DENR

Summary

DENR (density regulated re-initiation and release factor, HGNC:2769) is a protein-coding gene on chromosome 12q24.31, encoding Density-regulated protein (O43583). Translation regulator forming a complex with MCTS1 to promote translation reinitiation. It is a selective cancer dependency (DepMap: 89.7% of cell lines).

This gene encodes a protein whose expression was found to increase in cultured cells at high density but not during growth arrest. This gene was also shown to have increased expression in cells overexpressing HER-2/neu proto-oncogene. The protein contains an SUI1 domain. In budding yeast, SUI1 is a translation initiation factor that along with eIF-2 and the initiator tRNA-Met, directs the ribosome to the proper translation start site. Proteins similar to SUI have been found in mammals, insects, and plants.

Source: NCBI Gene 8562 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 26 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 89.7% of screened cell lines
• MANE Select transcript: NM_003677

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2769
Approved symbol	DENR
Name	density regulated re-initiation and release factor
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	DRP, DRP1, SMAP-3
Ensembl gene	ENSG00000139726
Ensembl biotype	protein_coding
OMIM	604550
Entrez	8562

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 retained_intron

ENST00000280557, ENST00000455982, ENST00000537955, ENST00000539463, ENST00000924842, ENST00000963727, ENST00000963728, ENST00000963729, ENST00000963730, ENST00000963731, ENST00000963732, ENST00000963733

RefSeq mRNA: 1 — MANE Select: NM_003677 NM_003677

CCDS: CCDS45003

Canonical transcript exons

ENST00000280557 — 8 exons

Exon	Start	End
ENSE00000996916	122767488	122767604
ENSE00000996917	122765304	122765387
ENSE00000996921	122768782	122768921
ENSE00001120946	122762845	122762929
ENSE00001318047	122769034	122771064
ENSE00001756817	122752824	122752950
ENSE00003489611	122762187	122762206
ENSE00003579737	122753693	122753807

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 70.7332 / max 775.5929, expressed in 1824 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128525	58.8509	1822
128526	10.7734	1748
128527	1.1089	743

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	98.99	gold quality
visceral pleura	UBERON:0002401	98.98	gold quality
parietal pleura	UBERON:0002400	98.95	gold quality
endothelial cell	CL:0000115	98.93	gold quality
pleura	UBERON:0000977	98.87	gold quality
esophagus squamous epithelium	UBERON:0006920	98.74	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.53	gold quality
palpebral conjunctiva	UBERON:0001812	98.51	gold quality
gingival epithelium	UBERON:0001949	98.49	gold quality
tibia	UBERON:0000979	98.47	gold quality
squamous epithelium	UBERON:0006914	98.42	gold quality
tongue squamous epithelium	UBERON:0006919	98.16	gold quality
gingiva	UBERON:0001828	98.08	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.08	gold quality
hair follicle	UBERON:0002073	98.08	gold quality
substantia nigra pars compacta	UBERON:0001965	97.81	gold quality
epithelium of esophagus	UBERON:0001976	97.62	gold quality
biceps brachii	UBERON:0001507	97.59	gold quality
epithelium of nasopharynx	UBERON:0001951	97.55	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.55	gold quality
eye	UBERON:0000970	97.50	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.21	gold quality
oral cavity	UBERON:0000167	97.17	gold quality
amniotic fluid	UBERON:0000173	97.13	gold quality
renal glomerulus	UBERON:0000074	97.07	gold quality
corpus epididymis	UBERON:0004359	97.04	gold quality
seminal vesicle	UBERON:0000998	97.02	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.02	gold quality
mammalian vulva	UBERON:0000997	96.96	gold quality
metanephric glomerulus	UBERON:0004736	96.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.07

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
JAK2	Activation

miRNA regulators (miRDB)

