DNER

Summary

DNER (delta/notch like EGF repeat containing, HGNC:24456) is a protein-coding gene on chromosome 2q36.3, encoding Delta and Notch-like epidermal growth factor-related receptor (Q8NFT8). Activator of the NOTCH1 pathway.

Predicted to enable Notch binding activity. Involved in central nervous system development. Located in dendrite; early endosome; and plasma membrane.

Source: NCBI Gene 92737 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 151 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_139072

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24456
Approved symbol	DNER
Name	delta/notch like EGF repeat containing
Location	2q36.3
Locus type	gene with protein product
Status	Approved
Aliases	UNQ26, bet
Ensembl gene	ENSG00000187957
Ensembl biotype	protein_coding
OMIM	607299
Entrez	92737

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000341772, ENST00000482831, ENST00000898994, ENST00000898995, ENST00000898996, ENST00000898997, ENST00000898998, ENST00000898999, ENST00000899000, ENST00000965600, ENST00000965601, ENST00000965602, ENST00000965603, ENST00000965604

RefSeq mRNA: 1 — MANE Select: NM_139072 NM_139072

CCDS: CCDS33390

Canonical transcript exons

ENST00000341772 — 13 exons

Exon	Start	End
ENSE00001369002	229588394	229588488
ENSE00001369600	229512783	229512936
ENSE00001370453	229714148	229714555
ENSE00001370514	229418108	229418230
ENSE00001379900	229447316	229447540
ENSE00001380033	229477140	229477253
ENSE00001381270	229546947	229547092
ENSE00001384187	229591580	229591888
ENSE00001390233	229357629	229358651
ENSE00001391125	229366873	229367119
ENSE00001505005	229388265	229388396
ENSE00001505006	229407232	229407345
ENSE00003609520	229585858	229586024

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 99.34.

FANTOM5 (CAGE): breadth broad, TPM avg 12.2313 / max 553.9189, expressed in 730 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34420	11.4439	590
34417	0.4359	187
34419	0.1995	94
34418	0.1521	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	99.34	gold quality
cerebellar vermis	UBERON:0004720	99.32	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.21	gold quality
substantia nigra pars compacta	UBERON:0001965	99.12	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.98	gold quality
parotid gland	UBERON:0001831	98.86	gold quality
subthalamic nucleus	UBERON:0001906	98.73	gold quality
lateral globus pallidus	UBERON:0002476	98.69	gold quality
inferior vagus X ganglion	UBERON:0005363	98.47	gold quality
superior vestibular nucleus	UBERON:0007227	98.44	gold quality
globus pallidus	UBERON:0001875	98.40	gold quality
medulla oblongata	UBERON:0001896	98.39	gold quality
medial globus pallidus	UBERON:0002477	98.30	gold quality
ventral tegmental area	UBERON:0002691	98.20	gold quality
midbrain	UBERON:0001891	98.07	gold quality
substantia nigra	UBERON:0002038	98.03	gold quality
pons	UBERON:0000988	97.94	gold quality
hypothalamus	UBERON:0001898	97.94	gold quality
ventricular zone	UBERON:0003053	97.42	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.36	gold quality
spinal cord	UBERON:0002240	97.33	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.16	gold quality
postcentral gyrus	UBERON:0002581	97.13	gold quality
parietal lobe	UBERON:0001872	96.68	gold quality
amygdala	UBERON:0001876	96.55	gold quality
prefrontal cortex	UBERON:0000451	96.35	gold quality
Ammon’s horn	UBERON:0001954	96.35	gold quality
corpus callosum	UBERON:0002336	96.24	gold quality
right adrenal gland cortex	UBERON:0035827	96.11	gold quality
ganglionic eminence	UBERON:0004023	95.90	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	1654.80
E-HCAD-5	yes	15.76
E-HCAD-10	yes	12.81
E-GEOD-137537	yes	6.07
E-ANND-3	yes	5.56

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1, NEUROG3, NKX6-1, PDX1

miRNA regulators (miRDB)

80 targeting DNER, 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-548C-3P	99.99	74.01	7587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-1303	99.65	69.77	1662

Literature-anchored findings (GeneRIF, showing 23)

