NR4A1

Summary

NR4A1 (nuclear receptor subfamily 4 group A member 1, HGNC:7980) is a protein-coding gene on chromosome 12q13.13, encoding Nuclear receptor subfamily 4immunitygroup A member 1 (P22736). Orphan nuclear receptor.

This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. Expression is induced by phytohemagglutinin in human lymphocytes and by serum stimulation of arrested fibroblasts. The encoded protein acts as a nuclear transcription factor. Translocation of the protein from the nucleus to mitochondria induces apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3164 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 85 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Transcription factor: yes — 118 downstream targets (CollecTRI)
• MANE Select transcript: NM_173157

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7980
Approved symbol	NR4A1
Name	nuclear receptor subfamily 4 group A member 1
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	TR3, N10, NAK-1, NGFIB, NUR77
Ensembl gene	ENSG00000123358
Ensembl biotype	protein_coding
OMIM	139139
Entrez	3164

Gene structure

Transcript identifiers

Ensembl transcripts: 59 — 48 protein_coding, 8 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000243050, ENST00000360284, ENST00000394824, ENST00000394825, ENST00000478250, ENST00000545748, ENST00000546842, ENST00000547206, ENST00000548232, ENST00000548733, ENST00000548977, ENST00000549102, ENST00000550082, ENST00000550339, ENST00000550557, ENST00000550582, ENST00000550763, ENST00000553200, ENST00000562373, ENST00000564201, ENST00000565848, ENST00000567890, ENST00000850963, ENST00000875309, ENST00000875310, ENST00000875311, ENST00000875312, ENST00000875313, ENST00000875314, ENST00000875315, ENST00000875316, ENST00000875317, ENST00000875318, ENST00000875319, ENST00000875320, ENST00000875321, ENST00000875322, ENST00000875323, ENST00000875324, ENST00000914800, ENST00000914801, ENST00000914802, ENST00000914803, ENST00000914804, ENST00000914805, ENST00000914806, ENST00000914807, ENST00000914808, ENST00000948102, ENST00000948103, ENST00000948104, ENST00000948105, ENST00000948106, ENST00000948107, ENST00000948108, ENST00000948109, ENST00000948110, ENST00000948111, ENST00000948112

RefSeq mRNA: 4 — MANE Select: NM_173157 NM_001202233, NM_001202234, NM_002135, NM_173157

CCDS: CCDS55828, CCDS73471, CCDS8818

Canonical transcript exons

ENST00000394825 — 7 exons

Exon	Start	End
ENSE00003468169	52057057	52057259
ENSE00003550655	52057352	52057530
ENSE00003662635	52056494	52056645
ENSE00003892014	52056030	52056159
ENSE00003892698	52054327	52055204
ENSE00004283044	52058688	52059503
ENSE00004283045	52051442	52051568

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 79.9451 / max 2527.4167, expressed in 1579 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125557	69.8919	1441
125555	4.0752	176
125552	1.5542	747
125553	1.0329	440
125562	0.5686	246
125559	0.5670	239
125561	0.4629	199
125558	0.4315	178
125560	0.3109	148
125567	0.2530	123

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	99.86	gold quality
left uterine tube	UBERON:0001303	99.66	gold quality
gall bladder	UBERON:0002110	99.62	gold quality
left ovary	UBERON:0002119	99.61	gold quality
tibial nerve	UBERON:0001323	99.43	gold quality
popliteal artery	UBERON:0002250	99.43	gold quality
tibial artery	UBERON:0007610	99.43	gold quality
right ovary	UBERON:0002118	99.38	gold quality
omental fat pad	UBERON:0010414	99.28	gold quality
peritoneum	UBERON:0002358	99.23	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.04	gold quality
vena cava	UBERON:0004087	98.98	gold quality
aorta	UBERON:0000947	98.97	gold quality
right atrium auricular region	UBERON:0006631	98.83	gold quality
trachea	UBERON:0003126	98.81	gold quality
adenohypophysis	UBERON:0002196	98.75	gold quality
right lung	UBERON:0002167	98.73	gold quality
ascending aorta	UBERON:0001496	98.70	gold quality
lower esophagus mucosa	UBERON:0035834	98.69	gold quality
upper lobe of left lung	UBERON:0008952	98.57	gold quality
endocervix	UBERON:0000458	98.53	gold quality
cardia of stomach	UBERON:0001162	98.47	gold quality
cardiac atrium	UBERON:0002081	98.47	gold quality
pituitary gland	UBERON:0000007	98.46	gold quality
thoracic aorta	UBERON:0001515	98.41	gold quality
gastrocnemius	UBERON:0001388	98.15	gold quality
coronary artery	UBERON:0001621	98.01	gold quality
left coronary artery	UBERON:0001626	98.01	gold quality
left lobe of thyroid gland	UBERON:0001120	97.96	gold quality
right lobe of thyroid gland	UBERON:0001119	97.95	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	2574.01
E-GEOD-81547	yes	1891.01
E-CURD-119	yes	1700.52
E-CURD-79	yes	808.66
E-ENAD-20	yes	344.68
E-GEOD-89232	yes	324.27
E-HCAD-1	yes	37.72
E-MTAB-10287	yes	35.74
E-GEOD-135922	yes	21.11
E-CURD-122	yes	14.64
E-GEOD-125970	yes	14.39
E-GEOD-137537	yes	6.62
E-MTAB-6678	yes	5.01
E-MTAB-8381	no	2301.57
E-HCAD-29	no	779.53

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

118 targets.

Target	Regulation
ADAM2
ADCYAP1
AKT1
ALDOC	Unknown
APOA2
APOA5	Unknown
APOC3
AR
BABAM2	Repression
BCL2	Activation
BIRC5
CABIN1
CAT
CCL2	Repression
CCL3	Repression
CCNA2	Repression
CCND1	Activation
CCNE1
CDKN1A	Unknown
CDKN1B	Activation
CKM
CNTFR
CNTN2
CPT1A
CRH
CYP11A1	Unknown
CYP11B2
CYP17A1	Unknown
CYP19A1	Repression
CYP21A1P

JASPAR motifs

Motif	Name	Family
MA1112.1	NR4A1	NGFI-B-related receptors (NR4)
MA1112.2	NR4A1	NGFI-B-related receptors (NR4)
MA1112.3	NR4A1	NGFI-B-related receptors (NR4)

