8	PPP3CB	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (3): ATOH8 (Positive Genetic), ATOH8 (Affinity Capture-MS), CYP3A5 (Two-hybrid)

ESM2 similar proteins: A0A8I5KY20, A2A9T0, A2IDD5, B0BNK9, B8ZZ34, C9JI98, C9JLR9, F5GYI3, O18734, P0CG25, P84157, Q0IIA6, Q0PHV7, Q0X0E2, Q13387, Q1RMK9, Q2M3D2, Q2TAM9, Q3ZCQ3, Q4VA45, Q673H1, Q69YZ2, Q6NS60, Q6P6N5, Q6PJ61, Q7Z6J2, Q80ZJ8, Q810I0, Q86SX3, Q86UD0, Q86XT2, Q8BNN1, Q8IUW3, Q8N4Y2, Q8N6N2, Q8QZV0, Q8R4T5, Q8TF61, Q8VCR9, Q8WXF8

Diamond homologs: A8E5T6, B6VQA1, D2CLZ9, O09029, O09105, O13125, O13126, O16867, O35437, O42202, O42606, O43680, O57598, O60682, O88940, O96642, P13903, P26687, P34555, P41894, P46581, P48985, P48986, P48987, P57102, P59101, P70447, P70595, P70660, P70661, P79765, P79766, P79782, P79920, P97831, Q01664, Q08DI0, Q0V9X5, Q10574, Q13516

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	60
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1526840	GRCh37/hg19 2p12-11.2(chr2:82486900-87322042)	Pathogenic
153632	GRCh38/hg38 2p11.2(chr2:85014686-88826619)x1	Pathogenic
562678	GRCh37/hg19 2p13.1-11.2(chr2:74527522-89125488)x1	Pathogenic
685879	GRCh37/hg19 2p12-11.2(chr2:77907114-87330965)x1	Pathogenic

SpliceAI

872 predictions. Top by Δscore:

Variant	Effect	Δscore
2:85754951:G:GT	donor_gain	1.0000
2:85764180:AAGG:A	donor_loss	1.0000
2:85764183:G:GG	donor_gain	1.0000
2:85754953:AGCAG:A	donor_loss	0.9900
2:85754955:C:T	donor_gain	0.9900
2:85754955:CAGGT:C	donor_loss	0.9900
2:85754956:AGGTA:A	donor_loss	0.9900
2:85754957:GGTAC:G	donor_loss	0.9900
2:85754958:G:T	donor_loss	0.9900
2:85754959:T:G	donor_loss	0.9900
2:85763986:CTCA:C	acceptor_loss	0.9900
2:85763988:CAG:C	acceptor_loss	0.9900
2:85763989:A:AG	acceptor_gain	0.9900
2:85763990:G:GC	acceptor_loss	0.9900
2:85763990:G:GG	acceptor_gain	0.9900
2:85763990:GGT:G	acceptor_gain	0.9900
2:85764163:G:T	donor_gain	0.9900
2:85764178:GCAAG:G	donor_gain	0.9900
2:85764181:AG:A	donor_gain	0.9900
2:85764182:GG:G	donor_gain	0.9900
2:85754954:GCAG:G	donor_gain	0.9800
2:85763989:AG:A	acceptor_gain	0.9800
2:85763990:GG:G	acceptor_gain	0.9800
2:85763989:AGGT:A	acceptor_gain	0.9700
2:85763990:GGTG:G	acceptor_gain	0.9700
2:85763990:GGTGC:G	acceptor_gain	0.9700
2:85754417:GCC:G	donor_gain	0.9500
2:85764180:AAG:A	donor_gain	0.9500
2:85763988:CAGG:C	acceptor_gain	0.9400
2:85764163:G:GT	donor_gain	0.9300

AlphaMissense

2015 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:85754897:C:A	N236K	1.000
2:85754897:C:G	N236K	1.000
2:85754902:G:T	R238M	1.000
2:85754903:G:C	R238S	1.000
2:85754903:G:T	R238S	1.000
2:85754904:G:A	E239K	1.000
2:85754905:A:T	E239V	1.000
2:85754906:G:C	E239D	1.000
2:85754906:G:T	E239D	1.000
2:85754908:G:C	R240P	1.000
2:85754919:C:G	H244D	1.000
2:85754926:T:A	I246N	1.000
2:85754926:T:C	I246T	1.000
2:85754926:T:G	I246S	1.000
2:85754928:A:C	S247R	1.000
2:85754930:C:A	S247R	1.000
2:85754930:C:G	S247R	1.000
2:85754931:G:C	A248P	1.000
2:85754937:T:C	F250L	1.000
2:85754938:T:C	F250S	1.000
2:85754938:T:G	F250C	1.000
2:85754939:C:A	F250L	1.000
2:85754939:C:G	F250L	1.000
2:85754947:T:A	L253H	1.000
2:85754947:T:C	L253P	1.000
2:85754950:G:T	R254M	1.000
2:85763995:C:A	P258Q	1.000
2:85764022:C:A	S267Y	1.000
2:85764022:C:T	S267F	1.000
2:85764024:A:C	K268Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000072961 (2:85789298 A>G,T), RS1000112249 (2:85788048 C>A), RS1000137133 (2:85767528 A>C,T), RS1000175199 (2:85766766 C>T), RS1000196374 (2:85771755 A>G), RS1000232228 (2:85788231 C>T), RS1000248993 (2:85772012 C>A,T), RS1000325452 (2:85783193 G>A), RS1000412145 (2:85756371 G>C), RS1000461230 (2:85760423 C>A), RS1000514534 (2:85760712 T>C), RS1000672681 (2:85773196 C>A,T), RS1000744115 (2:85766433 G>A), RS1000758622 (2:85779104 T>C), RS1000832735 (2:85777367 A>T)

Disease associations

OMIM: gene MIM:619820 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): congenital portosystemic shunt (MONDO:0018811)

Orphanet (1): Congenital portosystemic shunt (Orphanet:480531)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009318_1	Blood metabolite levels	5.000000e-08
GCST009462_33	Optic disc size	9.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004578	homocysteine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, increases expression	3
sodium arsenite	decreases expression	2
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Formaldehyde	decreases expression, increases expression	2
Smoke	increases expression, decreases expression, increases abundance	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	decreases expression, increases expression, increases methylation	2
Nanotubes, Carbon	decreases expression	2
daidzein	affects cotreatment, increases expression	1
bisphenol A	decreases methylation	1
hydroxyhydroquinone	decreases expression	1
daidzin	affects cotreatment, increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	decreases expression	1
ferrous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
cupric chloride	decreases expression	1
genistin	affects cotreatment, increases expression	1
indeno(1,2,3-cd)pyrene	increases expression	1
picene	increases expression	1
glycitein	affects cotreatment, increases expression	1
tebuconazole	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
glycitin	affects cotreatment, increases expression	1
abrine	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06041906	Not specified	ENROLLING_BY_INVITATION	International Registry of Congenital Portosystemic Shunt (IRCPSS)
NCT07314814	Not specified	NOT_YET_RECRUITING	Genetic Hallmarks of Patients With Congenital Portosystemic Shunts and Portopulmonary Hypertension