• expression in developing and mature central nervous system (PMID:11950833)
• The inhibition of DNER protein resulted in an increase in adipocyte maturation, partly via a reduction of cell proliferation through elevation of CCAAT-Enhancer-Binding Protein-delta expression. (PMID:20070733)
• Our data suggest that clathrin-independent endocytosis is critical for the polarized targeting of somatodendritic proteins(DNER). (PMID:20367751)
• These studies implicate DNER as a susceptibility gene for T2DM in American Indians. (PMID:24101674)
• DNER rs1861612 C to T change and variant T genotype may contribute to T2DM in a Chinese Han population (PMID:25300688)
• we review and discuss the structural biology of BET family BDs and their applications in major diseases. (PMID:27240990)
• is not a Notch ligand (PMID:27622512)
• Collectively, our study identified an unexpected transcriptional repression function of the BET bromodomain and a novel mechanism for TAZ upregulation. (PMID:27717711)
• our findings show that targeting BET proteins for degradation represents an effective therapeutic strategy for Triple-negative breast cancers (TNBC)treatment (PMID:28209615)
• quantum dot-based immunofluorescent imaging and quantitative analytical system (QD-IIQAS) is an easy and accurate method for assessing DNER and the DNER expression was an independent prognostic factor in prostate cancer. (PMID:29843212)
• Taken together, DNER could promote proliferation, migration, and invasion of HCC cells by regulating the activation of PI3K/AKT pathway. (PMID:30235011)
• Synergistic inhibition of BDs encoded in BAZ2A/B, BRD9, and BET proteins induces apoptosis of triple-negative breast cancer (TNBC) by a combinatorial suppression of ribosomal DNA transcription and ETS-regulated genes. (PMID:31000582)
• DNER is a novel protein induced in COPD patients and 6months CS-exposed mice that regulates IFNgamma secretion via non-canonical Notch in pro-inflammatory recruited macrophages. (PMID:31060902)
• PROTAC induced-BET protein degradation exhibits potent anti-osteosarcoma activity by triggering apoptosis. (PMID:31653826)
• These findings are important for all SIRT1 and BET inhibitor-related research, and they show that different BET inhibitors might have important individual effects (PMID:32165310)
• Epigenetic targeting of Waldenstrom macroglobulinemia cells with BET inhibitors synergizes with BCL2 or histone deacetylase inhibition. (PMID:33356554)
• Development of an intracellular quantitative assay to measure compound binding kinetics. (PMID:34520747)
• Repressing MYC by targeting BET synergizes with selective inhibition of PI3Kalpha against B cell lymphoma. (PMID:34688842)
• mTOR inhibition overcomes RSK3-mediated resistance to BET inhibitors in small cell lung cancer. (PMID:36883564)
• Role of Delta/Notch-like EGF-related receptor in blood glucose homeostasis. (PMID:37223028)
• Delta/Notch-like Epidermal Growth Factor-Related Receptor (DNER), a Potential Prognostic Marker of Gastric Cancer Regulates Cell Survival and Cell Cycle Progression. (PMID:37373228)
• BET protein-dependent E2F pathway activity confers bell-shaped type resistance to tankyrase inhibitors in APC-mutated colorectal cancer. (PMID:38216082)
• Co-inhibition of BET and NAE enhances BIM-dependent apoptosis with augmented cancer therapeutic efficacy. (PMID:38588830)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	dner	ENSDARG00000061031
mus_musculus	Dner	ENSMUSG00000036766
rattus_norvegicus	Dner	ENSRNOG00000016640
drosophila_melanogaster	Delta	FBGN0000463
drosophila_melanogaster	Ser	FBGN0004197
caenorhabditis_elegans	paml-2	WBGENE00009114
caenorhabditis_elegans	F55H12.3	WBGENE00010134
caenorhabditis_elegans		WBGENE00013498

Paralogs (5): JAG1 (ENSG00000101384), DLL4 (ENSG00000128917), JAG2 (ENSG00000184916), DLL1 (ENSG00000198719), NOTCH4 (ENSG00000204301)

Protein

Protein identifiers

Delta and Notch-like epidermal growth factor-related receptor — Q8NFT8 (reviewed: Q8NFT8)

All UniProt accessions (1): Q8NFT8

UniProt curated annotations — full annotation on UniProt →

Function. Activator of the NOTCH1 pathway. May mediate neuron-glia interaction during astrocytogenesis.