JASPAR matrix evidence (PMIDs): PMID:12082103

Upstream regulators (CollecTRI, top): AP1, C1QTNF1, CEBPB, CTNNB1, CTNNBL1, EGR1, ELK1, ESR1, ETS1, FLI1, FOS, HDAC7, HIF1A, IRF6, JUN, JUND, KCNH2, MEF2A, MEF2C, MEF2D, NCOA1, NFKB1, NFKB, NR0B1, NR0B2, NR3C1, PML, RARA, RELA, SP1, SPI1, SRF, TFAP2A

miRNA regulators (miRDB)

50 targeting NR4A1, 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-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-608	98.93	67.83	2013

Literature-anchored findings (GeneRIF, showing 40)

• Hepatitis B virus X protein induced transcription (PMID:11700033)
• We review here recent studies on the glucocorticoid receptor and the orphan receptors Nur77 and RORgamma (PMID:11983153)
• Promyelocytic leukemia protein PML inhibits Nur77-mediated transcription through specific functional interactions. (PMID:12032831)
• Induction of apoptosis by TPA and VP-16 is through induction of TR3 expression and translocation from nucleus to cytosol, which may be a novel signal pathway for TR, and a new biological function to exert its effect on apoptosis in gastric cancer cells. (PMID:12046067)
• upregulation by Wnt-1 (PMID:12153396)
• plays a dual role in selective regulation of apoptosis and cell cycle in gastric cancer cells (PMID:12376465)
• Nur77 drives transcription of PAI-1 through direct binding to an NGFI-B responsive element (NBRE), indicating monomeric binding and a ligand-independent mechanism. Nur77, itself, is transcriptionally up-regulated by TNFalpha. (PMID:12506026)
• TR3 is a modulator of vascular endothelial cell proliferation and arrests endothelial cells in the G1 phase of the cell cycle by influencing cell cycle protein levels. (PMID:12842839)
• TR3 orphan nuclear receptor mediates apoptosis through up-regulating E2F1 in human prostate cancer cells (PMID:12947120)
• TR3/Nur77 translocation from the nucleus may initiate the apoptotic cascade in colon cancer cells by stimulating other cytosolic proapoptotic molecules to associate with mitochondria. (PMID:14500374)
• The genes identified here are novel candidates as key early mediators of VEGF-induced endothelial functions. (PMID:14525795)
• TR3 has a distinct role and functional mode in mediating tretinoin-induced signalling. (PMID:14592536)
• Ectopic expression of TR3 in both H460 and Calu-6 lung cancer cell lines promoted their cell cycle progression and BrdU incorporation. (PMID:14612408)
• In transgenic mice expressing human TR3 orphan receptor, as described in this review, TR3 inhibits formation of smooth muscle cell-rich atherosclerotic lesions. (PMID:14678255)
• Nur77 activated by HIF under hypoxic conditions regulates production of the peptide hormone precursor POMC. (PMID:14729605)
• Nur77, which is regulated by a MAPK pathway activated via arrestin 2, modulates NK(1)R-mediated nonapoptotic programmed cell death (PMID:14769794)
• NUR77 binds to BCL-2 and effects its role and phenotype (PMID:14980220)
• Chenodeoxycholic acid derivative-induced apoptosis of SNU-1 gastric cancer cell lines is mediated by mitochondria and by Nur77. (PMID:15033715)
• P. 743:“Nothern blot analysis of Nur77 mRNA expression revealed that PGF(2alpha) and Butaprost, but not Bimatoprost, induced upregulation of Nur77 mRNA expression in human trabecular meshwork cells.” (PMID:15159280)
• NGFIB plays a crucial role in adrenal zonation by regulating 3beta-hydroxysteriod dehydrogenase 2 gene transcription (PMID:15208301)
• Expression of Nurr1 and NGFI-B plays an important role in human adrenal cortex and its neoplasms, including possible regulation of steroidogenesis. (PMID:15292355)
• Nur77 has a role in the stabilization of HIF-1alpha and in tumor progression and metastasis (PMID:15385570)
• The repressive effect of Nur77 on IL-2 promoter activation is mediated through inhibition of the transcription factor complex nuclear factor-kappaB. (PMID:15466594)
• Causal relationship between the rapid decline of aromatase mRNA and induction of orphan nuclear receptors NURR1 and NGFI-B expression, which concomitantly occur upon LH surge at the later stages of ovarian follicular development. (PMID:15486232)
• RXRalpha is responsible for TR3 nucleocytoplasmic translocation (PMID:15494375)
• Nur77 is an important regulator of HSD3B2 promoter activity (PMID:15498889)
• nongenotropic function of RXRalpha and its involvement in the regulation of the Nur77-dependent apoptotic pathway (PMID:15509776)
• NGFI-B-dependent transcription of proopiomelanocortin gene is antogonized by glucocorticoid receptor. (PMID:15591535)
• Nur77 activation and its apoptotic activity are regulated by small heterodimer partner protein. (PMID:15625237)
• ligand-dependent activation of Nur77 through nuclear pathways induces cell death (PMID:15871945)
• NR4A nuclear receptors NR4A1, NR4A2, NR4A3 are potential transcriptional mediators of inflammatory signals in activated macrophages (PMID:15964844)
• results show that Nur77 can modulate apoptosis through NF-kappaB crosstalk (PMID:16082387)
• Menin’s dynamic regulation of histone modifiers with JunD is responsible for PKC theta-synergistic effect on Nur77 expression in T cell (PMID:16264271)
• Both activation of JNK and inhibition of Akt play a role in translocation of Nur77 from the nucleus to the cytoplasm. mutation of an Akt phosphorylation residue Ser351 in Nur77 abolished the effect of Akt or the PI3-K inhibitor. (PMID:16434970)
• Thus, the human INSL3 promoter constitutes a novel target for the orphan nuclear receptor Nur77. (PMID:16467267)
• Formation of Nur77 nuclear bodies might be involved in programmed cell death modulation upon exposure to DNA damaging agents. (PMID:16480977)
• TR3 represents inhibitory mechanisms to restrict venous SMC proliferation and may contribute to prevention of vein-graft disease (PMID:16723716)
• Interaction of NR4A1 with human papillomavirus type 16 (HPV16) E2 protein may be involved in transcription regulation of HPV16 genes and regulation of infected cell homeostasis. (PMID:16847753)
• Nur77, Nurr1, and NOR-1 are expressed in human atherosclerotic lesion macrophages and reduce human macrophage lipid loading and inflammatory responses, providing further evidence for a protective role of these factors in atherogenesis. (PMID:16873729)
• Nur77 is a physiological binding partner of protein kinase C (PKC) and regulates PKC activity via direct inhibition of its catalytic activity. (PMID:16904076)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nr4a1	ENSDARG00000000796
mus_musculus	Nr4a1	ENSMUSG00000023034
rattus_norvegicus	Nr4a1	ENSRNOG00000007607
drosophila_melanogaster	Hr38	FBGN0014859
caenorhabditis_elegans		WBGENE00003605

