MATN2

Summary

MATN2 (matrilin 2, HGNC:6908) is a protein-coding gene on chromosome 8q22.1-q22.2, encoding Matrilin-2 (O00339). Involved in matrix assembly.

This gene encodes a member of the von Willebrand factor A domain containing protein family. This family of proteins is thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. This protein contains five von Willebrand factor A domains. The specific function of this gene has not yet been determined. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4147 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 147 total
• MANE Select transcript: NM_002380

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6908
Approved symbol	MATN2
Name	matrilin 2
Location	8q22.1-q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000132561
Ensembl biotype	protein_coding
OMIM	602108
Entrez	4147

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 36 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000254898, ENST00000517321, ENST00000518154, ENST00000518238, ENST00000518370, ENST00000519582, ENST00000519585, ENST00000520016, ENST00000520160, ENST00000521041, ENST00000521689, ENST00000521952, ENST00000522025, ENST00000522135, ENST00000522270, ENST00000523490, ENST00000523561, ENST00000524308, ENST00000896675, ENST00000896676, ENST00000896677, ENST00000896678, ENST00000896679, ENST00000896680, ENST00000896681, ENST00000896682, ENST00000896683, ENST00000896684, ENST00000896685, ENST00000921302, ENST00000945049, ENST00000945050, ENST00000945051, ENST00000945052, ENST00000945053, ENST00000945054, ENST00000945055, ENST00000945056, ENST00000945057, ENST00000945058, ENST00000945059, ENST00000945060

RefSeq mRNA: 3 — MANE Select: NM_002380 NM_001317748, NM_002380, NM_030583

CCDS: CCDS55264, CCDS55265, CCDS83309

Canonical transcript exons

ENST00000254898 — 19 exons

Exon	Start	End
ENSE00001224755	97869064	97869287
ENSE00001795904	98035657	98036724
ENSE00003483221	98030462	98030614
ENSE00003505704	98033561	98033659
ENSE00003517284	97961408	97961530
ENSE00003538104	97978886	97979008
ENSE00003555715	97888075	97888242
ENSE00003600638	97941777	97941899
ENSE00003604040	97994480	97994602
ENSE00003606285	98033042	98033176
ENSE00003639014	97930953	97931522
ENSE00003660840	98032246	98032317
ENSE00003890790	98007479	98007601
ENSE00003891208	98021205	98021327
ENSE00003892198	98017994	98018116
ENSE00003892369	98016540	98016662
ENSE00003893210	98007105	98007227
ENSE00003895286	98027416	98027829
ENSE00003895464	98003661	98003783

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.9165 / max 528.2535, expressed in 1151 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89911	11.3239	1084
89915	2.1485	190
89913	0.8347	192
89923	0.2590	109
89918	0.1066	15
89912	0.0770	31
89920	0.0569	6
89914	0.0551	36
89921	0.0197	3
89919	0.0191	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.21	gold quality
trigeminal ganglion	UBERON:0001675	99.20	gold quality
dorsal root ganglion	UBERON:0000044	98.95	gold quality
seminal vesicle	UBERON:0000998	98.78	gold quality
endocervix	UBERON:0000458	98.67	gold quality
calcaneal tendon	UBERON:0003701	98.45	gold quality
cauda epididymis	UBERON:0004360	98.41	gold quality
thyroid gland	UBERON:0002046	98.27	gold quality
right ovary	UBERON:0002118	98.19	gold quality
left lobe of thyroid gland	UBERON:0001120	98.14	gold quality
tibial nerve	UBERON:0001323	98.10	gold quality
sural nerve	UBERON:0015488	98.08	gold quality
myometrium	UBERON:0001296	98.06	gold quality
left ovary	UBERON:0002119	98.04	gold quality
urethra	UBERON:0000057	98.03	gold quality
right lobe of thyroid gland	UBERON:0001119	98.02	gold quality
vena cava	UBERON:0004087	98.00	gold quality
body of uterus	UBERON:0009853	97.98	gold quality
jejunal mucosa	UBERON:0000399	97.87	gold quality
mammary duct	UBERON:0001765	97.41	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.23	gold quality
tendon of biceps brachii	UBERON:0008188	97.02	gold quality
ectocervix	UBERON:0012249	97.00	gold quality
saphenous vein	UBERON:0007318	96.98	gold quality
periodontal ligament	UBERON:0008266	96.92	gold quality
cardiac atrium	UBERON:0002081	96.90	gold quality
skin of hip	UBERON:0001554	96.86	gold quality
right atrium auricular region	UBERON:0006631	96.83	gold quality
corpus epididymis	UBERON:0004359	96.77	gold quality
ovary	UBERON:0000992	96.64	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	38.46
E-HCAD-11	yes	32.49
E-MTAB-8410	yes	23.06
E-MTAB-10287	yes	22.02
E-CURD-46	yes	12.46
E-ANND-3	yes	10.00
E-CURD-10	no	472.75
E-CURD-112	no	3.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting MATN2, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-7157-5P	99.66	69.33	1829