Subunit / interactions. Interacts with AP1G1. Interacts with NOTCH1.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in brain, spinal cord and adrenal gland.

RefSeq proteins (1): NP_620711* (*=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
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR013032	EGF-like_CS	Conserved_site
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR045769	DNER_C	Domain
IPR051022

Pfam: PF00008, PF12661, PF19330

UniProt features (54 total): disulfide bond 29, domain 11, modified residue 4, region of interest 2, topological domain 2, glycosylation site 2, signal peptide 1, chain 1, transmembrane region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFT8-F1	70.51	0.12

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 (4): 685, 711, 721, 722

Disulfide bonds (29): 48–59, 53–80, 82–91, 98–108, 103–121, 123–132, 319–336, 338–347, 353–364, 358–378, 380–389, 396–407, 401–416, 418–427, 434–445, 439–454, 456–465, 472–482, 477–491, 493–502 …

Glycosylation sites (2): 223, 564

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2122948	Activated NOTCH1 Transmits Signal to the Nucleus

MSigDB gene sets: 186 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, REACTOME_SIGNALING_BY_NOTCH, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_SYNAPSE_ASSEMBLY, GOBP_NOTCH_RECEPTOR_PROCESSING, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, COLIN_PILOCYTIC_ASTROCYTOMA_VS_GLIOBLASTOMA_UP, GOBP_CELL_JUNCTION_ORGANIZATION, MODULE_205

GO Biological Process (9): neuron migration (GO:0001764), endocytosis (GO:0006897), Notch signaling pathway (GO:0007219), Notch receptor processing (GO:0007220), synapse assembly (GO:0007416), central nervous system development (GO:0007417), glial cell differentiation (GO:0010001), skeletal muscle fiber development (GO:0048741), nervous system development (GO:0007399)

GO Molecular Function (5): transmembrane signaling receptor activity (GO:0004888), Notch binding (GO:0005112), calcium ion binding (GO:0005509), clathrin binding (GO:0030276), protein binding (GO:0005515)

GO Cellular Component (5): early endosome (GO:0005769), plasma membrane (GO:0005886), dendrite (GO:0030425), neuronal cell body (GO:0043025), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by NOTCH1	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nervous system development	2
system development	2
cell migration	1
generation of neurons	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
cell surface receptor signaling pathway	1
protein metabolic process	1
cell junction assembly	1
synapse organization	1
cell differentiation	1
gliogenesis	1
skeletal muscle tissue development	1
myotube cell development	1
signaling receptor activity	1
signaling receptor binding	1
metal ion binding	1
protein binding	1
binding	1
endosome	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
somatodendritic compartment	1
cell body	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2096 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNER	ZIC4	Q8N9L1	780
DNER	AMPH	P49418	755
DNER	LGI1	O95970	750
DNER	ARHGAP26	Q9UNA1	738
DNER	DTX1	Q86Y01	727
DNER	PNMA2	Q9UL42	727
DNER	RBPJ	Q06330	697
DNER	DPYSL5	Q9BPU6	694
DNER	IGLON5	A6NGN9	689
DNER	DPP10	Q8N608	672
DNER	BIN1	O00499	671
DNER	DPP6	P42658	666
DNER	CNTNAP2	Q9UHC6	662
DNER	RCVRN	P35243	640
DNER	SOX1	O00570	602

IntAct

12 interactions, top by confidence:

A	B	Type	Score
DNER	PDLIM7	psi-mi:“MI:0915”(physical association)	0.560
DNER	PSEN1	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
CACNA1C	CACNB4	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
DNER	PDLIM7	psi-mi:“MI:0915”(physical association)	0.000
DNER	ZNF24	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	DNER	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): DNER (Affinity Capture-RNA), PDLIM7 (Two-hybrid), DNER (Proximity Label-MS), DNER (Proximity Label-MS), DNER (Two-hybrid), DNER (Affinity Capture-RNA)