Paralogs (2): NR4A3 (ENSG00000119508), NR4A2 (ENSG00000153234)

Protein

Protein identifiers

Nuclear receptor subfamily 4immunitygroup A member 1 — P22736 (reviewed: P22736)

Alternative names: Early response protein NAK1, Nuclear hormone receptor NUR/77, Orphan nuclear receptor HMR, Orphan nuclear receptor TR3, ST-59, Testicular receptor 3

All UniProt accessions (8): P22736, F5GXF0, F8VVX9, H3BPN8, H3BQG5, H3BSB9, H3BSM8, H3BT85

UniProt curated annotations — full annotation on UniProt →

Function. Orphan nuclear receptor. Binds the NGFI-B response element (NBRE) 5’-AAAGGTCA-3’. Binds 9-cis-retinoic acid outside of its ligand-binding (NR LBD) domain. Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation. Regulates the inflammatory response in macrophages by regulating metabolic adaptations during inflammation, including repressing the transcription of genes involved in the citric acid cycle (TCA). Inhibits NF-kappa-B signaling by binding to low-affinity NF-kappa-B binding sites, such as at the IL2 promoter. May act concomitantly with NR4A2 in regulating the expression of delayed-early genes during liver regeneration. Plays a role in the vascular response to injury. In the cytosol, upon its detection of both bacterial lipopolysaccharide (LPS) and NBRE-containing mitochondrial DNA released by GSDMD pores during pyroptosis, it promotes non-canonical NLRP3 inflammasome activation by stimulating association of NLRP3 and NEK7.

Subunit / interactions. Binds the NGFI-B response element (NBRE) as a monomer. Binds the Nur response element (NurRE), consisting of two inverse NBRE-related octanucleotide repeats separated by 6 base-pairs, as a dimer. Interacts (via N-terminus) with NLRP3 (via LRR repeat domain); the interaction is direct, requires binding of NR4A1/Nur77 to NBRE-containing dsDNA and lipopolysaccharide, and leads to non-canonical NLRP3 inflammasome activation. Interacts with GADD45GIP1. Interacts with STK11. Interacts with IFI27. Heterodimer (via DNA-binding domain) with RXRA (via C-terminus); DNA-binding of the heterodimer is enhanced by 9-cis retinoic acid. Competes for the RXRA interaction with EP300 and thereby attenuates EP300 mediated acetylation of RXRA. Interacts with NCOA1. Interacts with NCOA2. Interacts with NCOA3.

Subcellular location. Nucleus. Cytoplasm. Cytosol. Mitochondrion.

Tissue specificity. Fetal muscle and adult liver, brain and thyroid.

Post-translational modifications. Phosphorylated at Ser-351 by RPS6KA1 and RPS6KA3 in response to mitogenic or stress stimuli. Acetylated by p300/CBP, acetylation increases stability. Deacetylated by HDAC1.

Activity regulation. Its transcription factor activity is activated by binding cytosporone B (Csn-B) via its ligand-binding (NR LBD) domain and stimulates recruitment of coactivators NCOA1 and NCOA2, but not NCOA3, to promoters. Csn-B-binding is also accompanied by its translocation to the mitochondrion. Its transcription factor activity is activated by corticotropin-releasing hormone (CRH) and forskolin. Not activated by binding cytosporone C (Csn-C).

Cofactor. Binds 2 zinc ions.

Domain organisation. The NR LBD domain binds the lipid A moiety of lipopolysaccharide (LPS) in the cytosol.

Induction. Induced by cytosporone B (Csn-B); directly stimulates its own expression. Induced by corticotropin-releasing hormone (CRH). Induced by growth-stimulating agents.

Similarity. Belongs to the nuclear hormone receptor family. NR4 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P22736-1	1	yes
P22736-2	2
P22736-3	3

RefSeq proteins (4): NP_001189162, NP_001189163, NP_002126, NP_775180* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR003070	NR4A1-3	Family
IPR003071	NR4A1	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR035500	NHR-like_dom_sf	Homologous_superfamily

Pfam: PF00104, PF00105

UniProt features (53 total): helix 15, region of interest 10, strand 5, mutagenesis site 4, sequence conflict 4, splice variant 3, turn 3, modified residue 2, zinc finger region 2, chain 1, domain 1, compositionally biased region 1, DNA-binding region 1, sequence variant 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
4RZF	X-RAY DIFFRACTION	1.99
3V3E	X-RAY DIFFRACTION	2.06
4REF	X-RAY DIFFRACTION	2.1
4KZJ	X-RAY DIFFRACTION	2.12
4RE8	X-RAY DIFFRACTION	2.16
8Z5A	X-RAY DIFFRACTION	2.18
4WHG	X-RAY DIFFRACTION	2.18
3V3Q	X-RAY DIFFRACTION	2.22
4WHF	X-RAY DIFFRACTION	2.27
4KZM	X-RAY DIFFRACTION	2.3
4REE	X-RAY DIFFRACTION	2.37
9V5K	X-RAY DIFFRACTION	2.37
4KZI	X-RAY DIFFRACTION	2.41
4RZE	X-RAY DIFFRACTION	2.49
9M2E	X-RAY DIFFRACTION	2.58
8WUY	X-RAY DIFFRACTION	2.6
8Y7L	X-RAY DIFFRACTION	2.68
4RZG	X-RAY DIFFRACTION	2.7
2QW4	X-RAY DIFFRACTION	2.8
4JGV	X-RAY DIFFRACTION	3.01
6LC1	X-RAY DIFFRACTION	3.12
6KZ5	X-RAY DIFFRACTION	4.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22736-F1	67.09	0.43

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 (2): 341, 351

Mutagenesis-validated functional residues (4):

Position	Phenotype
1–50	no impact on the interaction with rxra.
299–361	loss of interaction with rxra.
453	abolishes binding to activity regulator cytosporone b.
595	strongly weakens interaction with stk11.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-198693	AKT phosphorylates targets in the nucleus
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-5674400	Constitutive Signaling by AKT1 E17K in Cancer

MSigDB gene sets: 585 (showing top): AHRARNT_01, RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_MUSCLE_TISSUE_DEVELOPMENT, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_CELL_CHEMOTAXIS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_INFLAMMATORY_RESPONSE, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, DORN_ADENOVIRUS_INFECTION_12HR_UP, LFA1_Q6, KEGG_MAPK_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP

GO Biological Process (25): positive regulation of endothelial cell proliferation (GO:0001938), cell migration involved in sprouting angiogenesis (GO:0002042), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), protein import into nucleus (GO:0006606), apoptotic process (GO:0006915), inflammatory response (GO:0006954), signal transduction (GO:0007165), detection of lipopolysaccharide (GO:0032497), endothelial cell chemotaxis (GO:0035767), skeletal muscle cell differentiation (GO:0035914), cellular response to vascular endothelial growth factor stimulus (GO:0035924), macrophage activation (GO:0042116), positive regulation of apoptotic process (GO:0043065), cellular response to fibroblast growth factor stimulus (GO:0044344), fat cell differentiation (GO:0045444), negative regulation of cell cycle (GO:0045786), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of type B pancreatic cell proliferation (GO:0061469), cellular response to corticotropin-releasing hormone stimulus (GO:0071376), non-canonical inflammasome complex assembly (GO:0160075), regulation of DNA-templated transcription (GO:0006355), regulation of gene expression (GO:0010468), intracellular receptor signaling pathway (GO:0030522), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (16): 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), lipopolysaccharide binding (GO:0001530), DNA binding (GO:0003677), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), nuclear glucocorticoid receptor binding (GO:0035259), identical protein binding (GO:0042802), protein heterodimerization activity (GO:0046982), sequence-specific double-stranded DNA binding (GO:1990837), double-stranded DNA binding (GO:0003690), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (10): chromatin (GO:0000785), fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), mitochondrion (GO:0005739), cytosol (GO:0005829), nuclear speck (GO:0016607), nuclear membrane (GO:0031965), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
PIP3 activates AKT signaling	1
Generic Transcription Pathway	1
PI3K/AKT Signaling in Cancer	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
cell differentiation	2
cellular response to growth factor stimulus	2
regulation of transcription by RNA polymerase II	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
DNA binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
sprouting angiogenesis	1
blood vessel endothelial cell migration	1
DNA-templated transcription	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
detection of molecule of bacterial origin	1
response to lipopolysaccharide	1
endothelial cell migration	1
cell chemotaxis	1
skeletal muscle tissue development	1
myeloid leukocyte activation	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
response to fibroblast growth factor	1

Protein interactions and networks

STRING

2568 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NR4A1	BCL2	P10415	985
NR4A1	EP300	Q09472	961
NR4A1	FOS	P01100	860
NR4A1	HDAC2	Q92769	820
NR4A1	JUN	P05412	761
NR4A1	EGR3	Q06889	752
NR4A1	FOSB	P53539	751
NR4A1	SMARCA4	P51532	741
NR4A1	RXRA	P19793	740
NR4A1	EGR1	P18146	721
NR4A1	HSD3B2	P26439	713
NR4A1	PLXND1	Q9Y4D7	695
NR4A1	DUSP12	Q9UNI6	692
NR4A1	HDAC7	Q8WUI4	688
NR4A1	DUSP1	P28562	686

IntAct

171 interactions, top by confidence:

A	B	Type	Score
NR4A1	CDKN2D	psi-mi:“MI:0915”(physical association)	0.670
CDKN2D	NR4A1	psi-mi:“MI:0915”(physical association)	0.670
BCL2	NR4A1	psi-mi:“MI:0915”(physical association)	0.670
BCL2	NR4A1	psi-mi:“MI:0914”(association)	0.670
NR4A1	BCL2	psi-mi:“MI:0915”(physical association)	0.670
NR4A1	BCL2	psi-mi:“MI:0407”(direct interaction)	0.670
	NR4A1	psi-mi:“MI:0407”(direct interaction)	0.650
	NR4A1	psi-mi:“MI:0915”(physical association)	0.650
NR4A1	PRMT1	psi-mi:“MI:0915”(physical association)	0.620
PRMT1	NR4A1	psi-mi:“MI:0915”(physical association)	0.620
NR4A1	IFI27	psi-mi:“MI:0915”(physical association)	0.610
NR4A1	GK	psi-mi:“MI:0915”(physical association)	0.580

BioGRID (279): NR4A1 (Affinity Capture-Western), NR4A1 (Affinity Capture-Western), NR4A1 (Affinity Capture-Western), NR4A1 (Reconstituted Complex), NR4A1 (Two-hybrid), PGBD1 (Two-hybrid), LONRF1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-5 (Two-hybrid), NR4A1 (Protein-peptide), NR4A1 (Affinity Capture-Western), RXRA (Two-hybrid), RXRA (Reconstituted Complex), NR4A1 (Two-hybrid), NR4A1 (Affinity Capture-MS)

ESM2 similar proteins: A1YF56, A2AEV7, A6NCS4, A7Y7W2, D3ZJK7, E1BEA8, F1MUS9, O15534, O35973, O43435, O43638, O60248, O75333, O77728, O94983, O95935, O95947, P22736, P46099, P51666, P56261, P57082, P70325, P70327, Q03484, Q0V8F0, Q15744, Q497V6, Q5DTT2, Q61660, Q61663, Q63HR2, Q64731, Q66JL1, Q6PZD9, Q6ZQN5, Q80Y50, Q810F8, Q861Q9, Q8AV66

Diamond homologs: A0JNE3, A2T928, A4IIG7, G5ECR9, G5EDJ0, O02151, O45666, O76202, O97716, P10276, P10588, P10826, P10827, P10828, P11416, P12813, P13056, P13631, P16376, P18117, P18514, P18515, P18516, P18911, P20153, P22448, P22449, P22605, P22736, P22829, P28699, P31396, P33242, P33244, P41828, P41830, P43354, P45447, P49116, P49117

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
AKT	“down-regulates activity”	NR4A1	phosphorylation
NR3C1	“down-regulates quantity by repression”	NR4A1	“transcriptional regulation”
NR4A1	“down-regulates quantity by repression”	NR3C1	“transcriptional regulation”
MAPK8	down-regulates	NR4A1	phosphorylation
RPS6KA3	unknown	NR4A1	phosphorylation
RPS6KA5	unknown	NR4A1	phosphorylation
AKT1	“down-regulates activity”	NR4A1	phosphorylation
NR4A1	“up-regulates quantity by expression”	HSD3B2	“transcriptional regulation”
TRIM13	“down-regulates quantity by destabilization”	NR4A1	ubiquitination
RARA	“down-regulates quantity by repression”	NR4A1	“transcriptional regulation”
RPS6KA2	“down-regulates activity”	NR4A1	phosphorylation
MAPK1	“up-regulates activity”	NR4A1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
release of cytochrome c from mitochondria	6	49.0×	2e-06
intrinsic apoptotic signaling pathway in response to DNA damage	5	18.8×	1e-03
positive regulation of apoptotic process	10	6.6×	1e-03
protein stabilization	8	6.2×	8e-03
negative regulation of apoptotic process	12	4.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	5
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1201 predictions. Top by Δscore:

Variant	Effect	Δscore
12:52051520:GC:G	donor_gain	1.0000
12:52051564:GCCGG:G	donor_gain	1.0000
12:52051566:CGGGT:C	donor_loss	1.0000
12:52051567:GG:G	donor_gain	1.0000
12:52051568:GG:G	donor_gain	1.0000
12:52051568:GGTAG:G	donor_loss	1.0000
12:52051569:G:GG	donor_gain	1.0000
12:52051570:T:A	donor_loss	1.0000
12:52053866:G:GT	donor_gain	1.0000
12:52053893:G:GT	donor_gain	1.0000
12:52054307:G:A	acceptor_gain	1.0000
12:52054326:GAGA:G	acceptor_gain	1.0000
12:52056024:A:AG	acceptor_gain	1.0000
12:52056025:C:G	acceptor_gain	1.0000
12:52056028:A:AG	acceptor_gain	1.0000
12:52056029:G:GG	acceptor_gain	1.0000
12:52056029:GC:G	acceptor_gain	1.0000
12:52056029:GCGC:G	acceptor_gain	1.0000
12:52056128:G:GT	donor_gain	1.0000
12:52056155:GGAAG:G	donor_gain	1.0000
12:52056156:GAAGG:G	donor_gain	1.0000
12:52056157:A:T	donor_gain	1.0000
12:52056157:AAG:A	donor_loss	1.0000
12:52056158:AG:A	donor_loss	1.0000
12:52056159:GG:G	donor_loss	1.0000
12:52056160:G:GA	donor_loss	1.0000
12:52056161:T:A	donor_loss	1.0000
12:52056489:TGCA:T	acceptor_loss	1.0000
12:52056490:GCA:G	acceptor_loss	1.0000
12:52056492:A:AG	acceptor_gain	1.0000

AlphaMissense

3833 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:52055127:T:A	C267S	1.000
12:52055127:T:C	C267R	1.000
12:52055128:G:A	C267Y	1.000
12:52055128:G:C	C267S	1.000
12:52055128:G:T	C267F	1.000
12:52055129:T:G	C267W	1.000
12:52055133:G:A	V269M	1.000
12:52055134:T:A	V269E	1.000
12:52055136:T:A	C270S	1.000
12:52055136:T:C	C270R	1.000
12:52055137:G:A	C270Y	1.000
12:52055137:G:C	C270S	1.000
12:52055137:G:T	C270F	1.000
12:52055138:T:G	C270W	1.000
12:52055142:G:C	D272H	1.000
12:52055143:A:C	D272A	1.000
12:52055143:A:G	D272G	1.000
12:52055143:A:T	D272V	1.000
12:52055149:C:A	A274D	1.000
12:52055154:T:C	C276R	1.000
12:52055160:C:A	H278N	1.000
12:52055160:C:G	H278D	1.000
12:52055161:A:G	H278R	1.000
12:52055161:A:T	H278L	1.000
12:52055162:T:A	H278Q	1.000
12:52055162:T:G	H278Q	1.000
12:52055163:T:A	Y279N	1.000
12:52055163:T:C	Y279H	1.000
12:52055163:T:G	Y279D	1.000
12:52055164:A:C	Y279S	1.000

dbSNP variants (sampled 300 via entrez): RS1000020621 (12:52033790 A>G), RS1000059956 (12:52051033 C>G,T), RS1000125356 (12:52045614 G>C), RS1000171641 (12:52041093 G>A), RS1000256378 (12:52039722 G>A), RS1000347107 (12:52022867 C>T), RS1000373420 (12:52050647 G>C), RS1000430646 (12:52056360 G>A), RS1000708083 (12:52050821 C>T), RS1000943066 (12:52059710 C>T), RS1001002349 (12:52044142 T>C), RS1001234726 (12:52057758 C>T), RS1001298515 (12:52039141 C>A), RS1001301772 (12:52052098 T>C), RS1001354709 (12:52024138 A>C)

Disease associations

OMIM: gene MIM:139139 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293229 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 136,907 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL509	MECLOFENAMIC ACID	4	45,809
CHEMBL705	ALITRETINOIN	4	39,246
CHEMBL197194	VIDOFLUDIMUS	3	808

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: nhr — 4A. Nerve growth factor IB-like receptors

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 111 [PMID: 37918435]	Agonist	7.4	pEC50
pristimerin	Agonist	6.02	pKd

Binding affinities (BindingDB)