93 targeting DENR, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 89.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• both HuR and AUF1 bind to discrete regions of DENR/DRP mRNA and that AUF1 silencing increases DENR/DRP protein levels. (PMID:17878526)
• DENR binds to the P-site of the 40S ribosomal subunit and together with MCTS1 forms a tRNA binding surface and interfere with eIF1/eIF2/eIF3 binding, thus operating in ribosome recycling and translation re-initiation (PMID:28723557)
• findings elucidate how the DENR-MCT-1 dimer interacts with the ribosome and have functional implications for the mechanism of unconventional translation initiation and reinitiation. (PMID:28723557)
• Reinitiation complexes involving initiation factors eIF2D, MCT-1, and DENR controls the translation of a large fraction of mammalian cellular mRNAs. (PMID:28732596)
• Present the crystal structure of MCTS1 bound to a fragment of DENR. Based on this structure, we identify and experimentally validate that DENR residues Glu42, Tyr43, and Tyr46 are important for MCTS1 binding and that MCTS1 residue Phe104 is important for tRNA binding. Mutation of these residues reveals that DENR-MCTS1 dimerization and tRNA binding are both necessary for DENR and MCTS1 to promote translation reinitiation. (PMID:29889857)
• findings elucidate further the mechanism of regulation of DENR-MCT-1 activities in unconventional translation initiation, reinitiation, and recycling. (PMID:30584092)
• DENR promotes translation reinitiation via ribosome recycling to drive expression of oncogenes including ATF4. (PMID:32938922)
• Cyclin B/CDK1 and Cyclin A/CDK2 phosphorylate DENR to promote mitotic protein translation and faithful cell division. (PMID:35115540)
• To initiate or not to initiate: A critical assessment of eIF2A, eIF2D, and MCT-1.DENR to deliver initiator tRNA to ribosomes. (PMID:38433101)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	denr	ENSDARG00000037229
mus_musculus	Denr	ENSMUSG00000023106
rattus_norvegicus	Denr	ENSRNOG00000001106
drosophila_melanogaster	DENR	FBGN0030802
caenorhabditis_elegans		WBGENE00012932

Protein

Protein identifiers

Density-regulated protein — O43583 (reviewed: O43583)

Alternative names: Protein DRP1, Smooth muscle cell-associated protein 3

All UniProt accessions (2): O43583, F8VVL1

UniProt curated annotations — full annotation on UniProt →

Function. Translation regulator forming a complex with MCTS1 to promote translation reinitiation. Translation reinitiation is the process where the small ribosomal subunit remains attached to the mRNA following termination of translation of a regulatory upstream ORF (uORF), and resume scanning on the same mRNA molecule to initiate translation of a downstream ORF, usually the main ORF (mORF). The MCTS1/DENR complex is pivotal to two linked mechanisms essential for translation reinitiation. Firstly, the dissociation of deacylated tRNAs from post-termination 40S ribosomal complexes during ribosome recycling. Secondly, the recruitment in an EIF2-independent manner of aminoacylated initiator tRNA to P site of 40S ribosomes for a new round of translation. This regulatory mechanism governs the translation of more than 150 genes which translation reinitiation is MCTS1/DENR complex-dependent.

Subunit / interactions. Interacts with MCTS1 (via PUA domain); the complex regulates translation reinitiation.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in heart and skeletal muscle and moderately expressed in the brain, placenta, liver and pancreas. Weakly expressed in the lung and kidney.

Induction. Up-regulated with increasing cell-density by HNRNPD. Up-regulated in ovarian and breast cancer cells by ERBB2 overexpression. Not induced by TGFB1.

Similarity. Belongs to the DENR family.

RefSeq proteins (1): NP_003668* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001950	SUI1	Domain
IPR005873	DENR_eukaryotes	Family
IPR036877	SUI1_dom_sf	Homologous_superfamily
IPR046447	DENR_C	Domain
IPR048517	DENR_N	Domain
IPR050318	DENR/SUI1_TIF	Family

Pfam: PF01253, PF21023

UniProt features (26 total): helix 8, strand 5, modified residue 5, turn 2, initiator methionine 1, chain 1, sequence conflict 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6VPQ	X-RAY DIFFRACTION	1.74
6MS4	X-RAY DIFFRACTION	2
5ONS	X-RAY DIFFRACTION	2.14
6VPR	X-RAY DIFFRACTION	2.2
5VYC	X-RAY DIFFRACTION	6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43583-F1	63.04	0.00

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): 2, 20, 73, 86, 189

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 177 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MODULE_522, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, DARWICHE_SKIN_TUMOR_PROMOTER_DN, GOBP_TRANSLATIONAL_INITIATION, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, CAGCTG_AP4_Q5, GOBP_TRANSLATION, GOBP_FORMATION_OF_TRANSLATION_PREINITIATION_COMPLEX, ROZANOV_MMP14_TARGETS_UP

GO Biological Process (7): formation of translation preinitiation complex (GO:0001731), translation reinitiation (GO:0002188), ribosome disassembly (GO:0032790), IRES-dependent viral translational initiation (GO:0075522), cytoplasmic translational initiation (GO:0002183), translation (GO:0006412), translational initiation (GO:0006413)