ESM2 similar proteins: A0A096LNW5, B8JI71, D3ZHH1, G3I6Z6, O00548, O35516, O57409, P0DPK3, P0DPK4, P35442, P46531, P78504, P97677, Q01705, Q04721, Q05793, Q07008, Q08E66, Q2QI47, Q5G872, Q5ZQU0, Q61483, Q63722, Q66PY1, Q6DI48, Q6NZL8, Q70E20, Q7TQN3, Q7Z3S9, Q8IWY4, Q8IX30, Q8JZM4, Q8K3K1, Q8NFT8, Q8TER0, Q8TEU8, Q8UWJ4, Q8VHS2, Q90Y54, Q90Y57

Diamond homologs: A0A2K5V015, A8X481, B8JI71, P13508, P21956, P70490, P78504, Q5R6R1, Q5T1H1, Q8JZM4, Q8NFT8, Q90Y54, Q9NL29, Q9QXX0, Q9Y219, A2RUV0, A4FV93, B2LW77, D3ZHH1, D3ZUK3, O35474, O70534, O88277, P10041, P21783, P31695, P80370, P97607, Q09163, Q2PZL6, Q5IJ48, Q5ZQU0, Q63722, Q6DCQ6, Q6QNF4, Q6UY11, Q6V0I7, Q70E20, Q8K1E3, Q8TER0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DNER	up-regulates	NOTCH1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	120
Likely benign	7
Benign	10

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
441824	GRCh37/hg19 2q36.3-37.1(chr2:230491213-231404389)x1	Likely pathogenic

SpliceAI

3691 predictions. Top by Δscore:

Variant	Effect	Δscore
2:229358647:CAAAC:C	acceptor_gain	1.0000
2:229358649:AAC:A	acceptor_gain	1.0000
2:229358650:AC:A	acceptor_gain	1.0000
2:229358651:CC:C	acceptor_gain	1.0000
2:229358652:C:CC	acceptor_gain	1.0000
2:229366880:G:A	donor_gain	1.0000
2:229367117:GGT:G	acceptor_gain	1.0000
2:229367118:GTC:G	acceptor_loss	1.0000
2:229367119:TC:T	acceptor_loss	1.0000
2:229367120:C:CA	acceptor_loss	1.0000
2:229367120:C:CC	acceptor_gain	1.0000
2:229367127:C:CT	acceptor_gain	1.0000
2:229388263:A:AC	donor_gain	1.0000
2:229388264:C:CC	donor_gain	1.0000
2:229388264:CGGAT:C	donor_gain	1.0000
2:229407213:AGTC:A	donor_gain	1.0000
2:229447536:GTATC:G	acceptor_gain	1.0000
2:229447537:TATC:T	acceptor_gain	1.0000
2:229447538:ATC:A	acceptor_gain	1.0000
2:229447538:ATCC:A	acceptor_loss	1.0000
2:229447539:TC:T	acceptor_gain	1.0000
2:229447540:CCTG:C	acceptor_gain	1.0000
2:229447541:C:CC	acceptor_gain	1.0000
2:229447541:CT:C	acceptor_loss	1.0000
2:229447542:T:A	acceptor_loss	1.0000
2:229477136:TTACC:T	donor_loss	1.0000
2:229477137:TAC:T	donor_loss	1.0000
2:229477138:A:AT	donor_loss	1.0000
2:229477139:C:CA	donor_loss	1.0000
2:229477139:CCTT:C	donor_gain	1.0000

AlphaMissense

4853 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:229367017:A:C	M653R	0.999
2:229367017:A:T	M653K	0.999
2:229367005:A:G	L657P	0.998
2:229367036:A:G	C647R	0.998
2:229388272:A:C	C616W	0.998
2:229388273:C:A	C616F	0.998
2:229388273:C:G	C616S	0.998
2:229388273:C:T	C616Y	0.998
2:229388274:A:T	C616S	0.998
2:229388333:C:G	C596S	0.998
2:229388334:A:T	C596S	0.998
2:229388366:C:G	C585S	0.998
2:229388367:A:T	C585S	0.998
2:229388388:A:G	C578R	0.998
2:229407335:A:C	C540W	0.998
2:229407336:C:G	C540S	0.998
2:229407336:C:T	C540Y	0.998
2:229407337:A:T	C540S	0.998
2:229418191:C:G	C509S	0.998
2:229418192:A:T	C509S	0.998
2:229418211:A:C	C502W	0.998
2:229418212:C:G	C502S	0.998
2:229418212:C:T	C502Y	0.998
2:229418213:A:T	C502S	0.998
2:229366997:C:G	G660R	0.997
2:229366997:C:T	G660R	0.997
2:229367014:A:G	L654P	0.997
2:229367038:A:T	L646H	0.997
2:229367045:C:G	G644R	0.997
2:229367045:C:T	G644R	0.997