195 measured of 263 human assays (280 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
9-nitro-4-phenyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-6-carboxylic acid	EC50	0.65 nM
2-(2-furanyl)-4-quinolinecarboxylic acid [2-[4-[2-furanyl(oxo)methyl]-1-piperazinyl]-2-oxoethyl] ester	EC50	16.3 nM
4-methylbenzoic acid (4-salicyloylazoanilino) ester	IC50	23 nM
MLS000520023	IC50	23 nM
5-(tosylmethyl)-2-furoic acid	IC50	23 nM
(phenylmethyl) 4-[2-(diethylamino)ethyl]-3,5-dimethyl-1H-pyrrole-2-carboxylate;hydrobromide	IC50	23 nM
(4-acetamidophenyl) 2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetate	IC50	23 nM
2,3-dihydroindol-1-yl(2-pyrazinyl)methanone	IC50	23 nM
(E)-3-amino-2-[1-oxo-2-[[5-(propan-2-ylamino)-1,3,4-thiadiazol-2-yl]thio]ethyl]-2-butenenitrile	IC50	23 nM
3-[2-(hydroximinomethyl)pyrrol-1-yl]benzoic acid	IC50	23 nM
(3R,4S,5S)-2-(6,8-dimethyl-1-pyrrolo[2,3-g]quinolinyl)oxane-3,4,5-triol;hydrochloride	IC50	23 nM
3,4-dihydro-1H-isoquinolin-2-yl-[5-(tosylmethyl)-2-furyl]methanone	IC50	23 nM
MLS000520024	IC50	23 nM
3,4-diethoxybenzoic acid [2-(2-furanylmethylamino)-2-oxoethyl] ester	IC50	113 nM
MLS000068439	IC50	121 nM
MLS000119803	IC50	326 nM
3-(2-Chloro-acetyl)-8-methyl-1,2,3,3a,4,5-hexahydro-3,10b-diaza-acephenanthrylen-6-one	IC50	348 nM
5-(2,5-dimethyl-1-pyrrolyl)benzene-1,3-dicarboxylic acid	EC50	540 nM
3-bromanyl-4-ethoxy-N-[4-(4-methylpiperazin-1-yl)phenyl]benzamide	IC50	558 nM
2-(2,5-dimethyl-1-pyrrolyl)benzoic acid	EC50	620 nM
7-[3-(dimethylamino)propylamino]-2-methyl-14H-naphtho[3,2-a]phenoxazine-8,13-dione	EC50	670 nM
2-(7-chloranyl-2-oxidanylidene-5-phenyl-3H-1,4-benzodiazepin-1-yl)-N-[4-(dimethylamino)phenyl]ethanamide	IC50	856 nM
5-chloranyl-2-(2,5-dimethylpyrrol-1-yl)benzoic acid	EC50	940 nM
2-(2-furanyl)-N-[2-(4-morpholinyl)phenyl]-4-quinolinecarboxamide	IC50	1040 nM
BIM-0015619.P001	EC50	1050 nM
2-[2-oxidanylidene-2-[2-[(Z)-(3-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)methyl]hydrazinyl]ethoxy]-N’’-[(Z)-(3-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)methyl]benzohydrazide	IC50	1070 nM
6-nitro-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	EC50	1200 nM
BIM-0022140.P001	EC50	1350 nM
2-[[5-(1,3-benzothiazol-2-ylsulfanylmethyl)-4-ethyl-1,2,4-triazol-3-yl]sulfanyl]-1-(3,4-dihydroxyphenyl)ethanone	IC50	1520 nM
1-(3,4-dihydroxyphenyl)-2-[[5-(2-methoxyphenyl)-4-prop-2-enyl-1,2,4-triazol-3-yl]sulfanyl]ethanone	IC50	1550 nM
MLS000561572	IC50	1560 nM
2-(4-chlorophenyl)sulfanyl-1-(furan-2-yl)ethanone	IC50	1560 nM
6-Methyl-2-[5-(2-nitro-phenyl)-[1,3,4]oxadiazol-2-yl]-thieno[2,3-b]quinolin-3-ylamine	IC50	1630 nM
4-(5-{[(5E)-2-amino-3,7-dicyano-4,6-dimethyl-5H-cyclopenta[b]pyridin-5-ylidene]methyl}furan-2-yl)-2-chlorobenzoic acid	EC50	1650 nM
BIM-0020349.P001	EC50	1680 nM
4-(3-nitrophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-carboxylic acid	EC50	1750 nM
5,6-dihydro-4H-cyclopenta[b]thiophene-2-carboxylic acid [2-[(1,1-diketothiolan-3-yl)-isobutyl-amino]-2-keto-ethyl] ester	IC50	1910 nM
2-(5,6-Di-furan-2-yl-[1,2,4]triazin-3-ylsulfanyl)-N-o-tolyl-acetamide	IC50	1980 nM
2-(5,6-dihydro-4H-cyclopent[d]isoxazole-3-carbonylamino)benzoic acid methyl ester	IC50	2180 nM
2-[[5,6-bis(2-furanyl)-1,2,4-triazin-3-yl]thio]-N-phenylacetamide	IC50	2250 nM
6-(4-fluorobenzyl)-2-(2-furfurylidene)thiazolo[3,2-b][1,2,4]triazine-3,7-quinone	IC50	2350 nM
(3aR,6aS)-3-(2-chlorophenyl)-5-(2,5-dimethoxyphenyl)-3a,6a-dihydropyrrol[3,4-d]isoxazole-4,6-quinone	IC50	2490 nM
2-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-4-(3-ethoxy-4-hydroxybenzylidene)-5-phenyl-2,4-dihydro-3H-pyrazol-3-one	IC50	2540 nM
4-Amino-benzoic acid [5-(3,4-dimethyl-phenylazo)-2-hydroxy-benzylidene]-hydrazide	IC50	2620 nM
4-(2,3-dichlorophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-6-carboxylic acid	EC50	2670 nM
2-[(3Z)-2-oxidanylidene-3-[4-oxidanylidene-3-prop-2-enyl-2-(1,3-thiazol-2-ylimino)-1,3-thiazolidin-5-ylidene]indol-1-yl]ethanoic acid	IC50	2780 nM
BIM-0015618.P001	EC50	2950 nM
MLS000053522	IC50	2960 nM
6-bromanyl-2-(5-methylfuran-2-yl)quinoline-4-carboxylic acid	IC50	2980 nM
2-[[5,6-bis(2-furanyl)-1,2,4-triazin-3-yl]thio]-N-(4-methylphenyl)acetamide	IC50	3010 nM

ChEMBL bioactivities

121 potent at pChembl≥5 of 263 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.94	EC50	0.115	nM	CYTOSPORONE B
9.56	EC50	0.278	nM	CYTOSPORONE B
7.48	Kd	33	nM	CHEMBL4867199
7.44	Kd	36	nM	CHEMBL4857769
7.40	EC50	40	nM	CHEMBL5427562
7.40	EC50	40	nM	CHEMBL6175985
7.18	Kd	66	nM	CHEMBL4857769
7.18	Kd	66	nM	CHEMBL4867199
7.04	Kd	91	nM	CHEMBL5413288
6.96	Kd	110	nM	CHEMBL4877512
6.92	Kd	121	nM	CHEMBL5269226
6.85	EC50	140	nM	CHEMBL5405485
6.81	Kd	154	nM	CHEMBL5413288
6.66	Kd	220	nM	CHEMBL3417313
6.66	Kd	217	nM	CHEMBL4877512
6.57	Kd	270	nM	CHEMBL3980631
6.54	Kd	290	nM	CELASTROL
6.50	Kd	320	nM	CELASTROL
6.45	Kd	354	nM	CHEMBL5269226
6.45	Kd	354	nM	CHEMBL5398492
6.32	EC50	480	nM	CHEMBL1380619
6.31	IC50	492.6	nM	CHEMBL1381627
6.28	Kd	520	nM	CHEMBL3892041
6.27	EC50	540	nM	CHEMBL1447046
6.25	IC50	558.1	nM	CHEMBL1575787
6.21	EC50	620	nM	CHEMBL1332168
6.17	EC50	670	nM	CHEMBL1313070
6.14	Kd	720	nM	CHEMBL4459092
6.14	Kd	720	nM	CYTOSPORONE B
6.14	IC50	725.2	nM	CHEMBL1566165
6.13	Kd	740	nM	CYTOSPORONE B
6.11	IC50	783.4	nM	CHEMBL1504655
6.10	Kd	800	nM	CHEMBL3417314
6.09	Kd	810	nM	ALITRETINOIN
6.08	Kd	830	nM	CHEMBL3928971
6.06	Kd	870	nM	DIHYDROCELASTROL
6.03	EC50	940	nM	CHEMBL213849
6.02	Kd	960	nM	PRISTIMERIN
6.02	IC50	963.5	nM	CHEMBL1432963
6.00	EC50	1000	nM	CHEMBL1380619
5.99	EC50	1030	nM	CHEMBL1363824
5.98	EC50	1050	nM	CHEMBL1374488
5.97	IC50	1076	nM	CHEMBL1334633
5.97	IC50	1070	nM	CHEMBL1979849
5.95	IC50	1126	nM	CHEMBL213432
5.93	Kd	1170	nM	CHEMBL5279866
5.93	Kd	1170	nM	CHEMBL5419963
5.92	EC50	1200	nM	CHEMBL1556434
5.87	Kd	1340	nM	CHEMBL4795792
5.87	EC50	1350	nM	CHEMBL1411127