Literature-anchored findings (GeneRIF, showing 17)

• matrilin-2, a filament-forming protein widely distributed in extracellular matrices. (PMID:11852232)
• matrilin-2 is expressed in normal skin by keratinocytes and fibroblasts and may thus contribute to cutaneous homeostasis. (PMID:12164922)
• study of interactions by which matrilin-2 can be integrated into extracellular filamentous networks (PMID:12180907)
• These results suggest that matrilin-2 may be a specific and clinically useful biomarker for discriminating between indolent and clinically aggressive pilocytic astrocytoma. (PMID:16401863)
• DeltaNp63/BMP-7 signaling pathway modulates wound healing process through the regulation of matrilin-2. (PMID:18328806)
• data indicate matrilin-2 is a novel basement membrane component in the liver, synthesized during sinusoidal “capillarization” in cirrhosis & in hepatocellular carcinoma (PMID:18386166)
• Matrilin-2 induces post-burn inflammatory responses as an endogenous danger signal, partly through a TLR4-mediated mechanism (PMID:26271809)
• Taken together, our results showed that high-glucose-induced Matrilin-2 expression that was mediated by the TGF-beta1/Smad3 signaling pathway might play a role in Diabetic nephropathy (DN) pathogenesis and our finding provided a potential diagnostic and/or therapeutic target for DN. (PMID:27105914)
• Data show that the mRNA and protein levels of matrilin-2 were increased after irradiation treatment in both mouse lung tissue and human pulmonary alveolar epithelial cells (HPAEpiC). (PMID:27923659)
• findings showed that YopK binds to the cell surface-exposed endogenous MATN2 and that purified YopK protein strongly inhibits the bacterial adherence to HeLa cells (PMID:28533472)
• miR-202-5p could target MATN2 to induce M2 polarization involved in allergic rhinitis. (PMID:30408806)
• MiR-202-5p/MATN2 are associated with regulatory T-cells differentiation and function in allergic rhinitis. (PMID:31493245)
• Mechanistic Roles of Matrilin-2 and Klotho in Modulating the Inflammatory Activity of Human Aortic Valve Cells. (PMID:32046115)
• Extracellular matrix changes in corneal opacification vary depending on etiology. (PMID:33633437)
• Peritumoral matrilin-2 staining may be useful in distinguishing basal cell carcinoma from folliculocentric basaloid proliferation. (PMID:35274748)
• Low expression of TGF-beta2 and matrilin2 in human aqueous humour with acute primary angle closure. (PMID:38235996)
• MATN2 overexpression suppresses tumor growth in ovarian cancer via PTEN/PI3K/AKT pathway. (PMID:38568332)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Matn2	ENSMUSG00000022324
rattus_norvegicus	Matn2	ENSRNOG00000006060

Paralogs (12): COCH (ENSG00000100473), COL12A1 (ENSG00000111799), MATN4 (ENSG00000124159), MATN3 (ENSG00000132031), MATN1 (ENSG00000162510), COL6A3 (ENSG00000163359), VWA2 (ENSG00000165816), COL6A5 (ENSG00000172752), VWA1 (ENSG00000179403), COL14A1 (ENSG00000187955), VIT (ENSG00000205221), COL6A6 (ENSG00000206384)

Protein

Protein identifiers

Matrilin-2 — O00339 (reviewed: O00339)

All UniProt accessions (10): O00339, A0A140VKH7, E5RJM4, H0YBD5, H0YBF2, H0YBJ4, H0YBM3, H0YBN2, H0YBU5, H0YBV5

UniProt curated annotations — full annotation on UniProt →

Function. Involved in matrix assembly.