dbSNP variants (sampled 300 via entrez): RS1000005960 (2:229658124 G>C), RS1000006417 (2:229571835 G>A,C,T), RS1000013516 (2:229625929 T>G), RS1000020219 (2:229466880 T>C), RS1000020461 (2:229385520 G>C), RS1000027142 (2:229632718 A>T), RS1000036549 (2:229419931 A>T), RS1000046532 (2:229578394 G>C), RS1000049026 (2:229423976 G>A), RS1000077499 (2:229714542 C>A,T), RS1000088468 (2:229420184 G>A), RS1000089007 (2:229381599 C>A,T), RS1000096623 (2:229578084 G>A), RS1000112801 (2:229686289 C>T), RS1000116329 (2:229527066 G>A)

Disease associations

OMIM: gene MIM:607299 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001784_23	Pulmonary function (smoking interaction)	3.000000e-09
GCST001784_24	Pulmonary function (smoking interaction)	5.000000e-11
GCST002224_1	Type 2 diabetes	7.000000e-08
GCST005830_91	Hand grip strength	4.000000e-13
GCST006585_2772	Blood protein levels	2.000000e-08
GCST009391_2048	Metabolite levels	8.000000e-06
GCST010151_7	Carotid intima media thickness x smoking interaction	8.000000e-06
GCST012483_4	Cerebral amyloid angiopathy in APOEe4 non-carrier Alzheimer’s disease	6.000000e-06
GCST012484_8	Cerebral amyloid angiopathy x APOEe4 status interaction in Alzheimer’s disease	2.000000e-06
GCST012490_27	Femur bone mineral density x serum urate levels interaction	2.000000e-12
GCST012490_566	Femur bone mineral density x serum urate levels interaction	2.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0006941	grip strength measurement
EFO:0010508	malate measurement
EFO:0006527	smoking status measurement
EFO:0007659	APOE carrier status
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5291567 (SINGLE PROTEIN)

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

ChEMBL bioactivities

7 potent at pChembl≥5 of 7 total, top 7 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.85	IC50	142.3	nM	CHEMBL4303293
6.71	IC50	196	nM	CHEMBL4303293
6.51	IC50	310	nM	CHEMBL4303293
6.34	IC50	458.1	nM	CHEMBL4303293
6.30	IC50	500	nM	CHEMBL1957266
6.19	IC50	646.7	nM	CHEMBL4303293
5.16	IC50	6919	nM	CHEMBL4303293

PubChem BioAssay actives

7 with measured affinity, of 10 total; 2 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
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetamide	2196757: Inhibition of BET in bortezomib Resistant human RPMI-8226 cells assessed as reduction of cell growth incubated for 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay	ic50	0.1423	uM
tert-butyl 2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate	1924151: Inhibition of BET (unknown origin)	ic50	0.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation, affects cotreatment	8
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Arsenic	increases expression, affects methylation, affects cotreatment, increases abundance	2
Benzo(a)pyrene	decreases expression, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
domiphen	affects response to substance	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression, increases expression	1
3,4-dichloroaniline	increases expression	1
o,p’-DDT	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	decreases expression	1
cupric chloride	increases expression	1
hydroquinone	decreases expression	1
1-nitropyrene	increases expression	1
3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone	affects response to substance	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5227235	Binding	Inhibition of BET (unknown origin)	Small-Molecule Drug Discovery in Triple Negative Breast Cancer: Current Situation and Future Directions. — J Med Chem

Clinical trials (associated diseases)

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