GO Molecular Function (2): translation initiation factor activity (GO:0003743), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational initiation	3
cytoplasmic translational initiation	2
protein-RNA complex assembly	1
organelle disassembly	1
viral process	1
viral translation	1
cytoplasmic translation	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
formation of translation initiation ternary complex	1
translation	1
metabolic process	1
translation factor activity	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3584 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DENR	FIS1	Q9Y3D6	995
DENR	MFF	Q9GZY8	994
DENR	MIEF1	Q9NQG6	990
DENR	MIEF2	Q96C03	988
DENR	MCTS1	Q9ULC4	957
DENR	EIF2D	P41214	884
DENR	HCAR1	Q9BXC0	839
DENR	HCAR2	Q8TDS4	829
DENR	HCAR3	P49019	825
DENR	MFN2	O95140	807
DENR	MFN1	Q8IWA4	790
DENR	DNM1L	O00429	720
DENR	NOMO2	Q5JPE7	717
DENR	NOMO3	P69849	715
DENR	BCL2L1	Q07817	715

IntAct

61 interactions, top by confidence:

A	B	Type	Score
DENR	MCTS1	psi-mi:“MI:0915”(physical association)	0.870
MCTS1	DENR	psi-mi:“MI:0914”(association)	0.870
NFKBIA	POLRMT	psi-mi:“MI:0914”(association)	0.670
UBC	DENR	psi-mi:“MI:0915”(physical association)	0.660
DENR	MARCHF5	psi-mi:“MI:0915”(physical association)	0.590
DENR	TMA20	psi-mi:“MI:0915”(physical association)	0.560
MAPT	DENR	psi-mi:“MI:0915”(physical association)	0.560
MAPT	DENR	psi-mi:“MI:0914”(association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
FSD1	UBFD1	psi-mi:“MI:0914”(association)	0.530
CHGA	DENR	psi-mi:“MI:0914”(association)	0.530
NUDT6	DENR	psi-mi:“MI:0914”(association)	0.530
CDK5R1	DENR	psi-mi:“MI:0914”(association)	0.530
USP47	DENR	psi-mi:“MI:0914”(association)	0.530
DENR	NELFB	psi-mi:“MI:0915”(physical association)	0.520
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
	DENR	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (126): DENR (Affinity Capture-MS), DENR (Affinity Capture-MS), DENR (Affinity Capture-MS), DENR (Affinity Capture-MS), DENR (Affinity Capture-MS), DENR (Affinity Capture-MS), DENR (Affinity Capture-MS), DENR (Affinity Capture-MS), DENR (Co-fractionation), EIF2D (Co-fractionation), DENR (Proximity Label-MS), DENR (Two-hybrid), DENR (Affinity Capture-MS), DENR (Affinity Capture-MS), MCTS1 (Affinity Capture-MS)

ESM2 similar proteins: A1C8E3, A1DAY1, A2QHG9, A3GHD3, A3LSY0, A4QVI3, A5DGN9, A5DGV3, A5E3R9, A6SIZ0, A6ZPY2, A7TES6, G0S215, O42929, O43583, P0CR50, P0CR51, P0CR80, P0CR81, P38431, P47089, P55010, P55876, P59325, P93447, Q07205, Q09464, Q09689, Q1E556, Q2H5Z7, Q2HJ47, Q2TVZ2, Q40682, Q4WBL6, Q5R4L0, Q5RFP5, Q5ZJ39, Q6BH22, Q6CA08, Q6CJ30

Diamond homologs: A1C8E3, A1DAY1, A2QHG9, A3LSY0, A4QVI3, A5DGV3, A5E3R9, A6SIZ0, A6ZPY2, A7TES6, O42929, O43583, P0CR80, P0CR81, P47089, Q1E556, Q2H5Z7, Q2HJ47, Q2TVZ2, Q4WBL6, Q54WG0, Q5RFP5, Q5ZJ39, Q6BH22, Q6CA08, Q6CJ30, Q6DFN7, Q6FXQ4, Q75CN1, Q975S0, Q9NAH4, Q9P3T4, Q9VX98, A2BIX0, A8AC05, Q6GLZ1, Q9CQJ6, Q6DH65, P32911, Q4JAE7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MCTS1	“up-regulates activity”	DENR	binding
DENR	“up-regulates quantity by expression”	JAK2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1535 predictions. Top by Δscore:

Variant	Effect	Δscore
12:122753005:G:GT	donor_gain	1.0000
12:122753005:G:T	donor_gain	1.0000
12:122753009:C:G	donor_gain	1.0000
12:122753687:TTACA:T	acceptor_loss	1.0000
12:122753688:TACAG:T	acceptor_loss	1.0000
12:122753689:ACAGG:A	acceptor_loss	1.0000
12:122753690:CAGGT:C	acceptor_loss	1.0000
12:122753692:G:GC	acceptor_loss	1.0000
12:122753692:GGTTT:G	acceptor_gain	1.0000
12:122753812:GT:G	donor_gain	1.0000
12:122762177:A:AG	acceptor_gain	1.0000
12:122762185:A:AG	acceptor_gain	1.0000
12:122762186:G:GA	acceptor_gain	1.0000
12:122762841:CTAGT:C	acceptor_loss	1.0000
12:122762842:TAGTA:T	acceptor_loss	1.0000
12:122762843:A:AG	acceptor_gain	1.0000
12:122762844:G:GA	acceptor_gain	1.0000
12:122762844:GT:G	acceptor_gain	1.0000
12:122762844:GTA:G	acceptor_gain	1.0000
12:122762844:GTAC:G	acceptor_gain	1.0000
12:122762844:GTACT:G	acceptor_gain	1.0000
12:122762926:G:GG	donor_gain	1.0000
12:122765290:A:AG	acceptor_gain	1.0000
12:122765291:C:G	acceptor_gain	1.0000
12:122765296:A:AG	acceptor_gain	1.0000
12:122765297:T:G	acceptor_gain	1.0000
12:122765299:TCTAG:T	acceptor_loss	1.0000
12:122765300:CTAGA:C	acceptor_loss	1.0000
12:122765301:TAGAA:T	acceptor_loss	1.0000
12:122765302:AGAAA:A	acceptor_loss	1.0000

AlphaMissense

1308 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:122753801:T:C	C34R	1.000
12:122753802:G:A	C34Y	1.000
12:122762189:T:C	C37R	1.000
12:122762199:C:A	P40Q	1.000
12:122762848:T:C	C44R	1.000
12:122762849:G:A	C44Y	1.000
12:122762875:T:C	C53R	1.000
12:122762877:T:G	C53W	1.000
12:122762884:T:A	W56R	1.000
12:122762884:T:C	W56R	1.000
12:122762886:G:C	W56C	1.000
12:122762886:G:T	W56C	1.000
12:122765385:G:C	R98T	1.000
12:122765385:G:T	R98I	1.000
12:122765386:A:C	R98S	1.000
12:122765386:A:T	R98S	1.000
12:122767488:G:A	G99D	1.000
12:122767491:G:A	G100E	1.000
12:122767497:G:A	G102D	1.000
12:122767536:T:A	V115D	1.000
12:122767542:T:A	I117K	1.000
12:122767542:T:G	I117R	1.000
12:122767544:G:C	A118P	1.000
12:122767545:C:A	A118D	1.000
12:122767556:A:G	R122G	1.000
12:122767557:G:C	R122T	1.000
12:122767557:G:T	R122I	1.000
12:122767558:A:C	R122S	1.000
12:122767558:A:T	R122S	1.000
12:122767562:A:G	K124E	1.000

dbSNP variants (sampled 300 via entrez): RS1000183997 (12:122755151 C>T), RS1000189425 (12:122752240 GAGAC>G), RS1000323860 (12:122760701 G>A), RS1000794879 (12:122753296 A>G), RS1000890113 (12:122754828 T>C), RS1000988196 (12:122759703 A>G), RS1001052215 (12:122766966 G>T), RS1001380353 (12:122762494 A>C,G), RS1001439894 (12:122756294 C>A,G), RS1001540537 (12:122769311 T>TAA,TAC,TAG), RS1001612259 (12:122763515 G>A), RS1001726965 (12:122763677 G>A), RS1001944581 (12:122764884 C>A), RS1002059075 (12:122765169 C>T), RS1002152945 (12:122753024 G>T)

Disease associations

OMIM: gene MIM:604550 | 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
GCST005412_5	Thrombin-activatable fibrinolysis inhibitor levels	7.000000e-07
GCST010241_397	Apolipoprotein A1 levels	1.000000e-10
GCST90020026_34	Hip index	1.000000e-09
GCST90020028_1251	Hip circumference adjusted for BMI	4.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724775 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.02	Kd	9.571	nM	CHEMBL5653589
8.02	ED50	9.571	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148229: Binding affinity to human DENR incubated for 45 mins by Kinobead based pull down assay	kd	0.0096	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Quercetin	decreases expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
vanadyl sulfate	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Irinotecan	decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Carbamazepine	affects expression	1
Coumestrol	increases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Nickel	increases expression	1
Ribonucleotides	affects binding	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651271	Binding	Binding affinity to human DENR incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1Q1	Abcam HeLa DENR KO	Cancer cell line	Female

Clinical trials (associated diseases)

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