Subcellular location. Secreted.

Isoforms (4)

UniProt ID	Names	Canonical?
O00339-1	1, Long	yes
O00339-2	2, Short
O00339-3	3
O00339-4	4

RefSeq proteins (3): NP_001304677, NP_002371, NP_085072 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR002035	VWF_A	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR019466	Matrilin_CC_trimer	Domain
IPR026823	cEGF	Domain
IPR036337	Matrilin_CC_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain
IPR050525	ECM_Assembly_Org	Family

Pfam: PF00092, PF07645, PF10393, PF12662, PF14670

UniProt features (62 total): disulfide bond 30, domain 12, sequence variant 6, sequence conflict 6, splice variant 3, signal peptide 1, chain 1, region of interest 1, coiled-coil region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00339-F1	75.94	0.24

Functional residue map

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

Disulfide bonds (30): 242–253, 249–262, 264–277, 283–294, 290–303, 305–318, 324–335, 331–344, 346–359, 365–376, 372–385, 387–400, 406–417, 413–426, 428–441, 447–458, 454–467, 469–482, 488–499, 495–508 …

Glycosylation sites (1): 221

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 250 (showing top): GOBP_DENDRITE_DEVELOPMENT, JAEGER_METASTASIS_DN, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_RESPONSE_TO_AXON_INJURY, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, BROWNE_HCMV_INFECTION_48HR_DN, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, ROZANOV_MMP14_TARGETS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, DELYS_THYROID_CANCER_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_NEURON_MIGRATION

GO Biological Process (7): neuron migration (GO:0001764), axon guidance (GO:0007411), glial cell migration (GO:0008347), extracellular matrix organization (GO:0030198), dendrite regeneration (GO:0031104), response to axon injury (GO:0048678), neuron projection development (GO:0031175)

GO Molecular Function (3): extracellular matrix structural constituent (GO:0005201), calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), basement membrane (GO:0005604), extracellular matrix (GO:0031012), matrilin complex (GO:0120216)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell migration	2
extracellular matrix	2
generation of neurons	1
axonogenesis	1
neuron projection guidance	1
gliogenesis	1
extracellular structure organization	1
external encapsulating structure organization	1
dendrite development	1
neuron projection regeneration	1
response to wounding	1
neuron development	1
plasma membrane bounded cell projection organization	1
structural molecule activity	1
metal ion binding	1
binding	1
cellular anatomical structure	1
external encapsulating structure	1
non-collagenous component of interstitial matrix	1
extracellular protein-containing complex	1

Protein interactions and networks

STRING

1775 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MATN2	COL8A1	P27658	458
MATN2	ISOC1	Q96CN7	432
MATN2	GNB3	P16520	425
MATN2	GDF10	P55107	423
MATN2	POSTN	Q15063	418
MATN2	NIPAL2	Q9H841	406
MATN2	CST7	O76096	402
MATN2	CLU	P10909	394
MATN2	XPO4	Q9C0E2	392
MATN2	FZD6	O60353	389
MATN2	FGL2	Q14314	385
MATN2	CPQ	Q9Y646	373
MATN2	SPATA17	Q96L03	367
MATN2	C6orf132	Q5T0Z8	366
MATN2	DKK1	O94907	364
MATN2	WNT5A	P41221	364

IntAct

17 interactions, top by confidence:

A	B	Type	Score
SGF29	MATN2	psi-mi:“MI:0914”(association)	0.530
yopK	MATN2	psi-mi:“MI:0915”(physical association)	0.510
MATN2	yopK	psi-mi:“MI:0915”(physical association)	0.510
MATN2	ATXN7	psi-mi:“MI:0915”(physical association)	0.510
MATN2	CACNA1A	psi-mi:“MI:0915”(physical association)	0.510
CACNA1A	MATN2	psi-mi:“MI:0915”(physical association)	0.510
MATN2	CBFA2T3	psi-mi:“MI:0915”(physical association)	0.370
MATN2	DVL3	psi-mi:“MI:0915”(physical association)	0.370
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
NELL1	MATN2	psi-mi:“MI:0914”(association)	0.350
NELL2	MATN2	psi-mi:“MI:0914”(association)	0.350
MATN2	CORO1A	psi-mi:“MI:0914”(association)	0.350
MATN2	IGLL5	psi-mi:“MI:0914”(association)	0.350
CAVIN1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
ATXN1	MATN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (109): MATN2 (Synthetic Lethality), MATN2 (Affinity Capture-MS), MATN2 (Affinity Capture-MS), MATN2 (Affinity Capture-MS), RPL28 (Affinity Capture-MS), RPL7 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), NUFIP2 (Affinity Capture-MS), MAP2K3 (Affinity Capture-MS), RTCB (Affinity Capture-MS), RPL30 (Affinity Capture-MS), RPL27 (Affinity Capture-MS), NPM1 (Affinity Capture-MS), RRP1B (Affinity Capture-MS), NHP2L1 (Affinity Capture-MS)

ESM2 similar proteins: A2AX52, A6H584, A6NMZ7, A6X935, A8TX70, E1BMV3, E7FF10, O00339, O02668, O08746, O55123, O89029, P05099, P06681, P12111, P15989, P19823, P19827, P21180, P21941, P51942, P79263, P97278, P97279, Q0IIH7, Q0V8T0, Q0V8T5, Q0V8T6, Q0V8T7, Q0VCM5, Q14624, Q21540, Q29052, Q3SYW2, Q3T052, Q5GFL6, Q61702, Q61703, Q6DCQ6, Q70UZ7

Diamond homologs: A2AX52, A6H584, A6NMZ7, A6QLN9, A8TX70, E7FF10, O00339, O08746, O42401, O75578, O89029, P05099, P05555, P11215, P12111, P15989, P20701, P20702, P34576, P51942, P61625, Q02388, Q13349, Q21281, Q21540, Q28902, Q3V0T4, Q63870, Q642A6, Q6PCB0, Q6UXI7, Q8C6K9, Q8NFW1, Q8R2Z5, Q90615, Q91145, Q923P0, Q95LI2, Q96P44, Q9P218

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	121
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3461 predictions. Top by Δscore:

Variant	Effect	Δscore
8:97869234:G:GT	donor_gain	1.0000
8:97888073:A:AG	acceptor_gain	1.0000
8:97888074:G:GG	acceptor_gain	1.0000
8:97888074:GCCTT:G	acceptor_gain	1.0000
8:97888241:GG:G	donor_gain	1.0000
8:97888242:GG:G	donor_gain	1.0000
8:97930951:A:AG	acceptor_gain	1.0000
8:97930952:G:GG	acceptor_gain	1.0000
8:97930952:GA:G	acceptor_gain	1.0000
8:97930952:GAGA:G	acceptor_gain	1.0000
8:97931520:GCA:G	donor_gain	1.0000
8:97931523:G:GG	donor_gain	1.0000
8:97941775:A:AG	acceptor_gain	1.0000
8:97941776:G:GA	acceptor_gain	1.0000
8:97941776:GC:G	acceptor_gain	1.0000
8:97941897:G:GT	donor_gain	1.0000
8:97941897:GAA:G	donor_gain	1.0000
8:97941900:G:GG	donor_gain	1.0000
8:97961406:A:AG	acceptor_gain	1.0000
8:97961407:G:GG	acceptor_gain	1.0000
8:97961531:G:GG	donor_gain	1.0000
8:97961532:T:G	donor_loss	1.0000
8:97961533:GAGTA:G	donor_loss	1.0000
8:97961534:AGTAT:A	donor_loss	1.0000
8:97978882:CCAG:C	acceptor_loss	1.0000
8:97978883:CA:C	acceptor_loss	1.0000
8:97978884:A:AG	acceptor_gain	1.0000
8:97978884:AGCT:A	acceptor_gain	1.0000
8:97978885:G:A	acceptor_loss	1.0000
8:97978885:G:GA	acceptor_gain	1.0000