PubChem BioAssay actives

54 with measured affinity, of 254 total; 38 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
ethyl 2-(3,5-dihydroxy-2-octanoylphenyl)acetate	1925155: Inhibition of Gal4-fused Nur77-LBD in human BGC-823 cells	ec50	0.0001	uM
(3Z)-3-[1H-indol-3-yl-[4-(trifluoromethyl)phenyl]methylidene]-1-methylindol-1-ium;methanesulfonate	1760859: Binding affinity to recombinant human N-terminal His-tagged Nur77-LBD (367 to 598 residues) expressed in Escherichia coli BL21 DE3 by surface plasmon resonance assay	kd	0.0330	uM
(3Z)-1-ethyl-3-[1H-indol-3-yl-[4-(trifluoromethyl)phenyl]methylidene]indol-1-ium chloride	1760859: Binding affinity to recombinant human N-terminal His-tagged Nur77-LBD (367 to 598 residues) expressed in Escherichia coli BL21 DE3 by surface plasmon resonance assay	kd	0.0360	uM
3-[(2,4-dichlorophenyl)methoxy]benzoic acid	2037846: Agonist activity at human Nur77 LBD transiently transfected in HEK293T cells incubated for 16 hrs by Gal4-hybrid reporter gene based Dual-glo luciferase assay	ec50	0.0400	uM
N-[3-(diethylamino)propyl]-5-[[4-[4-methyl-2-(methylamino)-1,3-thiazol-5-yl]pyrimidin-2-yl]amino]-1H-indole-2-carboxamide	1992412: Binding affinity to His-tagged Nur77 ligand binding domain (unknown origin) by surface plasmon resonance assay	kd	0.0910	uM
3-[(Z)-indol-1-ium-3-ylidene-[4-(trifluoromethyl)phenyl]methyl]-1H-indole;methanesulfonate	1760859: Binding affinity to recombinant human N-terminal His-tagged Nur77-LBD (367 to 598 residues) expressed in Escherichia coli BL21 DE3 by surface plasmon resonance assay	kd	0.1100	uM
N-[3-(dimethylamino)propyl]-5-[(4-pyridin-3-ylpyrimidin-2-yl)amino]-1H-indole-2-carboxamide	1946181: Binding affinity to Nur77 ligand binding domain (unknown origin) by fluorescence quenching assay	kd	0.1210	uM
3-[(4-tert-butylphenyl)methoxy]benzoic acid	2037846: Agonist activity at human Nur77 LBD transiently transfected in HEK293T cells incubated for 16 hrs by Gal4-hybrid reporter gene based Dual-glo luciferase assay	ec50	0.1400	uM
ethyl (2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylate	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	0.2200	uM
(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-N-propyl-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxamide	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	0.2700	uM
(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylic acid	1597524: Binding affinity to purified Nur77 LBD (unknown origin) by SPR analysis	kd	0.2900	uM
N-[3-(dimethylamino)propyl]-6-[(4-pyridin-3-ylpyrimidin-2-yl)amino]-1H-indole-2-carboxamide	1992412: Binding affinity to His-tagged Nur77 ligand binding domain (unknown origin) by surface plasmon resonance assay	kd	0.3540	uM
propan-2-yl (2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylate	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	0.5200	uM
(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carbonyl fluoride	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	0.7200	uM
(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-N,2,4a,6a,6a,9,14a-heptamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxamide	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	0.8000	uM
alitretinoin	500645: Binding affinity to Nur77 Y453A mutant expressed in human BGC823 cells	kd	0.8100	uM
(2R,4aS,6aR,6aS,14aS,14bR)-N-ethyl-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxamide	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	0.8300	uM
(2R,4aS,6aS,6aS,14aS,14bR)-10,11-dihydroxy-2,4a,6a,6a,9,14a-hexamethyl-3,4,5,6,8,13,14,14b-octahydro-1H-picene-2-carboxylic acid	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	0.8700	uM
methyl (2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylate	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	0.9600	uM
N-[(E)-pyridin-4-ylmethylideneamino]-4-(quinolin-4-ylamino)benzamide	1992412: Binding affinity to His-tagged Nur77 ligand binding domain (unknown origin) by surface plasmon resonance assay	kd	1.1700	uM
N-[(E)-pyridin-4-ylmethylideneamino]-5-(quinolin-4-ylamino)-1H-indole-2-carboxamide	1946222: Binding affinity to Nur77 (unknown origin)	kd	1.1700	uM
5-[(8-methoxy-2-methylquinolin-4-yl)amino]-N-[(E)-(4-methylsulfanylphenyl)methylideneamino]-1H-indole-2-carboxamide	1741448: Binding affinity to Nur77 ligand binding domain (unknown origin) assessed as dissociation constant by fluorescence titration based analysis	kd	1.3400	uM
2-[[2-fluoro-4-(3-prop-2-ynoxyphenyl)phenyl]carbamoyl]cyclopentene-1-carboxylic acid	2031370: Agonist activity at Nur77 (unknown origin) by Gal4 hybrid reporter gene assay	ec50	1.4000	uM
(E)-3-(4,5-diphenyl-1,3-oxazol-2-yl)prop-2-enoic acid	2087298: Inverse agonist activity at human Nur77 (358 to 598 residues) transfected in HEK293T cells incubated for 16 hrs by firefly/renilla based Dual-Glo luciferase assay	ic50	1.9000	uM
(Z)-7-[(1R,2S)-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxocyclopent-3-en-1-yl]hept-5-enoic acid	1925158: Binding affinity to Nur77 (unknown origin) by SPR assay	kd	2.0500	uM
5-[(8-methoxy-2-methylquinolin-4-yl)amino]-N-[(E)-(2-methoxynaphthalen-1-yl)methylideneamino]-1H-indole-2-carboxamide	1946223: Binding affinity to Nur77-LBD (unknown origin)	kd	2.2500	uM
(2R,4aS,6aR,6aS,14aS,14bR)-10,11-dihydroxy-2,4a,6a,6a,9,14a-hexamethyl-8-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylic acid	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	2.6900	uM
methyl (2R,4aS,6aR,6aS,14aS,14bR)-10-methoxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylate	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	2.9400	uM
2-[[2-fluoro-4-(3-methoxyphenyl)phenyl]carbamoyl]cyclopentene-1-carboxylic acid	2031370: Agonist activity at Nur77 (unknown origin) by Gal4 hybrid reporter gene assay	ec50	3.1000	uM
methyl (2R,4aS,6aR,6aS,14aS,14bR)-10-(2,2-difluoroethoxy)-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylate	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	3.3000	uM
(2R,4aS,6aR,6aS,8R,14aS,14bR)-10,11-dihydroxy-2,4a,6a,6a,9,14a-hexamethyl-8-(2-oxopropyl)-3,4,5,6,8,13,14,14b-octahydro-1H-picene-2-carboxylic acid	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	3.8000	uM
methyl (2R,4aS,6aR,6aS,14aS,14bR)-10-ethoxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylate	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	4.1300	uM
Meclofenamic Acid	1925164: Inhibition of Gal4-fused Nur77 in HEK293T cells	ec50	4.7000	uM
(2R,4aS,6aR,6aS,8R,14aS,14bR)-10,11-dihydroxy-2,4a,6a,6a,9,14a-hexamethyl-8-(nitromethyl)-3,4,5,6,8,13,14,14b-octahydro-1H-picene-2-carboxylic acid	1597523: Binding affinity to recombinant human N-terminal His-tagged Nur77 LBD (367 to 598 residues) expressed in Escherichia coli BL21(DE3) incubated for 30 secs by fluorescence quenching assay	kd	5.5600	uM
2-(4,5-diphenyl-1,3-oxazol-2-yl)acetic acid	2087298: Inverse agonist activity at human Nur77 (358 to 598 residues) transfected in HEK293T cells incubated for 16 hrs by firefly/renilla based Dual-Glo luciferase assay	ic50	8.0000	uM
4-phenylmethoxybenzoic acid	2037846: Agonist activity at human Nur77 LBD transiently transfected in HEK293T cells incubated for 16 hrs by Gal4-hybrid reporter gene based Dual-glo luciferase assay	ec50	8.0000	uM
5-(3-fluorophenyl)furan-2-carboxylic acid	2037846: Agonist activity at human Nur77 LBD transiently transfected in HEK293T cells incubated for 16 hrs by Gal4-hybrid reporter gene based Dual-glo luciferase assay	ec50	9.0000	uM
4-(2-methylsulfanylimidazol-1-yl)benzoic acid	2037847: Inverse agonist activity at human Nur77 LBD transiently transfected in HEK293T cells incubated for 16 hrs by Gal4-hybrid reporter gene based Dual-glo luciferase assay	ic50	9.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, affects binding, decreases reaction (+1 more)	5
1,1-bis(3’-indolyl)-1-(4-hydroxyphenyl)methane	decreases expression, increases cleavage, increases expression, increases response to substance, affects binding (+3 more)	4
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	4
bis(tri-n-butyltin)oxide	increases expression	3
bisphenol A	affects expression, affects cotreatment, increases methylation, decreases expression, decreases methylation	3
Cisplatin	increases expression, affects response to substance, affects cotreatment	3
Doxorubicin	affects expression, decreases expression, decreases response to substance	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Tetradecanoylphorbol Acetate	affects localization, increases expression, affects cotreatment, affects expression	3
Tretinoin	decreases reaction, increases expression, decreases expression, increases activity, affects binding (+1 more)	3
Zinc	affects cotreatment, increases expression, affects expression	3
Genistein	increases expression, affects cotreatment, decreases expression	3
p-carboxymethylphenyl 1,1-bis(3’-indolyl)-1-(p-carboxymethylphenyl)methane	decreases reaction, affects binding, increases reaction, increases response to substance, affects localization	2
methylmercuric chloride	affects cotreatment, affects expression, affects reaction, affects methylation, affects binding (+1 more)	2
mono-(2-ethylhexyl)phthalate	decreases expression, increases expression	2
torcetrapib	increases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Fulvestrant	affects cotreatment, increases methylation, increases expression	2
Air Pollutants	increases expression, increases abundance	2
Atrazine	decreases expression, increases expression	2
Cadmium	increases expression, decreases reaction	2
Copper	decreases expression, increases expression, affects binding	2
Dichlorodiphenyl Dichloroethylene	decreases expression, increases activity	2
Fluorouracil	affects expression	2
Glutathione	affects cleavage, decreases reaction, affects expression, affects phosphorylation	2
Hydrogen Peroxide	affects expression, increases expression	2
Silver	increases expression	2
Smoke	increases expression	2
Fenretinide	affects localization, affects cotreatment, increases expression, increases reaction, affects reaction (+2 more)	2
Asbestos, Crocidolite	increases expression, affects expression	2

ChEMBL screening assays

194 unique, capped per target: 178 binding, 16 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1225186	Binding	Binding affinity to Nur77 receptor expressed in human BGC823 cells	Cytosporone B is an agonist for nuclear orphan receptor Nur77. — Nat Chem Biol
CHEMBL1225187	Functional	Agonist activity at nuclear orphan receptor Nur77 in human BGC823 cells bearing beta-galactosidase expression vector assessed as transcriptional activation of NurRE reporter gene after 12 hrs by luciferase assay	Cytosporone B is an agonist for nuclear orphan receptor Nur77. — Nat Chem Biol

Cellosaurus cell lines

14 cell lines: 10 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4W6	SEES3-1V human NR4A1, clone1	Embryonic stem cell	Male
CVCL_A4W7	SEES3-1V human NR4A1, clone2	Embryonic stem cell	Male
CVCL_A4W8	SEES3-1V human NR4A1, clone3	Embryonic stem cell	Male
CVCL_AW37	K562 eGFP-NR4A1	Cancer cell line	Female
CVCL_B8LM	Abcam HCT 116 NR4A1 KO	Cancer cell line	Male
CVCL_B8ZL	Abcam MCF-7 NR4A1 KO	Cancer cell line	Female
CVCL_B9NS	Abcam A-549 NR4A1 KO	Cancer cell line	Male
CVCL_B9VS	Abcam HeLa NR4A1 KO	Cancer cell line	Female
CVCL_D7W4	Ubigene A-549 NR4A1 KO	Cancer cell line	Male
CVCL_D8RP	Ubigene HCT 116 NR4A1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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