AlphaMissense

6360 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:97930998:A:T	D63V	0.999
8:97931103:T:C	L98P	0.999
8:98027455:A:T	D661V	0.999
8:98027686:T:C	L738P	0.999
8:97930997:G:C	D63H	0.998
8:97930998:A:C	D63A	0.998
8:97931000:A:C	S64R	0.998
8:97931002:C:A	S64R	0.998
8:97931002:C:G	S64R	0.998
8:97931004:C:T	S65F	0.998
8:97931226:C:A	A139D	0.998
8:97931394:G:A	G195D	0.998
8:97931432:G:T	G208W	0.998
8:98027440:T:C	L656P	0.998
8:98027460:T:C	S663P	0.998
8:98027461:C:T	S663F	0.998
8:98027560:T:C	L696P	0.998
8:98030510:T:C	L802P	0.998
8:97930983:T:C	L58P	0.997
8:97930989:T:C	F60S	0.997
8:97930999:C:A	D63E	0.997
8:97930999:C:G	D63E	0.997
8:97931124:T:A	V105D	0.997
8:97931321:G:T	G171W	0.997
8:97931333:G:C	D175H	0.997
8:97941821:T:A	C253S	0.997
8:97941822:G:C	C253S	0.997
8:97941823:C:G	C253W	0.997
8:98027454:G:C	D661H	0.997
8:98027461:C:A	S663Y	0.997

dbSNP variants (sampled 300 via entrez): RS1000008860 (8:98011754 T>C), RS1000014169 (8:97964486 C>A,T), RS1000044644 (8:97876569 T>C), RS1000053604 (8:97870924 C>G), RS1000061800 (8:98011764 C>T), RS1000075481 (8:97918772 G>T), RS1000108863 (8:98012042 T>C), RS1000127396 (8:97873816 C>T), RS1000155868 (8:98017003 A>C), RS1000164807 (8:97920269 G>A,T), RS1000165949 (8:98016737 A>C,G,T), RS1000166130 (8:97970952 A>C,T), RS1000169424 (8:98036306 A>C,G), RS1000183342 (8:97991669 C>G), RS1000206783 (8:97924964 C>T)

Disease associations

OMIM: gene MIM:602108 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001999_3	Adverse response to chemotherapy (neutropenia/leucopenia) (paclitaxel)	2.000000e-06
GCST006956_3	Erectile dysfunction	6.000000e-07
GCST007637_2	Diffusing capacity of carbon monoxide	6.000000e-07
GCST90027899_5	Eosinophilic esophagitis	7.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009369	diffusing capacity of the lung for carbon monoxide

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	6
Valproic Acid	decreases expression, affects expression	5
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, affects expression, decreases expression	4
Estradiol	affects cotreatment, increases expression, decreases expression	3
Aflatoxin B1	decreases expression, increases methylation, affects expression	3
bisphenol A	increases expression, affects cotreatment	2
sodium arsenite	affects cotreatment, increases abundance, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Cisplatin	affects cotreatment, decreases expression, decreases response to substance	2
Copper	affects binding, decreases expression, increases expression	2
Doxorubicin	affects expression, decreases response to substance	2
Progesterone	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression, decreases expression	2
Cyclosporine	decreases expression	2
Paclitaxel	affects cotreatment, decreases expression, decreases response to substance	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
lly-283	increases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
trichostatin A	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
didecyldimethylammonium	decreases expression	1
potassium chromate(VI)	increases expression	1
rutecarpine	decreases expression	1

Clinical trials (associated diseases)

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